{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:23:56Z","timestamp":1783646636361,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,30]],"date-time":"2020-09-30T00:00:00Z","timestamp":1601424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Eye Institute, NIH, U.S.A.","award":["#EY000306"],"award-info":[{"award-number":["#EY000306"]}]},{"name":"Fundaci\u00f3n S\u00e9neca, Agencia de Ciencia y Tecnolog\u00eda Regi\u00f3n de Murcia","award":["19881\/GERM\/15"],"award-info":[{"award-number":["19881\/GERM\/15"]}]},{"name":"Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna manera de hacer Europa\u201d","award":["SAF2015-67643-P"],"award-info":[{"award-number":["SAF2015-67643-P"]}]},{"name":"Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna manera de hacer Europa\u201d","award":["PI19\/00203"],"award-info":[{"award-number":["PI19\/00203"]}]},{"name":"Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional \u201cUna manera de hacer Europa\u201d","award":["RD16\/0008\/0026"],"award-info":[{"award-number":["RD16\/0008\/0026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Here, we evaluated the effects of PEDF (pigment epithelium-derived factor) and PEDF peptides on cone-photoreceptor cell damage in a mouse model of focal LED-induced phototoxicity (LIP) in vivo. Swiss mice were dark-adapted overnight, anesthetized, and their left eyes were exposed to a blue LED placed over the cornea. Immediately after, intravitreal injection of PEDF, PEDF-peptide fragments 17-mer, 17-mer[H105A] or 17-mer[R99A] (all at 10 pmol) were administered into the left eye of each animal. BDNF (92 pmol) and bFGF (27 pmol) injections were positive controls, and vehicle negative control. After 7 days, LIP resulted in a consistent circular lesion located in the supratemporal quadrant and the number of S-cones were counted within an area centered on the lesion. Retinas treated with effectors had significantly greater S-cone numbers (PEDF (60%), 17-mer (56%), 17-mer [H105A] (57%), BDNF (64%) or bFGF (60%)) relative to their corresponding vehicle groups (\u224842%). The 17-mer[R99A] with no PEDF receptor binding and no neurotrophic activity, PEDF combined with a molar excess of the PEDF receptor blocker P1 peptide, or with a PEDF-R enzymatic inhibitor had undetectable effects in S-cone survival. The findings demonstrated that the cone survival effects were mediated via interactions between the 17-mer region of the PEDF molecule and its PEDF-R receptor.<\/jats:p>","DOI":"10.3390\/ijms21197242","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T09:04:12Z","timestamp":1601543052000},"page":"7242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pigment Epithelium-Derived Factor (PEDF) Fragments Prevent Mouse Cone Photoreceptor Cell Loss Induced by Focal Phototoxicity In Vivo"],"prefix":"10.3390","volume":"21","author":[{"given":"Francisco J.","family":"Valiente-Soriano","sequence":"first","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-9247","authenticated-orcid":false,"given":"Johnny","family":"Di Pierdomenico","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7639-5366","authenticated-orcid":false,"given":"Diego","family":"Garc\u00eda-Ayuso","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-6604","authenticated-orcid":false,"given":"Arturo","family":"Ort\u00edn-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"},{"name":"Donald K Johnson Eye Institute, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan A.","family":"Miralles de Imperial-Ollero","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Gallego-Ortega","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Jim\u00e9nez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-482X","authenticated-orcid":false,"given":"M. Paz","family":"Villegas-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8004-4983","authenticated-orcid":false,"given":"S. Patricia","family":"Becerra","sequence":"additional","affiliation":[{"name":"Section of Protein Structure and Function, NEI-NIH, Bethesda, MD 20892-0608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-1615","authenticated-orcid":false,"given":"Manuel","family":"Vidal-Sanz","sequence":"additional","affiliation":[{"name":"Departamento de Oftalmolog\u00eda, Facultad de Medicina, Universidad de Murcia, e Instituto Murciano de Investigaci\u00f3n Biosanitaria Virgen de la Arrixaca (IMIB-Arrixaca), 30.120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/bjophthalmol-2017-311258","article-title":"Prevalence and causes of Vis. loss in high-income countries and in Eastern and Central Europe in 2015: Magnitude, temporal trends and projections","volume":"102","author":"Bourne","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1001\/archophthalmol.2010.92","article-title":"The prevalence of age-related macular degeneration and associated risk factors","volume":"128","author":"Klein","year":"2010","journal-title":"Arch. Ophthalmol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1136\/bjophthalmol-2012-302281","article-title":"Is sunlight exposure a risk factor for age-related macular degeneration? A systematic review and meta-analysis","volume":"97","author":"Sui","year":"2013","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1167\/iovs.61.3.47","article-title":"Coordinated Intervention of Microglial and Muller Cells in Light-Induced Retinal Degeneration","volume":"61","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1167\/iovs.17-23258","article-title":"Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration","volume":"59","author":"Marie","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.exer.2017.05.010","article-title":"Light-induced retinal degeneration causes a transient downregulation of melanopsin in the rat retina","volume":"161","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_7","first-page":"1716","article-title":"Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration","volume":"17","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/cne.21028","article-title":"Phototoxic-induced photoreceptor degeneration causes retinal ganglion cell degeneration in pigmented rats","volume":"498","author":"Lund","year":"2006","journal-title":"J. Comp. Neurol."},{"key":"ref_9","first-page":"450","article-title":"Retinal damage by light in rats","volume":"5","author":"Noell","year":"1966","journal-title":"Investig. Ophthalmol."},{"key":"ref_10","first-page":"997","article-title":"Hyperthermia accelerates retinal light damage in rats","volume":"36","author":"Organisciak","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vicente-Tejedor, J., Marchena, M., Ramirez, L., Garcia-Ayuso, D., Gomez-Vicente, V., Sanchez-Ramos, C., de la Villa, P., and Germain, F. (2018). Removal of the blue component of light significantly decreases retinal damage after high intensity exposure. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194218"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00417-015-3258-x","article-title":"Functional and morphological evaluation of blue light-emitting diode-induced retinal degeneration in mice","volume":"254","author":"Kim","year":"2016","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol. Albrecht Von Graefes Arch. Fur Klin. Und Exp. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.1038\/srep05223","article-title":"Damage of photoreceptor-derived cells in culture induced by light emitting diode-derived blue light","volume":"4","author":"Kuse","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1248\/bpb.b16-01008","article-title":"The Involvement of the Oxidative Stress in Murine Blue LED Light-Induced Retinal Damage Model","volume":"40","author":"Nakamura","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2018.07.022","article-title":"Exposure to excessive blue LED light damages retinal pigment epithelium and photoreceptors of pigmented mice","volume":"177","author":"Nakamura","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ortin-Martinez, A., Valiente-Soriano, F.J., Garcia-Ayuso, D., Alarcon-Martinez, L., Jimenez-Lopez, M., Bernal-Garro, J.M., Nieto-Lopez, L., Nadal-Nicolas, F.M., Villegas-Perez, M.P., and Wheeler, L.A. (2014). A novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: Neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113798"},{"key":"ref_17","first-page":"1981","article-title":"The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells","volume":"41","author":"Sparrow","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1167\/tvst.8.6.36","article-title":"Topical Brimonidine or Intravitreal BDNF, CNTF, or bFGF Protect Cones Against Phototoxicity","volume":"8","author":"Wheeler","year":"2019","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1167\/iovs.09-4861","article-title":"Automated quantification and topographical distribution of the whole population of S-and L-cones in adult albino and pigmented rats","volume":"51","author":"Sauve","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nadal-Nicolas, F.M., Kunze, V.P., Ball, J.M., Peng, B.T., Krishnan, A., Zhou, G., Dong, L., and Li, W. (2020). True S-cones are concentrated in the ventral mouse retina and wired for color detection in the upper visual field. eLife, 9.","DOI":"10.7554\/eLife.56840"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/s41419-018-0613-y","article-title":"Pigment epithelium-derived factor hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina","volume":"9","author":"Comitato","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1167\/iovs.18-24621","article-title":"Neuroprotective Effects of FGF2 and Minocycline in Two Animal Models of Inherited Retinal Degeneration","volume":"59","author":"Scholz","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.exer.2019.04.008","article-title":"PEDF peptides promote photoreceptor survival in rd10 retina models","volume":"184","author":"Polato","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.survophthal.2013.09.004","article-title":"Trophic factors in the pathogenesis and therapy for retinal degenerative diseases","volume":"59","author":"Kolomeyer","year":"2014","journal-title":"Surv. Ophthalmol."},{"key":"ref_25","first-page":"592","article-title":"Protection of mouse photoreceptors by survival factors in retinal degenerations","volume":"39","author":"LaVail","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1007\/978-3-319-17121-0_93","article-title":"Pigment Epithelium-Derived Factor, a Protective Factor for Photoreceptors in Vivo","volume":"854","author":"Polato","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23928","DOI":"10.1074\/jbc.M113.487884","article-title":"Pigment epithelium-derived factor (PEDF) prevents retinal cell death via PEDF Receptor (PEDF-R): Identification of a functional ligand binding site","volume":"288","author":"Subramanian","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.exer.2005.10.016","article-title":"Focus on Molecules: Pigment epithelium-derived factor (PEDF)","volume":"82","author":"Becerra","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"38022","DOI":"10.1074\/jbc.M600353200","article-title":"Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor","volume":"281","author":"Notari","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108121","DOI":"10.1016\/j.exer.2020.108121","article-title":"PEDF deficiency increases the susceptibility of rd10 mice to retinal degeneration","volume":"198","author":"Dixit","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25241","DOI":"10.1074\/jbc.M115.645846","article-title":"Small Retinoprotective Peptides Reveal a Receptor-binding Region on Pigment Epithelium-derived Factor","volume":"290","author":"Kenealey","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, Y., Yang, J., Geng, H., Li, L., Li, J., Cheng, B., Ma, X., Li, H., and Hou, L. (2019). Photoreceptor degeneration in microphthalmia (Mitf) mice: Partial rescue by pigment epithelium-derived factor. Dis. Models Mech., 12.","DOI":"10.1242\/dmm.035642"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/978-1-4614-3209-8_102","article-title":"Pigment epithelium-derived factor protects cone photoreceptor-derived 661W cells from light damage through Akt activation","volume":"801","author":"Rapp","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101026","DOI":"10.1016\/j.mex.2020.101026","article-title":"Cell-based assays to identify novel retinoprotective agents","volume":"7","author":"Bullock","year":"2020","journal-title":"MethodsX"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ortin-Martinez, A., Nadal-Nicolas, F.M., Jimenez-Lopez, M., Alburquerque-Bejar, J.J., Nieto-Lopez, L., Garcia-Ayuso, D., Villegas-Perez, M.P., Vidal-Sanz, M., and Agudo-Barriuso, M. (2014). Number and distribution of mouse retinal cone photoreceptors: Differences between an albino (Swiss) and a pigmented (C57\/BL6) strain. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102392"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.exer.2018.03.006","article-title":"Bilateral early activation of retinal microglial cells in a mouse model of unilateral laser-induced experimental ocular hypertension","volume":"171","author":"Ramirez","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1167\/iovs.16-19618","article-title":"Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats","volume":"57","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lucas-Ruiz, F., Galindo-Romero, C., Rodriguez-Ramirez, K.T., Vidal-Sanz, M., and Agudo-Barriuso, M. (2019). Neuronal Death in the Contralateral Un-Injured Retina after Unilateral Axotomy: Role of Microglial Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225733"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/(SICI)1097-4695(199901)38:1<116::AID-NEU9>3.0.CO;2-F","article-title":"Unilateral injury to the adult rat optic nerve causes multiple cellular responses in the contralateral site","volume":"38","author":"Bodeutsch","year":"1999","journal-title":"J. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.brainresbull.2006.09.005","article-title":"The growth factor response in ischemic rat retina and superior colliculus after brimonidine pre-treatment","volume":"71","author":"Lonngren","year":"2006","journal-title":"Brain Res. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30719","DOI":"10.1038\/srep30719","article-title":"Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function","volume":"6","author":"Fujii","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.preteyeres.2009.11.004","article-title":"Retinal light damage: Mechanisms and protection","volume":"29","author":"Organisciak","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1562\/0031-8655(2002)075<0547:EFACRO>2.0.CO;2","article-title":"Evidence for a circadian rhythm of susceptibility to retinal light damage","volume":"75","author":"Vaughan","year":"2002","journal-title":"Photochem. Photobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1002\/pro.5560051220","article-title":"Recombinant human pigment epithelium-derived factor (PEDF): Characterization of PEDF overexpressed and secreted by eukaryotic cells","volume":"5","author":"Stratikos","year":"1996","journal-title":"Protein Sci. A Publ. Protein Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3389\/fnins.2017.00235","article-title":"Shared and Differential Retinal Responses against Optic Nerve Injury and Ocular Hypertension","volume":"11","author":"Rovere","year":"2017","journal-title":"Front. Neuro Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pbr.2015.04.008","article-title":"Retinal neurodegeneration in experimental glaucoma","volume":"220","year":"2015","journal-title":"Prog. Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7242\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:26Z","timestamp":1760177726000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/19\/7242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,30]]},"references-count":46,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["ijms21197242"],"URL":"https:\/\/doi.org\/10.3390\/ijms21197242","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,30]]}}}