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.Hexafluoropro...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.Itwas 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.展开更多
Perfluorinated chemical GenX,formally known as hexafluoropropylene oxide dimer acid(HFPO−DA),has been applied as an alternative to the forever chemical perfluorooctanoic acid(PFOA).The applications of HFPO−DA have rap...Perfluorinated chemical GenX,formally known as hexafluoropropylene oxide dimer acid(HFPO−DA),has been applied as an alternative to the forever chemical perfluorooctanoic acid(PFOA).The applications of HFPO−DA have rapidly expanded from traditional nonstick coating industries into high-tech semiconductor manufacturing.Because of such facts in conjunction with its low biodegradation rate and high potential of long-distance atmospheric transport,the presence and accumulation of HFPO−DA have been ubiquitously detected in environmental media and biological species,including animals and human beings,posing alarming and urgent needs for the risk assessment of HFPO−DA.Building on the United States Environmental Protection Agency’s evaluation of HFPO−DA in 2021,this review first summarizes the interaction of HFPO−DA with the environment,elaborates on its known toxicities and potential carcinogenicity,along with their possible mechanisms,and briefly addresses its current exposure assessment and risk management strategies.These lines of evidence support that the safety of HFPO−DA necessitates further investigation and monitoring,albeit being considered as a less toxic and low persistence substitute of traditional PFOA.展开更多
Background:Perfluorooctanoic acid(PFOA)is an environmental contaminant associated with adverse metabolic outcomes in developmentally exposed human populations and mouse models.Hexafluoropropylene oxide-dimer acid(HFPO...Background:Perfluorooctanoic acid(PFOA)is an environmental contaminant associated with adverse metabolic outcomes in developmentally exposed human populations and mouse models.Hexafluoropropylene oxide-dimer acid(HFPO-DA,commonly called GenX)has replaced PFOA in many industrial applications in the U.S.and Europe and has been measured in global water systems from<1 to 9350 ng/L HFPO-DA.Health effects data for GenX are lacking.Objective:Determine the effects of gestational exposure to GenX on offspring weight gain trajectory,adult metabolic health,liver pathology and key adipose gene pathways in male and female CD-1 mice.Methods:Daily oral doses of GenX(0.2,1.0,2.0 mg/kg),PFOA(0.1,1.0 mg/kg),or vehicle control were administered to pregnant mice(gestation days 1.5-17.5).Offspring were fed a high-or low-fat diet(HFD or LFD)at weaning until necropsy at 6 or 18 weeks,and metabolic endpoints were measured over time.PFOA and GenX serum and urine concentrations,weight gain,serum lipid parameters,body mass composition,glucose tolerance,white adipose tissue gene expression,and liver histopathology were evaluated.Results:Prenatal exposure to GenX led to its accumulation in the serum and urine of 5-day old pups(P=0.007,P<0.001),which was undetectable by weaning.By 18 weeks of age,male mice fed LFD in the 2.0 mg/kg GenX group displayed increased weight gain(P<0.05),fat mass(P=0.016),hepatocellular microvesicular fatty change(P=0.015),and insulin sensitivity(P=0.014)in comparison to control males fed LFD.Female mice fed HFD had a significant increase in hepatocyte single cell necrosis in 1.0 mg/kg GenX group(P=0.022)and 1.0 mg/kg PFOA group(P=0.003)compared to control HFD females.Both sexes were affected by gestational GenX exposure;however,the observed phenotype varied between sex with males displaying more characteristics of metabolic disease and females exhibiting liver damage in response to the gestational exposure.Conclusions:Prenatal exposure to 1 mg/kg GenX and 1 mg/kg PFOA induces adverse metabolic outcomes in adult mice that are diet-and sex-dependent.GenX also accumulated in pup serum,suggesting that placental and potentially lactational transfer are important exposure routes for GenX.展开更多
Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.Howeve...Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.展开更多
Per-and polyfluoroalkyl substances(PFAS)are a class of ubiquitous,persistent,and hazardous pollutants that raise concerns for human health and the environment.Typically,PFAS removal from water relies on adsorption tec...Per-and polyfluoroalkyl substances(PFAS)are a class of ubiquitous,persistent,and hazardous pollutants that raise concerns for human health and the environment.Typically,PFAS removal from water relies on adsorption techniques using conventional sorption materials like activated carbons(ACs)and ion exchange resins(IERs).However,there is a continuous search for more efficient and performing adsorbent materials to better address the wide range of chemical structures of PFAS in the environment,to increase their selectivity,and to achieve an overall high adsorption capacity and faster uptake kinetics.In this context,results from the application of non-conventional sorption materials(i.e.,readily available biological-based materials like proteins and advanced materials like nanocomposites and cyclodextrins)are reported and discussed in consideration of the following criteria:i)removal efficiency and kinetics of legacy PFAS(e.g.,PFOA,PFBA)as well as newly-introduced and emerging PFAS(e.g.,GenX),ii)representativity of environmental conditions in the experimental setup(e.g.,use of environmentally relevant experimental concentrations),iii)regenerability,reusability and applicability of the materials,and iv)role of the material modifications on PFAS adsorption.From this review,it emerged that organic frameworks,nano(ligno)cellulosic-based materials,and layered double hydroxides are among the most promising materials herein investigated for PFAS adsorption,and it was also observed that the presence of fluorine-and amine-moieties in the material structure improve both the selectivity and PFAS uptake.However,the lack of data on their applicability in real environments and the costs involved means that this research is still in its infancy and need further investigation.展开更多
基金supported by the National Natural Science Foundation of China(Nos.31960196,31760255,and 82260637)Jiangxi Provincial Natural Science Foundation(No.20212BAB205016).
文摘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.Itwas 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.
基金supported,in part,by China CDC Key Laboratory of Environment and Population Health,National Institute of Environmental Health,Chinese Center for Disease Control and Prevention(2024-CKL-02)by Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease(DXWL2023-06)+2 种基金by Open Project Fund from Key Laboratory of Coal Environmental Pathogenicity and Prevention(Shanxi Medical University)Ministry of Education,China(MEKLCEPP/SXMU-201413)by Peking University Clinical Medicine Plus X Young Scholars Project,the Fundamental Research Funds for the Central Universities(PKU2023LCXQ005)to W.X.
文摘Perfluorinated chemical GenX,formally known as hexafluoropropylene oxide dimer acid(HFPO−DA),has been applied as an alternative to the forever chemical perfluorooctanoic acid(PFOA).The applications of HFPO−DA have rapidly expanded from traditional nonstick coating industries into high-tech semiconductor manufacturing.Because of such facts in conjunction with its low biodegradation rate and high potential of long-distance atmospheric transport,the presence and accumulation of HFPO−DA have been ubiquitously detected in environmental media and biological species,including animals and human beings,posing alarming and urgent needs for the risk assessment of HFPO−DA.Building on the United States Environmental Protection Agency’s evaluation of HFPO−DA in 2021,this review first summarizes the interaction of HFPO−DA with the environment,elaborates on its known toxicities and potential carcinogenicity,along with their possible mechanisms,and briefly addresses its current exposure assessment and risk management strategies.These lines of evidence support that the safety of HFPO−DA necessitates further investigation and monitoring,albeit being considered as a less toxic and low persistence substitute of traditional PFOA.
文摘Background:Perfluorooctanoic acid(PFOA)is an environmental contaminant associated with adverse metabolic outcomes in developmentally exposed human populations and mouse models.Hexafluoropropylene oxide-dimer acid(HFPO-DA,commonly called GenX)has replaced PFOA in many industrial applications in the U.S.and Europe and has been measured in global water systems from<1 to 9350 ng/L HFPO-DA.Health effects data for GenX are lacking.Objective:Determine the effects of gestational exposure to GenX on offspring weight gain trajectory,adult metabolic health,liver pathology and key adipose gene pathways in male and female CD-1 mice.Methods:Daily oral doses of GenX(0.2,1.0,2.0 mg/kg),PFOA(0.1,1.0 mg/kg),or vehicle control were administered to pregnant mice(gestation days 1.5-17.5).Offspring were fed a high-or low-fat diet(HFD or LFD)at weaning until necropsy at 6 or 18 weeks,and metabolic endpoints were measured over time.PFOA and GenX serum and urine concentrations,weight gain,serum lipid parameters,body mass composition,glucose tolerance,white adipose tissue gene expression,and liver histopathology were evaluated.Results:Prenatal exposure to GenX led to its accumulation in the serum and urine of 5-day old pups(P=0.007,P<0.001),which was undetectable by weaning.By 18 weeks of age,male mice fed LFD in the 2.0 mg/kg GenX group displayed increased weight gain(P<0.05),fat mass(P=0.016),hepatocellular microvesicular fatty change(P=0.015),and insulin sensitivity(P=0.014)in comparison to control males fed LFD.Female mice fed HFD had a significant increase in hepatocyte single cell necrosis in 1.0 mg/kg GenX group(P=0.022)and 1.0 mg/kg PFOA group(P=0.003)compared to control HFD females.Both sexes were affected by gestational GenX exposure;however,the observed phenotype varied between sex with males displaying more characteristics of metabolic disease and females exhibiting liver damage in response to the gestational exposure.Conclusions:Prenatal exposure to 1 mg/kg GenX and 1 mg/kg PFOA induces adverse metabolic outcomes in adult mice that are diet-and sex-dependent.GenX also accumulated in pup serum,suggesting that placental and potentially lactational transfer are important exposure routes for GenX.
基金supported by the Guangdong Provincial Key Area Research and Development Program[grant number 2022B0202090002]China Postdoctoral Science Foundation[grant number 2024M760977].
文摘Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.
文摘Per-and polyfluoroalkyl substances(PFAS)are a class of ubiquitous,persistent,and hazardous pollutants that raise concerns for human health and the environment.Typically,PFAS removal from water relies on adsorption techniques using conventional sorption materials like activated carbons(ACs)and ion exchange resins(IERs).However,there is a continuous search for more efficient and performing adsorbent materials to better address the wide range of chemical structures of PFAS in the environment,to increase their selectivity,and to achieve an overall high adsorption capacity and faster uptake kinetics.In this context,results from the application of non-conventional sorption materials(i.e.,readily available biological-based materials like proteins and advanced materials like nanocomposites and cyclodextrins)are reported and discussed in consideration of the following criteria:i)removal efficiency and kinetics of legacy PFAS(e.g.,PFOA,PFBA)as well as newly-introduced and emerging PFAS(e.g.,GenX),ii)representativity of environmental conditions in the experimental setup(e.g.,use of environmentally relevant experimental concentrations),iii)regenerability,reusability and applicability of the materials,and iv)role of the material modifications on PFAS adsorption.From this review,it emerged that organic frameworks,nano(ligno)cellulosic-based materials,and layered double hydroxides are among the most promising materials herein investigated for PFAS adsorption,and it was also observed that the presence of fluorine-and amine-moieties in the material structure improve both the selectivity and PFAS uptake.However,the lack of data on their applicability in real environments and the costs involved means that this research is still in its infancy and need further investigation.
