{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:26:18Z","timestamp":1787631978779,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of Shanxi Province","award":["202503021211147"],"award-info":[{"award-number":["202503021211147"]}]},{"name":"Open Fund from Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University","award":["CKD2025-04"],"award-info":[{"award-number":["CKD2025-04"]}]},{"award":["CKD2025-04"],"award-info":[{"award-number":["CKD2025-04"]}],"id":[{"id":"https:\/\/ror.org\/0265d1010","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Kansui Radix, the root of Euphorbia kansui, was first described in Shen Nong Ben Cao Jing as a traditional Chinese medicine, known for its effects of expelling water, reducing edema, and dissipating masses. It is traditionally indicated for conditions such as \u201cwatery accumulation\u201d and \u201cabdominal masses (zheng-jia)\u201d, which share certain similarities with the clinical manifestations of renal cell carcinoma (RCC), including renal masses, edema, and body cavity effusion. Despite the recognized antitumor effects of Kansui Radix, the pharmacological basis and specific molecular mechanisms underlying its inhibition of RCC progression remain unclear. The goal of this study was therefore to evaluate the antitumor efficacy of Kansui-DCM in RCC and to explore its potential mechanism. To this end, the chemical composition of the dichloromethane fraction of Kansui Radix (Kansui-DCM) was characterized by UPLC-MS. The antiproliferative effects of Kansui-DCM on 786-O and RENCA cells were evaluated using the CCK-8 assay. Apoptotic morphology, apoptosis rate, cell migration and invasion abilities were assessed. An RCC mouse model was established, and tumor growth and histopathological staining were evaluated after drug administration. Immunohistochemistry, transcriptomic analysis, WGCNA (weighted gene co-expression network analysis), network pharmacology, and immunofluorescence were employed to investigate the molecular pathway. Protein and gene expression were analyzed by Western blot and qRT-PCR, respectively. Finally, the interactions between the active components and key targets were substantiated through molecular docking and molecular dynamics simulations. A total of 1397 compounds were detected in Kansui-DCM by UPLC-MS. In vitro experiments demonstrated that Kansui-DCM inhibited the proliferation of 786-O and RENCA cells in a dose-dependent manner, induced apoptosis, and suppressed cell invasion and migration in RENCA cells. Treatment with Kansui-DCM markedly suppressed tumor growth in vivo, as reflected by a reduction in tumor volume. Immunohistochemical analysis indicated that the expression levels of CD31, COX-2, and Ki67 were markedly decreased, while the expression level of CD8 was significantly increased. Integrated analysis using WGCNA and network pharmacology predicted that Kansui-DCM may exert its effects through the regulation of the HIF\/VEGF signaling pathway, which was further validated by immunofluorescence, Western blot, and qRT-PCR assays. Molecular docking and molecular dynamics simulations demonstrated stable interactions between multiple active components of Kansui-DCM and key targets such as VEGFR2 and HIF-2\u03b1. In conclusion, these findings suggested that Kansui-DCM exerts anti-RCC effects associated with regulation of the HIF\/VEGF pathway.<\/jats:p>","DOI":"10.3390\/ijms27167325","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated WGCNA, Network Pharmacology, and UPLC-MS\/MS Profiling for Investigating the Antitumor Effects of the Kansui Radix Dichloromethane Fraction Against Renal Cell Carcinoma with Experimental Validation"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhuoyang","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunuan","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China"},{"name":"Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1093\/ndt\/gfae036","article-title":"Global epidemiology of kidney cancer","volume":"39","author":"Cirillo","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17009","DOI":"10.1038\/nrdp.2017.9","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Makino, T., Kadomoto, S., Izumi, K., and Mizokami, A. (2022). Epidemiology and prevention of renal cell carcinoma. Cancers, 14.","DOI":"10.3390\/cancers14164059"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2013). Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499, 43\u201349.","DOI":"10.1038\/nature12222"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.6004\/jnccn.2022.0001","article-title":"Kidney cancer, version 3.2022, NCCN clinical practice guidelines in oncology","volume":"20","author":"Motzer","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2174\/0115680096323507241101064127","article-title":"The clinical role of hypoxia inducible factor (HIF) inhibition in renal cancer: A focus on belzutifan","volume":"26","author":"Arduini","year":"2026","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1002\/ptr.8524","article-title":"Harnessing dietary phytochemicals to modulate signaling pathways in cancer chemoprevention-A review","volume":"39","author":"Pandit","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fang, X., Yang, X., Zhou, C., Zeng, D., Hu, Z., Tu, X., Yang, B., and Hou, Y. (2025). Multitarget antitumor effects of panacis japonici rhizoma. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1591638"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Feng, X., Li, J., Li, H., Chen, X., Liu, D., and Li, R. (2023). Bioactive C21 steroidal glycosides from Euphorbia kansui promoted HepG2 cell apoptosis via the degradation of ATP1A1 and inhibited macrophage polarization under co-cultivation. Molecules, 28.","DOI":"10.3390\/molecules28062830"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cary, D.C., Fujinaga, K., and Peterlin, B.M. (2016). Euphorbia Kansui reactivates latent HIV. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0168027"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1055\/a-0646-4306","article-title":"Anti-inflammatory ingenane diterpenoids from the roots of Euphorbia kansui","volume":"84","author":"Zhang","year":"2018","journal-title":"Planta Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"112775","DOI":"10.1016\/j.phytochem.2021.112775","article-title":"Ingenane and jatrophane-type diterpenoids from Euphorbia kansui with multidrug resistance reversal activity","volume":"188","author":"Wang","year":"2021","journal-title":"Phytochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1080\/13880209.2025.2471844","article-title":"Comprehensive analysis of the potential mechanism of gansui in blocking non-small cell lung cancer progression","volume":"63","author":"Yang","year":"2025","journal-title":"Pharm. Biol."},{"key":"ref_14","first-page":"766","article-title":"Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship","volume":"15","author":"Hou","year":"2017","journal-title":"Chin. J. Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2116\/analsci.32.581","article-title":"Bioassay-guided separation of anti-tumor components from Euphorbia kansui by means of two-dimensional preparative high performance liquid chromatography and real-time cell analysis","volume":"32","author":"Ma","year":"2016","journal-title":"Anal. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Feng, X., Wang, L., Pu, L., Li, J., Li, H., Liu, D., and Li, R. (2024). An ingenane-type diterpene from Euphorbia kansui promoted cell apoptosis and macrophage polarization via the regulation of PKC signaling pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810123"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Zhou, Q.R., Lou, J.W., Chen, P.D., Yao, W.F., Tao, W.W., Tang, Y.P., Dai, G.C., Wang, K., and Zhang, L. (2017). Chemical constituents from Euphorbia kansui. Molecules, 22.","DOI":"10.3390\/molecules22122176"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112257","DOI":"10.1016\/j.phytochem.2020.112257","article-title":"Ingenane and jatrophane diterpenoids from Euphorbia kansui and their antiproliferative effects","volume":"172","author":"Meng","year":"2020","journal-title":"Phytochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119871","DOI":"10.1016\/j.jep.2025.119871","article-title":"Therapeutic angiogenesis mediated by traditional Chinese Medicine: Advances in cardiovascular disease treatment","volume":"350","author":"Zhang","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhao, C., and Popel, A.S. (2015). Computational model of microRNA control of HIF-VEGF pathway: Insights into the pathophysiology of ischemic vascular disease and cancer. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004612"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc3183","article-title":"HIF1\u03b1 and HIF2\u03b1: Sibling rivalry in hypoxic tumour growth and progression","volume":"12","author":"Keith","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/cas.13503","article-title":"Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation","volume":"109","author":"Hasumi","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kim, H., Shim, B.Y., Lee, S.J., Lee, J.Y., Lee, H.J., and Kim, I.H. (2021). Loss of von hippel-lindau (VHL) tumor suppressor gene function: VHL-HIF pathway and advances in treatments for metastatic renal cell carcinoma (RCC). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189795"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.critrevonc.2018.09.005","article-title":"The role of endothelial colony forming cells in kidney cancer\u2019s pathogenesis, and in resistance to anti-VEGFR agents and mTOR inhibitors: A speculative review","volume":"132","author":"Poletto","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/ijc.24710","article-title":"Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1alpha\/VEGF signaling pathways in human breast cancer cells","volume":"126","author":"Tang","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"107133","DOI":"10.1016\/j.jbc.2024.107133","article-title":"High-throughput virtual search of small molecules for controlling the mechanical stability of human CD4","volume":"300","author":"Reifs","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.eururo.2025.02.020","article-title":"European association of urology guidelines on renal cell carcinoma: The 2025 update","volume":"87","author":"Bex","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1080\/14737140.2025.2491647","article-title":"Prevailing challenges in personalized treatment for metastatic renal cell carcinoma: A narrative review","volume":"25","author":"Oki","year":"2025","journal-title":"Expert. Rev. Anticancer Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kgosiemang, I.K.R., Lefojane, R., Adegoke, A.M., Ogunyemi, O., Mashele, S.S., and Sekhoacha, M.P. (2025). Pharmacological significance, medicinal use, and toxicity of extracted and isolated compounds from Euphorbia Species found in Southern Africa: A review. Plants, 14.","DOI":"10.3390\/plants14030469"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Majo, S., Courtois, S., Souleyreau, W., Bikfalvi, A., and Auguste, P. (2020). Impact of extracellular matrix components to renal cell carcinoma behavior. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00625"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"118136","DOI":"10.1016\/j.biopha.2025.118136","article-title":"Inhibition of the PI3K\/AKT signaling pathway contributes to the anti-renal cell carcinoma effects of deoxyelephantopin","volume":"187","author":"He","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s42003-025-07757-x","article-title":"New mouse models for exploring renal tumor extension into the inferior vena cava","volume":"8","author":"Li","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e70966","DOI":"10.1002\/cam4.70966","article-title":"Transcutaneous imiquimod combined with anti-programmed cell death-1 monoclonal antibody extends the survival of mice bearing renal cell carcinoma","volume":"14","author":"Karashima","year":"2025","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.phymed.2009.12.014","article-title":"A novel polysaccharide, isolated from Angelica sinensis (Oliv.) Diels induces the apoptosis of cervical cancer HeLa cells through an intrinsic apoptotic pathway","volume":"17","author":"Cao","year":"2010","journal-title":"Phytomedicine"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lai, Z.Q., Ip, S.P., Liao, H.J., Lu, Z., Xie, J.H., Su, Z.R., Chen, Y.L., Xian, Y.F., Leung, P.S., and Lin, Z.X. (2017). Brucein D, a naturally occurring tetracyclic triterpene quassinoid, induces apoptosis in pancreatic cancer through ROS-associated PI3K\/Akt signaling pathway. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00936"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"539","DOI":"10.21037\/atm.2019.10.07","article-title":"Ecliptasaponin A induces apoptosis through the activation of ASK1\/JNK pathway and autophagy in human lung cancer cells","volume":"7","author":"Han","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1101\/pdb.prot087205","article-title":"Analyzing cell death by nuclear staining with Hoechst 33342","volume":"2016","author":"Crowley","year":"2016","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/978-1-0716-1278-1_17","article-title":"An annexin V-FITC-propidium iodide-based method for detecting apoptosis in a non-small cell lung cancer cell line","volume":"2279","author":"Kumar","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.biopha.2018.02.028","article-title":"Huaier Granule extract inhibit the proliferation and metastasis of lung cancer cells through down-regulation of MTDH, JAK2\/STAT3 and MAPK signaling pathways","volume":"101","author":"Chen","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1084\/jem.115.3.453","article-title":"The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes","volume":"115","author":"Boyden","year":"1962","journal-title":"J. Exp. Med."},{"key":"ref_41","first-page":"e51046","article-title":"In vitro cell migration and invasion assays","volume":"88","author":"Justus","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1126\/science.1129139","article-title":"Type, density, and location of immune cells within human colorectal tumors predict clinical outcome","volume":"313","author":"Galon","year":"2006","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"djx066","DOI":"10.1093\/jnci\/djx066","article-title":"Tumor microvessel density as a potential predictive marker for bevacizumab benefit: GOG-0218 biomarker analyses","volume":"109","author":"Bais","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/sj.bjc.6603756","article-title":"Ki-67 as prognostic marker in early breast cancer: A meta-analysis of published studies involving 12,155 patients","volume":"96","author":"Cardoso","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8221","DOI":"10.1158\/1078-0432.CCR-08-1841","article-title":"Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer","volume":"14","author":"Ogino","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.bbrc.2012.08.021","article-title":"reprint of \u201cPituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells\u201d","volume":"425","author":"Ferrara","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S1470-2045(24)00649-1","article-title":"Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): An open-label, single-arm, phase 2 study","volume":"26","author":"Choueiri","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nrc2442","article-title":"Modes of resistance to anti-angiogenic therapy","volume":"8","author":"Bergers","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e173934","DOI":"10.1172\/JCI173934","article-title":"VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis","volume":"134","author":"Wolf","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Roviello, G., De Gennaro, I., Vascotto, I., Venturi, G., D\u2019Angelo, A., Winchler, C., Guarino, A., Cacioppo, S., Modesti, M., and Mela, M.M. (2024). Hypoxia-inducible factor in renal cell carcinoma: From molecular insights to targeted therapies. Genes, 16.","DOI":"10.3390\/genes16010006"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"374963","DOI":"10.1155\/2013\/374963","article-title":"Reactive oxygen species in vascular formation and development","volume":"2013","author":"Zhou","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ccr.2005.06.017","article-title":"HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability","volume":"8","author":"Isaacs","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s12013-011-9161-0","article-title":"Quantitative analysis of quercetin in Euphorbia helioscopia L by RP-HPLC","volume":"61","author":"Liu","year":"2011","journal-title":"Cell Biochem. Biophys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41419-020-2353-z","article-title":"Nontoxic concentration of ochratoxin A decreases the dosage of cyclosporine A to induce chronic nephropathy model via autophagy mediated by toll-like receptor 4","volume":"11","author":"Hou","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1038\/s41467-025-59621-5","article-title":"USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity","volume":"16","author":"Dai","year":"2025","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7325\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:10:43Z","timestamp":1787631043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7325"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,16]]},"references-count":55,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167325"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167325","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,16]]}}}