{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:07:20Z","timestamp":1782122840225,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["22\/2018"],"award-info":[{"award-number":["22\/2018"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American-European Congress of Ophthalmic Surgery","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dry eye is a multifactorial disease that affects the ocular surface and tear fluid. Current treatment options include lubricant eye drop application several times a day. However, these eye drops often cause local side effects like ocular allergies or blurred vision after the application. To test new treatment options, a robust dry eye model is needed. Here, a porcine ex vivo model was established by means of incubation of porcine corneas in low humidity (LH) and characterized by histological damage evaluation, epithelial thickness and by relevant dry eye markers, such as interleukin 1 beta (IL-1\u03b2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB), occludin and galectin-3. In the dry eye model proposed, an increased secretion of IL-1\u03b2 was observed, as well as an upregulation of NF-\u03baB, occludin and galectin-3 mRNA expression. Moreover, the model presented a higher rate of cell death in comparison to the controls. These effects could be reversed with successful treatment of dexamethasone (dexa) and partially reversed with hyaluronic acid (HA) containing eye drops. Furthermore, medium-molecular-weight HA stimulated an increase in IL-1\u03b2 in the model proposed. In conclusion, this dry eye model mimics the in vivo condition and hence allows for animal-free testing of novel dry eye treatments.<\/jats:p>","DOI":"10.3390\/ijms23094567","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T01:55:51Z","timestamp":1650506151000},"page":"4567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Porcine Corneas Incubated at Low Humidity Present Characteristic Features Found in Dry Eye Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7253-937X","authenticated-orcid":false,"given":"Alice Rocha Teixeira","family":"Netto","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology, Clinical Research University Eye Hospital T\u00fcbingen, Eberhard Karls Universit\u00e4t T\u00fcbingen, Elfriede-Aulhorn-Stra\u00dfe 7, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8697-2569","authenticated-orcid":false,"given":"Jos\u00e9","family":"Hurst","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology, Clinical Research University Eye Hospital T\u00fcbingen, Eberhard Karls Universit\u00e4t T\u00fcbingen, Elfriede-Aulhorn-Stra\u00dfe 7, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Ulrich","family":"Bartz-Schmidt","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology, Clinical Research University Eye Hospital T\u00fcbingen, Eberhard Karls Universit\u00e4t T\u00fcbingen, Elfriede-Aulhorn-Stra\u00dfe 7, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-5517","authenticated-orcid":false,"given":"Sven","family":"Schnichels","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology, Clinical Research University Eye Hospital T\u00fcbingen, Eberhard Karls Universit\u00e4t T\u00fcbingen, Elfriede-Aulhorn-Stra\u00dfe 7, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1542-0124(12)70081-2","article-title":"The Definition and Classification of Dry Eye Disease","volume":"5","author":"Lemp","year":"2007","journal-title":"Ocul. Surf."},{"key":"ref_2","first-page":"581","article-title":"Diagnosis of Dry Eye Disease and Emerging Technologies","volume":"8","author":"Zeev","year":"2014","journal-title":"Clin. Ophthalmol. Auckl. NZ"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, X., Jeyalatha M, V., Qu, Y., He, X., Ou, S., Bu, J., Jia, C., Wang, J., Wu, H., and Liu, Z. (2017). Dry Eye Management: Targeting the Ocular Surface Microenvironment. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071398"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/17469899.2019.1635456","article-title":"Medication Adherence in Patients with Ocular Hypertension or Glaucoma","volume":"14","author":"Robin","year":"2019","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and Physiology of the Cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J. Cataract. Refract. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.jtos.2017.05.011","article-title":"TFOS DEWS II Pathophysiology Report","volume":"15","author":"Bron","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.ajo.2015.02.008","article-title":"Alteration of Galectin-3 in Tears of Patients with Dry Eye Disease","volume":"159","author":"Uchino","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_8","unstructured":"B\u00e4uml, G. (2008). Interaktion des Humanen Tight Junction Proteins ZO-1 mit dem Ras-Effektor AF6 und Untersuchungen am Zellwandprotein Aga2 von Saccharomyces cerevisiae. [Ph.D. Thesis, Universit\u00e4t Regensburg]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.preteyeres.2012.02.003","article-title":"Ocular Surface Immunity: Homeostatic Mechanisms and Their Disruption in Dry Eye Disease","volume":"31","author":"Barabino","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1001\/archophthalmol.2009.316","article-title":"Essential Role for C-Jun N-Terminal Kinase 2 in Corneal Epithelial Response to Desiccating Stress","volume":"127","author":"Pangelinan","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0002-9440(10)62232-8","article-title":"Matrix Metalloproteinase-9 Knockout Confers Resistance to Corneal Epithelial Barrier Disruption in Experimental Dry Eye","volume":"166","author":"Pflugfelder","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.1167\/iovs.05-1382","article-title":"Desiccating Stress Stimulates Expression of Matrix Metalloproteinases by the Corneal Epithelium","volume":"47","author":"Corrales","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jaut.2017.02.006","article-title":"Mitochondrial DNA Oxidation Induces Imbalanced Activity of NLRP3\/NLRP6 Inflammasomes by Activation of Caspase-8 and BRCC36 in Dry Eye","volume":"80","author":"Chi","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1167\/iovs.03-1055","article-title":"Animal Models of Dry Eye: A Critical Assessment of Opportunities and Limitations","volume":"45","author":"Barabino","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3341\/kjo.2015.29.2.131","article-title":"Efficacy of the Mineral Oil and Hyaluronic Acid Mixture Eye Drops in Murine Dry Eye","volume":"29","author":"Choi","year":"2015","journal-title":"Korean J. Ophthalmol. KJO"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/cxo.12128","article-title":"Corneal Epithelial Cell Viability of an Ex Vivo Porcine Eye Model","volume":"97","author":"Chan","year":"2014","journal-title":"Clin. Exp. Optom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1089\/jop.2005.21.139","article-title":"Preservation of Tear Film Integrity and Inhibition of Corneal Injury by Dexamethasone in a Rabbit Model of Lacrimal Gland Inflammation-Induced Dry Eye","volume":"21","author":"Nagelhout","year":"2005","journal-title":"J. Ocul. Pharmacol. Ther. Off. J. Assoc. Ocul. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ajo.2003.10.036","article-title":"Antiinflammatory Therapy for Dry Eye","volume":"137","author":"Pflugfelder","year":"2004","journal-title":"Am. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.ajo.2009.09.023","article-title":"Demonstration of Efficacy in the Treatment of Dry Eye Disease with 0.18% Sodium Hyaluronate Ophthalmic Solution (Vismed, Rejena)","volume":"149","author":"Vogel","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.joco.2016.01.008","article-title":"Erythropoietin in Ophthalmology: A Literature Review","volume":"28","year":"2016","journal-title":"J. Curr. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.3389\/fimmu.2018.02338","article-title":"Lectin-Glycan Interactions in Corneal Infection and Inflammation","volume":"9","author":"AbuSamra","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s10787-018-0499-4","article-title":"Interferon-\u03b2 Inhibits Inflammatory Responses Mediators via Suppression of INOS Signaling Pathway in PBMCs from Patients with Primary Sj\u00f6gren\u2019s Syndrome","volume":"26","author":"Benchabane","year":"2018","journal-title":"Inflammopharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1167\/iovs.16-20789","article-title":"T Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Contributes to Dry Eye Disease Pathogenesis by Promoting CD11b+ Myeloid Cell Maturation and Migration","volume":"58","author":"Dohlman","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4824","DOI":"10.1167\/iovs.16-19757","article-title":"Tear Interferon-Gamma as a Biomarker for Evaporative Dry Eye Disease","volume":"57","author":"Jackson","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","first-page":"2222","article-title":"Lacrimal Gland Inflammatory Cytokine Gene Expression in the Botulinum Toxin B-Induced Murine Dry Eye Model","volume":"13","author":"Park","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cytogfr.2012.07.002","article-title":"Emerging Role of Interleukin-22 in Autoimmune Diseases","volume":"24","author":"Pan","year":"2013","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1167\/iovs.16-20993","article-title":"Osteoprotegerin Is a New Regulator of Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy","volume":"58","author":"Struyf","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3389\/fphar.2020.00111","article-title":"Progress in Research on the Role of FGF in the Formation and Treatment of Corneal Neovascularization","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1167\/iovs.13-13619","article-title":"Angiopoietin-1 Is Regulated by MiR-204 and Contributes to Corneal Neovascularization in KLEIP-Deficient Mice","volume":"55","author":"Kather","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000503636","article-title":"The Key Role of VEGF in the Cross Talk between Pterygium and Dry Eye and Its Clinical Significance","volume":"63","author":"Liu","year":"2020","journal-title":"Ophthalmic Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.exer.2018.12.004","article-title":"Corneal Regeneration by Conditioned Medium of Human Uterine Cervical Stem Cells Is Mediated by TIMP-1 and TIMP-2","volume":"180","author":"Seoane","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_32","first-page":"265","article-title":"Transforming Growth Factor Alpha: Expression, Regulation and Biological Action of Its Integral Membrane Precursor","volume":"1","author":"Luetteke","year":"1990","journal-title":"Semin. Cancer Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.tiv.2009.08.016","article-title":"Occludin Gene Expression as an Early in Vitro Sign for Mild Eye Irritation Assessment","volume":"24","author":"Meloni","year":"2010","journal-title":"Toxicol. In Vitro"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Smith, J. (2007). The Epidemiology of Dry Eye Disease. Acta Ophthalmol. Scand., 85.","DOI":"10.1111\/j.1600-0420.2007.01063_2858.x"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1007\/s00417-012-1999-3","article-title":"The Ex Vivo Eye Irritation Test (EVEIT) in Evaluation of Artificial Tears: Purite\u00ae-Preserved versus Unpreserved Eye Drops","volume":"250","author":"Schrage","year":"2012","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.clae.2017.09.003","article-title":"Characterisation of the Porcine Eyeball as an In-Vitro Model for Dry Eye","volume":"41","author":"Menduni","year":"2018","journal-title":"Contact Lens Anterior Eye J. Br. Contact Lens Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100880","DOI":"10.1016\/j.preteyeres.2020.100880","article-title":"Retina in a Dish: Cell Cultures, Retinal Explants and Animal Models for Common Diseases of the Retina","volume":"81","author":"Schnichels","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s12565-020-00590-8","article-title":"Animal Model with Structural Similarity to Human Corneal Collagen Fibrillar Arrangement","volume":"96","author":"Subasinghe","year":"2021","journal-title":"Anat. Sci. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/NHH.0000000000000652","article-title":"Dry Eye Disease: Prevalence, Assessment, and Management","volume":"36","author":"Rouen","year":"2018","journal-title":"Home Healthc. Now"},{"key":"ref_40","first-page":"113","article-title":"Molecular Mechanism of Ocular Surface Damage: Application to an in Vitro Dry Eye Model on Human Corneal Epithelium","volume":"17","author":"Meloni","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0014-4835(03)00033-2","article-title":"Comparison of Ultrastructure, Tight Junction-Related Protein Expression and Barrier Function of Human Corneal Epithelial Cells Cultivated on Amniotic Membrane with and without Air-Lifting","volume":"76","author":"Ban","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1167\/iovs.07-0744","article-title":"A Murine Model of Dry Eye Induced by an Intelligently Controlled Environmental System","volume":"49","author":"Chen","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.exer.2011.11.022","article-title":"Low Humidity Environmental Challenge Causes Barrier Disruption and Cornification of the Mouse Corneal Epithelium via a C-Jun N-Terminal Kinase 2 (JNK2) Pathway","volume":"94","author":"Pelegrino","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_44","first-page":"209","article-title":"Effect of death-to-preservation time on donor corneal epithelium","volume":"103","author":"Katz","year":"2005","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_45","first-page":"2283","article-title":"Pro- and Anti-Inflammatory Forms of Interleukin-1 in the Tear Fluid and Conjunctiva of Patients with Dry-Eye Disease","volume":"42","author":"Solomon","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","first-page":"192","article-title":"Dry Eye Syndrome","volume":"6","author":"Javadi","year":"2011","journal-title":"J. Ophthalmic Vis. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5443","DOI":"10.1167\/iovs.11-9417","article-title":"Correlations between Tear Cytokines, Chemokines, and Soluble Receptors and Clinical Severity of Dry Eye Disease","volume":"53","author":"Na","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ajo.2012.01.034","article-title":"Efficacy of Topical Blockade of Interleukin-1 in Experimental Dry Eye Disease","volume":"154","author":"Okanobo","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.exer.2006.02.004","article-title":"Corticosteroid and Doxycycline Suppress MMP-9 and Inflammatory Cytokine Expression, MAPK Activation in the Corneal Epithelium in Experimental Dry Eye","volume":"83","author":"Corrales","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_50","first-page":"1981","article-title":"Hyperosmolarity Stimulates Production of MMP-9, IL-1\u00df and TNF- by Human Corneal Epithelial Cells Via a c-Jun NH2-Terminal Kinase Pathway","volume":"43","author":"Li","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Roda, M., Corazza, I., Bacchi Reggiani, M.L., Pellegrini, M., Taroni, L., Giannaccare, G., and Versura, P. (2020). Dry Eye Disease and Tear Cytokine Levels\u2014A Meta-Analysis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093111"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/j.ajpath.2011.05.036","article-title":"EMMPRIN Modulates Epithelial Barrier Function through a MMP-Mediated Occludin Cleavage: Implications in Dry Eye Disease","volume":"179","author":"Huet","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1677\/jme.0.0280069","article-title":"Negative Regulation of Nuclear Factor-KappaB Activation and Function by Glucocorticoids","volume":"28","author":"Almawi","year":"2002","journal-title":"J. Mol. Endocrinol."},{"key":"ref_54","first-page":"78","article-title":"Hyaluronic Acid in Inflammation and Tissue Regeneration","volume":"28","author":"Litwiniuk","year":"2016","journal-title":"Wounds Compend. Clin. Res. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/tvst.8.6.2","article-title":"Physicochemical Properties of Hyaluronic Acid\u2013Based Lubricant Eye Drops","volume":"8","author":"Aragona","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1111\/jcmm.15091","article-title":"INOS-inhibitor Driven Neuroprotection in a Porcine Retina Organ Culture Model","volume":"24","author":"Hurst","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1080\/02713683.2017.1297461","article-title":"Characterization of a Standardized Ex-Vivo Porcine Model to Assess Short Term Intraocular Pressure Changes and Trabecular Meshwork Vitality After Pars Plana Vitrectomy with Different Silicone Oil and BSS Tamponades","volume":"42","author":"Ebner","year":"2017","journal-title":"Curr. Eye Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:57:48Z","timestamp":1760137068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,20]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23094567"],"URL":"https:\/\/doi.org\/10.3390\/ijms23094567","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,20]]}}}