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Monocytes, as major mediators of acute infection, are implicated in complications among critically ill patients. Identifying key monocyte subsets and their activation states is essential for diagnosis and delineating new therapeutic targets for sepsis. Here, single cell transcriptome sequencing and mass cytometry are used to assess alterations in the composition and function of peripheral monocytes of patients with sepsis, and CD38\n                    <jats:sup>high<\/jats:sup>\n                    monocytes in circulation are specifically accumulated within the first 24\u00a0h of sepsis. CD38\n                    <jats:sup>high<\/jats:sup>\n                    monocytes are detectable by conventional flow cytometry to discriminate sepsis and sterile inflammation, and are associated with 28\u2010day mortality in bacterial sepsis. Targeting CD38 therapy markedly reduces inflammatory response in primary monocytes and in sepsis mice model. Mechanistically, CD38\n                    <jats:sup>high<\/jats:sup>\n                    monocytes in sepsis exhibit hyperactivated glycolysis with activation of hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) due to NAD\n                    <jats:sup>+<\/jats:sup>\n                    consumption. Glycolytic metabolite methylglyoxal (MGO) is found to regulate expression of CD38, establishing a CD38\u2010HIF\u20101\u03b1\/glycolysis\/MGO loop that exacerbates sepsis\u2010induced immune dysregulation. These findings demonstrate that CD38\n                    <jats:sup>high<\/jats:sup>\n                    monocytes might serve as a candidate diagnostic biomarker and therapeutic target for sepsis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500457","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T05:12:01Z","timestamp":1743311521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification of CD38\n                    <sup>high<\/sup>\n                    Monocyte as a Candidate Diagnostic Biomarker and Therapeutic Target for Sepsis"],"prefix":"10.1002","volume":"12","author":[{"given":"Ning","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"},{"name":"Department of Intensive Care Unit The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"},{"name":"Department of Biophysics and neurology Center for Membrane Receptors and Brain Medicine the Fourth Affiliated Hospital of School of Medicine International School of Medicine International Institutes of Medicine Zhejiang University  Yiwu 322000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Bai","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Pharmacy College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 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 79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital School of Medicine Zhejiang University  79 Qingchun Road Hangzhou 310003 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