{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:46:46Z","timestamp":1791733606302,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012154","name":"Graduate Research and Innovation Projects of Jiangsu Province","doi-asserted-by":"publisher","award":["KYCX23_2123"],"award-info":[{"award-number":["KYCX23_2123"]}],"id":[{"id":"10.13039\/501100012154","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018556","name":"Science and Technology Program of Suzhou","doi-asserted-by":"publisher","award":["SKYD2023236"],"award-info":[{"award-number":["SKYD2023236"]}],"id":[{"id":"10.13039\/501100018556","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018556","name":"Science and Technology Program of Suzhou","doi-asserted-by":"publisher","award":["XZR2023089"],"award-info":[{"award-number":["XZR2023089"]}],"id":[{"id":"10.13039\/501100018556","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anxiety\u2010depressive disorder (ADD) is one of the important subtypes of depression, which has been shown to be closely related to neuroimmune abnormalities. Currently, specific biomarkers have not been identified as diagnostic, differential, and therapeutic targets. This study aimed to explore the molecular mechanisms and diagnostic biomarkers of ADD and elucidate its association with neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed circadian rhythm\u2010related genes were screened. Key genes were identified by machine learning. An ADD rat model was established using chronic restraint stress combined with corticosterone administration. Using AAV virus tools for KLF\u201010 overexpression and knockout (KLF10\u2010OE and shKLF10), depression\u2010like and anxiety\u2010like behaviors were evaluated through behavioral experiments, pathological changes in the hippocampus and amygdala were observed by Nissl staining, cytokine levels were detected by ELISA, molecular co\u2010localization was performed by RNAscope ISH and immunofluorescence, and molecular expression of NF\u2010\u03baB\/NLRP3 pathway was detected by Western blot and qRT PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine circadian rhythm\u2010related genes showed significant differential expression, with KLF10 identified as a diagnostic biomarker. KLF10 overexpression ameliorated depressive\u2010like and anxiety\u2010like behaviors, and reduced pro\u2010inflammatory factors (IL\u20101\u03b2, TNF\u2010\u03b1) and increased anti\u2010inflammatory factors (IL\u201010, TGF\u2010\u03b2) in both brain and serum, the treatment can be blocked by PMA. KLF10 suppressed I\u03baB\u2010\u03b1 phosphorylation\u2010mediated NF\u2010\u03baB nuclear translocation and inhibited downstream molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>KLF10 mitigates hippocampal\u2010amygdala neuroinflammation by downregulating the NF\u2010\u03baB\/NLRP3 pathway, thereby alleviating a ADD symptoms, and represents a potential diagnostic biomarker and therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70276","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:47:53Z","timestamp":1786380473000},"page":"1869-1883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The diagnostic value of the circadian rhythm gene\n                    <scp>KLF10<\/scp>\n                    in anxiety\u2010depressive disorders and its neuroimmune regulatory mechanisms"],"prefix":"10.1002","volume":"9","author":[{"given":"Anlan","family":"Liu","sequence":"first","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Guo","sequence":"additional","affiliation":[{"name":"Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiange","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangzhou University of Chinese Medicine  Guangzhou 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