{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:25:19Z","timestamp":1777861519733,"version":"3.51.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"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. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Metabolism-associated fatty liver disease (MAFLD) has emerged as a severe worldwide public health burden with insufficient available clinical therapeutic strategies, which underscores the urgent demand for safe, natural dietary interventions. Raspberry (\n                      <jats:italic>Rubus idaeus<\/jats:italic>\n                      L.), a typical food-medicine homologous fruit abundant in diverse bioactive components including anthocyanins, flavonoids and polysaccharides, possesses prominent nutritional and medicinal potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, raspberry aqueous extract (RE) was prepared to comprehensively investigate its ameliorative effects and underlying molecular mechanisms against MAFLD. MAFLD animal model was established in C57BL\/6 mice via 12-week high-fat diet (HFD) feeding. From the 9th week, model mice were intragastrically administered with RE at doses of 1 g\/kg\/d and 2 g\/kg\/d for continuous intervention. Integrated multi-omics analyses including 16S rRNA microbial sequencing, serum\/hepatic biochemical detection, histopathological examination, in vivo microbial colonization assay, and in vitro cellular and metabolomic experiments were performed to systematically clarify the regulatory mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RE treatment markedly improved the core pathological phenotypes of MAFLD mice, and significantly mitigated hepatic steatosis and hepatocellular injury. 16S rRNA sequencing demonstrated that RE remodeled the gut microbial dysbiosis, specifically elevating the abundance of beneficial genus\n                      <jats:italic>Ileibacterium<\/jats:italic>\n                      and suppressing pathogenic microbial taxa. Meanwhile, RE strengthened intestinal mucosal barrier integrity by upregulating tight junction protein expression, and activated hepatic purine metabolic reprogramming to boost the levels of critical metabolites including inosine and ADP. Spearman correlation analysis verified the significantly positive correlation between\n                      <jats:italic>Ileibacterium<\/jats:italic>\n                      abundance and hepatic inosine content, and both factors were closely correlated with the remission of MAFLD pathological indicators. In vivo colonization experiments further validated that\n                      <jats:italic>Ileibacterium<\/jats:italic>\n                      intervention alone remarkably alleviated hepatic lipid deposition and liver damage in MAFLD mice. In vitro strain metabolomics confirmed that\n                      <jats:italic>Ileibacterium<\/jats:italic>\n                      could directly biosynthesize and secrete inosine extracellularly. Furthermore, in vitro AML12 hepatocyte experiments revealed that 100 \u03bcM inosine remarkably relieved palmitic acid-induced lipotoxicity via reducing intracellular lipid overload, reactive oxygen species (ROS) accumulation and mitochondrial dysfunction, alongside modulating the expression of lipid metabolism, inflammatory and autophagy-related genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, our results elucidate that raspberry aqueous extract alleviates experimental MAFLD through the gut microbiota-purine metabolism-inosine regulatory axis, in which Ileibacterium and inosine act as the core synergistic mediators. This study provides solid preclinical experimental evidence for the development and application of raspberry as a promising functional food for the prevention and nutritional intervention of MAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1818086","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:21:28Z","timestamp":1777522888000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Raspberry aqueous extract ameliorates MAFLD in mice by regulating gut microbiota and purine metabolism"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanyan","family":"Gao","sequence":"first","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nian","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaxin","family":"Wei","sequence":"additional","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianchi","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangying","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]},{"name":"Lipid Metabolism Laboratory, Key Laboratory of State Administration of Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"Institute of Lipid Metabolism Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiannan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]},{"name":"Lipid Metabolism Laboratory, Key Laboratory of State Administration of Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"Institute of Lipid Metabolism Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobing","family":"Dou","sequence":"additional","affiliation":[{"name":"Zhejiang-Hong Kong Joint Laboratory of Liver and Spleen Simultaneous Treatment in Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"School of Life Sciences, Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]},{"name":"Lipid Metabolism Laboratory, Key Laboratory of State Administration of Traditional Chinese Medicine","place":["Zhejiang, China"]},{"name":"Institute of Lipid Metabolism Zhejiang Chinese Medical University","place":["Zhejiang, Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/S0140-6736(24)01811-7","article-title":"Steatotic liver disease","volume":"404","author":"Israelsen","year":"2024","journal-title":"Lancet (London, England)"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/s41573-024-01084-2","article-title":"Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (mash)","volume":"24","author":"Do","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.jhep.2025.02.033","article-title":"Integrative metabolism in masld and mash: pathophysiology and emerging mechanisms","volume":"83","author":"Steinberg","year":"2025","journal-title":"J Hepatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/S2213-8587(24)00318-8","article-title":"Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment","volume":"13","author":"Stefan","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"ITC1-16","DOI":"10.7326\/ANNALS-24-02933","article-title":"Metabolic dysfunction-associated steatotic liver disease","volume":"178","author":"Ali","year":"2025","journal-title":"Ann Intern Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41575-025-01089-1","article-title":"Gut microbiome in metabolic dysfunction-associated steatotic liver disease and associated hepatocellular carcinoma","volume":"22","author":"Lau","year":"2025","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"9408","DOI":"10.1021\/acs.jafc.4c09593","article-title":"Therapeutic potential of raspberry extract in high-fat diet-induced liver injury via apoptosis and ampk\/ppar\u03b1 pathways","volume":"73","author":"Xu","year":"2025","journal-title":"J Agric Food Chem"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3390\/nu12020463","article-title":"Phenolic composition, mineral content, and beneficial bioactivities of leaf extracts from black currant (ribes nigrum l.), raspberry (rubus idaeus), and aronia (aronia melanocarpa)","volume":"12","author":"Staszowska-Karkut","year":"2020","journal-title":"Nutrients"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"108946","DOI":"10.1016\/j.jnutbio.2022.108946","article-title":"Raspberry consumption: identification of distinct immune-metabolic response profiles by whole blood transcriptome profiling","volume":"101","author":"Franck","year":"2022","journal-title":"J Nutr Biochem"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"9529676","DOI":"10.1155\/2019\/9529676","article-title":"Red raspberry extract protects the skin against uvb-induced damage with antioxidative and anti-inflammatory properties","volume":"2019","author":"Wang","year":"2019","journal-title":"Oxidative Med Cell Longev"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"6943","DOI":"10.1039\/d4fo01050g","article-title":"Red raspberry (rubus idaeus) preserves intestinal barrier integrity and reduces oxidative stress in caco-2 cells exposed to a proinflammatory stimulus","volume":"15","author":"Marino","year":"2024","journal-title":"Food Funct"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"130007","DOI":"10.1016\/j.ijbiomac.2024.130007","article-title":"Raspberry polysaccharides attenuate hepatic inflammation and oxidative stress in diet-induced obese mice by enhancing butyrate-mediated intestinal barrier function","volume":"262","author":"Wu","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.foodchem.2017.01.097","article-title":"Red raspberry (rubus idaeus l.) intake decreases oxidative stress in obese diabetic (db\/db) mice","volume":"227","author":"Noratto","year":"2017","journal-title":"Food Chem"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"110796","DOI":"10.1016\/j.fct.2019.110796","article-title":"Red raspberry extract (rubus idaeus l shrub) intake ameliorates hyperlipidemia in hfd-induced mice through ppar signaling pathway","volume":"133","author":"Tu","year":"2019","journal-title":"Food Chem Toxicol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"15740","DOI":"10.1021\/acs.jafc.4c03286","article-title":"Raspberry ketone attenuates hepatic fibrogenesis and inflammation via regulating the crosstalk of fxr and pgc-1\u03b1 signaling","volume":"72","author":"Jiang","year":"2024","journal-title":"J Agric Food Chem"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"176001","DOI":"10.1016\/j.ejphar.2023.176001","article-title":"Raspberry ketone ameliorates nonalcoholic fatty liver disease in rats by activating the ampk pathway","volume":"957","author":"Askar","year":"2023","journal-title":"Eur J Pharmacol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1136\/gutjnl-2024-332398","article-title":"Interplay between gut microbiome, host genetic and epigenetic modifications in masld and masld-related hepatocellular carcinoma","volume":"74","author":"Ha","year":"2024","journal-title":"Gut"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1016\/j.immuni.2025.03.017","article-title":"Acute exposure to high-fat diet impairs ilc3 functions and gut homeostasis","volume":"58","author":"Xiong","year":"2025","journal-title":"Immunity"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1016\/j.jhep.2019.08.005","article-title":"Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development","volume":"71","author":"Mouries","year":"2019","journal-title":"J Hepatol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1007\/s00018-019-03011-w","article-title":"The links between the gut microbiome and non-alcoholic fatty liver disease (nafld)","volume":"76","author":"Safari","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J Hepatol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1126\/science.abc3421","article-title":"Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy","volume":"369","author":"Mager","year":"2020","journal-title":"Science (New York, N.Y.)"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1043970","DOI":"10.3389\/fphar.2022.1043970","article-title":"Inosine: a bioactive metabolite with multimodal actions in human diseases","volume":"13","author":"Kim","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/d41573-022-00126-x","article-title":"Inosine boosts fat burning","volume":"21","author":"Crunkhorn","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1056\/NEJMra1503519","article-title":"Cause, pathogenesis, and treatment of nonalcoholic steatohepatitis","volume":"377","author":"Diehl","year":"2017","journal-title":"N Engl J Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1039\/d5fo04185f","article-title":"Ellagitannins from red raspberry (rubus idaeus l.): a comprehensive review on chemistry characteristics and beneficial effects","volume":"17","author":"Tao","year":"2026","journal-title":"Food Funct"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"24417","DOI":"10.1021\/acs.jafc.4c04929","article-title":"Nuciferine alleviates high-fat diet- and apoe(\u2212\/\u2212)-induced hepatic steatosis and ferroptosis in nafld mice via the ppar\u03b1 signaling pathway","volume":"72","author":"Qiu","year":"2024","journal-title":"J Agric Food Chem"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"141151","DOI":"10.1016\/j.ijbiomac.2025.141151","article-title":"Metabolic restoration: rhubarb polysaccharides as a shield against non-alcoholic fatty liver disease","volume":"305","author":"Qiu","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"155799","DOI":"10.1016\/j.phymed.2024.155799","article-title":"Geniposide dosage and administration time: balancing therapeutic benefits and adverse reactions in liver disease treatment","volume":"132","author":"Qiu","year":"2024","journal-title":"Phytomed Int J Phytother Phytopharm"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"149278","DOI":"10.1016\/j.ijbiomac.2025.149278","article-title":"Raspberry polysaccharide extraction, purification, structural characterization, and biological activity research progress: a review","volume":"335","author":"Zhao","year":"2026","journal-title":"Int J Biol Macromol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.3390\/molecules23092103","article-title":"Raspberry polyphenolic extract regulates obesogenic signals in hepatocytes","volume":"23","author":"Fotschki","year":"2018","journal-title":"Molecules (Basel, Switzerland)"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"eabk0855","DOI":"10.1126\/scitranslmed.abk0855","article-title":"Risk assessment with gut microbiome and metabolite markers in nafld development","volume":"14","author":"Leung","year":"2022","journal-title":"Sci Transl Med"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.molmed.2023.07.002","article-title":"The global human gut microbiome: genes, lifestyles, and diet","volume":"29","author":"Parizadeh","year":"2023","journal-title":"Trends Mol Med"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"156992","DOI":"10.1016\/j.phymed.2025.156992","article-title":"Alisol b ameliorated metabolic dysfunction-associated steatotic liver disease via regulating purine metabolism and restoring the gut microbiota disorders","volume":"145","author":"Yiyou","year":"2025","journal-title":"Phytomed Int J Phytother Phytopharm"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/md22120573","article-title":"Lithium coupled with c6-carboxyl improves the efficacy of oligoguluronate in dss-induced ulcerative colitis in c57bl\/6j mice","volume":"22","author":"Li","year":"2024","journal-title":"Mar Drugs"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"3746","DOI":"10.3390\/nu17233746","article-title":"Partially hydrolyzed guar gum combined with a low-fat diet ameliorates type 2 diabetes mellitus via modulating gut microbiota and fecal metabolites","volume":"17","author":"Cao","year":"2025","journal-title":"Nutrients"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1186\/s12916-025-04260-2","article-title":"Faecalibacterium prausnitzii enhances intestinal IgA response by host-microbe derived inecalcitol in colitis","volume":"23","author":"Wenfei","year":"2025","journal-title":"BMC Med"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"5286","DOI":"10.1021\/acs.jafc.5c13455","article-title":"Polyphenol-rich coffee leaf extract alleviates high-fat diet-induced intestinal barrier dysfunction through modulation of barrier integrity, enterohepatic Axis, and gut microbiota","volume":"74","author":"Mei","year":"2026","journal-title":"J Agric Food Chem"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"155111","DOI":"10.1016\/j.phymed.2023.155111","article-title":"Xie zhuo tiao zhi formula modulates intestinal microbiota and liver purine metabolism to suppress hepatic steatosis and pyroptosis in nafld therapy","volume":"121","author":"Qiu","year":"2023","journal-title":"Phytomed Int J Phytother Phytopharm"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40168-021-01028-7","article-title":"Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through ppar\u03b3 signaling activation","volume":"9","author":"Li","year":"2021","journal-title":"Microbiome"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/s41586-022-05041-0","article-title":"Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine","volume":"609","author":"Niemann","year":"2022","journal-title":"Nature"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"83","DOI":"10.3390\/biomedicines10010083","article-title":"Intestinal barrier and permeability in health, obesity and nafld","volume":"10","author":"Portincasa","year":"2021","journal-title":"Biomedicine"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/j.cmet.2022.09.017","article-title":"Gut-liver axis: pathophysiological concepts and clinical implications","volume":"34","author":"Tilg","year":"2022","journal-title":"Cell Metab"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"21932","DOI":"10.1021\/acs.jafc.5c05570","article-title":"Hesperetin protects from palmitic-acid-induced lipotoxicity through the inhibition of glutaminolysis, mtorc1 signaling, and limited apoptosis","volume":"73","author":"Li","year":"2025","journal-title":"J Agric Food Chem"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"13039","DOI":"10.1021\/acs.jafc.3c09132","article-title":"Elevated pink1\/parkin-dependent mitophagy and boosted mitochondrial function mediate protection of hepg2 cells from excess palmitic acid by hesperetin","volume":"72","author":"Li","year":"2024","journal-title":"J Agric Food Chem"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1818086\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:21:31Z","timestamp":1777522891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1818086\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":45,"alternative-id":["10.3389\/fnut.2026.1818086"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1818086","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"article-number":"1818086"}}