{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:15:50Z","timestamp":1785161750802,"version":"3.55.0"},"reference-count":59,"publisher":"American Chemical Society (ACS)","issue":"14","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"crossref","award":["U23A20530"],"award-info":[{"award-number":["U23A20530"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complex diseases are commonly characterized by dysregulation across multiple targets and pathways, making drug combinations an important therapeutic strategy. This creates a growing need for computational methods to prioritize candidate combinations, yet current methods face several practical challenges, including cross-disease application, unified prediction of dual- and multidrug combinations, lack of reliable negative labels, and prediction for low-resource diseases. In this study, we proposed HyperDC, a unified cross-disease drug combination recommendation framework. HyperDC constructs a nonuniform hypergraph based on clinical and knowledge-driven drug-disease association data, representing single drugs and dual- and multidrug combinations in a unified modeling space. It further integrates knowledge graph pretraining and adversarial negative sampling to enhance model discrimination across tasks with different difficulty levels. In the unified dual-drug benchmark and disease-specific prediction tasks, HyperDC outperformed representative methods by up to 12.8 and 30.0 percentage points, respectively. In fixed-anchor clinical ranking tasks, HyperDC showed superior performance across multiple top-ranked recall settings and preferentially recalled FDA-approved dual-drug combinations and clinically supported three-drug combinations. In the data-sparse metabolic dysfunction-associated steatohepatitis (MASH) scenario, HyperDC completed a full workflow from anchor-drug identification and combination partner prioritization to in vitro experimental validation: 70% of the top 10 single-drug candidates were supported by recent literature, and 4 of 6 tested combinations showed synergistic lipid-lowering and anti-inflammatory effects, yielding a hit rate of 66.7%. Overall, HyperDC may narrow the screening space, improve prioritization efficiency, and provide methodological support for the development of combination therapy strategies for complex diseases.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01470","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:13:06Z","timestamp":1782936786000},"page":"8561-8578","source":"Crossref","is-referenced-by-count":0,"title":["HyperDC: A Non-Uniform\nHypergraph Framework for Dual-\nand Higher-Order Drug Combination Recommendation Across Diverse Complex\nDiseases"],"prefix":"10.1021","volume":"66","author":[{"given":"Hongbo","family":"Yu","sequence":"first","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Chen","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Song","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Xiong","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin","family":"Li","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Pan","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-9836","authenticated-orcid":true,"given":"Weihua","family":"Li","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9648-844X","authenticated-orcid":true,"given":"Guixia","family":"Liu","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-6998","authenticated-orcid":true,"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2340-1109","authenticated-orcid":true,"given":"Yun","family":"Tang","sequence":"additional","affiliation":[{"name":"East China University of Science and Technology , , ,","place":["Shanghai, China, 200237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"issue":"1","key":"2026072709091841000_cit1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network Medicine: A Network-Based\nApproach to Human Disease","volume":"12","author":"Baraba\u0301si","year":"2011","journal-title":"Nat. Rev. Genet."},{"issue":"9","key":"2026072709091841000_cit2","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/s41592-019-0509-5","article-title":"Assessment of Network\nModule Identification across Complex Diseases","volume":"16","author":"Choobdar","year":"2019","journal-title":"Nat. Methods"},{"issue":"2","key":"2026072709091841000_cit3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nrd2683","article-title":"Mechanisms\nof Drug Combinations: Interaction and Network Perspectives","volume":"8","author":"Jia","year":"2009","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"20","key":"2026072709091841000_cit4","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1056\/NEJMoa1406037","article-title":"Combined BRAF\nand MEK Inhibition versus BRAF Inhibition Alone in Melanoma","volume":"371","author":"Long","year":"2014","journal-title":"N. Engl. J. Med."},{"issue":"10305","key":"2026072709091841000_cit5","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/S0140-6736(21)01922-X","article-title":"Initial Treatment with\na Single Pill Containing Quadruple\nCombination of Quarter Doses of Blood Pressure Medicines versus Standard\nDose Monotherapy in Patients with Hypertension (QUARTET): A Phase\n3, Randomised, Double-Blind, Active-Controlled Trial","volume":"398","author":"Chow","year":"2021","journal-title":"Lancet"},{"issue":"1","key":"2026072709091841000_cit6","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1038\/s41467-019-09186-x","article-title":"Network-Based Prediction of Drug\nCombinations","volume":"10","author":"Cheng","year":"2019","journal-title":"Nat. Commun."},{"issue":"6","key":"2026072709091841000_cit7","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1158\/1535-7163.MCT-15-0843","article-title":"An Unbiased Oncology\nCompound Screen to Identify Novel Combination Strategies","volume":"15","author":"O\u2019Neil","year":"2016","journal-title":"Mol. Cancer Ther."},{"issue":"W1","key":"2026072709091841000_cit8","doi-asserted-by":"publisher","first-page":"W174","DOI":"10.1093\/nar\/gkab438","article-title":"DrugComb Update: A More Comprehensive\nDrug Sensitivity Data Repository and Analysis Portal","volume":"49","author":"Zheng","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2026072709091841000_cit9","doi-asserted-by":"publisher","first-page":"D871","DOI":"10.1093\/nar\/gkz1007","article-title":"DrugCombDB: A Comprehensive\nDatabase of Drug Combinations toward\nthe Discovery of Combinatorial Therapy","volume":"48","author":"Liu","year":"2020","journal-title":"Nucleic\nAcids Res."},{"issue":"4","key":"2026072709091841000_cit10","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.tips.2020.01.011","article-title":"Charting the Fragmented\nLandscape of Drug Synergy","volume":"41","author":"Meyer","year":"2020","journal-title":"Trends Pharmacol.\nSci."},{"issue":"2","key":"2026072709091841000_cit11","doi-asserted-by":"publisher","first-page":"bbab587","DOI":"10.1093\/bib\/bbab587","article-title":"PRODeepSyn: Predicting Anticancer\nSynergistic Drug Combinations by Embedding Cell Lines with Protein-Protein\nInteraction Network","volume":"23","author":"Wang","year":"2022","journal-title":"Brief Bioinform."},{"issue":"2","key":"2026072709091841000_cit12","doi-asserted-by":"publisher","first-page":"bbae015","DOI":"10.1093\/bib\/bbae015","article-title":"SynergyX: A Multi-Modality\nMutual Attention Network\nfor Interpretable Drug Synergy Prediction","volume":"25","author":"Guo","year":"2024","journal-title":"Brief\nBioinform."},{"key":"2026072709091841000_cit13","doi-asserted-by":"publisher","first-page":"bau124","DOI":"10.1093\/database\/bau124","article-title":"DCDB 2.0:\nA Major Update of the Drug Combination Database","volume":"2014","author":"Liu","year":"2014","journal-title":"Database"},{"issue":"1","key":"2026072709091841000_cit14","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41597-022-01360-z","article-title":"CDCDB: A Large\nand Continuously Updated Drug Combination Database","volume":"9","author":"Shtar","year":"2022","journal-title":"Sci. Data"},{"issue":"10","key":"2026072709091841000_cit15","doi-asserted-by":"publisher","first-page":"108020","DOI":"10.1016\/j.isci.2023.108020","article-title":"Multi-Task Learning\nfor Predicting Synergistic Drug Combinations Based on Auto-Encoding\nMulti-Relational Graphs","volume":"26","author":"Shan","year":"2023","journal-title":"iScience"},{"issue":"11","key":"2026072709091841000_cit16","doi-asserted-by":"publisher","first-page":"15034","DOI":"10.1109\/TNNLS.2023.3286280","article-title":"A Survey on Hyperlink\nPrediction","volume":"35","author":"Chen","year":"2024","journal-title":"IEEE Trans. Neural Netw. Learn.\nSyst."},{"key":"2026072709091841000_cit17","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/978-3-030-47436-2_46","article-title":"Negative Sampling\nfor Hyperlink Prediction in Networks","volume-title":"Advances\nin Knowledge Discovery and Data Mining: 24th Pacific-Asia Conference,\nPAKDD 2020, Singapore, May 11\u201314, 2020, Proceedings, Part II","author":"Patil","year":"2020"},{"issue":"8","key":"2026072709091841000_cit18","doi-asserted-by":"publisher","first-page":"5692","DOI":"10.1109\/TPAMI.2024.3371473","article-title":"Does Negative\nSampling Matter? A\nReview with Insights into Its Theory and Applications","volume":"46","author":"Yang","year":"2024","journal-title":"IEEE Trans. Pattern Anal. Mach. Intell."},{"issue":"1","key":"2026072709091841000_cit19","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41597-023-01960-3","article-title":"Building a\nKnowledge Graph to Enable\nPrecision Medicine","volume":"10","author":"Chandak","year":"2023","journal-title":"Sci. Data"},{"issue":"12","key":"2026072709091841000_cit20","doi-asserted-by":"publisher","first-page":"3601","DOI":"10.1038\/s41591-024-03233-x","article-title":"A Foundation Model for Clinician-Centered\nDrug Repurposing","volume":"30","author":"Huang","year":"2024","journal-title":"Nat. Med."},{"issue":"D1","key":"2026072709091841000_cit21","doi-asserted-by":"publisher","first-page":"D1265","DOI":"10.1093\/nar\/gkad976","article-title":"DrugBank 6.0: The DrugBank Knowledgebase\nfor 2024","volume":"52","author":"Knox","year":"2024","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"2026072709091841000_cit22","doi-asserted-by":"publisher","first-page":"D704","DOI":"10.1093\/nar\/gkz997","article-title":"The Monarch Initiative in 2019: An Integrative Data\nand Analytic Platform Connecting Phenotypes to Genotypes across Species","volume":"48","author":"Shefchek","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2026072709091841000_cit23","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.18653\/v1\/2021.naacl-main.334","article-title":"Self-Alignment\nPretraining\nfor Biomedical Entity Representations","volume-title":"Proceedings of the 2021 Conference of the North American Chapter\nof the Association for Computational Linguistics: Human Language Technologies","author":"Liu","year":"2021"},{"key":"2026072709091841000_cit24","doi-asserted-by":"crossref","first-page":"72","DOI":"10.18653\/v1\/W19-1909","article-title":"Publicly\nAvailable Clinical BERT\nEmbeddings","volume-title":"Proceedings of the 2nd Clinical\nNatural Language Processing Workshop","author":"Alsentzer","year":"2019"},{"issue":"4","key":"2026072709091841000_cit25","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1093\/bioinformatics\/btz682","article-title":"BioBERT: A Pre-Trained Biomedical\nLanguage Representation Model for Biomedical Text Mining","volume":"36","author":"Lee","year":"2020","journal-title":"Bioinformatics"},{"key":"2026072709091841000_cit26","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2006.12278","article-title":"HNHN:\nHypergraph Networks with\nHyperedge Neurons","author":"Dong","year":"2020","journal-title":"arXiv: 2006.12278"},{"key":"2026072709091841000_cit27","doi-asserted-by":"publisher","DOI":"10.1145\/3477495.3531836","article-title":"Ahp: Learning\nto Negative Sample for\nHyperedge Prediction","volume-title":"SIGIR\u201922:\nProceedings of the 45th International ACM SIGIR Conference on Research\nand Development in Information Retrieval","author":"Hwang","year":"2022"},{"key":"2026072709091841000_cit28","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1111\/j.1744-7348.1939.tb06990.x","article-title":"The Toxicity\nof Poisons Applied Jointly 1","volume":"26","author":"Bliss","year":"1939","journal-title":"Ann. Appl. Biol."},{"issue":"S6","key":"2026072709091841000_cit29","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12911-021-01534-6","article-title":"ICD-11: An International\nClassification of Diseases for the Twenty-First Century","volume":"21","author":"Harrison","year":"2021","journal-title":"BMC Med. Inf. Decis. Making"},{"issue":"1","key":"2026072709091841000_cit30","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1161\/HYPERTENSIONAHA.109.131300","article-title":"Triple\nAntihypertensive\nTherapy with Amlodipine, Valsartan, and Hydrochlorothiazide: A Randomized\nClinical Trial","volume":"54","author":"Calhoun","year":"2009","journal-title":"Hypertension"},{"issue":"11","key":"2026072709091841000_cit31","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.2337\/dc15-0779","article-title":"Randomized,\nDouble-Blind, Phase 3 Trial of Triple Therapy with Dapagliflozin Add-on\nto Saxagliptin plus Metformin in Type 2 Diabetes","volume":"38","author":"Mathieu","year":"2015","journal-title":"Diabetes Care"},{"key":"2026072709091841000_cit32","volume-title":"Guidelines for the Use of Antiretroviral\nAgents in Adults\nand Adolescents With HIV","author":"Panel on Antiretroviral Guidelines for Adults and Adolescents.","year":"2024"},{"issue":"6","key":"2026072709091841000_cit33","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S2468-1253(19)30094-9","article-title":"Long-Term Efficacy and Safety of Obeticholic Acid for\nPatients with Primary Biliary Cholangitis: 3-Year Results of an International\nOpen-Label Extension Study","volume":"4","author":"Trauner","year":"2019","journal-title":"Lancet Gastroenterol.\nHepatol."},{"issue":"5","key":"2026072709091841000_cit34","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41575-020-00404-2","article-title":"The Role of Farnesoid X Receptor\nin Metabolic Diseases,\nand Gastrointestinal and Liver Cancer","volume":"18","author":"Sun","year":"2021","journal-title":"Nat.\nRev. Gastroenterol. Hepatol."},{"key":"2026072709091841000_cit35","doi-asserted-by":"publisher","first-page":"109953","DOI":"10.1016\/j.cbi.2022.109953","article-title":"Obeticholic\nAcid Orchestrates the\nCrosstalk between Ileal Autophagy and Tight Junctions in Non-Alcoholic\nSteatohepatitis: Role of TLR4\/TGF-\u03921 Axis","volume":"361","author":"Tawfiq","year":"2022","journal-title":"Chem. Biol. Interact."},{"issue":"10215","key":"2026072709091841000_cit36","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic\nAcid for the Treatment of Non-Alcoholic\nSteatohepatitis: Interim Analysis from a Multicentre, Randomised,\nPlacebo-Controlled Phase 3 Trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"issue":"2","key":"2026072709091841000_cit37","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1002\/med.21991","article-title":"FXR Agonists\nfor MASH Therapy: Lessons and Perspectives from Obeticholic Acid","volume":"44","author":"Wang","year":"2024","journal-title":"Med. Res. Rev."},{"issue":"1","key":"2026072709091841000_cit38","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12967-024-05011-2","article-title":"The Clinical Efficacy and Safety of Berberine in the\nTreatment of Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and\nSystematic Review","volume":"22","author":"Nie","year":"2024","journal-title":"J. Transl. Med."},{"issue":"734","key":"2026072709091841000_cit39","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade7347","article-title":"Multispecies\nTranscriptomics Identifies SIKE as a MAPK Repressor That Prevents\nNASH Progression","volume":"16","author":"Bai","year":"2024","journal-title":"Sci. Transl. Med."},{"issue":"4","key":"2026072709091841000_cit40","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.apsb.2019.02.006","article-title":"Silibinin Ameliorates\nHepatic Lipid Accumulation and Oxidative Stress in Mice with Non-Alcoholic\nSteatohepatitis by Regulating CFLAR-JNK Pathway","volume":"9","author":"Liu","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"issue":"2","key":"2026072709091841000_cit41","doi-asserted-by":"publisher","first-page":"350","DOI":"10.3390\/nu15020350","article-title":"Novel Therapeutic\nPotentials of Taxifolin\nfor Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis","volume":"15","author":"Inoue","year":"2023","journal-title":"Nutrients"},{"issue":"4","key":"2026072709091841000_cit42","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41591-019-0379-5","article-title":"Platelet GPIb\u03b1 Is a Mediator and Potential Interventional\nTarget for NASH and Subsequent Liver Cancer","volume":"25","author":"Malehmir","year":"2019","journal-title":"Nat. Med."},{"issue":"1","key":"2026072709091841000_cit43","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/s13105-023-00988-8","article-title":"High Fat Diet-Induced Downregulation\nof TRPV2Mediates\nHepatic Steatosis via P21 Signalling","volume":"80","author":"Wei","year":"2024","journal-title":"J. Physiol.\nBiochem."},{"issue":"4","key":"2026072709091841000_cit44","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0002-9343(02)01529-2","article-title":"Troglitazone-Induced\nLiver Failure: A Case Study","volume":"114","author":"Graham","year":"2003","journal-title":"Am. J. Med."},{"issue":"2","key":"2026072709091841000_cit45","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/S2213-8587(24)00318-8","article-title":"Metabolic Dysfunction-Associated\nSteatotic Liver Disease: Heterogeneous Pathomechanisms and Effectiveness\nof Metabolism-Based Treatment","volume":"13","author":"Stefan","year":"2025","journal-title":"Lancet Diabetes\nEndocrinol."},{"issue":"10","key":"2026072709091841000_cit46","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1038\/s41423-025-01307-5","article-title":"Immunopathogenic Mechanisms\nand Immunoregulatory Therapies in MASLD","volume":"22","author":"He","year":"2025","journal-title":"Cell.\nMol. Immunol."},{"issue":"7","key":"2026072709091841000_cit47","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41573-019-0019-2","article-title":"AMP-Activated Protein Kinase: The\nCurrent Landscape\nfor Drug Development","volume":"18","author":"Steinberg","year":"2019","journal-title":"Nat. Rev. Drug Discovery"},{"issue":"6","key":"2026072709091841000_cit48","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.tips.2025.03.008","article-title":"Targeting AMPK as a Potential Treatment\nfor Hepatic Fibrosis in MASLD","volume":"46","author":"Palomer","year":"2025","journal-title":"Trends Pharmacol.\nSci."},{"issue":"5","key":"2026072709091841000_cit49","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1053\/j.gastro.2012.01.007","article-title":"Farnesoid X Receptor\nProtects Hepatocytes\nfrom Injury by Repressing miR-199a-3p, Which Increases Levels of LKB1","volume":"142","author":"Lee","year":"2012","journal-title":"Gastroenterology"},{"issue":"6","key":"2026072709091841000_cit50","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1016\/j.cell.2006.11.013","article-title":"Resveratrol Improves\nMitochondrial Function and Protects against Metabolic Disease by Activating\nSIRT1 and PGC-1\u03b1","volume":"127","author":"Lagouge","year":"2006","journal-title":"Cell"},{"issue":"15","key":"2026072709091841000_cit51","doi-asserted-by":"publisher","first-page":"7086","DOI":"10.7150\/ijbs.117669","article-title":"SIRT1 in Liver\nDiseases: Mechanistic Insights and Therapeutic\nProspects","volume":"21","author":"Zuo","year":"2025","journal-title":"Int. J. Biol. Sci."},{"issue":"2","key":"2026072709091841000_cit52","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.apsb.2022.08.019","article-title":"SIRT1 Activation Synergizes\nwith FXR Agonism in Hepatoprotection via Governing Nucleocytoplasmic\nShuttling and Degradation of FXR","volume":"13","author":"Cui","year":"2023","journal-title":"Acta Pharm.\nSin. B"},{"issue":"8","key":"2026072709091841000_cit53","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1002\/art.39684","article-title":"A Randomized,\nDouble-Blind, Active- and Placebo-Controlled Efficacy and Safety Study\nof Arhalofenate for Reducing Flare in Patients With Gout","volume":"68","author":"Poiley","year":"2016","journal-title":"Arthritis Rheumatol."},{"issue":"7","key":"2026072709091841000_cit54","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1210\/me.2008-0473","article-title":"MBX-102\/JNJ39659100,\na Novel Peroxisome Proliferator-Activated Receptor-Ligand with Weak\nTransactivation Activity Retains Antidiabetic Properties in the Absence\nof Weight Gain and Edema","volume":"23","author":"Gregoire","year":"2009","journal-title":"Mol. Endocrinol."},{"issue":"5","key":"2026072709091841000_cit55","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1016\/j.jhep.2023.07.004","article-title":"Treating NASH by Targeting Peroxisome\nProliferator-Activated Receptors","volume":"79","author":"Staels","year":"2023","journal-title":"J. Hepatol."},{"issue":"11","key":"2026072709091841000_cit56","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.tem.2011.07.002","article-title":"Hepatic FXR: Key Regulator of Whole-Body\nEnergy Metabolism","volume":"22","author":"Teodoro","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"2026072709091841000_cit57","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.ctrv.2017.06.003","article-title":"Targeting STAT3 with Silibinin to\nImprove Cancer Therapeutics","volume":"58","author":"Bosch-Barrera","year":"2017","journal-title":"Cancer Treat Rev."},{"issue":"3","key":"2026072709091841000_cit58","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70145","article-title":"Carabrone Attenuates Metabolic Dysfunction-Associated\nSteatohepatitis by Targeting STAT3 in Mice","volume":"6","author":"Pan","year":"2025","journal-title":"MedComm"},{"key":"2026072709091841000_cit59","doi-asserted-by":"publisher","first-page":"114497","DOI":"10.1016\/j.bcp.2021.114497","article-title":"Activation\nof FXR Modulates SOCS3\/Jak2\/STAT3\nSignaling Axis in a NASH-Dependent Hepatocellular Carcinoma Animal\nModel","volume":"186","author":"Attia","year":"2021","journal-title":"Biochem. Pharmacol."}],"container-title":["Journal of Chemical Information\nand Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.6c01470","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/14\/8561\/65316237\/acs.jcim.6c01470.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/14\/8561\/65316237\/acs.jcim.6c01470.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:31:16Z","timestamp":1785159076000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/66\/14\/8561\/5172492\/HyperDC-A-Non-Uniform-Hypergraph-Framework-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":59,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7,1]]},"published-print":{"date-parts":[[2026,7,27]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.6c01470","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]}}}