{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:32:15Z","timestamp":1785411135295,"version":"3.56.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,11,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      As a leading causative agent of pneumonia infection worldwide,\n                      <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      ) induces lung injury and presents substantial therapeutic challenges. To elucidate the role of methyltransferase-like 3 (METTL3) in modulating circular RNA_0001239 (circ_0001239), YTH domain containing protein 2 (YTHDC2), and Kr\u00fcppel-like factor 10 (KLF10) through m6A modification, we established\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      -induced neonatal mouse models. The survival rates, bacterial load in bronchoalveolar lavage fluid, and METTL3 expression in pulmonary tissue were evaluated. After METTL3 downregulation, lung wet-to-dry ratio, myeloperoxidase activity, and inflammatory markers were assessed. Methylated RNA immunoprecipitation detected enriched m6A modification on circ_0001239, while RNA immunoprecipitation validated the bindings of circ_0001239 to YTHDC2 and YTHDC2 to KLF10. The KLF10 mRNA stability was analyzed via actinomycin D treatment. METTL3 and circ_0001239 were upregulated in pneumonic lungs, while KLF10 was downregulated. METTL3 knockdown improved survival, alleviated lung injury, increased superoxide dismutase levels, and suppressed interleukin (IL)-6, IL-1\u03b2, and malondialdehyde levels. METTL3 promoted the binding of circ_0001239 to YTHDC2 via m6A modification, destabilizing KLF10 mRNA. Circ_0001239 overexpression or KLF10 knockdown reversed the protective effects of low expression of METTL3 on lung damage in neonatal mice with pneumonia. In conclusion, METTL3 aggravates\n                      <jats:italic toggle=\"yes\">Spn<\/jats:italic>\n                      -induced lung injury via m6A-dependent circ_0001239\/YTHDC2\/KLF10 axis, thereby providing potential therapeutic targets for severe pneumonia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00288-25","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:30:17Z","timestamp":1760722217000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["METTL3 aggravates lung injury in neonatal mice with\n                    <i>Streptococcus pneumoniae<\/i>\n                    -induced pneumonia via the circ_0001239\/KLF10 axis"],"prefix":"10.1128","volume":"93","author":[{"given":"Liping","family":"Yang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Qingpu Branch of Zhongshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Xie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Qingpu Branch of Zhongshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Yan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Qingpu Branch of Zhongshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Qingpu Branch of Zhongshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Qingpu Branch of Zhongshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2145-2310","authenticated-orcid":true,"given":"Caixia","family":"Ma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/037p24858","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pediatrics, Qingpu Branch of Zhongshan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00259-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20210879"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-023-04628-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127221"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00450-x"},{"key":"e_1_3_3_7_2","first-page":"1631","article-title":"METTL3 plays multiple functions in biological processes","volume":"10","author":"Liu S","year":"2020","unstructured":"Liu S, Zhuo L, Wang J, Zhang Q, Li Q, Li G, Yan L, Jin T, Pan T, Sui X, Lv Q, Xie T. 2020. 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