Endocrine Disruption

Potential Molecular Associations Between Triphenyl Phosphate Exposure and Thyroid Cancer: Integration of Network Toxicology and Machine Learning for Core Target Identification with Molecular Docking - July 15, 2026

Int J Mol Sci. 2026 Jul 4;27(13):6018. doi: 10.3390/ijms27136018.

ABSTRACT

Triphenyl phosphate (TPhP) is a ubiquitous environmental contaminant and endocrine disruptor potentially associated with an increased risk of thyroid cancer (TC). However, whether TPhP directly contributes to TC remains unclear. This study integrated network toxicology and machine learning to investigate potential molecular associations between TPhP exposure and thyroid oncogenesis. By integrating multi-source databases and transcriptomic data, we constructed a TPhP-TC interaction network and established a TC risk prediction model using 127 machine learning algorithm combinations, identifying ten candidate hub genes. GO and KEGG enrichment analyses indicated that these genes are predominantly enriched in phosphorus metabolism, purine metabolism, and nuclear receptor signaling pathways, implying that TPhP may be linked to tumorigenesis through the disruption of metabolic reprogramming. SHAP analysis highlighted AHR and SLC20A2 as critical contributors to model performance. Molecular docking predicted stable binding between TPhP and all hub proteins in silico, with binding energies ranging from -9.2 to -6.6 kcal/mol. This study offers two computational contributions: (1) a quantifiable framework for predicting pollutant-associated TC risk and (2) systematic computational evidence for potential TPhP thyroid toxicity. These findings address a critical gap in understanding potential links between endocrine-disrupting chemical exposure and thyroid carcinogenesis, generating hypotheses for future experimental validation.

PMID:42450283 | DOI:10.3390/ijms27136018

Ovarian toxic effects of micro- and nanoplastics (Review) - July 15, 2026

Exp Ther Med. 2026 Jun 26;32(2):227. doi: 10.3892/etm.2026.13222. eCollection 2026 Aug.

ABSTRACT

Microplastics and nanoplastics (MNPs) have become widespread contaminants with notable impacts on reproductive health. MNPs have been found in human specimens, including follicle fluid, causing concerns regarding their negative impact on female fertility. The present review aimed to comprehensively examine the ovarian deleterious impacts of MNPs, and to analyze their toxicological mechanisms, impact on folliculogenesis and oocyte quality, transgenerational effects and influencing factors. Previous evidence suggests that MNPs can trigger oxidative stress, inflammatory responses, disruption of endocrine function, programmed cell death, endoplasmic reticulum stress, membrane structural damage, epigenetic modifications and DNA lesions in the ovary, resulting in impaired folliculogenesis, disrupted steroidogenesis and reduced reproductive capacity. The present review emphasized the impact of the MNP polymer type, size and surface characteristics on ovarian reproductive toxicity, and highlights some knowledge gaps that require attention, providing a reference for deeper understanding and mitigation of MNPs-induced ovarian toxicity.

PMID:42453773 | PMC:PMC13365865 | DOI:10.3892/etm.2026.13222

Pesticide Residues in Vegetables: The Potential Risk Assessment of Endocrine and Reproductive Disruptors for Children and Adults - July 15, 2026

Foods. 2026 Jul 1;15(13):2336. doi: 10.3390/foods15132336.

ABSTRACT

Pesticide residues in vegetables constitute a potential source of exposure to endocrine- and reproductive-disrupting chemicals (EDCs/RDs), particularly in vulnerable populations such as children. This study assessed pesticide occurrence in vegetables from 12 countries worldwide and evaluated associated health risks for children and adults within the framework of European legislation. Of the 390 analyzed samples, 84.7% contained 40 pesticides, including nine non-approved compounds (26% of samples). Fungicides were among the detected groups (81.7%), with boscalid (0.005-0.36 mg kg^-1) and propamocarb (0.005-0.87 mg kg^-1) being the most commonly occurring compounds. Multiresidue contamination was observed in 75.7% of samples. Tomatoes and leeks exhibited the highest concentrations, and the European Union maximum residue level (MRL) was exceeded by up to 240% for flonicamid in Chinese cabbage. Propamocarb was the most commonly identified EDC, while tomatoes showed the greatest diversity of these compounds. RDs occurred less frequently, with pyraclostrobin being the most common. Risk assessment resulting from the presence of multiple pesticides in an individual sample expressed as the hazard index (HI) exceeded acceptable levels for BE toddlers consuming tomatoes (1.345 for EDCs and 1.264 for RDs) and leeks (1.010) containing propamocarb. These findings highlight an in-depth toxicological evaluation of the combined effects of multiple hazardous pesticides occurring simultaneously, which may support future legislative measures aimed at improving food safety.

PMID:42450454 | DOI:10.3390/foods15132336

Hypothalamic-Pituitary-Gonadal Axis Programming and Disrupted Ovarian-Endocrine Function in Female Offspring of the Preeclamptic-Like BPH/5 Mouse - July 15, 2026

Am J Physiol Endocrinol Metab. 2026 Jul 15. doi: 10.1152/ajpendo.00543.2025. Online ahead of print.

ABSTRACT

Children born after preeclampsia, the leading hypertensive disorder of pregnancy, are predisposed to long-term cardiometabolic and reproductive disorders that are likely associated with prenatal exposure to a dysregulated maternal endocrine milieu. We have previously described abnormal pubertal development and hyperandrogenism in female offspring from the preeclamptic-like Blood Pressure High Subline 5 (BPH/5) mouse, recapitulating patterns observed in adolescents born after preeclampsia. Herein, our objective was to elucidate BPH/5 offspring hypothalamic-pituitary-gonadal (HPG) axis programming and the associated hormonal profile of late-gestation BPH/5 dams. Reproductive and metabolic phenotypes of BPH/5 and Blood Pressure Normal Subline 3 (BPN/3) offspring were assessed from birth to adulthood, including anogenital distance, pubertal onset, ovarian function, and adiposity. Maternal late-gestation circulating hormones and placental steroidogenic enzymes were also investigated. Anogenital distance, indicative of prenatal androgen exposure, was longer in BPH/5 male and female offspring. BPH/5 female offspring exhibited precocious pubertal onset and, during adulthood, abnormal estrous cycles, increased visceral adiposity, increased serum Anti-Mullerian hormone (AMH), and ovarian morphology consistent with a polycystic ovary syndrome (PCOS)-like phenotype. Serum testosterone did not differ between late-gestation BPH/5 and BPN/3 dams. Conversely, serum AMH concentrations were threefold higher in late-gestation BPH/5 dams, a maternal endocrine disruption previously linked to abnormal female fetus HPG axis programming and PCOS-like offspring phenotype. In conclusion, BPH/5 offspring recapitulate aberrant reproductive phenotype seen in children born after preeclampsia and major PCOS-like characteristics. Furthermore, maternal AMH excess was identified in late-gestation BPH/5 females, highlighting this as a valuable model of the interplay between PCOS and preeclampsia.

PMID:42454568 | DOI:10.1152/ajpendo.00543.2025

Perithyroidal Adipose Tissue Drives Thyroid Tumorigenesis through Adipokine Signaling and Immune Suppression - July 15, 2026

Research (Wash D C). 2026 Jul 14;9:1360. doi: 10.34133/research.1360. eCollection 2026.

ABSTRACT

The perithyroidal adipose tissue (PAT), given its direct anatomical proximity to the thyroid gland, has long been postulated as a modulator of the thyroid tumor microenvironment. However, its cellular composition, functional heterogeneity, and specific roles in thyroid cancer progression remain unknown. To address these knowledge gap, we performed single-nucleus RNA sequencing of PAT from patients with papillary thyroid carcinoma (PTC) and multinodular goiter (MNG), combined with machine learning, proteomics, immunofluorescence, ex vivo assays, and human serum analysis. We constructed the first high-resolution atlas of human PAT, revealing an immune-rich niche and previously unrecognized adipocyte heterogeneity, including thermogenic subpopulations (BL-Ad1, BL-Ad2, OXPHOS-Ad) from distinct progenitors. Functionally, the PAT secretome from PTC substantially enhanced thyroid cancer cell proliferation compared to MNG. Integrated analyses identified a pathogenic adipokine triad characterized by loss of ADIPOQ and gain of NAMPT and IGF1. Restoring ADIPOQ signaling or inhibiting NAMPT/IGF1 suppressed tumor growth in vitro and in vivo. Additionally, we identified CCL14, down-regulated in PTC-derived OXPHOS-Ad, as a key immune regulator. Reduced CCL14-CCR1 signaling impaired CD80 expression in M1-like macrophages, disrupting CD80-CD28 costimulation and consequently diminishing T cell proliferation and recruitment. Consistently, circulating CCL14 levels were reduced in PTC patients. In conclusion, PAT acts as a dynamic endocrine and immunomodulatory component of the tumor microenvironment that promotes thyroid tumor growth through adipokine-mediated and immune-dependent mechanisms.

PMID:42453940 | PMC:PMC13365586 | DOI:10.34133/research.1360

What's in a name: the potential impact of the updated terminology of polyendocrine metabolic ovarian syndrome (PMOS) - July 15, 2026

Expert Rev Mol Diagn. 2026 Jul 15. doi: 10.1080/14737159.2026.2705467. Online ahead of print.

ABSTRACT

INTRODUCTION: Polycystic ovary syndrome (PCOS) was recently renamed polyendocrine metabolic ovarian syndrome (PMOS).

AREAS COVERED: We review the renaming process, the potential advantages, and the challenges associated with this global effort. A large consortium of experts and patient representatives debated whether renaming was justified, what principles should guide a new name, and how such a change could be implemented without disrupting clinical care, research, education, or patient communication. Surveys indicated that awareness of the broader features of the syndrome improved in the last years after dissemination strategies and patient advocacy initiatives, but important gaps remained, particularly around the risk of comorbidities.

EXPERT OPINION: New perspectives emerge with renaming PCOS into PMOS after a carefully planned effort to improve scientific accuracy, patient understanding, and clinical communication while minimizing confusion during implementation. The new terminology emphasizes the syndrome's endocrine and metabolic nature and removes the misleading reference to 'polycystic' ovaries. Similar to previous successful nomenclature updates in gynecology, this gradual transition aims to enhance education, interdisciplinary care, research, and long-term management, ultimately supporting more accurate diagnosis and improved patient outcomes.

PMID:42454868 | DOI:10.1080/14737159.2026.2705467

Nonylphenol stress intensifies phosphorus limitation and restructures microbial co-occurrence networks in soil - July 15, 2026

J Hazard Mater. 2026 Jul 9;515:142959. doi: 10.1016/j.jhazmat.2026.142959. Online ahead of print.

ABSTRACT

Nonylphenol (NP) is a globally concerned endocrine disruptor, yet its ecological risks in soil are often evaluated solely by residual concentrations or degradation rate, overlooking the more subtle functional and structural disturbances to soil microbiomes. Here, we conducted a 90-day concentration-gradient microcosm experiment to integrate NP degradation dynamics with extracellular enzyme stoichiometry, vector-based microbial nutrient limitation, community succession, and co-occurrence network reorganization. We found that NP was efficiently degraded (>75% even at 120 mg kg⁻¹ within 90 days), but rapid degradation did not prevent profound functional shifts. Medium-to-high NP concentrations (≥30 mg kg⁻¹) significantly suppressed β-glucosidase (max inhibition 68.4%) and, more importantly, altered enzyme stoichiometric ratios (Carbon (C): nitrogen (N) and C: phosphorus (P) decreased linearly with NP concentration). Vector analysis revealed a critical transition: Medium-to-high NP exposure shifted microbial metabolic indicators from C-P co-limitation toward stronger P limitation. Concurrently, NP exerted strong selective pressure, reducing α-diversity but enriching NP-tolerant and putative degradative taxa (Proteobacteria, Lysobacter, Pseudomonas). This compositional restructuring drove microbial co-occurrence networks toward a more connected yet topologically reorganized "NP-adapted" configuration, with keystone taxa shifting from conventional nutrient cyclers (Massilia, Nitrospira) to stress-tolerant degrader genera (Truepera, Pseudonocardia). Collectively, we demonstrate that NP's ecotoxicological fingerprint lies not in its persistence but in its ability to decouple C-N-P acquisition strategies and force a network‑level adaptive reorganization - even under substantial degradation. Thus, risk assessment for NP‑contaminated soils must move beyond degradation data alone to include enzymatic stoichiometric imbalances, microbial P‑limitation status, and co‑occurrence network topology.

PMID:42456576 | DOI:10.1016/j.jhazmat.2026.142959

Impact of parabens, individually and in mixture, on human neutrophil oxidative burst under physiological and hyperglycemic conditions - July 15, 2026

Food Chem Toxicol. 2026 Jul 15:116279. doi: 10.1016/j.fct.2026.116279. Online ahead of print.

ABSTRACT

Parabens are a family of alkyl esters of 4-hydroxybenzoic acid (4-HB), widely used as antimicrobial agents in various industries, including cosmetics, pharmaceuticals, and food. However, concerns have been raised regarding their potential to disrupt the endocrine system and contribute to chronic inflammation, leading to their classification as endocrine-disrupting chemicals. Neutrophils play a central role in innate immune responses, and can be influenced by the surrounding metabolic environment, including glucose levels. Hyperglycemia, characterized by elevated plasma glucose levels, is a common feature of metabolic disorders. Therefore, this study explored the impact of common parabens - namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP) and their metabolite 4-HB, tested alone or combined at different ratios, on human neutrophils' oxidative burst under physiological and hyperglycemic conditions. Results evidenced that single parabens induced neutrophils' oxidative burst, through activation of phospholipase C (PLC) and protein kinase C (PKC), leading to NADPH oxidase and myeloperoxidase (MPO) activation. No effects were observed following exposure to 4-HB. Additionally, paraben mixtures, tested at total concentrations up to 100 μM, predominantly exhibited additive effects under both physiological and hyperglycemic conditions. This study provides new insights into the potential risks of paraben exposure in exacerbating oxidative stress and inflammation.

PMID:42456959 | DOI:10.1016/j.fct.2026.116279

Differential Sensitivity of Endocrine and Non-Endocrine Tissues to Cadmium-Induced Lipid Peroxidation and the Protective Role of Melatonin - July 15, 2026

Int J Mol Sci. 2026 Jul 3;27(13):5991. doi: 10.3390/ijms27135991.

ABSTRACT

Cadmium is a toxic heavy metal classified by the International Agency for Research on Cancer as a human carcinogen and recognized as an endocrine-disrupting chemical. The present study aimed to evaluate tissue-specific susceptibility to cadmium-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) and to assess the antioxidative effects of melatonin in porcine tissue homogenates representing endocrine (the thyroid and the ovary) and non-endocrine (the liver, the kidney, and the brain) organs. Homogenates were incubated with cadmium chloride (CdCl₂; 2.5-1000 µM) without/with melatonin (0.1-5.0 mM). Lipid peroxidation was assessed spectrophotometrically by measuring malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) levels. Cadmium significantly increased LPO in the liver (2.5-1000 μM) and in the kidney (25-1000 μM), whereas no prooxidative effect was observed in endocrine tissues or in the brain. Liver damage was mitigated by melatonin doses as low as 0.1 μM across the 250-1000 μM cadmium range, while protection in the kidney was limited to higher melatonin concentrations (2.5-5.0 mM) against damage induced by 100-1000 μM cadmium concentrations. The findings demonstrate pronounced tissue-specific differences in susceptibility to cadmium-induced oxidative stress and support the potential of melatonin as a preventive agent against heavy metal-induced oxidative stress, particularly in non-endocrine organs.

PMID:42450258 | DOI:10.3390/ijms27135991

Functional Inactivation of PAX4 Results in Disrupted Endocrine Pancreas Development and Neonatal Diabetes in Pigs - July 15, 2026

Int J Mol Sci. 2026 Jun 23;27(13):5651. doi: 10.3390/ijms27135651.

ABSTRACT

Variants in the human PAX4 gene are associated with both monogenic and complex forms of diabetes, yet their pathogenic effects remain difficult to define in models that accurately mimic human islet architecture and neonatal metabolic transitions. Here, we created a porcine PAX4 loss-of-function model using CRISPR/Cas9 cytidine deaminase base editing to introduce a premature stop codon in the PAX4 coding sequence. PAX4 knockout piglets developed severe hyperglycemia within 24 h of birth, followed by rapid postnatal clinical deterioration and uniform death by day 3. Biochemical analysis showed significant diabetic decompensation, including electrolyte imbalances, hyperosmolality, azotemia, dyslipidemia, and metabolic acidosis. Gross and histological examinations revealed notable pancreatic hypoplasia with preservation of exocrine tissue. Single-nucleus RNA sequencing and immunohistochemistry demonstrated an almost complete loss of insulin- and somatostatin-producing β- and δ-cells, respectively, with relative preservation of glucagon-expressing α-cells. Overall, these results establish PAX4 as a crucial factor in pancreatic endocrine development and postnatal glucose regulation in a large-animal model. This platform offers a human-relevant system for studying diabetes-associated PAX4 variants and for testing regenerative and gene-based therapies for insulin-deficient diabetes.

PMID:42449928 | DOI:10.3390/ijms27135651

Association of formaldehyde with sex steroid hormones in US children and adolescents (NHANES 2013-2016) - July 15, 2026

Int J Environ Health Res. 2026 Jul 15:1-11. doi: 10.1080/09603123.2026.2701058. Online ahead of print.

ABSTRACT

Experimental studies suggest that formaldehyde may disrupt reproductive and endocrine function, but human evidence remains limited. We examined the association between formaldehyde exposure, measured as hemoglobin adducts, and serum sex steroid hormones among children (6-11 years) and adolescents (12-19 years) participating in NHANES 2013-2016. Multivariable regression models were used to evaluate associations between formaldehyde and total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), free testosterone, free estradiol (FE2), and the TT/E2 ratio. False discovery rate (FDR) correction was applied to account for multiple comparisons, and restricted cubic spline models were used to assess potential non-linear dose - response relationships. After FDR correction, significant associations were observed only among female adolescents. Each doubling of formaldehyde concentration was associated with lower E2 (-55.74%; 95% CI: -73.43, -26.24%) and a higher TT/E2 ratio (96.84%; 95% CI: 18.26, 227.61). Restricted cubic spline analyses supported non-linear dose - response relationships. Although inverse associations between formaldehyde and several sex steroid hormones were observed across age-sex groups, most did not remain significant after FDR correction. These findings suggest that formaldehyde exposure may be associated with altered sex steroid hormone profiles in female adolescents.

PMID:42458253 | DOI:10.1080/09603123.2026.2701058

Ovarian toxic effects of micro- and nanoplastics (Review) - July 15, 2026

Exp Ther Med. 2026 Jun 26;32(2):227. doi: 10.3892/etm.2026.13222. eCollection 2026 Aug.

ABSTRACT

PMID:42453773 | PMC:PMC13365865 | DOI:10.3892/etm.2026.13222

Contribution of Consumer Products to Emerging Chemical Exposures in a Preconception Cohort Study - July 15, 2026

Environ Sci Technol. 2026 Jul 15. doi: 10.1021/acs.est.5c18677. Online ahead of print.

ABSTRACT

In the United States (U.S.), 15% of couples attempting pregnancy experience infertility, and 20% of pregnancies end in miscarriage. Environmental chemical exposures, particularly endocrine-disrupting chemicals (EDCs) from consumer products, may contribute to reproductive health challenges. We mailed wearable passive samplers (Fresh Air wristbands) to 132 female participants across 39 U.S. states and 24 of their male partners in the Pregnancy Study Online (PRESTO) to characterize exposure among couples trying to conceive between January and October 2021. Wristbands were analyzed using thermal desorption gas chromatography-high-resolution mass spectrometry with targeted and nontargeted approaches. Nontargeted analysis revealed exposure to 491 chemicals, predominantly benzenoids (36.9%) and organoheterocyclic compounds (18.3%). Health hazard assessment identified 107 high-risk EDCs and 47 compounds predicted to have medium-to-high impacts on reproductive outcomes, including galaxolide, salicylates, and phthalates. Targeted analysis quantified 43 chemicals, revealing universal exposure to polycyclic aromatic hydrocarbons and phthalates. Lifestyle factors influenced exposures: frequent sunscreen users had up to 3.1 times higher ultraviolet filter exposures, while dog owners had 1.2-2.6 times higher exposure to fragrance compounds. Among cohabitating couples, few similarities were observed, despite shared environments. The findings demonstrate that consumer products contribute to complex exposure mixtures with reproductive health implications during preconception.

PMID:42457234 | DOI:10.1021/acs.est.5c18677

Endocrine Disruptors and Gynecological Malignancies - July 15, 2026

Diagnostics (Basel). 2026 Jul 6;16(13):2116. doi: 10.3390/diagnostics16132116.

ABSTRACT

Background/Objectives: Endocrine-disrupting chemicals (EDCs) interfere with hormonal homeostasis and have been implicated in gynecological malignancy pathogenesis. This narrative review synthesizes current evidence regarding EDC exposure and breast, endometrial, ovarian, and cervical cancers, examining molecular mechanisms, epidemiology, and diagnostic and clinical implications. Methods: We conducted a literature review using PubMed/MEDLINE, Embase, Scopus, and Cochrane databases through April 2026, including systematic reviews, meta-analyses, prospective cohorts, case-control studies, and mechanistic investigations examining EDC-cancer associations. Methodological quality was appraised using the Newcastle-Ottawa Scale and AMSTAR-2, with overall certainty of evidence rated using the GRADE framework. Results: Major EDC classes-bisphenol compounds, phthalates, polychlorinated biphenyls, organochlorine pesticides, and per- and polyfluoroalkyl substances-demonstrate carcinogenic potential through estrogen receptor modulation, epigenetic alterations, oxidative stress, and oncogenic signaling disruption. Breast cancer shows the strongest evidence, with prenatal and early-life DDT/DDE exposure associated with up to a 3.7-fold increased risk. Endometrial cancer demonstrates associations with xenoestrogen mixtures exhibiting non-monotonic dose-responses, whereas ovarian and cervical cancers show emerging but limited associations. Common mechanisms include receptor crosstalk, epigenetic dysregulation with transgenerational effects, oxidative genomic instability, metabolic reprogramming, and cancer stem cell enrichment. Conclusions: Evidence supports EDC contributions to gynecological malignancy through convergent pathways, though causal inference remains constrained by observational epidemiology, long latency periods, and challenges in characterizing real-world mixture exposures. Diagnostic and prevention strategies should integrate EDC exposure into risk-prediction models, leverage multi-omics biomarkers for early detection, and emphasize exposure reduction during critical developmental windows alongside regulatory reform.

PMID:42449897 | DOI:10.3390/diagnostics16132116

GDF9, NPHS1, and RET Mark Gastric Neuroendocrine Cells and Their Disruption in a PKA-Driven Gastric Preneoplasia Model - July 15, 2026

Int J Mol Sci. 2026 Jun 23;27(13):5642. doi: 10.3390/ijms27135642.

ABSTRACT

The gastric endocrine population comprises functionally distinct cell types that exhibit both neuronal and endocrine characteristics; however, their molecular markers remain incompletely defined. Here, we identify growth differentiation factor 9 (GDF9), nephrin (NPHS1), and rearranged during transfection (RET) as novel markers of gastric endocrine cells. A co-immunofluorescence (IF) analysis demonstrated that GDF9, NPHS1, and RET are co-expressed with chromogranin A (CHGA), a well-known marker of gastrointestinal endocrine cells. Further Co-IF analysis revealed that GDF9-expressing cells were negative for ghrelin and somatostatin, whereas NPHS1 was co-expressed with both hormones. A subpopulation of RET-positive cells co-expressed ghrelin but not somatostatin. Notably, GDF9- and RET-positive cells co-expressed dopamine decarboxylase (DDC), consistent with enrichment in enterochromaffin-like (ECL) cells. Revisitation of our previous mRNA-sequencing data revealed reduced transcript levels of Gdf9, Nphs1, and Ret in CA-PKA mice, which express constitutively active protein kinase A (PKA) and develop gastric preneoplastic lesions. Co-IF and cellular quantification showed a localized reduction in the density of GDF9 and CHGA-positive endocrine cells, together with altered abundance of NPHS1- and RET-expressing cells in CA-PKA stomachs. These changes occurred in the context of extensive hyperplasia of the surrounding epithelium, indicating that the observed alterations reflect localized reduction and non-cell-autonomous effects of epithelial expansion. Notably, we observed RET misexpression outside the endocrine compartment in CA-PKA mice, suggesting that aberrant RET signaling may contribute to lesions by promoting abnormal glandular branching. Together, these findings identify GDF9, NPHS1, and RET as novel markers of gastric endocrine cells and their potential role in gastric homeostasis.

PMID:42449921 | DOI:10.3390/ijms27135642

Bidirectional Associations Between Circulating Polyunsaturated Fatty Acids and Female Reproductive Endocrine-Related Diseases: A Mendelian Randomization Study - July 14, 2026

Int J Womens Health. 2026 Jul 9;18:598204. doi: 10.2147/IJWH.S598204. eCollection 2026.

ABSTRACT

OBJECTIVE: Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate female reproductive endocrine disorders, yet their causal relationships remain elusive. We employed Mendelian randomization (MR) to investigate bidirectional causality between circulating PUFAs (omega-3/6 subtypes, docosahexaenoic acid [DHA], linoleic acid) and endometriosis, infertility, polycystic ovary syndrome (PCOS), premenstrual syndrome, and premature ovarian insufficiency (POI).

MATERIALS AND METHODS: In this two-sample MR study, exposure data from a GWAS of 115,006 Europeans were analyzed against outcome data (FinnGen and other large-scale GWAS). Forward MR assessed PUFA effects on disorders; reverse MR evaluated disorder-driven PUFA alterations. Sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out) ensured robustness.

RESULTS: Elevated linoleic acid and total omega-6 levels increased endometriosis (OR=1.127, P=0.039; OR=1.123, P=0.037) and infertility risks (OR=1.155, P=0.019), while higher PUFA-to-total fatty acid ratios conferred protection (endometriosis: OR=0.857, P=0.017). PCOS genetically reduced DHA and total omega-3 levels while elevating omega-6/3 ratios (P<0.05). No reverse effects were observed for other disorders.

CONCLUSION: Our findings implicate linoleic acid and omega-6 PUFAs as potential risk factors for endometriosis and infertility, whereas balanced PUFA ratios may be protective. PCOS disrupts omega-3 homeostasis, suggesting bidirectional metabolic interplay. These results highlight PUFAs as modifiable targets for nutritional and therapeutic strategies in reproductive health, warranting further mechanistic and clinical validation.

PMID:42445362 | PMC:PMC13360956 | DOI:10.2147/IJWH.S598204

Elinzanetant for the Treatment of Menopausal Hot Flashes: A Plain Language Review of the OASIS-1-4 Clinical Trial Results - July 14, 2026

Womens Health (Lond). 2026 Jan-Dec;22:17455057261462773. doi: 10.1177/17455057261462773. Epub 2026 Jul 14.

ABSTRACT

What is this review about?During the menopausal transition, women may experience disruptive symptoms like hot flashes during the day or night (night sweats) and have trouble sleeping. Many current treatments for hot flashes do not work for everyone because of potential side effects, health concerns, or individual needs and preferences.Elinzanetant is a hormone-free treatment for hot flashes linked to menopause. It works by targeting the source of hot flashes in the brain. This summary covers the results from four randomized clinical trials that tested elinzanetant in women: OASIS-1, OASIS-2, OASIS-3, and OASIS-4.The OASIS trials looked at how well elinzanetant works for women with menopause symptoms. OASIS-1, OASIS-2, and OASIS-3 included women with hot flashes from natural or surgical menopause. OASIS-4 focused on women who had hot flashes because they were taking endocrine therapy after initial treatment for breast cancer.What were the results?The OASIS trials showed that elinzanetant rapidly reduces the number and severity of hot flashes experienced by women from natural or surgical menopause or due to endocrine therapy for breast cancer. Elinzanetant also improved their sleep and overall well-being. The side effects seen with elinzanetant were mainly mild and tolerable, the most common being headache, fatigue, and sleepiness.We use the term 'women' throughout for simplicity, but we recognize that menopause and its treatments may also be relevant to people who do not identify as women.

PMID:42447004 | DOI:10.1177/17455057261462773

The toxicity of petroleum pollutants on marine zooplankton: Multiscale effects from individuals to populations - July 14, 2026

Mar Pollut Bull. 2026 Jul 14;232:120133. doi: 10.1016/j.marpolbul.2026.120133. Online ahead of print.

ABSTRACT

Petroleum hydrocarbon pollution, particularly in combination with chemical dispersants, poses a severe threat to marine ecosystems. Zooplankton as a crucial link in the marine food chain, are highly sensitive to petroleum pollutants exposure, yet a systematic synthesis of its multigenerational and population-level impacts remain lacking. This review systematically elaborate on the multiple toxicological effects and their underlying mechanisms of petroleum pollutants on marine zooplankton, with a focus on copepods. We first analyzes the various existing forms of petroleum hydrocarbons in aquatic environments and clarifies their primary exposure pathways to zooplankton. We then summarize the temporal dynamics of toxic effects, including acute lethal effects, chronic sublethal impacts, and transgenerational toxicity. At the mechanistic level, we highlight key molecular initiating events such as oxidative stress, endocrine disruption, and gene expression dysregulation. Finally, we identify critical knowledge gaps and recommend integrated approaches combining multi-omics, ecological modeling, and multi-stressor experimental designs to improve ecological risk assessment and mitigation strategies. This review provides a comprehensive framework for understanding the cascading effects of oil spills on zooplankton populations and supports science-based decision-making in oil spill response.

PMID:42447784 | DOI:10.1016/j.marpolbul.2026.120133

Mechanistic Insights into the capture of bisphenol homologs by macroporous chitosan-bentonite composite foams - July 14, 2026

Bioresour Technol. 2026 Jul 14:135401. doi: 10.1016/j.biortech.2026.135401. Online ahead of print.

ABSTRACT

Bisphenols (BPA, BPF and BPS) are emerging contaminants with well-documented endocrine-disrupting effects, and their environmental occurrence often coincides with heavy metals and microplastics. In this study, a three-dimensional chitosan/bentonite composite foam (CBF) was fabricated via directional ice-templating and systematically evaluated as a recoverable adsorbent for bisphenols. The CBF exhibited stable adsorption performance, with kinetics following the pseudo-second-order model and isotherms well described by the Langmuir model, achieving moderate maximum capacities of 13.69 to 16.27 mg/g under a monolithic, manually recoverable design. High removal efficiencies were maintained over a wide pH range (2.0-10.0) and under varying ionic strength conditions. Spectroscopic and thermodynamic analyses indicate that bisphenol adsorption is governed by hydrogen bonding, polar interactions, and pore confinement effects, with selectivity among analogues modulated by their analogue-specific interaction pathways with the functional groups of CBF. The positive enthalpy change and increasingly negative Gibbs free energy further support a spontaneous and endothermic adsorption process. Preliminary tests further indicated that the macroporous framework was capable of capturing heavy metal ions (Pb(II), Cd(II)) and physically entrapping representative microplastics (PLA, PS, PE), suggesting potential applicability beyond bisphenols. Within its intended design scope of prioritizing operational simplicity over maximum capacity, CBF offers a monolithic platform with facile manual separation and minimal secondary turbidity. This combination of low-cost raw materials, monolithic recoverability, and multi-class pollutant applicability distinguishes CBF from conventional powdered adsorbents and is relevant to the practical treatment of bisphenol contaminated water under complex matrix conditions.

PMID:42448113 | DOI:10.1016/j.biortech.2026.135401

Seasonal changes in parental hormone levels and their association with mercury contamination in a tropical seabird - July 14, 2026

Environ Pollut. 2026 Jul 14:128780. doi: 10.1016/j.envpol.2026.128780. Online ahead of print.

ABSTRACT

Parental investment is a life-history trait whose expression is tightly regulated by endocrine mechanisms. Mercury (Hg) contamination poses a significant threat to wildlife physiology in tropical ecosystems, where naturally high concentrations have been exacerbated by anthropogenic activities. Although evidence remains limited, Hg may disrupt secretion of the pituitary hormone prolactin, a key regulator in the expression of avian parental care. In this study, we first evaluated whether prolactin secretion experienced a seasonal pattern across different stages of the breeding cycle in magnificent frigatebirds (Fregata magnificens) breeding in French Guiana. We then investigated whether Hg exposure was associated with prolactin secretion at any of these stages. Prolactin levels followed the expected seasonal pattern for altricial species, peaking during incubation, and declining sharply during chick-rearing in both sexes. Similarly low baseline prolactin levels were observed in displaying males and non-breeding adults. Prolactin levels did not differ between sexes. Despite high Hg concentrations in frigatebirds, Hg was not negatively associated with prolactin levels at any breeding stage. Our findings suggest that prolactin dynamics are closely linked to parental investment in breeding magnificent frigatebirds, but Hg contamination does not appear to impair prolactin at observed exposure levels. Further research is needed to determine whether Hg affects parental hormones in more sensitive altricial species, particularly during the critical, energetically demanding chick-rearing period.

PMID:42448267 | DOI:10.1016/j.envpol.2026.128780

Developmental neurotoxic effects of organophosphate flame retardants (OPFRs) across different life stages and the central role of pioneer transcription factors Neurog2/Ascl1 during the embryonic period - July 14, 2026

Environ Pollut. 2026 Jul 14:128679. doi: 10.1016/j.envpol.2026.128679. Online ahead of print.

ABSTRACT

In contemporary consumer products markets, organophosphorus flame retardants (OPFRs) are widely used, associated with non-carcinogenic health risks and exhibit multisystem toxicity. Based on the endocrine-disrupting properties, which are combined with the endocrine system's susceptibility and interaction with the nervous system during early developmental stages, developmental neurotoxicity (DNT) has been increasingly reported in epidemiological studies. Unfortunately, their toxic mechanisms remain unclear. Given the highly stage specific nature of neurogenesis-related gene expression across life stages, these mechanisms are highly time- and stage-dependent. This study employed network toxicology methods and machine learning algorithms to reveal that OPFRs cause abnormal protein translation during late embryonic neurogenesis by disrupting the expression of ribosome-associated genes-Rpl9, Rps21, Rps23, Rps28, and Rps29. Combining network toxicology with mouse cohort transcriptomics revealed that OPFRs induce DNT during early larval neurogenesis by disrupting the expression of pioneer transcription factors Neurog2 and Ascl1. Therefore, ribosome-associated genes and pioneer transcription factors can serve as sensitive candidate biomarkers in the mode of DNT action of OPFRs.

PMID:42448272 | DOI:10.1016/j.envpol.2026.128679

Mechanistic Insights into the capture of bisphenol homologs by macroporous chitosan-bentonite composite foams - July 14, 2026

Bioresour Technol. 2026 Jul 14:135401. doi: 10.1016/j.biortech.2026.135401. Online ahead of print.

ABSTRACT

PMID:42448113 | DOI:10.1016/j.biortech.2026.135401

Intervention Strategies using Agada (Ayurvedic Antitoxic Formulations) for Diseases caused by Endocrine Disruptors - July 14, 2026

Endocr Metab Immune Disord Drug Targets. 2026;26:e18715303426053. doi: 10.2174/0118715303426053260413072002.

ABSTRACT

INTRODUCTION: Chemicals consumed through food, water, air, and personal care products disrupt our endocrine system, contributing to a range of life-threatening diseases. Since this toxicity is cumulative, it is essential to incorporate the principles of toxicity treatment. The review was conducted to evaluate the potential utility of Agada formulations in managing diseases associated with endocrine-disrupting chemicals.

METHODS: Electronic searches were performed using terms "Agada", "Ayurveda", "antitoxic", "visha", "dūṣhivīṣha", "endocrine-disrupting chemicals", and "toxicity" including animal, clinical, or pharmacological studies of Agada formulations in any toxicant or cumulative toxin model; or conceptual reviews linking Agada to environmental/chemical toxicity. By reviewing Ayurvedic literature, studying research on Agada, and correlating the principles of treatment of dushivisha, this article examines the potential of Ayurvedic treatment for diseases induced by endocrine disruptors.

RESULTS: The conceptual framework of Dūṣhivīṣha provides a strong philosophical parallel to chronic low-dose EDC exposure, legitimizing research interest. Several formulations exhibit general antitoxic effects in chemical or drug toxicity models primarily mediated by antioxidant and anti- inflammatory mechanisms.

DISCUSSION: Agada formulations may offer an integrative approach to mitigating EDC-related diseases. Their known pharmacological actions, such as antioxidant activity, free radical scavenging, Nrf2 upregulation, NF-κB inhibition, and adaptogenic effects, align with the major pathophysiological pathways triggered by EDCs. However, the current evidence base is limited by the absence of standardized formulations, inconsistent dosing, lack of endocrine biomarker assessment, and a scarcity of clinical trials.

CONCLUSION: By applying the treatment principles of Garavisha (swallowed poison) and Dushivisha (latent poison), disorders resulting from endocrine disruptors can be effectively addressed using Agada directing to generate empirical evidences through clinical trials.

PMID:42444203 | DOI:10.2174/0118715303426053260413072002

Predicting the immunotoxic potential of chemical mixtures based on their endocrine activity profiles via computational modeling and in vitro bioassays - July 14, 2026

Environ Int. 2026 Jul 9;214:110413. doi: 10.1016/j.envint.2026.110413. Online ahead of print.

ABSTRACT

Exposure to endocrine disrupting chemicals (EDCs) is a known threat to the environment and human health, because EDCs can interfere with many developmental processes. As immune cells rely on signaling pathways than can be impacted by EDCs, the disruption of endocrine processes exhibits the potential to directly or indirectly adversely alter immune response. We employed a high-throughput in silico workflow to identify EDCs that are likely to alter endocrine and metabolic processes with direct or indirect immunotoxic potential. Initially included 83,693 chemicals were reduced to a priority list of 6,620 and matched with blood concentrations as reported in human biomonitoring studies. Mixtures in representative concentration ratios were prepared for five main groups of EDCs with five chemicals per mixture, covering per- and polyfluorinated compounds, halogenated pesticides, phthalates, phenols, and polycyclic aromatic hydrocarbons, and one mixture containing all 25 chemicals. Single compounds and mixtures were tested in high-throughput bioassays covering potential indirect modulators of immune response such as endocrine signaling through activation of estrogen receptor, androgen receptor, glucocorticoid receptor and aryl hydrocarbon receptor, thyroid hormone signaling through agonism and antagonism on the thyroid hormone receptor, thyroperoxidase inhibition, and transthyretin binding, or more direct endpoints such as pro-inflammatory signaling through the activation of nuclear factor κ-light-chain-enhancer of activated B cells, as well as redox and metabolic imbalance via oxidative stress response and mitochondrial disruption. 19 out of 33 bioactive mixtures confirmed concentration additivity across all tested endpoints within 3-fold deviation, indicating a clear relevance of commonly detected EDCs mixtures as potential immunomodulators.

PMID:42447793 | DOI:10.1016/j.envint.2026.110413

Plasticizing Diabetes Care: The Metabolic Threat of Plastic-Associated Endocrine Disruptors and Micro-/Nanoplastics in Clinical Medicine - July 13, 2026

Curr Diab Rep. 2026 Jul 13;26(1):21. doi: 10.1007/s11892-026-01635-4.

ABSTRACT

PURPOSE OF REVIEW: Diabetes care is characterized by the widespread use of plastics. With plastic-associated endocrine-disrupting chemicals (EDCs) implicated in diabetes pathogenesis, this review examines how medical plastics relate to diabetes and related disorders and proposes interventions to improve the situation.

RECENT FINDINGS: Plastic-associated EDCs and micro-/nanoplastics (MNPs) are linked to metabolic dysfunction. Medical care exposes patients to these agents; however, the precise contribution of diabetes care to these exposures and their associated adverse health effects remains poorly defined. Diabetes care is an increasingly important contributor to plastic pollution and climate change, yet inadequate systems exist to mitigate its environmental impact. Plastic-associated EDCs and MNPs remain an underappreciated metabolic health threat. Mitigating the deleterious impacts of plastics on human and planetary health requires concerted actions from manufacturers, scientists, policymakers, professional organizations, healthcare providers, and patients. Doing so has the potential to improve metabolic health and promote health equity.

PMID:42440155 | PMC:PMC13364795 | DOI:10.1007/s11892-026-01635-4

Protective effects of biogenic selenium nanoparticles synthesized by Chlorella Vulgaris against bisphenol a-induced metabolic disturbances in rats - July 13, 2026

Discov Nano. 2026 Jul 13;21(1):340. doi: 10.1186/s11671-026-04715-2.

ABSTRACT

BACKGROUND: Bisphenol A (BPA), a xenoestrogen and endocrine disruptor, is widely used in plastic and polycarbonate products, contributing to metabolic disorders such as dyslipidemia and obesity. Algae, like Chlorella vulgaris (CV), contain highly active compounds that act as natural reducing agents, converting inorganic selenium into nanoparticle form.

METHODS: In this study, we developed novel biologically synthesized selenium nanoparticles using CV (SeNPs-CV) and investigated their protective properties in comparison to physically synthesized selenium nanoparticles (SeNPs) against BPA-induced metabolic disturbances in rats. 40 male albino rats were allocated into four groups (n = 10) and received different oral treatments for 45 days: a control group, a BPA group (150 mg/kg/day), a SeNPs group (2 mg/kg/day alongside BPA), and a SeNPs-CV group (2 mg/kg/day alongside BPA).

RESULTS: BPA exposure caused oxidative stress and various metabolic disturbances, evidenced by changes in redox biomarkers, upregulation of fatty acid synthesis-related genes (SREBP1, FAS, ACC1, miRNA-122), and altered lipid profiles. Levels of leptin, adiponectin, NF-κB, TNF-α, and liver function markers were also affected. However, co-treatment with SeNPs and SeNPs-CV significantly alleviated these alterations caused by BPA. Histopathological analysis corroborated these biochemical findings, showing improved hepatic tissue structures with SeNPs and SeNPs-CV.

CONCLUSIONS: Overall, SeNPs-CV exhibit hypolipidemic, anti-inflammatory, and antioxidant properties that are on par with those of their physically synthesized equivalent, demonstrating their therapeutic potential and acting as an eco-friendly agent that promotes green innovation and environmental sustainability.

PMID:42440020 | PMC:PMC13365108 | DOI:10.1186/s11671-026-04715-2

Nutritional adaptation to circadian misalignment: implications for musculoskeletal health in modern lifestyles - July 13, 2026

Front Nutr. 2026 Jun 22;13:1833858. doi: 10.3389/fnut.2026.1833858. eCollection 2026.

ABSTRACT

Circadian rhythms regulate metabolic, endocrine, and cellular processes essential for maintaining musculoskeletal health. Accumulating experimental and epidemiological evidence indicates that circadian disruption, driven by modern lifestyle factors such as shift work, sleep restriction, and irregular eating patterns, is associated with an increased risk of musculoskeletal disorders. This narrative review summarizes current evidence linking circadian misalignment to alterations in bone, skeletal muscle, and cartilage biology. At the mechanistic level, disruption of core clock gene expression and desynchronization between central and peripheral clocks lead to hormonal imbalance, metabolic dysfunction, and chronic low-grade inflammation. These pathways are associated with bone loss, impaired muscle protein synthesis, and accelerated cartilage degeneration. Findings from both animal and human studies support associations with osteoporosis, sarcopenia, and osteoarthritis. Chrononutrition has emerged as a potential strategy to mitigate these effects. Approaches such as time-restricted eating, alignment of food intake with the biological day, and optimized protein distribution may help restore circadian alignment and improve musculoskeletal outcomes. In conclusion, integrating circadian biology with nutritional timing provides a promising framework for the prevention and management of musculoskeletal disorders, although large-scale human interventional trials with validated clinical endpoints are needed to confirm benefit.

PMID:42440614 | PMC:PMC13333481 | DOI:10.3389/fnut.2026.1833858

Integrated Proteomic and Phosphoproteomic Profiling Reveals Mechanisms of Bisphenol A Induced Placental Toxicity - July 13, 2026

Chem Res Toxicol. 2026 Jul 13. doi: 10.1021/acs.chemrestox.6c00191. Online ahead of print.

ABSTRACT

The global industrialization and rapid urbanization have elevated the risk of toxic pollutant exposure, which affects human health, especially during pregnancy. Pregnant mothers are daily exposed to bisphenol A (BPA), a common plastic leachate and a prominent toxic pollutant present in our environment. BPA acts as an endocrine-disrupting chemical (EDC) by altering feto-placental homeostasis. This persistent and potent exposure to BPA during gestation can trigger placental damage, affecting trophoblast cell function and survival. BPA even disrupts specific signaling cascades by altering post-translational protein phosphorylation. However, this BPA-mediated dysregulation of signaling nodes in the early trimester placenta remains unexplored. Therefore, this study investigates the global proteome changes in post-BPA-exposed extravillous trophoblast (EVT) cells, which revealed a BPA-mediated dynamic regulation of phospho-proteome signatures and their associated kinases. Further inspection shows that the altered phosphorylation of c-JUN (S63) and GSK3α (Y279) is associated with BPA toxicity in EVTs and the placenta. This altered phosphorylation affects cellular signaling downstream, imparting damage upon the growing feto-placental unit. This highlights an altered phosphorylation-mediated mechanism of BPA toxicity in the placenta, which can cause the onset of adverse pregnancy outcomes. Data are available via ProteomeXchange with the identifiers PXD074780 and PXD080006.

PMID:42440269 | DOI:10.1021/acs.chemrestox.6c00191

Metagenomic analysis of the vaginal microbiota in cows with ovarian cysts - July 13, 2026

J Vet Res. 2026 May 28;70(2):215-225. doi: 10.2478/jvetres-2026-0028. eCollection 2026 Jun.

ABSTRACT

INTRODUCTION: This study compared the vaginal microbiota composition of dairy cows with follicular and luteal ovarian cysts using metagenomic analysis.

MATERIAL AND METHODS: Ovarian cysts, which impair reproductive performance through endocrine disruption, were diagnosed by ultrasonography and serum hormone evaluation in Holstein cows 30-60 d postpartum. Forty-five cows were initially included and divided into follicular cyst, luteal cyst and control groups. Vaginal lavage samples were analysed using third-generation sequencing, and taxonomic classification was performed through 16S rRNA gene analysis.

RESULTS: A total of 258 operational taxonomic units (OTUs) were identified, with the highest diversity observed in the control group (mean of 56.8 OTUs) and the lowest in the luteal cyst group (mean of 49.0 OTUs). Proteobacteria was the dominant phylum across all groups (93.4%), followed by Tenericutes (5.9%). Firmicutes, Bacteroidetes and Fusobacteria accounted for less than 1%. At the family level, Burkholderiaceae (62.7%) and Pasteurellaceae (24.0%) were predominant, while of the genera, Ralstonia was the most abundant (62.2%). The luteal group had the highest relative abundance of Burkholderiaceae, whereas Pasteurellaceae was most abundant in the control group.

CONCLUSION: These results indicate that cystic cows exhibit reduced microbial diversity and altered bacterial composition in comparison with healthy animals. The predominance of Proteobacteria and Ralstonia suggests a potential link between endocrine imbalance and changes in the vaginal microenvironment. Hormonal analyses supported the classification of cyst types, with follicular cyst cows showing low progesterone (0.31 ± 0.05 ng/mL) and high oestradiol-17β concentrations (55.57 ± 7.91 pg/mL), whereas luteal cyst cows exhibited higher progesterone (2.89 ± 0.74 ng/mL) and lower oestradiol-17β concentrations (6.19 ± 0.56 pg/mL) (P < 0.001). These results may support future studies evaluating vaginal microbial profiles as complementary indicators of ovarian status in dairy cows.

PMID:42441094 | PMC:PMC13334294 | DOI:10.2478/jvetres-2026-0028

High-performance electrochemical sensing platform based on poly(arginine)@nickel ferrite nanocomposite-modified electrode for the detection of bisphenol a in food and environmental matrices - July 13, 2026

RSC Adv. 2026 Jul 6. doi: 10.1039/d6ra04423a. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a widespread industrial compound exploited mostly in the fabrication of epoxy resins and polycarbonate plastics, which are normally present in food containers, beverage bottles, and water pipes. As a renowned endocrine-disrupting chemical, BPA leaches from these materials into food and water, acting as a xenoestrogen that mimics natural estrogen in the human body, thus necessitating effective monitoring and removal strategies. Herein, a poly(arginine)@nickel ferrite, P-Arg@NiFe₂O₄, nanocomposite-based electrochemical sensor was constructed for identifying BPA in fruits and wastewater. The sensor leverages the magnetic and conductive properties of NiFe₂O₄ and the P-Arg's molecular recognition capability to enable sensitive detection. The synthesized materials were characterized using a complementary suite of analytical techniques such as XRD to analyze the crystalline structure, SEM to visualize surface morphology, and FT-IR spectroscopy to analyze the chemical composition and functional groups. A comprehensive approach to assess the performance, stability, and sensing mechanism of the developed sensor via pH optimization, cyclic voltammetry, and electrochemical impedance spectroscopy techniques was employed. Using differential pulse voltammetry, the sensor displayed a strong linear relationship with peak current and BPA levels across two ranges: 1.0 × 10^-3 to 1.0 × 10^-1 µM (R ² = 0.99962) and 5 × 10^-1 to 1 × 10² µM (R ² = 0.98757), with a 3.84 × 10^-4 µM detection limit. Recovery trials using fruit and wastewater samples verified the sensor's practical usability. Moreover, when numerous interfering substances and metal ions were present, the sensor demonstrated an outstanding selective detection of BPA. This is the first report on the fabrication and subsequent application of a P-Arg@NiFe₂O₄ nanocomposite for electrochemical identification of BPA.

PMID:42440842 | PMC:PMC13334381 | DOI:10.1039/d6ra04423a

Synergistic in silico models uncover endocrine and reproductive toxicity of organophosphates - July 13, 2026

iScience. 2026 Jun 12;29(7):116363. doi: 10.1016/j.isci.2026.116363. eCollection 2026 Jul 17.

ABSTRACT

Organophosphates (OPs) are ubiquitous environmental contaminants used in applications ranging from agriculture to home electronics. Their endocrine-disrupting properties have primarily been investigated for a limited number of legacy compounds. Here, we developed an in silico model integrating spherical harmonics, QSAR, and molecular docking, with 97% sensitivity for estrogen receptor (ER) disruptors, validated against in vitro assays targeting ERα and androgen receptor (AR), to assess endocrine activity across 42 OPs and commercial mixtures. A large proportion (88%) disrupted ERα and/or AR at sub-toxic levels, with aryl and triaryl phosphates showing the strongest effects and frequent dual receptor activity. Docking analyses indicate that many OPs interact within the ERα ligand-binding domain through predominantly hydrophobic contacts, showing ∼60% overlap with estradiol-binding residues, while reduced polar interactions may explain their antagonistic behavior. Endocrine activity was consistent with reproductive toxicity evidence. A distinct OP sub-cluster exhibited inactivity driven by steric constraints and limited flexibility.

PMID:42441274 | PMC:PMC13335010 | DOI:10.1016/j.isci.2026.116363

Biomass - derived N-doped carbon-supported CuMnO<sub>2</sub> for efficient bisphenol A degradation <em>via</em> visible light - activated peroxymonosulfate: synergistic radical and non-radical pathways - July 13, 2026

RSC Adv. 2026 Jul 6. doi: 10.1039/d6ra00777e. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is an endocrine-disrupting contaminant frequently detected in natural and engineered waters. Visible-light-driven peroxymonosulfate (PMS) activation offers a sustainable and efficient route for BPA abatement. Herein, a novel biomass-derived heterogeneous catalyst, crednerite CuMnO₂ anchored on N-doped rice-straw-lignin-derived carbon (RS-LC(N)), was successfully developed for BPA degradation via visible-light/PMS activation. The catalyst exhibited outstanding kinetics at neutral pH, achieving a pseudo-first-order rate constant (k _obs) of 0.1989 min^-1 under optimized conditions (10 mg L^-1 BPA, 1.0 mM PMS, and a catalyst dose of 1.0 g L^-1). Radical scavenging experiments revealed a dominant radical pathway (SO₄˙^-/˙OH), accompanied by a complementary non-radical contribution involving singlet oxygen (¹O₂) and interfacial electron-transfer mechanisms (ETM). LC-MS/MS (liquid chromatography - tandem mass spectrometry) analysis identified BPA transformation products consistent with two major degradation routes, including radical-mediated hydroxylation/ring cleavage and non-radical oxidation via ¹O₂/ETM, ultimately leading to mineralization. Structural characterization indicated that increasing CuMnO₂ loading moderately reduced the specific surface area while maintaining favorable mass transfer and adsorption characteristics at neutral pH. The catalyst exhibited good tolerance toward complex water matrices, with decreasing k _obs observed from deionized water to natural waters, treated wastewater, and brackish water, in agreement with increasing ionic strength and dissolved organic matter. Excellent stability was demonstrated over five consecutive cycles, with negligible morphological or phase changes and minimal activity loss. Metal leaching remained at the low 10^-2% level and further decreased with repeated use, highlighting the environmental robustness of the catalyst.

PMID:42441115 | PMC:PMC13335193 | DOI:10.1039/d6ra00777e

Maternal di-n-butyl phthalate exposure promotes renal fibrosis in IUGR offspring rats via HBB downregulation and Nrf2 pathway activation - July 13, 2026

Ecotoxicol Environ Saf. 2026 Jul 13;322:120449. doi: 10.1016/j.ecoenv.2026.120449. Online ahead of print.

ABSTRACT

Di-n-butyl phthalate (DBP) is an environmental endocrine disruptor with developmental nephrotoxicity, but its long-term effects on renal fibrotic remodeling in offspring remain incompletely understood. In this study, a maternal DBP exposure model was established in pregnant Sprague-Dawley rats (750 mg/kg/day, GD14-GD18), and adult male offspring were examined at postnatal day 42. DBP-exposed offspring showed intrauterine growth restriction, reduced relative kidney weight, renal collagen deposition, and epithelial-mesenchymal transition (EMT)-related molecular changes. Transcriptomic analysis identified hemoglobin subunit beta (HBB) as a prominently downregulated gene in renal tissues of DBP-exposed offspring. HBB expression was reduced by approximately four-fold and was accompanied by increased oxidative stress, including elevated reactive oxygen species and malondialdehyde levels and decreased total superoxide dismutase activity. DBP exposure was also associated with increased expression of NRF2 and its downstream antioxidant targets HO-1 and NQO1. In HK-2 cells, HBB overexpression attenuated DBP-induced oxidative stress and EMT-related marker changes, while N-acetylcysteine (NAC) reduced oxidative stress and restored HBB and EMT-related protein expression. In adult male offspring, renal AAV-HBB delivery partially restored HBB expression and reduced DBP-associated collagen deposition, oxidative stress, and EMT-related changes. These findings indicate that maternal DBP exposure is associated with adult renal fibrotic remodeling in male offspring, with HBB downregulation, oxidative stress, NRF2-related antioxidant responses, and EMT-related alterations as key molecular features. HBB may serve as a candidate biomarker and intervention target for DBP-associated developmental nephrotoxicity, pending further validation.

PMID:42442276 | DOI:10.1016/j.ecoenv.2026.120449

Bisphenol exposure and gynecological health: A narrative review of current evidence and knowledge gaps - July 13, 2026

Chemosphere. 2026 Jul 13;410:145027. doi: 10.1016/j.chemosphere.2026.145027. Online ahead of print.

ABSTRACT

The widespread use of plastic has led to exposure to chemicals like bisphenols (BPs), particularly bisphenol A (BPA), which are crucial in the production of polycarbonate plastics and epoxy resins. Recent studies have raised concerns about the effect of bisphenols as endocrine disruptors as the risk factor for hormone-dependent gynecological diseases. Taking into attention the mechanism of BPs' action, particularly their ability to bind to estrogen receptors and subsequently activate further estrogen pathways, it seems essential to understand their impact on different diseases. Moreover, it is not only the estrogen pathway, which is activated, but also signaling pathways, contributing to cell proliferation and potentially leading to carcinogenesis, particularly in tissues with hormonal dependencies. This review examines the mechanisms by which BPs interact with hormonal pathways and highlights their potential role in various hormone-related conditions, including benign gynecological diseases: endometriosis and polyendocrine metabolic ovarian syndrome (PMOS)/polycystic ovary syndrome (PCOS) and female gynecological cancers concerning breast, uterus and ovaries. The review also highlights the need to re-evaluate pre-analytical, analytical, and post-analytical standard operating procedures to reduce confounding factors in measuring BPs in clinical samples and to better model their potential roles as risk factors in disease etiology.

PMID:42442086 | DOI:10.1016/j.chemosphere.2026.145027

Predictors of bisphenol A exposure in pregnant women of the Barwon Infant Study - July 13, 2026

Toxicol Lett. 2026 Jul 13:113165. doi: 10.1016/j.toxlet.2026.113165. Online ahead of print.

ABSTRACT

Bisphenol-A (BPA) is a widely used chemical used in plastic and an endocrine disruptor ubiquitous in most developed settings. Exposure, particularly in early life, is implicated in a range of negative health outcomes. This study assessed whether various sources of BPA exposure in pregnant women, including diet, food preparation practices and personal care product use, are relevant predictors of measured BPA concentrations. Exposures were assessed via questionnaires. Maternal urine samples from 842 mothers were collected in trimester 3 and analysed for five bisphenols from the Barwon Infant Study, (infants born 2010-2013). Measurable BPA concentrations were detected in 54% of women. Positive associations with urinary BPA concentrations were observed for food-related factors, including a contemporaneous whole-foods dietary pattern and the proportion of raw foods introduced to the infant at 12 months, as well as renovation activities and use of dermal or spray products such as insect repellents. In contrast, cleaning frequency was negatively associated with BPA concentrations. Notably, women who reported attempting to reduce or avoid BPA exposure during pregnancy did not have lower urinary BPA concentrations. Findings show that BPA exposure goes beyond dietary and other ingestion-related factors, also occur via inhalation and skin absorption from the home environment and personal care products, respectively. Household cleaning practices offer a potential opportunity to reduce population-level exposure. The knowledge generated here will inform the design of bisphenol-reducing interventions for pregnant women or women of reproductive age.

PMID:42442490 | DOI:10.1016/j.toxlet.2026.113165

Neurosci Biobehav Rev. 2026 Jul 13;189:106869. doi: 10.1016/j.neubiorev.2026.106869. Online ahead of print.

ABSTRACT

Sleep disruption is a hallmark of aging and a plausible driver of Alzheimer's disease vulnerability. Reduced slow-wave sleep, increased fragmentation, and circadian instability may facilitate amyloid-β accumulation, tau propagation, neuroinflammation, oxidative stress, and impaired glymphatic clearance. Yet the physiological factors that predispose older adults to unstable sleep remain insufficiently integrated into models of brain aging. This Review advances a sleep-muscle-brain framework in which sarcopenia, sarcopenic obesity, and insulin resistance are conceptualized as modifiable muscle-metabolic conditions that may bias sleep continuity and shape the biological impact of sleep disruption. We examine irisin/FNDC5-BDNF signaling as a hypothesis-generating candidate modifier of metabolic regulation, neurotrophic support, and brain resilience, while emphasizing that direct evidence for a causal role in human sleep regulation remains insufficient. Irisin-related pathways intersect with insulin sensitivity, inflammatory control, and BDNF-dependent synaptic plasticity, all of which are relevant to the physiological context in which sleep disruption may influence Alzheimer's disease pathophysiology. We propose that age-related attenuation of muscle endocrine signaling, together with insulin resistance and low-grade inflammation, may lower the threshold at which sleep fragmentation translates into amyloid/tau dyshomeostasis, glial activation, and network dysfunction. Rather than treating sleep disturbance as an isolated brain-centered risk factor, this framework positions sleep as a biobehavioral hub through which peripheral aging processes can modulate neurodegenerative resilience. The Review integrates evidence from sleep neuroscience, geroscience, metabolism, and neurodegeneration, and identifies experimentally testable predictions. A sleep-muscle-brain perspective may help refine risk stratification and guide multimodal interventions combining sleep optimization, resistance exercise, metabolic targeting, and Alzheimer's disease biomarker monitoring.

PMID:42442566 | DOI:10.1016/j.neubiorev.2026.106869

Bisphenol A concentrations in isot spice and associated health risk assessment using Monte Carlo simulation in Türkiye - July 13, 2026

Regul Toxicol Pharmacol. 2026 Jul 13;171:106179. doi: 10.1016/j.yrtph.2026.106179. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, yet its potential migration into traditional spice matrices during processing remains a critical and overlooked food safety concern. To address this knowledge gap, this study presents the first comprehensive investigation of BPA concentrations in isot spice and assesses the associated dietary health risks. A total of 46 samples (23 homemade and 23 industrial) from Şanlıurfa, Turkey, were analyzed using a validated ELISA kit, along with pH and CIELAB color parameters. Estimated Daily Intake (EDI) and Target Hazard Quotient (THQ) were calculated for adult and pediatric populations using Monte Carlo simulations. BPA concentrations ranged from 0.40 to 361.30 μg/kg (mean: 73.88 ± 19.15 μg/kg) in homemade samples and from 0.49 to 285.39 μg/kg (mean: 67.15 ± 14.87 μg/kg) in industrial samples, with no significant differences between groups (p > 0.05). While dietary risks were within safe limits according to US EPA doses, assessment based on stricter European Food Safety Authority (EFSA) thresholds revealed that THQ values significantly exceeded 1, particularly for children, indicating potential chronic health risks. These findings highlight the prevalence of BPA in traditional spices and underscore the need for improved production and packaging practices to reduce consumer exposure.

PMID:42442595 | DOI:10.1016/j.yrtph.2026.106179

Plasticizing Diabetes Care: The Metabolic Threat of Plastic-Associated Endocrine Disruptors and Micro-/Nanoplastics in Clinical Medicine - July 13, 2026

Curr Diab Rep. 2026 Jul 13;26(1):21. doi: 10.1007/s11892-026-01635-4.

ABSTRACT

PMID:42440155 | PMC:PMC13364795 | DOI:10.1007/s11892-026-01635-4

Fine Particulate Matter (PM2.5), the Exposome, and Cumulative Health Risk: A Life-course Perspective - July 13, 2026

J Prev Med Public Health. 2026 Jul 1. doi: 10.3961/jpmph.26.219. Online ahead of print.

ABSTRACT

Fine particulate matter (PM2.5; aerodynamic diameter ≤2.5 µm) is a leading contributor to the global burden of disease and is associated with substantial morbidity and mortality. However, its health effects are often evaluated within single-exposure frameworks, limiting causal inference and reducing the translational relevance of evidence for policy development. In this study, we reconceptualise PM2.5 within the exposome framework by integrating external exposures, internal biological responses, and structural determinants of health across the life course. PM2.5 comprises a complex and dynamic mixture of pollutants from ambient and household sources, including biomass combustion, traffic emissions, and industrial activities. After inhalation, PM2.5 particles can penetrate the respiratory tract, and finer fractions may enter the systemic circulation, where they induce oxidative stress, inflammation, epigenetic dysregulation, and endocrine disruption. These mechanisms contribute to a broad spectrum of adverse health outcomes, including cardiovascular, respiratory, metabolic, and neurodegenerative diseases as well as cancers. The multi-level and temporally accumulated nature of these effects highlights the limitations of reductionist exposure assessment and underscores the need for integrative, systems-based approaches. Integrating cumulative impact assessment with exposome-wide approaches that leverage satellite, clinical, land-use, urban planning, and socioeconomic data can improve the characterisation of context-specific cumulative health effects. Positioning PM2.5 as a sentinel indicator of cumulative environmental risk provides a unifying framework for exposome-informed science and supports the development of more precise, equitable, and policy-relevant interventions.

PMID:42442744 | DOI:10.3961/jpmph.26.219

Disruption of GABAergic and GH/IGF-related signaling is associated with growth inhibition induced by dibutyl phthalate and dibutyl adipate in zebrafish - July 13, 2026

Comp Biochem Physiol C Toxicol Pharmacol. 2026 Jul 13:110625. doi: 10.1016/j.cbpc.2026.110625. Online ahead of print.

ABSTRACT

Dibutyl phthalate (DBP) and dibutyl adipate (DBA) are commonly used plasticizers that may pose risks to aquatic organisms. This study investigated whether DBP and DBA disrupt larval growth through neuroendocrine pathways using zebrafish (Danio rerio) as an in vivo model. Embryos were continuously exposed to DBP or DBA for 96 h, and growth-related morphological, transcriptional, and protein-level endpoints were assessed. DBP significantly reduced larval body length and increased locomotor activity, accompanied by decreased growth hormone (GH), insulin-like growth factor-1 (IGF-1), and gamma-aminobutyric acid-A (GABA) receptor alpha 2 protein levels, as well as marked suppression of gh1, igf1, gad2, gabrb2, and gabrg2 expression. DBA produced qualitatively similar but consistently weaker effects, primarily affecting growth endpoints and selected neuroendocrine markers. Continuous co-exposure with the GABA_A receptor antagonist bicuculline or the IGF-1 receptor inhibitor picropodophyllin did not further exacerbate growth inhibition or IGF signaling suppression compared with DBP or DBA exposure alone, revealing a non-additive interaction pattern. These findings suggest that DBP and DBA may impair larval growth through disruption of GABAergic and GH/IGF-related neuroendocrine regulation. Together, the results provide insight into the potential neuroendocrine mechanisms underlying plasticizer-induced developmental toxicity.

PMID:42442644 | DOI:10.1016/j.cbpc.2026.110625

Network toxicology and molecular docking reveal the mechanistic basis of bisphenol A-mediated cholestatic liver injury - July 12, 2026

Toxicol Rep. 2025 Nov 15;17:102167. doi: 10.1016/j.toxrep.2025.102167. eCollection 2026 Dec.

ABSTRACT

BACKGROUND: Bisphenol A (BPA), a widespread environmental endocrine-disrupting chemical, is suspected to contribute to liver injury, yet the underlying mechanisms, particularly for cholestatic liver injury (CLI), remain poorly defined. This study aims to systematically elucidate the molecular pathways by which BPA induces CLI.

METHODS: We applied an integrated network toxicology approach. BPA targets were predicted using chemical databases (ChEMBL, SwissTargetPrediction, TargetNet), while disease targets for CLI were sourced from GeneCards and OMIM. Bioinformatics analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were conducted on overlapping genes. A protein-protein interaction network was constructed to identify hub genes, followed by molecular docking simulations to validate BPA's binding affinity to these key targets.

RESULTS: We identified 200 common genes linking BPA exposure to CLI. Pathway analysis revealed that BPA perturbs multiple biological processes, including chemical detoxification, energy metabolism, inflammation, and bile secretion. Ten core genes (TP53, TNF, and key CYP450 enzymes) were pinpointed as central players. Molecular docking confirmed that BPA binds strongly to these hub targets, substantiating their mechanistic role.

CONCLUSION: Our findings provide a comprehensive mechanistic framework explaining how BPA exposure may lead to cholestatic liver injury. The study establishes a novel predictive strategy for evaluating the hepatotoxicity of environmental pollutants.

PMID:42437265 | PMC:PMC13355015 | DOI:10.1016/j.toxrep.2025.102167

Hyperparathyroidism: current concepts in diagnosis and surgical treatment - July 11, 2026

Front Endocrinol (Lausanne). 2026 Jun 26;17:1809252. doi: 10.3389/fendo.2026.1809252. eCollection 2026.

ABSTRACT

Hyperparathyroidism (HPT) is a complex endocrine disorder characterized by the dysregulated secretion of parathyroid hormone (PTH), leading to significant disruptions in calcium and phosphate homeostasis. This review provides a comprehensive analysis of the condition, beginning with the distinct clinical and biochemical profiles of its primary, secondary, and tertiary forms. It critically examines the evolving diagnostic pathways and the refined indications for surgical intervention, which remains the only curative treatment for primary HPT and a crucial therapy for advanced secondary and tertiary disease. Central to the discussion is a detailed exploration of modern surgical strategies, highlighting the paradigm shift from traditional bilateral neck exploration to precision-focused, minimally invasive parathyroidectomy, enabled by advanced preoperative localization and intraoperative PTH monitoring. The review further considers outcomes, postoperative management, and emerging techniques, including remote-access endoscopic approaches. By synthesizing current evidence and guidelines, this work aims to delineate a holistic framework for the effective management of HPT, from accurate diagnosis through to the selection and execution of the optimal surgical treatment strategy.

PMID:42434307 | PMC:PMC13350269 | DOI:10.3389/fendo.2026.1809252

Plastics as disruptors of feeding, digestive physiology, metabolism, and growth in fish and other aquatic ectothermic vertebrates - July 11, 2026

Front Endocrinol (Lausanne). 2026 Jun 26;17:1873239. doi: 10.3389/fendo.2026.1873239. eCollection 2026.

ABSTRACT

Plastics, particularly microplastics (MPs) and nanoplastics (NPs), are widespread contaminants in aquatic ecosystems that affect key physiological processes related to feeding, digestion, metabolism, and growth in aquatic ectotherms, particularly fish. Increasing evidence indicates that plastic exposure disrupts energy balance by reducing food intake through false satiety, gastrointestinal obstruction, and behavioral alterations, while also impairing digestive efficiency, nutrient absorption, and metabolic regulation. MPs and NPs can interfere with endocrine signaling pathways involved in appetite regulation. They may also disrupt the thyroid axis, a key regulator of metabolism and energy expenditure, and the growth hormone/insulin-like growth factor axis, which controls somatic growth and nutrient partitioning. These endocrine disturbances are often accompanied by oxidative stress, impaired hepatic function and gastrointestinal integrity, ultimately affecting growth performance, energy allocation, and overall fitness. While these effects are best documented in fish, amphibians show similar but less well-characterized responses, whereas evidence in reptiles remains limited and largely observational. The impacts of plastics are further modulated by environmental conditions associated with climate change. Factors such as temperature and salinity can influence the uptake, bioavailability, and toxicity of MPs and NPs, often exacerbating their effects on feeding behavior, metabolic performance, and endocrine function. In addition, climate-driven processes -including warming, extreme weather events, and changes in ocean circulation - can alter the breakdown, transport, and distribution of plastics, potentially increasing exposure risks. However, high heterogeneity in experimental protocols, such as differences in plastic characteristics, exposure concentrations and durations, species, and life stages, limits direct comparison across studies. This review synthesizes current knowledge on the effects of plastic exposure on feeding, digestion, metabolism, and growth in aquatic ectotherms, with a particular focus on fish, while integrating available evidence from amphibians and reptiles. It also highlights underlying mechanisms and the influence of environmental conditions, with implications for fish health, aquaculture productivity, and ecosystem functioning in increasingly polluted aquatic environments.

PMID:42434309 | PMC:PMC13349886 | DOI:10.3389/fendo.2026.1873239

Plastics as disruptors of feeding, digestive physiology, metabolism, and growth in fish and other aquatic ectothermic vertebrates - July 11, 2026

Front Endocrinol (Lausanne). 2026 Jun 26;17:1873239. doi: 10.3389/fendo.2026.1873239. eCollection 2026.

ABSTRACT

PMID:42434309 | PMC:PMC13349886 | DOI:10.3389/fendo.2026.1873239

Bridging the green skills gap: a framework to align the pharmaceutical workforce with sustainable drug discovery - July 11, 2026

Future Med Chem. 2026 Jul 11:1-9. doi: 10.1080/17568919.2026.2699691. Online ahead of print.

ABSTRACT

BACKGROUND: The pharmaceutical industry's R&D model faces unsustainable costs and environmental impact, yet educational pipelines lag in integrating AI and green chemistry skills essential for modern drug discovery.

METHODS: We conducted cheminformatics analysis of 50,000 bioactive compounds from ChEMBL v35 to quantify AI-driven discovery advantages. Natural language processing with BioBERT embeddings systematically analyzed international accreditation standards (ACPE, EAFP).

RESULTS: AI-driven approaches achieved 99.998% reduction in experimental burden and 32% lower endocrine disruption potential versus traditional high-throughput screening. Accreditation analysis revealed a critical deficit: mean Sustainability Integration Score of only 18.3% (range: 9.5-27.1%; SD = 6.2). The observed reductions in endocrine disruption potential and predicted E-factors for AI-designed compounds should be interpreted as signals of favorable computational toxicology profiles within the dimensions assessed, rather than comprehensively validated environmental safety.

CONCLUSIONS: We introduce the Accreditation-Aligned Sustainable Education (AASE) framework and GreenMedSim computational sandbox - an experiential platform virtualizing wet-lab activities for iterative molecular design. GreenMedSim is presented as a theoretically grounded and computationally specified educational prototype; empirical user trials and learning outcome data are planned for Phase 1 implementation (2026-2027).This work provides an actionable strategy aligning pharmaceutical workforce training with sustainable drug development, directly supporting UN Sustainable Development Goals 4.7, 9, and 12.

PMID:42434820 | DOI:10.1080/17568919.2026.2699691

Monomethyl phthalate promotes hepatocellular carcinoma progression through MMP9 upregulation - July 11, 2026

Cell Oncol (Dordr). 2026 Jul 11. doi: 10.1007/s13402-026-01265-8. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma (HCC) is recognized as the third leading cause of cancer-related death worldwide, and its epidemiological features are shifting from viral to non-viral etiologies. Phthalates (PAEs) are widely used plastic additives and major indoor environmental pollutants. Monomethyl phthalate (MMP), the primary hepatic metabolite of dimethyl phthalate, possesses endocrine-disrupting and immunosuppressive properties; however, whether a causal association exists between MMP and HCC remains unclear. Two-sample Mendelian randomization (MR) analysis with stringent instrumental variable selection criteria was performed to explore the association between MMP exposure and HCC. In addition, network toxicology, molecular docking, molecular dynamics simulations, together with TCGA database-based differential expression and survival analyses were conducted to identify core targets through which MMP promotes HCC. The specific mechanisms by which MMP facilitates HCC progression were investigated using CCK-8 assays, wound healing assays, and Western blot. MR analysis provided preliminary genetic evidence for a positive association between MMP exposure and elevated HCC risk, with no significant heterogeneity or horizontal pleiotropy detected. MMP promoted the proliferation and migration of HuH-7 cells in a dose-dependent manner. Six core targets were further identified, among which MMP9 was highly expressed in HCC and associated with poor prognosis. Inhibition of MMP9 significantly reversed the MMP-induced pro-carcinogenic effects, indicating that MMP promotes HCC by upregulating MMP9 expression. This study is the first to demonstrate that MMP contributes to HCC pathogenesis through the upregulation of MMP9, providing a novel biomarker and therapeutic target for HCC prevention and environmental risk control.

PMID:42435151 | DOI:10.1007/s13402-026-01265-8

An aptamer-integrated bimetallic MOF nanozyme for dual-mode colorimetric and fluorescence sensing of bisphenol A - July 11, 2026

Talanta. 2026 Jul 10;311:130273. doi: 10.1016/j.talanta.2026.130273. Online ahead of print.

ABSTRACT

As a representative endocrine-disrupting compound, bisphenol A (BPA) can leach from food packaging materials into food, thereby presenting potential risks to human health. Therefore, the development of rapid, sensitive, and reliable methods for BPA detection is of great importance. In this study, a dual-mode colorimetric/fluorescence aptasensor based on Cu/Zr-MOF nanozyme was developed for BPA detection, providing both colorimetric and fluorescence signal readouts. The aptasensor was immobilized on the Cu/Zr-MOF surface through coordination between Zr⁴⁺ sites and the phosphate group of the aptamer. Aptamer modification blocked the active sites of Cu/Zr-MOF, thereby suppressing its peroxidase-like activity and quenching the fluorescence signal in the Cu/Zr-MOF + TMB + H₂O₂ system. Upon exposure to BPA, the aptamer specifically recognized and bound BPA, leading to its dissociation from the Cu/Zr-MOF surface. Consequently, both the POD activity of Cu/Zr-MOF and the fluorescence intensity of the system were restored. Under optimal conditions, the aptasensor displayed linear ranges of 1-300 ng/mL (colorimetric) and 0.500-400 ng/mL (fluorescence), with detection limits of 0.084 and 0.053 ng/mL, respectively. This dual-mode design provided two signal outputs, thereby improving detection reliability over single-mode systems and enabling flexible mode selection based on the testing environment. The sensing system was further extended to paper-based test strips, affording linear ranges of 1-150 ng/mL for both modes and detection limits of 0.140 ng/mL (colorimetric mode) and 0.227 ng/mL (fluorescence mode). These results demonstrate that the proposed Cu/Zr-MOF@Apt sensing platform has promising potential for rapid on-site BPA detection in food safety and environmental monitoring applications.

PMID:42435546 | DOI:10.1016/j.talanta.2026.130273

Organ-specific carcinogenic risk heterogeneity of perfluorooctanoic acid exposure: Global evidence from bibliometric mapping, meta-analysis, and nonlinear dose-response modeling - July 11, 2026

J Hazard Mater. 2026 Jun 28;514:142831. doi: 10.1016/j.jhazmat.2026.142831. Online ahead of print.

ABSTRACT

To address the long-standing inconsistency in Perfluorooctanoic Acid (PFOA)-related carcinogenic evidence, a stepwise analytical framework was developed that integrated CiteSpace-based global hotspot mapping, organ-specific meta-analysis, and nonlinear restricted cubic spline (RCS) dose-response modeling to move from research landscape identification to quantitative heterogeneity synthesis and internal dose-based risk estimation. Bibliometric results revealed a recent frontier shift from organ-specific cancer risks toward serum PFOA biomonitoring, mixed exposure assessment, and endocrine-disruptive mechanisms, providing the conceptual basis for organ-oriented evaluation. Meta-analysis of 34 datasets across the four organ-specific cancers most associated with PFOA exposure demonstrated a heterogeneous and divergent risk profile, with modest yet measurable cumulative elevations in cancer risk of kidney (odds ratio (OR) = 1.27; 95% confidence interval (CI), 1.01-1.59; P = 0.04), borderline statistical significance in breast cancer risk (OR = 1.13; 95% CI: 1.00-1.27; p = 0.04), while liver cancers (OR = 1.02; 95% CI: 0.95-1.09; p = 0.64) and thyroid cancers (OR = 0.90; 95% CI: 0.76-1.05; p = 0.19) were statistically non-significant. The dose-response risk estimation with the RCS model further uncovered distinct nonlinear carcinogenic architectures, as characterized by Odds Ratios varying with serum/plasma PFOA concentration, including cumulative amplification in kidney, borderline statistical accumulation in breast cancers, and adaptive, non-monotonic modulation in liver and thyroid cancers. These findings highlighted organ-specific susceptibility rather than uniform carcinogenicity and advance a biomarker-driven, nonlinear, and prediction-oriented paradigm for global environmental carcinogenic risk assessment, providing mechanistically informed evidence to refine PFAS regulatory prioritization and precision public health decision-making.

PMID:42435682 | DOI:10.1016/j.jhazmat.2026.142831

Pesticides derived from egg yolks modulate cellular metabolic activity and proliferation, and increase steroidogenesis and oxidative stress in primary pheasant ovarian cells - July 11, 2026

Environ Toxicol Pharmacol. 2026 Jul 11;125:105093. doi: 10.1016/j.etap.2026.105093. Online ahead of print.

ABSTRACT

To investigate pesticide impacts on declining French pheasant populations, unhatched wild eggs were screened for over 600 compounds using mass spectrometry, identifying a mixture of six pesticides. Pheasant ovarian cells (granulosa (GCs) and theca interstitial (TICs) were exposed in vitro to this mixture at environmentally relevant concentrations in basal state and in response to exogenous hormones (IGF-1 and gonadotropins). Effects were evaluated using CCK8 (cellular metabolic activity), BrdU (proliferation), ELISA (hormone production), and RTqPCR (gene expression). While cellular metabolic activity mainly increased, proliferation significantly decreased. Basal and stimulated progesterone and testosterone production increased in GCs and TICs, respectively. Furthermore, TOS, TAC, and OSI analyses revealed marked oxidative stress in both cell types, accompanied by the upregulation of genes involved in mitochondrial fusion including MFN1 in GCs. Overall, these endocrine and cellular disruptions could contribute to the ongoing decline of bird populations across agricultural landscapes.

PMID:42435976 | DOI:10.1016/j.etap.2026.105093

Organ-specific carcinogenic risk heterogeneity of perfluorooctanoic acid exposure: Global evidence from bibliometric mapping, meta-analysis, and nonlinear dose-response modeling - July 11, 2026

J Hazard Mater. 2026 Jun 28;514:142831. doi: 10.1016/j.jhazmat.2026.142831. Online ahead of print.

ABSTRACT

PMID:42435682 | DOI:10.1016/j.jhazmat.2026.142831

Stem Cells of the Hypothalamic-Pituitary-Adrenal Axis - July 11, 2026

Endocr Rev. 2026 Jul 11:bnag024. doi: 10.1210/endrev/bnag024. Online ahead of print.

ABSTRACT

Endocrine tissues must continuously adjust their structure and function in response to circadian cues, metabolic state, and physiological stress. Within these dynamic systems, stem cells contribute not only to tissue maintenance and repair but also to functional plasticity. The hypothalamic-pituitary-adrenal (HPA) axis exemplifies this integration of local stem cell regulation with systemic endocrine control. In this Review, we highlight the shared regulatory principles and tissue-specific adaptations of stem cell populations across the hypothalamus, anterior pituitary and adrenal gland. We discuss tanycytes as hypothalamic stem cells, SOX2+ stem cells as key regulators of pituitary plasticity, and multipotent and lineage-restricted progenitors that sustain adrenal cortical and medullary renewal. Across HPA axis organs, conserved signaling pathways and multiple modes of cell-cell communication, including paracrine and feedback mechanisms, coordinate stem cell behavior with endocrine output. Importantly, we present growing evidence that endocrine stem cells influence organ function beyond direct cell replacement, shaping tissue responsiveness, and adaptation to physiological demand. Disruption of these processes contributes to endocrine dysfunction and tumorigenesis. Integrating insights from genetic models, human single-cell and spatial atlases, we outline how viewing the HPA axis as an integrated stem cell system provides a framework for understanding endocrine plasticity and identifies emerging opportunities and challenges for regenerative and therapeutic strategies.

PMID:42433191 | DOI:10.1210/endrev/bnag024

Occurrence and toxicity mechanisms of hexafluoropropylene oxide dimer acid (HPFO-DA, GenX) in aquatic species - July 10, 2026

Environ Sci Process Impacts. 2026 Jul 10. doi: 10.1039/d5em00971e. Online ahead of print.

ABSTRACT

Hexafluoropropylene oxide dimer acid (HPFO-DA) is marketed under the trade name "GenX" and is used as a replacement for other per- and polyfluoroalkyl substance (PFAS) like perfluorooctanoic acid (PFOA). However, there are growing concerns about its regulation due to environmental and health impacts in organisms. Here, we review literature regarding the prevalence and toxicity of GenX in aquatic species and performed molecular docking and computational analysis to identify mechanisms of GenX-induced toxicity. Studies report measurable body burden levels of GenX in fish and other aquatic species, indicating that exposure and uptake do occur, which can lead to sub-lethal biological effects (e.g., developmental toxicity, oxidative stress, metabolic disruption, immune modulation, endocrine activity, neurobehavioral alterations). Effects on hormone receptor - mediated signaling (i.e., estrogenic and thyroid pathways) were noted based on computational analysis. In silico molecular docking of GenX to several fish receptors (e.g., estrogen, androgen, and thyroid hormone receptors) supported the potential for GenX to interact with key nuclear receptors, suggesting plausible mechanisms of endocrine disruption in fish. Molecular and omics-based analyses also revealed that GenX interferes with several pathways related to lipid and energy metabolism, as well as redox balance. Notably, several transcripts altered in abundance by GenX are related to the AGE-RAGE signaling pathway (Advanced Glycation End products (AGEs) bind to the Receptor for Advanced Glycation End products (RAGE)), which is related to oxidative stress and inflammation, and glucagon receptor (GCGR) signaling that activates transcription factors like CREB/CRTC2 and FOXO1 to promote gluconeogenesis. This review underscores useful toxicological endpoints for GenX in aquatic animals to guide future risk assessments.

PMID:42429221 | DOI:10.1039/d5em00971e

Structure-activity relationship of per- and Polyfluoroalkyl substances as inhibitors of human and rat 17β-Hydroxysteroid dehydrogenase 3 - July 10, 2026

Toxicol Appl Pharmacol. 2026 Jul 10;515:117937. doi: 10.1016/j.taap.2026.117937. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals as carboxylic acid (PFCA) and sulfonic acid (PFSA) found in everyday products, from non-stick cookware to waterproof clothing, and are potential endocrine disruptors. However, whether they inhibit 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) and structure-activity relationship (SAR) and mode of action remains unclear. In this study, we screened 18 PFAS (11 PFCAs and 7 PFSAs) with different carbon-chain lengths from C4 to C14 to inhibit human and rat 17β-HSD3 from HSD17B3-overexpressed LNCaP cells and rat testicular microsomes. Of the 11 PFCAs, 6 compounds significantly inhibited human 17β-HSD3, with IC₅₀ values ranging from 5.36 (C10) to 145.15 μM (C8) and a V-shaped turn at C10, and of the 7 PFSAs, only perfluorooctanesulfonic acid markedly inhibited this enzyme (IC₅₀, 5.87 μM). Of the 18 PFAS, only 6 PFCAs inhibited rat 17β-HSD3, with IC₅₀ values ranging from 14.2 (C10) to no inhibition at 100 μM (C8). These PFAS are mixed/noncompetitive inhibitors of human and rat 17β-HSD3 enzymes. Molecular docking studies suggest that the degree of inhibition is linked to the carbon-chain length of the PFAS molecule. 3D-QSAR indicates that structural hydrophobic regions determine the inhibitory potency up to C10 (PFDA). Our in vitro observation of 17β-HSD3 inhibition represents a putative upstream mechanistic factor that may contribute to elevated reproductive dysfunction and hypogonadism risk reported in existing human epidemiological PFAS exposure cohorts. In conclusion, PFAS inhibit human and rat 17β-HSD3 with clear SAR and carbon-chain length determines their inhibitory potency, and C10 PFCA is the most potent inhibitor of human and rat 17β-HSD3.

PMID:42431555 | DOI:10.1016/j.taap.2026.117937

Retinoic acid disrupts cumulus granulosa cells function via EGFR downregulation: induction of PCOS and infertility in adult female mice - July 10, 2026

Histochem Cell Biol. 2026 Jul 10;164(1):58. doi: 10.1007/s00418-026-02508-3.

ABSTRACT

Polycystic ovarian syndrome (PCOS) is a prevalent metabolic and neuroendocrine disease affecting females of childbearing age. Irregular ovulation, elevated androgen levels, and the presence of multiple ovarian cysts characterize it. This study aimed to investigate the prolonged impact of RA on female fertility during three oestrus cycles, utilizing biochemical, histopathological, and immunohistochemical analyses. Twelve female mice were classified into two groups of 6 animals each: (1) the negative control group that received DMSO diluted with sunflower oil, and (2) the positive control group that received a 10 mg/kg dose of retinoic acid. For 15 days, intraperitoneal injections were given daily. The animals were physically euthanized by slaughter on day 16 after treatment. Histopathological and immunohistochemical expression of EGFR, as well as hormonal level investigations, including FSH and LH, were performed on day 16. A 10 mg/kg RA daily dose for 15 days significantly induces FSH and reduces LH. In addition, we revealed that exogenous excess RA leads to PCOS, which causes an increase in cystic follicles and a reduction in antral follicles and corpus luteum. Immunohistochemically, excessive RA suppresses the expression of EGFR, which is localized in granulosa cells. Our investigation concluded that inhibition of epidermal growth factor receptor (EGFR) signaling resulting from long-term high-dose treatment with retinoic acid (RA) affects cumulus granulosa cell proliferation and oocyte maturation. So, vitamin A may harm female fertility.

PMID:42429978 | DOI:10.1007/s00418-026-02508-3

Simulated shift work Schedules disrupts circadian rhythms and behavior in mice - July 10, 2026

Function (Oxf). 2026 Jul 10. doi: 10.1152/function.012.2026. Online ahead of print.

ABSTRACT

Shift work has become a major cause of circadian rhythm disruption in modern society. This study investigated the systemic consequences of shift schedules by subjecting mice to different light-dark (LD) cycles: non-24-hour cycles (rapidly rotating Groups A and B) and 24-hour cycles (Group C and Control group). We performed behavioral tests, serum hormone measurements, transcriptomic analysis of SCN genes, and gut microbiome analysis. The results showed that the mice exhibited significant body weight gain after altering LD cycle compared with the control group. In groups exposed to non-24-hour cycles, the circadian expression rhythms of core clock genes (Per, Cry, Bmal1) in the SCN were lost. GO and KEGG enrichment analyses revealed that genes in the SCN losing rhythmicity were significantly enriched in metabolic and regulatory pathways, disrupting endocrine and metabolic rhythms and ultimately compromising health. The circadian rhythms of key hormones like melatonin (MT) and dopamine (DA) were also lost. Concurrently, these central disruptions drove peripheral pathology, including gut microbiota dysbiosis (altered Firmicutes/Bacteroidota ratio, reduced Verrucomicrobia) and a profound loss of gut microbial diurnal oscillations. Behaviorally, this multi-system discord manifested as significantly increased anxiety-like, depression-like behaviors and fatigue (P<0.05), while spatial memory remained intact, indicating selective affective vulnerability. SCN collapse together with hormonal chaos, desynchronizes the gut microbiome, potentially promoting inflammation and metabolic dysfunction that further disrupts central regulation. These findings provide a physiological foundation for understanding the health consequences of circadian disruption and may help guide the future design of healthier shift work schedules.

PMID:42429295 | DOI:10.1152/function.012.2026

Environmental influences on macrophage epigenetics and trained immunity: a review - July 10, 2026

Mol Biol Rep. 2026 Jul 10;53(1):1130. doi: 10.1007/s11033-026-12318-4.

ABSTRACT

Macrophages are central to host immunity and tissue homeostasis, exhibiting remarkable functional plasticity across a continuum of states-ranging from pro-inflammatory (M1-like) to anti-inflammatory and tissue-reparative (M2-like) phenotypes. Environmental exposures can induce persistent epigenetic changes that shape macrophage responses well beyond the acute phase, a phenomenon now recognized as trained immunity. This narrative review synthesizes current knowledge on how diverse components of the exposome-including diet, air pollution, agricultural chemicals, heavy metals, endocrine-disrupting chemicals, per- and polyfluoroalkyl substances (PFAS), alcohol, smoking, the gut microbiome, maternal diet, and psychosocial stress-remodel the macrophage epigenome. We examine the underlying epigenetic mechanisms, namely DNA methylation, histone modifications, and non-coding RNAs, and discuss their impact on macrophage polarization, cytokine production, and trained immunity induction. Special emphasis is placed on the distinction between bona fide trained immunity and transient inflammatory skewing, the limitations of the classical M1/M2 framework, and the identification of "epigenetic vulnerability nodes" at which multiple environmental signals converge on a small set of chromatin-modifying enzymes and transcription factors. We also highlight critical knowledge gaps, including the lack of data for emerging contaminants such as micro- and nanoplastics, the uncertain reversibility of exposure-induced epigenetic marks, and the challenge of demonstrating transgenerational inheritance in humans. By connecting molecular mechanisms with broader public health implications, this review provides a critical framework for understanding environmentally driven immune dysregulation and outlines future research directions, including mixture toxicology, single-cell multi-omics, and the integration of epigenetic endpoints into chemical risk assessment.

PMID:42430007 | DOI:10.1007/s11033-026-12318-4

Occurrence and toxicity mechanisms of hexafluoropropylene oxide dimer acid (HPFO-DA, GenX) in aquatic species - July 10, 2026

Environ Sci Process Impacts. 2026 Jul 10. doi: 10.1039/d5em00971e. Online ahead of print.

ABSTRACT

PMID:42429221 | DOI:10.1039/d5em00971e

Environmental influences on macrophage epigenetics and trained immunity: a review - July 10, 2026

Mol Biol Rep. 2026 Jul 10;53(1):1130. doi: 10.1007/s11033-026-12318-4.

ABSTRACT

PMID:42430007 | DOI:10.1007/s11033-026-12318-4

Structure-activity relationship of per- and Polyfluoroalkyl substances as inhibitors of human and rat 17β-Hydroxysteroid dehydrogenase 3 - July 10, 2026

Toxicol Appl Pharmacol. 2026 Jul 10;515:117937. doi: 10.1016/j.taap.2026.117937. Online ahead of print.

ABSTRACT

PMID:42431555 | DOI:10.1016/j.taap.2026.117937

Environmental Endocrine-Disrupting Chemicals and Metabolic Dysfunction-Associated Steatotic Liver Disease - July 9, 2026

Liver Int. 2026 Aug;46(8):e70793. doi: 10.1111/liv.70793.

ABSTRACT

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed non-alcoholic fatty liver disease (NAFLD), represents the most prevalent chronic liver condition worldwide, affecting approximately 25%-30% of the global adult population. Endocrine-disrupting chemicals (EDCs)-including phthalates, bisphenols, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs) and heavy metals-are ubiquitous environmental contaminants with established metabolic toxicity. However, the quantitative association between EDC exposure and MASLD prevalence remains incompletely characterised. We conducted a systematic review and meta-analysis to synthesise the current epidemiological evidence on this association.

METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library from inception through January 2026, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (PROSPERO: CRD420261298624). Studies were eligible if they reported quantitative associations between measured EDC exposures and MASLD/NAFLD/metabolic-associated fatty liver disease (MAFLD) outcomes in human populations. Two investigators independently screened records, extracted data and assessed methodological quality using a customised Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed via the I² statistic. Funnel plot asymmetry and Egger's test were used to evaluate publication bias. Sensitivity analyses were performed using leave-one-out methods.

RESULTS: Of 427 records identified, 42 studies encompassing diverse global populations met inclusion criteria and were incorporated into the quantitative synthesis. The meta-analysis demonstrated that: Phthalates: mono (2-ethyl-5-carboxypentyl) phthalate (MECPP; weighted mean difference [WMD]: 2.40, 95% CI: 0.71-4.09), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP; WMD: 2.46, 95% CI: 0.81-4.10) and monobenzyl phthalate (MBzP; WMD: 1.84, 95% CI: 0.10-3.59) showed significant positive associations with MASLD prevalence; pooled analysis of phthalate mixtures yielded an overall OR of 1.17 (95% CI: 1.13-1.21; I² = 41.4%). Bisphenols: pooled analysis demonstrated a significant positive association with MASLD (OR: 1.29, 95% CI: 1.09-1.50; I² = 73.0%), with bisphenol A (BPA; OR: 1.32, 95% CI: 0.92-1.72), bisphenol S (BPS; OR: 1.47, 95% CI: 0.96-1.98) and bisphenol F (BPF; OR: 1.19, 95% CI: 0.77-1.61) contributing to this effect. PFAS: the overall pooled effect was OR 0.95 (95% CI: 0.91-1.00; I² = 22.9%). POPs: the overall OR was 1.30 (95% CI: 1.22-1.37; I² = 29.2%), with organochlorine pesticides (OCPs; OR: 1.30, 95% CI: 1.19-1.42) and polychlorinated biphenyl (PCB)/OCP combinations demonstrating significant associations. Heavy metals/metalloids: mercury (Hg) demonstrated the strongest positive association (OR: 1.60, 95% CI: 1.15-2.04; I² = 87.3%), followed by lead (Pb; OR: 1.40, 95% CI: 1.02-1.78) and cadmium (Cd; OR: 1.30, 95% CI: 1.09-1.51; I² = 79.2%); the overall metals pooled OR was 1.26 (95% CI: 1.16-1.37; I² = 79.9%). Methodological quality assessed by NOS ranged from 6 to 9 points, with the majority of studies scoring ≥ 7.

CONCLUSIONS: This meta-analysis of observational studies suggests that environmental exposure to several major EDC classes-including phthalates, bisphenols, persistent organic pollutants and certain heavy metals-is associated with a higher prevalence of MASLD, although the magnitude and consistency of associations vary substantially across chemical classes and individual compounds. Findings for PFAS were heterogeneous and compound-specific. Given the predominantly cross-sectional nature of the available evidence and the considerable between-study heterogeneity, causal inference cannot be drawn. These findings should be interpreted as hypothesis-generating and underscore the need for prospective multi-pollutant studies and mechanistic investigations to clarify the role of EDCs in MASLD pathogenesis.

PMID:42423535 | PMC:PMC13348493 | DOI:10.1111/liv.70793

Accumulation and temporal trends (2002-2023) of legacy and emerging persistent organic pollutants in common dolphins (Delphinus delphis) from Korean coastal waters - July 9, 2026

J Hazard Mater. 2026 Jul 8;514:142944. doi: 10.1016/j.jhazmat.2026.142944. Online ahead of print.

ABSTRACT

Elevated accumulation of persistent organic pollutants (POPs) in marine mammals remains a concern for the health and conservation of marine ecosystems. Long-term monitoring of POPs in marine mammals is essential to evaluate the effectiveness of regulations and to understand their environmental behavior in marine ecosystems. We investigated accumulation patterns and temporal trends of legacy and emerging POPs in the blubber of common dolphins (Delphinus delphis) from Korean coastal waters over the past two decades (2002-2023). Polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane and its metabolites (DDTs) were the dominant contaminants, whereas emerging compounds, such as novel brominated flame retardants (NBFRs) and dechlorane plus (DP), were detected at low concentrations and detection frequencies. Bioaccumulation of POPs was pronounced in mature male dolphins, whereas mature females exhibited lower concentrations, explained by maternal transfer via placenta and lactation. Temporal trend analysis using body length-adjusted concentrations revealed that PCBs, DDTs, and polybrominated diphenyl ethers (PBDEs) significantly declined over the study period, reflecting the effectiveness of domestic and global regulatory efforts. PCB concentrations decreased gradually, whereas PBDE concentrations exhibited the most rapid decline. Concentrations of BDE 184 showed an increasing trend, which is explained by debromination of highly brominated congeners. Unlike legacy POPs, NBFRs and DP did not show any predictable temporal trend in dolphin tissues. Despite declining trends, some dolphins are still exposed to PCB and DDT concentrations above the thresholds for endocrine disruption. These results highlight the need for continued long-term monitoring to better understand the fate and ecological effects of legacy and emerging POPs in marine ecosystems. Crucially, these monitoring data should be utilized to refine environmental quality standards and inform regional conservation policies for marine apex predators.

PMID:42424956 | DOI:10.1016/j.jhazmat.2026.142944

Bisphenol A alternatives (BPS and BPAF) disrupt anti-predatory behavior and intergenerational behavioral responses in zebrafish (Danio rerio) - July 9, 2026

Aquat Toxicol. 2026 Jul 4;298:107924. doi: 10.1016/j.aquatox.2026.107924. Online ahead of print.

ABSTRACT

Bisphenol S (BPS) and bisphenol AF (BPAF) are increasingly used as alternatives to bisphenol A and are now widely detected in aquatic environments. These compounds interfere in endocrine systems as the hypothalamus-pituitary-gonadal and the hypothalamus-pituitary-thyroid axes. However, their effects on ecologically relevant behaviors, such as exploration and anti-predatory responses, have received limited attention. This is particularly true for paternal transmission across generations. Here, we investigated exploratory and anti-predatory behavior in adult zebrafish exposed to BPS or BPAF and assessed whether paternal exposure induces behavioral alterations in the offspring. Adult males were exposed for 14 days to BPS (0.5 µg/L) or BPAF (0.15 µg/L) and tested for anti-predatory and anxiety-like behaviors. Exposed males were then crossed with unexposed females to generate F1 embryos. Embryos from unexposed parents were directly exposed to BPS or BPAF for 5 days. Larval visual locomotor response was assessed using the light-dark transition test. BPAF exposure impaired anti-predatory responses and increased anxiety-like behavior in adult males, whereas BPS had no detectable effects at this stage. In larvae, both BPS and BPAF altered visual locomotor responses, either following direct exposure or through paternal transmission. Directly exposed larvae showed reduced light-phase inhibition, while larvae derived from exposed males exhibited increased dark-phase activity, consistent with a hyperactive phenotype. These findings demonstrate that paternal exposure to BPS and BPAF is sufficient to disrupt offspring behavior and highlight that bisphenol A alternatives, even at low concentrations, pose ecological risks by impairing fish behavioral performance and potentially survival.

PMID:42425033 | DOI:10.1016/j.aquatox.2026.107924

An eyestalk-enriched GATA factor (NdGATA123c) modulates photosensitivity and molting in Neocaridina denticulata sinensis - July 9, 2026

J Exp Biol. 2026 Jul 9:jeb.252737. doi: 10.1242/jeb.252737. Online ahead of print.

ABSTRACT

GATA proteins are a class of important transcription factors with conserved zinc finger domains, playing essential roles in developmental regulation and tissue homeostasis in animals. However, the molecular characteristics and in-depth functional studies of the GATA family members in crustaceans are still lacking. In this study, we identified a cumulative total of 67 GATA genes across the 12 crustacean genomes, with most species harboring 5-6 members. Comparative analysis showed that the analyzed crustacean GATA genes exhibited clustered chromosomal distribution and highly conserved GATA-type zinc-finger domains. The expression profiles of GATAs in Neocaridina denticulata sinensis (NdGATAs) across different tissues showed that NdGATA123c was the only NdGATA gene highly expressed in the eyestalk. Through RNA interference and transcriptome sequencing, knockdown of NdGATA123c in the eyestalk led to the upregulation of multiple cuticle protein genes and disrupted the homeostasis of pathways associated with visual signaling, endocrine regulation, and intracellular signal transduction. These molecular changes were associated with altered phototactic responses to red and green light during the early stage of illumination, abnormal pigment granule arrangement in the ommatidia, and prolongation of the molting cycle. Together, these results suggest that NdGATA123c, as an eyestalk-enriched GATA zinc-finger transcription factor, may contribute to the maintenance of local signaling homeostasis linked to visual adaptation and molting rhythm in N. denticulata sinensis. This study provides new insights into the evolution and functional differentiation of GATA transcription factors in crustaceans.

PMID:42421577 | DOI:10.1242/jeb.252737

Hierarchical-circular model of biological memory: a multilevel hypothesis for pathogenesis and allostatic integrity in Alzheimer's disease and related dementias - July 9, 2026

Front Dement. 2026 Jun 24;5:1841647. doi: 10.3389/frdem.2026.1841647. eCollection 2026.

ABSTRACT

INTRODUCTION: Alzheimer's disease and related dementias remain largely resistant to disease-modifying therapies, despite decades of research focused on linear neuropathological pathways such as beta-amyloid and tau. Persistent paradoxes-including the dissociation between pathology burden and clinical expression, the impact of early-life stress, and the role of systemic factors-indicate the need for integrative theoretical frameworks. This article proposes a multilevel hypothesis conceptualizing dementias as disorders of biological memory and allostatic integrity rather than isolated brain pathologies.

HYPOTHESIS: The Hierarchical-Circular Model of Biological Memory posits that dementia emerges from progressive disruptions in a circular, multilevel system that encodes and stabilizes biological information across the lifespan. The model is organized around the unifying principle "Signal → Plasticity → Stable State" and integrates five interconnected levels: (1) morphogenetic programming and genetic architecture, (2) epigenetic molecular memory, (3) allostatic load and systemic physiological adaptation, (4) the Psychological-Neurological-Endocrine-Immunological (PNEI) network, and (5) interoceptive-neuronal integration. At any level, perturbation can propagate bidirectionally through the system, establishing maladaptive stable states that manifest clinically as dementia.

DEVELOPMENT OF THE HYPOTHESIS: Through a structured synthesis of longitudinal, mechanistic, and multisystem studies (2010-2025), the model specifies how gene-environment interactions, epigenetic modifications, cumulative allostatic load, neuroimmune dynamics, and altered interoceptive timescales jointly shape vulnerability and resilience. The concept of allostatic integrity is introduced as a dynamic systems-level property-distinct from allostatic load-that explains why similar neuropathological burdens may result in divergent clinical trajectories. Distinct dementia phenotypes are proposed to reflect different patterns of circular reinforcement across the five levels.

TESTABLE PREDICTIONS: This framework generates concrete, falsifiable predictions: (1) composite indices of allostatic integrity will outperform single biomarkers in predicting conversion from mild cognitive impairment to dementia; (2) multidomain interventions targeting more than one system level will have multiplicative, rather than additive, effects on slowing cognitive decline; (3) patients with similar amyloid/tau profiles but contrasting allostatic integrity will show markedly different trajectories of clinical progression; and (4) allostatic integrity moderates the protective effect of cognitive reserve, a pattern not predicted by reserve frameworks alone.

CONCLUSION: The Hierarchical-Circular Model of Biological Memory offers a unifying hypothesis for Alzheimer's disease and related dementias that bridges genetic, epigenetic, physiological, neuroimmune, and interoceptive processes across the lifespan. By reframing dementias as failures of biological memory and allostatic integrity, the model provides a conceptual roadmap for mechanistic research, multidomain prevention, and personalized treatment strategies.

PMID:42422549 | PMC:PMC13341510 | DOI:10.3389/frdem.2026.1841647

A Comprehensive Review on Microplastic Contamination in Food Packaging and Processing: Pathways, Exposure, and Implications - July 9, 2026

Compr Rev Food Sci Food Saf. 2026 Jul;25(4):e70564. doi: 10.1111/1541-4337.70564.

ABSTRACT

Due to widespread environmental presence and growing detection in food systems, microplastics (MPs), which are plastic particles smaller than 5 mm, along with nanoplastics with size <1 µm, collectively referred to as micro and nanoplastics (MNPs), have become a growing global concern. Previous exposure studies undermined the true burden of plastic contamination, owing to the limited analytical detection range that resulted in the omission of nanoscale fractions and a potential underestimation of related toxicological risks. Recent studies have reported that approximately 90% of plastic particles detected in bottled water are MNPs. Food packaging materials are a crucial but frequently disregarded source of MP contamination among the various exposure pathways. During handling, processing, and storage, packaging plastics can release MPs into food, which has a direct impact on consumer health and food safety. Measurable concentrations of MPs with variable contamination profiles have been found in packaged beverages, dairy products, meat, snacks, and ready-to-eat foods, as per recent case studies. Despite ongoing methodological issues with size resolution, polymer discrimination, and sample standardization, various analytical techniques have been used for detection and characterization of MPs. The necessity of reducing MPs' presence in food systems is highlighted by their toxicological effects, which include possible bioaccumulation, oxidative stress, endocrine disruption, and microbiota imbalance. Reducing exposure risks requires the implementation of preventive measures like better manufacturing techniques, sustainable packaging substitutes, and regulatory actions. The sources, migration, analytical techniques, health effects, and preventative measures of MPs in food packaging are summarized in this review. It also highlights research gaps and obstacles in developing sustainable and safe food packaging.

PMID:42422984 | DOI:10.1111/1541-4337.70564

Environmental Toxicants and Polycystic Ovary Syndrome: Implications for a Metabolic-Ovarian Framework (PMOS) - A Systematic Review - July 9, 2026

Biol Trace Elem Res. 2026 Jul 9. doi: 10.1007/s12011-026-05218-y. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is increasingly recognized as a systemic condition characterized by intricate endocrine and metabolic dysregulation. Emerging evidence suggests that environmental contaminants may drive its pathogenesis, supporting an expanded conceptualization of the disorder as polycystic metabolic-ovarian syndrome (PMOS). This systematic review aimed to evaluate the association between exposure to potentially toxic elements (PTEs) and endocrine disruptors and the reproductive, hormonal, and metabolic clinical features of PCOS.

METHODS: Following PRISMA guidelines, a systematic search was conducted across PubMed, Embase, Scopus, and Web of Science for human observational studies published up to 31 December 2025. Methodological quality was appraised using the Newcastle-Ottawa Scale (NOS). Due to heterogeneity in biological matrices and toxicant classes, a narrative synthesis was performed.

RESULTS: Fourteen high-quality studies (NOS scores 8-9) from seven countries met the inclusion criteria. The evidence consistently linked exposure to endocrine disrupting chemicals specifically bisphenol A (BPA) and phthalates-with hyperandrogenism, altered luteinizing hormone/follicle-stimulating hormone ratios, and impaired ovarian reserve. Furthermore, heavy metals (cadmium, lead, mercury, arsenic) and emerging rare earth elements were significantly elevated in women with PCOS across multiple matrices (serum, urine, and follicular fluid). These exposures were strongly associated with metabolic disturbances, including insulin resistance, obesity indices, and lipid abnormalities, mediated predominantly by oxidative stress pathways and impaired antioxidant defences.

CONCLUSION: Current observational evidence suggests associations between exposure to selected environmental toxicants and endocrine‑metabolic features of PCOS. However, heterogeneity in exposure assessment, biological matrices, PCOS diagnostic criteria, and confounder adjustment limits causal interpretation. Future prospective studies with repeated biomonitoring are needed.

PMID:42426543 | DOI:10.1007/s12011-026-05218-y

Environmental Endocrine-Disrupting Chemicals and Metabolic Dysfunction-Associated Steatotic Liver Disease - July 9, 2026

Liver Int. 2026 Aug;46(8):e70793. doi: 10.1111/liv.70793.

ABSTRACT

PMID:42423535 | PMC:PMC13348493 | DOI:10.1111/liv.70793

Mapping Steroidogenic Perturbations Under Endocrine Disruptor Mixtures Across Demographic Subgroups: Structural and Metabolomic Insights - July 9, 2026

Adv Sci (Weinh). 2026 Jul 9:e76381. doi: 10.1002/advs.76381. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are pervasive environmental chemicals affecting hormone homeostasis, yet mapping mixture exposures to mechanisms at the population scale remains challenging. Here, analyses of 4255 U.S. participants are integrated with computational and experimental validation, linking population signals to molecular targets. Profiling 37 EDCs reveals consistent associations between phthalate metabolites and lower testosterone, strongest in adult males. Mono-(3-carboxypropyl) phthalate (MCPP) is identified as a key disruptor and is shown to inhibit CYP17A1, consistent with engagement of the enzyme's iron-protoporphyrin IX (heme) center. Docking/molecular dynamics prioritizes this interaction, which is supported by surface plasmon resonance, multi-matrix metabolomics in vivo and in vitro, and functional assays in primary Leydig cells. An interactive web resource (https://chembio.njmu.edu.cn/edc-hormone-explorer.html) provides open access to the association landscape and supports risk prioritization.

PMID:42423525 | PMC:PMC13348348 | DOI:10.1002/advs.76381

Explainable machine learning integrating environmental chemical biomarkers and maternal clinical factors for prediction of hypertensive disorder of pregnancy - July 9, 2026

Sci Rep. 2026 Jul 9. doi: 10.1038/s41598-026-61841-8. Online ahead of print.

ABSTRACT

Hypertensive disorders of pregnancy (HDP) represent a leading cause of maternal morbidity, yet environmental chemical contributors to HDP risk remain poorly characterized within predictive frameworks. We developed and evaluated an explainable machine-learning model integrating environmental biomarkers with maternal clinical characteristics for HDP prediction using data from 4,260 pregnant women enrolled in the Korean Children's Environmental Health Study (Ko-CHENS) prospective birth cohort. An Extreme Gradient Boosting (XGBoost) classifier incorporating 18 environmental biomarkers-including blood lead, cadmium, mercury, and endocrine-disrupting chemicals-alongside maternal clinical covariates was trained using stratified 60/20/20 data splits with Bayesian hyperparameter optimization. The optimized model achieved a cross-validated ROC-AUC of 0.787 and an independent test ROC-AUC of 0.748 (95% CI: 0.587-0.887), with a negative predictive value of 0.994 under severe class imbalance (HDP prevalence: 1.7%). SHapley Additive exPlanations (SHAP) analysis identified late-pregnancy blood lead concentration and pre-pregnancy body mass index as the dominant predictors, each exhibiting non-linear risk gradients; formal SHAP interaction values (1.6% of combined attribution) and an independent logistic-regression interaction term (β = 0.418, 95% CI - 0.278-1.115, p = 0.239) indicated additive rather than synergistic BMI-lead pathways. These findings demonstrate that environmental biomarkers contribute independent, non-linear predictive value beyond established clinical risk factors, supporting integration of environmental exposure surveillance into precision obstetric risk stratification.

PMID:42426319 | DOI:10.1038/s41598-026-61841-8

A Comprehensive Review on Microplastic Contamination in Food Packaging and Processing: Pathways, Exposure, and Implications - July 9, 2026

Compr Rev Food Sci Food Saf. 2026 Jul;25(4):e70564. doi: 10.1111/1541-4337.70564.

ABSTRACT

PMID:42422984 | DOI:10.1111/1541-4337.70564

Widespread emerging and legacy contaminants across Alpine snow and surface waters revealed by non-target analysis - July 9, 2026

Environ Pollut. 2026 Jul 9;407:128754. doi: 10.1016/j.envpol.2026.128754. Online ahead of print.

ABSTRACT

High-mountain environments are increasingly recognized not as pristine systems, but as dynamic reservoirs of anthropogenic contaminants influenced by long-range atmospheric transport and regional emissions. Here, surface snow and river waters from the Monte Bianco area (Italian Alps) were investigated using an integrated non-target screening strategy combining liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and gas chromatography-mass spectrometry (GC-MS) with orthogonal extraction workflows. This approach revealed an unexpectedly complex chemical fingerprint comprising 283 tentatively identified compounds spanning industrial additives, plasticizers, pharmaceuticals, flame retardants, pesticides, and tire-derived compounds. Multivariate chemometric analysis indicated compositional differences between high- and low-altitude snow samples, as well as between upstream and downstream river-water samples, suggesting spatial variability in contaminant fingerprints across the Monte Bianco area. The probable detection of endocrine-disrupting phthalates, organophosphate flame retardants, pesticides (imidacloprid), and UV filters (oxybenzone) indicates the occurrence of diverse chemical classes in remote alpine systems. These findings position high-elevation environments as integrative archives of global contaminant mixtures and potentially relevant matrices for studying contaminant storage and release processes. The integration of complementary analytical platforms and advanced chemometric tools proved an effective framework for broad environmental characterization and contaminant prioritization in remote ecosystems.

PMID:42425292 | DOI:10.1016/j.envpol.2026.128754

Adolescent stress and alcohol are associated with CX(3)CR1-linked endocrine-cardiac signatures and anxiety-like behavior in mice - July 9, 2026

Front Pharmacol. 2026 Jun 24;17:1850815. doi: 10.3389/fphar.2026.1850815. eCollection 2026.

ABSTRACT

BACKGROUND: Adolescence is a vulnerable window in which stress and alcohol exposure can induce long-lasting neuroimmune, endocrine, and cardiac molecular alterations. The fractalkine axis (CX₃CL1/CX₃CR1) regulates neuron-microglia signaling and inflammatory responses, but its role in linking adolescent stress/alcohol exposure with adult anxiety-like behavior and cardiac biomarker/molecular signatures remains unclear.

AIMS: To test whether genetic or pharmacological disruption of CX₃CR1 modifies adult anxiety-like behavior, circulating biomarkers, and cardiac transcriptional responses after adolescent stress and/or alcohol exposure.

METHODS: Male and female C57BL/6J wild-type (WT) and CX₃CR1 knockout (KO) mice were exposed to restraint stress (90 min) and/or alcohol (2 g/kg, 14 days) during adolescence. In adulthood, elevated plus maze (EPM) behavior was assessed; plasma cTnI/cTnT, CX₃CL1, ACTH, and corticosterone were quantified; and cardiac mRNA expression of chemokines, inflammatory receptor/NF-κB-related genes, glucocorticoid/mineralocorticoid receptor-related genes, and RAAS-related transcripts was profiled. WT mice received the CX₃CR1 antagonist AZD8797 (20 mg/kg, i.p.) for behavioral validation.

RESULTS: CX₃CR1 loss or blockade was associated with increased anxiety index and reduced open-arm exploration under selected exposure conditions. CX₃CR1 KO mice showed higher plasma cTnI/cTnT, CX₃CL1, and ACTH, and lower corticosterone, stress and alcohol were also associated with lower corticosterone. In cardiac tissue, alcohol exposure, mainly under the no-stress condition, increased Cx3cl1, Ccl2, Ackr3, and selected RAAS-related transcripts, whereas CX₃CR1 deficiency was associated with broadly lower expression across chemokine, NF-κB-related, mineralocorticoid receptor-related, and RAAS-related targets. Correlation analyses indicated a chemokine/Cxcl12-anchored inflammatory-RAAS transcriptional architecture in WT mice that was attenuated and shifted toward glucocorticoid/mineralocorticoid receptor-NF-κB/IκBα-RAAS-related associations in CX₃CR1 KO mice.

CONCLUSION: These findings suggest that CX₃CR1 signaling contributes to the long-term coordination of behavioral stress-related responses, HPA-axis activity, circulating cardiac injury biomarkers, and cardiac inflammatory/RAAS-related transcriptional programs after adolescent stress and alcohol exposure. Because cardiac function and histopathology were not assessed, these results should be interpreted as evidence of cardiac biomarker and molecular vulnerability rather than definitive myocardial pathology.

PMID:42422081 | PMC:PMC13341564 | DOI:10.3389/fphar.2026.1850815

Non-Linear Transcriptional Responses Suggest Mechanisms of Tributyltin Toxicity in Triops longicaudatus - July 9, 2026

Environ Pollut. 2026 Jul 9:128735. doi: 10.1016/j.envpol.2026.128735. Online ahead of print.

ABSTRACT

Tributyltin (TBT), a persistent biocide banned in 2008, continues to pose a significant threat to aquatic ecosystems. While its role as an endocrine disruptor is well established, its complete mechanistic cascade, particularly across environmentally relevant concentrations in non-target organisms, remains poorly characterised. Here, RNA-seq was used to characterise the transcriptional response of the non-model crustacean Triops longicaudatus following 90 min exposure to TBT at three nopminal concentrations: 0.075 μg/L (96h-LC₅₀), 0.25 μg/L (a sub-acute concentration below the US EPA acute criterion of 0.46 μg/L), and 1.54 μg/L (a high environmental concentration). Rather than following a linear concentration-response pattern, TBT showed a quantitatively validated non-linear, tri-phasic mechanistic response characterised by three distinct signatures: (1) a U-shaped immunotoxic response at sub-lethal acute (0.075 μg/L) and high concentrations (1.54 μg/L), with the downregulation of the complement cascade; (2) a unique middle concentration (0.25 μg/L) compensatory response associated with signatures of AMPK-mediated stress mitigation, pointing to potential systemic metabolic adaptation through crustacean hyperglycemic hormone signalling and upregulation of digestive pathways; and (3) high concentration (1.54 μg/L) multi-system failure, associated with DNA repair failure, chromatin degradation, and suppression of cellular quality control mechanisms including autophagy and lysosomal acidification. This collapse can be mechanistically related to endocrine dysregulation: TBT's agonism of the RXR/PPAR heterodimer simultaneously coincides with changes in ecdysone signalling whilst attenuating juvenile hormone and cholesterol biosynthesis pathways. This study presents the first comprehensive transcriptomic evidence for concentration-dependent, non-monotonic mechanistic specificity in TBT toxicity, suggesting distinct modes of cellular failure that challenge conventional toxicological paradigms and carry significant implications for environmental risk assessment and regulatory frameworks.

PMID:42425285 | DOI:10.1016/j.envpol.2026.128735

Research progress on sample pretreatment technology for the analysis of new pollutants in food using composite covalent organic framework materials - July 9, 2026

Se Pu. 2026 Jul;44(7):731-740. doi: 10.3724/SP.J.1123.2025.08002.

ABSTRACT

New pollutants are recently identified or recognized chemical substances. They pose risks to ecosystems or human health. Many are not yet regulated or lack effective control measures. These pollutants show biological toxicity， environmental persistence， and bioaccumulation. They threaten human health. In recent years， their detection frequency in food has increased. Efficient detection technologies are urgently needed. Sample pretreatment is key for analyzing new pollutants in food. The core of pretreatment lies in the preparation and selection of adsorbent materials. Covalent organic frameworks （COFs） are porous crystalline materials. They are formed by light elements linked through covalent bonds. COFs have highly ordered crystal structures. Their pore sizes can be adjusted. Surface properties are functionalizable. They show excellent chemical and thermal stability. Composite covalent organic framework materials combine COFs with other materials. This is achieved through physical or chemical methods. The composites exhibit synergistic effects. They retain the unique properties of both COFs and the other materials. This article reviews common sample pretreatment techniques for new pollutants in food. These include solid-phase extraction （SPE）， solid-phase microextraction （SPME）， stir bar sorptive extraction （SBSE）， dispersive solid-phase extraction （DSPE）， and magnetic solid-phase extraction （MSPE）. SPE is a chromatographic technique. It removes impurities from solid or liquid samples. It also enriches target compounds. SPE offers high enrichment factors and low solvent use. It is easy to automate. SPME balances samples between solid and liquid phases. It integrates sampling， extraction， and concentration. SPME uses little or no solvent. It is simple and automatable. It can be coupled with other techniques online. SBSE evolved from SPME. It has a larger stationary phase volume and higher capacity. SBSE uses a stir bar with a magnetic core. The bar is coated with an extraction layer. Stirring ensures full contact with analytes. SBSE is solvent-free or uses minimal solvent. It is accurate， fast， and easy to automate. DSPE disperses adsorbents into sample matrices. It increases contact area between adsorbents and analytes. DSPE simplifies sample processing. It avoids sample loss. MSPE uses magnetic or magnetizable materials as adsorbents. It captures target analytes efficiently. MSPE is simple to prepare and separate. Pipette-tip-SPE （PT-SPE） is a newer technique. It packs adsorbents into pipette tips. PT-SPE is flexible， low-cost， and needs small sample volumes. This article details types of composite COF materials. These include magnetic COF （MCOF）， sponge-COF， molecularly imprinted polymer-COF （MIP-COF）， metal-organic framework-COF （MOF-COF）， and electrospun-COF. MCOF combines COFs with magnetic nanoparticles. It enables quick separation under a magnetic field. Sponge-COF grows COFs on sponge fibers. It enhances adsorption capacity and mass transfer. MIP-COF integrates molecularly imprinted polymers with COFs. It offers specific recognition sites. MOF-COF combines metal-organic frameworks with COFs. It introduces metal active sites. Electrospun-COF embeds COFs into polymer nanofibers. It improves mechanical performance and stability. These composite materials are utilized in the pretreatment of food samples， where they effectively enrich trace levels of new pollutants， including perfluoroalkyl substances， antibiotics， personal care products， endocrine disruptors， and flame retardants， within complex food matrices. When coupled with analytical techniques such as high-performance liquid chromatography （HPLC）， HPLC-tandem mass spectrometry （HPLC-MS/MS）， gas chromatography （GC）， gas chromatography-mass spectrometry （GC-MS）， molecular fluorescence spectroscopy， and Raman spectroscopy， they facilitate highly accurate and sensitive detection of these new pollutants in food products. Future directions include improving synthesis methods. Current methods are time-consuming and costly. New techniques like water-phase synthesis are promising. Multifunctional composites are needed. They should adsorb multiple pollutant types. Automated and high-throughput extraction technologies will be developed. Green and scalable production processes are essential for industrial applications. In conclusion， composite COF materials show great potential. They enhance the efficiency and accuracy of food pollutant analysis. Further research will expand their applications and improve performance.

PMID:

Quercetin restores oocyte maturation and embryo development in DEHP-exposed mice via mitochondrial protection and apoptosis inhibition - July 9, 2026

Chem Biol Interact. 2026 Jul 9;437:112253. doi: 10.1016/j.cbi.2026.112253. Online ahead of print.

ABSTRACT

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental endocrine-disrupting chemical known to impair female reproductive function. However, effective mitigation strategies and their underlying molecular mechanisms remain incompletely understood. Quercetin (QUE), a natural flavonoid with potent antioxidant and anti-apoptotic properties, represents a promising therapeutic candidate. In this study, we established a mouse model to evaluate the protective efficacy of QUE against DEHP-induced oocyte toxicity. Female ICR mice were treated with DEHP (500 mg/kg/day) with or without QUE (100 mg/kg/day) for 45 days. QUE co-treatment significantly alleviated DEHP-induced estrous cycle disruption, restored the ovarian reserve, and enhanced both nuclear and cytoplasmic oocyte maturation. Mechanistically, integrated network pharmacology and molecular docking analyses identified NRF2 and SIRT1 as key targets of QUE. Western blot validation confirmed that QUE reversed the DEHP-induced downregulation of NRF2 and normalized the compensatory overexpression of SIRT1. Functionally, QUE mitigated DEHP-triggered mitochondrial dysfunction, including aberrant clustering and loss of membrane potential, and suppressed the Bax/Caspase-dependent apoptotic pathway by downregulating Bax, Caspase-3, and Caspase-9 while upregulating Bcl-2. These protective effects ultimately led to improved preimplantation embryo development, reduced blastocyst apoptosis, normalized litter size, and prevention of abnormal postnatal catch-up growth trajectories in offspring. Collectively, our findings demonstrate that QUE counteracts DEHP-induced reproductive toxicity by preserving mitochondrial integrity and inhibiting apoptotic signaling via modulation of the SIRT1/NRF2 axis, providing a strong mechanistic foundation for dietary interventions against phthalate-associated female subfertility.

PMID:42425258 | DOI:10.1016/j.cbi.2026.112253

Harnessing probiotics to combat nonylphenol toxicity: a multiomics approach of gut microbiome remodelling in Silurus meridionalis - July 9, 2026

BMC Genomics. 2026 Jul 8. doi: 10.1186/s12864-026-13161-4. Online ahead of print.

ABSTRACT

BACKGROUND: As a ubiquitous environmental endocrine disruptor, nonylphenol (NP) threatens aquatic organisms, driving the need for sustainable mitigation strategies. While probiotics represent promising eco-friendly supplements, their molecular mechanisms against NP toxicity remain unclear. In this study, S. meridionalis received 7-week of probiotic (Bacillus subtilis and Lactobacillus acidophilus) pretreatment followed by 15 days of NP exposure. Integrated metagenomics, transcriptomics, and metabolomics analyses, with Reverse transcription quantitative real-time PCR (RT‒qPCR) and Enzyme-linked immunosorbent assay (ELISA) validation, were performed to elucidate microbial, genetic and metabolic responses. Growth performance, including the specific growth rate (SGR) and weight gain rate (WGR), was concurrently assessed.

RESULTS: NP exposure significantly suppressed WGR and SGR, and induced gut microbiota dysbiosis alongside and lipid metabolism disorders in S. meridionalis. Probiotic pretreatment effectively reversed these toxic effects and restored the inhibited WGR and SGR. Multiomics integration revealed that the protective effects of probiotics were mediated by a coherent "microbe-host" co-metabolism network across 3 progressive layers: (1) Microbial Remodelling: in which beneficial taxa (e.g., Bacteroides eggerthii and Cetobacterium sp.) were enriched, and the functional capacity for short-chain fatty acid (SCFA) synthesis and ethanolamine metabolism was enhanced; (2) Host Gene Regulation: in which key lipid metabolism genes (ek1, cept1, ept1, mogat2, and abcg2a) were upregulated, and lipase activity was restored; and (3) Metabolic Pathway Activation and Physiological Repair: in which the activity of the NP-suppressed Kennedy pathway was reactivated, thereby promoting phosphatidylethanolamine (PE) and phosphatidylcholine (PC) synthesis and ultimately restoring gut barrier function. These results were further were corroborated by RT‒qPCR and ELISA.

CONCLUSION: This study systematically elucidated that probiotics alleviated NP toxicity by remodelling a "microbiota-host Kennedy pathway gene-metabolite (PE and PC)-growth performance" regulatory network. The key mechanism is the beneficial microbiota activating the host Kennedy pathway and restoring gut phospholipid homeostasis and barrier function. These findings provide a theoretical basis for developing targeted, lipid metabolism focused probiotic feed additives for use in sustainable aquaculture.

PMID:42420833 | DOI:10.1186/s12864-026-13161-4

Physiological and Behavioral Effects of Chronic Diethylpropion Exposure During Development in Caenorhabditis elegans: An In Vivo and in Silico Toxicity Approach - July 8, 2026

J Appl Toxicol. 2026 Jul 8. doi: 10.1002/jat.70296. Online ahead of print.

ABSTRACT

Diethylpropion (DEP), a psychostimulant structurally related to amphetamine, is prescribed as an appetite suppressant but carries a potential risk of neurotoxicity and abuse. Here, we investigated the physiological and behavioral consequences of chronic DEP exposure during development in Caenorhabditis elegans, combining in vivo assays with in silico toxicity predictions. Age-synchronized larvae were exposed to DEP (100-500 μM) for up to 72 h, and survival, growth, reproduction, feeding, and neuromotor function were assessed. DEP reduced survival in a dose-dependent manner, delayed larval development, decreased body size, and impaired reproductive capacity, including brood size reduction, shorter egg-laying period, and increased intrauterine egg retention. Neuromotor activity, measured by head thrashes and body bends, as well as pharyngeal pumping rates, was significantly reduced. DEP also triggered oxidative stress, evidenced by upregulation of gst-4::GFP expression. In silico analysis predicted high neurotoxicity, oxidative stress potential, and endocrine disruption, with probable interactions in dopaminergic signaling and mitochondrial function. These findings indicate that developmental DEP exposure disrupts multiple physiological systems in C. elegans, highlighting its potential to cause lasting neuromuscular and reproductive impairments.

PMID:42415655 | DOI:10.1002/jat.70296

Exposure to Endocrine-disrupting Chemicals, Iron Metabolism, and Risk of Metabolic Dysfunction-associated Steatotic Liver Disease: A Nationwide Cross-sectional Study in China - July 8, 2026

Biomed Environ Sci. 2026 Jun 20;39(6):677-689. doi: 10.3967/bes2026.049.

ABSTRACT

OBJECTIVE: This study aimed to investigate the association between exposure to mixtures of environmental endocrine-disrupting chemicals (EDCs) and metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential mediating role of iron metabolism.

METHODS: A total of 6,989 adults from the China Health and Nutrition Survey (2015 cycle) were included. The serum concentrations of 22 EDCs were measured. Logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were used to evaluate the association between EDC exposure and risk of MASLD. Mediation analyses were performed to assess the mediating role of serum ferritin (SF).

RESULTS: Eight EDCs were positively associated with MASLD. The WQS regression model identified six major contributors, including β-hexachlorocyclohexane, p,p'-DDT, monoethyl phthalate, acenaphthene, perfluorooctanoic acid, and perfluoro-n-pentanoic acid, in mixture effects. The BKMR model demonstrated that higher levels of EDC mixture were associated with an increased risk of MASLD. Subgroup analyses suggested stronger correlations in males and in individuals aged < 65 years. SF was estimated to mediate 11.2%-32.1% of the association between key EDCs and MASLD.

CONCLUSION: Exposure to EDC mixtures was associated with an increased risk of MASLD, with iron metabolism playing a notable mediating role. Reducing the exposure to key EDCs may help alleviate the burden of MASLD.

PMID:42417236 | DOI:10.3967/bes2026.049

Peer review of the pesticide risk assessment for the active substance bifenazate in light of confirmatory data submitted - July 8, 2026

EFSA J. 2026 Jul 7;24(7):e10169. doi: 10.2903/j.efsa.2026.10169. eCollection 2026 Jul.

ABSTRACT

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State Sweden, for the pesticide active substance bifenazate are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information with regard to the endocrine disruption potential of bifenazate for humans and wild mammals regarding EAS-modalities. The conclusions were reached on the basis of the evaluation of the representative uses of bifenazate as an acaricide on strawberry, fruiting vegetables (tomatoes, peppers, aubergines, cucumbers, courgettes, melons and watermelons), flowering and ornamental plants and nursery of ornamentals. The reliable endpoints concluded as being appropriate for use in regulatory risk assessment, derived from the available studies and/or literature in the dossier peer reviewed, are presented. Concerns are not identified.

PMID:42416395 | PMC:PMC13339717 | DOI:10.2903/j.efsa.2026.10169

Fluoride exposure affects development, thyroid-related gene expression, and follicle histology in early life stages of rainbow trout (Oncorhynchus mykiss) - July 8, 2026

Environ Sci Pollut Res Int. 2026 Jul 8. doi: 10.1007/s11356-026-38004-3. Online ahead of print.

ABSTRACT

Endocrine-disrupting chemicals (EDCs) are attracting growing interest due to their effects on humans and on ecosystems. Among suspected EDCs, fluoride is a widespread pollutant in aquatic ecosystems, particularly as a result of fluoridation of drinking water. It has also been described to affect fish development. The aim of this study was to determine if chronic fluoride exposure could affect early life stages of rainbow trout (Oncorhynchus mykiss) especially their growth and thyroid hormone system. Trout embryos were exposed from 6 to 40 days post-fertilization, to 0, 1.5, 5, 17, 27.5, or 51.5 mg/L. Growth was significantly inhibited by the exposure with shorter larvae and delayed resorption of the yolk sac. Fluoride exposure increased axial skeleton malformations, but had no effect on the occurrence of edema or hemorrhage. Genes tshβ, dio1, dio2, dio3, and thrα, coding for proteins involved in the thyroid hormone system, were overexpressed in a dose-dependent manner. While histopathological changes of thyroid follicles were observed in larvae exposed to fluoride, no difference in the levels of thyroid hormones was highlighted. In conclusion, results indicate that fluoride exposure during early life stages of rainbow trout might affect their growth and development and exhibit multisite effects on the thyroid hormone system.

PMID:42417920 | DOI:10.1007/s11356-026-38004-3

Root accumulation and efficient translocation of steroids in mangrove plants: Implications for an overlooked coastal reservoir - July 8, 2026

Mar Pollut Bull. 2026 Jul 8;232:120079. doi: 10.1016/j.marpolbul.2026.120079. Online ahead of print.

ABSTRACT

Steroid hormones are potent endocrine disruptors with profound effects on aquatic organisms, yet their environmental fate in mangrove ecosystems remains poorly understood. Here, we present the first systematic investigation of the occurrence, bioaccumulation, and translocation of 24 steroids in a subtropical mangrove ecosystem in Kaozhou Bay, South China. Steroids were ubiquitously detected in water (0.52-627 ng/L) and sediments (1.5-5.3 ng/g dw), with contamination hotspots located near sewage discharge outlets. Eleven steroids were further detected across mangrove plant tissues, with total concentrations ranging from not detected (ND) to 285 ng/g dw, showing distinct tissue-specific accumulation in the order root (22.8-285 ng/g dw) > leaf (ND-91.9 ng/g dw) > stem (6.3-65.5 ng/g dw). Root concentration factor (RCF) and transfer factor (TF) analyses of synthetic steroids revealed high root accumulation capacity, with RCFs up to 2602, and efficient root-to-stem translocation. Substantial interspecies variation was observed, with steroids preferentially accumulated in stems of Avicennia marina (Forsk.) Vierh and Kandelia obovata Sheue, but predominantly retained in roots of other mangrove species. By integrating field measurements with provincial-scale biomass data, we estimated a total steroid inventory of approximately 102 kg in mangroves across Guangdong Province. Collectively, these findings identify mangroves as major and dynamic reservoirs of steroid contaminants, redefining their role in coastal contaminant cycling from passive filters to significant storage sinks, with critical implications for regional ecological risk assessment.

PMID:42418896 | DOI:10.1016/j.marpolbul.2026.120079

Recent advances in pretreatment and chromatographic detection methods of bisphenol A over the past decade - July 8, 2026

J Chromatogr A. 2026 Jun 30;1785:467238. doi: 10.1016/j.chroma.2026.467238. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is a key industrial chemical, primarily used as a monomer for polycarbonate and epoxy resins, and widely found in food contact materials and consumer products. Owing to its well‑documented endocrine‑disrupting properties, the migration and exposure of BPA have attracted considerable attention in food safety and environmental monitoring. In response to rising detection demands and increasingly stringent regulatory limits, recent years have seen continuous development of efficient pretreatment methods coupled with accurate and sensitive detection techniques. This review systematically examines the research progress over the past decade on BPA pretreatment approaches-including conventional liquid‑liquid extraction, solid‑phase extraction, and various emerging microextraction techniques-alongside chromatographic detection methods. The strengths and limitations of each technique are critically assessed, and future prospects for advancing BPA pretreatment and chromatographic detection are also outlined.

PMID:42418918 | DOI:10.1016/j.chroma.2026.467238

Toward safer bisphenols remediation: Range-Corrected DFT study of zero-valent metal-mediated bisphenols reduction - July 8, 2026

J Mol Graph Model. 2026 Jul 7;148:109510. doi: 10.1016/j.jmgm.2026.109510. Online ahead of print.

ABSTRACT

The environmental persistence and health implications of bisphenol A (BPA) and its structural analogues, aided by the shortfalls of existing remediation techniques, necessitate the development of safer and more efficient degradation strategies. In this study, density functional theory (DFT) calculations were employed to investigate the reductive degradation of BPA, bisphenol F (BPF), bisphenol E (BPE), and bisphenol AP (BPAP) initiated by zero-valent metals (Zn⁰, Mg⁰, and Ca⁰) in vacuum and simulated aqueous media. Geometry optimizations, transition-state searches, intrinsic reaction coordinate analyses, and thermochemical evaluations were performed at the ωB97XD/cc-pVTZ level of theory. The degradation proceeds through a two-step deoxygenation mechanism involving formation of an organometallic intermediate followed by protonation-assisted cleavage to yield monophenolic and fully reduced products. Kinetic and thermodynamic analyses reveal that Zn⁰-mediated reduction is highly endothermic and non-spontaneous, whereas Mg⁰ exhibits moderate facilitation of reductive degradation in aqueous phase. Ca⁰-mediated reduction offers the lowest activation barriers and exhibits strongly exothermic, and spontaneous behavior, indicating the most feasible bisphenol degradation. Substituent variation and number of phenolic hydroxyl groups exert minimal influence on the overall degradation tendency. Toxicity assessment using experimental endocrine-disruption data and QSAR-predicted aquatic toxicity and mutagenicity indicates that the degradation products are significantly less toxic than their parent bisphenols. Overall, zero-valent calcium emerges as the most promising reductive agent for efficient and environmentally safer degradation of BPA and related analogues, highlighting the potential of zero-valent metal-mediated reduction as an alternative to conventional advanced oxidation processes.

PMID:42419084 | DOI:10.1016/j.jmgm.2026.109510

Endocrine and metabolic dysregulation as potential contributors to disease progression in major depressive disorder: Mechanisms and therapeutic implications-A review - July 8, 2026

Neurobiol Dis. 2026 Jul 8;227:107525. doi: 10.1016/j.nbd.2026.107525. Online ahead of print.

ABSTRACT

Major depressive disorder (MDD) is one of the leading psychiatric causes of disability worldwide and is characterized by marked heterogeneity, high recurrence risk, and low treatment rates. Traditional models have emphasized monoaminergic neurotransmitter imbalance, hypothalamic-pituitary-adrenal axis dysfunction, structural and functional brain remodeling, and inflammatory activation. Although these perspectives have substantially advanced our understanding of MDD, they do not fully account for its complex pathogenesis, and further investigation may support the development of novel prevention and treatment strategies. Increasing evidence indicates that MDD is closely associated with endocrine and metabolic abnormalities. This review summarizes evidence suggesting that endocrine and metabolic dysregulation may provide mechanistic insights into symptom burden, variability in disease progression, and treatment difficulties in certain patients. Particular attention is given to five interrelated domains: shared genetic and environmental susceptibility, dysfunction of the hypothalamic-pituitary-target gland axes, chronic low-grade inflammation and immune imbalance, impaired insulin signaling, and disruption of cerebral energy metabolic homeostasis. The review further explores potential clinical implications, including targeted endocrine and metabolic assessment, metabolism-related pharmacological strategies, modulation of the gut-brain axis, and lifestyle interventions. Rather than simply describing associative findings, this review aims to identify endocrine and metabolic abnormalities with potential predictive, modifiable, and clinically meaningful value, thereby providing a cautious and evidence-based framework for future risk assessment, disease-course interpretation, and adjunctive treatment of depression.

PMID:42419634 | DOI:10.1016/j.nbd.2026.107525

Peer review of the pesticide risk assessment for the active substance bifenazate in light of confirmatory data submitted - July 8, 2026

Disruption of the Gut Microbiome and Mental Health Effects Connected to Environmental Pollutants via the Gut-Brain Axis - July 7, 2026

Curr Neuropharmacol. 2026 Jul 6. doi: 10.2174/011570159X478499260630105121. Online ahead of print.

ABSTRACT

Environmental pollutants, including heavy metals, endocrine-disrupting chemicals, persistent organic pollutants, microplastics, and particulate matter, are increasingly recognized as key modifiers of the gut microbiome. These exposures can induce dysbiosis, disrupting the microbiota-gut-brain axis and influencing neurodevelopment, neurotransmission, immune regulation, and behavior. Mechanistically, pollutant-induced alterations in microbial metabolites (e.g., short-chain fatty acids, indoles, and bile acids), intestinal permeability, neuroinflammation, vagal signaling, and activation of the hypothalamic-pituitary-adrenal axis contribute to adverse neurobehavioral outcomes. Evidence from human cohort studies and animal models supports associations between pollutant exposure, microbial functional changes, and cognitive or mental health effects. This review synthesizes current mechanistic insights, highlighting advances in exposomic, microbial xenobiotic metabolism, and microbiome-targeted interventions to mitigate neurotoxicity. While these findings offer promising directions for risk assessment and therapeutic development, human evidence remains limited, and quantitative links between microbiome alterations and neurobehavioral outcomes require further investigation.

PMID:42411211 | DOI:10.2174/011570159X478499260630105121

Discovery of Effective Dual PROTAC Degraders with Synergistic Antitumor Activity for Overcoming Tamoxifen-Resistant Breast Cancer - July 7, 2026

J Med Chem. 2026 Jul 7. doi: 10.1021/acs.jmedchem.6c01189. Online ahead of print.

ABSTRACT

Endocrine therapies for estrogen receptor-positive (ER⁺) breast cancer (BC) often encounter primary or acquired resistance, and elevated expression of histone deacetylase 6 (HDAC6) exacerbates therapeutic challenges. Emerging evidence indicates that simultaneous attenuation of estrogen receptor α (ERα) and HDAC6 activities represents a promising strategy to overcome endocrine resistance. Herein, we report a novel hybrid ERα/HDAC6 dual-targeting PROTAC V-12c, which selectively degraded ERα and HDAC6 in vitro and in vivo and exhibited superior antiproliferation efficacy across a panel of BC cell lines. Mechanistically, V-12c degraded both ERα and HDAC6 via the proteasome pathway, induced cell cycle arrest and apoptosis, attenuated hormonal response, disrupted the autophagy-lysosome function, and triggered ferroptosis, collectively contributing to overcoming tamoxifen resistance. Importantly, V-12c potently suppressed tumor growth in endocrine-resistant BC models, outperforming single-target therapies. This study identified a multimechanistic action of dual PROTAC V-12c with potent antitumor effects, providing a promising therapeutic strategy for endocrine-resistant BC.

PMID:42411996 | DOI:10.1021/acs.jmedchem.6c01189

Re-thinking peripheral dysfunctions in obesity: The emerging role of sulphaceutics and sulphanutraceutics - July 7, 2026

Br J Pharmacol. 2026 Jul 7. doi: 10.1111/bph.70557. Online ahead of print.

ABSTRACT

Obesity is a chronic, relapsing, multisystem disease in which cardiometabolic risk arises from excess adiposity and progressive dysfunction of peripheral organs, ultimately disrupting endocrine and metabolic crosstalk among tissues. Within this network, sulphur-based biology, centred on hydrogen sulphide and related reactive sulphur species, has emerged as a key regulator of metabolic homeostasis, vascular tone, inflammatory response and mitochondrial function. Here, we review the chemical and mechanistic landscape of sulphaceutics (pharmacological sulphur-releasing agents) and sulphanutraceutics (diet-derived organosulphur compounds), focusing on their capacity to reprogramme peripheral dysfunctions in obesity. Evidence from experimental models, also supported by emerging human data, indicates that sulphur-based interventions can enhance skeletal muscle insulin signalling and performance, restore endothelial reactivity and reduce vascular inflammation, thereby modulating adipose expansion and inflammatory tone. These actions reflect the engagement of upstream redox-sensitive regulatory nodes rather than non-specific antioxidant effects, consistent with a system pharmacology mode of action.

PMID:42411922 | DOI:10.1111/bph.70557

Widespread bisphenol S analogues in E-waste recycling dust and air: Gas-particle partitioning behavior and human exposure implications - July 7, 2026

J Hazard Mater. 2026 Jul 6;514:142909. doi: 10.1016/j.jhazmat.2026.142909. Online ahead of print.

ABSTRACT

Bisphenol S (BPS) analogues are increasingly used as alternatives to bisphenol A (BPA), but their occurrence, phase behavior, and exposure implications in e-waste recycling environments remain poorly characterized. Here, we conducted an integrated investigation of BPS analogues (BPSs) in indoor dust and paired gas- and particle-phase air samples from e-waste dismantling workshops in South China, to characterize their occurrence profiles, gas-particle partitioning, endocrine-disruption screening, and occupational exposure risks. BPS and 11 analogues were detected in dust, while BPS and 10 analogues were detected in indoor air. ∑₁₂BPSs ranged from 48.1 to 2120 ng/g in dust and 135-1790 pg/m³ in air. DBSP and BPS dominated dust, whereas DBSP dominated the particulate phase and DPS dominated the gaseous phase. Notably, DPS was the only compound detected in all gas-phase samples, indicating distinct phase preference. Gas-particle partitioning coefficients correlated significantly with predicted subcooled liquid vapor pressures and octanol-air partition coefficients (p < 0.01). EDC-Predictor screening indicated endocrine-related interaction potential for several analogues, particularly DBSP and DPS. Estimated daily intakes via dust ingestion and inhalation reached 3.32 ng/kg bw/day under the high-end scenario, higher than the recently revised BPA TDI in a screening-level comparison. These findings reveal that overlooked BPS substitutes, particularly DBSP and DPS, act as phase-specific contributors to occupational exposure in e-waste workshops.

PMID:42413406 | DOI:10.1016/j.jhazmat.2026.142909

From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS - July 7, 2026

Stem Cell Rev Rep. 2026 Jul 7. doi: 10.1007/s12015-026-11188-4. Online ahead of print.

ABSTRACT

Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine-metabolic disorder affecting up to 18% of women worldwide and remains the leading cause of anovulatory infertility. Despite extensive research, current treatments primarily target symptoms, including menstrual irregularities, hyperandrogenism, and metabolic dysfunction, without addressing the underlying molecular and tissue-level disturbances. Advances in multi‑omic profiling have identified disruptions across neuroendocrine, metabolic, inflammatory, and extracellular matrix pathways, alongside genetic susceptibility at loci such as DENND1A, CYP17A1, LHCGR, FSHR, IRS1, and PPARG. However, the functional roles of many variants remain unresolved. CRISPR/Cas9 gene editing enables precise interrogation of these pathways, while stem cell-based platforms, including mesenchymal stem cells (MSCs), exosomes, and gene-edited induced pluripotent stem cells (iPSCs), may serve as complementary platforms for regeneration and disease modeling. Preclinical studies demonstrate that MSCs and their derivatives modulate inflammation, restore ovarian structure, and improve metabolic parameters, while iPSC-based models enable patient-specific investigation of steroidogenic and metabolic abnormalities. Translational challenges remain, including targeted delivery, off-target effects, phenotypic heterogeneity, and regulatory considerations. Integrating CRISPR‑based functional genomics with stem cell research may shift PMOS management from symptom‑focused care to targeted, mechanism‑driven interventions that could modify the course of PMOS (Graphical Abstract).

PMID:42412303 | DOI:10.1007/s12015-026-11188-4

Interplay between thermal contact and hormonal activity: A kinetic analysis on smartphone-induced endocrine disruption - July 7, 2026

J Steroid Biochem Mol Biol. 2026 Jul 7;264:107081. doi: 10.1016/j.jsbmb.2026.107081. Online ahead of print.

ABSTRACT

Endocrine toxicology has largely overlooked persistent, behavior-linked thermal microenvironments established by smartphones, a phenomenon characterized by near-continuous human-thermal interaction. In this review, we propose a mechanistic model of the thermokinetic endocrine interface to explain how heat from smartphones might alter endocrine-relevant systems. Offering a new view on chemical interactions with consumer devices, we posit that localized thermal pulses, not continuous low-dose exposure, can accelerate the migration of polymer additives, influence desorption and diffusion dynamics, and intensify the transfer of surface chemicals to the skin. Materials science, dermal pharmacology, and endocrine signaling evidence indicate that gentle heating can alter the stratum corneum's permeability, tissue distribution, receptor mobility, and ligand-receptor residence kinetics. We hypothesize that smartphone-generated heat could act as a kinetic amplifier, repurposing intermittent contact into temporally regulated internal microdosing and altered signaling responsiveness thereby mitigating its role as a primary endocrine toxicant. Whereas current perspectives reorient risk evaluation from static external exposure benchmarks to evolving internal dose profiles, thermal exposure configurations, and biological temporal dynamics. We propose using temperature-integrated physiologically based pharmacokinetic models, warm-exposure endocrine assays, and real-world migration analytics for strategic prioritization. By incorporating thermal biology into endocrine risk assessment, new pathways linking everyday devices to hormonal disruption can be discovered.

PMID:42413587 | DOI:10.1016/j.jsbmb.2026.107081

Plant-associated microbial enrichment is linked to trace emerging contaminant removal in full-scale constructed wetland - July 7, 2026

Bioresour Technol. 2026 Jul 14;460:135345. doi: 10.1016/j.biortech.2026.135345. Online ahead of print.

ABSTRACT

Emerging contaminants (ECs) in wastewater treatment plant (WWTP) effluents pose increasing risks to aquatic ecosystems, necessitating advanced treatment solutions. Constructed wetlands offer a green, low-carbon approach for effluent polishing, yet field-scale evidence on EC removal mechanisms remains limited. This study conducted a 10-month operational monitoring (January-October 2025) of a full-scale constructed wetland receiving municipal WWTP effluent in Suzhou, China, to evaluate the removal of 154 ECs-including pharmaceuticals and personal care products (PPCPs), endocrine-disrupting chemicals (EDCs), per- and polyfluoroalkyl substances (PFAS), antibiotics, and pesticides-and elucidate the underlying mechanisms. The system achieved 40-50% EC removal alongside 14.7%-41.1% conventional pollutants reduction. EC removal efficiency correlated positively with influent concentration but showed no significant correlation with log Kow or molecular weight, indicating that mass transfer and metabolic thresholds govern trace-level EC removal. Direct plant uptake accounted for only 0.14% of the total mass of ECs removed. Instead, plants played an indirect role by shaping rhizosphere microbial communities: rhizosphere substrates exhibited higher microbial richness and greater abundance of complex organic pollutants degraders than deeper layers. Six plant species recruited distinct functional microbial assemblages, includingPantoeainAcorus calamus,ExiguobacteriuminCanna indicaandArundo donax, andComamonadaceaewithSphingobiuminThalia dealbata. Based on these findings, we propose several strategies to further enhance EC removal efficiency, including strengthening water-microorganism contact mechanisms, adopting mixed-species planting modes, and expanding the rhizosphere area. Collectively, these findings provide a theoretical foundation for optimizing plant-microbe-based technologies for EC removal in constructed wetlands and other nature-based systems.

PMID:42413588 | DOI:10.1016/j.biortech.2026.135345

Non-Destructive Extraction and Characterization of Human Pulmonary Microplastics and the Associated Endocrine Disrupting Chemicals - July 7, 2026

Environ Pollut. 2026 Jul 7:128705. doi: 10.1016/j.envpol.2026.128705. Online ahead of print.

ABSTRACT

Inhalation exposure to microplastics (MPs) and associated plastic additives has raised growing public health concerns, although their distribution and potential health impacts in human lungs remain poorly understood. To minimize interference from lipids and collagen fibers, particulate matter (PM) was first extracted from lung tissues using a non-destructive ultrasonic treatment and sequential centrifugation (USC) method, followed by obtaining the microplastic extract (MPE) using ultrasound and density separation (UDS), and subsequent detection of EDCs via GC-MS. This approach enabled characterization of both pulmonary MPs and associated EDCs. Sixteen polymer types were identified, with nylon (27.3%), polyester (10.7%), and polyurethane (7.8%) being the most abundant, alongside 71 EDCs, including phthalic acid esters (PAEs), organophosphate esters (OPEs), and polycyclic aromatic hydrocarbons (PAHs). Smokers and individuals over 60 years old showed significantly higher pulmonary MP abundances (P < 0.01). EDC concentrations were higher in MPE than in surrounding lung tissues, particularly for PAEs, which showed elevated enrichment factor MPs (EFMs range: 16.4-101; mean: 50.1). The average concentration of pulmonary MPs, estimated via PAEs under an upper-bound scenario, was 7.35 mg/kg. The heterogeneous distribution of MPs and additives within pulmonary tissues may have implications for localized exposure, although the biological effects remain to be further investigated. These findings underscore the importance of characterizing MPs and associated contaminants to better assess potential health risks.

PMID:42413852 | DOI:10.1016/j.envpol.2026.128705

Non-Destructive Extraction and Characterization of Human Pulmonary Microplastics and the Associated Endocrine Disrupting Chemicals - July 7, 2026

Environ Pollut. 2026 Jul 7:128705. doi: 10.1016/j.envpol.2026.128705. Online ahead of print.

ABSTRACT

PMID:42413852 | DOI:10.1016/j.envpol.2026.128705

Disruption of the Gut Microbiome and Mental Health Effects Connected to Environmental Pollutants via the Gut-Brain Axis - July 7, 2026

Curr Neuropharmacol. 2026 Jul 6. doi: 10.2174/011570159X478499260630105121. Online ahead of print.

ABSTRACT

PMID:42411211 | DOI:10.2174/011570159X478499260630105121

Plant-associated microbial enrichment is linked to trace emerging contaminant removal in full-scale constructed wetland - July 7, 2026

Bioresour Technol. 2026 Jul 14;460:135345. doi: 10.1016/j.biortech.2026.135345. Online ahead of print.

ABSTRACT

PMID:42413588 | DOI:10.1016/j.biortech.2026.135345

Zingerone ameliorates ovarian impairment by regulating steroidogenesis and apoptosis in letrozole-treated mouse - July 6, 2026

Endocrinology. 2026 Jul 6:bqag078. doi: 10.1210/endocr/bqag078. Online ahead of print.

ABSTRACT

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, disrupted folliculogenesis, and subfertility. This study evaluated the therapeutic efficacy of zingerone(4-(4-hydroxy-3-methoxyphenyl)-2-butanone) in a letrozole-induced hyperandrogenised PCOS-like mouse model. Zingerone administration, particularly at 25 and 50 mg/kg, significantly improved ovarian morphology by enhancing follicular development and corpus luteum formation. This was accompanied by increased granulosa cell proliferation (PCNA) and attenuation of apoptosis, evidenced by up-regulation of BCL2 and reduced TUNEL staining. Zingerone reprogrammed ovarian steroidogenesis by reducing circulating testosterone, down-regulating androgen receptor expression, suppressing StAR, and up-regulating aromatase, thereby promoting a shift toward estrogen biosynthesis. Autophagy analysis indicated restoration of autophagic flux, reflected by decreased p62 levels and modulation of Beclin1 and LC3B expression. These coordinated molecular and cellular changes resulted in functional recovery, with significant improvement in fertility and litter size at higher doses (25 and 50 mg/kg). Collectively, zingerone exerts dose-dependent, multi-target effects to restore endocrine, cellular, and autophagic homeostasis, thereby ameliorating ovarian dysfunction in PCOS.

PMID:42405496 | DOI:10.1210/endocr/bqag078

Next-generation biodegradation of chlorpyrifos: integrative microbial strategies, molecular mechanisms, and environmental impacts - July 6, 2026

Biodegradation. 2026 Jul 6;37(4):110. doi: 10.1007/s10532-026-10329-3.

ABSTRACT

Chlorpyrifos (CP) belongs to organophosphate pesticide group. It is extensively applied in agricultural and household settings due to its broad-spectrum insecticidal properties. However, its persistence, bioaccumulative behavior, and toxicological effects on non-target organisms, including humans, pose significant environmental and public health concerns. CP and its metabolites, particularly two including 3,5,6-trichloropyridinol (TCP) and chlorpyrifos-oxon (CPO), have been recently reported to be widely found various samples such as in soils, sediments, water bodies, crops, and even human biological fluids. These compounds disrupt biogeochemical cycles, alter soil microbial communities, inhibit enzyme activities, and are linked to neurotoxicity, endocrine disruption, and genotoxic effects. Conventional remediation strategies such as photodegradation, ultrasonication, and filtration remain ineffective due to incomplete degradation and secondary pollution risks. Recent studies highlight the efficiency of microbial degradation, especially by bacteria such as Bacillus, Klebsiella, Pseudomonas and Enterobacter as a promising, eco-friendly alternative. These microorganisms utilize CP as a only carbon source, and degradation calibre is greatly governed by various abiotic factors like pH, temperature, and moisture. The genetic as well as enzymatic analyses reveal key roles of organophosphorus hydrolases encoded by genes such as opd and mpd. The integration of plant growth-promoting traits and laccase activity further enhances their bioremediation capability. Additionally, recent advancements in biosensing techniques for CP detection offer improved sensitivity and real-time monitoring. This review provides a comprehensive analysis of CP's environmental fate, toxicological impact, degradation pathways, and the emerging role of bacterial bioremediation, highlighting its potential for sustainable environmental detoxification.

PMID:42406180 | DOI:10.1007/s10532-026-10329-3

Tributyltin chloride and triphenyltin chloride inhibit steroid hormone secretion by mouse Leydig cells TM3 and human adrenocortical cells H295R - July 6, 2026

Endocr Regul. 2026 Jul 5;60(1):159-171. doi: 10.2478/enr-2026-0016. Print 2026 Jan 1.

ABSTRACT

Objective. To find a possible balance between toxicity and potential anticancer activity of novel triorganotin compounds, retinoid X receptor (RXR) agonists, investigation the relationship between the structure, physicochemical properties, and biological activity of these compounds in non-tumorigenic and tumorigenic cells is required. This study aimed to investigate the effects of selected triorganotin compounds, tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPTCl), on viability and steroidogenic function of non-tumorigenic mouse Leydig cell line TM3 and human adrenocortical carcinoma cell line H295R. Methods. Gene and protein expression of RXR subtypes (RXRα, RXRβ, RXRγ) in TM3 Leydig cells was identified by qualitative PCR and immunofluorescence. The potency of TBT-Cl and TPTCl to induce mRNA expression of RXR subtypes in TM3 cells was analyzed by semi-quantitative real-time PCR. After exposure of TM3 and H295R cells to different concentration of TBT-Cl and TPT-Cl (0.1 nM-1 µM) for different time periods (24, 48, 72 h), cell viability was evaluated by detection of mitochondrial activity (MTT assay) and membrane integrity (LDH assay), and steroid hormone (testosterone, cortisol) levels in culture media were measured by radioimmunoassay. Results. Qualitative PCR and immunofluorescence examination revealed that all RXR subtypes, RXRα, RXRβ, RXRγ, are expressed in TM3 Leydig cells. TBT-Cl (500 nM) activated the expression of RXRα and RXRβ and at a concentration of 100 nM, RXRγ expression. TPT-Cl (10 and 100 nM) activated the expression of all three RXR subtypes and at a concentration of 500 nM, reduced RXRα expression similar to 9cRA (100 nM). Both compounds, TBT-Cl and TPT-Cl, induced a dose- and time-dependent significant decrease in the viability of TM3 Leydig cells and, in addition, TBT-Cl (500 nM and 1 µM) significantly inhibited androstenedione-induced testosterone secretion by these cells. Similarly, both tested triorganotin compounds (1 µM) significantly decreased viability of adrenocortical H295R cells and basal as well as forskolin-stimulated testosterone and cortisol secretions by these cells. Conclusion. TBT-Cl and TPT-Cl compromised cell viability and induced important functional alteration in Leydig cells probably through RXR activation with potential implications for male reproductive function. Endocrine-disrupting properties of TBT-Cl and TPT-Cl were demonstrated in adrenocortical H295R cells.

PMID:42406097 | DOI:10.2478/enr-2026-0016

Chronic toxicity and endocrine-disrupting effects of 4-tert-octylphenol and 4-tert-butylphenol in Daphnia magna - July 6, 2026

Comp Biochem Physiol C Toxicol Pharmacol. 2026 Jul 6;308:110609. doi: 10.1016/j.cbpc.2026.110609. Online ahead of print.

ABSTRACT

Alkylphenols such as 4-tert-octylphenol (4-tert-OP) and 4-tert-butylphenol (4-tert-BP) are recognized endocrine disruptors frequently detected in aquatic environments; however, their long-term effects on freshwater invertebrates remain insufficiently characterized. This study investigated the chronic toxicity and endocrine-disrupting effects of 4-tert-OP and 4-tert-BP on Daphnia magna using a comprehensive suite of endpoints, including life-history traits, physiological responses, oxidative stress markers, behavioral assessments, and gene expression analyses. Both compounds induced significant, concentration-dependent adverse effects, including reduced survival, growth inhibition, delayed reproduction, decreased offspring production, and reduced molting frequency. Biochemical assays revealed alterations in antioxidant enzyme activities, specifically changes in superoxide dismutase (SOD) and catalase (CAT), as well as elevated malondialdehyde (MDA) levels, indicative of oxidative stress and lipid peroxidation. Acetylcholinesterase (AChE) activity decreased, and swimming performance declined, indicating neurotoxic effects. At the molecular level, both alkylphenols downregulated genes associated with molting and hormonal regulation, including chitinase, cuticle protein, and key components of the ecdysteroid signaling pathway (ecra, ecrb, hr3, e75, and rxr). Additionally, the vitellogenin genes (vtg1 and vtg2), which are essential for reproduction, were suppressed. Collectively, these results demonstrate that 4-tert-OP and 4-tert-BP disrupt multiple biological targets in D. magna, with oxidative stress, neurotoxicity, and hormonal interference contributing to impaired growth and reproduction. These findings underscore the ecological risks posed by alkylphenol contamination and highlight the necessity of integrating multiple lines of evidence in environmental risk assessments.

PMID:42407138 | DOI:10.1016/j.cbpc.2026.110609