{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:16:13Z","timestamp":1766034973305,"version":"3.48.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF-RS-2024-00357447"],"award-info":[{"award-number":["NRF-RS-2024-00357447"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003654","name":"Korea Environmental Industry and Technology Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003654","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004080","name":"Korea Drug Development Fund","doi-asserted-by":"crossref","award":["RS-2023-00259081"],"award-info":[{"award-number":["RS-2023-00259081"]}],"id":[{"id":"10.13039\/501100004080","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chung-Ang university research grants in 2020"},{"name":"Seoul RISE Center","award":["2025-RISE-01-024-05"],"award-info":[{"award-number":["2025-RISE-01-024-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt\/\u03b2-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants\u2019 in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic\/proinflammatory factor expression and suppressed the epithelial\u2013mesenchymal transition (EMT) in RPE cells by promoting intracellular \u03b2-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of \u03b2-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina\/choroid tissue and downregulated \u03b2-catenin, angiogenic\/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28\u201342 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt\/\u03b2-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment.<\/jats:p>","DOI":"10.3390\/ph18121884","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T15:27:20Z","timestamp":1765553240000},"page":"1884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Therapeutic Effect of a Biodegradable Long-Acting Intravitreal Implant Containing CGK012 on Neovascular Age-Related Macular Degeneration by Promoting \u03b2-Catenin Degradation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-2594","authenticated-orcid":false,"given":"Seoyoung","family":"Park","sequence":"first","affiliation":[{"name":"Inspharmtech, Inc., Chuncheon 24341, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1296-2285","authenticated-orcid":false,"given":"Jihyun","family":"Won","sequence":"additional","affiliation":[{"name":"Inspharmtech, Inc., Chuncheon 24341, Republic of Korea"},{"name":"College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-6960","authenticated-orcid":false,"given":"Jong Beom","family":"Heo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1847-5314","authenticated-orcid":false,"given":"Juhyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Inspharmtech, Inc., Chuncheon 24341, Republic of Korea"},{"name":"College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye Woon","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geunji","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-4173","authenticated-orcid":false,"given":"Giseong","family":"Lee","sequence":"additional","affiliation":[{"name":"College of General Education, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jee-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"AREZ Co., Ltd., Daejeon 34036, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-5790","authenticated-orcid":false,"given":"Gyu-Yong","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea"},{"name":"AREZ Co., Ltd., Daejeon 34036, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonku","family":"Kang","sequence":"additional","affiliation":[{"name":"Inspharmtech, Inc., Chuncheon 24341, Republic of Korea"},{"name":"College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangtaek","family":"Oh","sequence":"additional","affiliation":[{"name":"Inspharmtech, Inc., Chuncheon 24341, Republic of Korea"},{"name":"Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mam.2012.04.005","article-title":"Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor\/retinal pigment epithelium\/Bruch\u2019s membrane\/choriocapillaris complex","volume":"33","author":"Bhutto","year":"2012","journal-title":"Mol. Aspects Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0039-6257(00)00140-5","article-title":"The role of oxidative stress in the pathogenesis of age-related macular degeneration","volume":"45","author":"Beatty","year":"2000","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1517\/14728220902942322","article-title":"Inflammation and the pathogenesis of age-related macular degeneration","volume":"13","author":"Augustin","year":"2009","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.preteyeres.2015.06.002","article-title":"Molecular pathogenesis of retinal and choroidal vascular diseases","volume":"49","author":"Campochiaro","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mitchell, P., Bressler, N., Doan, Q.V., Dolan, C., Ferreira, A., Osborne, A., Rochtchina, E., Danese, M., Colman, S., and Wong, T.Y. (2014). Estimated cases of blindness and visual impairment from neovascular age-related macular degeneration avoided in Australia by ranibizumab treatment. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101072"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1080\/07853890600946724","article-title":"Age-related macular degeneration--emerging pathogenetic and therapeutic concepts","volume":"38","author":"Gehrs","year":"2006","journal-title":"Ann. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.maturitas.2010.02.006","article-title":"Age-related macular degeneration: Current and novel therapies","volume":"66","author":"Prasad","year":"2010","journal-title":"Maturitas"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1136\/bjo.2006.113902","article-title":"Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions","volume":"91","author":"Lux","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/eye.2013.107","article-title":"Adverse events and complications associated with intravitreal injection of anti-VEGF agents: A review of literature","volume":"27","author":"Falavarjani","year":"2013","journal-title":"Eye"},{"key":"ref_10","first-page":"131","article-title":"The Role of Wnt Signalling in Angiogenesis","volume":"38","author":"Olsen","year":"2017","journal-title":"Clin. Biochem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jridi, I., Cante-Barrett, K., Pike-Overzet, K., and Staal, F.J.T. (2021). Inflammation and Wnt Signaling: Target for Immunomodulatory Therapy?. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.615131"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Antar, S.A., Ashour, N.A., Marawan, M.E., and Al-Karmalawy, A.A. (2023). Fibrosis: Types, Effects, Markers, Mechanisms for Disease Progression, and Its Relation with Oxidative Stress, Immunity, and Inflammation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044004"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/s41598-017-01119-2","article-title":"Decreased Circulating Levels of Dickkopf-1 in Patients with Exudative Age-related Macular Degeneration","volume":"7","author":"Qiu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4371","DOI":"10.1167\/iovs.09-4278","article-title":"The pathogenic role of the canonical Wnt pathway in age-related macular degeneration","volume":"51","author":"Zhou","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1167\/iovs.12-10281","article-title":"Pathogenic role of the Wnt signaling pathway activation in laser-induced choroidal neovascularization","volume":"54","author":"Hu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/labinvest.2011.201","article-title":"Wnt signaling induces epithelial-mesenchymal transition with proliferation in ARPE-19 cells upon loss of contact inhibition","volume":"92","author":"Chen","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1021\/pr400751k","article-title":"Exosomal proteins in the aqueous humor as novel biomarkers in patients with neovascular age-related macular degeneration","volume":"13","author":"Kang","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/15548627.2016.1256932","article-title":"Autophagy and KRT8\/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress","volume":"13","author":"Baek","year":"2017","journal-title":"Autophagy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/2045-3701-4-27","article-title":"Diabetic macular edema: New concepts in patho-physiology and treatment","volume":"4","author":"Zhang","year":"2014","journal-title":"Cell Biosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4274","DOI":"10.1167\/iovs.16-21334","article-title":"Evaluation of the Toxicity of Intravitreally Injected PLGA Microspheres and Rods in Monkeys and Rabbits: Effects of Depot Size on Inflammatory Response","volume":"58","author":"Thackaberry","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","first-page":"317","article-title":"Sustained release intraocular drug delivery devices for treatment of uveitis","volume":"6","author":"Haghjou","year":"2011","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.leukres.2017.07.001","article-title":"Anti-proliferative activity of CGK012 against multiple myeloma cells via Wnt\/beta-catenin signaling attenuation","volume":"60","author":"Yuseok","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1089\/jmf.2024.k.0194","article-title":"The Beneficial Effects of CGK012 Against Lipopolysaccharide-Induced Inflammation","volume":"28","author":"Lee","year":"2025","journal-title":"J. Med. Food"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"525","DOI":"10.5483\/BMBRep.2015.48.9.140","article-title":"Wnt5a attenuates the pathogenic effects of the Wnt\/beta-catenin pathway in human retinal pigment epithelial cells via down-regulating beta-catenin and Snail","volume":"48","author":"Kim","year":"2015","journal-title":"BMB Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.bbrc.2014.02.119","article-title":"Overexpression of Snail in retinal pigment epithelial triggered epithelial-mesenchymal transition","volume":"446","author":"Li","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/01.ATV.0000193569.12490.4b","article-title":"Beta-catenin overexpression augments angiogenesis and skeletal muscle regeneration through dual mechanism of vascular endothelial growth factor-mediated endothelial cell proliferation and progenitor cell mobilization","volume":"26","author":"Kim","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"475","DOI":"10.3109\/08820538.2014.889179","article-title":"The Sustained-Release Dexamethasone Implant: Expanding Indications in Vitreoretinal Disease","volume":"30","author":"Kapoor","year":"2015","journal-title":"Semin. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.ophtha.2017.05.035","article-title":"Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future","volume":"124","author":"Colijn","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/eye.2009.219","article-title":"Intravitreal bevacizumab (Avastin) for age-related macular degeneration: A critical analysis of literature","volume":"24","author":"Jyothi","year":"2010","journal-title":"Eye"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ejphar.2011.05.016","article-title":"Anti-angiogenic effects of the receptor tyrosine kinase inhibitor, pazopanib, on choroidal neovascularization in rats","volume":"666","author":"Yafai","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.exer.2013.05.006","article-title":"Antiangiogenic effects of tivozanib, an oral VEGF receptor tyrosine kinase inhibitor, on experimental choroidal neovascularization in mice","volume":"112","author":"Kang","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.2353\/ajpath.2009.080945","article-title":"Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models","volume":"175","author":"Chen","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1161\/ATVBAHA.114.304627","article-title":"Nanoparticle-mediated expression of a Wnt pathway inhibitor ameliorates ocular neovascularization","volume":"35","author":"Wang","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105146","DOI":"10.1016\/j.phrs.2020.105146","article-title":"Ilimaquinone inhibits neovascular age-related macular degeneration through modulation of Wnt\/beta-catenin and p53 pathways","volume":"161","author":"Son","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6900","DOI":"10.1073\/pnas.0906764107","article-title":"Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family","volume":"107","author":"Zhang","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Allegrini, D., Raimondi, R., Borgia, A., Sorrentino, T., Montesano, G., Tsoutsanis, P., Cancian, G., Verma, Y., De Rosa, F.P., and Romano, M.R. (2022). Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073557"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12974-024-03068-w","article-title":"Wnt5a\/beta-catenin-mediated epithelial-mesenchymal transition: A key driver of subretinal fibrosis in neovascular age-related macular degeneration","volume":"21","author":"Liu","year":"2024","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100527","DOI":"10.1016\/j.xops.2024.100527","article-title":"Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients with Wet Age-Related Macular Degeneration","volume":"4","author":"Patel","year":"2024","journal-title":"Ophthalmol. Sci."},{"key":"ref_39","first-page":"931","article-title":"The DAVIO trial: A phase 1, open-label, dose-escalation study of a single injection of EYP-1901 (vorolanib in Durasert\u00ae platform) demonstrating reduced treatment burden in wet age-related macular degeneration","volume":"64","author":"Abbey","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","first-page":"218","article-title":"Phase 1 Study of an Intravitreal Axitinib Hydrogel-based Implant for the Treatment of Neovascular Age-Related Macular Degeneration (nAMD)","volume":"62","author":"Wong","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1089\/jop.2014.0082","article-title":"Comparison of the release profile and pharmacokinetics of intact and fragmented dexamethasone intravitreal implants in rabbit eyes","volume":"30","author":"Bhagat","year":"2014","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0092-8674(02)00685-2","article-title":"Control of beta-catenin phosphorylation\/degradation by a dual-kinase mechanism","volume":"108","author":"Liu","year":"2002","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1242\/jcs.03256","article-title":"Protein-kinase-C-mediated beta-catenin phosphorylation negatively regulates the Wnt\/beta-catenin pathway","volume":"119","author":"Gwak","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.leukres.2005.05.001","article-title":"Decursin and PDBu: Two PKC activators distinctively acting in the megakaryocytic differentiation of K562 human erythroleukemia cells","volume":"29","author":"Kim","year":"2005","journal-title":"Leuk. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gwak, J., Lee, J.H., Chung, Y.H., Song, G.Y., and Oh, S. (2012). Small molecule-based promotion of PKCalpha-mediated beta-catenin degradation suppresses the proliferation of CRT-positive cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046697"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1093\/nar\/11.5.1475","article-title":"Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei","volume":"11","author":"Dignam","year":"1983","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"113458","DOI":"10.1016\/j.jpba.2020.113458","article-title":"Characterization of CGK012 in rat plasma by high performance liquid chromatography and mass spectrometry (HPLC-MS\/MS): Application to a pharmacokinetic study","volume":"189","author":"Ha","year":"2020","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.exer.2015.05.003","article-title":"Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data","volume":"137","author":"Urtti","year":"2015","journal-title":"Exp. Eye Res."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:12:40Z","timestamp":1766034760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":48,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ph18121884"],"URL":"https:\/\/doi.org\/10.3390\/ph18121884","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2025,12,12]]}}}