{"id":"https://openalex.org/W7225799758","doi":"https://doi.org/10.1021/acs.est.6c10549","title":"Emerging Hexafluoropropylene Oxide Trimer Acid Potently Targets Farnesoid X Receptor and Triggers Hepatic Cholestasis","display_name":"Emerging Hexafluoropropylene Oxide Trimer Acid Potently Targets Farnesoid X Receptor and Triggers Hepatic Cholestasis","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225799758","doi":"https://doi.org/10.1021/acs.est.6c10549"},"language":"en","primary_location":{"id":"doi:10.1021/acs.est.6c10549","doi":"https://doi.org/10.1021/acs.est.6c10549","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.est.6c10549","pdf_url":null,"source":{"id":"https://openalex.org/S13479253","display_name":"Environmental Science & Technology","issn_l":"0013-936X","issn":["0013-936X","1520-5851"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","fnege-4","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Environmental Science &amp; Technology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5101368226","display_name":"Jingyue Du","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I108688024","display_name":"Qingdao University","ror":"https://ror.org/021cj6z65","country_code":"CN","type":"education","lineage":["https://openalex.org/I108688024"]},{"id":"https://openalex.org/I4210165038","display_name":"University of Chinese Academy of Sciences","ror":"https://ror.org/05qbk4x57","country_code":"CN","type":"education","lineage":["https://openalex.org/I19820366","https://openalex.org/I4210165038"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jingyue Du","raw_affiliation_strings":["Qingdao University , , , ,","University of Chinese Academy of Sciences , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Qingdao University , , , ,","institution_ids":["https://openalex.org/I108688024"]},{"raw_affiliation_string":"University of Chinese Academy of Sciences , , , ,","institution_ids":["https://openalex.org/I4210165038"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083045974","display_name":"Huizi Yang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I108688024","display_name":"Qingdao University","ror":"https://ror.org/021cj6z65","country_code":"CN","type":"education","lineage":["https://openalex.org/I108688024"]},{"id":"https://openalex.org/I4210165038","display_name":"University of Chinese Academy of Sciences","ror":"https://ror.org/05qbk4x57","country_code":"CN","type":"education","lineage":["https://openalex.org/I19820366","https://openalex.org/I4210165038"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Huizi Yang","raw_affiliation_strings":["Qingdao University , , , ,","University of Chinese Academy of Sciences , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Qingdao University , , , ,","institution_ids":["https://openalex.org/I108688024"]},{"raw_affiliation_string":"University of Chinese Academy of Sciences , , , ,","institution_ids":["https://openalex.org/I4210165038"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5144988077","display_name":"\u8c37\u7389\u65b0","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I181877577","display_name":"Shanxi University","ror":"https://ror.org/03y3e3s17","country_code":"CN","type":"education","lineage":["https://openalex.org/I181877577"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yuxin Gu","raw_affiliation_strings":["Shanxi University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Shanxi University , , , ,","institution_ids":["https://openalex.org/I181877577"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161460833","display_name":"Chenting Wei","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210165038","display_name":"University of Chinese Academy of Sciences","ror":"https://ror.org/05qbk4x57","country_code":"CN","type":"education","lineage":["https://openalex.org/I19820366","https://openalex.org/I4210165038"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Chenting Wei","raw_affiliation_strings":["University of Chinese Academy of Sciences , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chinese Academy of Sciences , , , ,","institution_ids":["https://openalex.org/I4210165038"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101278181","display_name":"Zeyu Song","orcid":"https://orcid.org/0009-0005-1094-2223","observed_orcids":["https://orcid.org/0009-0005-1094-2223","https://orcid.org/0009-0005-9760-3493"]},"institutions":[{"id":"https://openalex.org/I55538621","display_name":"China Jiliang University","ror":"https://ror.org/05v1y0t93","country_code":"CN","type":"education","lineage":["https://openalex.org/I55538621"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zeyu Song","raw_affiliation_strings":["China Jiliang University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"China Jiliang University , , , ,","institution_ids":["https://openalex.org/I55538621"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5104315348","display_name":"Lanchao Sun","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I108688024","display_name":"Qingdao University","ror":"https://ror.org/021cj6z65","country_code":"CN","type":"education","lineage":["https://openalex.org/I108688024"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Lanchao Sun","raw_affiliation_strings":["Qingdao University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Qingdao University , , , ,","institution_ids":["https://openalex.org/I108688024"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5028518831","display_name":"Chuanhai Li","orcid":"https://orcid.org/0000-0003-1448-183X","observed_orcids":["https://orcid.org/0000-0003-1448-183X"]},"institutions":[{"id":"https://openalex.org/I4210165038","display_name":"University of Chinese Academy of Sciences","ror":"https://ror.org/05qbk4x57","country_code":"CN","type":"education","lineage":["https://openalex.org/I19820366","https://openalex.org/I4210165038"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Chuanhai Li","raw_affiliation_strings":["University of Chinese Academy of Sciences , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Chinese Academy of Sciences , , , ,","institution_ids":["https://openalex.org/I4210165038"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061240384","display_name":"\u674e\u654f\u6d01","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I114539943","display_name":"Zhejiang Chinese Medical University","ror":"https://ror.org/04epb4p87","country_code":"CN","type":"education","lineage":["https://openalex.org/I114539943"]},{"id":"https://openalex.org/I55538621","display_name":"China Jiliang University","ror":"https://ror.org/05v1y0t93","country_code":"CN","type":"education","lineage":["https://openalex.org/I55538621"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Minjie Li","raw_affiliation_strings":["China Jiliang University , , , ,","Zhejiang Chinese Medical University , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"China Jiliang University , , , ,","institution_ids":["https://openalex.org/I55538621"]},{"raw_affiliation_string":"Zhejiang Chinese Medical University , , , ,","institution_ids":["https://openalex.org/I114539943"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5001603792","display_name":"Liang\u2010Hong Guo","orcid":"https://orcid.org/0000-0003-1399-5716","observed_orcids":["https://orcid.org/0000-0003-1399-5716"]},"institutions":[{"id":"https://openalex.org/I4210165038","display_name":"University of Chinese Academy of Sciences","ror":"https://ror.org/05qbk4x57","country_code":"CN","type":"education","lineage":["https://openalex.org/I19820366","https://openalex.org/I4210165038"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Liang-Hong Guo","raw_affiliation_strings":["University of Chinese Academy of Sciences , , , ,"],"raw_orcid":"https://orcid.org/0000-0003-1399-5716","affiliations":[{"raw_affiliation_string":"University of Chinese Academy of Sciences , , , ,","institution_ids":["https://openalex.org/I4210165038"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":5,"corresponding_author_ids":["https://openalex.org/A5028518831","https://openalex.org/A5061240384"],"corresponding_institution_ids":["https://openalex.org/I114539943","https://openalex.org/I4210165038","https://openalex.org/I55538621"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11869","display_name":"Per- and polyfluoroalkyl substances research","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2304","display_name":"Environmental Chemistry"},"field":{"id":"https://openalex.org/fields/23","display_name":"Environmental Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11869","display_name":"Per- and polyfluoroalkyl substances research","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2304","display_name":"Environmental Chemistry"},"field":{"id":"https://openalex.org/fields/23","display_name":"Environmental Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10122","display_name":"Toxic Organic Pollutants Impact","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2307","display_name":"Health, Toxicology and Mutagenesis"},"field":{"id":"https://openalex.org/fields/23","display_name":"Environmental Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C203862802","wikidata":"https://www.wikidata.org/wiki/Q14905041","display_name":"Farnesoid X receptor","level":5,"score":0.9850000143051147},{"id":"https://openalex.org/C2781089062","wikidata":"https://www.wikidata.org/wiki/Q419028","display_name":"Chenodeoxycholic acid","level":3,"score":0.84170001745224},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.8057000041007996},{"id":"https://openalex.org/C2779399885","wikidata":"https://www.wikidata.org/wiki/Q413288","display_name":"Bile acid","level":2,"score":0.7616000175476074},{"id":"https://openalex.org/C2775979320","wikidata":"https://www.wikidata.org/wiki/Q418348","display_name":"Perfluorooctanoic acid","level":2,"score":0.682699978351593},{"id":"https://openalex.org/C2778593092","wikidata":"https://www.wikidata.org/wiki/Q1075923","display_name":"Cholestasis","level":2,"score":0.5726000070571899},{"id":"https://openalex.org/C2780420665","wikidata":"https://www.wikidata.org/wiki/Q3323035","display_name":"Lithocholic acid","level":3,"score":0.44839999079704285},{"id":"https://openalex.org/C2780965833","wikidata":"https://www.wikidata.org/wiki/Q241374","display_name":"Ursodeoxycholic acid","level":2,"score":0.44749999046325684},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4178999960422516},{"id":"https://openalex.org/C183481951","wikidata":"https://www.wikidata.org/wiki/Q15312971","display_name":"Small heterodimer partner","level":5,"score":0.3921999931335449},{"id":"https://openalex.org/C2776403692","wikidata":"https://www.wikidata.org/wiki/Q898416","display_name":"Trimer","level":3,"score":0.38100001215934753},{"id":"https://openalex.org/C89673097","wikidata":"https://www.wikidata.org/wiki/Q14907373","display_name":"Cholesterol 7 alpha-hydroxylase","level":3,"score":0.36419999599456787},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.3418000042438507},{"id":"https://openalex.org/C39321552","wikidata":"https://www.wikidata.org/wiki/Q18052005","display_name":"G protein-coupled bile acid receptor","level":3,"score":0.30730000138282776},{"id":"https://openalex.org/C2777616060","wikidata":"https://www.wikidata.org/wiki/Q412845","display_name":"Dichloroacetic acid","level":2,"score":0.30480000376701355},{"id":"https://openalex.org/C2776279336","wikidata":"https://www.wikidata.org/wiki/Q2701638","display_name":"Glycocholic acid","level":4,"score":0.28999999165534973},{"id":"https://openalex.org/C10213722","wikidata":"https://www.wikidata.org/wiki/Q17912191","display_name":"CYP8B1","level":4,"score":0.28439998626708984},{"id":"https://openalex.org/C102747710","wikidata":"https://www.wikidata.org/wiki/Q824237","display_name":"Endosome","level":3,"score":0.2759999930858612},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2734000086784363},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.26809999346733093},{"id":"https://openalex.org/C2777575235","wikidata":"https://www.wikidata.org/wiki/Q558404","display_name":"Alcoholic liver disease","level":3,"score":0.26249998807907104},{"id":"https://openalex.org/C2776637226","wikidata":"https://www.wikidata.org/wiki/Q6658207","display_name":"Liver injury","level":2,"score":0.25540000200271606},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.2522999942302704}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1021/acs.est.6c10549","doi":"https://doi.org/10.1021/acs.est.6c10549","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.est.6c10549","pdf_url":null,"source":{"id":"https://openalex.org/S13479253","display_name":"Environmental Science & Technology","issn_l":"0013-936X","issn":["0013-936X","1520-5851"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","fnege-4","jufo-2","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Environmental Science &amp; Technology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":53,"referenced_works":["https://openalex.org/W1982293068","https://openalex.org/W2074631079","https://openalex.org/W2078810890","https://openalex.org/W2082184791","https://openalex.org/W2105781444","https://openalex.org/W2744815276","https://openalex.org/W2750612244","https://openalex.org/W2766892908","https://openalex.org/W2787033164","https://openalex.org/W2801936321","https://openalex.org/W2809368137","https://openalex.org/W2917598327","https://openalex.org/W2963623187","https://openalex.org/W2996722208","https://openalex.org/W3041054603","https://openalex.org/W3111128202","https://openalex.org/W3155404950","https://openalex.org/W3194156453","https://openalex.org/W3196254098","https://openalex.org/W3203871248","https://openalex.org/W3207205184","https://openalex.org/W3212440973","https://openalex.org/W3213475957","https://openalex.org/W3217291471","https://openalex.org/W4210539613","https://openalex.org/W4212954224","https://openalex.org/W4220823825","https://openalex.org/W4221066727","https://openalex.org/W4223475745","https://openalex.org/W4295776234","https://openalex.org/W4308958839","https://openalex.org/W4321438520","https://openalex.org/W4367367555","https://openalex.org/W4376629567","https://openalex.org/W4385968768","https://openalex.org/W4390876517","https://openalex.org/W4391850812","https://openalex.org/W4399992915","https://openalex.org/W4400663123","https://openalex.org/W4400981606","https://openalex.org/W4401993665","https://openalex.org/W4403251339","https://openalex.org/W4405443407","https://openalex.org/W4405987378","https://openalex.org/W4406058016","https://openalex.org/W4406860369","https://openalex.org/W4408505605","https://openalex.org/W4410951672","https://openalex.org/W4414722425","https://openalex.org/W4415205376","https://openalex.org/W4415541046","https://openalex.org/W4417535019","https://openalex.org/W7128299323"],"related_works":[],"abstract_inverted_index":{"Abstract":[0],"Per-":[1],"and":[2,13,46,59,77,86,116,131,151,191],"polyfluoroalkyl":[3],"substance":[4],"(PFAS)":[5],"hepatotoxicity":[6,74],"is":[7,18],"a":[8,20],"critical":[9],"global":[10],"health":[11,57,189],"threat,":[12],"disrupted":[14],"bile":[15,88,98],"acid":[16,44,48,66,89,99,150],"metabolism":[17],"considered":[19],"key":[21],"driver":[22],"of":[23,39,171],"PFAS-triggered":[24],"liver":[25,197],"injury,":[26],"yet":[27],"the":[28,36,96,125],"underlying":[29],"mechanisms":[30,38],"remain":[31],"unclear.":[32],"Herein,":[33],"we":[34],"explored":[35],"hepatotoxic":[37],"emerging":[40],"hexafluoropropylene":[41],"oxide":[42],"trimer":[43],"(HFPO-TA)":[45],"dimer":[47],"(HFPO\u2013DA)":[49],"via":[50,128],"farnesoid":[51],"X":[52],"receptor":[53],"(FXR),":[54],"assessed":[55],"their":[56,62],"risks,":[58],"further":[60],"compared":[61],"effects":[63],"against":[64],"perfluorooctanoic":[65],"(PFOA).":[67],"In":[68],"rat,":[69],"HFPO-TA":[70,108,140,175],"exerted":[71],"more":[72],"potent":[73,107],"than":[75,147,155],"PFOA":[76,110,117],"HFPO\u2013DA,":[78,115],"triggering":[79],"typical":[80],"cholestasis":[81,186],"through":[82],"impaired":[83],"biliary":[84],"excretion":[85],"altered":[87],"pool.":[90],"Mechanistically,":[91],"all":[92],"three":[93],"PFASs":[94],"promoted":[95],"intracellular":[97],"accumulation":[100],"by":[101,158],"inhibiting":[102],"FXR":[103,122,142,179],"transcriptional":[104],"activity,":[105],"with":[106,143],">":[109,111],"HFPO\u2013DA.":[112],"Accordingly,":[113],"HFPO-TA,":[114],"can":[118],"directly":[119,176],"bind":[120],"to":[121,134,178,180],"though":[123],"entering":[124],"ligand-binding":[126],"domain":[127],"hydrogen":[129],"bonding":[130],"hydrophobic":[132],"interactions":[133],"stabilize":[135],"an":[136],"antagonizing":[137],"conformation.":[138],"Notably,":[139],"bound":[141],"3.25-fold":[144],"higher":[145,153],"affinity":[146,154],"endogenous":[148],"chenodeoxycholic":[149],"50-fold":[152],"PFOA,":[156],"accompanied":[157],"elevated":[159],"receptor-bound":[160],"concentrations":[161],"(RBCs).":[162],"RBC-based":[163],"risk":[164,168],"assessment":[165],"revealed":[166],"moderate":[167],"in":[169],"28.3%":[170],"HFPO-TA-exposed":[172],"residents.":[173],"Overall,":[174],"binds":[177],"induce":[181],"hepatic":[182],"cholestasis;":[183],"such":[184],"FXR-mediated":[185],"poses":[187],"notable":[188],"risks":[190],"warrants":[192],"broad":[193],"vigilance":[194],"toward":[195],"PFAS":[196],"hazards.":[198]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}
