{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:48:00Z","timestamp":1790362080527,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["81974415"],"award-info":[{"award-number":["81974415"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["82172923"],"award-info":[{"award-number":["82172923"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clear cell renal cell carcinoma (ccRCC) is a highly immunogenic tumor and immune dysfunction is associated with ccRCC poor prognosis. The RhoGTPase-activating proteins (RhoGAPs) family was reported to affect ccRCC development, but its role in immunity and prognosis prediction for ccRCC remain unknown. In the current study, we found ARHGAP11A was the only independent risk factor among 33 RhoGAPs (hazard ratio [HR] 1.949, 95% confidence interval [CI] 1.364\u20132.785). High ARHGAP11A level was associated with shorter overall survival (OS, HR 2.040, 95% CI 1.646\u20133.417) and ARHGAP11A is a prognostic biomarker for ccRCC. ARHGAP11A knockdown suppressed renal cell carcinoma (RCC) cell proliferation, colony formation, and migration, suggesting the promoting role of ARHGAP11A on RCC development. Mechanistically, ARHGAP11A might contribute to the suppressive tumor immune microenvironment (TIME). High ARHGAP11A level was correlated with infiltration of immunosuppressive cells (including T helper 2 (Th2) cells, regulatory T (Treg) cells, myeloid derived suppressor cells (MDSC), and M2 macrophage cells), activation of immunosuppressive pathways (IL6-JAK-STAT3 signaling and IFN\u03b3 response), and expression of inhibitory immune checkpoints (ICs). ARHGAP11A could promote T cell exhaustion and induce immune escape. ccRCC patients with low ARHGAP11A level were more suitable for immune checkpoint inhibitors (ICIs) therapy, while those with high ARHGAP11A level might benefit from a combination of ARHGAP11A blockade and ICIs. In all, ARHGAP11A might serve as a novel prognostic marker, therapeutic target, and predictor in the clinical response to ICIs therapy for ccRCC.<\/jats:p>","DOI":"10.3390\/ijms24097755","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T04:01:23Z","timestamp":1682308883000},"page":"7755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["ARHGAP11A Is a Novel Prognostic and Predictive Biomarker Correlated with Immunosuppressive Microenvironment in Clear Cell Renal Cell Carcinoma"],"prefix":"10.3390","volume":"24","author":[{"given":"Huihui","family":"Yang","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7712-8868","authenticated-orcid":false,"given":"Hongning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuxu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paizigul","family":"Tusuphan","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4071-4764","authenticated-orcid":false,"given":"Junfang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","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_2","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1038\/s41388-020-1234-3","article-title":"Modeling clear cell renal cell carcinoma and therapeutic implications","volume":"39","author":"Wolf","year":"2020","journal-title":"Oncogene"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The Immune Landscape of Cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1016\/j.celrep.2018.06.032","article-title":"The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma","volume":"23","author":"Ricketts","year":"2018","journal-title":"Cell. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","article-title":"Molecular and genetic properties of tumors associated with local immune cytolytic activity","volume":"160","author":"Rooney","year":"2015","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/s41591-020-0839-y","article-title":"Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma","volume":"26","author":"Braun","year":"2020","journal-title":"Nat. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.2217\/fon-2018-0951","article-title":"The future of perioperative therapy in advanced renal cell carcinoma: How can we PROSPER?","volume":"15","author":"Patel","year":"2019","journal-title":"Future Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/s41581-020-0316-3","article-title":"The immunology of renal cell carcinoma","volume":"16","author":"Rini","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kim, I.H., and Lee, H.J. (2022). The Frontline Immunotherapy-Based Treatment of Advanced Clear Cell Renal Cell Carcinoma: Current Evidence and Clinical Perspective. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020251"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3322\/caac.21411","article-title":"Treatment of renal cell carcinoma: Current status and future directions","volume":"67","author":"Barata","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s10555-020-09923-5","article-title":"Rho GTPases in cancer radiotherapy and metastasis","volume":"39","author":"Zeng","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7447","DOI":"10.1038\/s41388-019-0963-7","article-title":"Rho GTPases in cancer: Friend or foe?","volume":"38","author":"Svensmark","year":"2019","journal-title":"Oncogene"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/nrm.2016.67","article-title":"Regulating Rho GTPases and their regulators","volume":"17","author":"Hodge","year":"2016","journal-title":"Nat. Rev. Mol. Cell. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0962-8924(02)00004-1","article-title":"Rho GTPase-activating proteins in cell regulation","volume":"13","author":"Moon","year":"2003","journal-title":"Trends Cell. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.canlet.2009.03.025","article-title":"Overexpression of DLC-1 induces cell apoptosis and proliferation inhibition in the renal cell carcinoma","volume":"283","author":"Zhang","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23003","DOI":"10.18632\/oncotarget.25190","article-title":"Bromodomain protein BRD4 inhibitor JQ1 regulates potential prognostic molecules in advanced renal cell carcinoma","volume":"9","author":"Sakaguchi","year":"2018","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51829","DOI":"10.18632\/oncotarget.10386","article-title":"ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tranon.2016.12.004","article-title":"Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1","volume":"10","author":"Miyazaki","year":"2017","journal-title":"Transl. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15649","DOI":"10.1007\/s13277-016-5135-6","article-title":"Establishment of a miRNA-mRNA regulatory network in metastatic renal cell carcinoma and screening of potential therapeutic targets","volume":"37","author":"Zhu","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"720645","DOI":"10.3389\/fmolb.2021.720645","article-title":"ARHGAP11A Is a Prognostic Biomarker and Correlated with Immune Infiltrates in Gastric Cancer","volume":"8","author":"Fan","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"657219","DOI":"10.3389\/fcell.2021.657219","article-title":"Transcriptomic Analysis Identified ARHGAP Family as a Novel Biomarker Associated with Tumor-Promoting Immune Infiltration and Nanomechanical Characteristics in Bladder Cancer","volume":"9","author":"Yang","year":"2021","journal-title":"Front. Cell. Dev. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ccell.2020.02.004","article-title":"m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer","volume":"37","author":"Huang","year":"2020","journal-title":"Cancer Cell."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, Mechanisms, and Significance of Macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40364-020-00228-x","article-title":"Roles of IFN-gamma in tumor progression and regression: A review","volume":"8","author":"Jorgovanovic","year":"2020","journal-title":"Biomark. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00281-019-00744-5","article-title":"CD8(+) T cell exhaustion","volume":"41","author":"Kurachi","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41571-020-00455-z","article-title":"Beyond conventional immune-checkpoint inhibition\u2014Novel immunotherapies for renal cell carcinoma","volume":"18","author":"Braun","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1038\/s41591-018-0136-1","article-title":"Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response","volume":"24","author":"Jiang","year":"2018","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s12964-018-0312-4","article-title":"Blockade of ARHGAP11A reverses malignant progress via inactivating Rac1B in hepatocellular carcinoma","volume":"16","author":"Dai","year":"2018","journal-title":"Cell. Commun. Signal."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1158\/0008-5472.CAN-15-2923","article-title":"Rho GTPase Transcriptome Analysis Reveals Oncogenic Roles for Rho GTPase-Activating Proteins in Basal-like Breast Cancers","volume":"76","author":"Lawson","year":"2016","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kagawa, Y., Matsumoto, S., Kamioka, Y., Mimori, K., Naito, Y., Ishii, T., Okuzaki, D., Nishida, N., Maeda, S., and Naito, A. (2013). Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083629"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4146910","DOI":"10.1155\/2021\/4146910","article-title":"ARHGAP11A Promotes the Malignant Progression of Gastric Cancer by Regulating the Stability of Actin Filaments through TPM1","volume":"2021","author":"Guan","year":"2021","journal-title":"J. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.celrep.2013.04.017","article-title":"RhoGAPs attenuate cell proliferation by direct interaction with p53 tetramerization domain","volume":"3","author":"Xu","year":"2013","journal-title":"Cell. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11507","DOI":"10.2147\/OTT.S222564","article-title":"ARHGAP10 Inhibits the Proliferation and Metastasis of CRC Cells via Blocking the Activity of RhoA\/AKT Signaling Pathway","volume":"12","author":"Liu","year":"2019","journal-title":"Onco Targets Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1038\/s41467-018-04907-0","article-title":"Prognostic significance of frequent CLDN18-ARHGAP26\/6 fusion in gastric signet-ring cell cancer","volume":"9","author":"Shu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3892\/mmr.2014.2778","article-title":"Skewed T-helper (Th)1\/2- and Th17\/T regulatorycell balances in patients with renal cell carcinoma","volume":"11","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1158\/0008-5472.CAN-08-4323","article-title":"Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells","volume":"69","author":"Xin","year":"2009","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.3389\/fimmu.2018.03120","article-title":"The Evolving Landscape of Immunotherapy-Based Combinations for Frontline Treatment of Advanced Renal Cell Carcinoma","volume":"9","author":"Amin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1158\/0008-5472.CAN-16-0274","article-title":"Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma","volume":"77","author":"Granier","year":"2017","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1186\/s12935-020-01603-2","article-title":"CTLA4 has a profound impact on the landscape of tumor-infiltrating lymphocytes with a high prognosis value in clear cell renal cell carcinoma (ccRCC)","volume":"20","author":"Liu","year":"2020","journal-title":"Cancer Cell. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5547","DOI":"10.1038\/s41467-021-25865-0","article-title":"Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy","volume":"12","author":"Takamatsu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12943-017-0676-x","article-title":"The noncoding RNA HOXD-AS1 is a critical regulator of the metastasis and apoptosis phenotype in human hepatocellular carcinoma","volume":"16","author":"Lu","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1093\/carcin\/bgv105","article-title":"PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome","volume":"36","author":"Fu","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41556-018-0045-z","article-title":"Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation","volume":"20","author":"Huang","year":"2018","journal-title":"Nat. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and interpreting cancer genomics data via the Xena platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1002\/jbm.a.37090","article-title":"GSVA score reveals molecular signatures from transcriptomes for biomaterials comparison","volume":"109","author":"Ferreira","year":"2021","journal-title":"J. Biomed. Mater. Res. A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1093\/nar\/gkw104","article-title":"SRAMP: Prediction of mammalian N6-methyladenosine (m6A) sites based on sequence-derived features","volume":"44","author":"Zhou","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109750","DOI":"10.1016\/j.biopha.2019.109750","article-title":"ECHS1 suppresses renal cell carcinoma development through inhibiting mTOR signaling activation","volume":"123","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"639408","DOI":"10.3389\/fonc.2021.639408","article-title":"SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis","volume":"11","author":"Fang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1038\/psp.2013.56","article-title":"Application of ggplot2 to Pharmacometric Graphics","volume":"2","author":"Ito","year":"2013","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4200","DOI":"10.1093\/bioinformatics\/btz210","article-title":"TISIDB: An integrated repository portal for tumor-immune system interactions","volume":"35","author":"Ru","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling Tumor Infiltrating Immune Cells with CIBERSORT","volume":"1711","author":"Chen","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1093\/plcell\/koab042","article-title":"Co-expression networks in Chlamydomonas reveal significant rhythmicity in batch cultures and empower gene function discovery","volume":"33","author":"Salome","year":"2021","journal-title":"Plant. Cell."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"461","DOI":"10.21037\/atm.2016.08.61","article-title":"Semi-parametric regression model for survival data: Graphical visualization with R","volume":"4","author":"Zhang","year":"2016","journal-title":"Ann. Transl. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:22:13Z","timestamp":1760124133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,24]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24097755"],"URL":"https:\/\/doi.org\/10.3390\/ijms24097755","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,24]]}}}