{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:39:19Z","timestamp":1792607959543,"version":"4.5.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Sepsis is heterogeneous, and transcripts that distinguish sepsis from health may lack clinical specificity. We tested whether\n                    <jats:italic>S100A8<\/jats:italic>\n                    is reproducibly associated with sepsis and maps to a donor-aware myeloid state defined independently of\n                    <jats:italic>S100A8<\/jats:italic>\n                    . A discovery whole-blood cohort was analyzed on the log2 robust multi-array average scale using maximum-probe aggregation, limma, weighted gene co-expression network analysis (WGCNA), and leakage-controlled feature prioritization. The analysis identified 1,508 differentially expressed genes; 265 overlapped the strongest sepsis-positive WGCNA module. The network retained all 802 samples and 11,719 genes; the black-module eigengene correlated with sepsis status (r\u2009=\u20090.409; false-discovery rate 3.72\u2009\u00d7\u200910\u2009\u2212\u200933), and\n                    <jats:italic>S100A8<\/jats:italic>\n                    belonged to this module (module membership 0.700).\n                    <jats:italic>S100A8<\/jats:italic>\n                    was upregulated (log2 fold change 1.87; false-discovery rate 2.15\u2009\u00d7\u200910\u2009\u2212\u2009171). Discrimination against clinical comparators was contrast dependent, and outcome analyses did not support a stable prognostic association. Donor-level monocyte pseudo-bulk analysis supported increased\n                    <jats:italic>S100A8<\/jats:italic>\n                    and decreased\n                    <jats:italic>HLA-DRA<\/jats:italic>\n                    but included only two control and four sepsis donors. Across single-cell datasets,\n                    <jats:italic>S100A8<\/jats:italic>\n                    tracked an emergency-myeloid program and inversely tracked antigen presentation. In THP-1 cells,\n                    <jats:italic>S100A8<\/jats:italic>\n                    knockdown attenuated lipopolysaccharide-associated reductions in\n                    <jats:italic>CD74<\/jats:italic>\n                    and HLA-DR\u03b1. Triptolide retained a similar NF-\u03baB phosphorylation effect after\n                    <jats:italic>S100A8<\/jats:italic>\n                    knockdown, providing no evidence that this effect required\n                    <jats:italic>S100A8<\/jats:italic>\n                    .\n                    <jats:italic>S100A8<\/jats:italic>\n                    is therefore prioritized as a marker of a sepsis-associated emergency-myeloid, HLA-DR-low state, not as an established diagnostic, prognostic, direct drug-binding, or therapeutic target.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359578","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:55:09Z","timestamp":1792605309000},"page":"e0359578","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2624-1165","authenticated-orcid":true,"given":"Changlong","family":"Zhang","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Bengbu Medical University","place":["Bengbu, Anhui, China"]},{"name":"Bengbu Medical University","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Cui","sequence":"additional","affiliation":[{"name":"Bengbu Medical University","place":["Bengbu, Anhui, China"]},{"name":"Anhui Provincial Key Laboratory of Infection and Immunity, Bengbu Medical University","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyun","family":"Wu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Bengbu Medical University","place":["Bengbu, Anhui, China"]},{"name":"Bengbu Medical University","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Bengbu Medical University","place":["Bengbu, Anhui, China"]},{"name":"Bengbu Medical University","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Bengbu Medical University","place":["Bengbu, Anhui, China"]},{"name":"Bengbu Medical University","place":["Bengbu, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8257-7326","authenticated-orcid":true,"given":"Liang","family":"Chu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Bengbu Medical University","place":["Bengbu, Anhui, China"]},{"name":"Bengbu Medical University","place":["Bengbu, 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