{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:28:17Z","timestamp":1780072097786,"version":"3.54.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460201"],"award-info":[{"award-number":["82460201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202208535051"],"award-info":[{"award-number":["202208535051"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>This study aimed to develop a human acellular amniotic membrane (HAAM) scaffold suitable for corneal endothelial transplantation. The HAAM was engineered using sequential chemical treatments and physical agitation to remove cellular components while preserving the extracellular matrix structure. The study sought to evaluate the biocompatibility and functional properties of the HAAM when seeded with immortalized human corneal endothelial cells (HCECs), with the ultimate goal of providing a potential therapeutic option for corneal endothelial dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The HAAM was fabricated through a series of chemical treatments involving trypsin\/EDTA, Triton X-100, sodium deoxycholate, and peracetic acid\/ethanol, combined with physical agitation. Following lyophilization, the HAAM was sterilized and coated with fibronectin and chondroitin sulfate (FNC) to enhance cell adhesion. HCECs were then seeded onto the HAAM scaffold. Biocompatibility was assessed by evaluating cell adhesion using microscopy, cell viability using CCK-8 and EdU assays, and cell proliferation. Functional validation included immunofluorescence detection of tight junction proteins (ZO-1), transcriptome sequencing (RNA-seq), and quantitative PCR (qPCR) to analyze the expression of genes regulating barrier function, ion transport, and extracellular matrix synthesis. Additionally, the expression of key genes critical for endothelial function was assessed to validate the functionality of the HAAM-based corneal endothelial transplantation membrane.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The HAAM was successfully prepared, maintaining an intact collagen fiber structure. HCECs adhered closely to the HAAM scaffold, forming a continuous monolayer. The HAAM promoted cell viability and proliferation, as evidenced by positive expression of tight junction proteins and upregulation of key functional genes. Transcriptome analysis identified genes involved in proliferation and matrix synthesis, further supporting the biocompatibility and functional properties of the HAAM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The HAAM scaffold demonstrated excellent transparency, mechanical properties, and biocompatibility, making it suitable for the attachment and proliferation of HCECs. The effective maintenance of key functional gene expression levels suggests that the HAAM functionally mimics the characteristics of the natural corneal endothelial layer. These findings provide experimental evidence for the potential clinical application of the HAAM in corneal endothelial transplantation, offering a promising therapeutic option for patients with corneal endothelial dysfunction. Further studies are warranted to explore the long-term efficacy and safety of the HAAM in preclinical and clinical settings.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1592123","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:07Z","timestamp":1751347687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Research on the construction of corneal endothelium transplantation with acellular amniotic membrane as a scaffold"],"prefix":"10.3389","volume":"12","author":[{"given":"Ya-Nan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Qin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Yu","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Qin","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Jie","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Fang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S0161-6420(82)34746-6","article-title":"The corneal endothelium. Normal and pathologic structure and function","volume":"89","author":"Waring","year":"1982","journal-title":"Ophthalmology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/0002-9394(66)90921-4","article-title":"The human corneal endothelium","volume":"61","author":"Kaufman","year":"1966","journal-title":"Am J Ophthalmol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1097\/ico.0000000000002122","article-title":"A review of the literature on the global epidemiology of corneal blindness","volume":"38","author":"Porth","year":"2019","journal-title":"Cornea"},{"key":"ref4","article-title":"Cornea transplantation","volume-title":"StatPearls","author":"Maghsoudlou","year":"2024"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ajo.2004.09.045","article-title":"Corneal endothelium and postoperative outcomes 15 years after penetrating keratoplasty","volume":"139","author":"Patel","year":"2005","journal-title":"Am J Ophthalmol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s10792-024-02994-1","article-title":"Fuchs endothelial corneal dystrophy: an updated review","volume":"44","author":"Altamirano","year":"2024","journal-title":"Int Ophthalmol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.ajo.2019.06.012","article-title":"Descemet membrane endothelial keratoplasty versus descemet stripping automated endothelial keratoplasty and penetrating keratoplasty","volume":"207","author":"Woo","year":"2019","journal-title":"Am J Ophthalmol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e0295434","DOI":"10.1371\/journal.pone.0295434","article-title":"Five-year clinical outcomes of 107 consecutive DMEK surgeries","volume":"18","author":"Bichet","year":"2023","journal-title":"PLoS One"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1097\/ico.0000000000002565","article-title":"Endothelial keratoplasty update 2020","volume":"40","author":"Price","year":"2021","journal-title":"Cornea"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"100904","DOI":"10.1016\/j.preteyeres.2020.100904","article-title":"Corneal endothelial dysfunction: evolving understanding and treatment options","volume":"82","author":"Price","year":"2021","journal-title":"Prog Retin Eye Res"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"100768","DOI":"10.1016\/j.preteyeres.2019.07.001","article-title":"Immune reactions after modern lamellar (DALK, DSAEK, DMEK) versus conventional penetrating corneal transplantation","volume":"73","author":"Hos","year":"2019","journal-title":"Prog Retin Eye Res"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"771","DOI":"10.3760\/cma.j.issn.0412-4081.2010.09.002","article-title":"Focus on the challenge of basic research on corneal tissue engineering","volume":"46","author":"Li","year":"2010","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3760\/cma.j.issn.2095-1477.2010.11.030","article-title":"Research progress on seed cells for the construction of corneal endothelial membrane using tissue engineering","volume":"32","author":"Sun","year":"2010","journal-title":"Zhongguo yan wai shang zhi ye yan bing za zhi"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"871","DOI":"10.2217\/rme-2020-0202","article-title":"Challenges in corneal endothelial cell culture","volume":"16","author":"Wongvisavavit","year":"2021","journal-title":"Regen Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3760\/cma.j.issn.2095-0160.2008.04.003","article-title":"Replacement of corneal endothelium with auto-vascular endothelium","volume":"26","author":"Zhewen","year":"2008","journal-title":"Chin Ophthalmic Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"540","DOI":"10.3760\/j.issn:0412-4081.2007.06.013","article-title":"Transplantation of autologous bone marrow mesenchymal stem cells for the treatment of corneal endothelium damages in rabbits","volume":"43","author":"Liu","year":"2007","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"9636897211017830","DOI":"10.1177\/09636897211017830","article-title":"Long-term observation and sequencing analysis of SKPs-derived corneal endothelial cell-like cells for treating corneal endothelial dysfunction","volume":"30","author":"Shen","year":"2021","journal-title":"Cell Transplant"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s43246-022-00247-1","article-title":"In vivo engraftment into the cornea endothelium using extracellular matrix shrink-wrapped cells","volume":"3","author":"Palchesko","year":"2022","journal-title":"Commun Mater"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1056\/NEJMoa1712770","article-title":"Injection of cultured cells with a ROCK inhibitor for bullous keratopathy","volume":"378","author":"Kinoshita","year":"2018","journal-title":"N Engl J Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3760\/cma.j.issn.0412-4081.2013.11.011","article-title":"Experimental study on the rhesus monkey corneal endothelial cells substituted by the allogeneic vascular endothelial cells cultivated in vitro","volume":"49","author":"Zhu","year":"2013","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.ajpath.2012.03.033","article-title":"ROCK inhibitor converts corneal endothelial cells into a phenotype capable of regenerating in vivo endothelial tissue","volume":"181","author":"Okumura","year":"2012","journal-title":"Am J Pathol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.nano.2014.12.002","article-title":"Magnetic field-guided cell delivery with nanoparticle-loaded human corneal endothelial cells","volume":"11","author":"Moysidis","year":"2015","journal-title":"Nanomedicine"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"26113","DOI":"10.1038\/srep26113","article-title":"Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction","volume":"6","author":"Okumura","year":"2016","journal-title":"Sci Rep"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1136\/bjo.83.6.748","article-title":"Amniotic membrane transplantation","volume":"83","author":"Dua","year":"1999","journal-title":"Br J Ophthalmol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s10561-015-9540-7","article-title":"Ophthalmic indications of amniotic membrane transplantation in Mexico: an eight years amniotic membrane bank experience","volume":"17","author":"Ch\u00e1vez-Garc\u00eda","year":"2016","journal-title":"Cell Tissue Bank"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1111\/pde.14376","article-title":"Infantile toxic epidermal necrolysis: successful treatment of an 8-week-old with intravenous immunoglobulin and amniotic membrane transplant","volume":"38","author":"Nassim","year":"2021","journal-title":"Pediatr Dermatol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"4698","DOI":"10.1167\/iovs.03-0272","article-title":"Propagation and phenotypic preservation of rabbit limbal epithelial cells on amniotic membrane","volume":"44","author":"Wang","year":"2003","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1007\/s10792-022-02493-1","article-title":"Impact of adjuvant amniotic membrane transplantation in infectious ulcerative keratitis","volume":"43","author":"Bulut","year":"2023","journal-title":"Int Ophthalmol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"13007","DOI":"10.1038\/s41598-021-92366-x","article-title":"Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis","volume":"11","author":"Ting","year":"2021","journal-title":"Sci Rep"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/bs.mcb.2019.11.004","article-title":"Protocols for decellularization of human amniotic membrane","volume":"157","author":"Khosravimelal","year":"2020","journal-title":"Methods Cell Biol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s13287-019-1179-z","article-title":"Transplantation of oral mucosal epithelial cells seeded on decellularized and lyophilized amniotic membrane for the regeneration of injured endometrium","volume":"10","author":"Chen","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1002\/jbm.a.37509","article-title":"Positive effect of acellular amniotic membrane dressing with immobilized growth factors in skin wound healing","volume":"111","author":"Laleh","year":"2023","journal-title":"J Biomed Mater Res A"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1002\/jbm.10349","article-title":"Extracellular matrix of human amnion manufactured into tubes as conduits for peripheral nerve regeneration","volume":"63","author":"Mligiliche","year":"2002","journal-title":"J Biomed Mater Res"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1177\/0885328217739753","article-title":"Human acellular amniotic membrane: a potential osteoinductive biomaterial for bone regeneration","volume":"32","author":"Tang","year":"2018","journal-title":"J Biomater Appl"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"121032","DOI":"10.1016\/j.lfs.2022.121032","article-title":"Applications of acellular human amniotic membrane in regenerative medicine","volume":"310","author":"Doudi","year":"2022","journal-title":"Life Sci"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1186\/s12886-024-03680-7","article-title":"Construction of living-cell tissue engineered amniotic membrane for ocular surface disease","volume":"24","author":"Hu","year":"2024","journal-title":"BMC Ophthalmol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.15909\/j.cnki.cn61-1347\/r.2011.09.094","article-title":"Application of staining amnion extracellular matrix on secondary hydroxyapatite orbital implantation combined with conjunctival reconstruction","volume":"20","author":"Liu","year":"2011","journal-title":"Chin J Aesthetic Med"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e79632","DOI":"10.1371\/journal.pone.0079632","article-title":"A simple alkaline method for decellularizing human amniotic membrane for cell culture","volume":"8","author":"Saghizadeh","year":"2013","journal-title":"PLoS One"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s00417-005-0095-3","article-title":"Comparison of intact and denuded amniotic membrane as a substrate for cell-suspension culture of human limbal epithelial cells","volume":"245","author":"Koizumi","year":"2007","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref40","first-page":"1656","article-title":"Isolation and long-term cultivation of human corneal endothelial cells","volume":"29","author":"Engelmann","year":"1988","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"109376","DOI":"10.1016\/j.exer.2022.109376","article-title":"The soil and the seed: the relationship between Descemet\u2019s membrane and the corneal endothelium","volume":"227","author":"Petrela","year":"2023","journal-title":"Exp Eye Res"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12929-018-0492-7","article-title":"Advances in culture, expansion and mechanistic studies of corneal endothelial cells: a systematic review","volume":"26","author":"Chen","year":"2019","journal-title":"J Biomed Sci"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"101364","DOI":"10.1016\/j.mtbio.2024.101364","article-title":"Perspectives on the use of decellularized\/devitalized and lyophilized human perinatal tissues for bone repair: advantages and remaining challenges","volume":"30","author":"Solecki","year":"2025","journal-title":"Mater Today Bio"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"27","author":"Ogata","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1001\/archopht.1940.00860130586006","article-title":"Plastic repair of conjunctival defects with fetal membrane","volume":"23","author":"Rotth","year":"1940","journal-title":"Arch Ophthalmol"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.3390\/biom10091208","article-title":"Decellularized human chorion membrane as a novel biomaterial for tissue regeneration","volume":"10","author":"Fraz\u00e3o","year":"2020","journal-title":"Biomol Ther"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.3390\/pharmaceutics15092249","article-title":"Human acellular amniotic membrane as skin substitute and biological scaffold: a review of its preparation, preclinical research, and clinical application","volume":"15","author":"Li","year":"2023","journal-title":"Pharmaceutics"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"925","DOI":"10.3760\/j:issn:0412-4081.2006.10.013","article-title":"Amniotic membrane as a carrier for cultivated and labeled corneal endothelial cell transplantation","volume":"42","author":"Fu","year":"2006","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1007\/s00417-008-0904-6","article-title":"Cultivation of an immortalized human corneal endothelial cell population and two distinct clonal subpopulations on thermo-responsive carriers","volume":"246","author":"G\u00f6tze","year":"2008","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1159\/000113406","article-title":"Two clonal cell lines of immortalized human corneal endothelial cells show either differentiated or precursor cell characteristics","volume":"187","author":"Valtink","year":"2008","journal-title":"Cells Tissues Organs"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"3861","DOI":"10.1242\/jcs.00059","article-title":"Fibronectin at a glance","volume":"115","author":"Pankov","year":"2002","journal-title":"J Cell Sci"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"109390","DOI":"10.1016\/j.exer.2023.109390","article-title":"Role of aquaporins in corneal healing post chemical injury","volume":"228","author":"Bhend","year":"2023","journal-title":"Exp Eye Res"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"116138","DOI":"10.1016\/j.taap.2022.116138","article-title":"GJA1 reverses arsenic-induced EMT via modulating MAPK\/ERK signaling pathway","volume":"450","author":"Wu","year":"2022","journal-title":"Toxicol Appl Pharmacol"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"e25191","DOI":"10.1016\/j.heliyon.2024.e25191","article-title":"System biology approaches to identify hub genes linked with ECM organization and inflammatory signaling pathways in schizophrenia pathogenesis","volume":"10","author":"Bhuiyan","year":"2024","journal-title":"Heliyon"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1002\/glia.23974","article-title":"Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation","volume":"69","author":"Lanfranco","year":"2021","journal-title":"Glia"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"116127","DOI":"10.1016\/j.bcp.2024.116127","article-title":"Identification of 18\u03b2-glycyrrhetinic acid as an AGT inhibitor against LPS-induced myocardial dysfunction via high throughput screening","volume":"223","author":"Shi","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e2206798","DOI":"10.1002\/advs.202206798","article-title":"Donafenib and GSK-J4 synergistically induce ferroptosis in liver cancer by upregulating HMOX1 expression","volume":"10","author":"Zheng","year":"2023","journal-title":"Adv Sci"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1592123\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:13Z","timestamp":1751347693000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1592123\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":59,"alternative-id":["10.3389\/fmed.2025.1592123"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1592123","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"article-number":"1592123"}}