Yankai Xia

Thyroid homeostasis is essential for human health, and arsenic (As) and mercury (Hg) have drawn considerable attention due to their bioaccumulation and potential health risks. However, evidence on their thyroid-disrupting effects remains inconsistent and largely derived from cross-sectional studies, hindering causal inference and risk integration. Here, a meta-analysis was first conducted, which confirmed that both As (Cohen’s d = 0.45, 95% CI: 0.10, 0.81) and Hg (Cohen’s d = 0.40, 95% CI: 0.16, 0.65) exposure were associated with an increased risk of thyroid dysfunction. To further clarify temporality, we analyzed prospective cohort data from 800 adult women in Jiangsu, China. Results showed that As exposure was linearly and positively associated with free thyroxine (FT4) (β = 0.19, 95% CI: 0.01, 0.37), while Hg showed an inverted U-shaped dose–response relationship with FT4 levels. Based on the above epidemiological evidence, we further integrated in vivo and in vitro evidence from published related literature, applied the Targeted Risk Assessment for Environmental Chemicals (TRAEC, ver.1.1) strategy, and obtained final scores of 7.79 for As and 7.09 for Hg (out of 10), indicating a moderate level of thyroid-related health risk. Collectively, these findings suggest that As and Hg exposure may disturb thyroid function, supporting the need for targeted mitigation and further mechanistic research.

Background: Although fine particulate matter (PM _2.5 ) has been linked to spontaneous abortion (SAB), the roles of its components remained unclear, and the potential modifying effects of green space and maternal psychological factors were unknown. In this study, we aimed to explore whether green space and maternal psychological status modify the associations of PM _2.5 and its components with SAB risk. Methods: We included 20,117 pregnant women from Nanjing, China and estimated the average concentration of PM _2.5 and its components based on the residential addresses, including nitrate (NO ₃ ^– ), sulfate (SO ₄ ^2- ), ammonium (NH ₄ ⁺ ), black carbon (BC), and organic matter (OM). Green space was indicated by Enhanced Vegetation Index (EVI) and Normalized Difference Vegetation Index (NDVI). The maternal psychological status was assessed using the Self-Rating Anxiety Scale (SAS) for anxiety, the Self-Rating Depression Scale (SDS) for depression, and the Impact of Event Scale-Revised (IES-R) for post-traumatic stress symptoms (PTSD). Multivariable logistic regression combined with propensity score matching (PSM) was applied to estimate the associations of PM _2.5 and its components with SAB risk. Two-pollutant models, weighted quantile sum regression (WQS), and Bayesian kernel machine regression (BKMR) were utilized to assess the joint effect of PM _2.5 components. Interactions and the Johnson-Neyman method were used to examine the modifying effects of green space and maternal psychological factors. Results: Long-term exposure to PM _2.5 and its components was positively associated with the risk of SAB. After adjustment, each interquartile range (IQR) increase in PM _2.5 and its components might increase the odds of SAB (PM _2.5 , OR = 1.18, 95% CI: 1.11–1.26, P 4 ⁺ , OR = 1.19, 95% CI: 1.11–1.26, P 3 ^– , OR = 1.18, 95% CI: 1.11–1.26, P 4 ^2- , OR = 1.17, 95% CI: 1.10–1.25, P P P 2.5 and its components remained significantly associated with the risk of SAB. However, OM (OR = 1.08, 95% CI: 0.99–1.18, P = 0.08) and BC (OR = 1.07, 95% CI: 0.97–1.18, P = 0.19) showed null associations. Significant effect modification was observed between PM _2.5 and its components and green space measured by NDVI within a 1000-m buffer (NDVI 1000 m; P for interaction 2.5 and SAB was strongest in the lowest greenness quartile and was attenuated or became non-significant in some higher greenness quartiles (Q1, OR = 1.30, 95% CI: 1.14–1.48, P P = 0.80; Q3, OR = 1.29, 95% CI: 1.14–1.46, P P = 0.12). Higher psychological distress may be associated with an elevated risk of SAB (SDS: OR = 1.90, 95% CI: 1.40–2.56, P P 2.5 and its major components, particularly NO ₃ ^– , NH ₄ ⁺ , and SO ₄ ^2- , were associated with an increased risk of SAB. Residential green space, especially NDVI 1000 m, may attenuate these associations, while maternal depressive and anxiety symptoms were independently associated with SAB risk without significant effect modification.

Prenatal exposures influence infant health, yet the microbiota related mechanisms remain unclear. We profiled 776 maternal exposome variables and meconium microbiota in 1,689 mother–infant pairs, establishing a network linking maternal exposures, neonatal microbiota, and 10 infant outcomes. Using multiomics, pathway enrichment, and robust regression, we identified maternal anthropometrics and clinical indicators as key predictors of infant development, and specific metabolic and chemical exposures as major factors associated with microbiota composition. These microbial changes were associated with infant growth, eczema, and neurodevelopment. Notably, maternal metabolites (e.g., cholesterol) and environmental chemicals (e.g., triphenyl phosphate and perfluorobutane sulfonic acid) were associated with microbiota composition, particularly in Firmicutes, Proteobacteria, and Bacteroidetes. Our findings establish a prenatal exposome–microbiota–host axis, offering a scalable framework to understand early-life health determinants and guide preventive strategies.

Polystyrene nanoplastics (PS-NPs) are widespread environmental pollutants that have attracted growing concerns regarding reproductive health. Nevertheless, their effects on spontaneous abortion (SAB) and the underlying mechanisms remain unclear. In this study, we investigated the reproductive toxicity of 50 nm PS-NPs using a pregnant mouse exposure model and HTR-8/SVneo trophoblast cells. In vivo, PS-NPs crossed the placental barrier, disrupted placental structure, altered pregnancy-related hormone levels, and increased embryo resorption. In vitro, PS-NPs reduced trophoblast cell viability and migration, induced cell cycle arrest and apoptosis, and caused mitochondrial dysfunction. Combined transcriptomic and metabolomic analyses further demonstrated that PS-NPs disrupted glutathione and glycerophospholipid metabolism and enriched pathways associated with ferroptosis. Mechanistically, PS-NPs induced reactive oxygen species (ROS) accumulation, glutathione depletion, iron overload, lipid peroxidation, GPX4 downregulation, and ACSL4 upregulation, indicating activation of ferroptosis. Functional rescue experiments in HTR-8/SVneo cells revealed that the ferroptosis inhibitor Ferrostatin-1 partially alleviated PS-NPs-induced ferroptotic injury, whereas the ROS scavenger N-acetylcysteine partially reduced ROS accumulation and improved mitochondrial function. Collectively, our findings suggest that PS-NPs exposure impairs placental function and pregnancy maintenance, with ROS-mediated ferroptosis-related trophoblast injury potentially involved, providing novel insights into the reproductive toxicity of nanoplastics during pregnancy.

Ductular reaction (DR) is a hallmark of biliary atresia (BA), but its underlying mechanisms remain unclear. In this study, we identified an expanded NCAM1 ⁺ EpCAM ⁺ hepatic progenitor cells (HPCs) as the predominant DR‐related cell cluster using single‐nucleus RNA sequencing, and NCAM1 ⁺ EpCAM ⁺ HPC‐derived organoids exhibited impaired biliary differentiation in BA. α‐synuclein was characterized as the signature gene of this cluster, exhibiting upregulated expression in liver tissues from both human BA and mouse BA models, as well as in the serum of patients with BA. Biliary organoids derived from mouse single cells and human induced pluripotent stem cells (iPSCs) confirmed that α‐synuclein accumulation drove aberrant biliary development in both mouse and human organoids, and induced BA‐like transcriptomic alterations, characterized by significant enrichment of the glutathione (GSH) metabolic pathway. Consistently, hepatic GSH was reduced in both human BA and mouse BA models. In human intrahepatic biliary epithelial cells (HiBECs), α‐synuclein overexpression decreased cellular GSH content and increased mitochondrial reactive oxygen species (ROS) under oxidative stress. The present study showed that NCAM1 ⁺ EpCAM ⁺ HPCs were expanded and characterized by an aggregation of α‐synuclein in BA, which could increase cellular susceptibility to GSH‐associated redox imbalance, and lead to aberrant bile duct regeneration.