{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:54Z","timestamp":1787026674454,"version":"build-2736575974"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aims to observe the effect of Electroacupuncture (EA) on improving ocular surface inflammation and\n                      <jats:italic>HMGB1<\/jats:italic>\n                      -related signaling pathways in dry eye disease (DED). Methods: Healthy male C57BL\/6\u202fJ mice were treated with scopolamine hydrobromide for 21 consecutive days to establish the animal models for DED. After 21\u202fdays, fluorometholone (Flu), EA, and sham EA (Sham) treatments were performed. The effect of EA on DED surface inflammation was evaluated by corneal fluorescence staining, phenol red thread test,\n                      <jats:italic>in vivo<\/jats:italic>\n                      confocal microscopy (IVCM), and corneal histopathology. The influence of EA on high-mobility group box 1 (\n                      <jats:italic>HMGB1<\/jats:italic>\n                      ), receptor for advanced glycation end products (\n                      <jats:italic>RAGE<\/jats:italic>\n                      ), toll-like receptor 2 (\n                      <jats:italic>TLR2<\/jats:italic>\n                      ) and toll-like receptor 4 (\n                      <jats:italic>TLR4<\/jats:italic>\n                      ) was assessed by immunohistochemistry, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot. The influence of EA on interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay (ELISA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EA can significantly increase tear flow and reduce corneal staining and corneal stromal inflammation, while also improving the morphologic structure of the cornea and lacrimal glands. The levels of HMGB1, RAGE, TLR2, TLR4, and IL-6 were significantly decreased while IL-10 level was significantly increased after EA treatment, indicating that EA may improve dry eye surface inflammation by inhibiting HMGB1-related signaling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings presented in our study demonstrate that EA may improve ocular surface inflammation in mice with DED by inhibiting the HMGB1-related signaling pathways. Therefore, EA may be a potential therapeutic target for DED.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1664376","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:36:27Z","timestamp":1761197787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Electroacupuncture improves scopolamine hydrobromide induced dry eye in mice via inhibiting ocular surface inflammation and regulating the HMGB1-related signaling pathways"],"prefix":"10.3389","volume":"12","author":[{"given":"Xia","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangjie","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingbo","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II definition and classification report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul Surf"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.jtos.2017.05.003","article-title":"TFOS DEWS II epidemiology report","volume":"15","author":"Stapleton","year":"2017","journal-title":"Ocul Surf"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.ajo.2025.05.040","article-title":"TFOS DEWS III Digest report","volume":"279","author":"Stapleton","year":"2025","journal-title":"Am J Ophthalmol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.jtos.2015.11.002","article-title":"Economic and humanistic burden of dry eye disease in Europe, North America, and Asia: a systematic literature review","volume":"14","author":"McDonald","year":"2016","journal-title":"Ocul Surf"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.ajo.2025.05.033","article-title":"Tfos dews III diagnostic methodology","volume":"279","author":"Wolffsohn","year":"2025","journal-title":"Am J Ophthalmol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"ND01","DOI":"10.7860\/JCDR\/2017\/24149.9645","article-title":"A case of bilateral corneal perforation in a patient with severe dry eye","volume":"11","author":"Deswal","year":"2017","journal-title":"J Clin Diagn Res"},{"key":"ref7","doi-asserted-by":"publisher","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":"ref8","doi-asserted-by":"publisher","first-page":"7782","DOI":"10.62347\/puny8378","article-title":"Efficacy of moisture chamber goggles combined with fluorometholone eye drops on visual function and oxidative stress in patients with dry eye disease","volume":"16","author":"Zhou","year":"2024","journal-title":"Am J Transl Res"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.jtos.2017.05.006","article-title":"TFOS DEWS II management and therapy report","volume":"15","author":"Jones","year":"2017","journal-title":"Ocul Surf"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S2005-2901(10)60014-3","article-title":"Defining meridians: a modern basis of understanding","volume":"3","author":"Longhurst","year":"2010","journal-title":"J Acupunct Meridian Stud"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e315","DOI":"10.1111\/aos.15271","article-title":"Effects of electroacupuncture on dry eye: a pilot randomized controlled trial","volume":"101","author":"Yang","year":"2023","journal-title":"Acta Ophthalmol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e069369","DOI":"10.1136\/bmjopen-2022-069369","article-title":"Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial","volume":"13","author":"Lu","year":"2023","journal-title":"BMJ Open"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.explore.2023.10.010","article-title":"A novel approach to the immediate effects of electroacupuncture on dry eye: a case series","volume":"20","author":"Wu","year":"2024","journal-title":"Explore"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.13702\/j.1000-0607.20210292","article-title":"Acupuncture and moxibustion treatment for dry eye disease: a network meta-analysis of rando-mized controlled trial","volume":"46","author":"Wang","year":"2021","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"975","DOI":"10.13702\/j.1000-0607.20220015","article-title":"Acupuncture mitigates ocular surface inflammatory response via \u03b17nAChR\/NF-\u03baB p65 signaling in dry eye guinea pigs","volume":"47","author":"Sun","year":"2022","journal-title":"Zhen Ci Yan Jiu"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/6613144","article-title":"Acupuncture alleviates corneal inflammation in New Zealand white rabbits with dry eye diseases by regulating \u03b17nAChR and NF-\u03baB signaling pathway","volume":"2022","author":"Ding","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s11302-024-09991-0","article-title":"Electroacupuncture regulates the P2X7R-NLRP3 inflammatory cascade to relieve decreased sensation on ocular surface of type 2 diabetic rats with dry eye","volume":"21","author":"Wan","year":"2024","journal-title":"Purinergic Signal"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"6673610","DOI":"10.1155\/2021\/6673610","article-title":"Electroacupuncture alleviates inflammation of dry eye diseases by regulating the \u03b1 7nAChR\/NF- \u03ba b signaling pathway","volume":"2021","author":"Ding","year":"2021","journal-title":"Oxidative Med Cell Longev"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1080\/02713683.2019.1666997","article-title":"A mechanism study of Electroacupuncture for dry eye syndrome by targeting conjunctival cytokine expressions","volume":"45","author":"Zhang","year":"2020","journal-title":"Curr Eye Res"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"S2090-1232(25)00577-6","DOI":"10.1016\/j.jare.2025.07.047","article-title":"DAMP signaling networks: from receptors to diverse pathophysiological functions","volume":"31","author":"Chen","year":"2025","journal-title":"J Adv Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-sensing receptors in inflammation and diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"5224","DOI":"10.1111\/bph.15261","article-title":"Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation via HMGB1\/TLR4\/NF-\u03baB and TNF-\u03b1\/TNFR1\/NF-\u03baB pathways","volume":"177","author":"Xu","year":"2020","journal-title":"Br J Pharmacol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3892\/ijmm.2019.4402","article-title":"HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE\/NF-\u03baB signaling pathways","volume":"45","author":"Wang","year":"2020","journal-title":"Int J Mol Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/jvh.12152","article-title":"Enhanced high-mobility group box 1 (HMGB1) modulates regulatory T cells (Treg)\/T helper 17 (Th17) balance via toll-like receptor (TLR)-4-interleukin (IL)-6 pathway in patients with chronic hepatitis B","volume":"21","author":"Li","year":"2014","journal-title":"J Viral Hepat"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1007\/s00125-020-05105-8","article-title":"Extracellular HMGB1 exacerbates autoimmune progression and recurrence of type 1 diabetes by impairing regulatory T cell stability","volume":"63","author":"Zhang","year":"2020","journal-title":"Diabetologia"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.3390\/cells10051044","article-title":"The effect and regulatory mechanism of high mobility group Box-1 protein on immune cells in inflammatory diseases","volume":"10","author":"Ge","year":"2021","journal-title":"Cells"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12974-019-1673-3","article-title":"HMGB1\/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia","volume":"17","author":"Zhang","year":"2020","journal-title":"J Neuroinflammation"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1001\/jama.2021.19963","article-title":"Dry eye disease: an update in 2022","volume":"327","author":"Hakim","year":"2022","journal-title":"JAMA"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1097\/jcma.0000000000001226","article-title":"Electroacupuncture treatment enhances synaptic plasticity in middle cerebral artery occlusion mice via the miR-670-3p\/HMGB1 axis","volume":"88","author":"Cheng","year":"2025","journal-title":"J Chin Med Assoc"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"110397","DOI":"10.1016\/j.intimp.2023.110397","article-title":"Salidroside alleviates oxidative stress in dry eye disease by activating autophagy through AMPK-Sirt1 pathway","volume":"121","author":"Liang","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/icu.0000000000000569","article-title":"Advances in dry eye disease treatment","volume":"30","author":"O'Neil","year":"2019","journal-title":"Curr Opin Ophthalmol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s10384-018-00645-4","article-title":"Tear-film-oriented diagnosis for dry eye","volume":"63","author":"Yokoi","year":"2019","journal-title":"Jpn J Ophthalmol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1016\/j.ophtha.2017.08.029","article-title":"Inflammation in dry eye disease: how do we break the cycle?","volume":"124","author":"Rhee","year":"2017","journal-title":"Ophthalmology"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e2200435","DOI":"10.1002\/advs.202200435","article-title":"Anti-oxidative and anti-inflammatory micelles: break the dry eye vicious cycle","volume":"9","author":"Li","year":"2022","journal-title":"Adv Sci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.14715\/cmb\/2024.70.5.15","article-title":"Electroacupuncture modulates the TLR4-NF-\u03baB inflammatory signaling pathwayto attenuate ocular surface inflammation in dry eyes of type 2 diabetic rats","volume":"70","author":"Fu","year":"2024","journal-title":"Cell Mol Biol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e35750","DOI":"10.1016\/j.heliyon.2024.e35750","article-title":"Electroacupuncture improves retinal function in myopia Guinea pigs probably via inhibition of the RhoA\/ROCK2 signaling pathway","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.explore.2022.06.005","article-title":"Acupuncture for abducens nerve palsy after radiochemotherapy: a CARE-compliant case report","volume":"19","author":"Huang","year":"2023","journal-title":"Explore"},{"key":"ref38","first-page":"632","article-title":"A mouse model of keratoconjunctivitis sicca","volume":"43","author":"Dursun","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"R203","DOI":"10.1186\/cc8210","article-title":"Combination effect of antithrombin and recombinant human soluble thrombomodulin in a lipopolysaccharide induced rat sepsis model","volume":"13","author":"Iba","year":"2009","journal-title":"Crit Care"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.3892\/or.2015.3782","article-title":"Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1\/2","volume":"33","author":"Zhang","year":"2015","journal-title":"Oncol Rep"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1080\/14728222.2018.1439924","article-title":"Extracellular HMGB1 as a therapeutic target in inflammatory diseases","volume":"22","author":"Andersson","year":"2018","journal-title":"Expert Opin Ther Targets"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"705","DOI":"10.3389\/fimmu.2018.00705","article-title":"High-mobility group box 1-induced complement activation causes sterile inflammation","volume":"9","author":"Kim","year":"2018","journal-title":"Front Immunol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13045-020-00950-x","article-title":"HMGB1 in inflammation and cancer","volume":"13","author":"Wang","year":"2020","journal-title":"J Hematol Oncol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.7150\/thno.81406","article-title":"The STAT1\/HMGB1\/NF-\u03baB pathway in chronic inflammation and kidney injury after cisplatin exposure","volume":"13","author":"Fu","year":"2023","journal-title":"Theranostics"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1111\/febs.16678","article-title":"Regulatory mechanisms of HMGB1 and its receptors in polycystic ovary syndrome-driven gravid uterine inflammation","volume":"290","author":"Hu","year":"2023","journal-title":"FEBS J"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1002\/bab.2635","article-title":"CircMYO1C silencing alleviates chondrocytes inflammation and apoptosis through m(6)a\/HMGB1 axis in osteoarthritis","volume":"71","author":"Sun","year":"2024","journal-title":"Biotechnol Appl Biochem"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.trim.2015.11.001","article-title":"The protective effect of neutralizing high-mobility group box1 against chronic cyclosporine nephrotoxicity in mice","volume":"34","author":"Park","year":"2016","journal-title":"Transpl Immunol"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"5833","DOI":"10.3390\/ijms22115833","article-title":"Role played by receptors for advanced glycosylation end products in corneal endothelial cells after HSV-1 infection","volume":"22","author":"Miyazaki","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"8782","DOI":"10.3390\/ijms26188782","article-title":"Inhibition of the HMGB1-RAGE Axis attenuates microglial inflammation and ameliorates hypoxia-induced cognitive impairment","volume":"26","author":"Liu","year":"2025","journal-title":"Int J Mol Sci"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1365015","DOI":"10.3389\/fimmu.2024.1365015","article-title":"Elevated levels of damage-associated molecular patterns HMGB1 and S100A8\/A9 coupled with toll-like receptor-triggered monocyte activation are associated with inflammation in patients with myelofibrosis","volume":"15","author":"De Luca","year":"2024","journal-title":"Front Immunol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"04","DOI":"10.35946\/arcr.v44.1.04","article-title":"Alcohol, HMGB1, and innate immune signaling in the brain","volume":"44","author":"Crews","year":"2024","journal-title":"Alcohol Res"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.smim.2018.02.011","article-title":"High-mobility group box 1 protein (HMGB1) operates as an alarmin outside as well as inside cells","volume":"38","author":"Andersson","year":"2018","journal-title":"Semin Immunol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/cmi.2016.34","article-title":"HMGB1, IL-1\u03b1, IL-33 and S100 proteins: dual-function alarmins","volume":"14","author":"Bertheloot","year":"2017","journal-title":"Cell Mol Immunol"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"Saraiva","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"3001","DOI":"10.3390\/nu17183001","article-title":"Alfalfa polysaccharide alleviates colitis by regulating intestinal microbiota and the intestinal barrier against the TLR4\/MyD88\/NF-\u03baB pathway","volume":"17","author":"La","year":"2025","journal-title":"Nutrients"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1172\/jci20762","article-title":"Antagonistic antibody prevents toll-like receptor 2-driven lethal shock-like syndromes","volume":"113","author":"Meng","year":"2004","journal-title":"J Clin Invest"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1074\/jbc.M117.786756","article-title":"Receptor for advanced glycation end products mediates sepsis-triggered amyloid-\u03b2 accumulation, tau phosphorylation, and cognitive impairment","volume":"293","author":"Gasparotto","year":"2018","journal-title":"J Biol Chem"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"112130","DOI":"10.1016\/j.intimp.2024.112130","article-title":"HMGB1 promotes neutrophil PD-L1 expression through TLR2 and mediates T cell apoptosis leading to immunosuppression in sepsis","volume":"133","author":"Liu","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/nm0410-369","article-title":"Taming TLR4 may ease seizures","volume":"16","author":"Kleen","year":"2010","journal-title":"Nat Med"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nm.2127","article-title":"Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures","volume":"16","author":"Maroso","year":"2010","journal-title":"Nat Med"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1664376\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T05:36:29Z","timestamp":1761197789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1664376\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":60,"alternative-id":["10.3389\/fmed.2025.1664376"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1664376","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]},"article-number":"1664376"}}