{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T22:17:48Z","timestamp":1788214668179,"version":"build-2803163510"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"36","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2026,9,22]]},"DOI":"10.1038\/s41388-026-03902-w","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:49:36Z","timestamp":1785296976000},"page":"3828-3841","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HERC4 synergizes with USP16 to promote lung adenocarcinoma growth by augmenting protein translation via stabilizing RPS15"],"prefix":"10.1038","volume":"45","author":[{"given":"Qiuyun","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2692-6648","authenticated-orcid":false,"given":"Wenshuang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunshu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuening","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-0559","authenticated-orcid":false,"given":"Hongbiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3499-5133","authenticated-orcid":false,"given":"Jia","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1391-8238","authenticated-orcid":false,"given":"Wenhua","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinliang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"3902_CR1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nrc.2017.104","volume":"18","author":"J Pelletier","year":"2018","unstructured":"Pelletier J, Thomas G, Volarevi\u0107 S. Ribosome biogenesis in cancer: new players and therapeutic avenues. Nat Rev Cancer. 2018;18:51\u201363.","journal-title":"Nat Rev Cancer"},{"key":"3902_CR2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.trecan.2020.08.003","volume":"7","author":"S Bursa\u0107","year":"2021","unstructured":"Bursa\u0107 S, Prodan Y, Pullen N, Bartek J, Volarevi\u0107 S. Dysregulated ribosome biogenesis reveals therapeutic liabilities in cancer. Trends Cancer. 2021;7:57\u201376.","journal-title":"Trends Cancer"},{"key":"3902_CR3","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1126\/science.aay0939","volume":"367","author":"RY Ebright","year":"2020","unstructured":"Ebright RY, Lee S, Wittner BS, Niederhoffer KL, Nicholson BT, Bardia A, et al. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis. Science. 2020;367:1468\u201373.","journal-title":"Science"},{"key":"3902_CR4","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.omtn.2020.05.019","volume":"21","author":"J Xie","year":"2020","unstructured":"Xie J, Zhang W, Liang X, Shuai C, Zhou Y, Pan H, et al. RPL32 promotes lung cancer progression by facilitating p53 degradation. Mol Ther Nucleic Acids. 2020;21:75\u201385.","journal-title":"Mol Ther Nucleic Acids"},{"key":"3902_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/srep37690","volume":"6","author":"S Luo","year":"2016","unstructured":"Luo S, Zhao J, Fowdur M, Wang K, Jiang T, He M. Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma and its knockdown suppresses osteosarcoma proliferation probably through translational control. Sci Rep. 2016;6:37690.","journal-title":"Sci Rep"},{"key":"3902_CR6","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.gene.2015.10.053","volume":"576","author":"S Yang","year":"2016","unstructured":"Yang S, Cui J, Yang Y, Liu Z, Yan H, Tang C, et al. Over-expressed RPL34 promotes malignant proliferation of non-small cell lung cancer cells. Gene. 2016;576:421\u20138.","journal-title":"Gene"},{"key":"3902_CR7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.archoralbio.2017.06.035","volume":"83","author":"J Dai","year":"2017","unstructured":"Dai J, Wei W. Influence of the RPL34 gene on the growth and metastasis of oral squamous cell carcinoma cells. Arch Oral Biol. 2017;83:40\u201346.","journal-title":"Arch Oral Biol"},{"key":"3902_CR8","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.1002\/jcb.27592","volume":"120","author":"P Ji","year":"2019","unstructured":"Ji P, Wang L, Liu J, Mao P, Li R, Jiang H, et al. Knockdown of RPL34 inhibits the proliferation and migration of glioma cells through the inactivation of JAK\/STAT3 signaling pathway. J Cell Biochem. 2019;120:3259\u201367.","journal-title":"J Cell Biochem"},{"key":"3902_CR9","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.cell.2017.05.022","volume":"169","author":"D Simsek","year":"2017","unstructured":"Simsek D, Tiu GC, Flynn RA, Byeon GW, Leppek K, Xu AF, et al. The mammalian ribo-interactome reveals ribosome functional diversity and heterogeneity. Cell. 2017;169:1051\u20131065.e1018.","journal-title":"Cell"},{"key":"3902_CR10","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.semcdb.2021.12.009","volume":"132","author":"A Mart\u00ednez-F\u00e9rriz","year":"2022","unstructured":"Mart\u00ednez-F\u00e9rriz A, Ferrando A, Fathinajafabadi A, Farr\u00e0s R. Ubiquitin-mediated mechanisms of translational control. Semin Cell Dev Biol. 2022;132:146\u201354.","journal-title":"Semin Cell Dev Biol"},{"key":"3902_CR11","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/j.molcel.2019.12.024","volume":"77","author":"C Meyer","year":"2020","unstructured":"Meyer C, Garzia A, Morozov P, Molina H, Tuschl T. The G3BP1-family-USP10 deubiquitinase complex rescues ubiquitinated 40S subunits of ribosomes stalled in translation from lysosomal degradation. Mol Cell. 2020;77:1193\u20131205.e1195.","journal-title":"Mol Cell"},{"key":"3902_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109468","volume":"36","author":"A Garzia","year":"2021","unstructured":"Garzia A, Meyer C, Tuschl T. The E3 ubiquitin ligase RNF10 modifies 40S ribosomal subunits of ribosomes compromised in translation. Cell Rep. 2021;36:109468.","journal-title":"Cell Rep"},{"key":"3902_CR13","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1038\/s41388-022-02581-7","volume":"42","author":"T Wang","year":"2023","unstructured":"Wang T, Jin C, Yang P, Chen Z, Ji J, Sun Q, et al. UBE2J1 inhibits colorectal cancer progression by promoting ubiquitination and degradation of RPS3. Oncogene. 2023;42:651\u201364.","journal-title":"Oncogene"},{"key":"3902_CR14","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s13046-021-02008-3","volume":"40","author":"Y Liao","year":"2021","unstructured":"Liao Y, Shao Z, Liu Y, Xia X, Deng Y, Yu C, et al. USP1-dependent RPS16 protein stability drives growth and metastasis of human hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2021;40:201.","journal-title":"J Exp Clin Cancer Res"},{"key":"3902_CR15","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1007\/s00018-005-5119-y","volume":"62","author":"FR Garcia-Gonzalo","year":"2005","unstructured":"Garcia-Gonzalo FR, Rosa JL. The HERC proteins: functional and evolutionary insights. Cell Mol Life Sci. 2005;62:1826\u201338.","journal-title":"Cell Mol Life Sci"},{"key":"3902_CR16","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.ygeno.2004.10.006","volume":"85","author":"K Hochrainer","year":"2005","unstructured":"Hochrainer K, Mayer H, Baranyi U, Binder B, Lipp J, Kroismayr R. The human HERC family of ubiquitin ligases: novel members, genomic organization, expression profiling, and evolutionary aspects. Genomics. 2005;85:153\u201364.","journal-title":"Genomics"},{"key":"3902_CR17","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1182\/blood-2015-07-658203","volume":"127","author":"Z Zhang","year":"2016","unstructured":"Zhang Z, Tong J, Tang X, Juan J, Cao B, Hurren R, et al. The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice. Blood. 2016;127:1676\u201386.","journal-title":"Blood"},{"key":"3902_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104675","volume":"299","author":"Z Zhang","year":"2023","unstructured":"Zhang Z, Li M, Lin P, Ren Y, He Y, Wang S, et al. The ubiquitin ligase HERC4 suppresses MafA transcriptional activity triggered by GSK3\u03b2 in myeloma by atypical K63-linked polyubiquitination. J Biol Chem. 2023;299:104675.","journal-title":"J Biol Chem"},{"key":"3902_CR19","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1007\/s13238-019-0607-2","volume":"10","author":"Y Xu","year":"2019","unstructured":"Xu Y, Ji K, Wu M, Hao B, Yao KT, Xu Y. A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1. Protein Cell. 2019;10:595\u2013605.","journal-title":"Protein Cell"},{"key":"3902_CR20","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1089\/dna.2016.3626","volume":"36","author":"Y Zheng","year":"2017","unstructured":"Zheng Y, Li J, Pan C, Zhou G, Zhuge L, Jin L, et al. HERC4 is overexpressed in hepatocellular carcinoma and contributes to the proliferation and migration of hepatocellular carcinoma cells. DNA Cell Biol. 2017;36:490\u2013500.","journal-title":"DNA Cell Biol"},{"key":"3902_CR21","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1038\/s41419-021-03732-6","volume":"12","author":"S Jiang","year":"2021","unstructured":"Jiang S, Wang X, He Y, Huang H, Cao B, Zhang Z, et al. Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis. Cell Death Dis. 2021;12:456.","journal-title":"Cell Death Dis"},{"key":"3902_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102314","volume":"298","author":"H Zhuang","year":"2022","unstructured":"Zhuang H, Ren Y, Mao C, Zhong Y, Zhang Z, Cao B, et al. Induction of zinc finger protein RNF6 auto-ubiquitination for the treatment of myeloma and chronic myeloid leukemia. J Biol Chem. 2022;298:102314.","journal-title":"J Biol Chem"},{"key":"3902_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101088","volume":"297","author":"Y He","year":"2021","unstructured":"He Y, Jiang S, Mao C, Zheng H, Cao B, Zhang Z, et al. The deubiquitinase USP10 restores PTEN activity and inhibits non-small cell lung cancer cell proliferation. J Biol Chem. 2021;297:101088.","journal-title":"J Biol Chem"},{"key":"3902_CR24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13046-021-01843-8","volume":"40","author":"J Ge","year":"2021","unstructured":"Ge J, Yu W, Li J, Ma H, Wang P, Zhou Y, et al. USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc. J Exp Clin Cancer Res. 2021;40:59.","journal-title":"J Exp Clin Cancer Res"},{"key":"3902_CR25","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1158\/0008-5472.CAN-21-4087","volume":"82","author":"AR Elhamamsy","year":"2022","unstructured":"Elhamamsy AR, Metge BJ, Alsheikh HA, Shevde LA, Samant RS. Ribosome biogenesis: a central player in cancer metastasis and therapeutic resistance. Cancer Res. 2022;82:2344\u201353.","journal-title":"Cancer Res"},{"key":"3902_CR26","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1182\/blood-2017-09-804401","volume":"132","author":"G Bretones","year":"2018","unstructured":"Bretones G, \u00c1lvarez MG, Arango JR, Rodr\u00edguez D, Nadeu F, Prado MA, et al. Altered patterns of global protein synthesis and translational fidelity in RPS15-mutated chronic lymphocytic leukemia. Blood. 2018;132:2375\u201388.","journal-title":"Blood"},{"key":"3902_CR27","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.1182\/bloodadvances.2020001717","volume":"5","author":"S Ntoufa","year":"2021","unstructured":"Ntoufa S, Gerousi M, Laidou S, Psomopoulos F, Tsiolas G, Moysiadis T, et al. RPS15 mutations rewire RNA translation in chronic lymphocytic leukemia. Blood Adv. 2021;5:2788\u201392.","journal-title":"Blood Adv"},{"key":"3902_CR28","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1038\/s41392-023-01428-1","volume":"8","author":"Y Zhao","year":"2023","unstructured":"Zhao Y, Li Y, Zhu R, Feng R, Cui H, Yu X, et al. RPS15 interacted with IGF2BP1 to promote esophageal squamous cell carcinoma development via recognizing m(6)A modification. Signal Transduct Target Ther. 2023;8:224.","journal-title":"Signal Transduct Target Ther"},{"key":"3902_CR29","doi-asserted-by":"publisher","first-page":"4253","DOI":"10.1038\/onc.2010.189","volume":"29","author":"C Deisenroth","year":"2010","unstructured":"Deisenroth C, Zhang Y. Ribosome biogenesis surveillance: probing the ribosomal protein-Mdm2-p53 pathway. Oncogene. 2010;29:4253\u201360.","journal-title":"Oncogene"},{"key":"3902_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.216991","volume":"594","author":"M Liu","year":"2024","unstructured":"Liu M, Zhao Z, Wang C, Sang S, Cui Y, Lv C, et al. Harnessing genetic interactions for prediction of immune checkpoint inhibitors response signature in cancer cells. Cancer Lett. 2024;594:216991.","journal-title":"Cancer Lett"},{"key":"3902_CR31","doi-asserted-by":"publisher","first-page":"513","DOI":"10.7314\/APJCP.2015.16.2.513","volume":"16","author":"WL Zeng","year":"2015","unstructured":"Zeng WL, Chen YW, Zhou H, Zhou JY, Wei M, Shi R. Expression of HERC4 in lung cancer and its correlation with clinicopathological parameters. Asian Pac J Cancer Prev. 2015;16:513\u20137.","journal-title":"Asian Pac J Cancer Prev"},{"key":"3902_CR32","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1182\/blood-2015-10-674572","volume":"127","author":"V Ljungstr\u00f6m","year":"2016","unstructured":"Ljungstr\u00f6m V, Cortese D, Young E, Pandzic T, Mansouri L, Plevova K, et al. Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations. Blood. 2016;127:1007\u201316.","journal-title":"Blood"},{"key":"3902_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115050","volume":"43","author":"PW Ford","year":"2024","unstructured":"Ford PW, Narasimhan M, Bennett EJ. Ubiquitin-dependent translation control mechanisms: Degradation and beyond. Cell Rep. 2024;43:115050.","journal-title":"Cell Rep"},{"key":"3902_CR34","doi-asserted-by":"publisher","first-page":"3282","DOI":"10.7150\/ijbs.72014","volume":"18","author":"Z Zhang","year":"2022","unstructured":"Zhang Z, Wu Q, Fang M, Liu Y, Jiang J, Feng Q, et al. HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle. Int J Biol Sci. 2022;18:3282\u201397.","journal-title":"Int J Biol Sci"},{"key":"3902_CR35","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.molcel.2010.05.002","volume":"38","author":"LA Durfee","year":"2010","unstructured":"Durfee LA, Lyon N, Seo K, Huibregtse JM. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. Mol Cell. 2010;38:722\u201332.","journal-title":"Mol Cell"},{"key":"3902_CR36","doi-asserted-by":"crossref","unstructured":"Zheng J, Chen C, Guo C, Caba C, Tong Y, Wang H. The pleiotropic ubiquitin-specific peptidase 16 and its many substrates. Cells. 2023;12:886.","DOI":"10.3390\/cells12060886"},{"key":"3902_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2022.215862","volume":"547","author":"S Liu","year":"2022","unstructured":"Liu S, Li H, Zhu Y, Ma X, Shao Z, Yang Z, et al. LncRNA MNX1-AS1 sustains inactivation of Hippo pathway through a positive feedback loop with USP16\/IGF2BP3 axis in gallbladder cancer. Cancer Lett. 2022;547:215862.","journal-title":"Cancer Lett"},{"key":"3902_CR38","doi-asserted-by":"publisher","first-page":"5482","DOI":"10.1038\/s41388-021-01964-6","volume":"40","author":"G Xu","year":"2021","unstructured":"Xu G, Yang Z, Ding Y, Liu Y, Zhang L, Wang B, et al. The deubiquitinase USP16 functions as an oncogenic factor in K-RAS-driven lung tumorigenesis. Oncogene. 2021;40:5482\u201394.","journal-title":"Oncogene"},{"key":"3902_CR39","doi-asserted-by":"publisher","first-page":"6601","DOI":"10.1093\/nar\/gkac053","volume":"50","author":"Y Luan","year":"2022","unstructured":"Luan Y, Tang N, Yang J, Liu S, Cheng C, Wang Y, et al. Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human cells. Nucleic Acids Res. 2022;50:6601\u201317.","journal-title":"Nucleic Acids Res"},{"key":"3902_CR40","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.trecan.2016.03.002","volume":"2","author":"Y Liu","year":"2016","unstructured":"Liu Y, Deisenroth C, Zhang Y. RP-MDM2-p53 pathway: linking ribosomal biogenesis and tumor surveillance. Trends Cancer. 2016;2:191\u2013204.","journal-title":"Trends Cancer"}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-03902-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-03902-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-03902-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T22:02:32Z","timestamp":1788213752000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41388-026-03902-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":40,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2026,9,22]]}},"alternative-id":["3902"],"URL":"https:\/\/doi.org\/10.1038\/s41388-026-03902-w","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"assertion":[{"value":"19 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This study strictly adhered to medical ethics principles. All participants were informed of the purpose, methods, possible risks and benefits of the study, and voluntarily signed the informed consent form after full understanding in accordance with the Helsinki Declaration principles and this study was approved by the Medical Ethics Board of the First Affiliated Hospital of Guangzhou Medical University (Approval No. #ES2021-145). All experimental procedures involving animals were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals of China and the Guidelines for the Care and Use of Laboratory Animals. Animal experiments were approved by the Review Board for Animal Welfare and Ethics of Guangzhou Medical University (Approval #GY2024-721).","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Ethics"}}]}}