{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:01:28Z","timestamp":1785423688670,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan","award":["2025ZR107"],"award-info":[{"award-number":["2025ZR107"]}]},{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation of China","doi-asserted-by":"publisher","award":["LQN25H280007"],"award-info":[{"award-number":["LQN25H280007"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"award":["LQN25H280007"],"award-info":[{"award-number":["LQN25H280007"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82505029"],"award-info":[{"award-number":["82505029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82505029"],"award-info":[{"award-number":["82505029"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004863","name":"Zhejiang Chinese Medical University","doi-asserted-by":"publisher","award":["2024JKZKTS22"],"award-info":[{"award-number":["2024JKZKTS22"]}],"id":[{"id":"10.13039\/501100004863","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024JKZKTS22"],"award-info":[{"award-number":["2024JKZKTS22"]}],"id":[{"id":"https:\/\/ror.org\/04epb4p87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: The acute kidney injury (AKI) to chronic kidney disease (CKD) transition has been associated with a failed-repair proximal tubule (FR-PT) cell state. Hyperuricemia is an established CKD risk factor, but whether FR-PT cells have a coordinated metabolic signature reproducibly detectable across mouse models and human kidney disease remains unresolved. Methods: We assembled a pre-registered meta-analysis of 16 public mouse-kidney metabolomic cohorts (383 samples; five model classes; three injury phases) through a three-path harmonization pipeline. Convergent validation drew on KPMP single-nucleus RNA-seq (78,480 proximal tubule cells), two-sample Mendelian randomization of serum urate (102 instruments) against AKI\/CKD\/eGFR GWAS, and cross-cohort human plasma metabolomics across 2058 CKD\/DKD patients. Results: Mouse meta-analysis identified uric acid (g = +2.70) and AICAR (g = +1.50) as the only cross-class conserved metabolites, with uric acid peaking during the AKI-to-CKD transition and returning to baseline in mouse CKD due to uricase clearance. Cross-class overlap between model classes was low (mean pairwise Jaccard = 0.109, below the pre-registered 0.20 threshold), invoking the pre-registered M-S1 stop rule: model-specific metabolic responses dominate, and the conserved signal is a small two-metabolite core superimposed on these largely model-specific programs. KPMP failed-repair PT cells exhibited transcriptional patterns consistent with coordinated four-arm purine-pathway dysregulation (de novo synthesis \u2191, AMPK \u2191, MOCOS \u2191, URAT1 \u2193), with this transcriptional pattern observed in both AKI and CKD donors (Spearman \u03c1 = +0.900). Mendelian randomization was consistent with a possible causal contribution of serum urate to AKI\/CKD\/eGFR risk, with colocalization evidence at GCKR (PP.H4 = 1.000). Cross-cohort human plasma profiling across 2058 patients confirmed the systemic detectability of 29 purine-pathway metabolites in uricase-deficient humans (a translational-plausibility check, not validation of cellular source). Conclusions: The integrated data support a model in which FR-PT-associated purine-pathway reprogramming may contribute to the elevated urate signal observed during AKI-to-CKD transition, with uric acid as the candidate metabolic readout. Differences in uricase activity between mice and humans may help explain why chronic-phase urate signals are attenuated in mice but persist in humans. This work nominates a candidate cell-state metabolic readout of the AKI-to-CKD transition as a hypothesis for prospective testing; it does not establish causation, and therapeutic translation would require dedicated interventional studies.<\/jats:p>","DOI":"10.3390\/metabo16080538","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:55:11Z","timestamp":1785419711000},"page":"538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Purine-Metabolism Reprogramming Associated with Failed-Repair Proximal Tubule States in the AKI-to-CKD Transition"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiahui","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keze","family":"Song","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Han","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-5084","authenticated-orcid":false,"given":"Zhichao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/ki.2011.379","article-title":"Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis","volume":"81","author":"Coca","year":"2012","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1016\/S0140-6736(10)61271-8","article-title":"Alberta Kidney Disease Network. Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: A cohort study","volume":"376","author":"James","year":"2010","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4018","DOI":"10.1038\/s41467-022-31772-9","article-title":"Single-cell analysis highlights differences in druggable pathways underlying adaptive or fibrotic kidney regeneration","volume":"13","author":"Balzer","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15874","DOI":"10.1073\/pnas.2005477117","article-title":"Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury","volume":"117","author":"Kirita","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-023-05769-3","article-title":"An atlas of healthy and injured cell states and niches in the human kidney","volume":"619","author":"Lake","year":"2023","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/s41467-024-45706-0","article-title":"Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing","volume":"15","author":"Ledru","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature17184","article-title":"PGC1\u03b1 drives NAD biosynthesis linking oxidative metabolism to renal protection","volume":"531","author":"Tran","year":"2016","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nm.3762","article-title":"Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development","volume":"21","author":"Kang","year":"2015","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.kint.2016.10.011","article-title":"Pyruvate dehydrogenase kinase 4 deficiency attenuates cisplatin-induced acute kidney injury","volume":"91","author":"Oh","year":"2017","journal-title":"Kidney Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/ndt\/gfaa124","article-title":"Differential role of nicotinamide adenine dinucleotide deficiency in acute and chronic kidney disease","volume":"36","author":"Faivre","year":"2021","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1681\/ASN.2015020177","article-title":"Mitochondrial pathology and glycolytic shift during proximal tubule atrophy after ischemic AKI","volume":"27","author":"Lan","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D463","DOI":"10.1093\/nar\/gkv1042","article-title":"Metabolomics Workbench: An international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools","volume":"44","author":"Sud","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1159\/000238824","article-title":"Uric acid: A novel risk factor for acute kidney injury in high-risk cardiac surgery patients?","volume":"30","author":"Ejaz","year":"2009","journal-title":"Am. J. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1053\/j.ajkd.2017.12.009","article-title":"Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: Report of a scientific workshop organized by the National Kidney Foundation","volume":"71","author":"Johnson","year":"2018","journal-title":"Am. J. Kidney Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/nbt.2377","article-title":"A cross-platform toolkit for mass spectrometry and proteomics","volume":"30","author":"Chambers","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: Data-independent MS\/MS deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41592-023-02012-9","article-title":"Flash entropy search to query all mass spectral libraries in real time","volume":"20","author":"Li","year":"2023","journal-title":"Nat. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/s41586-023-06906-8","article-title":"Reverse metabolomics for the discovery of chemical structures from humans","volume":"626","author":"Gentry","year":"2024","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41592-019-0344-8","article-title":"SIRIUS 4: A rapid tool for turning tandem mass spectra into metabolite structure information","volume":"16","author":"Fleischauer","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1021\/es5002105","article-title":"Identifying small molecules via high resolution mass spectrometry: Communicating confidence","volume":"48","author":"Schymanski","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1038\/s41587-022-01368-1","article-title":"Enhancing untargeted metabolomics using metadata-based source annotation","volume":"40","author":"Gauglitz","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1021\/acs.jproteome.4c01051","article-title":"metLinkR: Facilitating meta-analysis of human metabolomics data through automated linking of metabolite identifiers","volume":"24","author":"Patt","year":"2025","journal-title":"J. Proteome Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13321-016-0174-y","article-title":"ClassyFire: Automated chemical classification with a comprehensive, computable taxonomy","volume":"8","author":"Eisner","year":"2016","journal-title":"J. Cheminform."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4281","DOI":"10.1021\/ac051632c","article-title":"Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures: Application in 1H NMR metabonomics","volume":"78","author":"Dieterle","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/jrsm.1164","article-title":"Methods to estimate the between-study variance and its uncertainty in meta-analysis","volume":"7","author":"Veroniki","year":"2016","journal-title":"Res. Synth. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"R\u00f6ver, C., Knapp, G., and Friede, T. (2015). Hartung-Knapp-Sidik-Jonkman approach and its modification for random-effects meta-analysis with few studies. BMC Med. Res. Methodol., 15.","DOI":"10.1186\/s12874-015-0091-1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J. Stat. Softw."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D480","DOI":"10.1093\/nar\/gkp1002","article-title":"SMPDB: The Small Molecule Pathway Database","volume":"38","author":"Frolkis","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/s41588-019-0504-x","article-title":"Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels","volume":"51","author":"Tin","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1038\/s41467-021-24491-0","article-title":"Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals","volume":"12","author":"Stanzick","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Giambartolomei, C., Vukcevic, D., Schadt, E.E., Franke, L., Hingorani, A.D., Wallace, C., and Plagnol, V. (2014). Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004383"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Pletinck, A., Schepers, E., and Glorieux, G. (2018). Biochemical and clinical impact of organic uremic retention solutes: A comprehensive update. Toxins, 10.","DOI":"10.3390\/toxins10010033"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.2215\/CJN.02660221","article-title":"Classification of uremic toxins and their role in kidney failure","volume":"16","author":"Rosner","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/s41591-018-0138-z","article-title":"De novo NAD+ biosynthetic impairment in acute kidney injury in humans","volume":"24","author":"Tran","year":"2018","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s44321-024-00071-9","article-title":"Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression","volume":"16","author":"Clerici","year":"2024","journal-title":"EMBO Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Halperin Kuhns, V.L., and Woodward, O.M. (2020). Sex differences in urate handling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124269"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/nrm2249","article-title":"AMP-activated\/SNF1 protein kinases: Conserved guardians of cellular energy","volume":"8","author":"Hardie","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cmet.2017.10.009","article-title":"AMPK: Sensing glucose as well as cellular energy status","volume":"27","author":"Lin","year":"2018","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1056\/NEJMra0904569","article-title":"The tumor lysis syndrome","volume":"364","author":"Howard","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1080\/15257770802138558","article-title":"Uric acid: The oxidant\u2013antioxidant paradox","volume":"27","author":"Sautin","year":"2008","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/BF00163854","article-title":"Two independent mutational events in the loss of urate oxidase during hominoid evolution","volume":"34","author":"Wu","year":"1992","journal-title":"J. Mol. Evol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/oxfordjournals.molbev.a004123","article-title":"Loss of urate oxidase activity in hominoids and its evolutionary implications","volume":"19","author":"Oda","year":"2002","journal-title":"Mol. Biol. Evol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1172\/JCI63679","article-title":"Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1\u03b2 secretion","volume":"123","author":"Mulay","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1053\/j.jrn.2010.05.002","article-title":"Indoxyl sulfate is a nephro-vascular toxin","volume":"20","author":"Niwa","year":"2010","journal-title":"J. Ren. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1681\/ASN.2013101062","article-title":"The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review","volume":"25","author":"Vanholder","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chom.2017.06.007","article-title":"Indoleacrylic acid produced by commensal Peptostreptococcus species suppresses inflammation","volume":"22","author":"Wlodarska","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Nakano, T., Watanabe, H., Imafuku, T., Tokumaru, K., Fujita, I., Arimura, N., Maeda, H., Tanaka, M., Matsushita, K., and Fukagawa, M. (2021). Indoxyl sulfate contributes to mTORC1-induced renal fibrosis via the OAT\/NADPH oxidase\/ROS pathway. Toxins, 13.","DOI":"10.3390\/toxins13120909"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1080\/0886022X.2022.2036620","article-title":"Research progress on related mechanisms of uric acid activating NLRP3 inflammasome in chronic kidney disease","volume":"44","author":"Wang","year":"2022","journal-title":"Ren. Fail."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Juszczak, F., Caron, N., Mathew, A.V., and Decl\u00e8ves, A.-E. (2020). Critical role for AMPK in metabolic disease-induced chronic kidney disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217994"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1111\/j.1476-5381.2012.01895.x","article-title":"AMPK activator AICAR ameliorates ischaemia reperfusion injury in the rat kidney","volume":"166","author":"Finckenberg","year":"2012","journal-title":"Br. J. Pharmacol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/8\/538\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:06:53Z","timestamp":1785420413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/8\/538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["metabo16080538"],"URL":"https:\/\/doi.org\/10.3390\/metabo16080538","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}