{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:45:21Z","timestamp":1778867121211,"version":"3.51.4"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":41,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digit. Med."],"DOI":"10.1038\/s41746-026-02468-x","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:35:42Z","timestamp":1772188542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Machine learning\u2013guided Huanglian Jiedu decoction targets STING in periodontitis-induced Alzheimer\u2019s Disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Furong","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganggang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiran","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manru","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyuan","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"2468_CR1","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","volume":"388","author":"P Scheltens","year":"2016","unstructured":"Scheltens, P. et al. Alzheimer\u2019s disease. Lancet 388, 505\u2013517 (2016).","journal-title":"Lancet"},{"key":"2468_CR2","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/nrneurol.2017.111","volume":"13","author":"J Wang","year":"2017","unstructured":"Wang, J., Gu, B. J., Masters, C. L. & Wang, Y.-J. A systemic view of Alzheimer\u2019s disease - insights from amyloid-\u03b2 metabolism beyond the brain. Nat. Rev. Neurol 13, 612\u2013623 (2017).","journal-title":"Nat. Rev. Neurol"},{"key":"2468_CR3","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb1654","volume":"6","author":"S Toden","year":"2020","unstructured":"Toden, S. et al. Noninvasive characterization of Alzheimer\u2019s disease by circulating, cell-free messenger RNA next-generation sequencing. Sci. Adv. 6, eabb1654 (2020).","journal-title":"Sci. Adv."},{"key":"2468_CR4","doi-asserted-by":"publisher","DOI":"10.1002\/alz.062215","volume":"19","author":"D Im","year":"2023","unstructured":"Im, D. & Kim, H. I. Kinetic modulation of amyloid-\u03b2 (1-42) fibrillation and alleviated cytotoxicity with rationally designed point mutants. Alzheimer\u2019s Dement. 19, e062215 (2023).","journal-title":"Alzheimer\u2019s Dement."},{"key":"2468_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102649","volume":"105","author":"C Ar\u00e9valo-Caro","year":"2025","unstructured":"Ar\u00e9valo-Caro, C. et al. APOE4, Alzheimer\u2019s and periodontal disease: a scoping review. Ageing Res. Rev 105, 102649 (2025).","journal-title":"Ageing Res. Rev"},{"key":"2468_CR6","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/s41564-020-0716-y","volume":"5","author":"M Madej","year":"2020","unstructured":"Madej, M. et al. Structural and functional insights into oligopeptide acquisition by the RagAB transporter from Porphyromonas gingivalis. Nat. Microbiol. 5, 1016\u20131025 (2020).","journal-title":"Nat. Microbiol."},{"key":"2468_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02790-1","volume":"20","author":"H Chen","year":"2023","unstructured":"Chen, H. et al. Age- and sex-related differences of periodontal bone resorption, cognitive function, and immune state in APP\/PS1 murine model of Alzheimer\u2019s disease. J. Neuroinflamm. 20, 153 (2023).","journal-title":"J. Neuroinflamm."},{"key":"2468_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03256-8","volume":"21","author":"X Qian","year":"2024","unstructured":"Qian, X. et al. Intestinal homeostasis disrupted by periodontitis exacerbates Alzheimer\u2019s disease in APP\/PS1 mice. J. Neuroinflamm. 21, 263 (2024).","journal-title":"J. Neuroinflamm."},{"key":"2468_CR9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333","volume":"5","author":"SS Dominy","year":"2019","unstructured":"Dominy, S. S. et al. Porphyromonas gingivalis in Alzheimer\u2019s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 5, eaau3333 (2019).","journal-title":"Sci. Adv."},{"key":"2468_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02743-8","volume":"20","author":"X Cheng","year":"2023","unstructured":"Cheng, X. et al. Exogenous monocyte myeloid-derived suppressor cells ameliorate immune imbalance, neuroinflammation and cognitive impairment in 5xFAD mice infected with Porphyromonas gingivalis. J Neuroinflamm. 20, 55 (2023).","journal-title":"J Neuroinflamm."},{"key":"2468_CR11","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41368-022-00215-y","volume":"15","author":"S Lei","year":"2023","unstructured":"Lei, S. et al. Porphyromonas gingivalis bacteremia increases the permeability of the blood\u2013brain barrier via the Mfsd2a\/caveolin-1 mediated transcytosis pathway. Int. J. Oral Sci. 15, 3 (2023).","journal-title":"Int. J. Oral Sci."},{"key":"2468_CR12","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1515\/revneuro-2023-0049","volume":"35","author":"Z Li","year":"2024","unstructured":"Li, Z., Wang, H. & Yin, Y. Peripheral inflammation is a potential etiological factor in Alzheimer\u2019s disease. Rev. Neurosci. 35, 99\u2013120 (2024).","journal-title":"Rev. Neurosci."},{"key":"2468_CR13","doi-asserted-by":"publisher","first-page":"166836","DOI":"10.1016\/j.jmb.2021.166836","volume":"433","author":"I Lunar Silva","year":"2021","unstructured":"Lunar Silva, I. & Cascales, E. Molecular strategies underlying Porphyromonas gingivalis virulence. J. Mol. Biol. 433, 166836 (2021).","journal-title":"J. Mol. Biol."},{"key":"2468_CR14","doi-asserted-by":"crossref","unstructured":"Ishida, N. et al. Periodontitis induced by bacterial infection exacerbates features of Alzheimer\u2019s disease in transgenic mice. NPJ Aging Mech. Dis. 3, 15 (2017).","DOI":"10.1038\/s41514-017-0015-x"},{"key":"2468_CR15","doi-asserted-by":"publisher","first-page":"658","DOI":"10.3389\/fnins.2020.00658","volume":"14","author":"Y Hu","year":"2020","unstructured":"Hu, Y. et al. Periodontitis induced by P. gingivalis-LPS is associated with neuroinflammation and learning and memory impairment in Sprague-Dawley rats. Front. Neurosci. 14, 658 (2020).","journal-title":"Front. Neurosci."},{"key":"2468_CR16","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jare.2023.02.006","volume":"54","author":"X Ma","year":"2023","unstructured":"Ma, X., Shin, Y.-J., Yoo, J.-W., Park, H.-S. & Kim, D.-H. Extracellular vesicles derived from Porphyromonas gingivalis induce trigeminal nerve-mediated cognitive impairment. J. Adv. Res. 54, 293\u2013303 (2023).","journal-title":"J. Adv. Res."},{"key":"2468_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02071-9","volume":"18","author":"Y Hu","year":"2021","unstructured":"Hu, Y. et al. Activated STAT3 signaling pathway by ligature-induced periodontitis could contribute to neuroinflammation and cognitive impairment in rats. J. Neuroinflamm. 18, 80 (2021).","journal-title":"J. Neuroinflamm."},{"key":"2468_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-1052-x","volume":"15","author":"J Zhang","year":"2018","unstructured":"Zhang, J. et al. Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL\/6 mice. J. Neuroinflamm. 15, 37 (2018).","journal-title":"J. Neuroinflamm."},{"key":"2468_CR19","doi-asserted-by":"crossref","unstructured":"Chen, Q., Sun, L. & Chen, Z. J. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing. Nat. Immunol. 17, 1142\u20131149 (2016).","DOI":"10.1038\/ni.3558"},{"key":"2468_CR20","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","volume":"339","author":"L Sun","year":"2013","unstructured":"Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z. J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786\u2013791 (2013).","journal-title":"Science"},{"key":"2468_CR21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011226118","volume":"118","author":"Y Hou","year":"2021","unstructured":"Hou, Y. et al. NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer\u2019s disease via cGAS\u2013STING. Proc. Natl. Acad. Sci. USA. 118, e2011226118 (2021).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2468_CR22","doi-asserted-by":"publisher","first-page":"15989","DOI":"10.1073\/pnas.2002144117","volume":"117","author":"M Sharma","year":"2020","unstructured":"Sharma, M., Rajendrarao, S., Shahani, N., Ram\u00edrez-Jarqu\u00edn, U. N. & Subramaniam, S. Cyclic GMP-AMP synthase promotes the inflammatory and autophagy responses in Huntington disease. Proc. Natl. Acad. Sci. USA 117, 15989\u201315999 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2468_CR23","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1021\/acscentsci.1c00440","volume":"7","author":"AF Cordova","year":"2021","unstructured":"Cordova, A. F., Ritchie, C., B\u00f6hnert, V. & Li, L. Human SLC46A2 is the dominant cGAMP importer in extracellular cGAMP-sensing macrophages and monocytes. ACS Cent. Sci. 7, 1073\u20131088 (2021).","journal-title":"ACS Cent. Sci."},{"key":"2468_CR24","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202410910","volume":"12","author":"S He","year":"2025","unstructured":"He, S. et al. Microglial cGAS deletion preserves intercellular communication and alleviates amyloid-\u03b2-induced pathogenesis of Alzheimer\u2019s disease. Adv Sci 12, e2410910 (2025).","journal-title":"Adv Sci"},{"key":"2468_CR25","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13024-025-00815-2","volume":"20","author":"S Quan","year":"2025","unstructured":"Quan, S. et al. The neuroimmune nexus: unraveling the role of the mtDNA\u2013cGAS\u2013STING signal pathway in Alzheimer\u2019s disease. Mol. Neurodegener. 20, 25 (2025).","journal-title":"Mol. Neurodegener."},{"key":"2468_CR26","doi-asserted-by":"publisher","first-page":"101444","DOI":"10.1016\/j.mam.2025.101444","volume":"107","author":"F Fazal","year":"2026","unstructured":"Fazal, F. et al. cGAS-STING signaling in Alzheimer\u2019s disease: microglial mechanisms and therapeutic opportunities. Mol. Aspects Med. 107, 101444 (2026).","journal-title":"Mol. Aspects Med."},{"key":"2468_CR27","doi-asserted-by":"publisher","first-page":"1183415","DOI":"10.3389\/fmicb.2023.1183415","volume":"14","author":"R Bi","year":"2023","unstructured":"Bi, R. et al. Porphyromonas gingivalis induces an inflammatory response via the cGAS\u2013STING signaling pathway in a periodontitis mouse model. Front. Microbiol. 14, 1183415 (2023).","journal-title":"Front. Microbiol."},{"key":"2468_CR28","doi-asserted-by":"publisher","first-page":"111984","DOI":"10.1016\/j.intimp.2024.111984","volume":"132","author":"T Wang","year":"2024","unstructured":"Wang, T. et al. IGF2 promotes alveolar bone regeneration in murine periodontitis via inhibiting cGAS\/STING-mediated M1 macrophage polarization. Int. Immunopharmacol. 132, 111984 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"2468_CR29","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1038\/aps.2014.124","volume":"36","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y. et al. Deciphering the pharmacological mechanism of the Chinese formula Huanglian-Jie-Du decoction in the treatment of ischemic stroke using a systems biology-based strategy. Acta Pharmacol. Sin. 36, 724\u2013733 (2015).","journal-title":"Acta Pharmacol. Sin."},{"key":"2468_CR30","doi-asserted-by":"publisher","first-page":"115244","DOI":"10.1016\/j.jep.2022.115244","volume":"293","author":"J Shang","year":"2022","unstructured":"Shang, J. et al. Systems pharmacology, proteomics and in vivo studies identification of mechanisms of cerebral ischemia injury amelioration by Huanglian Jiedu decoction. J. Ethnopharmacol. 293, 115244 (2022).","journal-title":"J. Ethnopharmacol."},{"key":"2468_CR31","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s13195-021-00779-7","volume":"13","author":"X Gu","year":"2021","unstructured":"Gu, X. et al. Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer\u2019s disease progression based on the \u201cbrain\u2013gut\u201d axis through multiple integrated omics. Alzheimer\u2019s Res. Ther. 13, 44 (2021).","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"2468_CR32","doi-asserted-by":"publisher","first-page":"931","DOI":"10.2147\/DDDT.S357061","volume":"16","author":"Y-Y Qi","year":"2022","unstructured":"Qi, Y.-Y. et al. Involvement of Huanglian Jiedu decoction on microglia with abnormal sphingolipid metabolism in Alzheimer\u2019s disease. Drug Des. Dev. Ther. 16, 931\u2013950 (2022).","journal-title":"Drug Des. Dev. Ther."},{"key":"2468_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118787","volume":"337","author":"G-D Zhuang","year":"2025","unstructured":"Zhuang, G.-D. et al. Huang-Lian-Jie-Du decoction alleviates diabetic encephalopathy by regulating inflammation and pyroptosis via suppression of AGEs\/RAGE\/NF-\u03baB pathways. J. Ethnopharmacol. 337, 118787 (2025).","journal-title":"J. Ethnopharmacol."},{"key":"2468_CR34","doi-asserted-by":"publisher","first-page":"8249013","DOI":"10.1155\/2018\/8249013","volume":"2018","author":"F Zhang","year":"2018","unstructured":"Zhang, F. et al. Effects of Huanglian Jiedu decoration in rat gingivitis. Evid. Based Complement. Alternat. Med. 2018, 8249013 (2018).","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"2468_CR35","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.ejphar.2019.02.026","volume":"851","author":"R Zhang","year":"2019","unstructured":"Zhang, R. et al. Berberine promotes osteogenic differentiation of mesenchymal stem cells with therapeutic potential in periodontal regeneration. Eur. J. Pharmacol. 851, 144\u2013150 (2019).","journal-title":"Eur. J. Pharmacol."},{"key":"2468_CR36","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.intimp.2016.04.012","volume":"36","author":"J-Y Sun","year":"2016","unstructured":"Sun, J.-Y. et al. Baicalin inhibits toll-like receptor 2\/4 expression and downstream signaling in rat experimental periodontitis. Int. Immunopharmacol. 36, 86\u201393 (2016).","journal-title":"Int. Immunopharmacol."},{"key":"2468_CR37","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.addr.2015.01.009","volume":"86","author":"S Tian","year":"2015","unstructured":"Tian, S. et al. The application of in silico drug-likeness predictions in pharmaceutical research. Adv. Drug Deliv. Rev. 86, 2\u201310 (2015).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2468_CR38","doi-asserted-by":"publisher","first-page":"101157","DOI":"10.1016\/j.jpha.2024.101157","volume":"15","author":"Y Hong","year":"2025","unstructured":"Hong, Y. et al. The integration of machine learning into traditional Chinese medicine. J. Pharm. Anal. 15, 101157 (2025).","journal-title":"J. Pharm. Anal."},{"key":"2468_CR39","doi-asserted-by":"publisher","first-page":"114224","DOI":"10.1016\/j.bcp.2020.114224","volume":"182","author":"Y Gao","year":"2020","unstructured":"Gao, Y. et al. Dual inhibitors of histone deacetylases and other cancer-related targets: a pharmacological perspective. Biochem. Pharmacol. 182, 114224 (2020).","journal-title":"Biochem. Pharmacol."},{"key":"2468_CR40","doi-asserted-by":"publisher","first-page":"bbae067","DOI":"10.1093\/bib\/bbae067","volume":"25","author":"L Hu","year":"2024","unstructured":"Hu, L. et al. Dual-channel hypergraph convolutional network for predicting herb-disease associations. Brief. Bioinf. 25, bbae067 (2024).","journal-title":"Brief. Bioinf."},{"key":"2468_CR41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-31380-7","volume":"13","author":"Y Fu","year":"2023","unstructured":"Fu, Y. et al. Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19. Sci. Rep. 13, 5844 (2023).","journal-title":"Sci. Rep."},{"key":"2468_CR42","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.neurobiolaging.2014.10.038","volume":"36","author":"AR Kamer","year":"2015","unstructured":"Kamer, A. R. et al. Periodontal disease associates with higher brain amyloid load in normal elderly. Neurobiol. Aging 36, 627\u2013633 (2015).","journal-title":"Neurobiol. Aging"},{"key":"2468_CR43","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/j.1532-5415.2010.02788.x","volume":"58","author":"EK Kaye","year":"2010","unstructured":"Kaye, E. K. et al. Tooth loss and periodontal disease predict poor cognitive function in older men. J. Am. Geriatr. Soc. 58, 713\u2013718 (2010).","journal-title":"J. Am. Geriatr. Soc."},{"key":"2468_CR44","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s13195-025-01818-3","volume":"17","author":"L Kong","year":"2025","unstructured":"Kong, L. et al. Periodontitis-induced neuroinflammation triggers IFITM3-a\u03b2 axis to cause Alzheimer\u2019s disease-like pathology and cognitive decline. Alzheimer\u2019s Res. Ther. 17, 166 (2025).","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"2468_CR45","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3233\/JAD-190298","volume":"72","author":"R Nie","year":"2019","unstructured":"Nie, R. et al. Porphyromonas gingivalis infection induces amyloid-\u03b2 accumulation in monocytes\/macrophages. J. Alzheimer\u2019s Dis. 72, 479\u2013494 (2019).","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"2468_CR46","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1177\/13872877251397406","volume":"109","author":"T Chac\u00f3n","year":"2026","unstructured":"Chac\u00f3n, T. & Hern\u00e1ndez-Hincapi\u00e9, H. Relationship periodontitis and Alzheimer\u2019s disease: relevant aspects from an epigenetic view. J. Alzheimer\u2019s Dis. 109, 499\u2013525 (2026).","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"2468_CR47","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.immuni.2014.10.019","volume":"41","author":"L Deng","year":"2014","unstructured":"Deng, L. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843\u2013852 (2014).","journal-title":"Immunity"},{"key":"2468_CR48","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1016\/j.immuni.2025.05.023","volume":"58","author":"S Naguib","year":"2025","unstructured":"Naguib, S. et al. The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS\u2013STING\u2013IFN pathway. Immunity 58, 1931\u20131947.e9 (2025).","journal-title":"Immunity"},{"key":"2468_CR49","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1038\/s12276-024-01295-y","volume":"56","author":"S Chung","year":"2024","unstructured":"Chung, S. Blockade of STING activation alleviates microglial dysfunction and a broad spectrum of Alzheimer\u2019s disease pathologies. Exp. Mol. Med. 56, 1936\u20131951 (2024).","journal-title":"Exp. Mol. Med."},{"key":"2468_CR50","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.7150\/ijbs.91543","volume":"20","author":"N-S-Y Yang","year":"2024","unstructured":"Yang, N.-S. -Y. et al. mtDNA\u2013cGAS\u2013STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice. Int. J. Biol. Sci. 20, 1927\u20131946 (2024).","journal-title":"Int. J. Biol. Sci."},{"key":"2468_CR51","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1016\/j.neuron.2024.09.006","volume":"112","author":"GK Carling","year":"2024","unstructured":"Carling, G. K. et al. Alzheimer\u2019s disease-linked risk alleles elevate microglial cGAS-associated senescence and neurodegeneration in a tauopathy model. Neuron 112, 3877\u20133896.e8 (2024).","journal-title":"Neuron"},{"key":"2468_CR52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2427257122","volume":"122","author":"L Tian","year":"2025","unstructured":"Tian, L. et al. Nanoimmunomodulation of the a\u03b2-STING feedback machinery in microglia for Alzheimer\u2019s disease treatment. Proc. Natl. Acad. Sci. USA. 122, e2427257122 (2025).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2468_CR53","doi-asserted-by":"publisher","first-page":"6212907","DOI":"10.1155\/2020\/6212907","volume":"2020","author":"X Gu","year":"2020","unstructured":"Gu, X. et al. Effects of Huang-Lian-Jie-Du decoction on oxidative stress and AMPK-SIRT1 pathway in Alzheimer\u2019s disease rat. Evid.-based Complement. Altern. Med. 2020, 6212907 (2020).","journal-title":"Evid.-based Complement. Altern. Med."},{"key":"2468_CR54","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.3389\/fphar.2019.01288","volume":"10","author":"P Wang","year":"2019","unstructured":"Wang, P. et al. Intermodule coupling analysis of Huang-Lian-Jie-Du decoction on stroke. Front. Pharmacol. 10, 1288 (2019).","journal-title":"Front. Pharmacol."},{"key":"2468_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2021.122764","volume":"1176","author":"Z-T Zhang","year":"2021","unstructured":"Zhang, Z.-T. et al. Rapid screening of neuroprotective components from Huang-Lian-Jie-Du decoction by living cell biospecific extraction coupled with HPLC-Q-orbitrap-HRMS\/MS analysis. J. Chromatogr. B 1176, 122764 (2021).","journal-title":"J. Chromatogr. B"},{"key":"2468_CR56","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.phrs.2017.04.016","volume":"121","author":"D Xu","year":"2017","unstructured":"Xu, D., Lv, Y., Wang, J., Yang, M. & Kong, L. Deciphering the mechanism of Huang-Lian-Jie-Du-decoction on the treatment of sepsis by formula decomposition and metabolomics: enhancement of cholinergic pathways and inhibition of HMGB-1\/TLR4\/NF-\u03baB signaling. Pharmacol. Res. 121, 94\u2013113 (2017).","journal-title":"Pharmacol. Res."},{"key":"2468_CR57","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.jep.2011.01.049","volume":"134","author":"J Lu","year":"2011","unstructured":"Lu, J., Wang, J.-S. & Kong, L.-Y. Anti-inflammatory effects of Huang-Lian-Jie-Du decoction, its two fractions and four typical compounds. J. Ethnopharmacol. 134, 911\u2013918 (2011).","journal-title":"J. Ethnopharmacol."},{"key":"2468_CR58","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s13024-015-0035-6","volume":"10","author":"I-S Lee","year":"2015","unstructured":"Lee, I.-S. et al. Human neural stem cells alleviate Alzheimer-like pathology in a mouse model. Mol. Neurodegener. 10, 38 (2015).","journal-title":"Mol. Neurodegener."},{"key":"2468_CR59","doi-asserted-by":"publisher","first-page":"2540","DOI":"10.1093\/brain\/aww160","volume":"139","author":"A Leuzy","year":"2016","unstructured":"Leuzy, A. et al. Pittsburgh compound B imaging and cerebrospinal fluid amyloid-\u03b2 in a multicentre European memory clinic study. Brain: J. Neurol. 139, 2540\u20132553 (2016).","journal-title":"Brain: J. Neurol."},{"key":"2468_CR60","first-page":"1329","volume":"23","author":"H Chen","year":"2025","unstructured":"Chen, H. et al. Applications of artificial intelligence in the research of molecular mechanisms of traditional Chinese medicine formulas. Chin. J. Nat. Med. 23, 1329\u20131341 (2025).","journal-title":"Chin. J. Nat. Med."},{"key":"2468_CR61","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13020-025-01094-1","volume":"20","author":"J Ma","year":"2025","unstructured":"Ma, J. et al. Machine learning-assisted analysis of serum metabolomics and network pharmacology reveals the effective compound from herbal formula against alcoholic liver injury. Chin. Med. 20, 48\u201371 (2025).","journal-title":"Chin. Med."},{"key":"2468_CR62","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41746-025-01967-7","volume":"8","author":"J Kuang","year":"2025","unstructured":"Kuang, J. et al. Machine learning analysis reveals tumor heterogeneity and stromal-immune niches in breast cancer. npj Digit. Med. 8, 565\u2013579 (2025).","journal-title":"npj Digit. Med."},{"key":"2468_CR63","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156795","volume":"142","author":"X Zheng","year":"2025","unstructured":"Zheng, X. et al. Bioactive components of Jiedu Sangen decoction against colorectal cancer: a novel and comprehensive research strategy for natural drug development. Phytomedicine 142, 156795 (2025).","journal-title":"Phytomedicine"},{"key":"2468_CR64","doi-asserted-by":"publisher","first-page":"23643","DOI":"10.1021\/acs.jmedchem.5c03159","volume":"68","author":"S Ali","year":"2025","unstructured":"Ali, S., Tian, X., Chen, H. & Zhou, J. A new era of artificial intelligence (AI): transforming drug discovery and development. J. Med. Chem. 68, 23643\u201323652 (2025).","journal-title":"J. Med. Chem."}],"container-title":["npj Digital Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41746-026-02468-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-026-02468-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41746-026-02468-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T11:04:17Z","timestamp":1775732657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41746-026-02468-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2468"],"URL":"https:\/\/doi.org\/10.1038\/s41746-026-02468-x","relation":{},"ISSN":["2398-6352"],"issn-type":[{"value":"2398-6352","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]},"assertion":[{"value":"13 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"293"}}