Toxics最新文献

Per- and polyfluoroalkyl substances (PFASs), as a class of "permanent chemicals" with high environmental persistence and bioaccumulation, have attracted much attention. In this study, we focused on the molecular mechanism of the interaction between perfluoroalkyl acids (PFAAs) and peroxisome proliferator-activated receptor δ (PPARδ). Using molecular docking, binding free energy calculation, and structural analysis, we systematically investigated the binding modes, key amino acid residues, and binding energies of 20 structurally diverse PFAAs with PPARδ. The results showed that the binding energies of PFAAs with PPARδ were significantly affected by the molecular weight, the number of hydrogen bond donors, and the melting point of PFAAs. PFAAs with smaller molecular weights and fewer hydrogen bond donors showed stronger binding affinity. The binding sites were concentrated in high-frequency amino acid residues such as TRP-256, ASN-269, and GLY-270, and the interaction forces were dominated by hydrogen and halogen bonds. PFAAs with branched structure of larger molecular weight (e.g., 3m-PFOA, binding energy of -2.92 kcal·mol^-1; 3,3m₂-PFOA, binding energy of -2.45 kcal·mol^-1) had weaker binding energies than their straight-chain counterparts due to spatial site-blocking effect. In addition, validation group experiments further confirmed the regulation law of binding strength by physicochemical properties. In order to verify the binding stability of the key complexes predicted by molecular docking, and to investigate the dynamic behavior under the conditions of solvation and protein flexibility, molecular dynamics simulations were conducted on PFBA, PFOA, 3,3m₂-PFOA, and PFHxA. The results confirmed the dynamic stability of the binding of the high-affinity ligands selected through docking to PPARδ. Moreover, the influence of molecular weight and branched structure on the binding strength was quantitatively verified from the perspectives of energy and RMSD trajectories. The present study revealed the molecular mechanism of PFAAs interfering with metabolic homeostasis through the PPARδ pathway, providing a theoretical basis for assessing its ecological and health risks.

Aquaculture faces environmental challenges from sediment contamination by potentially toxic elements. This study investigated how aquaculture patterns and seasons jointly affect the distribution and ecological risks of these potentially toxic elements in sediments. By analyzing and comparing sediment samples from different aquaculture systems across seasons, we found that Mn (mean = 435.42 mg/kg) was the most abundant, followed by Zn (mean = 172.69 mg/kg), Cr (mean = 106.79 mg/kg), and Cu (mean = 63.44 mg/kg). Aquaculture patterns were the primary factor determining the composition of potentially toxic elements, followed by season. Fish farming tended to promote their accumulation in sediments, whereas the rice-crayfish co-culture model effectively reduced the enrichment of potentially toxic elements and their associated ecological risks. Therefore, optimizing aquaculture practices proves more effective in controlling these risks than managing seasonal variations. Moreover, total phosphorus was identified as a key driver of potentially toxic element accumulation in sediments. The results from the rice-crayfish co-culture system indicate that enhanced phosphorus management is crucial for mitigating such risks. Accordingly, it is necessary to develop systematic monitoring and integrated remediation strategies focused on priority metals and their main drivers.

Accurate assessment of dietary exposure to cadmium in mushrooms is crucial for food safety. The inherent limitation lies in relying solely on total cadmium content, failing to reflect its actual bioaccessibility. This study integrated speciation analysis and bioaccessibility to provide a comprehensive risk evaluation. The results showed that cadmium primarily existed in the residual state across Lentinus edodes, Morchella esculenta, Cordyceps militaris, Lyophyllum decastes, Agaricus blazei, and Stropharia rugosoannulata, indicating that a significant portion of the cadmium is tightly bound within insoluble cellular structures, rendering it relatively inert and low mobility. Among them, A. blazei exhibited the highest total cadmium (3.84 mg/kg) and contained detectable acid-soluble cadmium. However, the in vitro bioaccessibility of A. blazei was low (~6%), and no cadmium was detected in the other five mushrooms after biomimetic digestion, reflecting "high content, low release" characteristics. For A. blazei, digestion significantly increased soluble polysaccharides, suggesting that the substantial release of polysaccharides in the gastrointestinal environment not only contributes to their bioactive functions but may also inhibit the dissolution and absorption of cadmium through mechanisms such as adsorption and complexation. Concludingly, this study underscores the necessity of integrating bioaccessibility data for the accurate safety assessment of cadmium in mushrooms.

Silicosis is an irreversible and progressive pulmonary fibrotic disease caused by the long-term inhalation of silica dust. The precise molecular mechanisms underlying the disease remain incompletely understood, and effective early diagnostic biomarkers are still lacking. In this study, we used a silicosis mouse model and transcriptomic sequencing to identify 2950 mRNAs, 461 lncRNAs, 81 miRNAs, and 44 circRNAs that were differentially expressed in lung tissue. Enrichment analysis revealed that these differentially expressed genes were significantly enriched in the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. The constructed competing endogenous RNA (ceRNA) network highlighted extensive regulatory interactions among lncRNAs/circRNAs, miRNAs, and mRNAs. Human validation showed that the expression levels of hsa-miR-215-5p and hsa-miR-146b-5p were significantly upregulated in the peripheral blood of early-stage pneumoconiosis patients, while hsa-miR-485-5p was downregulated. Logistic regression analysis revealed that hsa-miR-215-5p (OR = 1.966, 95% CI: 1.6938-2.2796, p < 0.001) and hsa-miR-146b-5p (OR = 1.9367, 95% CI: 1.697-2.201, p < 0.001) were independent risk factors for pneumoconiosis (p < 0.001). ROC curve analysis showed that both miRNAs demonstrated good diagnostic efficacy for pneumoconiosis, with AUC values of 0.9563 and 0.8876, respectively. These results provide novel insights into the complex ceRNA regulatory network involved in silicosis pathogenesis and suggest potential early, non-invasive diagnostic biomarkers.

This study aims to develop a cost-effective and scalable modification strategy for valorizing lignin-rich biogas residue (BR) into high-performance adsorbents for anionic dye removal. To screen the optimal modification pathway, three distinct reagents, L-cysteine-based amino acid ionic liquids (AAILs, as green alternatives), conventional hydrochloric acid (HCl) and sodium hydroxide (NaOH, as traditional modification reagents), were compared in modifying non-carbonized BR for Congo Red (CR) adsorption. Comprehensive characterizations and adsorption tests revealed that each modifier exerted unique effects: NaOH only caused mild surface etching with limited performance improvement; AAILs achieved moderate adsorption capacity via a green, mild route; while HCl modification (BR-HCl) stood out with the most superior performance through a "selective dissolution-pore reconstruction" mechanism. Notably, despite a modest specific surface area increase to 12.05 m²/g, BR-HCl's high CR adsorption capacity (120.21 mg/g at 45 °C) originated from the synergy of chemical bonding and enhanced electrostatic attraction-its isoelectric point (pH_PZC ≈ 9.02) was significantly higher than that of AAIL- and NaOH-modified samples, enabling strong affinity for anionic CR across a wide pH range. BR-HCl attained over 99% CR removal at a dosage of 0.4 g/L, fitted well with Langmuir isotherm and pseudo-second-order kinetic models (confirming monolayer chemisorption), and retained 82% of its initial capacity after five regeneration cycles. These results demonstrate that while AAILs show promise as green modifiers and NaOH serves as a baseline, the facile, low-cost HCl modification offers the most pragmatic pathway to unlock BR's potential for sustainable wastewater treatment.

Chlorinated paraffins (CPs) are a class of persistent organic pollutants that pose potential human health risks through dietary exposure. In this study, we analyzed CPs in 55 chicken egg samples collected from five regions across China. Short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) were detected using a two-dimensional gas chromatograph coupled with an electron-capture negative-ionization mass spectrometer. Dietary exposure risks were assessed using the margin of exposure (MOE) approach based on the food consumption data of Chinese residents from 2018 to 2020. The average concentrations of SCCPs and MCCPs in all samples were 28.4 ng/g wet weight (ww) and 176.5 ng/g ww, respectively. The congener profiles of SCCPs and MCCPs were similar across different regions, with C_10-11 Cl_6-7 as the dominant homologs. For MCCPs, the average contributions of C₁₄-CP, C₁₅-CP, C₁₆-CP, and C₁₇-CP were 25%, 21%, 27%, and 27%, respectively. The estimated daily intake (EDI) for the entire population was 18.3 ng/kg body weight (bw)/d for SCCPs and 118.3 ng/kg bw/d for MCCPs. In the consumer-only group, the average exposure levels of SCCPs and MCCPs were 27.8 ng/kg bw/d and 174.1 ng/kg bw/d, respectively. This preliminary risk assessment indicates that there is no health risk to the Chinese population from exposure to CP through consumption of chicken eggs.

The buccal micronucleus cytome assay (BMCyt) is a validated, non-invasive biomonitoring method used to detect early genotoxic and cytotoxic changes linked to environmental and occupational exposures. Healthcare workers, especially nurses and dentists, are routinely exposed to genotoxic agents such as anesthetic gases, cytotoxic drugs, ionizing radiation, and heavy metals. This study compared seven cytological biomarkers in exfoliated buccal cells from female nurses, dentists, and teachers to assess multivariate cytogenetic differences and potential occupational influences. Samples were collected from 32 nurses, 41 dentists, and 47 teachers, and 3000 cells per participant were evaluated for micronuclei (MN) and six additional nuclear abnormalities. Group differences were examined using MANOVA and permutation MANOVA, followed by pairwise tests, and visualized with Principal Component Analysis (PCA). Significant multivariate differences were found between nurses and both dentists and teachers (p = 0.003), supported by permutation tests, while dentists and teachers did not differ. PCA explained 56% of the variance and showed apparent clustering of nurses. Chromatin condensation and MN were the main contributors to group separation. Nurses had significantly higher MN (p ≤ 0.001) and karyorrhexis (p ≤ 0.0004) than dentist and teachers. Overall, nurses showed a distinct cytogenetic profile consistent with greater genotoxic susceptibility.

Sewage sludge is increasingly recognized as a major reservoir for pharmaceuticals and emerging contaminants that are only partially removed by conventional wastewater treatment. This study provides the first comprehensive assessment of these contaminants in biosolids generated from ten major wastewater treatment plants (WWTPs) across Jordan. Different pharmaceuticals were quantified in the sludge samples generated. The results revealed concentrations ranging from 10 to over 2000 µg kg^-1, with antibiotics typically showing the highest enrichment (e.g., ciprofloxacin up to 2165 µg kg^-1, ofloxacin up to 303 µg kg^-1). Anti-inflammatory compounds such as diclofenac reached 196 µg kg^-1, while the antimicrobial triclosan exceeded 4700 µg kg^-1 in some sludge samples. Carbamazepine, a recalcitrant antiepileptic drug, ranged between 50 and 223 µg kg^-1, reflecting both widespread use and strong persistence. Elevated levels of quaternary ammonium compounds (QACs) were also detected. The highest levels were generally associated with large urban WWTPs and plants receiving industrial discharges. Environmental risk assessment (ERA) indicated that the risk for soil biota was acceptable for most cases for low application doses (5-10 t/ha) except for WWTP6-MD, WWTP8-S, and WWTP9-IC, where the risk was non-acceptable. Severe limitations in the risk assessment were noted: reliable toxicity endpoints in terrestrial soil organisms such as microbiota, collembola, and earthworms are few, while deriving endpoints via aquatic available data is not always reliable. Overall, the findings demonstrate that Jordanian sewage sludge contains environmentally relevant levels of pharmaceuticals and QACs and that risk assessment is, therefore, pertinent before any stabilization and realistic land application scenarios are chosen.

Glyphosate (GLY), the active ingredient in widely used herbicides, was long considered specific to plants and bacteria, yet mounting evidence shows it can impair endocrine and reproductive functions in animals. Given its widespread use and environmental persistence, assessing its effects at regulatory-approved doses is critical. Here, adult female zebrafish (Danio rerio) were exposed for 21 days to different concentrations of dietary GLY at 0.5 mg/kg body weight/day (GLY0.5, acceptable daily intake, ADI), 5 mg/kg/day (GLY5), and 50 mg/kg/day (GLY50, no-observed-adverse-effect level, NOAEL). Our findings show that dietary GLY induces dose-dependent perturbations along the hepato-gonadal axis. At the highest dose, chronic stress responses were evident through elevated cortisol and cortisone, accompanied by hepatic glycogen accumulation and ferroptotic stress. Although follicle histology appeared normal, alterations in several genes involved in oocyte maturation and estrogen receptor signaling translated into reduced fertilization, revealing compromised gamete quality rather than overt follicular development abnormality. Likewise, the lowest dose triggered modifications in genes crucial for oogenesis without altering the follicle development, although in this case, potential compensatory mechanisms could have led to enhanced fertilization. GLY5 did not alter the number of fertilized eggs but significantly increased embryo mortality. Overall, dietary GLY disrupted hepatic metabolism, endocrine signaling, and reproduction in a non-monotonic manner, even at levels considered safe by EFSA. These findings highlight the need to reevaluate current safety thresholds with attention to female-specific reproductive risks.

In this study, for the first time urinary NMR-based metabolomics was applied to investigate the physiological alterations associated with occupational exposure in ceramic manufacturing workers. Multivariate analysis revealed a distinctive metabolic signature with exposure, characterized by a depletion of both aliphatic and aromatic amino acids and a concomitant accumulation of branched-chain amino acid catabolites. Alterations in tricarboxylic acid (TCA) cycle intermediates, including citrate and succinate, suggest an involvement of mitochondrial energy metabolism, reflecting adaptive responses to oxidative stress and increased protein turnover. Notably, glycine levels were found increased, consistent with its central role in antioxidant defense and xenobiotic detoxification. Furthermore, changes in urinary host-microbiome co-metabolites, such as 4-hydroxyphenylacetate and phenylacetylglycine, indicate the potential modulation of gut microbial activity in response to occupational exposure. While limited by the small cohort, this study demonstrates the feasibility of NMR-based urinary metabolomics for the non-invasive biomonitoring of workers and suggests its potential as a useful tool for detecting subtle metabolic perturbations associated with complex occupational exposures.