Ecotoxicology and Environmental Safety最新文献

Per- and polyfluoroalkyl substances (PFAS) have been reported to possess endocrine-disrupting and tumor-promoting activity. However, the association between PFAS exposure and papillary thyroid carcinoma (PTC) remains poorly understood. This case-control study investigated whether PFAS exposure is associated with PTC risk, and if so, whether this association is mediated through thyroid hormone disruption and linked to specific clinicopathological and genetic features of the tumor. We recruited 60 PTC patients and 60 healthy controls from Shanghai, China. Serum levels of PFAS and thyroid hormones were measured. Multiple linear regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were used to analyze associations between PFAS mixtures and individual congeners with PTC risk and thyroid function. A chronic reference dose (CRfD) for PFOS was derived from animal studies using benchmark dose modeling. PTC patients had significantly elevated serum levels of several PFAS, including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), and 8:2 chlorinated perfluoroalkyl ether sulfonic acid (8:2Cl-PFESA), compared to controls. WQS regression indicated a significant positive association between PFAS mixture exposure and PTC risk (OR = 2.01, p = 0.023), with 8:2CI-PFESA, PFDoDA, PFBS, and PFOS identified as the primary contributors. Furthermore, specific PFAS congeners were associated with more aggressive tumor features, including advanced TNM stage and with high-risk genetic alterations such as TERT mutation, and RAS&TERT promoter co-mutations. In terms of hormonal effects, Furthermore, perfluorobutanesulfonic acid (PFBS) and 8:2Cl-PFESA showed significant negative dose-response relationships with FT3 levels in patients, suggesting a potential link between PFAS-induced thyroid disruption and carcinogenesis. The derived oral CRfD for PFOS, based on triiodothyronine reduction, was 40 ng/kg·bw/day. Our findings indicate that PFAS exposure is associated with an increased risk of PTC, potentially through mechanisms involving thyroid hormone disruption and the promotion of more aggressive tumor characteristics. These results underscore the need for stricter regulation of industrial PFAS emissions and enhanced thyroid function monitoring in high-risk populations.

Fetoplacental ratio (FPR), the ratio of birthweight (BW) to placental weight (PW), indicates placental efficiency. Changes in FPR are linked to poor pregnancy outcomes and child health risks. Bisphenols and phthalates are endocrine disruptors found in plastics and personal care products that can cross the placenta and have been linked to pregnancy complications and adverse child health outcomes. We examined prenatal exposure to these chemicals in relation to FPR as a possible explanation for these risks. Our analysis included 393 participants in the New York University Children's Health and Environment Study with data on prenatal chemical exposure, BW, and PW from singleton live births. We calculated molar sums of bisphenols and of metabolites of low and high molecular weight (LMW, HMW) phthalates, diethylhexyl phthalate (DEHP), and antiandrogenic phthalates. Linear regression models were adjusted for maternal age, prepregnancy BMI, parity, gestational age at delivery, and fetal sex. Analyses were stratified by fetal sex. HMW were positively associated with FPR in the combined fetal sex sample (beta=0.26, [0.01, 0.50]) with a similar trend for DEHP and antiandrogenic phthalates (betas=0.21 [-0.04, 0.45] and 0.21 [-0.04, 0.45], respectively). Stratified analyses revealed that these results were driven by females, among whom LMW were also associated with higher FPR (beta=0.23 [0.003, 0.45]). No associations were observed between chemicals and BW in either combined or sex-stratified models. In contrast, HMW, LMW, DEHP, di-n-octylphthalate and bisphenols had negative associations with PW, suggesting placental growth as a target for phthalate-mediated endocrine disruption.

Diabetic retinopathy (DR), a leading cause of vision loss in diabetes, arises from intricate metabolic and environmental interactions. This study investigates how polychlorinated biphenyls (PCBs) contribute to DR pathogenesis. Network toxicology was employed to identify overlapping gene targets between PCBs and DR. Machine learning analyses subsequently refined these targets to four core genes: TP53, ESR1, EGR1, and HSPA5. Diagnostic modeling validated using human retinal transcriptomes demonstrated TP53's robust diagnostic accuracy, yielding area under the curve (AUC) values of 0.740 for non-proliferative DR (NPDR) and 0.920 for proliferative DR (PDR), with expression levels positively correlated with DR severity and ETDRS scores. Molecular docking confirmed strong binding affinities of toxic PCB congeners to TP53 and ESR1. Single-cell RNA sequencing in a DR mouse model revealed enriched Trp53 expression in microglia, alongside microglial depletion and a pro-inflammatory shift. In vitro PCB138 exposure upregulated TP53 in high-glucose-cultured human microglial cells, promoting M1 polarization and cytokine secretion, effects that were attenuated upon pharmacological inhibition of p53 protein activity. These findings suggest that PCBs exacerbate DR through a TP53-driven pathway that promotes pro-inflammatory microglial activation, disrupting retinal homeostasis. TP53 emerges as a key biomarker and therapeutic target, highlighting the importance of reducing PCB exposure to mitigate DR progression.

Substitute for perfluorooctanoic acid (PFOA), like hexafluoropropylene oxide trimer acid (HFPO-TA), are sparking growing environmental and health worries because of their persistence and capacity for bioaccumulation. Here, we employed an integrated multi-omics approach to systematically investigate HFPO-TA-induced hepatic lipid metabolic dysregulation in zebrafish. Exposed to a series of concentrations (0, 5, 50, 500 μg/L) of HFPO-TA induced hepatic lipid accumulation and significantly elevated serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Integrated transcriptomic and epigenome analyses revealed that HFPO-TA reprogrammed the hepatic epigenome by selectively activating lipid synthesis-associated enhancers while suppressing lipid oxidation pathways, predisposing to metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, HFPO-TA preferentially remodeled chromatin accessibility and distal enhancers, driving lipogenic gene activation through nuclear receptors, such as peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR). Finally, functions of PPARα and FXR in HFPO‑TA‑induced lipid imbalance were validated by pharmacological modulators. Overall, our study delivers comprehensive evidence connecting PFOA alternatives to epigenetically driven hepatic steatosis, providing mechanistic understanding to support environmental risk evaluations of emerging perfluoroalkyl and polyfluoroalkyl substances (PFAS) compounds.

The risk assessment of soil-rice system at the cross-provincial and national scales is of great significance for the prevention of heavy metal pollution and corresponding hazards. In this study, based on 183 studies, the concentrations of heavy metals in soil-rice systems, and the associated ecological and health risks in three main rice cultivated regions in China were determined. The species sensitivity distribution (SSD) curves were used to evaluate the predicted no effect concentrations (PNEC), hazardous concentration for 5 % of species (HC₅) and the percentages of local species affected. The average Cd content in paddy soils in YRB (0.50 mg/kg) and SCR (0.64 mg/kg) exceeded the standards (0.4 mg/kg for YRB, 0.3 mg/kg for SCR). The ecological risks caused by Cadmium (Cd) and Mercury (Hg) were unneglectable. Chromium (Cr) and Arsenic (As) had the greatest effects on all local species, and the affected ratios in YRB, NP, and SCR were 46.4 % and 21.3 %, 45.7 % and 18.0 %, 42.1 % and 21.9 %, respectively. Arsenic (As) was the main contributor of non-carcinogenic health risks and influenced 41.9 %, 38.1 % and 86.6 % of men, women, and child, respectively. The estimated blood lead (Pb) concentration of child was approximately 8 times higher than adult groups, which was mainly caused by higher Pb gastrointestinal absorption rate due to long-term high demand for iron. This study provides a reference for the large-scale and long-term management of heavy metal pollution in soil-rice systems in China. In the future, in-field experiments should be conducted to further validate the outcomes based on literatures.

Co-present mineral colloids affect the transport and distribution of microplastics (MPs) in porous media, however, the transport mechanism remains unclear. In this study, the combined effects of montmorillonite and goethite colloids on the transport/retention behavior of MPs in porous media were investigated. The results show that the type of mineral colloids affects the transport and deposition behavior of MPs in porous media. The coexistence of mineral colloids at an equal ratio promotes MPs transport, while excessively high concentrations of either goethite or montmorillonite colloids inhibit MPs transport. Coexisting mineral colloids promote the transport of MPs in coarse sand media, while play an inhibitory role in medium/fine sand media. Divalent cations reduce MPs fluidity through charge shielding and heteroaggregate formation and the inhibition ability is much higher than that of monovalent cation. Co-present mineral colloids exert an inhibitory effect on MPs transport under acidic and alkaline conditions. The high flow rate promoted the penetration of MPs and induced their deep retention through the fluid drag force. The selective adsorption of coexisting mineral colloids on natural river sand may be a key interface mechanism for regulating transport. These results provide new insights into the theory of colloid-MPs cotransport in groundwater systems.

With the increasingly serious water pollution, effectively removing heavy metal ions and drug residues from wastewater has become a key issue in environmental protection. A 3D network Fe-MIL/magnetic P-doped biochar material (Fe-MIL/Fe-PBC) has been constructed through the strategies of simultaneous heteroatom doping and morphology modulation, magnetization modification, charge modulation and confined recombination to achieve the co-adsorption of drug residues and anionic heavy metals within the pH range of 3-12. Therefore, in real water samples (pH 6-9), Fe-MIL/Fe-PBC can achieve good co-adsorption. The Fe-MIL/Fe-PBC showed excellent adsorption ability for As(V) (AsO₄^3-) and meloxicam (MLX) in the single and binary systems (single: q_As=250.00 mg g^-1, q_MLX=352.58 mg g^-1; binary: q_As=303.03 mg g^-1, q_MLX=400.00 mg g^-1). This is mainly due to the inert activation effect as well as the additional active sites brought by P doping and MIL recombination to the BC-based materials, aided by the charge regulation of the magnetic components. The sponge-packed column filled with Fe-MIL/Fe-PBC demonstrates the ability to continuously remove MLX (195 B.V.) and As(V) (85 B.V.) from water. Fe-MIL/Fe-PBC possesses strong water treatment capabilities and high resistance to interference. Furthermore, the removal efficiency of MLX and As for Fe-MIL/Fe-PBC in 7 cycles was both above 80 %, proving that the material has favorable reusability. The outcomes of the experiment and the characterization findings mutually validate one another, offering robust support for the hypothesized adsorption mechanism. In conclusion, the Fe-MIL/Fe-PBC exhibits extensive application potential in the realm of environmental remediation.

Small molecules play a critical role in the biomedical, environmental, and agrochemical domains, each with distinct physicochemical requirements and success criteria. Although biomedical research benefits from extensive datasets and established benchmarks, agrochemical data remain scarce, particularly with respect to species-specific toxicity. This work focuses on ApisTox, the most comprehensive dataset of experimentally validated chemical toxicity to the honey bee (Apis mellifera), an ecologically vital pollinator. The primary goal of this study was to determine the suitability of diverse machine learning approaches for modeling such toxicity, including molecular fingerprints, graph kernels, and graph neural networks, as well as pretrained models. Comparative analysis with medicinal datasets from the MoleculeNet benchmark reveals that ApisTox represents a distinct chemical space. Performance degradation on non-medicinal datasets, such as ApisTox, demonstrates their limited generalizability of current state-of-the-art algorithms trained solely on biomedical data. Our study highlights the need for more diverse datasets and for targeted model development geared towards the agrochemical domain.

Acrylamide (ACR) is a chemical compound widely used in industrial production and food processing, the underlying mechanisms of its neurotoxicity have yet to be fully elucidated. Through the integration of network toxicology, molecular docking, and experimental validation, this study systematically explored the underlying molecular mechanisms of ACR-induced neurotoxicity. Through database analysis, 183 ACR-related targets and 2725 neurotoxicity-associated targets were identified, among which 100 overlapping genes were predominantly enriched in the PI3K/Akt signaling pathway and apoptosis-related biological processes. Molecular docking and molecular dynamics simulations suggested potential interactions between ACR and key target proteins. While causing minimal alterations in peripheral organs, ACR exposure in vivo resulted in hippocampal neuronal disorganization and Nissl body loss, indicating potential neurotoxicity. In vitro studies demonstrated that ACR not only decreased cell viability in PC12 and HT22 cells but also significantly enhanced apoptosis and inflammation, while markedly activating the PI3K/Akt and NF-κB signaling pathway. The significant attenuation of these effects was observed following treatment with the PI3K inhibitor LY294002. These findings suggest that ACR-induced neurotoxicity involves the coexistence and imbalance of survival and inflammatory-apoptotic signaling, providing mechanistic insight into its neurotoxic effects and a theoretical basis for potential preventive strategies.

Bisphenol AF (BPAF) is a fluorinated derivative of bisphenol A and widely used as an alternative in industry. BPAF is often detected in various environmental media. The cardiovascular toxicity of bisphenols has been previously reported; however, how epigenetic regulation plays a role in bisphenol-induced cardiotoxicity remains unclear. Here, we aimed to assess the cardiovascular toxicity-related endpoints of BPAF. Using zebrafish as an experimental model, we combined an acute 120-h exposure to a series of BPAF concentrations (10, 100, and 1000 μg/L) with a sub-chronic (28 days) exposure of adults to an environmentally relevant concentration of BPAF at 10 μg/L. Acute BPAF exposure exerted dose-dependent impairment on cardiac development, morphology, and function in zebrafish embryos and larvae. Following 28-day exposure of adult zebrafish to an environmentally relevant concentration of BPAF, inflammatory infiltration was observed in both male and female zebrafish heart tissues. Whole-transcriptome sequencing revealed significant changes in the expression patterns of messenger RNAs (mRNAs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circulatory RNAs (circRNAs), and subsequent competing endogenous RNA (ceRNA) network analysis identified upstream regulators that differed between sexes. We also identified BPAF-disrupted key pathways (complement cascades, arachidonic acid metabolism, PPAR signaling) whose core genes (fga, fgb, gpx3, ptgdsb, cd36, apoa1) are potentially ncRNA-regulated. Paternal exposure had a more significant impact on the cardiac function of the next generation. These findings help to advance our understanding of the toxicity and action mechanisms of bisphenols, and provide scientific data for screening specific biomarkers for assessing bisphenol-induced cardiac toxicity.