{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:54:23Z","timestamp":1786946063029,"version":"build-2736575974"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573434"],"award-info":[{"award-number":["82573434"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic reprogramming underpins the acquisition of radioresistance in esophageal squamous cell carcinoma (ESCC); however, the specific bioenergetic vulnerabilities and direct pharmacological targets remain to be fully elucidated. This study defines a distinct metabolic phenotype conferring radioresistance and evaluates the natural alkaloid Cepharanthine (CEP) as a mechanism-driven radiosensitizer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Matched clinical cohorts of radiosensitive and radioresistant ESCC patients were analyzed using widely-targeted and targeted metabolomics. Bioenergetic profiling (ECAR\/OCR) was performed on established isogenic radioresistant cells. The mechanistic interactions between CEP and its target were mapped via network pharmacology, surface plasmon resonance (SPR), cellular thermal shift assays (CETSA), ubiquitin-proteasomal degradation assays, and Q347A site-directed mutagenesis. In vivo efficacy was validated across human cell-derived xenografts (CDX) and immunocompetent syngeneic (AKR\/C57BL\/6) mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical multi-omics revealed a \"metabolic duality\" in radioresistant ESCC, characterized by the concurrent hyperactivation of glycolysis and oxidative phosphorylation (OXPHOS). CEP administration disrupted this metabolic network, significantly sensitizing ESCC cells to irradiation [Dose-modifying factor at 37% survival (DMF\n                      <jats:sub>37<\/jats:sub>\n                      ) &gt; 1]. Mechanistically, CEP directly engages the kinase domain of p70S6K\u2014a structural interaction dependent on the Q347 residue\u2014and triggers its ubiquitin-proteasomal degradation. This targeted clearance disrupts the upstream PI3K\/Akt\/mTOR survival axis. Genetic overexpression of wild-type p70S6K, but not the Q347A mutant, rescued the dual hypermetabolic phenotype and reinstated radioresistance. Clinically, elevated p70S6K expression correlated with poor disease-free survival and therapeutic failure. In vivo, CEP synergized with radiotherapy to suppress tumor kinetics in both CDX and syngeneic models, while concurrently enhancing CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell infiltration in the immunocompetent microenvironment, with no observable systemic toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Radioresistant ESCC relies on a dual hypermetabolic state driven by the PI3K\/Akt\/mTOR\/p70S6K cascade. CEP overcomes this radioresistance by physically binding to and degrading p70S6K, thereby inducing bioenergetic exhaustion and reshaping the anti-tumor microenvironment. These findings provide a solid mechanistic rationale for translating CEP into clinical radiotherapeutic regimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08550-y","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:55:20Z","timestamp":1783083320000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing cepharanthine as a radiosensitizer in esophageal squamous cell carcinoma through dual metabolic intervention and direct targeting of p70s6K"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4074-1826","authenticated-orcid":false,"given":"Zhihua","family":"Hao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiantao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpeng","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenguang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1761-1671","authenticated-orcid":false,"given":"Yutong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"issue":"2","key":"8550_CR1","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1093\/jjco\/hyad144","volume":"54","author":"Y Yoshinami","year":"2024","unstructured":"Yoshinami Y, Nishimura E, Hosokai T, Yamamoto S, Matsuda S, Nomura M, et al. Rare malignant neoplasm of the esophagus: current status and future perspectives. Jpn J Clin Oncol. 2024;54(2):111\u201320.","journal-title":"Jpn J Clin Oncol"},{"issue":"9","key":"8550_CR2","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1002\/ijc.34301","volume":"152","author":"H Zhu","year":"2023","unstructured":"Zhu H, Ma X, Ye T, Wang H, Wang Z, Liu Q, et al. Esophageal cancer in China: Practice and research in the new era. Int J Cancer. 2023;152(9):1741\u201351.","journal-title":"Int J Cancer"},{"issue":"1","key":"8550_CR3","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s12943-023-01839-2","volume":"22","author":"L An","year":"2023","unstructured":"An L, Li M, Jia Q. Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma. Mol Cancer. 2023;22(1):140.","journal-title":"Mol Cancer"},{"issue":"8","key":"8550_CR4","doi-asserted-by":"publisher","first-page":"2332","DOI":"10.1007\/s12094-023-03134-4","volume":"25","author":"D An","year":"2023","unstructured":"An D, Zhai D, Wan C, Yang K. The role of lipid metabolism in cancer radioresistance. Clin Transl Oncol. 2023;25(8):2332\u201349.","journal-title":"Clin Transl Oncol"},{"issue":"19","key":"8550_CR5","doi-asserted-by":"publisher","first-page":"4896","DOI":"10.1158\/0008-5472.CAN-21-2647","volume":"81","author":"AM Hosios","year":"2021","unstructured":"Hosios AM, Manning BD. Cancer Signaling Drives Cancer Metabolism: AKT and the Warburg Effect. Cancer Res. 2021;81(19):4896\u20138.","journal-title":"Cancer Res"},{"issue":"5","key":"8550_CR6","doi-asserted-by":"publisher","first-page":"4101","DOI":"10.3892\/mmr.2016.5010","volume":"13","author":"S Jiang","year":"2016","unstructured":"Jiang S, Wang R, Yan H, Jin L, Dou X, Chen D. MicroRNA-21 modulates radiation resistance through upregulation of hypoxia-inducible factor-1alpha-promoted glycolysis in non-small cell lung cancer cells. Mol Med Rep. 2016;13(5):4101\u20137.","journal-title":"Mol Med Rep"},{"key":"8550_CR7","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.3389\/fonc.2019.01152","volume":"9","author":"S Dadgar","year":"2019","unstructured":"Dadgar S, Rajaram N. Optical Imaging Approaches to Investigating Radiation Resistance. Front Oncol. 2019;9:1152.","journal-title":"Front Oncol"},{"key":"8550_CR8","doi-asserted-by":"crossref","unstructured":"Andryszkiewicz W, Gasiorowska J, Kubler M, Kublinska K, Palkiewicz A, Wiatkowski A et al. Glucose Metabolism and Tumor Microenvironment: Mechanistic Insights and Therapeutic Implications. Int J Mol Sci. 2025;26(5).","DOI":"10.3390\/ijms26051879"},{"issue":"18","key":"8550_CR9","doi-asserted-by":"publisher","first-page":"5201","DOI":"10.1158\/0008-5472.CAN-16-0266","volume":"76","author":"C Lehuede","year":"2016","unstructured":"Lehuede C, Dupuy F, Rabinovitch R, Jones RG, Siegel PM. Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis. Cancer Res. 2016;76(18):5201\u20138.","journal-title":"Cancer Res"},{"issue":"11","key":"8550_CR10","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/nrc1478","volume":"4","author":"RA Gatenby","year":"2004","unstructured":"Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 2004;4(11):891\u20139.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"8550_CR11","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1038\/s41420-023-01752-z","volume":"9","author":"YY Lu","year":"2023","unstructured":"Lu YY, Zhu CY, Ding YX, Wang B, Zhao SF, Lv J, et al. Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway. Cell Death Discov. 2023;9(1):450.","journal-title":"Cell Death Discov"},{"key":"8550_CR12","doi-asserted-by":"publisher","first-page":"156161","DOI":"10.1016\/j.phymed.2024.156161","volume":"135","author":"YY Lu","year":"2024","unstructured":"Lu YY, Fang YY, Wang SS, Guo J, Song JL, Zhu L, et al. Cepharanthine sensitizes gastric cancer cells to chemotherapy by targeting TRIB3-FOXO3-FOXM1 axis to inhibit autophagy. Phytomedicine. 2024;135:156161.","journal-title":"Phytomedicine"},{"key":"8550_CR13","doi-asserted-by":"publisher","first-page":"117667","DOI":"10.1016\/j.jep.2023.117667","volume":"323","author":"J Yang","year":"2024","unstructured":"Yang J, Qin L, Zhou S, Li J, Tu Y, Mo M, et al. Network pharmacology, molecular docking and experimental study of CEP in nasopharyngeal carcinoma. J Ethnopharmacol. 2024;323:117667.","journal-title":"J Ethnopharmacol"},{"key":"8550_CR14","doi-asserted-by":"publisher","first-page":"145358","DOI":"10.1016\/j.gene.2020.145358","volume":"772","author":"L Bi","year":"2021","unstructured":"Bi L, Wang H, Tian Y. Silencing FAM135B enhances radiosensitivity of esophageal carcinoma cell. Gene. 2021;772:145358.","journal-title":"Gene"},{"issue":"23","key":"8550_CR15","doi-asserted-by":"publisher","first-page":"4558","DOI":"10.1016\/j.molcel.2024.10.037","volume":"84","author":"T Ogawa","year":"2024","unstructured":"Ogawa T, Isik M, Wu Z, Kurmi K, Meng J, Cho S, et al. Nutrient control of growth and metabolism through mTORC1 regulation of mRNA splicing. Mol Cell. 2024;84(23):4558\u2013e45754558.","journal-title":"Mol Cell"},{"issue":"2","key":"8550_CR16","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228\u201347.","journal-title":"Eur J Cancer"},{"issue":"4","key":"8550_CR17","first-page":"761","volume":"31","author":"T Tamatani","year":"2007","unstructured":"Tamatani T, Azuma M, Motegi K, Takamaru N, Kawashima Y, Bando T. Cepharanthin-enhanced radiosensitivity through the inhibition of radiation-induced nuclear factor-kappaB activity in human oral squamous cell carcinoma cells. Int J Oncol. 2007;31(4):761\u20138.","journal-title":"Int J Oncol"},{"issue":"4","key":"8550_CR18","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1097\/IGC.0b013e31828a05fd","volume":"23","author":"ZH Fang","year":"2013","unstructured":"Fang ZH, Li YJ, Chen Z, Wang JJ, Zhu LH. Inhibition of signal transducer and activator of transcription 3 and cyclooxygenase-2 is involved in radiosensitization of cepharanthine in HeLa cells. Int J Gynecol cancer: official J Int Gynecol Cancer Soc. 2013;23(4):608\u201314.","journal-title":"Int J Gynecol cancer: official J Int Gynecol Cancer Soc"},{"issue":"8","key":"8550_CR19","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/aps.2016.47","volume":"37","author":"XS Chen","year":"2016","unstructured":"Chen XS, Li LY, Guan YD, Yang JM, Cheng Y. Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect. Acta Pharmacol Sin. 2016;37(8):1013\u20139.","journal-title":"Acta Pharmacol Sin"},{"issue":"45","key":"8550_CR20","doi-asserted-by":"publisher","first-page":"4917","DOI":"10.1038\/s41388-022-02487-4","volume":"41","author":"SG Pelaz","year":"2022","unstructured":"Pelaz SG, Tabernero A. Src: coordinating metabolism in cancer. Oncogene. 2022;41(45):4917\u201328.","journal-title":"Oncogene"},{"issue":"1","key":"8550_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41392-025-02311-x","volume":"10","author":"H Du","year":"2025","unstructured":"Du H, Xu T, Yu S, Wu S, Zhang J. Mitochondrial metabolism and cancer therapeutic innovation. Signal Transduct Target Ther. 2025;10(1):245.","journal-title":"Signal Transduct Target Ther"},{"issue":"8","key":"8550_CR22","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41419-022-05157-1","volume":"13","author":"W Zhu","year":"2022","unstructured":"Zhu W, Wang J, Liu X, Xu Y, Zhai R, Zhang J, et al. lncRNA CYTOR promotes aberrant glycolysis and mitochondrial respiration via HNRNPC-mediated ZEB1 stabilization in oral squamous cell carcinoma. Cell Death Dis. 2022;13(8):703.","journal-title":"Cell Death Dis"},{"issue":"1","key":"8550_CR23","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12964-024-01643-5","volume":"22","author":"M Cordani","year":"2024","unstructured":"Cordani M, Dando I, Ambrosini G, Gonzalez-Menendez P. Signaling, cancer cell plasticity, and intratumor heterogeneity. Cell Commun Signal. 2024;22(1):255.","journal-title":"Cell Commun Signal"},{"issue":"4","key":"8550_CR24","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.cell.2016.12.039","volume":"168","author":"MG Vander Heiden","year":"2017","unstructured":"Vander Heiden MG, DeBerardinis RJ. Understanding the Intersections between Metabolism and Cancer Biology. Cell. 2017;168(4):657\u201369.","journal-title":"Cell"},{"issue":"7524","key":"8550_CR25","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/nature13611","volume":"514","author":"A Viale","year":"2014","unstructured":"Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sanchez N, Marchesini M, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014;514(7524):628\u201332.","journal-title":"Nature"},{"key":"8550_CR26","doi-asserted-by":"crossref","unstructured":"Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression. Science. 2020;368(6487).","DOI":"10.1126\/science.aaw5473"},{"issue":"1","key":"8550_CR27","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","volume":"23","author":"NN Pavlova","year":"2016","unstructured":"Pavlova NN, Thompson CB. The Emerging Hallmarks of Cancer Metabolism. Cell Metab. 2016;23(1):27\u201347.","journal-title":"Cell Metab"},{"issue":"6","key":"8550_CR28","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1002\/hep.32177","volume":"75","author":"Y Fang","year":"2022","unstructured":"Fang Y, Zhan Y, Xie Y, Du S, Chen Y, Zeng Z, et al. Integration of glucose and cardiolipin anabolism confers radiation resistance of HCC. Hepatology. 2022;75(6):1386\u2013401.","journal-title":"Hepatology"},{"issue":"3","key":"8550_CR29","first-page":"100413","volume":"4","author":"J Li","year":"2023","unstructured":"Li J, Chen X, Lu A, Liang C. Targeted protein degradation in cancers: Orthodox PROTACs and beyond. Innov (Cambridge (Mass)). 2023;4(3):100413.","journal-title":"Innov (Cambridge (Mass))"},{"key":"8550_CR30","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1016\/j.biopha.2018.07.075","volume":"106","author":"G Hou","year":"2018","unstructured":"Hou G, Zhao Q, Zhang M, Fan T, Liu M, Shi X, et al. Down-regulation of Rictor enhances cell sensitivity to PI3K inhibitor LY294002 by blocking mTORC2-medicated phosphorylation of Akt\/PRAS40 in esophageal squamous cell carcinoma. Biomed Pharmacother. 2018;106:1348\u201356.","journal-title":"Biomed Pharmacother"},{"key":"8550_CR31","doi-asserted-by":"publisher","first-page":"108726","DOI":"10.1016\/j.cbi.2019.108726","volume":"310","author":"W Xu","year":"2019","unstructured":"Xu W, Wang X, Tu Y, Masaki H, Tanaka S, Onda K, et al. Tetrandrine and cepharanthine induce apoptosis through caspase cascade regulation, cell cycle arrest, MAPK activation and PI3K\/Akt\/mTOR signal modification in glucocorticoid resistant human leukemia Jurkat T cells. Chem Biol Interact. 2019;310:108726.","journal-title":"Chem Biol Interact"},{"issue":"10","key":"8550_CR32","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/s41419-023-06171-7","volume":"14","author":"H Deng","year":"2023","unstructured":"Deng H, Chen Y, Wang L, Zhang Y, Hang Q, Li P, et al. PI3K\/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer. Cell Death Dis. 2023;14(10):652.","journal-title":"Cell Death Dis"},{"issue":"8","key":"8550_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11033-021-06607-3","volume":"48","author":"A Mardanshahi","year":"2021","unstructured":"Mardanshahi A, Gharibkandi NA, Vaseghi S, Abedi SM, Molavipordanjani S. The PI3K\/AKT\/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines. Mol Biol Rep. 2021;48(8):1\u201314.","journal-title":"Mol Biol Rep"},{"issue":"2","key":"8550_CR34","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nri.2016.107","volume":"17","author":"L Galluzzi","year":"2017","unstructured":"Galluzzi L, Buqu\u00e9 A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97\u2013111.","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"8550_CR35","first-page":"e331","volume":"17","author":"M Wiesweg","year":"2018","unstructured":"Wiesweg M, Reis H, Koster T, Goetz M, Worm K, Herold T, et al. Phosphorylation of p70 Ribosomal Protein S6 Kinase beta-1 is an Independent Prognostic Parameter in Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2018;17(2):e331\u201352.","journal-title":"Clin Colorectal Cancer"},{"issue":"1","key":"8550_CR36","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41389-025-00564-3","volume":"14","author":"CL Zhang","year":"2025","unstructured":"Zhang CL, Zhao CY, Dong JM, Du CP, Wang BS, Wang CY, et al. CD147-high extracellular vesicles promote gastric cancer metastasis via VEGF\/AKT\/eNOS and AKT\/mTOR pathways. Oncogenesis. 2025;14(1):21.","journal-title":"Oncogenesis"},{"issue":"10","key":"8550_CR37","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1002\/1878-0261.13188","volume":"16","author":"R Sabatier","year":"2022","unstructured":"Sabatier R, Vicier C, Garnier S, Guille A, Carbuccia N, Isambert N, et al. Circulating tumor DNA predicts efficacy of a dual AKT\/p70S6K inhibitor (LY2780301) plus paclitaxel in metastatic breast cancer: plasma analysis of the TAKTIC phase IB\/II study. Mol Oncol. 2022;16(10):2057\u201370.","journal-title":"Mol Oncol"},{"key":"8550_CR38","doi-asserted-by":"crossref","unstructured":"Hernandez-Valencia J, Garcia-Villarreal R, Rodriguez-Jimenez M, Hernandez-Avalos AD, Rivero IA, Vique-Sanchez JL et al. Lapatinib-Resistant HER2\u2009+\u2009Breast Cancer Cells Are Associated with Dysregulation of MAPK and p70S6K\/PDCD4 Pathways and Calcium Management, Influence of Cryptotanshinone. Int J Mol Sci. 2025;26(8).","DOI":"10.3390\/ijms26083763"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08550-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08550-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08550-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:01:37Z","timestamp":1783969297000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08550-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8550"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08550-y","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]},"assertion":[{"value":"1 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human studies were approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (2023KY027), and informed consent was obtained. Animal experiments adhered to ARRIVE guidelines (2023204\/20260166).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent to publish has been obtained from all authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no potential competing of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competting of interests"}}],"article-number":"893"}}