{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:06:10Z","timestamp":1790139970076,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["BG16RFPR002-1.014-0014-C01"],"award-info":[{"award-number":["BG16RFPR002-1.014-0014-C01"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"award":["BG16RFPR002-1.014-0014-C01"],"award-info":[{"award-number":["BG16RFPR002-1.014-0014-C01"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Plant extracts remain an important source of antiviral agents, while nanocarrier-based delivery systems have emerged as a promising strategy for improving their therapeutic safety and efficacy. Building on previous findings indicating that nanoliposomal encapsulation improved the anti-coronavirus activity of Aesculus hippocastanum seed extract against human coronavirus strain OC43 (HCoV-OC43), the present study evaluated whether encapsulation reduces the genotoxic effects of the extract and explored a potential molecular basis for the previously observed antiviral activity. Genotoxicity assessment using the alkaline comet assay in MRC-5 human lung fibroblasts demonstrated that at 1 mg\/mL, liposomal encapsulation was associated with an approximately 86.0% reduction in %Tail DNA, from 21.301 \u00b1 0.368% for the free extract to 2.984 \u00b1 1.523% for the liposome-encapsulated extract. In parallel, chemical profiling by high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (HPLC\u2013HRMS\/MS) enabled the identification and tentative annotation of 46 metabolites, including triterpenoid saponins, flavonoids, indole-3-acetic acid glycosides, and organic acids. Based on this phytochemical profile, representative constituents were subjected to molecular docking against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nonstructural proteins Nsp5 and Nsp12 to investigate their potential contribution to the previously demonstrated antiviral activity of the extract. Among the evaluated compounds, hesperidin exhibited the most favorable predicted binding affinity toward both targets, while quercetin also showed favorable interactions, suggesting that flavonoid constituents may contribute to the antiviral activity of the extract. These findings indicate that liposomal encapsulation improves the biological safety profile of A. hippocastanum seed extract, while phytochemical characterization and molecular docking provide preliminary insights into the constituents that may contribute to its previously demonstrated anti-coronavirus activity.<\/jats:p>","DOI":"10.3390\/ijms27188372","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HPLC\u2013HRMS\/MS Characterization, Molecular Docking, and Comparative Genotoxicity of Free and Liposome-Encapsulated Aesculus hippocastanum Seed Extract"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5628-0695","authenticated-orcid":false,"given":"Boyka","family":"Andonova-Lilova","sequence":"first","affiliation":[{"name":"Research and Development and Innovation Consortium, 1784 Sofia, Bulgaria"},{"name":"Department Agrobiotechnology, Agricultural Academy, AgroBio Institute, 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-4157","authenticated-orcid":false,"given":"Plamena","family":"Staleva","sequence":"additional","affiliation":[{"name":"Research and Development and Innovation Consortium, 1784 Sofia, Bulgaria"},{"name":"Laboratory Organic Synthesis and Stereochemistry, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4101-7036","authenticated-orcid":false,"given":"Zhanina","family":"Petkova","sequence":"additional","affiliation":[{"name":"Laboratory Organic Synthesis and Stereochemistry, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"Centre of Competence \u201cSustainable Utilization of Bio-Resources and Waste of Medicinal and Aromatic Plants for Innovative Bioactive Products\u201d (BIORESOURCES BG), 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-7213","authenticated-orcid":false,"given":"Emilio","family":"Mateev","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5604-2719","authenticated-orcid":false,"given":"Tzvetelina","family":"Zagorcheva","sequence":"additional","affiliation":[{"name":"Research and Development and Innovation Consortium, 1784 Sofia, Bulgaria"},{"name":"Department Agrobiotechnology, Agricultural Academy, AgroBio Institute, 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6737-1936","authenticated-orcid":false,"given":"Viktoria","family":"Milkova","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry \u2018Acad. R. Kaischew\u2019, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Anna","family":"Gyurova","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry \u2018Acad. R. Kaischew\u2019, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Martinov","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry \u2018Acad. R. Kaischew\u2019, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2613-6259","authenticated-orcid":false,"given":"Viktor","family":"Rashev","sequence":"additional","affiliation":[{"name":"Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-4471","authenticated-orcid":false,"given":"Neli","family":"Vilhelmova-Ilieva","sequence":"additional","affiliation":[{"name":"Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., 26, 1113 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","first-page":"1189","article-title":"Review of coronavirus in rats: A potential zoonotic threat","volume":"52","author":"Hamid","year":"2023","journal-title":"Sains Malays."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liu, D.X., Liang, J.Q., and Fung, T.S. (2021). Human Coronavirus-229E, -OC43, -NL63, and -HKU1 (Coronaviridae). Encyclopedia of Virology, Academic Press.","DOI":"10.1016\/B978-0-12-809633-8.21501-X"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nassar, A., Ibrahim, I.M., Amin, F.G., Magdy, M., Elgharib, A.M., Azzam, E.B., Nasser, F., Yousry, K., Shamkh, I.M., and Mahdy, S.M. (2021). A Review of Human Coronaviruses\u2019 Receptors: The Host-Cell Targets for the Crown Bearing Viruses. Molecules, 26.","DOI":"10.3390\/molecules26216455"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF01317891","article-title":"Comparison of the morphology of three coronaviruses","volume":"59","author":"Davies","year":"1979","journal-title":"Arch. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.17537\/2022.17.289","article-title":"On Classification and Taxonomy of Coronaviruses (Riboviria, Nidovirales, Coronaviridae) with Special Focus on Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2)","volume":"17","author":"Mavrodiev","year":"2022","journal-title":"Math. Biol. Bioinform."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2282","DOI":"10.1002\/rmv.2282","article-title":"An overview on the seven pathogenic human coronaviruses","volume":"32","author":"Kesheh","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ianevski, A., Yao, R., Zusinaite, E., Lello, L.S., Wang, S., Jo, E., Yang, J., Ravlo, E., Wang, W., and Lysvand, H. (2021). Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections. Viruses, 13.","DOI":"10.21203\/rs.3.rs-189394\/v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An overview of their replication and pathogenesis","volume":"Volume 1282","author":"Fehr","year":"2015","journal-title":"Coronaviruses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.46795\/ijhcbs.v2i3.222","article-title":"Brief Review on Remdesivir","volume":"2","author":"Daka","year":"2021","journal-title":"Int. J. Health Care Biol. Sci."},{"key":"ref_10","first-page":"3131","article-title":"Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro","volume":"13","author":"Radoshitzky","year":"2023","journal-title":"Dent. Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rodriguez, L., Zamora, J.L.R., Han, D., Moshiri, J., Peinovich, N., Martinez, C., Ho, P.Y., Li, J., Aeschbacher, T., and Martin, R. (2025). Remdesivir and Obeldesivir Retain Potent Antiviral Activity Against SARS-CoV-2 Omicron Variants. Viruses, 17.","DOI":"10.3390\/v17020168"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bhatla, S.C., and Lal, M.A. (2023). Secondary Metabolites. Plant Physiology, Development and Metabolism, Springer Nature.","DOI":"10.1007\/978-981-99-5736-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2019.01.018","article-title":"Aesculus hippocastanum L. seed extract shows virucidal and antiviral activities against respiratory syncytial virus (RSV) and reduces lung inflammation in vivo","volume":"164","author":"Salinas","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6418","DOI":"10.1038\/s41598-024-56759-y","article-title":"Aesculus hippocastanum extract and the main bioactive constituent \u03b2-escin as antivirals agents against coronaviruses, including SARS-CoV-2","volume":"14","author":"Vicente","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1111\/jphp.13002","article-title":"Virucidal, antiviral and immunomodulatory activities of \u03b2-escin and Aesculus hippocastanum extract","volume":"70","author":"Michelini","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nikolova, I., Paunova-Krasteva, T., Petrova, Z., Grozdanov, P., Nikolova, N., Tsonev, G., Triantafyllidis, A., Andreev, S., Trepechova, M., and Milkova, V. (2022). Bulgarian Medicinal Extracts as Natural Inhibitors with Antiviral and Antibacterial Activity. Plants, 11.","DOI":"10.3390\/plants11131666"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vilhelmova-Ilieva, N., Petrova, Z., Georgieva, A., Tzvetanova, E., Trepechova, M., and Mileva, M. (2022). Anti-Coronavirus Efficiency and Redox-Modulating Capacity of Polyphenol-Rich Extracts from Traditional Bulgarian Medicinal Plants. Life, 12.","DOI":"10.3390\/life12071088"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dridi, A., Reis, F.S., Pires, T.C.S.P., Calhelha, R.C., Pereira, C., Zaghdoudi, K., Ferreira, I.C.F.R., Barros, L., and Barreira, J.C.M. (2023). Aesculus hippocastanum L.: A Simple Ornamental Plant or a Source of Compelling Molecules for Industry?. Separations, 10.","DOI":"10.3390\/separations10030160"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, N., Cao, S., Huang, W., Li, P., Kang, N., Ding, L., and Qiu, F. (2019). New Indole Glycosides from Aesculus chinensis var. chekiangensis and Their Neuroprotective Activities. Molecules, 24.","DOI":"10.3390\/molecules24224063"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Owczarek, A., Ko\u0142odziejczyk-Czepas, J., Marczuk, P., Siwek, J., W\u0105sowicz, K., and Olszewska, M.A. (2021). Bioactivity Potential of Aesculus hippocastanum L. Flower: Phytochemical Profile, Antiradical Capacity and Protective Effects on Human Plasma Components under Oxidative\/Nitrative Stress In Vitro. Pharmaceuticals, 14.","DOI":"10.3390\/ph14121301"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Savarino, P., Colson, E., Andr\u00e9, J., and Gerbaux, P. (2023). Horse Chestnut Saponins\u2013Escins, Isoescins, Transescins, and Desacylescins. Molecules, 28.","DOI":"10.3390\/molecules28052087"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s13659-017-0148-4","article-title":"Triterpenoid Saponins from the Seeds of Aesculus chinensis and Their Cytotoxicities","volume":"8","author":"Cheng","year":"2018","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhang, N., Wei, S., Cao, S., Zhang, Q., Kang, N., Ding, L., and Qiu, F. (2020). Bioactive Triterpenoid Saponins From the Seeds of Aesculus chinensis Bge. var. chekiangensis. Front. Chem., 7.","DOI":"10.3389\/fchem.2019.00908"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sharipov, A., Tursunov, K., Fazliev, S., Azimova, B., and Razzokov, J. (2021). Hypoglycemic and Anti-Inflammatory Effects of Triterpene Glycoside Fractions from Aeculus hippocastanum Seeds. Molecules, 26.","DOI":"10.3390\/molecules26133784"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gyurova, A., Milkova, V., Iliev, I., Lazarova-Zdravkova, N., Rashev, V., Simeonova, L., and Vilhelmova-Ilieva, N. (2024). Anti-Coronavirus Activity of Chitosan-Stabilized Liposomal Nanocarriers Loaded with Natural Extracts from Bulgarian Flora. Life, 14.","DOI":"10.3390\/life14091180"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yang, X., Xing, X., Liu, Y., and Zheng, Y. (2022). Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.962863"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"124169","DOI":"10.1016\/j.ijbiomac.2023.124169","article-title":"Identification of RdRp inhibitors against SARS-CoV-2 through E-pharmacophore-based virtual screening, molecular docking and MD simulations approaches","volume":"237","author":"Rehman","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1038\/s41467-022-31210-w","article-title":"Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance","volume":"13","author":"Shaqra","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1002\/jcc.26717","article-title":"Identification of novel inhibitors of SARS-CoV-2 main protease (Mpro) from Withania sp. by molecular docking and molecular dynamics simulation","volume":"42","author":"Verma","year":"2021","journal-title":"J. Comput. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cell.2020.05.034","article-title":"Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase","volume":"182","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/s41467-019-10280-3","article-title":"Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors","volume":"10","author":"Kirchdoerfer","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41586-020-2368-8","article-title":"Structure of replicating SARS-CoV-2 polymerase","volume":"584","author":"Hillen","year":"2020","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ngo, V., and Duennwald, M.L. (2022). Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11122345"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Boyadzhieva, S.S., Tsvetanova, F.V., Coelho, J.A.P., Staleva, P., Kamenova-Nacheva, M., Taneva, S., and Stateva, R.P. (2026). Boosting the Sustainable Transformation of Cornus mas L. Stones Using a Hybrid Strategy Involving Microwave-Assisted Extraction. Molecules, 31.","DOI":"10.3390\/molecules31030525"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Trendafilova, A., Ivanova, V., Novakovic, M., Jadranin, M., Staleva, P., Dimitrova, P., Veleva, R., Topouzova-Hristova, T., and Paunova-Krasteva, T. (2026). Comparative Phytochemical Profiling and In Vitro Antibiofilm Activity of the Aerial and Underground Parts of Primula veris subsp. columnae (Ten.) L\u0215di. Plants, 15.","DOI":"10.3390\/plants15152259"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1021\/jacs.1c08402","article-title":"Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses","volume":"144","author":"Luttens","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2021946118","DOI":"10.1073\/pnas.2021946118","article-title":"Structure of the SARS-CoV-2 RNA-dependent RNA polymerase in the presence of favipiravir-RTP","volume":"118","author":"Naydenova","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:42:29Z","timestamp":1790138549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188372"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188372","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}