{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:53:56Z","timestamp":1790873636939,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Funds","award":["GURDTI 2018-1828-0002370"],"award-info":[{"award-number":["GURDTI 2018-1828-0002370"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Actinobacteria are known for their production of bioactive specialized metabolites, but they are still under-exploited. This study uses the \u201cOne Strain Many Compounds\u201d (OSMAC) method to explore the potential of three preselected marine-derived actinobacteria: Salinispora\u00a0arenicola (SH-78) and two Micromonospora sp. strains (SH-82 and SH-57). Various parameters, including the duration of the culture and the nature of the growth medium, were modified to assess their impact on the production of specialized metabolites. This approach involved a characterization based on chemical analysis completed with the construction of molecular networks and biological testing to evaluate cytotoxic and antiplasmodial activities. The results indicated that the influence of culture parameters depended on the studied species and also varied in relation with the microbial metabolites targeted. However, common favorable parameters could be observed for all strains such as an increase in the duration of the culture or the use of the A1 medium. For Micromonospora sp. SH-82, the solid A1 medium culture over 21 days favored a greater chemical diversity. A rise in the antiplasmodial activity was observed with this culture duration, with a IC50 twice as low as for the 14-day culture. Micromonospora sp. SH-57 produced more diverse natural products in liquid culture, with approximately 54% of nodes from the molecular network specifically linked to the type of culture support. Enhanced biological activities were also observed with specific sets of parameters. Finally, for Salinispora\u00a0arenicola SH-78, liquid culture allowed a greater diversity of metabolites, but intensity variations were specifically observed for some metabolites under other conditions. Notably, compounds related to staurosporine were more abundant in solid culture. Consequently, in the range of the chosen parameters, optimal conditions to enhance metabolic diversity and biological activities in these three marine-derived actinobacteria were identified, paving the way for future isolation works.<\/jats:p>","DOI":"10.3390\/md22010023","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T11:44:57Z","timestamp":1703763897000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["OSMAC Method to Assess Impact of Culture Parameters on Metabolomic Diversity and Biological Activity of Marine-Derived Actinobacteria"],"prefix":"10.3390","volume":"22","author":[{"given":"Alexandre","family":"Le Loarer","sequence":"first","affiliation":[{"name":"Laboratory of Chemistry and Biotechnology of Natural Products, Faculty of Sciences and Technology, University of La R\u00e9union, 15 Avenue Ren\u00e9 Cassin, CS 92003, CEDEX 09, 97744 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-355X","authenticated-orcid":false,"given":"Laurent","family":"Dufoss\u00e9","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry and Biotechnology of Natural Products, Faculty of Sciences and Technology, University of La R\u00e9union, 15 Avenue Ren\u00e9 Cassin, CS 92003, CEDEX 09, 97744 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-9671","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Bignon","sequence":"additional","affiliation":[{"name":"Institute of Chemistry of Natural Substances (ICSN), CNRS UPR 2301, Universit\u00e9 Paris-Saclay, 1, av. de la Terrasse, 91198 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0770-9990","authenticated-orcid":false,"given":"Michel","family":"Fr\u00e9d\u00e9rich","sequence":"additional","affiliation":[{"name":"Pharmacognosy Laboratory, Department of Pharmacy, Centre Interfacultaire de Recherche sur le M\u00e9dicament (CIRM), University of Li\u00e8ge, Campus du Sart-Tilman, Quartier H\u00f4pital, Avenue Hippocrate, 15, B36, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4052-6336","authenticated-orcid":false,"given":"Allison","family":"Ledoux","sequence":"additional","affiliation":[{"name":"Pharmacognosy Laboratory, Department of Pharmacy, Centre Interfacultaire de Recherche sur le M\u00e9dicament (CIRM), University of Li\u00e8ge, Campus du Sart-Tilman, Quartier H\u00f4pital, Avenue Hippocrate, 15, B36, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0562-2154","authenticated-orcid":false,"given":"Mireille","family":"Fouillaud","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry and Biotechnology of Natural Products, Faculty of Sciences and Technology, University of La R\u00e9union, 15 Avenue Ren\u00e9 Cassin, CS 92003, CEDEX 09, 97744 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-0704","authenticated-orcid":false,"given":"Anne","family":"Gauvin-Bialecki","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry and Biotechnology of Natural Products, Faculty of Sciences and Technology, University of La R\u00e9union, 15 Avenue Ren\u00e9 Cassin, CS 92003, CEDEX 09, 97744 Saint-Denis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lu, W.-Y., Li, H.-J., Li, Q.-Y., and Wu, Y.-C. (2021). Application of Marine Natural Products in Drug Research. Bioorg. Med. Chem., 35.","DOI":"10.1016\/j.bmc.2021.116058"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jose, P.A., Maharshi, A., and Jha, B. (2021). Actinobacteria in Natural Products Research: Progress and Prospects. Microbiol. Res., 246.","DOI":"10.1016\/j.micres.2021.126708"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Srinivasan, R., Kannappan, A., Shi, C., and Lin, X. (2021). Marine Bacterial Secondary Metabolites: A Treasure House for Structurally Unique and Effective Antimicrobial Compounds. Mar. Drugs, 19.","DOI":"10.3390\/md19100530"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Subramani, R., and Sipkema, D. (2019). Marine Rare Actinomycetes: A Promising Source of Structurally Diverse and Unique Novel Natural Products. Mar. Drugs, 17.","DOI":"10.3390\/md17050249"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.biopha.2016.12.086","article-title":"Marine Actinobacteria as a Drug Treasure House","volume":"87","author":"Hassan","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"929161","DOI":"10.3389\/fphar.2022.929161","article-title":"Natural Products from Actinobacteria as a Potential Source of New Therapies Against Colorectal Cancer: A Review","volume":"13","author":"Bahrami","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.3390\/md13084754","article-title":"The Sound of Silence: Activating Silent Biosynthetic Gene Clusters in Marine Microorganisms","volume":"13","author":"Reen","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Netzker, T., Fischer, J., Weber, J., Mattern, D.J., K\u00f6nig, C.C., Valiante, V., Schroeckh, V., and Brakhage, A.A. (2015). Microbial Communication Leading to the Activation of Silent Fungal Secondary Metabolite Gene Clusters. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00299"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/femsre\/fuw035","article-title":"Antibiotic Dialogues: Induction of Silent Biosynthetic Gene Clusters by Exogenous Small Molecules","volume":"41","author":"Okada","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pinedo-Rivilla, C., Aleu, J., and Dur\u00e1n-Patr\u00f3n, R. (2022). Cryptic Metabolites from Marine-Derived Microorganisms Using OSMAC and Epigenetic Approaches. Mar. Drugs, 20.","DOI":"10.3390\/md20020084"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Romano, S., Jackson, S.A., Patry, S., and Dobson, A.D.W. (2018). Extending the \u201cOne Strain Many Compounds\u201d (OSMAC) Principle to Marine Microorganisms. Mar. Drugs, 16.","DOI":"10.3390\/md16070244"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Palma Esposito, F., Giugliano, R., Della Sala, G., Vitale, G.A., Buonocore, C., Ausuri, J., Galasso, C., Coppola, D., Franci, G., and Galdiero, M. (2021). Combining OSMAC Approach and Untargeted Metabolomics for the Identification of New Glycolipids with Potent Antiviral Activity Produced by a Marine Rhodococcus. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22169055"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fan, B., Parrot, D., Bl\u00fcmel, M., Labes, A., and Tasdemir, D. (2019). Influence of OSMAC-Based Cultivation in Metabolome and Anticancer Activity of Fungi Associated with the Brown Alga Fucus Vesiculosus. Mar. Drugs, 17.","DOI":"10.3390\/md17010067"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Said Hassane, C., Fouillaud, M., Le Goff, G., Sklirou, A.D., Boyer, J.B., Trougakos, I.P., Jerabek, M., Bignon, J., de Voogd, N.J., and Ouazzani, J. (2020). Microorganisms Associated with the Marine Sponge Scopalina Hapalia: A Reservoir of Bioactive Molecules to Slow Down the Aging Process. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091262"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8735","DOI":"10.1021\/acs.jmedchem.2c00626","article-title":"Micromonospora: A Prolific Source of Bioactive Secondary Metabolites with Therapeutic Potential","volume":"65","author":"Yan","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Haque, N., Parveen, S., Tang, T., Wei, J., and Huang, Z. (2022). Marine Natural Products in Clinical Use. Mar. Drugs, 20.","DOI":"10.3390\/md20080528"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1039\/C4NP00167B","article-title":"The Marine Actinomycete Genus Salinispora: A Model Organism for Secondary Metabolite Discovery","volume":"32","author":"Jensen","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Le Loarer, A., Marcellin-Gros, R., Dufoss\u00e9, L., Bignon, J., Fr\u00e9d\u00e9rich, M., Ledoux, A., Queiroz, E.F., Wolfender, J.-L., Gauvin-Bialecki, A., and Fouillaud, M. (2023). Prioritization of Microorganisms Isolated from the Indian Ocean Sponge Scopalina Hapalia Based on Metabolomic Diversity and Biological Activity for the Discovery of Natural Products. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030697"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1038\/s41467-021-23953-9","article-title":"Ion Identity Molecular Networking for Mass Spectrometry-Based Metabolomics in the GNPS Environment","volume":"12","author":"Schmid","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41592-019-0344-8","article-title":"SIRIUS 4: A Rapid Tool for Turning Tandem Mass Spectra into Metabolite Structure Information","volume":"16","author":"Fleischauer","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70780","DOI":"10.7554\/eLife.70780","article-title":"The LOTUS Initiative for Open Knowledge Management in Natural Products Research","volume":"11","author":"Rutz","year":"2022","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.3389\/fpls.2019.01329","article-title":"Taxonomically Informed Scoring Enhances Confidence in Natural Products Annotation","volume":"10","author":"Rutz","year":"2019","journal-title":"Front. Plant Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1007\/s00449-012-0873-3","article-title":"Application of Solid-Phase Extraction to Agar-Supported Fermentation","volume":"36","author":"Adelin","year":"2013","journal-title":"Bioprocess. Biosyst. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Farinella, V.F., Kawafune, E.S., Tangerina, M.M.P., Domingos, H.V., Costa-Lotufo, L.V., and Ferreira, M.J.P. (2021). OSMAC Strategy Integrated with Molecular Networking for Accessing Griseofulvin Derivatives from Endophytic Fungi of Moquiniastrum Polymorphum (Asteraceae). Molecules, 26.","DOI":"10.3390\/molecules26237316"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.7164\/antibiotics.22.259","article-title":"Isolation, purification and preliminary characterization of megalomicin","volume":"22","author":"Marquez","year":"1969","journal-title":"J. Antibiot."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Useglio, M., Peir\u00fa, S., Rodr\u00edguez, E., Labadie, G.R., Carney, J.R., and Gramajo, H. (2010). TDP-l-Megosamine Biosynthesis Pathway Elucidation and Megalomicin A Production in Escherichia coli. Appl. Environ. Microbiol., 76.","DOI":"10.1128\/AEM.03083-09"},{"key":"ref_28","unstructured":"(2023, July 27). MetaCyc: Metabolic Pathways from All Domains of Life. Available online: https:\/\/metacyc.org\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1128\/AAC.01825-12","article-title":"Chemobiosynthesis of New Antimalarial Macrolides","volume":"57","author":"Goodman","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Armin, R., Z\u00fchlke, S., Grunewaldt-St\u00f6cker, G., Mahnkopp-Dirks, F., and Kusari, S. (2021). Production of Siderophores by an Apple Root-Associated Streptomyces Ciscaucasicus Strain GS2 Using Chemical and Biological OSMAC Approaches. Molecules, 26.","DOI":"10.3390\/molecules26123517"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.7164\/antibiotics.48.326","article-title":"Isolation and Structural Elucidation of Antioxidative Substances, Carbazoquinocins A to F","volume":"48","author":"Tanaka","year":"1995","journal-title":"J. Antibiot."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1248\/cpb.32.3493","article-title":"Studies on Rhubarb (Rhei Rhizoma). V. Isolation and Characterization of Chromone and Chromanone Derivatives","volume":"32","author":"Kashiwada","year":"1984","journal-title":"Chem. Pharm. Bull."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"952","DOI":"10.7164\/antibiotics.51.952","article-title":"GTRI-02, a New Lipid Peroxidation Inhibitor from Micromonospora Sp. SA246","volume":"51","author":"Yeo","year":"1998","journal-title":"J. Antibiot."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/cbdd.13951","article-title":"Chromones: Privileged Scaffold in Anticancer Drug Discovery","volume":"98","author":"Patil","year":"2021","journal-title":"Chem. Bio. Drug Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2100277","DOI":"10.1002\/ardp.202100277","article-title":"The Anticancer Activity of Carbazole Alkaloids","volume":"355","author":"Song","year":"2022","journal-title":"Arch. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejphar.2017.07.023","article-title":"Aristeromycin and DZNeP Cause Growth Inhibition of Prostate Cancer via Induction of Mir-26a","volume":"812","author":"Uchiyama","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/acs.jnatprod.6b00722","article-title":"Prioritizing Natural Product Diversity in a Collection of 146 Bacterial Strains Based on Growth and Extraction Protocols","volume":"80","author":"Larson","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1128\/AEM.01891-06","article-title":"Species-Specific Secondary Metabolite Production in Marine Actinomycetes of the Genus Salinispora","volume":"73","author":"Jensen","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bauermeister, A., Velasco-Alzate, K., Dias, T., Macedo, H., Ferreira, E.G., Jimenez, P.C., Lotufo, T.M.C., Lopes, N.P., Gaud\u00eancio, S.P., and Costa-Lotufo, L.V. (2018). Metabolomic Fingerprinting of Salinispora From Atlantic Oceanic Islands. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.03021"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1002\/cbic.201900764","article-title":"Extending the Salinilactone Family","volume":"21","author":"Schlawis","year":"2020","journal-title":"Chembiochem"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"396","DOI":"10.7164\/antibiotics.55.396","article-title":"New Insights into Rifamycin B Biosynthesis: Isolation of Proansamycin B and 34a-Deoxy-Rifamycin W as Early Macrocyclic Intermediates Indicating Two Separated Biosynthetic Pathways","volume":"55","author":"Stratmann","year":"2002","journal-title":"J. Antibiot."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.3390\/md10051092","article-title":"Structure Elucidation and Anticancer Activity of 7-Oxostaurosporine Derivatives from the Brazilian Endemic Tunicate Eudistoma Vannamei","volume":"10","author":"Jimenez","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1021\/acs.jnatprod.8b00103","article-title":"Staurosporine Derivatives Generated by Pathway Engineering in a Heterologous Host and Their Cytotoxic Selectivity","volume":"81","author":"Xiao","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Pluskal, T., Castillo, S., Villar-Briones, A., and Ore\u0161i\u010d, M. (2010). MZmine 2: Modular Framework for Processing, Visualizing, and Analyzing Mass Spectrometry-Based Molecular Profile Data. BMC Bioinform., 11.","DOI":"10.1186\/1471-2105-11-395"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8696","DOI":"10.1021\/acs.analchem.7b00947","article-title":"One Step Forward for Reducing False Positive and False Negative Compound Identifications from Mass Spectrometry Metabolomics Data: New Algorithms for Constructing Extracted Ion Chromatograms and Detecting Chromatographic Peaks","volume":"89","author":"Myers","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and Community Curation of Mass Spectrometry Data with Global Natural Products Social Molecular Networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1021\/acs.analchem.5b04804","article-title":"Integration of Molecular Networking and In-Silico MS\/MS Fragmentation for Natural Products Dereplication","volume":"88","author":"Allard","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12580","DOI":"10.1073\/pnas.1509788112","article-title":"Searching Molecular Structure Databases with Tandem Mass Spectra Using CSI:FingerID","volume":"112","author":"Shen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/s41587-020-0740-8","article-title":"Systematic Classification of Unknown Metabolites Using High-Resolution Fragmentation Mass Spectra","volume":"39","author":"Nothias","year":"2021","journal-title":"Nat. Biotechnol."},{"key":"ref_51","first-page":"61","article-title":"ClassyFire: Automated Chemical Classification with a Comprehensive, Computable Taxonomy","volume":"8","author":"Eisner","year":"2016","journal-title":"J. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human Malaria Parasites in Continuous Culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/22\/1\/23\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:43:46Z","timestamp":1760132626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/22\/1\/23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,28]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["md22010023"],"URL":"https:\/\/doi.org\/10.3390\/md22010023","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,28]]}}}