{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:32:15Z","timestamp":1786681935206,"version":"build-2736575974"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key R&D Program of China","award":["2024YFC2309600"],"award-info":[{"award-number":["2024YFC2309600"]}]},{"name":"the Key Project of the Natural Science Foundation of Guangxi","award":["2025GXNSFDA069044"],"award-info":[{"award-number":["2025GXNSFDA069044"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82460405, 82302550"],"award-info":[{"award-number":["82460405, 82302550"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Guangxi Medical University Training Program for Young Leading Talents"},{"name":"Research Project of the Health Commission of Guangxi Zhuang Autonomous Region","award":["Z-A20221219"],"award-info":[{"award-number":["Z-A20221219"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic><jats:italic>Talaromyces marneffei<\/jats:italic><\/jats:italic> (<jats:italic><jats:italic>T. marneffei<\/jats:italic><\/jats:italic>), a life-threatening opportunistic fungal pathogen, is endemic to Southeast Asia. Although elevated aspartate aminotransferase (AST) levels are commonly observed in infected individuals, the origin and mechanism of this phenomenon remain unclear. This study aimed to determine whether AST is a specific clinical indicator of <jats:italic><jats:italic>T. marneffei<\/jats:italic><\/jats:italic> infection and to investigate the underlying mechanisms associated with tissue damage and cell death.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We retrospectively analyzed clinical and laboratory data of HIV\/AIDS patients with or without <jats:italic><jats:italic>T. marneffei<\/jats:italic><\/jats:italic> infection from the Fourth People\u2019s Hospital of Nanning, Guangxi. A murine model of <jats:italic><jats:italic>T. marneffei<\/jats:italic><\/jats:italic> infection was constructed to investigate AST distribution in tissues. Additionally, PANoptosis-related proteins expression and inflammatory cytokines levels were assessed using ELISA, qPCR, and Western blotting.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Patients with HIV\/ <jats:italic><jats:italic>T. marneffei<\/jats:italic><\/jats:italic> co-infection demonstrated significantly higher serum AST levels than HIV-only individuals, which declined following antifungal therapy. In infected mice, AST levels increased progressively in plasma and organs, with hepatic levels elevated throughout days 7, 14, and 21 post-infection. The liver exhibited the highest AST concentration, while the spleen showed the greatest fold increase. PANoptosis markers, including P-RIP, RIPK1, RIPK3, P-MLKL, GSDME, GSDMD, cleaved GSDMD, caspase-3, caspase-7, caspase-8, caspase-9, were markedly upregulated in liver tissues. Concurrently, proinflammatory cytokines Tnf-\u03b1, Il-1\u03b2, and Il-18 were consistently elevated in the liver but suppressed in the spleen, indicating organ-specific immune responses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our findings demonstrate that <jats:italic><jats:italic>T. marneffei<\/jats:italic><\/jats:italic> infection triggers PANoptosis- mediated hepatocyte death and hepatic inflammatory activation, which contributes to AST elevation. AST may serve as a potential auxiliary biomarker for early diagnosis and therapeutic monitoring in Talaromycosis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013443","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T17:36:28Z","timestamp":1756834588000},"page":"e0013443","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["PANoptosis-mediated mechanisms underlying AST elevation in Talaromyces marneffei infection"],"prefix":"10.1371","volume":"19","author":[{"given":"Wudi","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baili","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotao","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiman","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-9348","authenticated-orcid":true,"given":"Junjun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7534-5124","authenticated-orcid":true,"given":"Hao","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-4867","authenticated-orcid":true,"given":"Li","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"pntd.0013443.ref001","unstructured":"Organization W H. 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