{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:21:32Z","timestamp":1787667692265,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574688"],"award-info":[{"award-number":["82574688"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin Municipality","doi-asserted-by":"publisher","award":["25JCYBJC00620"],"award-info":[{"award-number":["25JCYBJC00620"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and closely associated with persistent inflammatory responses and impairment of the mucosal barrier integrity. In this work, we demonstrated that Th17\/Treg immune imbalance drove inflammation and pyroptosis in IBD, as revealed by single\u2010cell RNA sequencing, and pyruvate kinase M2 (PKM2) and ubiquitin\u2010like with PHD and RING finger domains 1\u200c (Uhrf1) displayed a negative correlation in IBD clinic samples. Target fishing analysis revealed that eupatolide (EPT) covalently bound to C165 of PKM2 with a dissociation constant (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    ) of 106 nM, corroborated by follow\u2010up chemical biology assays. We gained a deeper understanding of the mechanistic by which EPT interfered PKM2 function, specifically by promoting its interaction with Uhrf1, enhancing the K48\u2010linked ubiquitylation and degradation of PKM2 to block its nuclear translocation. Critically, PKM2 silencing mitigated dextran sodium sulfate (DSS)\u2010driven inflammation and pyroptosis across in vitro and in vivo models, with EPT showing no further efficacy upon\n                    <jats:italic>PKM2<\/jats:italic>\n                    knockdown in IBD mice. This work uncovered Uhrf1\u2010dependent PKM2 ubiquitination\/degradation as a previously unrecognized therapeutic axis for IBD, while positioning EPT as a molecular glue capable of targeting the Uhrf1\u2013PKM2 complex.\n                  <\/jats:p>","DOI":"10.1002\/advs.77403","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:28:53Z","timestamp":1787664533000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uhrf1\u2010Mediated PKM2 Degradation via Ubiquitination Alleviates Inflammation and Pyroptosis in Inflammatory Bowel Disease"],"prefix":"10.1002","author":[{"given":"Juan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica School of Medical Technology Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica School of Medical Technology Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica School of Medical Technology Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi\u2010Meng","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica School of Medical Technology Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica School of Medical Technology Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u2010Peng","family":"Shang","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Hui","family":"Du","sequence":"additional","affiliation":[{"name":"First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5672-6631","authenticated-orcid":false,"given":"Christophe","family":"Morisseau","sequence":"additional","affiliation":[{"name":"Department of Entomology and Nematology UC Davis Comprehensive Cancer Center University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-8670","authenticated-orcid":false,"given":"Feng","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica School of Medical Technology Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine Tianjin University of Traditional Chinese Medicine  Tianjin People's Republic of 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010022\u201000738\u2010z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20230142"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2403417121"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)32448\u20100"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.01.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102019\u2010318936"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155973"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307395120"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2319833121"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2024.08.003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.10.014"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.936967"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2527086122"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202514514"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010019\u20100317\u20108"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.748573"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2629"},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190613","article-title":"PKM2 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