{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T12:37:39Z","timestamp":1782218259625,"version":"3.54.5"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a significant medical challenge due to its high mortality rates and requires a deeper understanding of its underlying mechanisms. This study aims to elucidate the differential expression of necroptosis-related genes in sepsis and their impact on immune characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained gene expression profiles and single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the limma package, and functional enrichment analysis was performed using the clusterProfiler package for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were conducted to explore pathway enrichments. Immune cell infiltration differences between sepsis (SE) and healthy control (HC) groups were quantified using the single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Differential marker genes between SE and HC groups were identified by single-cell data analysis using the Seurat and SingleR packages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed 849 necroptosis-related DEGs, with 843 upregulated and 16 downregulated in the SE group. Least Absolute Shrinkage and Selection Operator (LASSO) regression identified 22 key DEGs, including <jats:italic>CTSS<\/jats:italic>, <jats:italic>MAPK8<\/jats:italic>, and <jats:italic>MPRIP<\/jats:italic>. Among these, 157 necroptosis-related DEGs were consistently identified between SE and HC groups. GO analysis indicated significant enrichment in biological processes such as the regulation of apoptotic signaling pathways and I\u03baB kinase\/NF-\u03baB signaling. KEGG pathway analysis revealed involvement in necroptosis, apoptosis, and NOD-like receptor signaling pathways. GSVA demonstrated that Wnt signaling was upregulated in the SE group. Significant differences in immune cell infiltration were observed between sepsis and healthy control groups, particularly in activated B cells and CD4 T cells. Single-cell RNA sequencing identified 33,287 cells categorized into 26 clusters, with neutrophils predominating. Key necroptosis genes such as <jats:italic>CTSS<\/jats:italic>, <jats:italic>TXN<\/jats:italic>, <jats:italic>MYH9<\/jats:italic>, <jats:italic>FPR1<\/jats:italic>, <jats:italic>FMR1<\/jats:italic>, and <jats:italic>MPRIP<\/jats:italic> exhibited differential expression patterns across various immune cell types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our integrated bioinformatics approach provides insights into the role of necroptosis-related genes in sepsis pathogenesis and their influence on immune responses. These findings improve our understanding of sepsis mechanisms and may guide future therapeutic strategies targeting necroptosis pathways.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1618438","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T05:24:30Z","timestamp":1754889870000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The relationship between immune cell infiltration and necroptosis gene expression in sepsis: an analysis using single-cell transcriptomic data"],"prefix":"10.3389","volume":"15","author":[{"given":"Shouyi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nrn1667","article-title":"From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome","volume":"6","author":"Bagni","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1146\/annurev-neuro-060909-153138","article-title":"The pathophysiology of fragile X (and what it teaches us about synapses)","volume":"35","author":"Bhakar","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00635","article-title":"The Wnt blows: on the functional role of Wnt signaling in mycobacterium tuberculosis infection and beyond","volume":"7","author":"Brandenburg","year":"2016","journal-title":"Front. Immunol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0140-6736(18)30696-2","article-title":"Sepsis and septic shock","volume":"392","author":"Cecconi","year":"2018","journal-title":"Lancet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1186\/s13054-023-04552-0","article-title":"A targeted metabolomics approach for sepsis-induced ARDS and its subphenotypes","volume":"27","author":"Chang","year":"2023","journal-title":"Crit. Care"},{"key":"B6","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.celrep.2016.12.019","article-title":"Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade","volume":"18","author":"Charoentong","year":"2017","journal-title":"Cell Rep."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.922195","article-title":"A novel immune-related gene signature to identify the tumor microenvironment and prognose disease among patients with oral squamous cell carcinoma patients using ssGSEA: A bioinformatics and biological validation study","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1172\/JCI32730","article-title":"Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice","volume":"118","author":"Chung","year":"2008","journal-title":"J. Clin. Invest."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.3390\/ijms20163913","article-title":"Roles of myosin-mediated membrane trafficking in TGF-\u03b2 Signaling","volume":"20","author":"Chung","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1242\/jcs.007112","article-title":"Nonmuscle myosin II moves in new directions","volume":"121","author":"Conti","year":"2008","journal-title":"J. Cell Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/s12974-018-1235-0","article-title":"Necroptosis: a regulated inflammatory mode of cell death","volume":"15","author":"Dhuriya","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"B12","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1016\/j.devcel.2008.04.003","article-title":"A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome","volume":"14","author":"Dictenberg","year":"2008","journal-title":"Dev. Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40779-014-0029-7","article-title":"Current knowledge and future directions of TLR and NOD signaling in sepsis","volume":"2","author":"Foley","year":"2015","journal-title":"Mil Med. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1089\/ars.2020.8063","article-title":"Selenocompounds and sepsis: redox bypass hypothesis for early diagnosis and treatment: part A-early acute phase of sepsis: an extraordinary redox situation (Leukocyte\/endothelium interaction leading to endothelial damage)","volume":"35","author":"Forceville","year":"2021","journal-title":"Antioxid Redox Signal"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1007\/s11739-021-02735-7","article-title":"Management of sepsis and septic shock in the emergency department","volume":"16","author":"Gavelli","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1146\/annurev.bi.54.070185.001321","article-title":"Thioredoxin","volume":"54","author":"Holmgren","year":"1985","journal-title":"Annu. Rev. Biochem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"105301","DOI":"10.1016\/j.isci.2022.105301","article-title":"Single-cell transcriptome profiling reveals heterogeneous neutrophils with prognostic values in sepsis","volume":"25","author":"Hong","year":"2022","journal-title":"iScience"},{"key":"B18","doi-asserted-by":"publisher","first-page":"4658","DOI":"10.1038\/s41467-022-32320-1","article-title":"Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening","volume":"13","author":"Ioannou","year":"2022","journal-title":"Nat. Commun."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007338","article-title":"Klebsiella pneumoniae infection of murine neutrophils impairs their efferocytic clearance by modulating cell death machinery","volume":"14","author":"Jondle","year":"2018","journal-title":"PLoS Pathog."},{"key":"B20","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/S1471-4906(02)02316-5","article-title":"Formyl-peptide receptors revisited","volume":"23","author":"Le","year":"2002","journal-title":"Trends Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.bbrc.2018.02.060","article-title":"Intracellular formyl peptide receptor regulates na\u00efve CD4 T cell migration","volume":"497","author":"Lee","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1002\/jcb.25877","article-title":"Formyl peptide receptors in cellular differentiation and inflammatory diseases","volume":"118","author":"Lee","year":"2017","journal-title":"J. Cell Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"18575","DOI":"10.1038\/s41598-025-03282-3","article-title":"Immunogenic cell death biomarkers for sepsis diagnosis and mechanism via integrated bioinformatics","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1152\/physrev.00012.2018","article-title":"The neutrophil\u2019s role during health and disease","volume":"99","author":"Liew","year":"2019","journal-title":"Physiol. Rev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMra1310050","article-title":"Necroptosis","volume":"370","author":"Linkermann","year":"2014","journal-title":"N Engl. J. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40779-022-00422-y","article-title":"Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options","volume":"9","author":"Liu","year":"2022","journal-title":"Mil Med. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1002\/mco2.108","article-title":"The role of necroptosis in disease and treatment","volume":"2","author":"Liu","year":"2021","journal-title":"MedComm (2020)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1126\/science.1188510","article-title":"Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine","volume":"329","author":"Manicassamy","year":"2010","journal-title":"Science"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.624272","article-title":"Immune checkpoints: novel therapeutic targets to attenuate sepsis-induced immunosuppression","volume":"11","author":"McBride","year":"2020","journal-title":"Front. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.4049\/jimmunol.1303380","article-title":"Cathepsins limit macrophage necroptosis through cleavage of Rip1 kinase","volume":"192","author":"McComb","year":"2014","journal-title":"J. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1097\/MOP.0000000000000352","article-title":"Inflammation and innate immune function in critical illness","volume":"28","author":"Muszynski","year":"2016","journal-title":"Curr. Opin. Pediatr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.imlet.2016.11.006","article-title":"Lipid mediators foster the differentiation of T follicular helper cells","volume":"181","author":"Nagaya","year":"2017","journal-title":"Immunol. Lett."},{"key":"B33","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1146\/annurev.immunol.15.1.351","article-title":"Redox regulation of cellular activation","volume":"15","author":"Nakamura","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"139","DOI":"10.5492\/wjccm.v12.i3.139","article-title":"Sepsis-induced mitochondrial dysfunction: A narrative review","volume":"12","author":"Nedel","year":"2023","journal-title":"World J. Crit. Care Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1146\/annurev-biochem-060815-014830","article-title":"Necroptosis and inflammation","volume":"85","author":"Newton","year":"2016","journal-title":"Annu. Rev. Biochem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/nature20559","article-title":"RIPK1 inhibits ZBP1-driven necroptosis during development","volume":"540","author":"Newton","year":"2016","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"F209","DOI":"10.1136\/fn.88.3.F209","article-title":"Proinflammatory and anti-inflammatory cytokine responses in preterm infants with systemic infections","volume":"88","author":"Ng","year":"2003","journal-title":"Arch. Dis. Child Fetal Neonatal Ed"},{"key":"B38","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nature14191","article-title":"Necroptosis and its role in inflammation","volume":"517","author":"Pasparakis","year":"2015","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","first-page":"E297","DOI":"10.1152\/ajpendo.00243.2024","article-title":"The influence of interleukin-27 on metabolic fitness in a murine neonatal model of bacterial sepsis","volume":"328","author":"Povroznik","year":"2025","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/s41574-023-00822-7","article-title":"The G protein-coupled oestrogen receptor GPER in health and disease: an update","volume":"19","author":"Prossnitz","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1097\/SHK.0000000000001936","article-title":"Necroptosis, pyroptosis, ferroptosis in sepsis and treatment","volume":"57","author":"Qu","year":"2022","journal-title":"Shock"},{"key":"B42","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0952-7915(99)00058-8","article-title":"Cathepsins and compartmentalization in antigen presentation","volume":"12","author":"Riese","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"B44","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ejcb.2010.11.004","article-title":"Wnt signaling in macrophages: augmenting and inhibiting mycobacteria-induced inflammatory responses","volume":"90","author":"Schaale","year":"2011","journal-title":"Eur. J. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"9235","DOI":"10.1038\/s41598-017-08711-6","article-title":"Mitigation of sepsis-induced inflammatory responses and organ injury through targeting Wnt\/\u03b2-catenin signaling","volume":"7","author":"Sharma","year":"2017","journal-title":"Sci. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s00467-015-3181-8","article-title":"How does your kidney smell? Emerging roles for olfactory receptors in renal function","volume":"31","author":"Shepard","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1182\/blood.2021011525","article-title":"Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation","volume":"138","author":"Silva","year":"2021","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B49","doi-asserted-by":"publisher","first-page":"101106","DOI":"10.1016\/j.mam.2022.101106","article-title":"Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential","volume":"88","author":"Smyth","year":"2022","journal-title":"Mol. Aspects Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s41422-019-0164-5","article-title":"The molecular machinery of regulated cell death","volume":"29","author":"Tang","year":"2019","journal-title":"Cell Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.addr.2010.09.012","article-title":"The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators","volume":"62","author":"Teo","year":"2010","journal-title":"Adv. Drug Delivery Rev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"4345","DOI":"10.1016\/j.jmb.2019.07.002","article-title":"Function of SLAM-associated protein (SAP) in acute pneumoseptic bacterial infection","volume":"431","author":"Tripathi","year":"2019","journal-title":"J. Mol. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","article-title":"Cysteine cathepsins: from structure, function and regulation to new frontiers","volume":"1824","author":"Turk","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B54","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The immunopathology of sepsis and potential therapeutic targets","volume":"17","author":"van der Poll","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-5411388\/v1","article-title":"The relationship between immune cell infiltration and necroptosis gene expression in sepsis: an analysis using single-cell transcriptomic data","author":"Wang","year":"2024","journal-title":"Research Square"},{"key":"B56","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1097\/ALN.0000000000000525","article-title":"Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study","volume":"122","author":"Wang","year":"2015","journal-title":"Anesthesiology"},{"key":"B57","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1182\/blood.2020009417","article-title":"Upregulated PD-L1 delays human neutrophil apoptosis and promotes lung injury in an experimental mouse model of sepsis","volume":"138","author":"Wang","year":"2021","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.3390\/jcm10112412","article-title":"Metabolic alterations in sepsis","volume":"10","author":"Wasyluk","year":"2021","journal-title":"J. Clin. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1097\/PCC.0000000000001222","article-title":"The epidemiology of hospital death following pediatric severe sepsis: when, why, and how children with sepsis die","volume":"18","author":"Weiss","year":"2017","journal-title":"Pediatr. Crit. Care Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1164\/rccm.201412-2323OC","article-title":"Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study","volume":"191","author":"Weiss","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2644","DOI":"10.1038\/s41467-018-05062-2","article-title":"Intermedin protects against sepsis by concurrently re-establishing the endothelial barrier and alleviating inflammatory responses","volume":"9","author":"Xiao","year":"2018","journal-title":"Nat. Commun."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.847624","article-title":"A necroptosis-related prognostic model of uveal melanoma was constructed by single-cell sequencing analysis and weighted co-expression network analysis based on public databases","volume":"13","author":"Xie","year":"2022","journal-title":"Front. Immunol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/cr.2007.52","article-title":"Apoptosis signaling pathways and lymphocyte homeostasis","volume":"17","author":"Xu","year":"2007","journal-title":"Cell Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1177\/1753425920966380","article-title":"Identification of key genes and novel immune infiltration-associated biomarkers of sepsis","volume":"26","author":"Xu","year":"2020","journal-title":"Innate Immun."},{"key":"B65","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1186\/s12864-023-09896-z","article-title":"A comprehensive analysis of immune features and construction of an immune gene diagnostic model for sepsis","volume":"24","author":"Xue","year":"2023","journal-title":"BMC Genomics"},{"key":"B66","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S1054-3589(08)60073-3","article-title":"Structure and function of leukocyte chemoattractant receptors","volume":"39","author":"Ye","year":"1997","journal-title":"Adv. Pharmacol."},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax7964","article-title":"Nanoparticle-induced neutrophil apoptosis increases survival in sepsis and alleviates neurological damage in stroke","volume":"5","author":"Zhang","year":"2019","journal-title":"Sci. Adv."},{"key":"B68","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/s41392-021-00816-9","article-title":"Signaling pathways and intervention therapies in sepsis","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct Target Ther."},{"key":"B69","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s10495-023-01905-6","article-title":"Necroptosis inhibitors: mechanisms of action and therapeutic potential","volume":"29","author":"Zhou","year":"2024","journal-title":"Apoptosis"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1183769","article-title":"The development of endoplasmic reticulum-related gene signatures and the immune infiltration analysis of sepsis","volume":"14","author":"Zhou","year":"2023","journal-title":"Front. Immunol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.immuni.2009.03.021","article-title":"Notch and wingless signaling cooperate in regulation of dendritic cell differentiation","volume":"30","author":"Zhou","year":"2009","journal-title":"Immunity"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1168780","article-title":"Identification of aging-related biomarkers and immune infiltration characteristics in osteoarthritis based on bioinformatics analysis and machine learning","volume":"14","author":"Zhou","year":"2023","journal-title":"Front. Immunol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1136\/gutjnl-2019-318215","article-title":"Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury","volume":"69","author":"Zhuang","year":"2020","journal-title":"Gut"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1618438\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T05:24:32Z","timestamp":1754889872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1618438\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":73,"alternative-id":["10.3389\/fcimb.2025.1618438"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1618438","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,11]]},"article-number":"1618438"}}