{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:56:18Z","timestamp":1787003778428,"version":"build-2736575974"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Shandong Provincial Medical and Health Science and Technology Development Program Project","award":["202117011071"],"award-info":[{"award-number":["202117011071"]}]},{"name":"Jinan Municipal Clinical Medical Science and Technology Innovation Program Project","award":["202134069"],"award-info":[{"award-number":["202134069"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-38559-8","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:36:45Z","timestamp":1770140205000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative analysis of transcriptome and single-cell sequencing combined with experimental validation identifies biomarkers associated with T cell and senescence in sepsis"],"prefix":"10.1038","volume":"16","author":[{"given":"Kairui","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafeng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunliang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"38559_CR1","doi-asserted-by":"publisher","first-page":"1543517","DOI":"10.3389\/fimmu.2025.1543517","volume":"16","author":"J Lu","year":"2025","unstructured":"Lu, J. et al. Identification and validation of m(6)A RNA methylation and ferroptosis-related biomarkers in sepsis: Transcriptome combined with single-cell RNA sequencing. Front. Immunol. 16, 1543517. https:\/\/doi.org\/10.3389\/fimmu.2025.1543517 (2025).","journal-title":"Front. Immunol."},{"key":"38559_CR2","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s13054-025-05600-7","volume":"29","author":"V Chechulina","year":"2025","unstructured":"Chechulina, V., Sheikh, F., L\u00f3ser, M., Englesakis, M. & Barrett, K. Healthcare costs after sepsis: A systematic review. Crit. Care (London, England) 29, 381. https:\/\/doi.org\/10.1186\/s13054-025-05600-7 (2025).","journal-title":"Crit. Care (London, England)"},{"key":"38559_CR3","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1186\/s12967-020-02561-z","volume":"18","author":"Z Zhang","year":"2020","unstructured":"Zhang, Z. et al. Gene correlation network analysis to identify regulatory factors in sepsis. J. Transl. Med. 18, 381. https:\/\/doi.org\/10.1186\/s12967-020-02561-z (2020).","journal-title":"J. Transl. Med."},{"key":"38559_CR4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40779-022-00422-y","volume":"9","author":"D Liu","year":"2022","unstructured":"Liu, D. et al. Sepsis-induced immunosuppression: Mechanisms, diagnosis and current treatment options. Mil. Med. Res. 9, 56. https:\/\/doi.org\/10.1186\/s40779-022-00422-y (2022).","journal-title":"Mil. Med. Res."},{"key":"38559_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.111938","volume":"132","author":"G Li","year":"2024","unstructured":"Li, G. et al. Single-cell RNA sequencing reveals cell-cell communication and potential biomarker in sepsis and septic shock patients. Int. Immunopharmacol. 132, 111938. https:\/\/doi.org\/10.1016\/j.intimp.2024.111938 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"38559_CR6","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s13054-020-02950-2","volume":"24","author":"M Bauer","year":"2020","unstructured":"Bauer, M. et al. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis. Crit. Care (London, England) 24, 239. https:\/\/doi.org\/10.1186\/s13054-020-02950-2 (2020).","journal-title":"Crit. Care (London, England)"},{"key":"38559_CR7","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.mcna.2020.02.011","volume":"104","author":"MD Font","year":"2020","unstructured":"Font, M. D., Thyagarajan, B. & Khanna, A. K. Sepsis and Septic Shock\u2014Basics of diagnosis, pathophysiology and clinical decision making. Med. Clin. North Am. 104, 573\u2013585. https:\/\/doi.org\/10.1016\/j.mcna.2020.02.011 (2020).","journal-title":"Med. Clin. North Am."},{"key":"38559_CR8","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41420-023-01766-7","volume":"9","author":"M Cao","year":"2023","unstructured":"Cao, M., Wang, G. & Xie, J. Immune dysregulation in sepsis: Experiences, lessons and perspectives. Cell Death Discov. 9, 465. https:\/\/doi.org\/10.1038\/s41420-023-01766-7 (2023).","journal-title":"Cell Death Discov."},{"key":"38559_CR9","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1007\/s13577-025-01189-9","volume":"38","author":"S Sun","year":"2025","unstructured":"Sun, S. et al. MTHFD2 stabilizes LOX expression through RNA methylation modification to promote sepsis-induced acute kidney injury progression. Hum. Cell 38, 62. https:\/\/doi.org\/10.1007\/s13577-025-01189-9 (2025).","journal-title":"Hum. Cell"},{"key":"38559_CR10","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1186\/s13054-024-05069-w","volume":"28","author":"D Hu","year":"2024","unstructured":"Hu, D. et al. Mitochondrial dysfunction in sepsis: Mechanisms and therapeutic perspectives. Crit. Care (London, England) 28, 292. https:\/\/doi.org\/10.1186\/s13054-024-05069-w (2024).","journal-title":"Crit. Care (London, England)"},{"key":"38559_CR11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12865-025-00790-9","volume":"27","author":"X Liu","year":"2025","unstructured":"Liu, X., Liting, M., Li, P., Chen, Z. & Yu, Z. T cell immunometabolic dysfunction in a mouse model of cecal ligation and puncture-induced sepsis. BMC Immunol. 27, 3. https:\/\/doi.org\/10.1186\/s12865-025-00790-9 (2025).","journal-title":"BMC Immunol."},{"key":"38559_CR12","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","volume":"8","author":"L Sun","year":"2023","unstructured":"Sun, L., Su, Y., Jiao, A., Wang, X. & Zhang, B. T cells in health and disease. Signal Transduct. Target. Ther. 8, 235. https:\/\/doi.org\/10.1038\/s41392-023-01471-y (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"38559_CR13","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","volume":"8","author":"X Li","year":"2023","unstructured":"Li, X. et al. Inflammation and aging: Signaling pathways and intervention therapies. Signal Transduct. Target. Ther. 8, 239. https:\/\/doi.org\/10.1038\/s41392-023-01502-8 (2023).","journal-title":"Signal Transduct. Target. Ther."},{"key":"38559_CR14","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1101\/gad.343129.120","volume":"34","author":"J Birch","year":"2020","unstructured":"Birch, J. & Gil, J. Senescence and the SASP: Many therapeutic avenues. Genes Dev. 34, 1565\u20131576. https:\/\/doi.org\/10.1101\/gad.343129.120 (2020).","journal-title":"Genes Dev."},{"key":"38559_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212539","author":"L M\u00fcller","year":"2021","unstructured":"M\u00fcller, L. & Di Benedetto, S. How immunosenescence and inflammaging may contribute to hyperinflammatory syndrome in COVID-19. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms222212539 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"38559_CR16","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev-immunol-101721-064501","volume":"41","author":"G Soto-Heredero","year":"2023","unstructured":"Soto-Heredero, G., G\u00f3mez de Las Heras, M. M., Escrig-Larena, J. I. & Mittelbrunn, M. Extremely differentiated T cell subsets contribute to tissue deterioration during aging. Annu. Rev. Immunol. 41, 181\u2013205. https:\/\/doi.org\/10.1146\/annurev-immunol-101721-064501 (2023).","journal-title":"Annu. Rev. Immunol."},{"key":"38559_CR17","doi-asserted-by":"publisher","first-page":"1260053","DOI":"10.3389\/fragi.2023.1260053","volume":"4","author":"M Vrbic","year":"2023","unstructured":"Vrbic, M. & Milinkovic, A. Two vicious circles associated with the aging of the immune system in the development of severe forms of COVID-19. Front. Aging 4, 1260053. https:\/\/doi.org\/10.3389\/fragi.2023.1260053 (2023).","journal-title":"Front. Aging"},{"key":"38559_CR18","doi-asserted-by":"publisher","first-page":"6881","DOI":"10.1038\/s41467-022-34660-4","volume":"13","author":"L Xu","year":"2022","unstructured":"Xu, L. et al. IL-33 induces thymic involution-associated naive T cell aging and impairs host control of severe infection. Nat. Commun. 13, 6881. https:\/\/doi.org\/10.1038\/s41467-022-34660-4 (2022).","journal-title":"Nat. Commun."},{"key":"38559_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.696536","volume":"12","author":"DB Darden","year":"2021","unstructured":"Darden, D. B. et al. A novel single cell RNA-seq analysis of non-myeloid circulating cells in late sepsis. Front. Immunol. 12, 696536. https:\/\/doi.org\/10.3389\/fimmu.2021.696536 (2021).","journal-title":"Front. Immunol."},{"key":"38559_CR20","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1182\/blood.2020009499","volume":"137","author":"V Chaturvedi","year":"2021","unstructured":"Chaturvedi, V. et al. T-cell activation profiles distinguish hemophagocytic lymphohistiocytosis and early sepsis. Blood 137, 2337\u20132346. https:\/\/doi.org\/10.1182\/blood.2020009499 (2021).","journal-title":"Blood"},{"key":"38559_CR21","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1042\/cs20230517","volume":"138","author":"K Davies","year":"2024","unstructured":"Davies, K. & McLaren, J. E. Destabilisation of T cell-dependent humoral immunity in sepsis. Clin. Sci. (London, England: 1979) 138, 65\u201385. https:\/\/doi.org\/10.1042\/cs20230517 (2024).","journal-title":"Clin. Sci. (London, England: 1979)"},{"key":"38559_CR22","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1097\/shk.0000000000002086","volume":"59","author":"J Chen","year":"2023","unstructured":"Chen, J. et al. Cellular senescence implicated in sepsis-induced muscle weakness and ameliorated with metformin. Shock (Augusta, Ga) 59, 646\u2013656. https:\/\/doi.org\/10.1097\/shk.0000000000002086 (2023).","journal-title":"Shock (Augusta, Ga)"},{"key":"38559_CR23","doi-asserted-by":"publisher","first-page":"8533","DOI":"10.1038\/s41467-024-52917-y","volume":"15","author":"S Patel","year":"2024","unstructured":"Patel, S. et al. Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors. Nat. Commun. 15, 8533. https:\/\/doi.org\/10.1038\/s41467-024-52917-y (2024).","journal-title":"Nat. Commun."},{"key":"38559_CR24","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41392-021-00823-w","volume":"6","author":"K Shah","year":"2021","unstructured":"Shah, K., Al-Haidari, A., Sun, J. & Kazi, J. U. T cell receptor (TCR) signaling in health and disease. Signal Transduct. Target. Ther. 6, 412. https:\/\/doi.org\/10.1038\/s41392-021-00823-w (2021).","journal-title":"Signal Transduct. Target. Ther."},{"key":"38559_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112087","volume":"133","author":"W Zhang","year":"2024","unstructured":"Zhang, W. et al. EFHD2 regulates T cell receptor signaling and modulates T helper cell activation in early sepsis. Int. Immunopharmacol. 133, 112087. https:\/\/doi.org\/10.1016\/j.intimp.2024.112087 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"38559_CR26","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.7499\/j.issn.1008-8830.2106044","volume":"23","author":"XB Huang","year":"2021","unstructured":"Huang, X. B. et al. Diversity of the T cell receptor \u03b2 chain complementarity-determining region 3 in peripheral blood of neonates with sepsis: An analysis based on immune repertoire sequencing. Zhongguo dang dai er ke za zhi = Chin. J. Contemp. Pediatr. 23, 1154\u20131160. https:\/\/doi.org\/10.7499\/j.issn.1008-8830.2106044 (2021).","journal-title":"Zhongguo dang dai er ke za zhi = Chin. J. Contemp. Pediatr."},{"key":"38559_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02390-6","author":"MT Stier","year":"2026","unstructured":"Stier, M. T. et al. Metabolic adaptations rewire CD4(+) T cells in a subset-specific manner in human critical illness with and without sepsis. Nat. Immunol. https:\/\/doi.org\/10.1038\/s41590-025-02390-6 (2026).","journal-title":"Nat. Immunol."},{"key":"38559_CR28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1615\/CritRevImmunol.2016017098","volume":"36","author":"DB Danahy","year":"2016","unstructured":"Danahy, D. B., Strother, R. K., Badovinac, V. P. & Griffith, T. S. Clinical and experimental sepsis impairs CD8 T-cell-mediated immunity. Crit. Rev. Immunol. 36, 57\u201374. https:\/\/doi.org\/10.1615\/CritRevImmunol.2016017098 (2016).","journal-title":"Crit. Rev. Immunol."},{"key":"38559_CR29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.535039","volume":"12","author":"AF G\u00fclich","year":"2021","unstructured":"G\u00fclich, A. F. et al. Complex interplay between MAZR and Runx3 regulates the generation of cytotoxic T lymphocyte and memory T cells. Front. Immunol. 12, 535039. https:\/\/doi.org\/10.3389\/fimmu.2021.535039 (2021).","journal-title":"Front. Immunol."},{"key":"38559_CR30","doi-asserted-by":"publisher","first-page":"e2402244","DOI":"10.1002\/advs.202402244","volume":"11","author":"Z Zhang","year":"2024","unstructured":"Zhang, Z. et al. SIN3B loss heats up cold tumor microenvironment to boost immunotherapy in pancreatic cancer. Adv. Sci. (Weinheim, Baden-Wurttemberg, Germany) 11, e2402244. https:\/\/doi.org\/10.1002\/advs.202402244 (2024).","journal-title":"Adv. Sci. (Weinheim, Baden-Wurttemberg, Germany)"},{"key":"38559_CR31","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40001-025-03590-4","volume":"31","author":"K Yang","year":"2025","unstructured":"Yang, K., Zhao, Q., Sun, Y., Lin, L. & Han, X. Mitochondrial immunometabolism in sepsis: Orchestrating macrophage polarization and dysfunction. Eur. J. Med. Res. 31, 36. https:\/\/doi.org\/10.1186\/s40001-025-03590-4 (2025).","journal-title":"Eur. J. Med. Res."},{"key":"38559_CR32","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1080\/14728222.2017.1386655","volume":"21","author":"DJ Cantor","year":"2017","unstructured":"Cantor, D. J. & David, G. The potential of targeting Sin3B and its associated complexes for cancer therapy. Expert Opin. Ther. Targets 21, 1051\u20131061. https:\/\/doi.org\/10.1080\/14728222.2017.1386655 (2017).","journal-title":"Expert Opin. Ther. Targets"},{"key":"38559_CR33","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1182\/blood-2016-06-721746","volume":"129","author":"DJ Cantor","year":"2017","unstructured":"Cantor, D. J. & David, G. The chromatin-associated Sin3B protein is required for hematopoietic stem cell functions in mice. Blood 129, 60\u201370. https:\/\/doi.org\/10.1182\/blood-2016-06-721746 (2017).","journal-title":"Blood"},{"key":"38559_CR34","doi-asserted-by":"publisher","first-page":"109789","DOI":"10.1016\/j.isci.2024.109789","volume":"27","author":"M Giovannetti","year":"2024","unstructured":"Giovannetti, M. et al. SIN-3 transcriptional coregulator maintains mitochondrial homeostasis and polyamine flux. iScience 27, 109789. https:\/\/doi.org\/10.1016\/j.isci.2024.109789 (2024).","journal-title":"iScience"},{"key":"38559_CR35","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.70213","author":"C Alemany","year":"2025","unstructured":"Alemany, C. & Morel, E. Phosphoinositides in membrane remodeling during infections and cellular stresses. FEBS Lett. https:\/\/doi.org\/10.1002\/1873-3468.70213 (2025).","journal-title":"FEBS Lett."},{"key":"38559_CR36","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1111\/cns.13738","volume":"27","author":"BW Yin","year":"2021","unstructured":"Yin, B. W. et al. BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder. CNS Neurosci. Ther. 27, 1549\u20131560. https:\/\/doi.org\/10.1111\/cns.13738 (2021).","journal-title":"CNS Neurosci. Ther."},{"key":"38559_CR37","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s10753-020-01355-1","volume":"44","author":"X Zhang","year":"2021","unstructured":"Zhang, X., Mei, D., Zhang, L. & Wei, W. Src family protein kinase controls the fate of B cells in autoimmune diseases. Inflammation 44, 423\u2013433. https:\/\/doi.org\/10.1007\/s10753-020-01355-1 (2021).","journal-title":"Inflammation"},{"key":"38559_CR38","doi-asserted-by":"publisher","first-page":"R613","DOI":"10.1152\/ajpregu.00003.2023","volume":"324","author":"J Arora","year":"2023","unstructured":"Arora, J., Mendelson, A. A. & Fox-Robichaud, A. Sepsis: Network pathophysiology and implications for early diagnosis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 324, R613-r624. https:\/\/doi.org\/10.1152\/ajpregu.00003.2023 (2023).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"38559_CR39","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.imlet.2020.12.012","volume":"231","author":"WY Tang","year":"2021","unstructured":"Tang, W. Y. et al. Abnormal thymic B cell activation and impaired T cell differentiation in pristane-induced lupus mice. Immunol. Lett. 231, 49\u201360. https:\/\/doi.org\/10.1016\/j.imlet.2020.12.012 (2021).","journal-title":"Immunol. Lett."},{"key":"38559_CR40","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109487","volume":"114","author":"J Ni","year":"2023","unstructured":"Ni, J. et al. Halofuginone ameliorates systemic lupus erythematosus by targeting Blk in myeloid-derived suppressor cells. Int. Immunopharmacol. 114, 109487. https:\/\/doi.org\/10.1016\/j.intimp.2022.109487 (2023).","journal-title":"Int. Immunopharmacol."},{"key":"38559_CR41","doi-asserted-by":"publisher","first-page":"891","DOI":"10.3389\/fimmu.2019.00891","volume":"10","author":"F Haussner","year":"2019","unstructured":"Haussner, F., Chakraborty, S., Halbgebauer, R. & Huber-Lang, M. Challenge to the intestinal mucosa during sepsis. Front. Immunol. 10, 891. https:\/\/doi.org\/10.3389\/fimmu.2019.00891 (2019).","journal-title":"Front. Immunol."},{"key":"38559_CR42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12967-022-03320-y","volume":"20","author":"Q Chen","year":"2022","unstructured":"Chen, Q. et al. Integrative analysis of metabolomics and proteomics reveals amino acid metabolism disorder in sepsis. J. Transl. Med. 20, 123. https:\/\/doi.org\/10.1186\/s12967-022-03320-y (2022).","journal-title":"J. Transl. Med."},{"key":"38559_CR43","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1038\/s41590-023-01540-y","volume":"24","author":"R Sharma","year":"2023","unstructured":"Sharma, R. et al. Distinct metabolic requirements regulate B cell activation and germinal center responses. Nat. Immunol. 24, 1358\u20131369. https:\/\/doi.org\/10.1038\/s41590-023-01540-y (2023).","journal-title":"Nat. Immunol."},{"key":"38559_CR44","doi-asserted-by":"publisher","first-page":"1451650","DOI":"10.3389\/fonc.2024.1451650","volume":"14","author":"J Xia","year":"2024","unstructured":"Xia, J., Wang, C. & Li, B. Hepatocellular carcinoma cells induce \u03b3\u03b4 T cells through metabolic reprogramming into tumor-progressive subpopulation. Front. Oncol. 14, 1451650. https:\/\/doi.org\/10.3389\/fonc.2024.1451650 (2024).","journal-title":"Front. Oncol."},{"key":"38559_CR45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.immuni.2021.10.011","volume":"55","author":"A Sugiura","year":"2022","unstructured":"Sugiura, A. et al. MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function. Immunity 55, 65-81.e69. https:\/\/doi.org\/10.1016\/j.immuni.2021.10.011 (2022).","journal-title":"Immunity"},{"key":"38559_CR46","doi-asserted-by":"publisher","first-page":"2369342","DOI":"10.1080\/0886022x.2024.2369342","volume":"46","author":"W Hu","year":"2024","unstructured":"Hu, W. EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction in lipopolysaccharide-induced tubular epithelial cells. Ren. Fail. 46, 2369342. https:\/\/doi.org\/10.1080\/0886022x.2024.2369342 (2024).","journal-title":"Ren. Fail."},{"key":"38559_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2020.106462","volume":"267","author":"MA Siddiqui","year":"2020","unstructured":"Siddiqui, M. A., Pandey, S., Azim, A., Sinha, N. & Siddiqui, M. H. Metabolomics: An emerging potential approach to decipher critical illnesses. Biophys. Chem. 267, 106462. https:\/\/doi.org\/10.1016\/j.bpc.2020.106462 (2020).","journal-title":"Biophys. Chem."},{"key":"38559_CR48","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1039\/d0mo00177e","volume":"17","author":"S Pandey","year":"2021","unstructured":"Pandey, S., Adnan Siddiqui, M., Azim, A., Trigun, S. K. & Sinha, N. Serum metabolic profiles of septic shock patients based upon co-morbidities and other underlying conditions. Mol. Omics 17, 260\u2013276. https:\/\/doi.org\/10.1039\/d0mo00177e (2021).","journal-title":"Mol. Omics"},{"key":"38559_CR49","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3760\/cma.j.cn121430-20220919-00846","volume":"35","author":"Y Chen","year":"2023","unstructured":"Chen, Y., Dong, P. & Zhang, X. Research advance on the role of pro-inflammatory cytokines in sepsis. Zhonghua wei zhong bing ji jiu yi xue 35, 212\u2013216. https:\/\/doi.org\/10.3760\/cma.j.cn121430-20220919-00846 (2023).","journal-title":"Zhonghua wei zhong bing ji jiu yi xue"},{"key":"38559_CR50","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40170-018-0185-4","volume":"6","author":"C Koufaris","year":"2018","unstructured":"Koufaris, C. & Nilsson, R. Protein interaction and functional data indicate MTHFD2 involvement in RNA processing and translation. Cancer Metab. 6, 12. https:\/\/doi.org\/10.1186\/s40170-018-0185-4 (2018).","journal-title":"Cancer Metab."},{"key":"38559_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166831","volume":"11","author":"HM Liu","year":"2016","unstructured":"Liu, H. M., Ferrington, D. A., Baumann, C. W. & Thompson, L. V. Denervation-induced activation of the standard proteasome and immunoproteasome. PLoS ONE 11, e0166831. https:\/\/doi.org\/10.1371\/journal.pone.0166831 (2016).","journal-title":"PLoS ONE"},{"key":"38559_CR52","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.intimp.2018.07.031","volume":"63","author":"L de Lima Thomaz","year":"2018","unstructured":"de Lima Thomaz, L. et al. The impact of metabolic reprogramming on dendritic cell function. Int. Immunopharmacol. 63, 84\u201393. https:\/\/doi.org\/10.1016\/j.intimp.2018.07.031 (2018).","journal-title":"Int. Immunopharmacol."},{"key":"38559_CR53","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12916-025-03945-y","volume":"23","author":"Y Li","year":"2025","unstructured":"Li, Y. et al. MTHFD2 promotes osteoclastogenesis and bone loss in rheumatoid arthritis by enhancing CKMT1-mediated oxidative phosphorylation. BMC Med. 23, 124. https:\/\/doi.org\/10.1186\/s12916-025-03945-y (2025).","journal-title":"BMC Med."},{"key":"38559_CR54","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1002\/ptr.7833","volume":"37","author":"M Valipour","year":"2023","unstructured":"Valipour, M., Hosseini, A., Di Sotto, A. & Irannejad, H. Dual action anti-inflammatory\/antiviral isoquinoline alkaloids as potent naturally occurring anti-SARS-CoV-2 agents: A combined pharmacological and medicinal chemistry perspective. Phytother. Res. PTR 37, 2168\u20132186. https:\/\/doi.org\/10.1002\/ptr.7833 (2023).","journal-title":"Phytother. Res. PTR"},{"key":"38559_CR55","doi-asserted-by":"publisher","first-page":"6139","DOI":"10.2147\/jir.S435596","volume":"16","author":"J Lin","year":"2023","unstructured":"Lin, J. et al. Unveiling FOS as a potential diagnostic biomarker and emetine as a prospective therapeutic agent for diabetic nephropathy. J. Inflamm. Res. 16, 6139\u20136153. https:\/\/doi.org\/10.2147\/jir.S435596 (2023).","journal-title":"J. Inflamm. Res."},{"key":"38559_CR56","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0924-8579(96)00013-1","volume":"7","author":"YC Chen","year":"1996","unstructured":"Chen, Y. C., Hung, C. C., Lin, S. F., Chang, S. C. & Hsieh, W. C. Comparison of flomoxef with latamoxef in the treatment of sepsis and\/or Gram-negative bacteremia in adult patients. Int. J. Antimicrob. Agents 7, 69\u201374. https:\/\/doi.org\/10.1016\/0924-8579(96)00013-1 (1996).","journal-title":"Int. J. Antimicrob. Agents"},{"key":"38559_CR57","doi-asserted-by":"publisher","first-page":"279","DOI":"10.2165\/00003495-198326040-00001","volume":"26","author":"AA Carmine","year":"1983","unstructured":"Carmine, A. A. et al. Moxalactam (latamoxef). A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 26, 279\u2013333. https:\/\/doi.org\/10.2165\/00003495-198326040-00001 (1983).","journal-title":"Drugs"},{"key":"38559_CR58","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112703","volume":"139","author":"Y Shi","year":"2024","unstructured":"Shi, Y. et al. Minocycline prevents photoreceptor degeneration in Retinitis pigmentosa through modulating mitochondrial homeostasis. Int. Immunopharmacol. 139, 112703. https:\/\/doi.org\/10.1016\/j.intimp.2024.112703 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"38559_CR59","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/head.13700","volume":"60","author":"SD Silberstein","year":"2020","unstructured":"Silberstein, S. D., Shrewsbury, S. B. & Hoekman, J. Dihydroergotamine (DHE)\u2014Then and now: A narrative review. Headache 60, 40\u201357. https:\/\/doi.org\/10.1111\/head.13700 (2020).","journal-title":"Headache"},{"key":"38559_CR60","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cellsig.2018.01.002","volume":"44","author":"RD Martin","year":"2018","unstructured":"Martin, R. D. et al. Receptor- and cellular compartment-specific activation of the cAMP\/PKA pathway by \u03b1(1)-adrenergic and ETA endothelin receptors. Cell. Signal. 44, 43\u201350. https:\/\/doi.org\/10.1016\/j.cellsig.2018.01.002 (2018).","journal-title":"Cell. Signal."},{"key":"38559_CR61","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.molcel.2023.12.015","volume":"84","author":"X Wang","year":"2024","unstructured":"Wang, X. et al. A GAPDH serotonylation system couples CD8(+) T cell glycolytic metabolism to antitumor immunity. Mol. Cell 84, 760-775.e767. https:\/\/doi.org\/10.1016\/j.molcel.2023.12.015 (2024).","journal-title":"Mol. Cell"},{"key":"38559_CR62","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13104-021-05488-w","volume":"14","author":"V Herwanto","year":"2021","unstructured":"Herwanto, V. et al. Blood transcriptome analysis of patients with uncomplicated bacterial infection and sepsis. BMC. Res. Notes 14, 76. https:\/\/doi.org\/10.1186\/s13104-021-05488-w (2021).","journal-title":"BMC. Res. Notes"},{"key":"38559_CR63","doi-asserted-by":"publisher","first-page":"R149","DOI":"10.1186\/cc10274","volume":"15","author":"A Sutherland","year":"2011","unstructured":"Sutherland, A. et al. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit. Care (London, England) 15, R149. https:\/\/doi.org\/10.1186\/cc10274 (2011).","journal-title":"Crit. Care (London, England)"},{"key":"38559_CR64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0280548","volume":"18","author":"Y Huang","year":"2023","unstructured":"Huang, Y., Peng, J. & Liang, Q. Identification of key ferroptosis genes in diabetic retinopathy based on bioinformatics analysis. PLoS ONE 18, e0280548. https:\/\/doi.org\/10.1371\/journal.pone.0280548 (2023).","journal-title":"PLoS ONE"},{"key":"38559_CR65","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1007\/s10495-023-01868-8","volume":"28","author":"Y Shi","year":"2023","unstructured":"Shi, Y. et al. Crosstalk of ferroptosis regulators and tumor immunity in pancreatic adenocarcinoma: Novel perspective to mRNA vaccines and personalized immunotherapy. Apoptosis 28, 1423\u20131435. https:\/\/doi.org\/10.1007\/s10495-023-01868-8 (2023).","journal-title":"Apoptosis"},{"key":"38559_CR66","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573-3587.e3529. https:\/\/doi.org\/10.1016\/j.cell.2021.04.048 (2021).","journal-title":"Cell"},{"key":"38559_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.906753","volume":"9","author":"Y Zheng","year":"2022","unstructured":"Zheng, Y. et al. Ferroptosis and autophagy-related genes in the pathogenesis of ischemic cardiomyopathy. Front. Cardiovasc. Med. 9, 906753. https:\/\/doi.org\/10.3389\/fcvm.2022.906753 (2022).","journal-title":"Front. Cardiovasc. Med."},{"key":"38559_CR68","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu, T. et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Cambridge (Mass)) 2, 100141. https:\/\/doi.org\/10.1016\/j.xinn.2021.100141 (2021).","journal-title":"Innovation (Cambridge (Mass))"},{"key":"38559_CR69","doi-asserted-by":"publisher","first-page":"3023127","DOI":"10.1155\/2020\/3023127","volume":"2020","author":"P Liu","year":"2020","unstructured":"Liu, P., Xu, H., Shi, Y., Deng, L. & Chen, X. Potential molecular mechanisms of plantain in the treatment of gout and hyperuricemia based on network pharmacology. Evid.-Based Complement. Altern. Med. eCAM 2020, 3023127. https:\/\/doi.org\/10.1155\/2020\/3023127 (2020).","journal-title":"Evid.-Based Complement. Altern. Med. eCAM"},{"key":"38559_CR70","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.60439","volume":"16","author":"H Huang","year":"2024","unstructured":"Huang, H., Ge, C., Dai, Y., Wu, Y. & Zhu, J. Exploring ferroptosis-associated gene signatures as diagnostic and therapeutic targets for sepsis-induced cardiomyopathy. Cureus 16, e60439. https:\/\/doi.org\/10.7759\/cureus.60439 (2024).","journal-title":"Cureus"},{"key":"38559_CR71","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1093\/jhered\/esac006","volume":"113","author":"L Yang","year":"2022","unstructured":"Yang, L. et al. Powerful identification of large quantitative trait loci using genome-wide R\/glmnet-based regression. J. Hered. 113, 472\u2013478. https:\/\/doi.org\/10.1093\/jhered\/esac006 (2022).","journal-title":"J. Hered."},{"key":"38559_CR72","doi-asserted-by":"publisher","first-page":"5667","DOI":"10.2147\/jir.S438838","volume":"16","author":"Y Wu","year":"2023","unstructured":"Wu, Y., Xiao, Q., Wang, S., Xu, H. & Fang, Y. Establishment and analysis of an artificial neural network model for early detection of polycystic ovary syndrome using machine learning techniques. J. Inflamm. Res. 16, 5667\u20135676. https:\/\/doi.org\/10.2147\/jir.S438838 (2023).","journal-title":"J. Inflamm. Res."},{"key":"38559_CR73","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000034577","volume":"102","author":"W Lu","year":"2023","unstructured":"Lu, W. et al. Comprehensive analysis of HDAC7 expression and its prognostic value in diffuse large B cell lymphoma: A review. Medicine 102, e34577. https:\/\/doi.org\/10.1097\/md.0000000000034577 (2023).","journal-title":"Medicine"},{"key":"38559_CR74","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.4240\/wjgs.v16.i6.1803","volume":"16","author":"XZ Xie","year":"2024","unstructured":"Xie, X. Z. et al. FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma. World J. Gastrointest. Surg. 16, 1803\u20131824. https:\/\/doi.org\/10.4240\/wjgs.v16.i6.1803 (2024).","journal-title":"World J. Gastrointest. Surg."},{"key":"38559_CR75","doi-asserted-by":"publisher","DOI":"10.3390\/sports11070135","author":"S Orifjon","year":"2023","unstructured":"Orifjon, S. et al. Translation and adaptation of the adult developmental coordination disorder\/dyspraxia checklist (ADC) into Asian Uzbekistan. Sports (Basel, Switzerland) https:\/\/doi.org\/10.3390\/sports11070135 (2023).","journal-title":"Sports (Basel, Switzerland)"},{"key":"38559_CR76","doi-asserted-by":"publisher","first-page":"1601982","DOI":"10.3389\/fimmu.2025.1601982","volume":"16","author":"M Li-Fei","year":"2025","unstructured":"Li-Fei, M. et al. Risk scoring model for lung adenocarcinoma based on PD-L1 related signature reveals prognostic predictability and correlation with tumor immune microenvironment genes was constructed. Front. Immunol. 16, 1601982. https:\/\/doi.org\/10.3389\/fimmu.2025.1601982 (2025).","journal-title":"Front. Immunol."},{"key":"38559_CR77","doi-asserted-by":"publisher","first-page":"1438364","DOI":"10.3389\/fimmu.2024.1438364","volume":"15","author":"Y Zhong","year":"2024","unstructured":"Zhong, Y. et al. Investigating the impact of STING pathway activation on breast cancer treatment outcomes: Development and validation of a prognostic model. Front. Immunol. 15, 1438364. https:\/\/doi.org\/10.3389\/fimmu.2024.1438364 (2024).","journal-title":"Front. Immunol."},{"key":"38559_CR78","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.841813","volume":"13","author":"Z Meng","year":"2022","unstructured":"Meng, Z. et al. Exploring the immune infiltration landscape and M2 macrophage-related biomarkers of proliferative diabetic retinopathy. Front. Endocrinol. 13, 841813. https:\/\/doi.org\/10.3389\/fendo.2022.841813 (2022).","journal-title":"Front. Endocrinol."},{"key":"38559_CR79","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27093041","author":"S Tang","year":"2022","unstructured":"Tang, S. et al. Accelerating AutoDock Vina with GPUs. Molecules (Basel Switzerland) https:\/\/doi.org\/10.3390\/molecules27093041 (2022).","journal-title":"Molecules (Basel Switzerland)"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38559-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38559-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38559-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T18:03:24Z","timestamp":1771783404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38559-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["38559"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-38559-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8343291\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"12 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki and approved by the Ethics Committee of the 960th Hospital of the PLA Joint Logistic Support Force located in Jinan. The approval number and date of approval are as follows: No. 2021-44 and March 5, 2021.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients provided written informed consent at the time of clinical sample collection for experiments, ensuring that the research process complied with ethical norms and that patients\u2019 rights and wishes were fully respected.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}}],"article-number":"7109"}}