{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:04:19Z","timestamp":1784624659684,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"EU-H2020","doi-asserted-by":"publisher","award":["101000373"],"award-info":[{"award-number":["101000373"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The skin barrier is essential for maintaining epidermal homeostasis and preventing transepidermal water loss (TEWL). This study investigated the ability of a Hyssopus officinalis cell culture hydroethanolic extract to support epidermal barrier function by modulating ceramide-related enzymes and structural proteins. Hydroethanolic extracts from cell cultures grown under light and dark conditions were characterized by high-resolution mass spectrometry. Dark-grown cultures accumulated higher levels of rosmarinic acid, hydroxytyrosol glycosides, and polymethoxyflavones than light-grown cultures and intact plants. In keratinocytes, the extract from dark-grown cells (HoEx) at 0.002% w\/v exhibited significant antioxidant activity (20% ROS reduction) and increased \u03b2-glucocerebrosidase (GBA) activity (25%) as well as the expression of \u03b2-glucocerebrosidase (44%), serine palmitoyltransferase (34%), involucrin (17%), and filaggrin (44%) compared with control. In human skin explants, 0.5% w\/w HoEx increased ceramide content (36%) and total epidermal lipid levels (99%) relative to control. In a clinical study involving 10 volunteers with mechanically stressed skin, 0.5% w\/w HoEx increased GBA activity by 30% and reduced TEWL by 15%, whereas placebo treatment led to a 55% decrease in GBA activity and a 25% increase in TEWL. Collectively, these findings indicate that HoEx modulates multiple epidermal pathways involved in lipid processing and differentiation under in vitro, ex vivo, and stressed in vivo conditions. While the study was not designed to establish mechanistic causality, the coordinated modulation of ceramide-related enzymes, structural proteins, and TEWL suggests that HoEx may support epidermal barrier function within the limits of the tested models. HoEx therefore represents a standardized source of bioactive compounds with potential relevance for dermocosmetic applications.<\/jats:p>","DOI":"10.3390\/cells15141300","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:14:27Z","timestamp":1784621667000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyssopus officinalis L. (Lamiaceae) Cell Culture Extract Modulates Epidermal Lipid-Related and Differentiation Markers"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6017-1253","authenticated-orcid":false,"given":"Annalisa","family":"Tito","sequence":"first","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2451-2004","authenticated-orcid":false,"given":"Eleonora","family":"Vardaro","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"De Lucia","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danila","family":"Falanga","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7011-5047","authenticated-orcid":false,"given":"Cristiana","family":"De Musis","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-838X","authenticated-orcid":false,"given":"Antonio","family":"Colantuono","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Cefariello","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7479-6289","authenticated-orcid":false,"given":"Lucia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuditta","family":"Vitiello","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Arra","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1406-6214","authenticated-orcid":false,"given":"Ritamaria","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-0233","authenticated-orcid":false,"given":"Gianfranco","family":"Diretto","sequence":"additional","affiliation":[{"name":"Italian National Agency for New Technologies, Energy, and Sustainable Development (ENEA), Green Bi Technology Laboratory, Casaccia Research Centre, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-5754","authenticated-orcid":false,"given":"Olivia Costantina","family":"Demurtas","sequence":"additional","affiliation":[{"name":"Italian National Agency for New Technologies, Energy, and Sustainable Development (ENEA), Green Bi Technology Laboratory, Casaccia Research Centre, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6875-2546","authenticated-orcid":false,"given":"Maria","family":"Sulli","sequence":"additional","affiliation":[{"name":"Italian National Agency for New Technologies, Energy, and Sustainable Development (ENEA), Green Bi Technology Laboratory, Casaccia Research Centre, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos","family":"Pappas","sequence":"additional","affiliation":[{"name":"CRB S.A., CH-1070 Puidoux, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4632-4620","authenticated-orcid":false,"given":"Giovanni","family":"Greco","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-1592","authenticated-orcid":false,"given":"Sonia","family":"Laneri","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Colucci","sequence":"additional","affiliation":[{"name":"Arterra Bioscience Spa, 80142 Naples, Italy"},{"name":"Vitalab S.r.l., 80142 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1111\/exd.14635","article-title":"\u201cNormal\u201d TEWL-how Can It Be Defined? A Systematic Review","volume":"31","author":"Green","year":"2022","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/ics.12832","article-title":"Moisturizing at a Molecular Level\u2014The Basis of Corneocare","volume":"45","author":"Voegeli","year":"2023","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1016\/j.ajic.2006.05.295","article-title":"Structure and Function of the Epidermal Barrier","volume":"34","author":"Wickett","year":"2006","journal-title":"Am. J. Infect. Control"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000441539","article-title":"Filaggrin and Skin Barrier Function","volume":"49","author":"Kezic","year":"2016","journal-title":"Curr. Probl. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/ics.12974","article-title":"Protein Degradation in the Stratum Corneum","volume":"46","author":"Stamatas","year":"2024","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101252","DOI":"10.1016\/j.plipres.2023.101252","article-title":"The Skin Barrier: An Extraordinary Interface with an Exceptional Lipid Organization","volume":"92","author":"Bouwstra","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Quinville, B.M., Deschenes, N.M., Ryckman, A.E., and Walia, J.S. (2021). A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115793"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41594-020-00551-9","article-title":"Structural Insights into the Regulation of Human Serine Palmitoyltransferase Complexes","volume":"28","author":"Wang","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1038\/jid.2013.199","article-title":"Barrier Abnormality Due to Ceramide Deficiency Leads to Psoriasiform Inflammation in a Mouse Model","volume":"133","author":"Nakajima","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Boer, D.E.C., van Smeden, J., Bouwstra, J.A., and Aerts, J.M.F.G. (2020). Glucocerebrosidase: Functions in and Beyond the Lysosome. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030736"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1111\/bjd.20979","article-title":"Children with Atopic Dermatitis Show Increased Activity of \u0392-glucocerebrosidase and Stratum Corneum Levels of Glucosylcholesterol That Are Strongly Related to the Local Cytokine Milieu","volume":"186","author":"Kezic","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/ics.12236","article-title":"An Oil-soluble Extract of Rubus Idaeus Cells Enhances Hydration and Water Homeostasis in Skin Cells","volume":"37","author":"Tito","year":"2015","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Iannuzzo, F., Piccolo, V., Novellino, E., Schiano, E., Salviati, E., Summa, V., Campiglia, P., Tenore, G.C., and Maisto, M. (2022). A Food-Grade Method for Enhancing the Levels of Low Molecular Weight Proanthocyanidins with Potentially High Intestinal Bioavailability. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113557"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000445776","article-title":"Controlled Penetration of a Novel Dimeric Ceramide into and across the Stratum Corneum Using Microemulsions and Various Types of Semisolid Formulations","volume":"29","author":"Neubert","year":"2016","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhao, C., Wu, S., and Wang, H. (2025). Medicinal Plant Extracts Targeting UV-Induced Skin Damage: Molecular Mechanisms and Therapeutic Potential. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052278"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"T\u00fc\u011fen, A., and Buruleanu, C.L. (2025). The Role of Plant-Derived Bioactive Compounds in Mitigating Oxidative Stress. Foods, 15.","DOI":"10.3390\/foods15010108"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ceccacci, S., De Lucia, A., Tito, A., Tortora, A., Falanga, D., Arciello, S., Ausanio, G., Di Cicco, C., Monti, M.C., and Apone, F. (2021). An Oenothera Biennis Cell Cultures Extract Endowed with Skin Anti-Ageing Activity Improves Cell Mechanical Properties. Metabolites, 11.","DOI":"10.3390\/metabo11080527"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ceccacci, S., Lucia, A.D., Tortora, A., Colantuono, A., Carotenuto, G., Tito, A., and Monti, M.C. (2022). Jasminum Sambac Cell Extract as Antioxidant Booster against Skin Aging. Antioxidants, 11.","DOI":"10.3390\/antiox11122409"},{"key":"ref_19","first-page":"1","article-title":"Cosm\u2019Innov Congress, 5th Edition, 24 & 25 May 2023, Orl\u00e9ans, France","volume":"45","author":"Yoo","year":"2023","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Barrea, L., Muscogiuri, G., Pugliese, G., de Alteriis, G., Maisto, M., Donnarumma, M., Tenore, G.C., Colao, A., Fabbrocini, G., and Savastano, S. (2021). Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa). Nutrients, 13.","DOI":"10.3390\/nu13061997"},{"key":"ref_21","first-page":"195","article-title":"Antioxidant and Anti-Melanogenic Activities of Hyssopus Officinalis Extracts","volume":"42","author":"Shin","year":"2016","journal-title":"J. Soc. Cosmet. Sci. Korea"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Maisto, M., Iannuzzo, F., Novellino, E., Schiano, E., Piccolo, V., and Tenore, G.C. (2023). Natural Polyphenols for Prevention and Treatment of Urinary Tract Infections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043277"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9250121","DOI":"10.26599\/FSHW.2024.9250121","article-title":"Rosmarinic Acid Regulates Lipid Accumulation through Lipid Metabolism and Anti-Inflammatory","volume":"14","author":"Lin","year":"2025","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Luo, C., Zou, L., Sun, H., Peng, J., Gao, C., Bao, L., Ji, R., Jin, Y., and Sun, S. (2020). A Review of the Anti-Inflammatory Effects of Rosmarinic Acid on Inflammatory Diseases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00153"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jung, S.-W., Park, G.H., Kim, E., Yoo, K.M., Kim, H.W., Lee, J.S., Chang, M.Y., Shin, K.-O., Park, K., and Choi, E.H. (2022). Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface PH and Improves the Skin Barrier Function. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073910"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11240-014-0467-7","article-title":"Production of Secondary Metabolites from Cell and Organ Cultures: Strategies and Approaches for Biomass Improvement and Metabolite Accumulation","volume":"118","author":"Murthy","year":"2014","journal-title":"Plant Cell Tissue Organ Cult. (PCTOC)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1002\/elsc.201800066","article-title":"Plant Cell Culture as Emerging Technology for Production of Active Cosmetic Ingredients","volume":"18","author":"Georgiev","year":"2018","journal-title":"Eng. Life Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cuciniello, R., Di Meo, F., Sulli, M., Demurtas, O.C., Tanori, M., Mancuso, M., Villano, C., Aversano, R., Carputo, D., and Baldi, A. (2023). Aglianico Grape Seed Semi-Polar Extract Exerts Anticancer Effects by Modulating MDM2 Expression and Metabolic Pathways. Cells, 12.","DOI":"10.3390\/cells12020210"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103478","DOI":"10.1016\/j.bcab.2024.103478","article-title":"Capsicum Chinense Cell Cultures: A Biotechnological Platform for the Sustainable Production of Bioactive Metabolites for the Cosmetics Market","volume":"63","author":"Akhgari","year":"2025","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Skrypnik, L., Feduraev, P., Styran, T., Golovin, A., Katserov, D., Nebreeva, S., and Maslennikov, P. (2022). Biomass, Phenolic Compounds, Essential Oil Content, and Antioxidant Properties of Hyssop (Hyssopus officinalis L.) Grown in Hydroponics as Affected by Treatment Type and Selenium Concentration. Horticulturae, 8.","DOI":"10.3390\/horticulturae8111037"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/ics.12972","article-title":"The Role of Ceramides in Skin Barrier Function and the Importance of Their Correct Formulation for Skincare Applications","volume":"46","author":"Schild","year":"2024","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s40257-021-00619-2","article-title":"Ceramides in Skin Health and Disease: An Update","volume":"22","author":"Uchida","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_33","first-page":"350","article-title":"A Mini Review on the Chemodiversity of Lamiaceae Plants That Are Native to T\u00fcrkiye and Turkish Republic of Northern Cyprus","volume":"19","year":"2025","journal-title":"Rec. Nat. Prod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0031-9422(02)00513-7","article-title":"Rosmarinic Acid","volume":"62","author":"Petersen","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7068","DOI":"10.3390\/molecules16087068","article-title":"Activity and Stability Studies of Verbascoside, a Novel Antioxidant, in Dermo-Cosmetic and Pharmaceutical Topical Formulations","volume":"16","author":"Vertuani","year":"2011","journal-title":"Molecules"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An Overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1468-2494.2010.00522.x","article-title":"Clinical Efficacy Comparison of Anti-wrinkle Cosmetics Containing Herbal Flavonoids","volume":"32","author":"Chuarienthong","year":"2010","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2676307","DOI":"10.1155\/2019\/2676307","article-title":"Benefits of Hesperidin for Cutaneous Functions","volume":"2019","author":"Man","year":"2019","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0022-2275(20)39184-7","article-title":"Permeability Barrier Requirements Regulate Epidermal \u03b2-Glucocerebrosidase","volume":"35","author":"Holleran","year":"1994","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1600-0625.2008.00786.x","article-title":"The Skin: An Indispensable Barrier","volume":"17","author":"Proksch","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1208\/s12249-021-02154-z","article-title":"In Vitro Modeling of Skin Barrier Disruption and Its Recovery by Ceramide-Based Formulations","volume":"23","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108681","DOI":"10.1016\/j.pharmthera.2024.108681","article-title":"Bioactive Lipids in the Skin Barrier Mediate Its Functionality in Health and Disease","volume":"260","author":"Nicolaou","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/1523-1747.ep12472288","article-title":"Involucrin\u2014Structure and Role in Envelope Assembly","volume":"100","author":"Eckert","year":"1993","journal-title":"J. Investig. Dermatol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:33:21Z","timestamp":1784622801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/14\/1300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":43,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cells15141300"],"URL":"https:\/\/doi.org\/10.3390\/cells15141300","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}