FOOD AND CHEMICAL TOXICOLOGY
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2026
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IF 3.5
Chenghao He,Jiaxin Jiang,Shuguang Hou,Runchun Xu,Qinwan Huang
Perfluorohexanesulfonic acid (PFHxS), a prevalent short-chain per- and polyfluoroalkyl substance, has been implicated in hepatocellular carcinoma (HCC), but mechanisms remain unclear. We integrated transcriptomic analyses of The Cancer Genome Atlas (TCGA) liver cancer cohort and an HCC single-cell dataset with molecular docking and molecular dynamics simulations and in vitro assays to examine a PFHxS-relevant hypothesis involving KEAP1–NRF2 signaling. Across clinical datasets, higher NQO1, an NRF2-associated gene, was linked to adverse clinicopathologic features; NQO1-high tumor cells showed elevated NRF2-activity signatures and computationally inferred increased MIF signaling toward macrophages. Because exposure information is unavailable, these observations indicate association and define a PFHxS-relevant vulnerability axis rather than PFHxS-driven tumor states. Docking/dynamics suggested PFHxS can bind the KEAP1 Kelch domain near the NRF2-binding site. In HepG2 cells, PFHxS modestly increased viability/DNA-synthesis readouts and enhanced NRF2 nuclear localization, NQO1 protein abundance, and MIF secretion; pharmacologic NRF2 inhibition partially attenuated NRF2/NQO1 readouts and reduced MIF secretion. Together, the data support the hypothesis that PFHxS may engage a KEAP1–NRF2-related vulnerability axis, accompanied by NRF2/NQO1 pathway readouts and increased MIF secretion, motivating exposure-characterized and genetic studies to establish causality.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Tao Cang,Lu Lv,Yue Yin,Dou Wang,Kan Shao,Zhenlan Xu,Xinquan Wang,Yanhua Wang
Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS), as persistent global contaminants, pose substantial threats to pollinators like honeybees ( Apis mellifera L.), yet their sub-lethal effects remain insufficiently explored. Here, we exposed bees to environmentally relevant concentrations (0.5–50 μg/L) of PFOA and PFHxS for 10 days, assessing midgut toxicity through pathology, metabolomics, and gene expression, and examined curcumin (Cur) as a potential mitigator. Although acute toxicity assays indicated relatively high LC₅₀ values (266–331 mg/L), sub-lethal exposures induced pronounced midgut injury, characterized by decreased epithelial cell density and thinning of the protective gel layer. Disruption of glycerophospholipid metabolism was detected, impairing membrane integrity. Additionally, PFOA and PFHxS downregulated barrier integrity genes ( ZO-2 and Mucin-1 ), while upregulating inflammatory ( Eiger and Relish ) and apoptotic indicators ( Caspase-3 , Caspase-8 , and Caspase-9 ). For several sub-lethal endpoints, PFHxS triggered more pronounced effects than PFOA. Notably, curcumin treatment restored midgut integrity and reversed many of the associated molecular disruptions. These results demonstrated that environmentally relevant concentrations of PFAS could substantially compromise honeybee gut health, offering critical insights for ecological risk assessments aimed at safeguarding these essential pollinators.
研究领域:
昆虫学
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环境毒理学
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生态毒理学
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代谢组学
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分子生物学
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传粉生态学
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高影响因子
ENVIRONMENTAL POLLUTION
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2018
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IF 4.358
Shuyan Zhao,Tao Zhou,Lingyan Zhu,Bohui Wang,Ze Li,Liping Yang,Lifen Liu
N-ethyl perfluorooctane sulfonamide (N-EtFOSA) is an important perfluorooctanesulfonate (PFOS) precursor (PreFOS) which is used in sulfluramid. The present work studied the uptake, translocation and metabolism of N-EtFOSA in wheat ( Triticum aestivum L.), soybean ( Glycine max L. Merrill) and pumpkin ( Cucurbita maxima L.) by hydroponic exposure. Except for parent N-EtFOSA, its metabolites of perfluorooctane sulfonamide acetate (FOSAA), perfluorooctane sulfonamide (PFOSA), PFOS, perfluorohexane sulfonate (PFHxS) and perfluorobutane sulfonate (PFBS) were detected in the roots and shoots of all the three plant species examined. This suggested that plant roots could take up N-EtFOSA from solutions efficiently, and translocate to shoots. A positive correlation was found between root concentration factors (RCFs) of N-EtFOSA and root lipid content. Much higher proportion of N-EtFOSA transformation products in plant tissues than in the solutions suggested that N-EtFOSA could be in vivo metabolized in plant roots and shoots to FOSAA, PFOSA and PFOS, and other additional shorter-chain perfluoroalkane sulfonates (PFSAs), including PFHxS and PFBS. The results suggested that plants had biotransformation pathways to N-EtFOSA that were different than those from microorganisms and animals. This study provides important information about the uptake and metabolism of PreFOSs in plants.
研究领域:
环境科学
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植物生理学
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毒理学
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Lan Shi,Tianrui Gao,Zhipeng Zhu,Fan Yang,Bing Han,Jia Lv,Lin Tao,Yang Gao,Rong Hua,Huan Wu,Yichao Huang,Xiaojin He
Our recent large-scale population study demonstrated that several per- and polyfluoroalkyl substances (PFAS) are potential risk factors for sperm quality—with perfluorohexane sulfonate (PFHxS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) emerging as the strongest effect contributors to asthenospermia, yet their causal relationships remain unclear. Here, we provide in vivo experimental evidence and evaluation of the combined effects of 6:2 Cl-PFESA and PFHxS under human-relevant exposure. Male ICR mice were orally exposed to each compound alone or in combination for 35 days, covering one full spermatogenic cycle. Both single and combined exposures were associated with alterations of the male reproductive axis, including reduced serum testosterone and elevations in the gonadotropins luteinising hormone (LH) and follicle-stimulating hormone (FSH), and in sex hormone-binding globulin (SHBG). Testicular injury included disturbed seminiferous architecture, decreased sperm motility, and increased germ-cell apoptosis. Transcriptomics highlighted pathways related to cell adhesion, junctional integrity, and apoptosis, and Western blotting and TUNEL confirmed blood-testis barrier (BTB) protein disruption and increased germ-cell apoptosis. Toxic potency differed by endpoint, with endpoint-specific patterns across endocrine, BTB, and motility outcomes. Combined-effect analysis identified a positive non-additive interaction for LH, whereas most BTB-associated proteins showed no statistically significant interaction despite endpoint-specific deviations from the concentration-addition expectation. Collectively, these findings indicate that human-relevant co-exposure to 6:2 Cl-PFESA and PFHxS is associated with asthenospermia-related sperm and testicular alterations. The converging phenotypic, molecular, and functional findings support BTB impairment and germ-cell apoptosis as plausible contributing processes, yet the precise mechanisms still need further investigation.
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高影响因子
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