{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:21:44Z","timestamp":1766553704628,"version":"3.48.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"crossref","award":["S3137537"],"award-info":[{"award-number":["S3137537"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Non-alcoholic steatohepatitis (NASH) lacks approved pharmacotherapies despite affecting approximately 25% of the global population. Agrimonia pilosa, a traditional herb with anti-inflammatory and antioxidant properties, remains unexplored for NASH treatment. Objective: This study investigated the hepatoprotective effects and mechanisms of Agrimonia pilosa extract (APE) in NASH models. Methods: HepG2 cells were treated with free fatty acids (0.125 mM) and APE (+12.5\u201350 \u03bcg\/mL). C57BL\/6J mice received a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 12 weeks with APE (25\u2013100 mg\/kg\/day), silymarin (100 mg\/kg\/day), or luteolin (20 mg\/kg\/day). Lipid accumulation, liver enzymes, histopathology, and molecular markers were assessed. Results: APE dose-dependently reduced lipid accumulation in FFA-treated cells, suppressed lipogenic factors (SREBF1, CEBPA, and PPARG), and upregulated fatty acid oxidation enzymes (CPT1A and PPARA) via AMPK\/SIRT1 activation. In NASH mice, APE (100 mg\/kg) significantly decreased serum ALT (160.0 \u00b1 49.1 vs. 311.2 \u00b1 66.7 U\/L) and AST (96.0 \u00b1 18.7 vs. 219.0 \u00b1 55.7 U\/L, p &lt; 0.001), reduced hepatic macrophage infiltration by 68%, and substantially attenuated inflammatory markers (Ccl2, Tnf, and IL6), oxidative stress indicators (NRF2, HMOX1, and CYBB), and fibrogenic markers (ACTA2, COL1A1, and TGFB1) by 83\u201385% (p &lt; 0.001). Collagen deposition decreased from 5.63 \u00b1 0.39% to 1.54 \u00b1 0.03% (p &lt; 0.001). Conclusions: APE exerts potent hepatoprotective effects through multi-targeted modulation of lipid metabolism, inflammation, oxidative stress, and fibrosis via AMPK\/SIRT1 pathway activation, supporting its potential as a natural therapeutic intervention for NASH.<\/jats:p>","DOI":"10.3390\/nu18010042","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:30:18Z","timestamp":1766489418000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Agrimonia pilosa Extract Alleviates CDAHFD-Induced Non-Alcoholic Steatohepatitis and Fibrosis in Mice"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-2481","authenticated-orcid":false,"given":"Min-Jeong","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Histology, College of Veterinary Medicine, Kyungpook National University, Daegu-si 41566, North Gyeongsang-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2037-7876","authenticated-orcid":false,"given":"Sun Jin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Histology, College of Veterinary Medicine, Kyungpook National University, Daegu-si 41566, North Gyeongsang-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9436-3571","authenticated-orcid":false,"given":"Myung-Gi","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Histology, College of Veterinary Medicine, Kyungpook National University, Daegu-si 41566, North Gyeongsang-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4120-0821","authenticated-orcid":false,"given":"Jun-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Histology, College of Veterinary Medicine, Kyungpook National University, Daegu-si 41566, North Gyeongsang-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9482-8332","authenticated-orcid":false,"given":"Jae Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"BTC Corporation, Gwacheon Creation Tower, 46, Gwacheon-daero 7-gil, Gwacheon-si 13840, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-9927","authenticated-orcid":false,"given":"Yoon Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"BTC Corporation, Gwacheon Creation Tower, 46, Gwacheon-daero 7-gil, Gwacheon-si 13840, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4512-1597","authenticated-orcid":false,"given":"Yongduk","family":"Kim","sequence":"additional","affiliation":[{"name":"BTC Corporation, Gwacheon Creation Tower, 46, Gwacheon-daero 7-gil, Gwacheon-si 13840, Gyeonggi-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4275-6060","authenticated-orcid":false,"given":"Sang-Joon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Histology, College of Veterinary Medicine, Kyungpook National University, Daegu-si 41566, North Gyeongsang-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/nrgastro.2013.171","article-title":"The global NAFLD epidemic","volume":"10","author":"Loomba","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.7861\/clinmedicine.18-3-245","article-title":"Non-alcoholic fatty liver disease","volume":"18","author":"Maurice","year":"2018","journal-title":"Clin. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/hep.23280","article-title":"Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications","volume":"51","author":"Fabbrini","year":"2010","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9330","DOI":"10.3748\/wjg.v20.i28.9330","article-title":"Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations","volume":"20","year":"2014","journal-title":"World J. Gastroenterol."},{"doi-asserted-by":"crossref","unstructured":"Kitade, H., Chen, G., Ni, Y., and Ota, T. (2017). Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments. Nutrients, 9.","key":"ref_6","DOI":"10.3390\/nu9040387"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s11892-015-0607-4","article-title":"Nonalcoholic fatty liver disease and type 2 diabetes: Common pathophysiologic mechanisms","volume":"15","author":"Saponaro","year":"2015","journal-title":"Curr. Diabetes Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"78","DOI":"10.14218\/JCTH.2014.00037","article-title":"Nonalcoholic Fatty Liver Disease: Dyslipidemia, Risk for Cardiovascular Complications, and Treatment Strategy","volume":"3","author":"Zhang","year":"2015","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jhep.2020.01.013","article-title":"NAFLD as a driver of chronic kidney disease","volume":"72","author":"Byrne","year":"2020","journal-title":"J. Hepatol."},{"doi-asserted-by":"crossref","unstructured":"Nassir, F. (2022). NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules, 12.","key":"ref_10","DOI":"10.3390\/biom12060824"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"305","DOI":"10.7326\/M15-1774","article-title":"Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus: A Randomized Trial","volume":"165","author":"Cusi","year":"2016","journal-title":"Ann. Intern. Med."},{"doi-asserted-by":"crossref","unstructured":"Perumpail, B.J., Li, A.A., John, N., Sallam, S., Shah, N.D., Kwong, W., Cholankeril, G., Kim, D., and Ahmed, A. (2018). The Role of Vitamin E in the Treatment of NAFLD. Diseases, 6.","key":"ref_12","DOI":"10.3390\/diseases6040086"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: Interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Younossi","year":"2019","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metab. Clin. Exp."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_16","first-page":"127","article-title":"The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis","volume":"18","author":"Ucar","year":"2013","journal-title":"Redox Rep. Commun. Free Radic. Res."},{"key":"ref_17","first-page":"3742208","article-title":"Agrimonia pilosa: A Phytochemical and Pharmacological Review","volume":"2022","author":"Jin","year":"2022","journal-title":"Evid. -Based Complement. Altern. Med. Ecam"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e09972","DOI":"10.1016\/j.heliyon.2022.e09972","article-title":"Agrimonia pilosa Ledeb.: A review of its traditional uses, botany, phytochemistry, pharmacology, and toxicology","volume":"8","author":"Wen","year":"2022","journal-title":"Heliyon"},{"key":"ref_19","first-page":"846","article-title":"Agrimonolide from Agrimonia pilosa suppresses inflammatory responses through down-regulation of COX-2\/iNOS and inactivation of NF-\u03baB in lipopolysaccharide-stimulated macrophages","volume":"23","author":"Chen","year":"2016","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"doi-asserted-by":"crossref","unstructured":"Feng, J.H., Kim, H.Y., Sim, S.M., Zuo, G.L., Jung, J.S., Hwang, S.H., Kwak, Y.G., Kim, M.J., Jo, J.H., and Kim, S.C. (2021). The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract. Plants, 10.","key":"ref_20","DOI":"10.3390\/plants10061234"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.3945\/jn.114.193128","article-title":"Luteolin Alleviates Alcoholic Liver Disease Induced by Chronic and Binge Ethanol Feeding in Mice","volume":"144","author":"Liu","year":"2014","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.2337\/db14-0631","article-title":"Luteolin Attenuates Hepatic Steatosis and Insulin Resistance Through the Interplay Between the Liver and Adipose Tissue in Mice with Diet-Induced Obesity","volume":"64","author":"Kwon","year":"2015","journal-title":"Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jep.2018.12.033","article-title":"Exploring the Multicomponent Synergy Mechanism of Banxia Xiexin Decoction on Irritable Bowel Syndrome by a Systems Pharmacology Strategy","volume":"233","author":"Li","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.3748\/wjg.v17.i18.2288","article-title":"Silybin and the Liver: From Basic Research to Clinical Practice","volume":"17","author":"Loguercio","year":"2011","journal-title":"World J. Gastroenterol."},{"doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-P\u00e9rez, C., Garc\u00eda-Villanova, B., Guerra-Hern\u00e1ndez, E., and Verardo, V. (2019). Grape Seeds Proanthocyanidins: An Overview of In Vivo Bioactivity in Animal Models. Nutrients, 11.","key":"ref_25","DOI":"10.3390\/nu11102435"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.3892\/etm.2021.10543","article-title":"Berberine Ameliorates Nonalcoholic Fatty Liver Disease by Decreasing the Liver Lipid Content via Reversing the Abnormal Expression of MTTP and LDLR","volume":"22","author":"Chen","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_27","first-page":"1523","article-title":"Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats","volume":"44","author":"Xia","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"G483","DOI":"10.1152\/ajpgi.00079.2013","article-title":"Diet-Induced Mouse Model of Fatty Liver Disease and Nonalcoholic Steatohepatitis Reflecting Clinical Disease Progression and Methods of Assessment","volume":"305","author":"Clapper","year":"2013","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_29","first-page":"18","article-title":"Dietary Choline Deficiency Causes Nonalcoholic Steatohepatitis with Fibrosis in Mice","volume":"44","author":"Ito","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/j.1745-7254.2008.00807.x","article-title":"Resveratrol Improves Non-Alcoholic Fatty Liver Disease by Activating AMP-Activated Protein Kinase","volume":"29","author":"Shang","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11596-019-1997-3","article-title":"Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of the 33. SIRT3\/AMPK\/ACC Pathway","volume":"39","author":"Zhang","year":"2019","journal-title":"Curr. Med. Sci."},{"key":"ref_32","first-page":"155285","article-title":"Formononetin Promotes Fatty Acid \u03b2-Oxidation to Treat Non-Alcoholic Steatohepatitis Through SIRT1\/PGC-1\u03b1\/PPAR\u03b1 Pathway","volume":"119","author":"Liao","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.bbrc.2008.06.077","article-title":"The Anti-Obesity Effect of Quercetin Is Mediated by the AMPK Signaling Pathway","volume":"373","author":"Hwang","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","first-page":"1143","article-title":"Silymarin Attenuated Hepatic Steatosis Through Regulation of Lipid Metabolism and Oxidative Stress in a Mouse Model of Non-Alcoholic Fatty Liver Disease","volume":"23","author":"Ni","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.3945\/jn.112.165274","article-title":"Quercetin Treatment Ameliorates Inflammation and Fibrosis in MCD Diet-Induced Nonalcoholic Steatohepatitis in Mice","volume":"142","author":"Marcolin","year":"2012","journal-title":"J. Nutr."},{"key":"ref_36","first-page":"34","article-title":"Double-Blind Randomized Placebo-Controlled Clinical Trial of Omega-3 Fatty Acids for the Treatment of Nonalcoholic Steatohepatitis","volume":"63","author":"Dasarathy","year":"2015","journal-title":"J. Hepatol."},{"doi-asserted-by":"crossref","unstructured":"Fan, M., Choi, Y.J., Tang, Y., Bae, S.M., Yang, H.P., and Kim, E.-K. (2019). Efficacy and Mechanism of Polymerized Anthocyanin from Grape-Skin Extract on High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease. Nutrients, 11.","key":"ref_37","DOI":"10.3390\/nu11112586"},{"key":"ref_38","first-page":"414","article-title":"Ginsenoside Rg1 Attenuates Nonalcoholic Steatohepatitis by Inhibiting Hepatic Macrophage Infiltration and Inflammatory Cytokine Production","volume":"41","author":"Kim","year":"2017","journal-title":"J. Ginseng Res."},{"key":"ref_39","first-page":"354","article-title":"Celastrol Attenuates Hepatic Inflammation by Suppressing COX-2 and NF-\u03baB Signaling in Experimental Nonalcoholic Steatohepatitis","volume":"67","author":"Zhang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biocel.2008.06.010","article-title":"Potential Therapeutic Effects of Curcumin, the Anti-Inflammatory Agent, Against Cancer and Inflammatory Diseases","volume":"41","author":"Aggarwal","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","first-page":"104959","article-title":"Natural Products Targeting Inflammatory Signaling Pathways: NF-\u03baB, MAPK, and JAK-STAT","volume":"159","author":"Zhou","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.freeradbiomed.2009.11.007","article-title":"Loss of Nrf2 Markedly Exacerbates Nonalcoholic Steatohepatitis","volume":"48","author":"Chowdhry","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_43","first-page":"93","article-title":"Grape Seed Proanthocyanidin Extract Reduces Oxidative Stress and Improves Liver Pathology in Experimental Nonalcoholic Steatohepatitis","volume":"75","author":"Bagchi","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_44","first-page":"1180","article-title":"Astaxanthin Prevents and Reverses Diet-Induced Insulin Resistance and Hepatic Steatosis by Attenuating Oxidative Stress and Inflammation","volume":"26","author":"Ni","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.jhep.2010.11.005","article-title":"Endoplasmic Reticulum Stress in Liver Disease","volume":"54","author":"Malhi","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_46","first-page":"1915","article-title":"Tauroursodeoxycholic Acid Reduces ER Stress and Hepatocyte Apoptosis in Experimental Nonalcoholic Steatohepatitis","volume":"52","author":"Yang","year":"2010","journal-title":"Hepatology"},{"key":"ref_47","first-page":"817","article-title":"4-Phenylbutyric Acid Attenuates ER Stress-Mediated Hepatic Injury and Apoptosis in Experimental Nonalcoholic Steatohepatitis","volume":"60","author":"Zhang","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110550","DOI":"10.1016\/j.intimp.2023.110550","article-title":"Salvianolic Acid B Inhibits Hepatic Stellate Cell Activation and Liver Fibrosis by Targeting PDGFR\u03b2","volume":"122","author":"Liu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.intimp.2018.04.018","article-title":"Glycyrrhizin Ameliorates Liver Fibrosis by Suppressing TGF-\u03b21\/Smad Signaling and Hepatic Stellate Cell Activation","volume":"55","author":"Li","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_50","first-page":"1143","article-title":"Silymarin Attenuated Hepatic Steatosis and Fibrosis in Diet-Induced NAFLD by Modulating Lipid Metabolism and Inflammatory Responses","volume":"23","author":"Ni","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol. Rev."},{"doi-asserted-by":"crossref","unstructured":"Dewidar, B., Meyer, C., Dooley, S., and Meindl-Beinker, N. (2019). TGF-\u03b2 in Hepatic Stellate Cell Activation and Liver Fibrogenesis\u2014Updated 2019. Cells, 8.","key":"ref_52","DOI":"10.3390\/cells8111419"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/1\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T05:19:58Z","timestamp":1766553598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/1\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["nu18010042"],"URL":"https:\/\/doi.org\/10.3390\/nu18010042","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2025,12,22]]}}}