{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T04:27:44Z","timestamp":1787372864765,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82374315"],"award-info":[{"award-number":["82374315"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82374315"],"award-info":[{"award-number":["82374315"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"State Key Research Development Program of China","award":["2024YFC2607504"],"award-info":[{"award-number":["2024YFC2607504"]}]},{"name":"Guangzhou Key Research and Development Program","award":["202206010066"],"award-info":[{"award-number":["202206010066"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Malaria pathogenesis involves complex immunopathological mechanisms that hinder early diagnosis and effective treatment. This study integrates multi-omics data and experimental models to identify host-derived biomarkers and elucidate their functional roles. By combining human transcriptomic datasets, weighted gene co-expression network analysis (WGCNA), and machine learning (LASSO, SVM, RF), we identified C1QB as a key hub gene. In human data, C1QB was significantly upregulated in both training and validation cohorts (AUC 0.983 and 0.970). Single-gene GSEA and immune infiltration analyses linked C1QB to apoptosis, inflammation, and altered immune cell composition, including increased activated dendritic cells and neutrophils, and decreased na\u00efve B cells and CD8+ T cells. In a murine malaria model (Plasmodium berghei ANKA), C1QB expression rose as early as day one post-infection, preceding detectable parasitemia. Immunohistochemistry revealed C1QB accumulation in the liver and spleen. Single-cell RNA sequencing in the murine model confirmed monocyte-predominant expression, and scTenifoldKnk analysis suggested its role in immune regulation. Crucially, inhibiting C1q in mice via antibody intervention alleviated malaria-induced inflammation, tissue damage, and apoptosis, indicating that C1QB\/C1q actively contributes to immunopathology. AI-based drug prediction and molecular docking further supported its therapeutic potential. Collectively, our findings establish C1QB as a dual biomarker and pathogenic driver in malaria, with diagnostic and therapeutic implications. Further studies are required to validate direct target engagement and clarify upstream regulatory mechanisms.<\/jats:p>","DOI":"10.3390\/ijms27167459","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"7459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["C1QB-Mediated Immunopathology in a Murine Malaria Model: A Multi-Omics Validation for Diagnostic and Therapeutic Targeting"],"prefix":"10.3390","volume":"27","author":[{"given":"Yue","family":"Xie","sequence":"first","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8439-1082","authenticated-orcid":false,"given":"Jianan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Temple University Philadelphia, Philadelphia, PA 19122-6096, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixuan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanchao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Ye","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Xiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsheng","family":"Deng","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510080, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101073","DOI":"10.1016\/j.lanmic.2025.101073","article-title":"WHO World Malaria Report 2024","volume":"6","author":"Venkatesan","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1016\/S0140-6736(20)30223-3","article-title":"Malaria Eradication","volume":"395","author":"Wang","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s41467-024-52223-7","article-title":"The Spatiotemporal Transcriptional Profiling of Murine Brain during Cerebral Malaria Progression and after Artemisinin Treatment","volume":"16","author":"Chen","year":"2025","journal-title":"Nat. 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