{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:53:23Z","timestamp":1781870003106,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":169,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2021LL-JB-06"],"award-info":[{"award-number":["2021LL-JB-06"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2023-ZDLSF-40"],"award-info":[{"award-number":["2023-ZDLSF-40"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Background<\/jats:title>\n Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and a leading cause of blindness despite available therapies, underscoring the need for novel therapeutic targets.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Integrated multiomics analysis combining (1) exploratory single\u2010cell RNA sequencing of rat retinal tissues (three DRs vs. two controls), (2) Mendelian randomization (MR) using whole\u2010blood eQTL data and DR GWAS data (14,584 cases vs. 202,082 controls), and (3) supportive RT\u2010qPCR validation in peripheral\u2010blood clinical samples (30 DRs vs. 30 controls).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n (1) Genetic causality was as follows: MR analysis demonstrated\n ZFP36L1<\/jats:italic>\n as a novel DR risk gene (OR = 1.156, 95% CI\u2009=\u20091.054\u20131.269,\n p<\/jats:italic>\n = 0.002), with significant upregulation in patient blood samples (\n p<\/jats:italic>\n < 0.0001). (2) Inflammatory regulation was as follows:\n ZFP36L1<\/jats:italic>\n showed strong correlations with proinflammatory markers (TNF\u2010\n \u03b1<\/jats:italic>\n and IL\u20106) and immune cell infiltration (parainflammation and Tregs), while negatively correlating with B cells. (3) Pathway mechanisms were as follows: Functional enrichment analyses suggested potential links between\n ZFP36L1<\/jats:italic>\n and NF\u2010\n \u03ba<\/jats:italic>\n B\u2013related inflammatory signaling as well as TGF\u2010\n \u03b2<\/jats:italic>\n \u2013related angiogenic pathways. Despite its known VEGF mRNA destabilizing function, we observed a positive\n ZFP36L1<\/jats:italic>\n \u2013\n VEGF<\/jats:italic>\n correlation (\n r<\/jats:italic>\n = 0.180,\n p<\/jats:italic>\n < 0.001), an unexpected finding under diabetic conditions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n ZFP36L1<\/jats:italic>\n is a candidate DR susceptibility gene whose genetically regulated expression in blood is associated with DR risk. Retinal single\u2010cell and pathway analyses provide supportive, hypothesis\u2010generating evidence that\n ZFP36L1<\/jats:italic>\n may be linked to inflammatory and angiogenic processes relevant to DR. Further retina\u2010specific and functional studies are required to determine whether\n ZFP36L1<\/jats:italic>\n directly regulates retinal inflammation or angiogenesis in human DR.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1155\/jdr\/4312504","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:28:24Z","timestamp":1781868504000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiomics Integration Prioritizes\n ZFP36L1<\/i>\n as a Candidate Susceptibility Gene Associated With Inflammatory and Angiogenic Pathways in Diabetic Retinopathy"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-5801","authenticated-orcid":false,"given":"Ruiqing","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-636X","authenticated-orcid":false,"given":"Xiaoli","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6661-9047","authenticated-orcid":false,"given":"Chenwen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0635-7724","authenticated-orcid":false,"given":"Shengnan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2284-7351","authenticated-orcid":false,"given":"Ning","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1239-5740","authenticated-orcid":false,"given":"Mingqian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1505-8892","authenticated-orcid":false,"given":"Bingyin","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0701-2998","authenticated-orcid":false,"given":"Wei","family":"Qiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"e_1_2_14_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)62124-3"},{"key":"e_1_2_14_2_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59980"},{"key":"e_1_2_14_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1909637"},{"key":"e_1_2_14_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2022.6142"},{"key":"e_1_2_14_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.227"},{"key":"e_1_2_14_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03893-9"},{"key":"e_1_2_14_7_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i3.489"},{"key":"e_1_2_14_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-00451-4"},{"key":"e_1_2_14_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/db20-0839"},{"key":"e_1_2_14_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3041"},{"key":"e_1_2_14_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_14_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00292-7"},{"key":"e_1_2_14_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1191768"},{"key":"e_1_2_14_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417045"},{"key":"e_1_2_14_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114949"},{"key":"e_1_2_14_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-025-01829-y"},{"key":"e_1_2_14_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04233-0"},{"key":"e_1_2_14_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-019-00647-9"},{"key":"e_1_2_14_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-2796"},{"key":"e_1_2_14_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.035"},{"key":"e_1_2_14_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.711633"},{"key":"e_1_2_14_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-021-00867-0"},{"key":"e_1_2_14_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.341"},{"key":"e_1_2_14_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194755"},{"key":"e_1_2_14_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564077"},{"key":"e_1_2_14_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abo0981"},{"key":"e_1_2_14_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02605-9"},{"key":"e_1_2_14_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-008-0868-6"},{"key":"e_1_2_14_29_2","doi-asserted-by":"publisher","DOI":"10.3109\/09273948.2015.1034804"},{"key":"e_1_2_14_30_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-9233.92116"},{"key":"e_1_2_14_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1055087"},{"key":"e_1_2_14_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1201-1291"},{"key":"e_1_2_14_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11050779"},{"key":"e_1_2_14_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.07.021"},{"key":"e_1_2_14_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010096"},{"key":"e_1_2_14_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.02.007"},{"key":"e_1_2_14_37_2","doi-asserted-by":"publ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