{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T18:24:24Z","timestamp":1787250264125,"version":"build-2736575974"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008871","name":"Science and Technology Department of Yunnan Province","doi-asserted-by":"crossref","award":["No:202401AY070001-005"],"award-info":[{"award-number":["No:202401AY070001-005"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic kidney disease (DKD) and Parkinson\u2019s disease (PD) affect different organs but share epidemiological associations and innate immune abnormalities. The extent and cellular basis of reproducible cross-disease transcriptomic convergence remain uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two DKD glomerular and three PD substantia nigra microarray cohorts were analyzed independently and combined using disease-specific and cross-disease meta-analysis. Independent DKD single-cell RNA-sequencing, PD single-nucleus RNA-sequencing, and spatial transcriptomic datasets were used for cell-type localization and donor- or sample-level analyses. CellChat, Monocle2, scTenifoldKnk, and previously generated UNAGI-compatible outputs were used to evaluate predicted intercellular communication, transcriptional-state continua, in-silico IRF8 perturbation, and compound prioritization. Threshold, leave-one-cohort-out, root-orientation, downsampling, and statistical-unit sensitivity analyses were performed where applicable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The original nominal-threshold intersection of 36 genes was not retained after cohort-wise multiple-testing correction. Genome-wide overlap between DKD and PD was limited in the expanded analysis. IRF8 and TLR7 showed positive effect directions in both diseases but did not pass cross-disease false-discovery-rate correction and were therefore treated as exploratory candidates. Donor-level analyses did not detect statistically significant increases in broad myeloid-lineage proportions, although the confidence intervals did not establish equivalence. Selected DKD CCL and TNF interactions were retained in both of two targeted balanced-downsampling iterations, whereas the PD TGF-\u03b2 signal was sampling-sensitive. Monocle2 identified branched and partially overlapping transcriptional-state continua. Spatial analyses provided marker-supported localization evidence without treating individual spatial observations as independent replicates. In-silico IRF8 deletion predicted regulatory-network changes but was not experimentally validated. NVP-AUY922 was the highest-ranked cross-disease computational candidate, but its association was not significant after correction across the matched compound universe.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DKD and PD show limited genome-wide overlap but partial convergence of myeloid- and microglia-enriched inflammatory signals associated with IRF8 and TLR7. These findings provide testable hypotheses rather than evidence of a conserved causal pathway or validated cross-disease treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0356691","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T17:32:51Z","timestamp":1787247171000},"page":"e0356691","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A multimodal analysis suggests partial IRF8\/TLR7-associated myeloid transcriptional convergence between diabetic kidney disease and Parkinson\u2019s 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