{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:03:21Z","timestamp":1791864201729,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31660704"],"award-info":[{"award-number":["31660704"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["31660704"],"award-info":[{"award-number":["31660704"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Project of Yunnan Vocational College of Agriculture in 2023","award":["ynavc202316"],"award-info":[{"award-number":["ynavc202316"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Porcine epidemic diarrhea virus (PEDV) causes lethal enteritis in neonatal piglets, yet the mechanisms underlying rapid intestinal injury remain unclear. In particular, it is unknown whether different regulated cell death pathways act separately or cooperatively to worsen mucosal damage. To address this question, we performed multi-omics analyses of infected intestinal tissues and found concurrent activation of pyroptosis and ferroptosis during PEDV infection. PEDV infection activated the Caspa-se-1\/GSDMD pathway in the duodenum and jejunum, as shown by generation of the Caspase-1 p20 fragment and cleavage of GSDMD into its active N-terminal form, indicating pyroptosis. At the same time, infected tissues displayed key features of ferroptosis, including weakened antioxidant defenses, increased lipid peroxidation, iron accumulation, lipid remodeling, and dysregulated ACSL4 and GPX4 expression. These two processes were closely linked and together contributed to tight junction disruption and barrier instability. Molecular docking further suggested that PEDV NSP1 and S proteins may interact with Caspase-1, providing a possible explanation for pyroptosis induction. Correlation analysis also showed strong associations between pyroptosis-related genes and ferroptosis-associated metabolites. Overall, our findings indicate that pyroptosis and ferroptosis cooperate to drive PEDV-induced intestinal inflammation and barrier damage, highlighting their joint inhibition as a potential strategy to reduce PEDV pathogenicity.<\/jats:p>","DOI":"10.3390\/biom16050629","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:40:12Z","timestamp":1777981212000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cross-Talk Between Pyroptosis and Ferroptosis Promotes Intestinal Inflammation and Barrier Failure During PEDV Infection"],"prefix":"10.3390","volume":"16","author":[{"given":"Jie","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Animal Husbandry and Veterinary Medicine, Yunnan Agricultural Vocational and Technical College, Kunming 650212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Gen","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Dong","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Animal Husbandry and Veterinary Medicine, Yunnan Agricultural Vocational and Technical College, Kunming 650212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Bao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Animal Husbandry and Veterinary Medicine, Yunnan Agricultural Vocational and Technical College, Kunming 650212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Neng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Animal Husbandry and Veterinary Medicine, Yunnan Agricultural Vocational and Technical College, Kunming 650212, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s11671-025-04220-y","article-title":"Advances in porcine epidemic diarrhea virus research: Genome, epidemiology, vaccines, and detection methods","volume":"20","author":"Zhuang","year":"2025","journal-title":"Discov. 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