{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:42:43Z","timestamp":1792784563460,"version":"4.5.0"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","award":["2025ZD1203302"],"award-info":[{"award-number":["2025ZD1203302"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["22576003"],"award-info":[{"award-number":["22576003"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>While exposure to PPAR active compounds can lead to various adverse health effects, studies on the environmental contaminants and their transformation products with PPAR activity remain limited. This study employed PPAR\u03b3 protein affinity selection-mass spectrometry (AS-MS) to comprehensively identify and prioritize PPAR\u03b3-active contaminants in the Yangtze and Yellow Rivers, key drinking water sources in China. From wastewater treatment plant effluents, river, and source water samples, 61 PPAR\u03b3 ligands were identified, including 18 antagonists not reported previously. Notably, a novel biodegradation product of di-2-ethylhexyl phthalate (DEHP), phthalic acid 1-(2-ethylhexyl) 2-(2-ethyl-5-carboxypentyl) ester (5CX-DEHP), was discovered and characterized as a potent PPAR\u03b3 antagonist (IC50 = 8.5 \u03bcM). Semi-quantification revealed total concentrations of 61 chemicals ranging from 965.2 to 5748 ng\/L in source waters, with priority agonistic chemicals such as 4-dodecylbenzenesulfonic acid and priority antagonistic chemicals such as 2-amino-6-methylmercaptopurine and 5CX-DEHP posing high ranking. This study comprehensively revealed the widespread occurrence of PPAR\u03b3 agonistic and antagonistic chemicals in the water samples and identified a previously overlooked transformation product of DEHP as a relatively strong PPAR\u03b3 antagonist.<\/jats:p>","DOI":"10.1021\/acs.est.6c03326","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:02:16Z","timestamp":1790704936000},"page":"29018-29030","source":"Crossref","is-referenced-by-count":0,"title":["High-Throughput\nIdentification of PPAR\u03b3-Active\nChemicals in Riverine Drinking Water Sources: Discover a Novel DEHP\nBiodegradation Product"],"prefix":"10.1021","volume":"60","author":[{"given":"Qiang","family":"Li","sequence":"first","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, China, 200433"]},{"name":"Peking University , , ,","place":["Beijing, China, 100871"]},{"name":"Xihua University , , ,","place":["Chengdu, China, 610039"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6846-3484","authenticated-orcid":true,"given":"Kaisheng","family":"Hong","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenke","family":"Xu","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linwan","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Yue","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9034-3175","authenticated-orcid":true,"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1965-7494","authenticated-orcid":true,"given":"Jianying","family":"Hu","sequence":"additional","affiliation":[{"name":"Fudan University , , ,","place":["Shanghai, China, 200433"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"2026101310151985900_cit1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1475-2891-13-17","article-title":"Peroxisome\nproliferator-activated receptors and their ligands: nutritional and\nclinical implications\u2500a review","volume":"13","author":"Grygiel-Go\u0301rniak","year":"2014","journal-title":"Nutr.\nJ."},{"key":"2026101310151985900_cit2","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.plipres.2013.12.001","article-title":"Regulation of energy metabolism by\nlong-chain fatty acids","volume":"53","author":"Nakamura","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"2026101310151985900_cit3","doi-asserted-by":"publisher","first-page":"3203161","DOI":"10.1155\/2017\/3203161","article-title":"Mediating roles of\nPPARs in the effects of environmental chemicals\non sex steroids","volume":"2017","author":"Huang","year":"2017","journal-title":"PPAR Res."},{"key":"2026101310151985900_cit4","doi-asserted-by":"publisher","first-page":"s50","DOI":"10.1210\/en.2005-1129","article-title":"Environmental obesogens: organotins and endocrine disruption\nvia nuclear receptor signaling","volume":"147","author":"Gru\u0308n","year":"2006","journal-title":"Endocrinol."},{"key":"2026101310151985900_cit5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.mce.2009.02.017","article-title":"PPAR-mediated\nactivity of phthalates:\nA link to the obesity epidemic?","volume":"304","author":"Desvergne","year":"2009","journal-title":"Mol. Cell.\nEndocrinol."},{"key":"2026101310151985900_cit6","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1289\/ehp.1408522","article-title":"Characterizing\nthe peroxisome proliferator-activated receptor (PPAR\u03b3) ligand\nbinding potential of several major flame retardants, their metabolites,\nand chemical mixtures in house dust","volume":"123","author":"Fang","year":"2015","journal-title":"Environ.\nHealth Perspect."},{"key":"2026101310151985900_cit7","doi-asserted-by":"publisher","first-page":"106730","DOI":"10.1016\/j.envint.2021.106730","article-title":"Alternatives for the\nworse: Molecular insights into adverse effects of bisphenol a and\nsubstitutes during human adipocyte differentiation","volume":"156","author":"Schaffert","year":"2021","journal-title":"Environ. 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Technol."},{"key":"2026101310151985900_cit14","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1007\/s10529-010-0359-9","article-title":"A recombinant peroxisome\nproliferator response element-driven\nluciferase assay for evaluation of potential environmental obesogens","volume":"32","author":"Wang","year":"2010","journal-title":"Biotechnol. Lett."},{"key":"2026101310151985900_cit15","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1021\/tx500529x","article-title":"Effects of diisodecyl\nphthalate on PPAR:RXR-dependent gene expression pathways in sea bream\nhepatocytes","volume":"28","author":"Cocci","year":"2015","journal-title":"Chem. Res. Toxicol."},{"key":"2026101310151985900_cit16","doi-asserted-by":"publisher","first-page":"11913","DOI":"10.1021\/acs.est.3c02898","article-title":"Disclosing environmental ligands of L-FABP and PPAR\u0393: should\nwe re-evaluate the chemical safety of hydrocarbon surfactants?","volume":"57","author":"Gong","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"2026101310151985900_cit17","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.toxlet.2005.11.001","article-title":"Mono(2-ethylhexyl)phthalate and mono-n-butyl\nphthalate activation of peroxisome proliferator activated-receptors\n\u03b1 and \u03b3 in breast","volume":"163","author":"Gopisetty Venkata","year":"2006","journal-title":"Toxicol. 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Biotechnol."},{"key":"2026101310151985900_cit25","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS: Processing\nmass spectrometry data for metabolite profiling using nonlinear peak\nalignment, matching, and identification","volume":"78","author":"Smith","year":"2006","journal-title":"Anal.\nChem."},{"key":"2026101310151985900_cit26","doi-asserted-by":"publisher","first-page":"4089","DOI":"10.1093\/bioinformatics\/btz207","article-title":"CliqueMS:\na computational tool for annotating in-source\nmetabolite ions from LC-MS untargeted metabolomics data based on a\ncoelution similarity network","volume":"35","author":"Senan","year":"2019","journal-title":"Bioinformatics"},{"key":"2026101310151985900_cit27","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1021\/acs.est.5b05824","article-title":"Estimating emissions\nand environmental fate of di-(2-ethylhexyl)\nphthalate in Yangtze River delta, China: application of inverse modeling","volume":"50","author":"Zhan","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"2026101310151985900_cit28","first-page":"14","article-title":"Comparison\nand prospect of economic and population development in seven major\nriver basins","volume":"36","author":"Song","year":"2023","journal-title":"Nat. Resour. Econ. China"},{"key":"2026101310151985900_cit29","doi-asserted-by":"publisher","first-page":"697","DOI":"10.2131\/jts.38.697","article-title":"Sodium\ndodecyl sulfate and sodium dodecyl benzenesulfonate are ligands for\nperoxisome proliferator-activated receptor &gamma","volume":"38","author":"Iida","year":"2013","journal-title":"J. Toxicol. Sci."},{"key":"2026101310151985900_cit30","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1111\/j.1476-5381.2011.01265.x","article-title":"Biotransformation\nof 6-thioguanine in inflammatory bowel disease patients: a comparison\nof oral and intravenous administration of 6-thioguanine","volume":"163","author":"Jharap","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"2026101310151985900_cit31","unstructured":"Department of Health and Aged Care, Australian Industrial Chemicals Introduction Scheme.\n          .  Long chain (C\u226510) alkyl benzene sulfonates,\nEvaluation Statement, 2022."}],"container-title":["Environmental Science &amp;\nTechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.est.6c03326","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/40\/29018\/68701959\/acs.est.6c03326.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/esthag\/article-pdf\/60\/40\/29018\/68701959\/acs.est.6c03326.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:49:38Z","timestamp":1791917378000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/esthag\/article\/60\/40\/29018\/5441785\/High-Throughput-Identification-of-PPAR-Active"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":31,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,9,29]]},"published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.est.6c03326","relation":{},"ISSN":["0013-936X","1520-5851"],"issn-type":[{"value":"0013-936X","type":"print"},{"value":"1520-5851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}