{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:01Z","timestamp":1787028481034,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"public institutions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We evaluated the presence of tight junction (TJ) remnants in the stratum corneum (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed an increased presence of TJ remnants in the two lowermost layers of the SC, as quantified with standard electron microscopy. The topical aggression-induced overexpression of TJ-like cell\u2013cell envelope fusions may influence SC functions: (1) directly, through an enhanced cohesion, and (2) indirectly, by impeding accessibility of peripheral corneodesmosomes to extracellular hydrolytic enzymes and, thus, slowing down desquamation. Observations of ichthyotic epidermis in peeling skin disease (PSD; corneodesmosin deficiency; two cases) and ichthyosis hypotrichosis sclerosing cholangitis syndrome (IHSC\/NISCH; absence of claudin-1; two cases) also demonstrated increased persistence of TJ-like intercellular fusions in pathological SC and contributed to the interpretation of the diseases\u2019 pathological mechanisms.<\/jats:p>","DOI":"10.3390\/ijms23137486","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"7486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Fate of Epidermal Tight Junctions in the stratum corneum: Their Involvement in the Regulation of Desquamation and Phenotypic Expression of Certain Skin Conditions"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3359-5154","authenticated-orcid":false,"given":"Marek","family":"Haftek","sequence":"first","affiliation":[{"name":"UMR5305, Laboratory of Tissue Biology and Therapeutic Engineering, CNRS and University of Lyon, 8 Avenue Rockefeller, F-69373 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinzenz","family":"Oji","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital of Muenster, D-48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Feldmeyer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hohl","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sma\u00efl","family":"Hadj-Rabia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), Institut Imagine, Necker-Enfants Malades Hospital, AP-HP5, University Paris-Centre, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-2105","authenticated-orcid":false,"given":"Rawad","family":"Abdayem","sequence":"additional","affiliation":[{"name":"UMR5305, Laboratory of Tissue Biology and Therapeutic Engineering, CNRS and University of Lyon, 8 Avenue Rockefeller, F-69373 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/bjd.13243","article-title":"\u2018Memory\u2019 of the stratum corneum: Exploration of the epidermis\u2019 past","volume":"171","author":"Haftek","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_2","unstructured":"Haftek, M., and Dragomir, A. Cell Junctions. Ghadially\u2019s Ultrastructural Pathology of the Cell and Matrix, Tylor and Francis Group. [5th ed.]. in press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0955-0674(02)00362-9","article-title":"Claudin-based barrier in simple and stratified cellular sheets","volume":"14","author":"Tsukita","year":"2002","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1600-0625.2006.00539.x","article-title":"Tight junction proteins in keratinocytes: Localization and contribution to barrier function","volume":"16","author":"Yuki","year":"2007","journal-title":"Exp. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e974451","DOI":"10.4161\/21688370.2014.974451","article-title":"Epidermal tight junctions in health and disease","volume":"3","author":"Brandner","year":"2015","journal-title":"Tissue Barriers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.ejcb.2010.07.010","article-title":"Tight junctions form a barrier in human epidermis","volume":"89","author":"Kirschner","year":"2010","journal-title":"Eur. J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/1523-1747.ep12292052","article-title":"Intercellular Spaces of the Human Epidermis as Demonstrated with Lanthanum","volume":"57","author":"Hashimoto","year":"1971","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-024924-4.50005-5","article-title":"Structural and Lipid Biochemical Correlates of the Epidermal Permeability Barrier","volume":"24","author":"Elias","year":"1991","journal-title":"Adv. Lipid Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1046\/j.1523-1747.2003.12359.x","article-title":"Barrier Function of the Skin: \u201cLa Raison d\u2019\u00catre\u201d of the Epidermis","volume":"121","author":"Madison","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.bbamem.2006.06.021","article-title":"The skin barrier in healthy and diseased state","volume":"1758","author":"Bouwstra","year":"2006","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wertz, P. (2021). Roles of Lipids in the Permeability Barriers of Skin and Oral Mucosa. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105229"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1083\/jcb.200110122","article-title":"Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice","volume":"156","author":"Furuse","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Seker, M., Fern\u00e1ndez-Rodr\u00edguez, C., Mart\u00ednez-Cruz, L.A., and M\u00fcller, D. (2019). Mouse Models of Human Claudin-Associated Disorders: Benefits and Limitations. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215504"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1078\/0171-9335-00244","article-title":"Organization and formation of the tight junction system in human epidermis and cultured keratinocytes","volume":"81","author":"Brandner","year":"2002","journal-title":"Eur. J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ishida-Yamamoto, A., Kishibe, M., Murakami, M., Honma, M., Takahashi, H., and Iizuka, H. (2012). Lamellar Granule Secretion Starts before the Establishment of Tight Junction Barrier for Paracellular Tracers in Mammalian Epidermis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031641"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/exd.13742","article-title":"Maintenance of tight junction barrier integrity in cell turnover and skin diseases","volume":"27","author":"Yokouchi","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12800","DOI":"10.1038\/s41598-018-30341-9","article-title":"Tight Junction barriers in human hair follicles\u2014Role of claudin-1","volume":"8","author":"Houdek","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","first-page":"s5","article-title":"Skin barrier in the neonate","volume":"35","year":"2018","journal-title":"Pediatr. Dermatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.clindermatol.2019.04.009","article-title":"Aging of the skin barrier","volume":"37","author":"Choi","year":"2019","journal-title":"Clin. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Krug, S.M., and Fromm, M. (2020). Special Issue on \u201cThe Tight Junction and Its Proteins: More than Just a Barrier\u201d. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134612"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/bjd.19390","article-title":"Tight junctions in the skin: Still a lot to learn","volume":"184","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_22","first-page":"1029","article-title":"Epidermal Tight Junctions: How Do They Fit into the Barrier Function?","volume":"19","author":"Haftek","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/j.1600-0625.2011.01315.x","article-title":"Compartmentalization of the human stratum corneum by persistent tight junction-like structures","volume":"20","author":"Haftek","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1600-0625.2010.01170.x","article-title":"Tight junctions in the stratum corneum explain spatial differences in corneodesmosome degradation","volume":"20","author":"Igawa","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/bies.10144","article-title":"Epithelial barrier function: Assembly and structural features of the cornified cell envelope","volume":"24","author":"Kalinin","year":"2002","journal-title":"BioEssays"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2147\/CCID.S84765","article-title":"Salicylic acid as a peeling agent: A comprehensive review","volume":"8","author":"Arif","year":"2015","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_27","first-page":"554","article-title":"Influence of keratolytics on cutaneous pharmacokinetics of glucocorticoids","volume":"19","author":"Wohlrab","year":"2021","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_28","first-page":"XXXIX","article-title":"A comparative ultrastructural study of hydroxyacids induced desquamation","volume":"12","author":"Corcuff","year":"2002","journal-title":"Eur. J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jaci.2020.05.048","article-title":"Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis","volume":"147","author":"He","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.jaci.2010.10.018","article-title":"Tight junction defects in patients with atopic dermatitis","volume":"127","author":"Rafaels","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.alit.2017.10.002","article-title":"Barrier dysfunction in the skin allergy","volume":"67","author":"Egawa","year":"2018","journal-title":"Allergol. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/1346-8138.15664","article-title":"Basics and recent advances in the pathophysiology of atopic dermatitis","volume":"48","author":"Nakahara","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.jid.2020.02.025","article-title":"Rosacea Is Characterized by a Profoundly Diminished Skin Barrier","volume":"140","author":"Medgyesi","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e23363","DOI":"10.1002\/jcla.23363","article-title":"Rosacea is associated with conjoined interactions between physical barrier of the skin and microorganisms: A pilot study","volume":"34","author":"Yuan","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/1346-8138.14792","article-title":"Claudin reduction may relate to an impaired skin barrier in rosacea","volume":"46","author":"Deng","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/ics.12449","article-title":"Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes","volume":"40","author":"Tohgasaki","year":"2018","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1053\/j.gastro.2004.07.022","article-title":"Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: A tight junction disease","volume":"127","author":"Baala","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1002\/humu.20333","article-title":"Confirmation of the origin of NISCH syndrome","volume":"27","author":"Feldmeyer","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ajhg.2010.07.005","article-title":"Loss of Corneodesmosin Leads to Severe Skin Barrier Defect, Pruritus, and Atopy: Unraveling the Peeling Skin Disease","volume":"87","author":"Oji","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e2722","DOI":"10.1002\/jmr.2722","article-title":"Changes in nano-mechanical properties of human epidermal cornified cells depending on their proximity to the skin surface","volume":"31","author":"Milani","year":"2018","journal-title":"J. Mol. Recognit."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jdermsci.2012.11.595","article-title":"Impaired tight junctions obstruct stratum corneum formation by altering polar lipid and profilaggrin processing","volume":"69","author":"Yuki","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1038\/s41598-020-58718-9","article-title":"Claudin-1 decrease impacts epidermal barrier function in atopic dermatitis lesions dose-dependently","volume":"10","author":"Bergmann","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/exd.13531","article-title":"3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function","volume":"27","author":"Niehues","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/term.3221","article-title":"Observation of a tight junction structure generated in LbL-3D skin reconstructed by layer-by-layer cell coating technique","volume":"15","author":"Murakami","year":"2021","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Brewer, M.G., Yoshida, T., Kuo, F.I., Fridy, S., Beck, L.A., and De Benedetto, A. (2019). Antagonistic Effects of IL-4 on IL-17A-Mediated Enhancement of Epidermal Tight Junction Function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174070"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ejpb.2005.03.004","article-title":"The human epidermis models EpiSkin\u00ae, SkinEthic\u00ae and EpiDerm\u00ae: An evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport","volume":"60","author":"Netzlaff","year":"2005","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mieremet, A., Helder, R., Nadaban, A., Boiten, W., Gooris, G., El Ghalbzouri, A., and Bouwstra, J. (2021). Multitargeted Approach for the Optimization of Morphogenesis and Barrier Formation in Human Skin Equivalents. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115790"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3349\/ymj.2013.54.2.523","article-title":"Acute Modulations in stratum corneum Permeability Barrier Function Affect Claudin Expression and Epidermal Tight Junction Function via Changes of Epidermal Calcium Gradient","volume":"54","author":"Baek","year":"2013","journal-title":"Yonsei Med. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jdermsci.2018.03.005","article-title":"An overview of epidermal lamellar bodies: Novel roles in biological adaptations and secondary barriers","volume":"92","author":"Menon","year":"2018","journal-title":"J. Dermatol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bbrc.2011.02.057","article-title":"Tight junction regulates epidermal calcium ion gradient and differentiation","volume":"406","author":"Kurasawa","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kapit\u00e1ny, A., Medgyesi, B., Jenei, A., Somogyi, O., Szab\u00f3, L., G\u00e1sp\u00e1r, K., M\u00e9hes, G., Hendrik, Z., D\u00f3cs, K., and Sz\u00fccs, P. (2021). Regional Differences in the Permeability Barrier of the Skin\u2014Implications in Acantholytic Skin Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910428"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"712","DOI":"10.7150\/ijbs.45885","article-title":"Tight junctions and their regulation by non-coding RNAs","volume":"17","author":"Zhao","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s00795-021-00299-1","article-title":"Increased integrity of cell\u2013cell junctions accompanied by increased expression of claudin 4 in keratinocytes stimulated with vitamin D3","volume":"54","author":"Minowa","year":"2021","journal-title":"Med. Mol. Morphol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Marras, L., Caputo, M., Bisicchia, S., Soato, M., Bertolino, G., Vaccaro, S., and Inturri, R. (2021). The Role of Bifidobacteria in Predictive and Preventive Medicine: A Focus on Eczema and Hypercholesterolemia. Microorganisms, 9.","DOI":"10.3390\/microorganisms9040836"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/bjd.19162","article-title":"Organic osmolytes increase expression of specific tight junction proteins in skin and alter barrier function in keratinocytes*","volume":"184","author":"Foster","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1038\/s41598-018-22533-0","article-title":"Organic osmolytes preserve the function of the developing tight junction in ultraviolet B-irradiated rat epidermal keratinocytes","volume":"8","author":"Haslam","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120601","DOI":"10.1016\/j.ijpharm.2021.120601","article-title":"Overcoming thickened pathological skin in psoriasis via iontophoresis combined with tight junction-opening peptide AT1002 for intradermal delivery of NF-\u03baB decoy oligodeoxynucleotide","volume":"602","author":"Fukuta","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jid.2019.06.145","article-title":"Peptides Derived from the Tight Junction Protein CLDN1 Disrupt the Skin Barrier and Promote Responsiveness to an Epicutaneous Vaccine","volume":"140","author":"Brewer","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gorzelanny, C., Mess, C., Schneider, S.W., Huck, V., and Brandner, J.M. (2020). Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them?. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070684"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.addr.2020.06.007","article-title":"Engineering the drug carrier biointerface to overcome biological barriers to drug delivery","volume":"167","author":"Finbloom","year":"2020","journal-title":"Adv. Drug Deliv. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7486\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:43:12Z","timestamp":1760139792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,5]]},"references-count":60,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137486"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137486","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,5]]}}}