{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:09:02Z","timestamp":1789016942675,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Social Science Fund of China","award":["22XTY001"],"award-info":[{"award-number":["22XTY001"]}]},{"name":"the First-Class Discipline Team of Kunming Medical University","award":["2024XKTDPY19"],"award-info":[{"award-number":["2024XKTDPY19"]}]},{"award":["2024XKTDPY19"],"award-info":[{"award-number":["2024XKTDPY19"]}],"id":[{"id":"https:\/\/ror.org\/038c3w259","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A high-fat diet (HFD) promotes lipid metabolic disorders, chronic low-grade inflammation and skeletal muscle dysfunction. Kukoamine B (KB), a Lycium-derived polyamine alkaloid with reported anti-inflammatory and antioxidant activities, may protect against HFD-associated muscle impairment. C57BL\/6J mice were fed an HFD and orally administered KB for 12 weeks. Muscle function was evaluated using inverted grid, forelimb grip strength and treadmill exhaustion tests. Histological, transcriptomic, ELISA, immunofluorescence and Western blot analyses were used to assess muscle injury and inflammatory signalling. KB reduced intramuscular lipid deposition, collagen accumulation and myofibre damage, improved muscle strength and exercise endurance, and partially restored AKT\/mTOR-associated protein metabolic signalling. Transcriptomic analysis showed that KB downregulated HFD-activated inflammatory responses, chemokine signalling, lipopolysaccharide responses and Toll-like receptor-related pathways. KB also reduced plasma and skeletal muscle LPS levels, inhibited TLR4\/MyD88\/NF-\u03baB signalling, and decreased TNF-\u03b1 and IL-1\u03b2 expression. TAK-242 mimicked the anti-inflammatory and muscle function-improving effects of KB, whereas their combination produced no statistically detectable additional effect under the conditions tested. These findings suggest that KB attenuates HFD-induced skeletal muscle dysfunction, potentially involving reduced LPS burden and suppression of TLR4\/NF-\u03baB-mediated metabolic inflammation.<\/jats:p>","DOI":"10.3390\/biom16091275","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:21:21Z","timestamp":1788452481000},"page":"1275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kukoamine B, a Lycium-Derived Polyamine Alkaloid, Attenuates High-Fat-Diet-Induced Skeletal Muscle Dysfunction with the Involvement of LPS\/TLR4\/NF-\u03baB-Mediated Metabolic Inflammation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2687-561X","authenticated-orcid":false,"given":"Shunling","family":"Yuan","sequence":"first","affiliation":[{"name":"Provincial University Key Laboratory of Sport and Health Science, School of Physical Education and Sport Sciences, Fujian Normal University, Fuzhou 350117, China"},{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3235-7669","authenticated-orcid":false,"given":"Lihan","family":"Lin","sequence":"additional","affiliation":[{"name":"Provincial University Key Laboratory of Sport and Health Science, School of Physical Education and Sport Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Liu","sequence":"additional","affiliation":[{"name":"Provincial University Key Laboratory of Sport and Health Science, School of Physical Education and Sport Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangwu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0140-6736(19)32497-3","article-title":"Dynamics of the double burden of malnutrition and the changing nutrition reality","volume":"395","author":"Popkin","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1753-4887.2011.00456.x","article-title":"Global nutrition transition and the pandemic of obesity in developing countries","volume":"70","author":"Popkin","year":"2012","journal-title":"Nutr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Duan, Y., Zeng, L., Zheng, C., Song, B., Li, F., Kong, X., and Xu, K. (2018). Inflammatory Links Between High Fat Diets and Diseases. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02649"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jiang, S., Liu, H., and Li, C. (2021). Dietary Regulation of Oxidative Stress in Chronic Metabolic Diseases. Foods, 10.","DOI":"10.3390\/foods10081854"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Da Silva Rodrigues, G., Lopes Da Silva, L.S., Crystine Da Silva Sobrinho, A., Benjamim, J., Abud, G.F., Ortiz, G.U., Cristini De Freitas, E., and Bueno Junior, C.R. (2025). Dietary polyphenols and sarcopenia: Epigenetic mechanisms and geroscience perspectives for muscle health in aging. Front. Aging, 6.","DOI":"10.3389\/fragi.2025.1696473"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/j.2040-4603.2020.tb00136.x","article-title":"Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake","volume":"10","author":"Merz","year":"2020","journal-title":"Compr. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Malesza, I.J., Malesza, M., Walkowiak, J., Mussin, N., Walkowiak, D., Aringazina, R., Bartkowiak-Wieczorek, J., and Madry, E. (2021). High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells, 10.","DOI":"10.3390\/cells10113164"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1136\/bjsports-2023-106807","article-title":"Resistance training prescription for muscle strength and hypertrophy in healthy adults: A systematic review and Bayesian network meta-analysis","volume":"57","author":"Currier","year":"2023","journal-title":"Br. J. Sports Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1152\/physrev.00022.2022","article-title":"Physiology of sedentary behavior","volume":"103","author":"Pinto","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hulett, N.A., Scalzo, R.L., and Reusch, J.E.B. (2022). Glucose Uptake by Skeletal Muscle within the Contexts of Type 2 Diabetes and Exercise: An Integrated Approach. Nutrients, 14.","DOI":"10.3390\/nu14030647"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1093\/jn\/nxz236","article-title":"Amyotrophy Induced by a High-Fat Diet Is Closely Related to Inflammation and Protein Degradation Determined by Quantitative Phosphoproteomic Analysis in Skeletal Muscle of C57BL\/6 J Mice","volume":"150","author":"Sun","year":"2020","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Poggiogalle, E., Rossignon, F., Carayon, A., Capel, F., Rigaudiere, J.P., De Saint Vincent, S., Le-Bacquer, O., Salles, J., Giraudet, C., and Patrac, V. (2021). Deleterious Effect of High-Fat Diet on Skeletal Muscle Performance Is Prevented by High-Protein Intake in Adult Rats but Not in Old Rats. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.749049"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9047821","DOI":"10.1155\/2016\/9047821","article-title":"High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis","volume":"2016","author":"Abrigo","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1136\/gutjnl-2011-301689","article-title":"Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice","volume":"61","author":"Caesar","year":"2012","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.2337\/db07-1403","article-title":"Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice","volume":"57","author":"Cani","year":"2008","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2010.12.008","article-title":"NF-kappaB, inflammation, and metabolic disease","volume":"13","author":"Baker","year":"2011","journal-title":"Cell Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xiao, J., Li, C., Pei, Y., Xu, S., Zhao, H., Xiang, W., and Wei, J. (2025). Lycium ruthenicum Polysaccharides Alleviate CCl4-Induced Acute Liver Injury Through Antioxidant and Anti-Inflammatory Effects. Nutrients, 17.","DOI":"10.3390\/nu17213359"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E988","DOI":"10.1152\/ajpendo.00307.2009","article-title":"Toll-like receptor 4 modulates skeletal muscle substrate metabolism","volume":"298","author":"Frisard","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1172\/JCI88880","article-title":"Skeletal muscle inflammation and insulin resistance in obesity","volume":"127","author":"Wu","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"166508","DOI":"10.1016\/j.bbadis.2022.166508","article-title":"The ameliorating effects of metformin on disarrangement ongoing in gastrocnemius muscle of sarcopenic and obese sarcopenic mice","volume":"1868","author":"Lyu","year":"2022","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, X., Lin, J., Chen, B., Xie, H., and Chen, D. (2018). Antioxidant and Cytoprotective Effects of Kukoamines A and B: Comparison and Positional Isomeric Effect. Molecules, 23.","DOI":"10.3390\/molecules23040973"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, Y.Y., Stewart, D.A., Ye, X.M., Yin, L.H., Pathmasiri, W.W., Mcritchie, S.L., Fennell, T.R., Cheung, H.Y., and Sumner, S.J. (2018). A Metabolomics Approach to Investigate Kukoamine B-A Potent Natural Product With Anti-diabetic Properties. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01575"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1111\/j.1476-5381.2010.01114.x","article-title":"Kukoamine B, a novel dual inhibitor of LPS and CpG DNA, is a potential candidate for sepsis treatment","volume":"162","author":"Liu","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3892\/etm.2015.2188","article-title":"A novel role of kukoamine B: Inhibition of the inflammatory response in the livers of lipopolysaccharide-induced septic mice via its unique property of combining with lipopolysaccharide","volume":"9","author":"Qin","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.2147\/DMSO.S247844","article-title":"Kukoamine B Ameliorate Insulin Resistance, Oxidative Stress, Inflammation and Other Metabolic Abnormalities in High-Fat\/High-Fructose-Fed Rats","volume":"13","author":"Zhao","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1124\/mol.110.068064","article-title":"TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules","volume":"79","author":"Matsunaga","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"118143","DOI":"10.1016\/j.biopha.2025.118143","article-title":"Inhibitory effects of kukoamine B on adipogenesis and lipid accumulation in vitro and obesity in vivo","volume":"187","author":"Oh","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1186\/s12974-018-1340-0","article-title":"TLR4 inhibitor TAK-242 attenuates the adverse neural effects of diet-induced obesity","volume":"15","author":"Moser","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2237","DOI":"10.21769\/BioProtoc.2237","article-title":"Evaluation of Muscle Performance in Mice by Treadmill Exhaustion Test and Whole-limb Grip Strength Assay","volume":"7","author":"Castro","year":"2017","journal-title":"Bio-Protocol"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Burch, N., Arnold, A.S., Item, F., Summermatter, S., Brochmann Santana Santos, G., Christe, M., Boutellier, U., Toigo, M., and Handschin, C. (2010). Electric pulse stimulation of cultured murine muscle cells reproduces gene expression changes of trained mouse muscle. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010970"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00421-018-4017-6","article-title":"Investigating a dose-response relationship between high-fat diet consumption and the contractile performance of isolated mouse soleus, EDL and diaphragm muscles","volume":"119","author":"Hurst","year":"2019","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1152\/japplphysiol.00530.2019","article-title":"A chronic high-fat diet exacerbates contractile dysfunction with impaired intracellular Ca2+ release capacity in the skeletal muscle of aged mice","volume":"128","author":"Eshima","year":"2020","journal-title":"J. Appl. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.1002\/fsn3.4157","article-title":"Gracilaria chorda attenuates obesity-related muscle wasting through activation of SIRT1\/PGC1alpha in skeletal muscle of mice","volume":"12","author":"Yoo","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13914","DOI":"10.1038\/s41598-017-14214-1","article-title":"Association of muscle lipidomic profile with high-fat diet-induced insulin resistance across five mouse strains","volume":"7","author":"Montgomery","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Roszczyc-Owsiejczuk, K., Imierska, M., Sokolowska, E., Kuzmicki, M., Pogodzinska, K., Blachnio-Zabielska, A., and Zabielski, P. (2024). shRNA-mediated down-regulation of Acsl1 reverses skeletal muscle insulin resistance in obese C57BL6\/J mice. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0307802"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.smhs.2021.09.003","article-title":"The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration","volume":"3","author":"Deaver","year":"2021","journal-title":"Sports Med. Health Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vainshtein, A., and Sandri, M. (2020). Signaling Pathways That Control Muscle Mass. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134759"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E469","DOI":"10.1152\/ajpendo.00204.2014","article-title":"Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx\/atrogin-1","volume":"307","author":"Bodine","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Wu, X., Wu, W., Tang, Y., Meng, X., Peng, M., Tang, C., Zheng, L., and Liu, W. (2024). The Potential Related Genes and Mechanisms Involved in Improving the Treadmill Exercise Ability of APP\/PS1 Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910244"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1113\/JP275444","article-title":"The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: Different routes to similar end-points","volume":"597","author":"Crossland","year":"2019","journal-title":"J. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, N., Shi, H., Guo, Q., Gan, Y., Zhang, Y., Jia, J., Zhang, L., and Zhou, Y. (2022). Aerobic Exercise Prevents Chronic Inflammation and Insulin Resistance in Skeletal Muscle of High-Fat Diet Mice. Nutrients, 14.","DOI":"10.3390\/nu14183730"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wang, S., Song, R., Wang, Z., Jing, Z., Wang, S., and Ma, J. (2018). S100A8\/A9 in Inflammation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01298"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.7150\/thno.67174","article-title":"Overexpression of S100A9 in obesity impairs macrophage differentiation via TLR4-NFkB-signaling worsening inflammation and wound healing","volume":"12","author":"Franz","year":"2022","journal-title":"Theranostics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/09637486.2017.1343286","article-title":"Impact of dietary fat on gut microbiota and low-grade systemic inflammation: Mechanisms and clinical implications on obesity","volume":"69","author":"Candido","year":"2018","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"747","DOI":"10.4014\/jmb.2312.12031","article-title":"Diet-Induced Gut Dysbiosis and Leaky Gut Syndrome","volume":"34","author":"Chae","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1186\/s12964-025-02299-5","article-title":"Common mechanisms of Gut microbe-based strategies for the treatment of intestine-related diseases: Based on multi-target interactions with the intestinal barrier","volume":"23","author":"Chen","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zamyatina, A., and Heine, H. (2020). Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4\/11 Mediated Inflammatory Pathways. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.585146"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wei, J., Wang, L., Wei, C., Guang, J., Wang, H., Zhou, J., Li, H., Ma, X., and Yue, B. (2024). Comparison of TLR4 Genotype and TLR4 Pathway-Related Cytokines in Different Strains of Mice in Response to Pertussis Toxin Challenge. Genes, 15.","DOI":"10.3390\/genes15111435"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"114429","DOI":"10.1016\/j.intimp.2025.114429","article-title":"TAK-242 attenuates NLRP3-ASC inflammasome-mediated neuroinflammation via TLR4\/NF-\u03baB pathway in rat experimental autoimmune neuritis","volume":"153","author":"Li","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s41598-020-57714-3","article-title":"TAK-242, a specific inhibitor of Toll-like receptor 4 signalling, prevents endotoxemia-induced skeletal muscle wasting in mice","volume":"10","author":"Ono","year":"2020","journal-title":"Sci. Rep."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:19:14Z","timestamp":1789013954000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":51,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091275"],"URL":"https:\/\/doi.org\/10.3390\/biom16091275","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}