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While MCB's significant anti\u2010inflammatory properties are confirmed, it is also observed that its treatment may impair macrophage\u2010mediated innate immune responses. Comprehensive RNA\u2010seq, ATAC\u2010seq, and CUT&amp;Tag analyses revealed that MCB reduces inflammation and weakens innate immunity by limiting chromatin accessibility at NF\u2010\u03baB and EGR1 binding sites, leading to decreased IFNB1 production and enhanced viral immune evasion. To address this challenge, a deep learning model, VDLIN (\n                    <jats:italic>Vitamin B12\u2010derived Deep Learning for Innate Immunity<\/jats:italic>\n                    ), is developed to identify compounds capable of both suppressing inflammation and boosting innate immunity. As anticipated, VDLIN identified a novel compound, \u201cCo7,\u201d which retains MCB's strong anti\u2010inflammatory effects while also enhancing immune activation via the TLR4 signaling pathway. Co7 thus emerges as a promising therapeutic candidate, offering advantages over MCB by balancing anti\u2010inflammatory and immune\u2010stimulatory functions. Taken together, this study sheds light on the intricate interplay between chromatin dynamics and immune regulation, presenting new opportunities for therapeutic interventions in inflammatory diseases and SARS\u2010CoV\u20102 infection.\n                  <\/jats:p>","DOI":"10.1002\/advs.202413775","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:28:52Z","timestamp":1761658132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["VDLIN: A Deep Learning\u2010Based Platform for Methylcobalamin\u2010Inspired Immunomodulatory Compound Screening"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9590-8235","authenticated-orcid":false,"given":"Xuefei","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Systems Biomedicine Department of Microbiology and Infectious Disease Center School of Basic Medical Sciences Beijing Key Laboratory of Tumor Systems Biology NHC Key Laboratory of Medical Immunology Peking University Health Science Center  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Systems Biomedicine Department of Microbiology and Infectious Disease Center School of Basic Medical Sciences Beijing Key Laboratory of Tumor Systems Biology NHC Key Laboratory of Medical Immunology Peking University Health Science Center  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianle","family":"Rong","sequence":"additional","affiliation":[{"name":"Center of Basic Molecular Science (CBMS) Department of Chemistry Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Pathology Xiangya Hospital School of Basic Medical Sciences Central South University Changsha 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Systems Biomedicine Department of Microbiology and Infectious Disease Center School of Basic Medical Sciences Beijing Key Laboratory of Tumor Systems Biology NHC Key Laboratory of Medical Immunology Peking University Health Science Center  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Basic Molecular Science (CBMS) Department of Chemistry Tsinghua University  Beijing 100084 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuping","family":"You","sequence":"additional","affiliation":[{"name":"Institute of Systems Biomedicine Department of Microbiology and Infectious Disease Center School of Basic Medical Sciences Beijing Key Laboratory of Tumor Systems Biology NHC Key Laboratory of Medical Immunology Peking University Health Science Center  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03493-4"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2001737"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.12.016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-021-00495-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1294020"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-65629-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.025"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001651"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.52"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_8_11_1","volume":"93","author":"Hu B.","year":"2021","journal-title":"J. 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