{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:36:07Z","timestamp":1786703767217,"version":"build-2736575974"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"\"Pioneer and Leading Goose\" R&D Program of Zhejiang Province","award":["2026C04055"],"award-info":[{"award-number":["2026C04055"]}]},{"name":"Prevention and Control of Emerging and Major Infectious Diseases - National Science and Technology Major Project","award":["2025ZD0190640"],"award-info":[{"award-number":["2025ZD0190640"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Infection"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease with rapid progression and high mortality. This study aimed to assess the predictive power of serum neutrophil gelatinase-associated lipocalin (NGAL) for mortality risk and elucidate its cellular origin at the single-cell level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective multicenter study, we analyzed clinical data from 215 SFTS patients across three Chinese hospitals (152 in the training cohort and 63 in the external validation cohort). We further analyzed publicly available single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from SFTS patients and healthy controls to investigate the cellular source of NGAL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum NGAL was identified as an independent risk factor for 14-day and 28-day all-cause mortality (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). High NGAL levels were linearly associated with increased mortality and remained stable across various clinical subgroups. Crucially, unbiased scRNA-seq analysis revealed that the elevated NGAL (encoded by the LCN2 gene) primarily originated from low-density neutrophils (LDNs) that co-purified with PBMCs. These LCN2-expressing LDNs were highly enriched in non-survivors and exhibited a hyper-inflammatory, interferon-stimulated transcriptomic signature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings establish serum NGAL as a robust early predictor of mortality risk in SFTS patients, with its elevation intrinsically linked to the pathogenic emergence of highly activated LDNs, providing novel insights into the immunopathology of fatal SFTS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s15010-026-02840-9","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:44:47Z","timestamp":1780307087000},"page":"2085-2097","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyper-activated low-density neutrophil-derived NGAL predicts fatal SFTS: a multi-cohort and single-cell study"],"prefix":"10.1007","volume":"54","author":[{"given":"Guangqi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuolin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SuKun","family":"Kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"issue":"6","key":"2840_CR1","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.virs.2025.12.008","volume":"40","author":"XG Hong","year":"2025","unstructured":"Hong XG, Ge HH, Cui N, et al. Predicting mortality risk of severe fever with thrombocytopenia syndrome: a multi-center retrospective cohort study. Virol Sin. 2025;40(6):1011\u201320.","journal-title":"Virol Sin"},{"issue":"6","key":"2840_CR2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0013207","volume":"19","author":"B Zhang","year":"2025","unstructured":"Zhang B, Gong JL, Zeng HL, et al. Unveiling fatal risk factors: predicting hemophagocytic lymphohistiocytosis in SFTS patients. PLoS Negl Trop Dis. 2025;19(6):e0013207.","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"2840_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-023-15379-3","volume":"23","author":"S Liang","year":"2023","unstructured":"Liang S, Li Z, Zhang N, et al. Epidemiological and spatiotemporal analysis of severe fever with thrombocytopenia syndrome in Eastern China, 2011\u20132021. BMC Public Health. 2023;23(1):508.","journal-title":"BMC Public Health"},{"issue":"10","key":"2840_CR4","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.29941","volume":"96","author":"Y Hao","year":"2024","unstructured":"Hao Y, Sun J, Wang X, et al. Difference in hematocrit and plasma albumin levels as an early biomarker of severity and prognosis in patients with severe fever and thrombocytopenia syndrome. J Med Virol. 2024;96(10):e29941.","journal-title":"J Med Virol"},{"issue":"4","key":"2840_CR5","doi-asserted-by":"publisher","first-page":"e0012068","DOI":"10.1371\/journal.pntd.0012068","volume":"18","author":"S Zhang","year":"2024","unstructured":"Zhang S, Wang J, Zhang Q, et al. Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome. 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Role of neutrophil gelatinase-associated lipocalin (NGAL) and other clinical parameters as predictors of bacterial sepsis in patients presenting to the emergency department with fever. Indian J Crit Care Med. 2023;27(3):176\u201382.","journal-title":"Indian J Crit Care Med"},{"issue":"4","key":"2840_CR15","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/cre2.295","volume":"6","author":"L Walvik","year":"2020","unstructured":"Walvik L, Kirchmann M, Jensen CAJ, et al. Neutrophil gelatinase associated lipocalin a biomarker for bacterial-induced pharyngeal infection-a pilot study. Clin Exp Dent Res. 2020;6(4):433\u20138.","journal-title":"Clin Exp Dent Res"},{"issue":"4","key":"2840_CR16","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.7150\/ijbs.79915","volume":"19","author":"HS An","year":"2023","unstructured":"An HS, Yoo JW, Jeong JH, et al. Lipocalin-2 promotes acute lung inflammation and oxidative stress by enhancing macrophage iron accumulation. 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