{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:17:34Z","timestamp":1790630254174,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisciplinary Programs of Chinese Medicine and Aging Science of the Nanjing University of Chinese Medicine","award":["2025YLFWYGL020"],"award-info":[{"award-number":["2025YLFWYGL020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cancer stem cells (CSCs), a subpopulation of tumor cells endowed with self-renewal capacity, drive cancer initiation and progression. While long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators of CSC stemness, their specific roles in gastric cancer stem cells (GCSCs) remain poorly understood. This study investigates the functional significance of lncRNA TSPEAR-AS2 in modulating GCSC properties and uncovers its underlying molecular mechanisms. Through integrated whole-transcriptome sequencing, bioinformatics analysis, and validation in 48 paired gastric cancer tissues and adjacent normal tissues, TSPEAR-AS2 was identified as a differentially expressed lncRNA upregulated in both GCSCs and tumor samples. Functional experiments revealed that TSPEAR-AS2 overexpression significantly enhanced GCSC sphere-forming ability, proliferation, cell cycle progression, epithelial\u2013mesenchymal transition (EMT), and expression of stemness markers (CD54, CD44, OCT4, NANOG, and SOX2) while suppressing apoptosis. Conversely, TSPEAR-AS2 knockdown attenuated these malignant phenotypes. In vivo tumorigenicity assays in nude mice further confirmed that TSPEAR-AS2 promotes tumor growth, with overexpression accelerating and knockdown inhibiting tumor formation. Mechanistically, bioinformatics predictions and dual-luciferase reporter assays established TSPEAR-AS2 as a competing endogenous RNA (ceRNA) that sponges miR-15a-5p, thereby derepressing the miR-15a-5p target gene CCND1. Rescue experiments demonstrated that overexpression of miR-15a-5p phenocopied TSPEAR-AS2 knockdown, reducing GCSC stemness, while miR-15a-5p inhibition rescued the effects of TSPEAR-AS2 suppression. Collectively, these findings reveal a novel TSPEAR-AS2\/miR-15a-5p\/CCND1 regulatory axis that sustains GCSC stemness and tumorigenicity. These results highlight TSPEAR-AS2 as a potential therapeutic target for eradicating gastric cancer stem cells and improving clinical outcomes.<\/jats:p>","DOI":"10.3390\/biom15091227","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T10:35:17Z","timestamp":1756204517000},"page":"1227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["LncRNA TSPEAR-AS2 Maintains the Stemness of Gastric Cancer Stem Cells by Regulating the miR-15a-5p\/CCND1 Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Qiong","family":"Li","sequence":"first","affiliation":[{"name":"School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"School of Nursing, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"},{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"},{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengyuan","family":"Yue","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-1359","authenticated-orcid":false,"given":"Xiaowei","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"School of Aging Industry, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","article-title":"Gastric cancer","volume":"396","author":"Smyth","year":"2020","journal-title":"Lancet"},{"key":"ref_2","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/hel.12339","article-title":"Gastric cancer\u2013clinical and epidemiological aspects","volume":"21","author":"Venerito","year":"2016","journal-title":"Helicobacter"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Machlowska, J., Baj, J., Sitarz, M., Maciejewski, R., and Sitarz, R. (2020). Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114012"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.asjsur.2021.05.004","article-title":"Association of clinicopathological features and gastric cancer incidence in a single institution","volume":"45","author":"Warsinggih","year":"2022","journal-title":"Asian J. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1053\/j.gastro.2021.03.023","article-title":"Global Patterns and Trends in Gastric Cancer Incidence Rates (1988-2012) and Predictions to 2030","volume":"161","author":"Lin","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1056\/NEJMoa1909666","article-title":"Family History of Gastric Cancer and Helicobacter pylori Treatment","volume":"382","author":"Choi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.3748\/wjg.v22.i8.2403","article-title":"Advanced gastric cancer: Current treatment landscape and future perspectives","volume":"22","author":"Digklia","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_9","first-page":"1097","article-title":"Impact of HER2 and microsatellite instability status on response to neoadjuvant\/conversion therapy and survival in patients with gastric cancer","volume":"10","author":"Piccioni","year":"2025","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.stem.2012.05.007","article-title":"Cancer stem cells: Current status and evolving complexities","volume":"10","author":"Visvader","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/367645a0","article-title":"A cell initiating human acute myeloid leukaemia after transplantation into SCID mice","volume":"367","author":"Lapidot","year":"1994","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105320","DOI":"10.1016\/j.phrs.2020.105320","article-title":"Breast cancer stem cells, heterogeneity, targeting therapies and therapeutic implications","volume":"163","author":"Zeng","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Norollahi, S.E., Mansour-Ghanaei, F., Joukar, F., Ghadarjani, S., Mojtahedi, K., Nejad, K.G., Hemmati, H., Gharibpoor, F., Khaksar, R., and Samadani, A.A. (2019). Therapeutic approach of Cancer stem cells (CSCs) in gastric adenocarcinoma; DNA methyltransferases enzymes in cancer targeted therapy. Biomed. Pharmacother., 115.","DOI":"10.1016\/j.biopha.2019.108958"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1158\/0008-5472.CAN-04-3931","article-title":"Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer","volume":"65","author":"Bapat","year":"2005","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41575-021-00508-3","article-title":"Cancer stem cells in hepatocellular carcinoma\u2014from origin to clinical implications","volume":"19","author":"Lee","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bcp.2018.12.010","article-title":"Lung cancer stem cells: Origin, features, maintenance mechanisms and therapeutic targeting","volume":"160","author":"Heng","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rao, X., Zhang, C., Luo, H., Zhang, J., Zhuang, Z., Liang, Z., and Wu, X. (2022). Targeting Gastric Cancer Stem Cells to Enhance Treatment Response. Cells, 11.","DOI":"10.3390\/cells11182828"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8721","DOI":"10.7150\/thno.41648","article-title":"Stem cell programs in cancer initiation, progression, and therapy resistance","volume":"10","author":"Huang","year":"2020","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4252\/wjsc.v14.i1.76","article-title":"Molecular mechanism of therapeutic approaches for human gastric cancer stem cells","volume":"14","author":"Hsieh","year":"2022","journal-title":"World J. Stem Cells"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5420","DOI":"10.3748\/wjg.v20.i18.5420","article-title":"Gastric cancer stem cells in gastric carcinogenesis, progression, prevention and treatment","volume":"20","author":"Li","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10120-013-0254-x","article-title":"Gastric cancer stem cells: Therapeutic targets","volume":"17","author":"Stojnev","year":"2014","journal-title":"Gastric Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Otaegi-Ugartemendia, M., Matheu, A., and Carrasco-Garcia, E. (2022). Impact of Cancer Stem Cells on Therapy Resistance in Gastric Cancer. Cancers, 14.","DOI":"10.3390\/cancers14061457"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.molcel.2011.08.018","article-title":"Molecular mechanisms of long noncoding RNAs","volume":"43","author":"Wang","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cell.2018.01.011","article-title":"Functional Classification and Experimental Dissection of Long Noncoding RNAs","volume":"172","author":"Kopp","year":"2018","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1016\/j.molcel.2022.05.027","article-title":"Integrated lncRNA function upon genomic and epigenomic regulation","volume":"82","author":"Herman","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_26","first-page":"1354","article-title":"Emerging roles of lncRNA in cancer and therapeutic opportunities","volume":"9","author":"Jiang","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D1295","DOI":"10.1093\/nar\/gkab1035","article-title":"lncRNAfunc: A knowledgebase of lncRNA function in human cancer","volume":"50","author":"Yang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.semcancer.2020.12.012","article-title":"lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions","volume":"75","author":"McCabe","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.canlet.2021.04.002","article-title":"LncRNA-miRNA axes in breast cancer: Novel points of interaction for strategic attack","volume":"509","author":"Venkatesh","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1756-9966-32-96","article-title":"Regulation of microRNAs by epigenetics and their interplay involved in cancer","volume":"32","author":"Liu","year":"2013","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.canlet.2018.01.027","article-title":"Non-coding RNAs in cancer stem cells","volume":"421","author":"Yan","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA hypothesis: The Rosetta Stone of a hidden RNA language?","volume":"146","author":"Salmena","year":"2011","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Urrutia, E., Bustamante Montes, L.P., Ladr\u00f3n de Guevara Cervantes, D., P\u00e9rez-Plasencia, C., and Campos-Parra, A.D. (2019). Crosstalk Between Long Non-coding RNAs, Micro-RNAs and mRNAs: Deciphering Molecular Mechanisms of Master Regulators in Cancer. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00669"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5114\/pg.2018.80001","article-title":"Epidemiology of gastric cancer: Global trends, risk factors and prevention","volume":"14","author":"Rawla","year":"2019","journal-title":"Gastroenterol. Rev.\/Przegl\u0105d Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","article-title":"Updates on global epidemiology, risk and prognostic factors of gastric cancer","volume":"29","author":"Yang","year":"2023","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8381","DOI":"10.1002\/jcp.27740","article-title":"Cancer stem cells (CSCs) in cancer progression and therapy","volume":"234","author":"Najafi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.stem.2015.02.015","article-title":"The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells?","volume":"16","author":"Plaks","year":"2015","journal-title":"Cell Stem Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5483\/BMBRep.2017.50.3.222","article-title":"Cancer stem cell heterogeneity: Origin and new perspectives on CSC targeting","volume":"50","author":"Eun","year":"2017","journal-title":"BMB Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s12253-018-0453-1","article-title":"Non-Coding RNA Pvt1 Promotes Cancer Stem Cell-Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207","volume":"25","author":"Cui","year":"2019","journal-title":"Pathol. Oncol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.canlet.2017.09.019","article-title":"LncRNA HOTTIP modulates cancer stem cell properties in human pancreatic cancer by regulating HOXA9","volume":"410","author":"Fu","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12943-019-0949-7","article-title":"Exosomal FMR1-AS1 facilitates maintaining cancer stem-like cell dynamic equilibrium via TLR7\/NF\u03baB\/c-Myc signaling in female esophageal carcinoma","volume":"18","author":"Li","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Peng, Y., Xu, C., Wen, J., Zhang, Y., Wang, M., Liu, X., Zhao, K., Wang, Z., Liu, Y., and Zhang, T. (2021). Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.704038"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2217663","DOI":"10.1155\/2021\/2217663","article-title":"lncRNA TSPEAR-AS2, a Novel Prognostic Biomarker, Promotes Oral Squamous Cell Carcinoma Progression by Upregulating PPM1A via Sponging miR-487a-3p","volume":"2021","author":"Xia","year":"2021","journal-title":"Dis. Markers"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1016\/j.omtn.2020.10.022","article-title":"BTEB2-Activated lncRNA TSPEAR-AS2 Drives GC Progression through Suppressing GJA1 Expression and Upregulating CLDN4 Expression","volume":"22","author":"Ma","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"116781","DOI":"10.1016\/j.lfs.2019.116781","article-title":"Cancer stem cell (CSC) resistance drivers","volume":"234","author":"Najafi","year":"2019","journal-title":"Life Sci."},{"key":"ref_46","first-page":"1132","article-title":"Long non-coding RNA MEG3 functions as a tumour suppressor and has prognostic predictive value in human pancreatic cancer","volume":"39","author":"Ma","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1038\/s41417-022-00456-3","article-title":"LncRNA SNHG5 promotes the proliferation and cancer stem cell-like properties of HCC by regulating UPF1 and Wnt-signaling pathway","volume":"29","author":"Li","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s12935-021-01993-x","article-title":"LncRNA WDFY3-AS2 promotes cisplatin resistance and the cancer stem cell in ovarian cancer by regulating hsa-miR-139-5p\/SDC4 axis","volume":"21","author":"Wu","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1075481","DOI":"10.1155\/2021\/1075481","article-title":"lncRNA TUG1 Facilitates Colorectal Cancer Stem Cell Characteristics and Chemoresistance by Enhancing GATA6 Protein Stability","volume":"2021","author":"Sun","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_50","first-page":"4589","article-title":"Early deregulation of the the p16ink4a-cyclin D1\/cyclin-dependent kinase 4-retinoblastoma pathway in cell proliferation-driven esophageal tumorigenesis in zinc-deficient rats","volume":"60","author":"Fong","year":"2000","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12534","DOI":"10.1111\/cpr.12534","article-title":"H19 regulation of oestrogen induction of symmetric division is achieved by antagonizing Let-7c in breast cancer stem-like cells","volume":"52","author":"Wang","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12935-018-0540-0","article-title":"LncRNA XIST\/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells","volume":"18","author":"Xu","year":"2018","journal-title":"Cancer Cell Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1002\/jcp.26590","article-title":"LncRNA DGCR5 contributes to CSC-like properties via modulating miR-330-5p\/CD44 in NSCLC","volume":"233","author":"Wang","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1002\/jcb.26823","article-title":"Interaction of lncRNA-MALAT1 and miR-124 regulates HBx-induced cancer stem cell properties in HepG2 through PI3K\/Akt signaling","volume":"120","author":"He","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1177\/15353702211038496","article-title":"ONECUT2 which is targeted by hsa-miR-15a-5p enhances stemness maintenance of gastric cancer stem cells","volume":"246","author":"Shen","year":"2021","journal-title":"Exp. Biol. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/9\/1227\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:32:55Z","timestamp":1760034775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/9\/1227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biom15091227"],"URL":"https:\/\/doi.org\/10.3390\/biom15091227","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]}}}