{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:02:27Z","timestamp":1777867347878,"version":"3.51.4"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":119,"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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic retinopathy (DR) can significantly impair vision and lead to blindness. Vitamin D (VD) has been shown to enhance the production of anti\u2010inflammatory factors, alleviating the effects of hyperglycemia. However, downstream genes and molecular networks associated with VD signaling in DR remain unidentified. This study aimed to employ a systems biology approach to nominate high\u2010priority candidate genes and cellular contexts as a hypothesis\u2010generating effort to facilitate future functional studies on the role of VD in DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DR\u2010related datasets were obtained from public databases to identify differentially expressed genes (DEGs). Seven canonical VD metabolism\u2010related genes (VDRGs) were subjected to weighted gene co\u2010expression network analysis (WGCNA) to identify VD signaling\u2010associated model genes. Candidate genes were selected based on the intersection of DEGs and model genes. \u201cBoruta\u201d and support vector machine\u2013recursive feature elimination (SVM\u2013RFE), along with expression validation, were used to screen for biomarkers. Further analyses included immune infiltration, gene set enrichment analysis (GSEA), regulatory network construction, and drug prediction. Single\u2010cell RNA sequencing (scRNA\u2010seq) was utilized to assess cellular heterogeneity, identifying distinct cell clusters and key cells based on gene expression profiles. Cell\u2013cell communication within immune cells was also examined. Biomarker expression levels in clinical samples were validated through real\u2010time reverse transcription polymerase chain reaction (RT\u2010qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The biomarkers SLC36A1 and RAB23 were identified as VD signaling\u2010associated downstream candidates and validated. GSEA revealed their primary association with glucose metabolism. B cells and CD4 T cells were identified as differentially expressed immune cells. Both biomarkers were regulated by a competing endogenous RNA (ceRNA) network, and the drug \u201cmethyl methanesulfonate\u201d targeted both biomarkers simultaneously. Single\u2010cell analysis identified 11 distinct cell types, including classical monocytes, B cells, and T cells. B cells and classical monocytes were identified as key cells due to the differential expression of biomarkers. The cell\u2013cell communication network highlighted interactions, particularly between classical monocytes, B cells, and T cells. The differentiation of key cells and the stage of biomarker expression were also uncovered. RT\u2010qPCR analysis revealed a significant upregulation of SLC36A1 and RAB23 in the DR group compared to controls (\n                      <jats:italic>F<\/jats:italic>\n                      \u2009=\u20095.184\n                      <jats:italic>p<\/jats:italic>\n                      = 0.027 &lt; 0.05;\n                      <jats:italic>F<\/jats:italic>\n                      \u2009=\u20094.147\n                      <jats:italic>p<\/jats:italic>\n                      = 0.047 &lt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SLC36A1 and RAB23 were identified as VD signaling\u2010associated downstream biomarkers in DR, providing a framework for exploring the potential link between VD signaling and DR pathogenesis through these candidate genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/7240252","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:11:07Z","timestamp":1777543867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Vitamin D Signaling\u2010Associated Biomarkers and Their Diagnostic Value in Diabetic Retinopathy: A Combined Transcriptomic and Single\u2010Cell Analysis With Experimental Validation"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-6933","authenticated-orcid":false,"given":"Pengfei","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1156-0057","authenticated-orcid":false,"given":"Keren","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8331-2893","authenticated-orcid":false,"given":"Yuhua","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021024"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTO.S462498"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.04.027"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583687"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12112512"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.157"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1055087"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054642"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu17010090"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23084226"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-020-09575-4"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8193523"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/D4SC05700G"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1491318"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200223666220627104139"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu12040962"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_15_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac409"},{"key":"e_1_2_15_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_2_15_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04029-2"},{"key":"e_1_2_15_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_15_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.177"},{"key":"e_1_2_15_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"e_1_2_15_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_15_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03364-0"},{"key":"e_1_2_15_26_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.03.29"},{"key":"e_1_2_15_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_15_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12081918"},{"key":"e_1_2_15_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-024-02839-6"},{"key":"e_1_2_15_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_15_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"e_1_2_15_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109003"},{"key":"e_1_2_15_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_15_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04073-3"},{"key":"e_1_2_15_35_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20160410"},{"key":"e_1_2_15_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.187"},{"key":"e_1_2_15_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1191426"},{"key":"e_1_2_15_38_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9696521"},{"key":"e_1_2_15_39_2","volume-title":"The Eye and Foot in Diabetes","author":"de Faria J. M. L.","year":"2019"},{"key":"e_1_2_15_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4058-5"},{"key":"e_1_2_15_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1962681"},{"key":"e_1_2_15_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2021.108841"},{"key":"e_1_2_15_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy018"},{"key":"e_1_2_15_44_2","doi-asserted-by":"publisher","DOI":"10.13471\/j.cnki.j.sun.yat-sen.univ(med.sci).2019.0093"},{"key":"e_1_2_15_45_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13945"},{"key":"e_1_2_15_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1618333114"},{"key":"e_1_2_15_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11091314"},{"key":"e_1_2_15_48_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.035105"},{"key":"e_1_2_15_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010030"},{"key":"e_1_2_15_50_2","doi-asserted-by":"publisher","DOI":"10.3945\/jn.117.248823"},{"key":"e_1_2_15_51_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201610113"},{"key":"e_1_2_15_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-020-01553-3"},{"key":"e_1_2_15_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-019-1134-5"},{"key":"e_1_2_15_54_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2954721"},{"key":"e_1_2_15_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108703"},{"key":"e_1_2_15_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00888.x"},{"key":"e_1_2_15_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512467"},{"key":"e_1_2_15_58_2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.76395"},{"key":"e_1_2_15_59_2","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2012.661114"},{"key":"e_1_2_15_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0798-5"},{"key":"e_1_2_15_61_2","first-page":"1410","article-title":"Micro RNA-19a Suppresses Interleukin-10 in Peripheral B Cells of Patients With Diabetic Retinopathy","volume":"9","author":"Wang C.","year":"2017","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_15_62_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4631290"},{"key":"e_1_2_15_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05860-w"},{"key":"e_1_2_15_64_2","doi-asserted-by":"publisher","DOI":"10.4081\/ejh.2022.3333"},{"key":"e_1_2_15_65_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0295813"},{"key":"e_1_2_15_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.632040"},{"key":"e_1_2_15_67_2","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S255183"}],"container-title":["Journal of Diabetes Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jdr\/7240252","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/jdr\/7240252","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jdr\/7240252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:11:15Z","timestamp":1777543875000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/jdr\/7240252"}},"subtitle":[],"editor":[{"given":"Zhipeng","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/jdr\/7240252"],"URL":"https:\/\/doi.org\/10.1155\/jdr\/7240252","archive":["Portico"],"relation":{},"ISSN":["2314-6745","2314-6753"],"issn-type":[{"value":"2314-6745","type":"print"},{"value":"2314-6753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"7240252"}}