{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:43:02Z","timestamp":1789472582269,"version":"build-2803163510"},"reference-count":99,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005150","name":"Chinese Academy of Medical Sciences & Peking Union Medical College","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2021-I2M-1-009"],"award-info":[{"award-number":["2021-I2M-1-009"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2022-I2M-2-002"],"award-info":[{"award-number":["2022-I2M-2-002"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Acta Pharmaceutica Sinica B"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.apsb.2025.11.026","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T17:08:06Z","timestamp":1764004086000},"page":"231-238","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neg-entropy is the true drug target for chronic diseases"],"prefix":"10.1016","volume":"16","author":[{"given":"Rui","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Le","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Dong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.apsb.2025.11.026_bib1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/d41573-024-00057-9","article-title":"Novel drug targets in 2023","volume":"23","author":"Avram","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.apsb.2025.11.026_bib2","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41573-024-01025-z","article-title":"Protein isoform-centric therapeutics: expanding targets and increasing specificity","volume":"23","author":"Kjer-Hansen","year":"2024","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.apsb.2025.11.026_bib3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrd.2016.230","article-title":"A comprehensive map of molecular drug targets","volume":"16","author":"Santos","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.apsb.2025.11.026_bib4","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold protein structure database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.apsb.2025.11.026_bib5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s43588-024-00627-2","article-title":"MISATO: machine learning dataset of protein\u2013ligand complexes for structure-based drug discovery","volume":"4","author":"Siebenmorgen","year":"2024","journal-title":"Nat Comput Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2025.107863","article-title":"Viroporins beyond pathogenesis: ion channel properties as the key to unlocking a neglected antiviral target","volume":"219","author":"Peng","year":"2025","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.apsb.2025.11.026_bib7","article-title":"Quinazoline-based dual-target inhibitors disrupt influenza virus RNP complex: rational design, synthesis and mechanistic validation of potent anti-influenza agents","volume":"301","author":"Zhang","year":"2025","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.apsb.2025.11.026_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.112958","article-title":"Non-steroidal anti-inflammatory drugs (NSAIDs), pain and aging: adjusting prescription to patient features","volume":"150","author":"Ribeiro","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.apsb.2025.11.026_bib9","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrd2550","article-title":"Aliskiren: the first renin inhibitor for clinical treatment","volume":"7","author":"Jensen","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.apsb.2025.11.026_bib10","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.tree.2020.04.009","article-title":"The importance of genetic redundancy in evolution","volume":"35","author":"L\u00e1ruson","year":"2020","journal-title":"Trends Ecol Evol"},{"key":"10.1016\/j.apsb.2025.11.026_bib11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41572-022-00376-4","article-title":"Multimorbidity","volume":"8","author":"Skou","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"10.1016\/j.apsb.2025.11.026_bib12","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.mayocp.2025.02.021","article-title":"Clinical assessment of people with obesity: focus on adiposity-related multimorbidity","volume":"100","author":"Bianchettin","year":"2025","journal-title":"Mayo Clin Proc"},{"key":"10.1016\/j.apsb.2025.11.026_bib13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/ijp.ijp_442_21","article-title":"Aging, VO2 max, entropy, and COVID-19","volume":"54","author":"Spedding","year":"2022","journal-title":"Indian J Pharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib14","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1186\/s12888-023-05012-3","article-title":"Immediate visual reproduction negatively correlates with brain entropy of parahippocampal gyrus and inferior occipital gyrus in bipolar II disorder adolescents","volume":"23","author":"Liu","year":"2023","journal-title":"BMC Psychiatry"},{"key":"10.1016\/j.apsb.2025.11.026_bib15","doi-asserted-by":"crossref","first-page":"6321","DOI":"10.3390\/ijms25126321","article-title":"Decreasing intracellular entropy by increasing mitochondrial efficiency and reducing ROS formation-the effect on the ageing process and age-related damage","volume":"25","author":"Polj\u0161ak","year":"2024","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114754","article-title":"Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases","volume":"163","author":"Guo","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.apsb.2025.11.026_bib17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.eng.2024.05.007","article-title":"Neg-entropy mechanism as a target for natural medicines","volume":"38","author":"Gao","year":"2024","journal-title":"Engineering"},{"key":"10.1016\/j.apsb.2025.11.026_bib18","article-title":"A pathophysiology-informed, negentropy-oriented strategy for nanomedicine in MASLD","author":"Mao","year":"2025","journal-title":"Adv Healthcare Mater"},{"key":"10.1016\/j.apsb.2025.11.026_bib19","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.eng.2021.08.014","article-title":"The entropy perspective on human illness and aging","volume":"9","author":"Wang","year":"2022","journal-title":"Engineering"},{"key":"10.1016\/j.apsb.2025.11.026_bib20","series-title":"Entropy and its physical meaning","author":"Dugdale","year":"1996"},{"key":"10.1016\/j.apsb.2025.11.026_bib21","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.61138","article-title":"The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function","volume":"10","author":"Clemens","year":"2021","journal-title":"eLife"},{"key":"10.1016\/j.apsb.2025.11.026_bib22","doi-asserted-by":"crossref","first-page":"7025","DOI":"10.1016\/j.cell.2024.10.019","article-title":"Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging","volume":"187","author":"Ma","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.apsb.2025.11.026_bib23","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2109889118","article-title":"Broken detailed balance and entropy production in the human brain","volume":"118","author":"Lynn","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.apsb.2025.11.026_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms15599","article-title":"Single-cell entropy for accurate estimation of differentiation potency from a cell's transcriptome","volume":"8","author":"Teschendorff","year":"2017","journal-title":"Nat Commun"},{"key":"10.1016\/j.apsb.2025.11.026_bib25","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3390\/e23020222","article-title":"The entropy universe","volume":"23","author":"Ribeiro","year":"2021","journal-title":"Entropy"},{"key":"10.1016\/j.apsb.2025.11.026_bib26","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1038\/s41467-019-09852-0","article-title":"Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases","volume":"10","author":"Guo","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.apsb.2025.11.026_bib27","doi-asserted-by":"crossref","first-page":"4847","DOI":"10.3390\/ijms26104847","article-title":"Exploring the multi-faceted effects of berberine in ameliorating diastolic dysfunction in rats with heart failure with preserved ejection fraction","volume":"26","author":"Mu","year":"2025","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib28","doi-asserted-by":"crossref","DOI":"10.1111\/jav.02392","article-title":"Goose parents lead migration V","volume":"51","author":"K\u00f6lzsch","year":"2020","journal-title":"J Avian Biol"},{"key":"10.1016\/j.apsb.2025.11.026_bib29","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.anbehav.2009.07.007","article-title":"Organized flight in birds","volume":"78","author":"Bajec","year":"2009","journal-title":"Anim Behav"},{"key":"10.1016\/j.apsb.2025.11.026_bib30","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1126\/science.168.3934.1003","article-title":"Formation flight of birds","volume":"168","author":"Lissaman","year":"1970","journal-title":"Science"},{"key":"10.1016\/j.apsb.2025.11.026_bib31","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0022-5193(83)90110-8","article-title":"Aerodynamic aspects of formation flight in birds","volume":"104","author":"Hummel","year":"1983","journal-title":"J Theor Biol"},{"key":"10.1016\/j.apsb.2025.11.026_bib32","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/35099670","article-title":"Energy saving in flight formation","volume":"413","author":"Weimerskirch","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.apsb.2025.11.026_bib33","doi-asserted-by":"crossref","first-page":"eadu9628","DOI":"10.1126\/science.adu9628","article-title":"Interphase cell morphology defines the mode, symmetry, and outcome of mitosis","volume":"388","author":"Lovegrove","year":"2025","journal-title":"Science"},{"key":"10.1016\/j.apsb.2025.11.026_bib34","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0962-8924(01)02142-0","article-title":"Triggering the all-or-nothing switch into mitosis","volume":"11","author":"O'Farrell","year":"2001","journal-title":"Trends Cell Biol"},{"key":"10.1016\/j.apsb.2025.11.026_bib35","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202210093","article-title":"UHRF1 promotes spindle assembly and chromosome congression by catalyzing EG5 polyubiquitination","volume":"222","author":"Qi","year":"2023","journal-title":"J Cell Biol"},{"key":"10.1016\/j.apsb.2025.11.026_bib36","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tips.2025.03.008","article-title":"Targeting AMPK as a potential treatment for hepatic fibrosis in MASLD","volume":"46","author":"Palomer","year":"2025","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib37","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41580-022-00547-x","article-title":"New insights into activation and function of the AMPK","volume":"24","author":"Steinberg","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.apsb.2025.11.026_bib38","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1016\/j.molcel.2021.08.015","article-title":"AMPK: restoring metabolic homeostasis over space and time","volume":"81","author":"Trefts","year":"2021","journal-title":"Mol Cell"},{"key":"10.1016\/j.apsb.2025.11.026_bib39","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol Cell"},{"key":"10.1016\/j.apsb.2025.11.026_bib40","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev-cellbio-120420-094431","article-title":"The AMPK pathway: molecular rejuvenation of metabolism and mitochondria","volume":"41","author":"Malik","year":"2025","journal-title":"Annu Rev Cell Dev Biol"},{"key":"10.1016\/j.apsb.2025.11.026_bib41","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tem.2024.07.017","article-title":"The direct targets of metformin in diabetes and beyond","volume":"36","author":"Yao","year":"2025","journal-title":"Trends Endocrinol Metab"},{"key":"10.1016\/j.apsb.2025.11.026_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2025.157030","article-title":"Multiple target and regulatory pathways of berberine","volume":"146","author":"Zhou","year":"2025","journal-title":"Phytomedicine"},{"key":"10.1016\/j.apsb.2025.11.026_bib43","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1126\/science.aah5582","article-title":"Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy","volume":"357","author":"Myers","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.apsb.2025.11.026_bib44","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S2213-8587(17)30013-X","article-title":"Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial","volume":"5","author":"Sorli","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"10.1016\/j.apsb.2025.11.026_bib45","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41392-024-01931-z","article-title":"Glucagon-like peptide-1 receptor: mechanisms and advances in therapy","volume":"9","author":"Zheng","year":"2024","journal-title":"Signal Transduct Targeted Ther"},{"key":"10.1016\/j.apsb.2025.11.026_bib46","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.tips.2025.03.003","article-title":"Structural pharmacology and mechanisms of GLP-1R signaling","volume":"46","author":"Zhou","year":"2025","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib47","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1161\/CIRCULATIONAHA.123.067505","article-title":"Effects of semaglutide on symptoms, function, and quality of life in patients with heart failure with preserved ejection fraction and obesity: a prespecified analysis of the STEP-HFpEF trial","volume":"149","author":"Kosiborod","year":"2024","journal-title":"Circulation"},{"key":"10.1016\/j.apsb.2025.11.026_bib48","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.21305","article-title":"Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes","volume":"7","author":"Wang","year":"2024","journal-title":"JAMA Netw Open"},{"key":"10.1016\/j.apsb.2025.11.026_bib49","doi-asserted-by":"crossref","first-page":"eadl6164","DOI":"10.1126\/scisignal.adl6164","article-title":"Extracellular proximal interaction profiling by cell surface-targeted TurboID reveals LDLR as a partner of liganded EGFR","volume":"17","author":"Al Mismar","year":"2024","journal-title":"Sci Signal"},{"key":"10.1016\/j.apsb.2025.11.026_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107496","article-title":"Berberine in the treatment of metabolism-related chronic diseases: a drug cloud (dCloud) effect to target multifactorial disorders","volume":"209","author":"Kong","year":"2020","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.apsb.2025.11.026_bib51","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/S0140-6736(23)00215-5","article-title":"Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials","volume":"401","author":"Ridker","year":"2023","journal-title":"Lancet"},{"key":"10.1016\/j.apsb.2025.11.026_bib52","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1093\/eurheartj\/ehy862","article-title":"Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin\/kexin type 9 antibody treatment","volume":"40","author":"Stiekema","year":"2019","journal-title":"Eur Heart J"},{"key":"10.1016\/j.apsb.2025.11.026_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2025.117031","article-title":"PCSK9 inhibition mitigates vulnerable plaque formation induced by hyperhomocysteinemia through regulating lipid metabolism and inflammation","volume":"239","author":"Jin","year":"2025","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib54","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1093\/cvr\/cvac020","article-title":"Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications","volume":"118","author":"Ruscica","year":"2023","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.apsb.2025.11.026_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2024.108593","article-title":"Berberine prevents NAFLD and HCC by modulating metabolic disorders","volume":"254","author":"Lin","year":"2024","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.apsb.2025.11.026_bib56","article-title":"Berberine for preventing colorectal adenoma recurrence and neoplasm occurrence: 6-year follow-up of a randomized clinical trial","volume":"6","author":"Tan","year":"2025","journal-title":"Cell Rep Med"},{"key":"10.1016\/j.apsb.2025.11.026_bib57","doi-asserted-by":"crossref","first-page":"5038","DOI":"10.1111\/bph.70035","article-title":"Berberine partially ameliorates cardiolipotoxicity in diabetic cardiomyopathy by modulating SIRT3-mediated lipophagy to remodel lipid droplets homeostasis","volume":"182","author":"Chen","year":"2025","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib58","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1038\/nm1135","article-title":"Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins","volume":"10","author":"Kong","year":"2004","journal-title":"Nat Med"},{"key":"10.1016\/j.apsb.2025.11.026_bib59","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.metabol.2009.07.029","article-title":"Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression","volume":"59","author":"Zhang","year":"2010","journal-title":"Metabolism"},{"key":"10.1016\/j.apsb.2025.11.026_bib60","doi-asserted-by":"crossref","first-page":"28885","DOI":"10.1074\/jbc.M109.052407","article-title":"Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine","volume":"284","author":"Li","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1016\/j.apsb.2025.11.026_bib61","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1007\/s11427-024-2834-8","article-title":"Berberine dissociates mitochondrial complex I by SIRT3-dependent deacetylation of NDUFS1 to improve hepatocellular glucose and lipid metabolism","volume":"68","author":"Wang","year":"2025","journal-title":"Sci China Life Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib62","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105497","article-title":"Mechanistic insights into AMPK-SIRT3 positive feedback loop-mediated chondrocyte mitochondrial quality control in osteoarthritis pathogenesis","volume":"166","author":"Chen","year":"2021","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.apsb.2025.11.026_bib63","doi-asserted-by":"crossref","first-page":"531","DOI":"10.7150\/thno.80289","article-title":"SIRT3 mediates the effects of PCSK9 inhibitors on inflammation, autophagy, and oxidative stress in endothelial cells","volume":"13","author":"D'Onofrio","year":"2023","journal-title":"Theranostics"},{"key":"10.1016\/j.apsb.2025.11.026_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2025.112063","article-title":"SIRT3 mitigates osteoarthritis by suppressing ferroptosis through activating AMPK signaling pathway","volume":"135","author":"Tian","year":"2025","journal-title":"Cell Signal"},{"key":"10.1016\/j.apsb.2025.11.026_bib65","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102654","article-title":"Roles of SIRT3 in cardiovascular and neurodegenerative diseases","volume":"104","author":"Cheng","year":"2025","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.apsb.2025.11.026_bib66","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41413-024-00399-5","article-title":"Enhanced SIRT3 expression restores mitochondrial quality control mechanism to reverse osteogenic impairment in type 2 diabetes mellitus","volume":"13","author":"Xian","year":"2025","journal-title":"Bone Res"},{"key":"10.1016\/j.apsb.2025.11.026_bib67","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1111\/bph.17327","article-title":"Semaglutide protects against diabetes-associated cardiac inflammation via Sirt3-dependent RKIP pathway","volume":"182","author":"Lin","year":"2025","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib68","doi-asserted-by":"crossref","first-page":"5135","DOI":"10.7150\/ijbs.115518","article-title":"Roles of SIRT3 in aging and aging-related diseases","volume":"21","author":"You","year":"2025","journal-title":"Int J Biol Sci"},{"key":"10.1016\/j.apsb.2025.11.026_bib69","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3390\/e22111305","article-title":"Dissipative structures, organisms and evolution","volume":"22","author":"Kondepudi","year":"2020","journal-title":"Entropy"},{"key":"10.1016\/j.apsb.2025.11.026_bib70","doi-asserted-by":"crossref","DOI":"10.1016\/j.biosystems.2024.105214","article-title":"Bio-analog dissipative structures and principles of biological behavior","volume":"239","author":"De Bari","year":"2024","journal-title":"Biosystems"},{"key":"10.1016\/j.apsb.2025.11.026_bib71","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/med.21514","article-title":"Complex roles of the old drug aspirin in cancer chemoprevention and therapy","volume":"39","author":"Hua","year":"2019","journal-title":"Med Res Rev"},{"key":"10.1016\/j.apsb.2025.11.026_bib72","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1053\/j.ajkd.2021.07.003","article-title":"Incidence and outcomes of COVID-19 in people with CKD: a systematic review and meta-analysis","volume":"78","author":"Chung","year":"2021","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.apsb.2025.11.026_bib73","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1186\/s12879-021-06466-0","article-title":"Obesity, chronic disease, age, and in-hospital mortality in patients with COVID-19: analysis of ISARIC clinical characterisation protocol UK cohort","volume":"21","author":"Yates","year":"2021","journal-title":"BMC Infect Dis"},{"key":"10.1016\/j.apsb.2025.11.026_bib74","doi-asserted-by":"crossref","first-page":"8554","DOI":"10.1021\/acs.jmedchem.0c00940","article-title":"Mechanistic insight into antiretroviral potency of 2\u2032-deoxy-2\u2032-\u03b2-fluoro-4\u2032-azidocytidine (FNC) with a long-lasting effect on HIV-1 prevention","volume":"63","author":"Sun","year":"2020","journal-title":"J Med Chem"},{"key":"10.1016\/j.apsb.2025.11.026_bib75","article-title":"Azvudine, a novel nucleoside reverse transcriptase inhibitor showed good drug combination features and better inhibition on drug-resistant strains than lamivudine in vitro","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.apsb.2025.11.026_bib76","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41392-021-00835-6","article-title":"Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct Targeted Ther"},{"key":"10.1016\/j.apsb.2025.11.026_bib77","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1016\/j.apsb.2024.03.032","article-title":"Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect","volume":"14","author":"Sheng","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.apsb.2025.11.026_bib78","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.apsb.2024.12.032","article-title":"A retrospective cohort study of the efficacy and safety of oral azvudine versus nirmatrelvir\/ritonavir in elderly hospitalized COVID-19 patients aged over 60 years","volume":"15","author":"Yu","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.apsb.2025.11.026_bib79","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1016\/j.apsb.2023.07.007","article-title":"Azvudine reduces the in-hospital mortality of COVID-19 patients: a retrospective cohort study","volume":"13","author":"Zong","year":"2023","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.apsb.2025.11.026_bib80","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.110824","article-title":"Azvudine and mortality in patients with coronavirus disease 2019: a retrospective cohort study","volume":"124","author":"Liu","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib81","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/14787210.2024.2362900","article-title":"Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study","volume":"22","author":"Kapar","year":"2024","journal-title":"Expert Rev Anti Infect Ther"},{"key":"10.1016\/j.apsb.2025.11.026_bib82","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12879-023-08944-z","article-title":"Effectiveness and safety of azvudine in older adults with mild and moderate COVID-19: a retrospective observational study","volume":"24","author":"Zhou","year":"2024","journal-title":"BMC Infect Dis"},{"key":"10.1016\/j.apsb.2025.11.026_bib83","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41392-025-02126-w","article-title":"Real-world effectiveness and safety of oral azvudine versus nirmatrelvir\u2012ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study","volume":"10","author":"Wang","year":"2025","journal-title":"Signal Transduct Targeted Ther"},{"key":"10.1016\/j.apsb.2025.11.026_bib84","article-title":"Effectiveness and safety of oral azvudine for elderly hospitalized patients with COVID-19: a multicenter, retrospective, real-world study","author":"Sun","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"10.1016\/j.apsb.2025.11.026_bib85","article-title":"Azvudine alleviates SARS-CoV-2-induced inflammation by targeting myeloperoxidase in NETosis","volume":"36","author":"Li","year":"2025","journal-title":"Chin Chem Lett"},{"key":"10.1016\/j.apsb.2025.11.026_bib86","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1347047","article-title":"Understanding the action mechanisms of metformin in the gastrointestinal tract","volume":"15","author":"Cheng","year":"2024","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib87","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1016\/j.apsb.2023.02.017","article-title":"Berberine improves central memory formation of CD8+ T cells: implications for design of natural product-based vaccines","volume":"13","author":"Li","year":"2023","journal-title":"Acta Pharm Sin B"},{"key":"10.1016\/j.apsb.2025.11.026_bib88","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.jhep.2018.11.034","article-title":"Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish","volume":"70","author":"de Oliveira","year":"2019","journal-title":"J Hepatol"},{"key":"10.1016\/j.apsb.2025.11.026_bib89","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2024.217019","article-title":"Unlocking the potential of berberine: advancing cancer therapy through chemosensitization and combination treatments","volume":"597","author":"Sajeev","year":"2024","journal-title":"Cancer Lett"},{"key":"10.1016\/j.apsb.2025.11.026_bib90","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S2468-1253(19)30409-1","article-title":"Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blind, randomised controlled study","volume":"5","author":"Chen","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"10.1016\/j.apsb.2025.11.026_bib91","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.omto.2022.08.001","article-title":"Berberine inhibits carcinogenesis through antagonizing the ATX\u2013LPA\u2013LPAR2\u2013p38\u2013leptin axis in a mouse hepatoma model","volume":"26","author":"Ren","year":"2022","journal-title":"Mol Ther Oncolytics"},{"key":"10.1016\/j.apsb.2025.11.026_bib92","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1093\/jnci\/djae070","article-title":"Metformin boosts antitumor immunity and improves prognosis in upfront resected pancreatic cancer: an observational study","volume":"116","author":"van Eijck","year":"2024","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.apsb.2025.11.026_bib93","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S1470-2045(15)00565-3","article-title":"Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blinded placebo-controlled, randomised phase 3 trial","volume":"17","author":"Higurashi","year":"2016","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.apsb.2025.11.026_bib94","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217694","article-title":"Metformin inhibits the progression of castration-resistant prostate cancer by regulating PDE6D induced purine metabolic alternation and cGMP\/PKG pathway activation","volume":"622","author":"Cai","year":"2025","journal-title":"Cancer Lett"},{"key":"10.1016\/j.apsb.2025.11.026_bib95","article-title":"Analgesic alkaloids derived from traditional Chinese medicine in pain management","volume":"13","author":"Jiang","year":"2022","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.apsb.2025.11.026_bib96","doi-asserted-by":"crossref","first-page":"353","DOI":"10.2337\/dc15-1736","article-title":"Initial combination therapy with canagliflozin plus metformin versus each component as monotherapy for drug-na\u00efve type 2 diabetes","volume":"39","author":"Rosenstock","year":"2016","journal-title":"Diabetes Care"},{"key":"10.1016\/j.apsb.2025.11.026_bib97","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0140-6736(10)60746-5","article-title":"Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study","volume":"376","author":"Zinman","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.apsb.2025.11.026_bib98","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1038\/s41591-022-01803-5","article-title":"Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blinded, placebo-controlled phase 3 trial","volume":"28","author":"Yang","year":"2022","journal-title":"Nat Med"},{"key":"10.1016\/j.apsb.2025.11.026_bib99","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12958-025-01447-3","article-title":"Effects of combined metformin and semaglutide therapy on body weight, metabolic parameters, and reproductive outcomes in overweight\/obese women with polycystic ovary syndrome: a prospective, randomized, controlled, open-label clinical trial","volume":"23","author":"Chen","year":"2025","journal-title":"Reprod Biol Endocrinol"}],"container-title":["Acta Pharmaceutica Sinica B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211383525007762?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211383525007762?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:47:29Z","timestamp":1773917249000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211383525007762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":99,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S2211383525007762"],"URL":"https:\/\/doi.org\/10.1016\/j.apsb.2025.11.026","relation":{},"ISSN":["2211-3835"],"issn-type":[{"value":"2211-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neg-entropy is the true drug target for chronic diseases","name":"articletitle","label":"Article Title"},{"value":"Acta Pharmaceutica Sinica B","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.apsb.2025.11.026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.","name":"copyright","label":"Copyright"}]}}