Journal of Environmental Sciences
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2024
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IF 5.9
Shi-Ya Peng,Ya-Di Yang,Rong Tian,Naihao Lu
A key characteristic to be elucidated, to address the harmful health risks of environmental perfluorinated alkyl substances (PFAS), is their binding modes to serum albumin, the most abundant protein in blood. Hexafluoropropylene oxide-dimer acid (GenX or HFPO-DA) is a new industrial replacement for the widespread linear long-chain PFAS. However, the detailed interaction of new-generation short-chain PFAS with albumin is still lacking. Herein, the binding characteristics of bovine serum albumin (BSA) to GenX were explored at the molecular and cellular levels. It was found that this branched short-chain GenX could bind to BSA with affinity lower than that of legacy linear long-chain perfluorooctanoic acid (PFOA). Site marker competitive study and molecular docking simulation revealed that GenX interacted with subdomain IIIA to form BSA-GenX complex. Consistent with its weaker affinity to albumin protein, the cytotoxicity of branched short-chain GenX was less susceptible to BSA binding compared with that of the linear long-chain PFOA. In contrast to the significant effects of strong BSA-PFOA interaction, the weak affinity of BSA-GenX binding did not influence the structure of protein and the cytotoxicity of GenX. The detailed characterization and direct comparisons of serum albumin interaction with new generation short-chain GenX will provide a better understanding for the toxicological properties of this new alternative.
研究领域:
生物化学
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毒理学
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环境科学
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高影响因子
Journal of Environmental Chemical Engineering
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2025
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IF 7.2
Yang Wang,Hui Li,Ji Li,Lina Zhou,Chunkai Feng,Guangwei Liu,Jianzhi Wang,Chen Hou
Perfluorohexane-1,3-dicarboxylic acid (GenX) is now widely used as a substitute for the prohibited perfluorooctanoic acid (PFOA), which has caused growing concerns about its persistence and potential hazards to human health. This study developed a biomass gelatin-derived N and S self-doped porous carbon electrodes (NSGC), for the electro-Fenton (EF) degradation of GenX. To facilitate absorotion, diffusion, and degradation in EF, the NSGC was fluorinated to enhance the selectivit and binding energy between the catalyst and GenX by the “F-F interactions”. The resulted F-NSGC reach 58.8% electroadsorption efficiency to GenX in 60 min, and then degraded 95.8% with a mineralization rate of 63.2% within 180 min. The degradation mechanism was discussed by identifying intermediate products. Moreover, the F-NSGC can maintain a good degradation effect in complex ionic background conditions and actual water samples. These findings extend the applications of biomass-based carbon electrodes and consolidate the effect of F-F interactions on degradation of GenX and other per- and polyfluorinated alkyl substances.
研究领域:
环境科学
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材料科学
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高影响因子
TOXICOLOGY
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2026
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IF 5.2
Yiming Pang,Zhenzhong Wang,Yijun Liu,Chuanteng Feng,Yuchun Song,Shannan Cao,Dong Wang,Lianshuang Zhang,Peng Lu,Li Yu
Hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) is an environmentally persistent per- and polyfluoroalkyl substance (PFAS) alternative whose placental toxicity remains poorly understood. Pregnant Sprague-Dawley rats (n = 20, 5 dams/group) received oral HFPO-DA at 0, 1, 10, or 100 mg/kg·day from gestational day (GD) 0–19. Placental tissues collected on GD20 were analysed by targeted metabolomics, lipidomics, histopathology, immunohistochemistry (IHC), and immunofluorescence (IF). After false discovery rate (FDR) correction, three energy metabolites were significantly altered ( q < 0.05): oxaloacetate and glutamate were downregulated, while pyruvate was dose-dependently upregulated, consistent with restricted TCA cycle entry. Lipidomics identified 148 nominally significant lipid species, with elevated ceramides and long-chain fatty acids alongside reduced triglycerides, a pattern suggestive of impaired mitochondrial β-oxidation capacity. Histopathology revealed dose-dependent villous hyperplasia, trophoblast disorganization, and vascular lesions at the high dose. Protein analysis showed decreased SDHB, increased HIF-1α and PDK1, and a non-significant rise in PDHA1, collectively consistent with a shift toward Warburg-like metabolic reprogramming. These findings suggest that gestational HFPO-DA exposure may disrupt placental energy and lipid homeostasis at supra-environmental doses, identifying placental metabolism as a potentially sensitive target of next-generation PFAS.
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Journal of Environmental Chemical Engineering
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2025
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IF 7.2
Shiqi Xiao,Yao Liu,Sheng Ding,Dianxiang Lu,Jin Yang,Xiangke Niu,Xin Qi,Jiawei Wei
Microplastics (MPs) have been shown to adsorb per- and polyfluoroalkyl substances (PFAS) and serve as vehicles for their environmental transport. However, the combined intestinal toxicity of MPs and PFAS remains inadequately investigated. This study investigated the intestinal effects of polystyrene microplastics (PS MPs) loaded with perfluoro (2-methyl-3-oxahexanoic acid) (GenX) in a mouse model. Combined exposure to PS MPs and GenX resulted in marked intestinal tissue injury, characterized by elevated levels of pro-inflammatory cytokines and antioxidative enzymes in the colon, alongside impaired intestinal barrier protein expression. 16S rRNA sequencing revealed that co-exposure markedly altered gut microbiota composition, reducing beneficial genera (e.g., Alistipes and Bacillus ) and increasing pathogenic taxa (e.g., Shigella and Desulfovibrio ), while also disrupting microbial network stability. These shifts play an essential role in the synergistic toxicity induced by PS MPs and GenX. Transcriptomic analysis of intestinal tissue indicated enrichment of differentially expressed genes involved in metabolic and digestive processes, with concomitant activation of oxidative stress and immune-related pathways after exposure to PS MPs and GenX. Furthermore, genes associated with inflammatory factors and oxidative stress markers were upregulated. These findings demonstrate that co-exposure to PS MPs and GenX exacerbates intestinal damage compared to PS MPs alone, providing new insights for comprehensive risk assessment of microplastic exposure.
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MOLECULAR BIOLOGY REPORTS
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2026
·Vol. 53
·期 1
·440
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IF 3.2
Ding Hongran,Slack Maya,McClure Holly,Gu Wen,Gu Helene,Kappes Ferdinand,Schultz Thomas F.,Somarelli Jason A.,Tsigkou Anastasia
Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals extensively used as plastic additives. Their environmental persistence and potential for bioaccumulation have raised significant toxicological concerns. This study evaluates the cytotoxic and molecular effects of Perfluorooctanoic acid (PFOA) and its replacement compound, Perfluoro(2-methyl-3-oxohexanoic) acid (GenX), in human-derived skin (A375), liver (HepG2), kidney (SN12C), and colon (SW620) cell lines. The experimental design assessed cell viability, gene expression, and perturbations in key cellular stress pathways, with a particular focus on TGF-β/SMAD-mediated inflammation and the p53-driven DNA damage response. Our results demonstrate compound- and cell-type-specific toxicity, with GenX displaying reduced cytotoxicity compared to PFOA across all cell types. Molecular analyses revealed that both PFAS induced alterations in the TGF-β/SMAD pathway, consistent with a pro-inflammatory cellular state. Additionally, we observed activation of the DNA damage response, as evidenced by increased expression of ATM, ATR, and p53, alongside ribosomal stress-related changes in RPL5 and RPL11. Notably, while skin and liver cells exhibited similar response profiles, kidney and colon cells showed divergent modulation of SMAD signaling, suggesting tissue-specific susceptibility and mechanistic differences. These findings contribute to a deeper understanding of the differential toxicological profiles of legacy and replacement PFAS, with implications for health risk assessment and regulatory policy. Graphical abstract
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Yangyang Yuan,Binhui Wang,Yuyu Fan,Meiling Le,Lihai Wu,Shiyi Deng,Jian Huang,Dalei Zhang
Perfluorooctanoic acid (PFOA) is a legacy perfluoroalkyl substance (PFAS) with various detrimental health effects, prompting its replacement by hexafluoropropylene oxide dimer acid (GenX). However, the female reproductive toxicity and underlying mechanism of GenX remain inadequately understood. In this study, we comparatively evaluated the impacts of PFOA and GenX on ovarian function using integrated in vivo mouse and in vitro human granulosa cell models. Our experimental findings indicated that oral exposure to PFOA significantly reduced ovarian weight, impaired follicular development, disrupted estrous cyclicity, decreased estradiol level, and induced ovarian oxidative stress and apoptosis in mice. However, GenX did not display significant toxic effects on the ovaries at the doses tested, except for reducing ovarian GPX4 expression and serum estradiol level. Notably, both PFOA and GenX at high-concentration treatment in vitro dramatically impaired the viability and proliferation, elicited ROS overproduction and mitochondrial injury, and suppressed NRF2 and HO-1 expression in cultured KGN cells. Nevertheless, at equivalent exposure doses, GenX elicited markedly decreased adverse influences on KGN cells compared to PFOA. Molecular docking simulation indicated a stronger interaction of PFOA with NRF2 than GenX. In addition, treatment with PFOA also diminished estradiol secretion and induced apoptosis in KGN cells. In summary, PFOA exposure resulted in female reproductive impairment by inducing oxidative stress and apoptosis in mouse ovaries and human granulosa cells. Although GenX exhibited comparatively low ovarian detriment relative to PFOA, its potential risk of reproductive toxicity remains a nonnegligible concern.
研究领域:
毒理学
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生殖生物学
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环境健康
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分子生物学
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内分泌学
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Toxics
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2025
·Vol. 14
·期 1
·
IF 4.1
Yuntao Qi,Qianyue Yin,Penghang Ni,Wansong Zong,Qigui Niu,Rutao Liu
GenX, also known as hexafluoroepoxypropane dimer acid (HFPO-DA), an emerging perfluoroalkyl substance alternative, is extensively used in industrial processes and is resistant to degradation. This persistence heightens the potential for co-occurrence and combined toxicity with other environmental pollutants. Nanoplastics (NPs), ubiquitous environmental contaminants, can exacerbate the biological toxicity of GenX. However, the molecular mechanisms by which NPs influence GenX-induced structural damage to human serum albumin (HSA) remain unclear. This study, therefore, employed multi-spectroscopic techniques, characterization assays, and molecular simulations to investigate these mechanisms. A critical limitation is that the observed structural damage occurred at a GenX concentration of 0.05–0.1 mM. The results indicate that the presence of NPs exacerbated the loosening of the protein backbone and caused a more pronounced reduction inα-helical content (NPs@GenX: 37.3%; GenX alone: 41.5%). The binding is predicted to occur within the hydrophobic pocket of subdomain IIIA of HSA. Characterization assays further revealed significant protein aggregation in systems containing NPs. The study concludes that NPs adsorb HSA through the formation of a protein corona, while simultaneously binding GenX via hydrophobic interactions. This dual pathway—direct binding of HSA to GenX and an active surface-mediated perturbation by NPs—constitutes the primary mechanism leading to aggravated structural changes. Overall, this work elucidates the molecular mechanisms by which NPs exacerbate HSA denaturation in the presence of GenX, offering valuable insights for assessing the combined ecological risks of emerging and persistent environmental pollutants.
研究领域:
环境科学
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毒理学
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分子生物学
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纳米技术
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环境化学
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2026
·
IF 11.3
Wantong Tang,Xin Xiao,Enhui Wu,Kun Wang,Xinfei Ge,Xiaoying Zhu,Chiheng Chu,Baoliang Chen
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants with exceptional stability and significant ecological risk. However, their distribution and accumulation in soil–crop systems, especially for the replacement compound GenX, remain poorly characterized. Here, rice ( Oryza sativa , Nipponbare) was cultivated for five months in paddy soils amended with PFOA, PFOS, and GenX to map fate, bioaccumulation, and toxic responses across the soil–crop system and to derive soil safety thresholds protective of human health. PFAS exposure (10–100 μg/g) altered plant morphology and development and induced dose-linear oxidative stress (SOD, POD, CAT, MDA, H 2 O 2 , protein). Compound-specific translocation emerged: short-chain GenX showed greater upward transport and endosperm accumulation, whereas long-chain PFOA/PFOS were more root-retained (endosperm accumulation in total plant: PFOA 8.973–10.440%, PFOS 9.951–12.800%, GenX 10.286–20.773%). Overall toxic potency ranked PFOA ≥ PFOS > GenX. Based on measured plant uptake, we propose provisional exposure safety thresholds for rice cultivation of 3.157 ng/g (PFOA), 2.327 ng/g (PFOS), and 21.220 ng/g (GenX). This growth-cycle assessment provides an integrated evidence base for PFAS ecological risk evaluation and delivers actionable guidance to safeguard food security.
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高影响因子
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