{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:58:06Z","timestamp":1785524286959,"version":"3.56.0"},"reference-count":68,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Guidance Project of the Guizhou Provincial Basic Research Program","award":["Grant No. Qian Ke He Ji Chu [2026] 002-58"],"award-info":[{"award-number":["Grant No. Qian Ke He Ji Chu [2026] 002-58"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Neurodegenerative diseases, including Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD), and Huntington\u2019s disease (HD), are progressive disorders with limited therapeutic options.\n                      <jats:italic>Centella asiatica<\/jats:italic>\n                      (\n                      <jats:italic>C. asiatica<\/jats:italic>\n                      ), a medicinal and edible plant, has been reported to exert neuroprotective and anti-neuroinflammatory properties. Yet, the mechanisms underlying its effects against neurodegenerative diseases remain largely unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed an integrative strategy combining network pharmacology, transcriptomic analyses, machine learning and molecular docking to prioritize disease-associated molecular networks and candidate compound\u2013target relationships in AD, PD and HD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen candidate constituents of\n                      <jats:italic>C. asiatica<\/jats:italic>\n                      met the predefined drug-likeness, gastrointestinal absorption and blood\u2013brain barrier permeability criteria, yielding 370 unique predicted targets. Disease-gene mining identified 983 AD-associated genes, 1,103 PD-associated genes, and 3,316 HD-associated genes. Integration of compound targets, disease-associated genes, and transcriptomic profiles prioritized five hub genes in PD (CCKAR, MAPK8, PSEN2, SLC6A3, and TH), four in AD (APP, PGK1, PIK3CA, and TTR), and four in HD (CHRND, HSP90AA1, PRKCQ, and TH). Enrichment analyses highlighted disease-relevant processes involving neurotransmitter signalling, cAMP and calcium pathways, MAPK-related responses and inflammatory regulation. ROC analyses provided additional support for the discriminatory performance of the prioritized genes in independent datasets, whereas molecular docking identified favourable predicted Vina docking scores and structurally plausible interactions between selected compounds and hub targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This integrative computational analysis prioritizes candidate\n                      <jats:italic>C. asiatica<\/jats:italic>\n                      constituents, putative disease-associated targets, and molecular pathways in AD, PD, and HD. The findings provide a foundation for subsequent biochemical, cellular, and in vivo validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0354882","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:36:08Z","timestamp":1785519368000},"page":"e0354882","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative network pharmacology, transcriptomics, and molecular docking identify candidate Centella asiatica constituents and targets in neurodegenerative 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global macroeconomic burden of Alzheimer\u2019s disease and other dementias: Estimates and projections for 152 countries or territories","volume":"12","author":"S Chen","year":"2024","journal-title":"Lancet Glob Health"},{"key":"pone.0354882.ref002","doi-asserted-by":"crossref","first-page":"107778","DOI":"10.1016\/j.parkreldis.2025.107778","article-title":"Early-onset Parkinson\u2019s disease, regional and national burden, and its attributable risk factors in 204 countries and regions from 1990 to 2021: Results from the global burden of disease study 2021","volume":"134","author":"J Wang","year":"2025","journal-title":"Parkinsonism Relat Disord"},{"issue":"4","key":"pone.0354882.ref003","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1111\/ene.15645","article-title":"Economic burden of Huntington disease in Europe and the USA: Results from the Huntington\u2019s disease burden of illness study","volume":"30","author":"I Rodr\u00edguez-Santana","year":"2023","journal-title":"Eur J Neurol"},{"issue":"1","key":"pone.0354882.ref004","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40035-024-00432-x","article-title":"Updates in Alzheimer\u2019s disease: From basic research to diagnosis and therapies","volume":"13","author":"E Liu","year":"2024","journal-title":"Transl Neurodegener"},{"issue":"12","key":"pone.0354882.ref005","doi-asserted-by":"crossref","first-page":"168131","DOI":"10.1016\/j.jmb.2023.168131","article-title":"Molecular mechanisms of neurodegeneration in Parkinson\u2019s disease","volume":"435","author":"J-F Trempe","year":"2023","journal-title":"J Mol Biol"},{"issue":"10","key":"pone.0354882.ref006","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","article-title":"Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities","volume":"16","author":"SJ Tabrizi","year":"2020","journal-title":"Nat Rev Neurol"},{"issue":"4","key":"pone.0354882.ref007","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/ana.22615","article-title":"Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders","volume":"70","author":"M Jucker","year":"2011","journal-title":"Ann Neurol"},{"issue":"7465","key":"pone.0354882.ref008","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12481","article-title":"Self-propagation of pathogenic protein aggregates in neurodegenerative diseases","volume":"501","author":"M Jucker","year":"2013","journal-title":"Nature"},{"issue":"1","key":"pone.0354882.ref009","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13024-022-00524-0","article-title":"Solving neurodegeneration: common mechanisms and strategies for new treatments","volume":"17","author":"LK Wareham","year":"2022","journal-title":"Mol Neurodegener"},{"issue":"8","key":"pone.0354882.ref010","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s00702-018-1900-6","article-title":"Levodopa-induced dyskinesia: clinical features, incidence, and risk factors","volume":"125","author":"TN Tran","year":"2018","journal-title":"J Neural Transm (Vienna)"},{"key":"pone.0354882.ref011","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ibneur.2025.05.016","article-title":"A meta-analysis update evaluating the treatment effects of donepezil alone versus donepezil combined with memantine for Alzheimer\u2019s disease","volume":"19","author":"S Hajihosseini","year":"2025","journal-title":"IBRO Neurosci Rep"},{"key":"pone.0354882.ref012","doi-asserted-by":"crossref","first-page":"154295","DOI":"10.1155\/2014\/154295","article-title":"Effect of Centella asiatica on Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models","volume":"2014","author":"Y Zhao","year":"2014","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0354882.ref013","first-page":"4521","article-title":"Protective effects of Centella asiatica leaf extract on dimethylnitrosamine\u2011induced liver injury in rats. 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Junsi","year":"2022","journal-title":"Food Sci Technol"},{"issue":"2","key":"pone.0354882.ref017","doi-asserted-by":"crossref","first-page":"9420033","DOI":"10.26599\/FMH.2025.9420033","article-title":"The food and medicine homologous Chinese Medicine from Leguminosae species: A comprehensive review on bioactive constituents with neuroprotective effects on nervous system","volume":"2","author":"X-S Ye","year":"2025","journal-title":"Food & Medicine Homology"},{"issue":"2","key":"pone.0354882.ref018","doi-asserted-by":"crossref","first-page":"9420029","DOI":"10.26599\/FMH.2025.9420029","article-title":"Protective benefits and mechanisms of Phyllanthus emblica Linn. on aging induced by oxidative stress: A system review","volume":"2","author":"N Wu","year":"2025","journal-title":"Food & Medicine Homology"},{"key":"pone.0354882.ref019","doi-asserted-by":"crossref","first-page":"347569","DOI":"10.4061\/2011\/347569","article-title":"Centella asiatica attenuates D-galactose-induced cognitive impairment, oxidative and mitochondrial dysfunction in mice","volume":"2011","author":"A Kumar","year":"2011","journal-title":"International Journal of Alzheimer\u2019s Disease"},{"key":"pone.0354882.ref020","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neurobiolaging.2020.11.019","article-title":"Loss of NRF2 accelerates cognitive decline, exacerbates mitochondrial dysfunction, and is required for the cognitive enhancing effects of Centella asiatica during aging","volume":"100","author":"JA Zweig","year":"2021","journal-title":"Neurobiol Aging"},{"key":"pone.0354882.ref021","doi-asserted-by":"crossref","first-page":"116746","DOI":"10.1016\/j.jep.2023.116746","article-title":"Centella asiatica alleviates psoriasis through JAK\/STAT3-mediated inflammation: An in vitro and in vivo study","volume":"317","author":"P Lin","year":"2023","journal-title":"J Ethnopharmacol"},{"key":"pone.0354882.ref022","first-page":"60","article-title":"Bioavailability, distribution, and 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effect of a standardized extract of Centella asiatica ECa233 in rotenone-induced parkinsonism rats","volume":"44","author":"N Teerapattarakan","year":"2018","journal-title":"Phytomedicine"},{"issue":"2","key":"pone.0354882.ref026","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3390\/nu12020355","article-title":"Centella asiatica L. phytosome improves cognitive performance by promoting bdnf expression in rat prefrontal cortex","volume":"12","author":"G Sbrini","year":"2020","journal-title":"Nutrients"},{"key":"pone.0354882.ref027","doi-asserted-by":"crossref","first-page":"108541","DOI":"10.1016\/j.biotechadv.2025.108541","article-title":"Biosynthesis and bioactivities of triterpenoids from Centella asiatica: Challenges and opportunities","volume":"80","author":"W Zeng","year":"2025","journal-title":"Biotechnol Adv"},{"issue":"2","key":"pone.0354882.ref028","doi-asserted-by":"crossref","first-page":"9420036","DOI":"10.26599\/FMH.2025.9420036","article-title":"An in-silico assessment suggests the potential effects of goji (fruit of Lycium barbarum L.) against aging-related diseases","volume":"2","author":"R Yao","year":"2025","journal-title":"Food & Medicine Homology"},{"key":"pone.0354882.ref029","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaa1063","article-title":"HERB: A high-throughput experiment- and reference-guided database of traditional Chinese medicine","volume":"49","author":"S Fang","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"pone.0354882.ref030","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0354882.ref031","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules","volume":"47","author":"A Daina","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pone.0354882.ref032","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab835","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"D Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"52","key":"pone.0354882.ref033","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001059","article-title":"PGC-1\u03b1, a potential therapeutic target for early intervention in Parkinson\u2019s disease","volume":"2","author":"B Zheng","year":"2010","journal-title":"Sci Transl Med"},{"issue":"7","key":"pone.0354882.ref034","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s00702-014-1293-0","article-title":"Common mechanisms in neurodegeneration and neuroinflammation: A BrainNet Europe gene expression microarray study","volume":"122","author":"PF Durrenberger","year":"2015","journal-title":"J Neural Transm (Vienna)"},{"issue":"6","key":"pone.0354882.ref035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.0030098","article-title":"A genomic pathway approach to a complex disease: Axon guidance and Parkinson disease","volume":"3","author":"TG Lesnick","year":"2007","journal-title":"PLoS Genet"},{"issue":"11","key":"pone.0354882.ref036","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1073\/pnas.0709259105","article-title":"Alzheimer\u2019s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons","volume":"105","author":"WS Liang","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0354882.ref037","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1093\/cercor\/bht101","article-title":"Altered expression of diabetes-related genes in Alzheimer\u2019s disease brains: The Hisayama study","volume":"24","author":"M Hokama","year":"2014","journal-title":"Cereb Cortex"},{"key":"pone.0354882.ref038","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.bbi.2019.05.009","article-title":"Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains","volume":"80","author":"H Patel","year":"2019","journal-title":"Brain Behav Immun"},{"key":"pone.0354882.ref039","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3389\/fnmol.2017.00430","article-title":"Evidence for a pan-neurodegenerative disease response in huntington\u2019s and Parkinson\u2019s disease expression profiles","volume":"10","author":"A Labadorf","year":"2018","journal-title":"Front Mol Neurosci"},{"issue":"7","key":"pone.0354882.ref040","doi-asserted-by":"crossref","first-page":"743","DOI":"10.15252\/msb.20145304","article-title":"Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases","volume":"10","author":"M Narayanan","year":"2014","journal-title":"Mol Syst Biol"},{"key":"pone.0354882.ref041","first-page":"18","article-title":"The restoration of REST inhibits reactivity of Down syndrome iPSC-derived astrocytes","author":"T Huang","year":"2025","journal-title":"Front Mol Neurosci"},{"key":"pone.0354882.ref042","article-title":"CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting","volume":"50","author":"Y Liu","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"pone.0354882.ref043","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.neuron.2016.03.038","article-title":"Understanding dopaminergic cell death pathways in parkinson disease","volume":"90","author":"PP Michel","year":"2016","journal-title":"Neuron"},{"issue":"10","key":"pone.0354882.ref044","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/nn.3209","article-title":"Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson\u2019s disease","volume":"15","author":"JA Goldberg","year":"2012","journal-title":"Nat Neurosci"},{"issue":"3","key":"pone.0354882.ref045","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"F Leng","year":"2021","journal-title":"Nat Rev Neurol"},{"issue":"20","key":"pone.0354882.ref046","doi-asserted-by":"crossref","first-page":"13217","DOI":"10.1073\/pnas.172504199","article-title":"Amyloid beta -peptide inhibition of the PKA\/CREB pathway and long-term potentiation: Reversibility by drugs that enhance cAMP signaling","volume":"99","author":"OV Vitolo","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0354882.ref047","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.3390\/antiox11091642","article-title":"Deregulation of mitochondrial calcium handling due to presenilin loss disrupts redox homeostasis and promotes neuronal dysfunction","volume":"11","author":"KC Ryan","year":"2022","journal-title":"Antioxidants (Basel)"},{"issue":"3","key":"pone.0354882.ref048","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.bpsgos.2022.03.010","article-title":"Dysfunction of cAMP-Protein Kinase A-Calcium Signaling Axis in Striatal Medium Spiny Neurons: A Role in Schizophrenia and Huntington\u2019s Disease Neuropathology","volume":"3","author":"M Fjodorova","year":"2022","journal-title":"Biol Psychiatry Glob Open Sci"},{"issue":"38","key":"pone.0354882.ref049","doi-asserted-by":"crossref","first-page":"39317","DOI":"10.1074\/jbc.M403891200","article-title":"D1 dopamine receptor mediates dopamine-induced cytotoxicity via the ERK signal cascade","volume":"279","author":"J Chen","year":"2004","journal-title":"J Biol Chem"},{"key":"pone.0354882.ref050","doi-asserted-by":"crossref","first-page":"155019","DOI":"10.1016\/j.phymed.2023.155019","article-title":"Qiji Shujiang granules alleviates dopaminergic neuronal injury of parkinson\u2019s disease by inhibiting NLRP3\/Caspase-1 pathway mediated pyroptosis","volume":"120","author":"P Huan","year":"2023","journal-title":"Phytomedicine"},{"issue":"10","key":"pone.0354882.ref051","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.3390\/ijms19102973","article-title":"Role of mitogen activated protein kinase signaling in Parkinson\u2019s Disease","volume":"19","author":"A Bohush","year":"2018","journal-title":"Int J Mol Sci"},{"key":"pone.0354882.ref052","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3389\/fneur.2018.00693","article-title":"SLC6A3 polymorphism predisposes to dopamine overdose in Parkinson\u2019s disease","volume":"9","author":"BD Robertson","year":"2018","journal-title":"Front Neurol"},{"issue":"12","key":"pone.0354882.ref053","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00018-022-04574-x","article-title":"The role of tyrosine hydroxylase-dopamine pathway in Parkinson\u2019s disease pathogenesis","volume":"79","author":"ZD Zhou","year":"2022","journal-title":"Cell Mol Life Sci"},{"issue":"8","key":"pone.0354882.ref054","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1001\/archneur.61.8.1280","article-title":"Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: An analysis of the cholecystokinin system","volume":"61","author":"JG Goldman","year":"2004","journal-title":"Arch Neurol"},{"issue":"6","key":"pone.0354882.ref055","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1097\/00008571-200306000-00008","article-title":"Cholecystokinin, cholecystokinin-A receptor and cholecystokinin-B receptor gene polymorphisms in Parkinson\u2019s disease","volume":"13","author":"J Wang","year":"2003","journal-title":"Pharmacogenetics"},{"key":"pone.0354882.ref056","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fnins.2018.00230","article-title":"Pleiotropic effects of variants in dementia genes in parkinson disease","volume":"12","author":"L Ibanez","year":"2018","journal-title":"Front Neurosci"},{"issue":"1","key":"pone.0354882.ref057","doi-asserted-by":"crossref","first-page":"10412","DOI":"10.1038\/s41467-024-54777-y","article-title":"Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer\u2019s disease-relevant brain circuits","volume":"15","author":"A Perdok","year":"2024","journal-title":"Nat Commun"},{"issue":"5","key":"pone.0354882.ref058","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nn.3697","article-title":"Single App knock-in mouse models of Alzheimer\u2019s disease","volume":"17","author":"T Saito","year":"2014","journal-title":"Nat Neurosci"},{"issue":"7","key":"pone.0354882.ref059","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1073\/pnas.0712197105","article-title":"Transthyretin protects Alzheimer\u2019s mice from the behavioral and biochemical effects of Abeta toxicity","volume":"105","author":"JN Buxbaum","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pone.0354882.ref060","doi-asserted-by":"crossref","first-page":"5090","DOI":"10.1007\/s12035-023-03389-6","article-title":"Activation of Pgk1 results in reduced protein aggregation in diverse neurodegenerative conditions","volume":"60","author":"H Chen","year":"2023","journal-title":"Mol Neurobiol"},{"issue":"28","key":"pone.0354882.ref061","doi-asserted-by":"crossref","first-page":"25066","DOI":"10.1021\/acsomega.3c01683","article-title":"Revealing the Mechanisms of Byu dMar 25 in the Treatment of Alzheimer\u2019s disease through network pharmacology, molecular docking, and in vivo experiment","volume":"8","author":"Y Du","year":"2023","journal-title":"ACS Omega"},{"key":"pone.0354882.ref062","author":"AY Huang","year":"2024"},{"issue":"12","key":"pone.0354882.ref063","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/hmg\/10.12.1307","article-title":"Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington\u2019s disease","volume":"10","author":"A Sittler","year":"2001","journal-title":"Hum Mol Genet"},{"issue":"8","key":"pone.0354882.ref064","doi-asserted-by":"crossref","first-page":"2972","DOI":"10.1172\/JCI59190","article-title":"Shock and awe: Unleashing the heat shock response to treat Huntington disease","volume":"121","author":"ME Jackrel","year":"2011","journal-title":"J Clin Invest"},{"key":"pone.0354882.ref065","first-page":"101182","article-title":"Acetylcholine receptor subunit expression in Huntington\u2019s disease mouse muscle","volume":"28","author":"B Simpson","year":"2021","journal-title":"Biochem Biophys 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