{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:17:45Z","timestamp":1787699865411,"version":"build-2784847793"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":71,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Discov."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The LIM domain and actin-binding protein 1 (LIMA1), as a cytoskeletal-associated tumor suppressor, has not yet been clearly characterized in bladder cancer (BLCA). This study found that the cytoskeletal protein LIMA1 plays a key tumor-suppressing role in BLCA. Clinical analysis revealed that LIMA1 is significantly downregulated in tumor tissues and serum, with its low expression positively correlated with clinical stage, pathological grade, and recurrence risk, and predictive of poor prognosis. Functionally, LIMA1 knockout promotes tumor cell proliferation, migration, and invasion, and increases tumor volume by 1.8-fold in a mouse subcutaneous xenograft model. Mechanistically, database prediction and molecular docking confirmed that LIMA1 directly binds to PINK1, enhancing mitochondrial autophagy by activating the PINK1-Parkin pathway. The mitochondrial autophagy inducer uric acid A reverses the malignant phenotype caused by LIMA1 deficiency. In summary, this study reveals the inhibitory role of the LIMA1\/PINK1\/mitochondrial autophagy pathway in BLCA progression, providing a theoretical basis for novel therapeutic strategies targeting this pathway.<\/jats:p>","DOI":"10.1038\/s41420-026-03136-5","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:55:54Z","timestamp":1781628954000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deficiency of LIMA1 accelerates bladder cancer progression by disrupting PINK1\/Parkin-mediated mitophagy"],"prefix":"10.1038","volume":"12","author":[{"given":"Shuchen","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinchun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6147-9876","authenticated-orcid":false,"given":"Zhong","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"3136_CR1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41571-023-00744-3","volume":"20","author":"LMC van Hoogstraten","year":"2023","unstructured":"van Hoogstraten LMC, Vrieling A, van der Heijden AG, Kogevinas M, Richters A, Kiemeney LA. Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice. Nat Rev Clin Oncol. 2023;20:287\u2013304.","journal-title":"Nat Rev Clin Oncol"},{"key":"3136_CR2","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.eururo.2020.12.033","volume":"79","author":"RJ Sylvester","year":"2021","unstructured":"Sylvester RJ, Rodriguez O, Hernandez V, Turturica D, Bauerova L, Bruins HM, et al. European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004\/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel. Eur Urol. 2021;79:480\u20138.","journal-title":"Eur Urol"},{"key":"3136_CR3","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1001\/jama.2020.17598","volume":"324","author":"AT Lenis","year":"2020","unstructured":"Lenis AT, Lec PM, Chamie K, Mshs MD. Bladder cancer: a review. JAMA. 2020;324:1980\u201391.","journal-title":"JAMA"},{"key":"3136_CR4","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1038\/sj.onc.1201715","volume":"16","author":"DD Chang","year":"1998","unstructured":"Chang DD, Park NH, Denny CT, Nelson SF, Pe M. Characterization of transformation related genes in oral cancer cells. Oncogene. 1998;16:1921\u201330.","journal-title":"Oncogene"},{"key":"3136_CR5","doi-asserted-by":"publisher","first-page":"7838","DOI":"10.1038\/sj.onc.1203206","volume":"18","author":"RS Maul","year":"1999","unstructured":"Maul RS, Chang DD. EPLIN, epithelial protein lost in neoplasm. Oncogene. 1999;18:7838\u201341.","journal-title":"Oncogene"},{"key":"3136_CR6","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1083\/jcb.200212057","volume":"160","author":"RS Maul","year":"2003","unstructured":"Maul RS, Song Y, Amann KJ, Gerbin SC, Pollard TD, Chang DD. EPLIN regulates actin dynamics by cross-linking and stabilizing filaments. J Cell Biol. 2003;160:399\u2013407.","journal-title":"J Cell Biol"},{"key":"3136_CR7","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1007\/s10555-015-9595-8","volume":"34","author":"RJ Collins","year":"2015","unstructured":"Collins RJ, Jiang WG, Hargest R, Mason MD, Sanders AJ. EPLIN: a fundamental actin regulator in cancer metastasis? Cancer Metastasis Rev. 2015;34:753\u201364.","journal-title":"Cancer Metastasis Rev"},{"key":"3136_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-7-71","volume":"7","author":"WG Jiang","year":"2008","unstructured":"Jiang WG, Martin TA, Lewis-Russell JM, Douglas-Jones A, Ye L, Mansel RE. Eplin-alpha expression in human breast cancer, the impact on cellular migration and clinical outcome. Mol Cancer. 2008;7:71.","journal-title":"Mol Cancer"},{"key":"3136_CR9","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.3892\/ijo.2016.3462","volume":"48","author":"R Liu","year":"2016","unstructured":"Liu R, Martin TA, Jordan NJ, Ruge F, Ye L, Jiang WG. Epithelial protein lost in neoplasm-alpha (EPLIN-alpha) is a potential prognostic marker for the progression of epithelial ovarian cancer. Int J Oncol. 2016;48:2488\u201396.","journal-title":"Int J Oncol"},{"key":"3136_CR10","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.gendis.2017.03.002","volume":"4","author":"D Wu","year":"2017","unstructured":"Wu D. Epithelial protein lost in neoplasm (EPLIN): Beyond a tumor suppressor. Genes Dis. 2017;4:100\u20137.","journal-title":"Genes Dis"},{"key":"3136_CR11","doi-asserted-by":"publisher","first-page":"4941","DOI":"10.1038\/onc.2011.199","volume":"30","author":"S Zhang","year":"2011","unstructured":"Zhang S, Wang X, Osunkoya AO, Iqbal S, Wang Y, Chen Z, et al. EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. Oncogene. 2011;30:4941\u201352.","journal-title":"Oncogene"},{"key":"3136_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11164-2","volume":"10","author":"MT Vo","year":"2019","unstructured":"Vo MT, Smith BJ, Nicholas J, Choi YB. Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus. Nat Commun. 2019;10:3203.","journal-title":"Nat Commun"},{"key":"3136_CR13","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/15548627.2019.1603547","volume":"16","author":"Y Xu","year":"2020","unstructured":"Xu Y, Shen J, Ran Z. Emerging views of mitophagy in immunity and autoimmune diseases. Autophagy. 2020;16:3\u201317.","journal-title":"Autophagy"},{"key":"3136_CR14","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.redox.2017.11.018","volume":"15","author":"TA Tabish","year":"2018","unstructured":"Tabish TA, Zhang S, Winyard PG. Developing the next generation of graphene-based platforms for cancer therapeutics: The potential role of reactive oxygen species. Redox Biol. 2018;15:34\u201340.","journal-title":"Redox Biol"},{"key":"3136_CR15","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00395-018-0682-1","volume":"113","author":"H Zhou","year":"2018","unstructured":"Zhou H, Wang J, Zhu P, Zhu H, Toan S, Hu S, et al. NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2alpha. Basic Res Cardiol. 2018;113:23.","journal-title":"Basic Res Cardiol"},{"key":"3136_CR16","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1038\/s41418-018-0086-7","volume":"25","author":"H Zhou","year":"2018","unstructured":"Zhou H, Zhu P, Wang J, Zhu H, Ren J, Chen Y. Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2alpha-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ. 2018;25:1080\u201393.","journal-title":"Cell Death Differ"},{"key":"3136_CR17","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s11658-024-00596-4","volume":"29","author":"S Li","year":"2024","unstructured":"Li S, Yang F, Cheng F, Zhu L, Yan Y. Lipotoxic hepatocyte derived LIMA1 enriched small extracellular vesicles promote hepatic stellate cells activation via inhibiting mitophagy. Cell Mol Biol Lett. 2024;29:82.","journal-title":"Cell Mol Biol Lett"},{"key":"3136_CR18","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1089\/ars.2019.7898","volume":"32","author":"HY Chiu","year":"2020","unstructured":"Chiu HY, Tay EXY, Ong DST, Taneja R. Mitochondrial Dysfunction at the Center of Cancer Therapy. Antioxid Redox Signal. 2020;32:309\u201330.","journal-title":"Antioxid Redox Signal"},{"key":"3136_CR19","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.4161\/auto.26550","volume":"9","author":"H Lu","year":"2013","unstructured":"Lu H, Li G, Liu L, Feng L, Wang X, Jin H. Regulation and function of mitophagy in development and cancer. Autophagy. 2013;9:1720\u201336.","journal-title":"Autophagy"},{"key":"3136_CR20","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1136\/gut.2009.202739","volume":"59","author":"L Zhao","year":"2010","unstructured":"Zhao L, Wang H, Liu C, Liu Y, Wang X, Wang S, et al. Promotion of colorectal cancer growth and metastasis by the LIM and SH3 domain protein 1. Gut. 2010;59:1226\u201335.","journal-title":"Gut"},{"key":"3136_CR21","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/onc.2014.64","volume":"34","author":"Z L, Y Z, Y T, K C, Z L, C W.","year":"2015","unstructured":"Z L, Y Z, Y T, K C, Z L, C W. PDZ and LIM domain protein 1(PDLIM1)\/CLP36 promotes breast cancer cell migration, invasion and metastasis through interaction with \u03b1-actinin. Oncogene. 2015;34:1300\u201311.","journal-title":"Oncogene"},{"key":"3136_CR22","doi-asserted-by":"publisher","first-page":"40547","DOI":"10.3390\/biom11040547","volume":"11","author":"W Gong","year":"2021","unstructured":"Gong W, Zeng J, Ji J, Jia Y, Jia S, Sanders AJ, et al. EPLIN Expression in Gastric Cancer and Impact on Prognosis and Chemoresistance. Biomolecules. 2021;11:40547.","journal-title":"Biomolecules"},{"key":"3136_CR23","doi-asserted-by":"publisher","first-page":"3857.","DOI":"10.3390\/cells11233857","volume":"11","author":"Y Qi","year":"2022","unstructured":"Qi Y, Wang H, Zhang Q, Liu Z, Wang T, Wu Z, et al. CAF-Released Exosomal miR-20a-5p Facilitates HCC Progression via the LIMA1-Mediated \u03b2-Catenin Pathway. Cells. 2022;11:3857.","journal-title":"Cells"},{"key":"3136_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07876-7","volume":"16","author":"Emma Lindell","year":"2025","unstructured":"Lindell Emma, Guo J, Zhao M, Rameika N, Lu X, Wacker T, et al. Identification of a small molecule targeting EPLIN as a novel strategy for the treatment of pediatric neuroblastoma and medulloblastoma. Cell Death Dis. 2025;16:554.","journal-title":"Cell Death Dis"},{"key":"3136_CR25","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.3892\/ijo.2016.3462","volume":"48","author":"R Liu","year":"2016","unstructured":"Liu R, Martin TA, Jordan NJ, Ruge F, Ye L, Jiang WG. Epithelial protein lost in neoplasm-\u03b1 (EPLIN-\u03b1) is a potential prognostic marker for the progression of epithelial ovarian cancer. Int J Oncol. 2016;48:2488\u201396.","journal-title":"Int J Oncol"},{"key":"3136_CR26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1080\/19336918.2024.2383068","volume":"18","author":"H Obulkasim","year":"2024","unstructured":"Obulkasim H, Adili A, Liu Y, Duan S. Expression and molecular insights of lima1 in cholangiocarcinoma. Cell Adhes Migr. 2024;18:4\u201317.","journal-title":"Cell Adhes Migr"},{"key":"3136_CR27","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1111\/odi.15263","volume":"31","author":"Y You","year":"2025","unstructured":"You Y, Du Z, Tian Z, Yu F, Li S, He J, et al. LIMA1 Is a Prognostic Senescence-Inhibitory Gene in Head and Neck Squamous Carcinoma. Oral Dis. 2025;31:1692\u2013703.","journal-title":"Oral Dis"},{"key":"3136_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-81485-w","volume":"14","author":"J Zeng","year":"2024","unstructured":"Zeng J, Wang C, Ruge F, Ji EK, Martin TA, Sanders AJ, et al. EPLIN, a prospective oncogenic molecule with contribution to growth, migration and drug resistance in pancreatic cancer. Sci Rep. 2024;14:30850.","journal-title":"Sci Rep"},{"key":"3136_CR29","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/s41420-024-02072-6","volume":"10","author":"Z Liu","year":"2024","unstructured":"Liu Z, Fan K, Abudukeremu A, Gao M, Tan X, Mao X, et al. LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism. Cell Death Discov. 2024;10:298.","journal-title":"Cell Death Discov"},{"key":"3136_CR30","doi-asserted-by":"publisher","first-page":"5201","DOI":"10.1073\/pnas.1619356114","volume":"114","author":"N-P Chen","year":"2017","unstructured":"Chen N-P, Uddin B, Hardt R, Ding W, Panic M, Lucibello I, et al. Human phosphatase CDC14A regulates actin organization through dephosphorylation of epithelial protein lost in neoplasm. Proc Natl Acad Sci. 2017;114:5201\u20136.","journal-title":"Proc Natl Acad Sci"},{"key":"3136_CR31","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202008060","volume":"220","author":"ES Linklater","year":"2021","unstructured":"Linklater ES, Duncan ED, Han K-J, Kaupinis A, Valius M, Lyons TR, et al. Rab40\u2013Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration. J Cell Biol. 2021;220:e202008060.","journal-title":"J Cell Biol"},{"key":"3136_CR32","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/ki.2014.85","volume":"86","author":"H Tsurumi","year":"2014","unstructured":"Tsurumi H, Harita Y, Kurihara H, Kosako H, Hayashi K, Matsunaga A, et al. Epithelial protein lost in neoplasm modulates platelet-derived growth factor\u2013mediated adhesion and motility of mesangial cells. Kidney Int. 2014;86:548\u201357.","journal-title":"Kidney Int"},{"key":"3136_CR33","doi-asserted-by":"publisher","first-page":"107033","DOI":"10.18632\/oncotarget.22300","volume":"8","author":"L Liang","year":"2017","unstructured":"Liang L, Zhao L, Zan Y, Zhu Q, Ren J, Zhao X. MiR-93-5p enhances growth and angiogenesis capacity of HUVECs by down-regulating EPLIN. Oncotarget. 2017;8:107033\u201343.","journal-title":"Oncotarget"},{"key":"3136_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28139-5","volume":"13","author":"B Duethorn","year":"2022","unstructured":"Duethorn B, Groll F, Rieger B, Drexler HCA, Brinkmann H, Kremer L, et al. Lima1 mediates the pluripotency control of membrane dynamics and cellular metabolism. Nat Commun. 2022;13:610.","journal-title":"Nat Commun"},{"key":"3136_CR35","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1038\/s41388-025-03460-7","volume":"44","author":"B Zhang","year":"2025","unstructured":"Zhang B, Dong G, Guo X, Li H, Chen W, Diao W, et al. SFXN1 promotes bladder cancer metastasis by restraining PINK1-dependent mitophagy. Oncogene. 2025;44:2893\u2013906.","journal-title":"Oncogene"},{"key":"3136_CR36","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.7150\/ijbs.107632","volume":"21","author":"D Li","year":"2025","unstructured":"Li D, Su H, Deng X, Huang Y, Wang Z, Zhang J, et al. DARS2 Promotes Bladder Cancer Progression by Enhancing PINK1-Mediated Mitophagy. Int J Biol Sci. 2025;21:1530\u201344.","journal-title":"Int J Biol Sci"},{"key":"3136_CR37","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41388-023-02907-z","volume":"43","author":"FR Palma","year":"2024","unstructured":"Palma FR, Gantner BN, Sakiyama MJ, Kayzuka C, Shukla S, Lacchini R, et al. ROS production by mitochondria: function or dysfunction? Oncogene. 2024;43:295\u2013303.","journal-title":"Oncogene"},{"key":"3136_CR38","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41586-018-0224-x","volume":"559","author":"C Gladkova","year":"2018","unstructured":"Gladkova C, Maslen SL, Skehel JM, Komander D. Mechanism of parkin activation by PINK1. Nature. 2018;559:410\u20134.","journal-title":"Nature"},{"key":"3136_CR39","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202519527","volume":"13","author":"W Wang","year":"2026","unstructured":"Wang W, Yan R, Lin L, Xiang L, Xia X, Peng L, et al. A Sirtuin-1-Targeted Gene-Activating Tetrahedral DNA Attenuates Bladder Fibrosis by Restoring Mitophagy in Fibroblasts via the SIRT1-FOXO3-BNIP3 Axis. Adv Sci. 2026;13:e19527.","journal-title":"Adv Sci"},{"key":"3136_CR40","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1080\/15548627.2021.2007027","volume":"18","author":"J Yao","year":"2022","unstructured":"Yao J, Wang J, Xu Y, Guo Q, Sun Y, Liu J, et al. CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma. Autophagy. 2022;18:1879\u201397.","journal-title":"Autophagy"},{"key":"3136_CR41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s42003-024-05935-x","volume":"7","author":"R Zhang","year":"2024","unstructured":"Zhang R, Jiang W, Wang G, Zhang Y, Liu W, Li M, et al. Parkin inhibits proliferation and migration of bladder cancer via ubiquitinating Catalase. Commun Biol. 2024;7:245.","journal-title":"Commun Biol"}],"container-title":["Cell Death Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03136-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03136-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03136-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:30:27Z","timestamp":1787697027000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41420-026-03136-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3136"],"URL":"https:\/\/doi.org\/10.1038\/s41420-026-03136-5","relation":{},"ISSN":["2058-7716"],"issn-type":[{"value":"2058-7716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"6 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 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 was approved by Ethics Committee of Jiangsu University (approved number: 2024-SR-016 and UJS-IACUC-AP-2024022801), and all steps and methods were carried out in accordance with the relevant guidelines and regulations.","order":2,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"We declare that this study obtained written informed consent from all involved individuals.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"345"}}