{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:34:02Z","timestamp":1788809642297,"version":"build-2803163510"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secondary spinal cord injury (SCI) involves persistent inflammation, oxidative stress, and multiple forms of programmed cell death. However, the dynamic activation of lytic cell death-related programs and their key regulatory nodes during SCI progression remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Public transcriptomic datasets were analyzed using single-sample gene set enrichment analysis (ssGSEA) to assess pyroptosis-, necroptosis-, and ferroptosis-related transcriptional activities, and integrated lytic cell death-related indices were constructed. Differential expression analysis, weighted gene co-expression network analysis, functional enrichment, and multiple machine learning models were combined to identify candidate hub genes associated with lytic cell death-related signatures. Key findings were further evaluated using an external human SCI-related cohort, RT-qPCR and immunofluorescence validation in a rat SCI model, and published single-cell RNA-seq data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pyroptosis-, necroptosis-, and ferroptosis-related transcriptional activities were all increased after SCI, with activation beginning in the acute phase and persisting over time. Enrichment analyses showed that lytic cell death-associated genes were mainly involved in inflammatory responses, immune regulation, myeloid activation, and related signaling pathways. Integrated multi-model analysis identified CD14 as the most robust candidate hub gene associated with the lytic cell death index. External validation in a human SCI-related peripheral blood cohort, RT-qPCR and immunofluorescence validation in a rat SCI model, and single-cell reanalysis further supported the upregulation of CD14 and its association with myeloid inflammatory activation and pyroptosis-, necroptosis-, and ferroptosis-related signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lytic cell death-related programs are dynamically and persistently activated after SCI and are closely associated with immune-inflammatory responses during secondary injury. CD14 was identified as a candidate hub gene associated with myeloid inflammatory activation and lytic cell death-related signatures. However, the current findings are primarily associative, and further functional studies are required to determine whether CD14 directly modulates lytic cell death-related pathways and contributes to secondary injury progression after SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1841784","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:37:26Z","timestamp":1783334246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Dynamic activation of lytic cell death-related programs identifies CD14 as a candidate hub gene associated with secondary injury after spinal cord injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Shenglong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, 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University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghua","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Xi\u2019an Jiaotong University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First 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