Ecotoxicology and Environmental Safety最新文献

Phthalates (PAEs) are ubiquitous neurotoxic contaminants, but their effects on cognitive function in the elderly remain unclear. In this study, we explored the associations between repeated urinary PAE measurements and plasma neurofilament light chain (NfL) levels, as well as cognitive function among older adults in Shanghai. Ten urinary PAE metabolites were measured in 330 participants in 2019, 2021, and 2023. Plasma NfL was measured and the Mini-Mental State Examination (MMSE) was administered during the third survey wave. A complementary cross-sectional analysis included 1020 participants assessed in 2023. Both single-pollutant and mixture models were applied. In the repeated-measures analysis, the 2021 PAE mixture (β = 0.071; 95% CI: 0.005, 0.138) and the joint mixture across all three waves (β = 0.096; 95% CI: 0.003, 0.189) were associated with higher NfL levels. No significant associations with MMSE outcomes were observed in the smaller cognitive subsample. In the 2023 analysis, the PAE mixture was associated with higher NfL levels, lower orientation, registration, and total MMSE scores, and higher odds of cognitive impairment. These findings suggest that the associations with NfL may vary according to the timing of exposure assessment and provide complementary cross-sectional evidence linking PAE exposure to selected cognitive outcomes. Further prospective studies are needed to confirm these findings.

Tebuconazole (TEB) is a widely used triazole fungicide with suspected endocrine-disrupting and reproductive toxicity. However, its effects on human placental trophoblasts and its association with unexplained recurrent pregnancy loss (RPL) remain poorly defined. Chorionic villi from 27 women with unexplained RPL and 25 women with normal pregnancies were analyzed by HPLC-MS/MS, and TEB effects were examined in BeWo and HTR-8/SVneo trophoblasts. Villus TEB residues were 1.82-fold higher in the RPL group (mean 0.0356 versus 0.0196 ng/g; P < 0.001), whereas TEB-OH did not differ significantly. In HTR-8/SVneo cells, 48-h TEB exposure reduced estradiol secretion at 20-80 µM and impaired migration at 40-80 µM without a significant loss of CCK-8 viability, and increased intracellular labile Fe^2 +. Transcriptome profiling at 80 µM identified 1680 differentially expressed genes (797 up-regulated, 883 down-regulated), and the downregulation of GPX4, TFRC, and SLC40A1 was confirmed by RT-qPCR and Western blotting. Network toxicology identified 72 core targets shared with RPL and fetal growth restriction, and docking predicted GPX4 as a candidate binding target of TEB (Ki= 44.74 µM). Consistent with a ferroptotic mechanism, ferrostatin-1 (2 µM) attenuated TEB-induced lipid peroxidation and Fe²⁺accumulation and partially restored GPX4, SLC40A1, and TFRC abundance, trophoblast migration, and estradiol secretion. These findings suggest that ferroptosis-related lipid peroxidation contributes to TEB-induced trophoblast dysfunction and links chorionic villus TEB residues to unexplained RPL. Because the effective in vitro concentrations exceed typical human exposure levels, the results provide mechanistic evidence of hazard and warrant further risk assessment.

Ambient ozone (O₃) is a highly reactive secondary air pollutant whose health relevance is increasingly recognized. Although epidemiological evidence has linked O₃ exposure to multiple diseases, the biological mechanisms underlying the health effects remain incompletely understood. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been implicated in diverse diseases and is increasingly considered a potential mechanism underlying pollutant-induced health injury. Notably, the core biochemical features of ferroptosis closely align with multiple O₃-induced molecular responses, including reactive oxygen species accumulation, excessive lipid peroxidation, and impaired antioxidant defenses, suggesting that ferroptosis may be a regulated cell death mechanism involved in O₃-related toxicity. However, evidence linking O₃ exposure to ferroptosis remains limited and fragmented. Therefore, this review synthesizes current mechanistic insights and available evidence connecting O₃ exposure with ferroptosis. Relevant literature was retrieved from databases including PubMed, Web of Science, and Scopus, covering studies published up to May 2026, and included studies addressing O₃ exposure in relation to ferroptosis, or to ferroptosis-relevant processes such as lipid peroxidation, antioxidant disruption, iron dyshomeostasis, or mitochondrial dysfunction. We further discuss current limitations and priorities for future research, with the aim of evaluating ferroptosis as a candidate mechanism underlying O₃-associated health effects.

Nanoplastics (NPs) are persistent environmental pollutants that can accumulate in the liver, but the mechanisms of their hepatotoxicity remain poorly understood. Here, using AML12 cells and a mouse model, we investigated how polystyrene nanoplastics (PS-NPs) cause liver injury. Exposure to PS-NPs induced dose-dependent cytotoxicity and ferroptosis, evidenced by elevated Fe²⁺ and reactive oxygen species (ROS) levels, enhanced lipid peroxidation, glutathione peroxidase 4 (GPX4) downregulation, and acyl-CoA synthetase long chain family member 4 (ACSL4) upregulation. PS-NPs exposure increased hepatic pathological injury scores and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in vivo. Treatment with ferrostatin-1 (Fer-1) markedly attenuated these changes. Mechanistically, PS-NPs exposure disrupted lysosomal function, as shown by reduced expression of lysosome-associated membrane proteins and increased lysosomal pH. This lysosomal impairment hindered degradative capacity and led to ACSL4 accumulation. Restoring lysosomal function with NKH477 reduced ACSL4 levels. Together, these findings suggest that PS-NPs promote hepatocyte ferroptosis through lysosomal dysfunction and subsequent ACSL4 accumulation. This study provides new insight into the mechanisms of PS-NPs-induced liver toxicity and highlights potential targets for intervention.

The incidence of central precocious puberty (CPP) has been steadily increasing, and plasticizers have been implicated in the onset of CPP. A thorough understanding of these mechanisms could enable early intervention to prevent CPP from its root cause, offering valuable directions for future basic research and treatment strategies. This study identified CPP-relevant targets for plasticizers via public databases, screening biomarkers with eight algorithms. Furthermore, GeneMANIA network analysis, chromosome localization, subcellular localization, ceRNA network analysis, and functional enrichment analysis were included to ascertain the molecular function of biomarkers. Molecular docking and molecular dynamics analyses provided valuable insights into ligand-target interaction mechanisms. A DEHP-induced CPP mouse model was validated by morphological, histological, hormonal, and molecular markers. EGFR, MYC, PTEN and MTOR were identified as CPP biomarkers, involved in cell cycle regulation and PI3K/AKT signaling. These targets were enriched in stress responses and cancer-related pathways. EGFR exhibited the broadest plasticizer binding spectrum, with EGFR-butyl benzyl phthalate showing the highest binding affinity (-8.0 kcal/mol); molecular dynamics confirmed stable target-plasticizer complexes. The DEHP-induced CPP model was successfully established, with model mice exhibiting an advanced vaginal opening time, increased absolute weights and indices of ovaries and uterus, accelerated estrous cycles, altered ovarian follicle developmental phenotypes, elevated serum FSH/LH/E2 (p < 0.001) and dysregulated biomarker expression (downregulated PTEN, upregulated EGFR/MYC/MTOR) in the HPG axis. The increased expression of canonical pubertal regulators indicates premature activation of the KNDy/kisspeptin-GnRH neuroendocrine axis in DEHP-induced CPP. Our study identified EGFR, MYC, PTEN and mTOR as core targets of plasticizer-triggered CPP, clarifying their regulatory mechanisms and providing novel molecular insights for CPP management.

Mercury (Hg) pollution endangers the environment and human health. Coix (Coix lacryma-jobi L.), an important medicinal and edible crop, requires study of its Hg, particularly methylmercury (MeHg) accumulation characteristics and exposure risks. Paired coix plants and rhizosphere soils were collected from cultivation areas in Southwest China to assess inorganic Hg (IHg) and MeHg distribution and transfer in root, stem, leaf and grain. Combined with partial least squares path modeling (PLS-PM), we quantified the effects of soil properties, bioavailable Hg fractions, and dissolved organic carbon on Hg transportation and accumulation in the soil-coix system. Across tissues, MeHg exhibited stronger bioconcentration than IHg. Approximately 55% of coix grain samples had MeHg bioconcentration factors (BCFs) exceeding 1 (mean = 3.44, comparable to MeHg-sensitive rice); coix grain accumulated MeHg, yet its MeHg concentration (0.281 ± 0.215 µg/kg) remained lower than rice from heavily Hg-contaminated sites. The positive correlations of MeHg concentrations between coix grain and leaf (p < 0.05), and particularly between leaf and rhizosphere soil (p < 0.001), suggest that rhizosphere soil is the primary source of MeHg accumulated in coix grain. In contrast, leaf IHg levels (61.3 ± 46.7 µg/kg) were significantly higher than those in stem and root tissues, and the IHg translocation factors (TFs) from root to aboveground tissues were low. Dietary coix intake was the primary Hg exposure pathway for residents. Although the non-carcinogenic hazard quotients for residents were below the safety threshold (HQ < 1), children faced greater IHg and MeHg health risks. This study is the first to clarify the differential accumulation mechanisms of IHg and MeHg in coix, and informs safe coix production, soil Hg monitoring, and dietary Hg risk management.