{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:12:30Z","timestamp":1788437550413,"version":"build-2803163510"},"reference-count":28,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/na","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"publisher","award":["CSTB2025NSCQ-GPX0395"],"award-info":[{"award-number":["CSTB2025NSCQ-GPX0395"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Thyroid dysfunction affects hundreds of millions of people worldwide, yet the environmental contributors remain poorly characterized. Dibromoacetic acid (DBA), an unregulated brominated disinfection byproduct, is frequently detected in drinking water and is widely present in human populations. Despite its widespread human exposure, its potential to disrupt thyroid function and induce hypothyroidism has remained largely unexplored. To address this knowledge gap, we adopted an integrative strategy combining network toxicology, transcriptomics, and in vivo and in vitro experimental validation. Phenotypic results showed that in DBA-exposed SD rats, plasma thyroid hormone (TH) levels decreased, and thyroid histomorphology and ultrastructure were impaired. Mechanistically, DBA dysregulated thyroid miRNA expression, particularly upregulating miR-365\u20135p\/miR-448\u20135p to downregulate SOCS1. Subsequently, SOCS1 depletion coupled with oxidative stress hyperactivated the Jak1\/Stat1 signaling cascade, which, in turn, positively regulated YY1 to transcriptionally repress TPO in thyrocytes, ultimately suppressing TH synthesis. Moreover, DBA disrupted TH metabolism, transport, selenium trafficking, and receptor expression, further exacerbating the hypothyroidism. Taken together, our results identify DBA as an unrecognized thyroid-disrupting chemical beyond a simple unregulated drinking-water DBP. This integrative paradigm bridges computational prediction and mechanistic validation, establishing a reliable workflow to assess endocrine disruption triggered by poorly characterized DBPs and emerging environmental contaminants.<\/jats:p>","DOI":"10.1021\/acs.est.6c07158","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:01:50Z","timestamp":1786964510000},"page":"23877-23891","source":"Crossref","is-referenced-by-count":0,"title":["Dibromoacetic Acid\nInduces Hypothyroidism: From Network\nToxicology to SOCS1-Mediated Mechanistic Validation"],"prefix":"10.1021","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6614-2456","authenticated-orcid":true,"given":"Changjiang","family":"Liu","sequence":"first","affiliation":[{"name":"Women and Children\u2019s Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 410013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suli","family":"Wang","sequence":"additional","affiliation":[{"name":"Women and Children\u2019s Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 410013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqin","family":"Hu","sequence":"additional","affiliation":[{"name":"Chongqing Medical and Pharmaceutical College , , ,","place":["Chongqing, China, 400030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Ha","sequence":"additional","affiliation":[{"name":"Chongqing Medical and Pharmaceutical College , , ,","place":["Chongqing, China, 400030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Women and Children\u2019s Hospital of Chongqing Medical University , , ,","place":["Chongqing, China, 410013"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"2026090307141969800_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108785","article-title":"Urinary haloacetic acid\nconcentrations in relation to sex and thyroid hormones among reproductive-aged\nmen","volume":"189","author":"Chen","year":"2024","journal-title":"Environ. Int."},{"key":"2026090307141969800_cit2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.172368","article-title":"Urinary haloacetic acid\nconcentrations and thyroid function among women: Results from the\nTREE study","volume":"927","author":"Wu","year":"2024","journal-title":"Sci. Total Environ."},{"key":"2026090307141969800_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114926","article-title":"Drinking water disinfection byproduct iodoacetic\nacid affects thyroid hormone synthesis in Nthy-ori 3\u20131 cells","volume":"257","author":"Xiao","year":"2023","journal-title":"Ecotoxicol. Environ. 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Cell.\nLongevity"},{"key":"2026090307141969800_cit6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2020.111401","article-title":"Dibromoacetic acid exposure is associated with\nabnormal melatonin rhythm in rats via inhibition of p-CREB1-AANAT\nsignalling pathway","volume":"208","author":"Jiang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026090307141969800_cit7","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-019-6319-4","article-title":"MiR-155 promotes\nanaplastic thyroid cancer progression\nby directly targeting SOCS1","volume":"19","author":"Zhang","year":"2019","journal-title":"BMC Cancer"},{"key":"2026090307141969800_cit8","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1210\/mend.14.3.0433","article-title":"Thyrotropin induces SOCS-1 (suppressor of cytokine\nsignaling-1) and SOCS-3 in FRTL-5 thyroid cells","volume":"14","author":"Park","year":"2000","journal-title":"Mol. 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