{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T03:36:31Z","timestamp":1783481791323,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Trinity College Dublin School of Medicine"},{"name":"National Children\u2019s Hospital, Tallaght University Hospital, Dublin, Ireland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Aspergillus fumigatus is the most commonly isolated fungus in chronic lung diseases, with a prevalence of up to 60% in cystic fibrosis patients. Despite this, the impact of A. fumigatus colonisation on lung epithelia has not been thoroughly explored. We investigated the influence of A. fumigatus supernatants and the secondary metabolite, gliotoxin, on human bronchial epithelial cells (HBE) and CF bronchial epithelial (CFBE) cells. CFBE (F508del CFBE41o\u2212) and HBE (16HBE14o\u2212) trans-epithelial electrical resistance (TEER) was measured following exposure to A. fumigatus reference and clinical isolates, a gliotoxin-deficient mutant (\u0394gliG) and pure gliotoxin. The impact on tight junction (TJ) proteins, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were determined by western blot analysis and confocal microscopy. A. fumigatus conidia and supernatants caused significant disruption to CFBE and HBE TJs within 24 h. Supernatants from later cultures (72 h) caused the greatest disruption while \u0394gliG mutant supernatants caused no disruption to TJ integrity. The ZO-1 and JAM-A distribution in epithelial monolayers were altered by A. fumigatus supernatants but not by \u0394gliG supernatants, suggesting that gliotoxin is involved in this process. The fact that \u0394gliG conidia were still capable of disrupting epithelial monolayers indicates that direct cell\u2013cell contact also plays a role, independently of gliotoxin production. Gliotoxin is capable of disrupting TJ integrity which has the potential to contribute to airway damage, and enhance microbial invasion and sensitisation in CF.<\/jats:p>","DOI":"10.3390\/jof9040490","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T02:01:11Z","timestamp":1681956071000},"page":"490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Aspergillus fumigatus Supernatants Disrupt Bronchial Epithelial Monolayers: Potential Role for Enhanced Invasion in Cystic Fibrosis"],"prefix":"10.3390","volume":"9","author":[{"given":"Katie","family":"Dunne","sequence":"first","affiliation":[{"name":"Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-5875","authenticated-orcid":false,"given":"Emma","family":"Reece","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-2542","authenticated-orcid":false,"given":"Siobh\u00e1n","family":"McClean","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Biology, Maynooth University, Maynooth, W23 F2K8 Kildare, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Murphy","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5060-2136","authenticated-orcid":false,"given":"Julie","family":"Renwick","sequence":"additional","affiliation":[{"name":"Discipline of Clinical Microbiology, School of Medicine, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S331","DOI":"10.1080\/13693780802266777","article-title":"Pathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis: Current understanding and future directions","volume":"47","author":"Rapaka","year":"2009","journal-title":"Med. Mycol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jcf.2013.02.003","article-title":"What is the clinical significance of filamentous fungi positive sputum cultures in patients with cystic fibrosis?","volume":"12","author":"Liu","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jcf.2009.11.010","article-title":"Prevalence and risk factors for recovery of filamentous fungi in individuals with cystic fibrosis","volume":"9","author":"Sudfeld","year":"2010","journal-title":"J. Cyst. Fibros."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1164\/rccm.201203-0478OC","article-title":"The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis","volume":"186","author":"Coughlan","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/00063198-200311000-00007","article-title":"Update on pathogenesis of cystic fibrosis lung disease","volume":"9","author":"Donaldson","year":"2003","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1002\/ppul.24129","article-title":"Inflammation in cystic fibrosis: An update","volume":"53","author":"Roesch","year":"2018","journal-title":"Pediatr. Pulmonol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"L493","DOI":"10.1152\/ajplung.2001.280.3.L493","article-title":"Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines","volume":"280","author":"Kube","year":"2001","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S225","DOI":"10.1086\/376525","article-title":"Allergic bronchopulmonary aspergillosis in cystic fibrosis\u2013state of the art: Cystic Fibrosis Foundation Consensus Conference","volume":"37","author":"Stevens","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1046\/j.1439-0507.2003.00830.x","article-title":"Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis","volume":"46","author":"Bakare","year":"2003","journal-title":"Mycoses"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1034\/j.1398-9995.2000.00342.x","article-title":"Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis","volume":"55","author":"Skov","year":"2000","journal-title":"Allergy"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jcf.2007.06.006","article-title":"Prevalence and antimicrobial susceptibility of microorganisms isolated from sputa of patients with cystic fibrosis","volume":"7","author":"Valenza","year":"2008","journal-title":"J. Cyst. Fibros."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105683","DOI":"10.1016\/j.mimet.2019.105683","article-title":"The prevalence of Aspergillus fumigatus in early cystic fibrosis disease is underestimated by culture-based diagnostic methods","volume":"164","author":"Reece","year":"2019","journal-title":"J. Microbiol. Methods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1378\/chest.09-1103","article-title":"The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis","volume":"137","author":"Amin","year":"2010","journal-title":"Chest"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jcf.2021.04.007","article-title":"Clinical characteristics of Pseudomonas and Aspergillus co-infected cystic fibrosis patients: A UK registry study","volume":"21","author":"Hughes","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"18999","DOI":"10.1038\/s41598-020-75886-w","article-title":"Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function","volume":"10","author":"Duesberg","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s11046-017-0190-0","article-title":"Aspergillus Bronchitis in Patients with Cystic Fibrosis","volume":"183","author":"Brandt","year":"2018","journal-title":"Mycopathologia"},{"key":"ref_17","unstructured":"McDermott, G., Reece, E., and Renwick, J. (2019). Encyclopedia of Microbiology, Academic Press. [4th ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Linnane, B., Walsh, A.M., Walsh, C.J., Crispie, F., O\u2019Sullivan, O., Cotter, P.D., McDermott, M., Renwick, J., and McNally, P. (2021). The Lung Microbiome in Young Children with Cystic Fibrosis: A Prospective Cohort Study. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030492"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1800242","DOI":"10.1183\/13993003.00242-2018","article-title":"Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: A multisite study","volume":"52","author":"Muhlebach","year":"2018","journal-title":"Eur Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Reece, E., Segurado, R., Jackson, A., McClean, S., Renwick, J., and Greally, P. (2017). Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: An Irish registry analysis. BMC Pulm. Med., 17.","DOI":"10.1186\/s12890-017-0416-4"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jhin.2021.04.012","article-title":"Incidence, diagnosis and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA): A systematic review","volume":"113","author":"Chong","year":"2021","journal-title":"J. Hosp. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s43088-022-00245-9","article-title":"Coinfection of fungi with SARS-CoV-2 is a detrimental health risk for COVID-19 patients","volume":"11","author":"Baten","year":"2022","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/myc.13135","article-title":"COVID-19-associated pulmonary aspergillosis (CAPA) in patients admitted with severe COVID-19 pneumonia: An observational study from Pakistan","volume":"63","author":"Nasir","year":"2020","journal-title":"Mycoses"},{"key":"ref_24","first-page":"F1","article-title":"Molecular structure and assembly of the tight junction","volume":"274","author":"Denker","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00418-008-0424-9","article-title":"Tight junctions and the modulation of barrier function in disease","volume":"130","author":"Forster","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1099\/mic.0.056986-0","article-title":"Interaction of environmental Burkholderia cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro","volume":"158","author":"Bevivino","year":"2012","journal-title":"Microbiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1183\/09031936.95.08101681","article-title":"Aspergillus culture filtrates and sputum sols from patients with pulmonary aspergillosis cause damage to human respiratory ciliated epithelium in vitro","volume":"8","author":"Amitani","year":"1995","journal-title":"Eur. Respir. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.jprot.2015.02.007","article-title":"Quantitative proteomic study of Aspergillus fumigatus secretome revealed deamidation of secretory enzymes","volume":"119","author":"Adav","year":"2015","journal-title":"J. Proteom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.micinf.2006.10.009","article-title":"Gliotoxin from Aspergillus fumigatus affects phagocytosis and the organization of the actin cytoskeleton by distinct signalling pathways in human neutrophils","volume":"9","author":"Comera","year":"2007","journal-title":"Microbes Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1128\/IAI.72.6.3373-3382.2004","article-title":"Fungal metabolite gliotoxin inhibits assembly of the human respiratory burst NADPH oxidase","volume":"72","author":"Tsunawaki","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.chembiol.2010.12.022","article-title":"The role of glutathione S-transferase GliG in gliotoxin biosynthesis in Aspergillus fumigatus","volume":"18","author":"Davis","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.fgb.2012.02.003","article-title":"Gliotoxin effects on fungal growth: Mechanisms and exploitation","volume":"49","author":"Carberry","year":"2012","journal-title":"Fungal Genet. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1128\/JCM.43.8.4112-4120.2005","article-title":"Use of a novel panel of nine short tandem repeats for exact and high-resolution fingerprinting of Aspergillus fumigatus isolates","volume":"43","author":"Meis","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1165\/ajrcmb.10.1.7507342","article-title":"CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells","volume":"10","author":"Cozens","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1080\/13693780802558959","article-title":"Interaction of Aspergillus with human respiratory mucosa: A study with organ culture model","volume":"47","author":"Amitani","year":"2009","journal-title":"Med. Mycol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1023\/B:MYCO.0000038434.55764.16","article-title":"Correlation between gliotoxin production and virulence of Aspergillus fumigatus in Galleria mellonella","volume":"158","author":"Reeves","year":"2004","journal-title":"Mycopathologia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1574-695X.2002.tb00578.x","article-title":"Spore diffusate isolated from some strains of Aspergillus fumigatus inhibits phagocytosis by murine alveolar macrophages","volume":"33","author":"Bertout","year":"2002","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/mmy.38.2.133.141","article-title":"The effects of diffusates from the spores of Aspergillus fumigatus and A. terreus on human neutrophils, Naegleria gruberi and Acanthamoeba castellanii","volume":"38","author":"Hobson","year":"2000","journal-title":"Med. Mycol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1086\/517272","article-title":"Julie Proteases from Aspergillus fumigatus induce release of proinflammatory cytokines and cell detachment in airway epithelial cell lines","volume":"176","author":"Tomee","year":"1997","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4161\/viru.1.3.11750","article-title":"Characterization of a 5-azacytidine-induced developmental Aspergillus fumigatus variant","volume":"1","author":"Varga","year":"2010","journal-title":"Virulence"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1099\/jmm.0.45626-0","article-title":"Amphotericin B enhances the synthesis and release of the immunosuppressive agent gliotoxin from the pulmonary pathogen Aspergillus fumigatus","volume":"53","author":"Reeves","year":"2004","journal-title":"J. Med. Microbiol."},{"key":"ref_42","first-page":"1251","article-title":"Identification of an agent in cultures of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro","volume":"131","author":"Mullbacher","year":"1985","journal-title":"J. Gen. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/0192-0561(86)90016-0","article-title":"The effect of gliotoxin upon macrophage function","volume":"8","author":"Eichner","year":"1986","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Khoufache, K., Puel, O., Loiseau, N., Delaforge, M., Rivollet, D., Coste, A., Cordonnier, C., Escudier, E., Botterel, F., and Bretagne, S. (2007). Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells. BMC Microbiol., 7.","DOI":"10.1186\/1471-2180-7-5"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.3389\/fmicb.2019.01345","article-title":"Gliotoxin Induces Cofilin Phosphorylation to Promote Actin Cytoskeleton Dynamics and Internalization of Aspergillus fumigatus Into Type II Human Pneumocyte Cells","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1113\/jphysiol.2009.182246","article-title":"Cystic fibrosis transmembrane conductance regulator trafficking modulates the barrier function of airway epithelial cell monolayers","volume":"588","author":"LeSimple","year":"2010","journal-title":"J. Physiol."},{"key":"ref_47","first-page":"4396","article-title":"CFTR interacts with ZO-1 to regulate tight junction assembly and epithelial differentiation through the ZONAB pathway","volume":"127","author":"Ruan","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1083\/jcb.138.1.181","article-title":"Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments","volume":"138","author":"Itoh","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/j.1749-6632.2012.06521.x","article-title":"Intracellular mediators of JAM-A-dependent epithelial barrier function","volume":"1257","author":"Monteiro","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/0006-2952(95)00039-3","article-title":"Gliotoxin inactivates alcohol dehydrogenase by either covalent modification or free radical damage mediated by redox cycling","volume":"49","author":"Waring","year":"1995","journal-title":"Biochem. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1046\/j.1365-2222.2000.00820.x","article-title":"Quantitative structural and biochemical analyses of tight junction dynamics following exposure of epithelial cells to house dust mite allergen Der p 1","volume":"30","author":"Wan","year":"2000","journal-title":"Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"254","DOI":"10.2174\/157339512800671985","article-title":"Innate Immunity and the Role of Epithelial Barrier During Aspergillus fumigatus Infection","volume":"8","author":"Svirshchevskaya","year":"2012","journal-title":"Curr. Immunol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1046\/j.1365-2222.2001.01025.x","article-title":"Peptidase allergens, occludin and claudins. Do their interactions facilitate the development of hypersensitivity reactions at mucosal surfaces?","volume":"31","author":"Robinson","year":"2001","journal-title":"Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cub.2013.10.030","article-title":"Solutions to the public goods dilemma in bacterial biofilms","volume":"24","author":"Drescher","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Reece, E., Bettio, P.H.A., and Renwick, J. (2021). Polymicrobial Interactions in the Cystic Fibrosis Airway Microbiome Impact the Antimicrobial Susceptibility of Pseudomonas aeruginosa. Antibiotics, 10.","DOI":"10.3390\/antibiotics10070827"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.3389\/fmicb.2018.01205","article-title":"Aspergillus fumigatus Inhibits Pseudomonas aeruginosa in Co-culture: Implications of a Mutually Antagonistic Relationship on Virulence and Inflammation in the CF Airway","volume":"9","author":"Reece","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/cdd.2013.78","article-title":"Apoptosis induced by the fungal pathogen gliotoxin requires a triple phosphorylation of Bim by JNK","volume":"20","author":"Geissler","year":"2013","journal-title":"Cell Death Differ."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/4\/490\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:18:55Z","timestamp":1760123935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/9\/4\/490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":57,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["jof9040490"],"URL":"https:\/\/doi.org\/10.3390\/jof9040490","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]}}}