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Serum from healthy controls, AGA, and CGA patients was analyzed using DIA proteomics and untargeted metabolomics. Differential analysis uncovered nine persistently dysregulated proteins and 11 consistently altered metabolites. KEGG enrichment implicated thyroid hormone synthesis, AMPK signaling, and taurine/hypotaurine metabolism, while correlation networks indicated immune dysregulation. Findings link disruption of the thyroid hormone–AMPK–taurine axis and immune remodeling to CGA progression and suggest candidate targets for early diagnosis and targeted intervention.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/multi-omics-mechanism-of-chronic-gout-arthritis-and-discovery-of-the-thyroid-hormoneampktaurine-metabolic-axis-article/465150/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/multi-omics-mechanism-of-chronic-gout-arthritis-and-discovery-of-the-thyroid-hormoneampktaurine-metabolic-axis-article/465150.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What distinguishes the transition from acute to chronic gouty arthritis in this study?","Question",{"text":112,"@type":113},"The study targets the AGA-to-CGA transition, a critical phase associated with irreversible joint damage and systemic complications, emphasizing coordinated molecular changes rather than single-omics signals.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which molecular systems and pathways are identified as central in chronic gout progression?",{"text":117,"@type":113},"KEGG enrichment highlights thyroid hormone synthesis, AMPK signaling, and taurine and hypotaurine metabolism, together with immune dysregulation shifting from acute activation to chronic inflammation.",{"name":119,"@type":110,"acceptedAnswer":120},"What biomarker and target potential do the multi-omics results provide?",{"text":121,"@type":113},"Nine persistently dysregulated proteins and 11 consistently altered metabolites show diagnostic potential, and the disrupted thyroid hormone–AMPK–taurine metabolic axis plus immune remodeling are proposed as key targets for early diagnosis and targeted interventions.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},465150,1791524259,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","Article  \nMulti-Omics Mechanism of Chronic Gout Arthritis and Discovery of the Thyroid Hormone–AMPK–Taurine Metabolic Axis  \nGuizhen Zhu 1,†, Yuan Luo 1,†, Xiangyi Zheng 1, Zhusong Mei 1, Qiao Ye 1, Jie Peng 1, Fengsen Duan 1, Yueying Cui 1, Peiyu An 1, Yangqian Song 2, Hongxia Li 2, Haitao Zhang 3,* and Guangyun Wang 1, *  \nAcademic Editor: Kin Hing William Lau  \nReceived: 14 October 2025  \nRevised: 13 November 2025  \nAccepted: 21 November 2025  \nPublished: 25 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Laboratory of Clinical Medicine, Air Force Medical Center, Air Force Medical University, People’s Liberation Army of China, Beijing 100142, China; [13121437811@163.com](13121437811@163.com) (G.Z.); [ly-navy@163.com](ly-navy@163.com) (Y.L.); [zhengxy12345@163.com](zhengxy12345@163.com) (X.Z.); [mzsa@163.com](mzsa@163.com) (Z.M.); [yeqiao333@163.com](yeqiao333@163.com) (Q.Y.); [19991205301@163.com](19991205301@163.com) (J.P.); [dfs_789@126.com](dfs_789@126.com) (F.D.); [cyygsjyg@163.com](cyygsjyg@163.com) (Y.C.); [yupeipyjj@sina.com](yupeipyjj@sina.com) (P.A.)  \n2 Rheumatology and Immunology Department, Air Force Medical Center, Air Force Medical University, People’s Liberation Army of China, Beijing 100142, China; [m15168405793@163.com](m15168405793@163.com) (Y.S.); [hxli2005@126.com](hxli2005@126.com) (H.L.)  \n3 Cardiovascular Department, Air Force Medical Center, Air Force Medical University, People’s Liberation Army of China, Beijing 100142, China  \n* [Correspondence: kjzht@sina.com](Correspondence: kjzht@sina.com) (H.Z.); [gfkdwgy@163.com](gfkdwgy@163.com) (G.W.)† These authors contributed equally to this work.  \nHighlights  \nWhat are the main findings?  \n• Multi-omics profiling reveals nine persistently dysregulated proteins and 11 consistently altered metabolites during the transition from acute to chronic gouty arthritis.  \n• Chronic gout development involves significant perturbations in key pathways—thyroid hormone synthesis, AMPK signaling, and taurine metabolism—and a concomitant shift in the immune response from acute activation to chronic inflammation.  \nWhat are the implications of the main finding?  \n• The study identifies a coordinated disruption of the thyroid hormone–AMPK–taurine metabolic axis and immune microenvironment remodeling as central to chronic gout progression.  \n• These findings offer potential targets for early diagnosis and targeted interventions to prevent irreversible joint damage in chronic gouty arthritis.  \nAbstract  \nThe acute gouty arthritis (AGA) to chronic gouty arthritis (CGA) transition is a critical phase leading to irreversible joint damage and systemic complications. However, current molecular mechanism investigations have remained limited to single-omics approaches that lack comprehensive multi-omics explorations. We integrate high-depth data-independent acquisition (DIA) proteomics and untargeted metabolomics to analyze serum samples from healthy controls (n =28), AGA (n = 31), and CGA (n = 14) patients to address this gap. Through differential expression analysis, we identified nine persistently dysregulated pivotal proteins with robust discriminative capacity, including the urate excretion regulator ZBTB20 and inflammation/immune-related proteins (GUCY1A2, CNDP1, LYZ, SERPINA5, GSN) . Additionally, 11 consistently altered core metabolites with diagnostic potential were detected, indicating perturbations in sex hormones, thyroid hormones, gut microbiotaderived metabolites, environmental exposures, and nutritional factors. Multi-omics KEGG enrichment analysis highlighted thyroid hormone synthesis, AMPK signaling pathway, and  \ntaurine and hypotaurine metabolism as central pathways. Correlation network analysis further revealed significant immune dysregulation, illustrating an evolution from acute immune a","cbCaif2sufuiJEZF","https://ap.wps.com/l/cbCaif2sufuiJEZF","pdf",3149017,"English","# Highlights\n## Main findings\n## Implications of the main finding\n# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What distinguishes the transition from acute to chronic gouty arthritis in this study?\",\"answer\":\"The study targets the AGA-to-CGA transition, a critical phase associated with irreversible joint damage and systemic complications, emphasizing coordinated molecular changes rather than single-omics signals.\"},{\"question\":\"Which molecular systems and pathways are identified as central in chronic gout progression?\",\"answer\":\"KEGG enrichment highlights thyroid hormone synthesis, AMPK signaling, and taurine and hypotaurine metabolism, together with immune dysregulation shifting from acute activation to chronic inflammation.\"},{\"question\":\"What biomarker and target potential do the multi-omics results provide?\",\"answer\":\"Nine persistently dysregulated proteins and 11 consistently altered metabolites show diagnostic potential, and the disrupted thyroid hormone–AMPK–taurine metabolic axis plus immune remodeling are proposed as key targets for early diagnosis and targeted interventions.\"}]","Multi-Omics Mechanism of Chronic Gout Arthritis and Discovery of the Thyroid Hormone–AMPK–Taurine Metabolic Axis - Article | PDF",1790769243,48]