{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:16:01Z","timestamp":1788455761782,"version":"build-2803163510"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/na","name":"Postgraduate Innovation Research Project of Heilongjiang Bayi Agricultural University","doi-asserted-by":"publisher","award":["YJSCX2025-KJQN46"],"award-info":[{"award-number":["YJSCX2025-KJQN46"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Postgraduate Innovation Research Project of Heilongjiang Bayi Agricultural University","doi-asserted-by":"publisher","award":["YJSCX2025-Z07"],"award-info":[{"award-number":["YJSCX2025-Z07"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High concentrations of free fatty acids (FFA) during early lactation cause metabolic stress and oxidative damage in bovine mammary epithelial cells. This study explored the protective mechanism of lycopene (LYC), a natural antioxidant, against FFA-induced injury in the MAC-T cells. We found that 1.2 mM FFA induced oxidative stress, reactive oxygen species (ROS) accumulation, apoptosis, and impaired autophagy. LYC dose-dependently alleviated FFA-induced oxidative damage, restored autophagy flux, upregulated ATG5 autophagy-related 5 (ATG5), LC3-II, and transcription factor EB (TFEB), and downregulated p62, ROS, and apoptosis. Inhibition of autophagy abolished the protective effects of the LYC. Overexpression of TFEB mitigated FFA-induced dysfunction, while TFEB knockdown aggravated cell injury. These results demonstrate that LYC protects mammary epithelial cells from FFA-induced oxidative damage via regulating TFEB-mediated autophagy, suggesting its potential use in alleviating metabolic stress in periparturient dairy cows.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05011","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T04:52:15Z","timestamp":1787460735000},"page":"27111-27122","source":"Crossref","is-referenced-by-count":0,"title":["Lycopene Alleviates\nFatty Acid-Induced Oxidative Stress\nand Apoptosis in Bovine Mammary Epithelial Cells via the TFEB-Mediated\nAutophagy Signaling Pathway"],"prefix":"10.1021","volume":"74","author":[{"given":"Xinyuan","family":"Sun","sequence":"first","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongdou","family":"Jia","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Wu","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Yan","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yu","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Ding","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushi","family":"Xu","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Loor","sequence":"additional","affiliation":[{"name":"University of Illinois , , , ,","place":["Urbana, Illinois, United States, 61801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4633-2138","authenticated-orcid":true,"given":"Chuang","family":"Xu","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5976-8960","authenticated-orcid":true,"given":"Xudong","family":"Sun","sequence":"additional","affiliation":[{"name":"Heilongjiang Bayi Agricultural University , , No. 5 Xinfeng Road , , ,","place":["Daqing, Heilongjiang Province, China, 163319"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026090311494487700_cit1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097742","article-title":"Puerarin Alleviates H(2)O(2)-Induced Oxidative Stress and Blood-Milk\nBarrier Impairment in Dairy Cows","volume":"24","author":"Lyu","year":"2023","journal-title":"Int. J. Mol.\nSci."},{"key":"2026090311494487700_cit2","doi-asserted-by":"publisher","DOI":"10.3390\/ani15243644","article-title":"Current Understanding\nof Bovine Ketosis: From Molecular Basis to Farm-Level Management","volume":"15","author":"Zhang","year":"2025","journal-title":"Animals"},{"key":"2026090311494487700_cit3","doi-asserted-by":"publisher","first-page":"3269","DOI":"10.3168\/jds.2023-24000","article-title":"Evaluation\nof hepatic AMPK, mTORC1, and autophagy-lysosomal pathway in cows with\nmild or moderate fatty liver","volume":"107","author":"Du","year":"2024","journal-title":"J. Dairy Sci."},{"key":"2026090311494487700_cit4","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3168\/jdsc.2024-0623","article-title":"Oxylipin\nDynamics in Dairy Cows During Clinical Ketosis and after Treatment\nwith Niacin and Flunixin Meglumine","volume":"6","author":"Chirivi","year":"2025","journal-title":"JDS Commun."},{"key":"2026090311494487700_cit5","doi-asserted-by":"publisher","first-page":"5775","DOI":"10.3168\/jds.2022-22907","article-title":"A High-Concentrate\nDiet Induces Mitochondrial Dysfunction by Activating the Mapk Signaling\nPathway in the Mammary Gland of Dairy Cows","volume":"106","author":"Meng","year":"2023","journal-title":"J. Dairy Sci."},{"key":"2026090311494487700_cit6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2026.107037","article-title":"Acetoacetyl-Coa Synthetase Modulates Lipid Partitioning\nand Cholesterol-Related Gene Expression in Nefa-Challenged Neonatal\nBovine Hepatocytes","volume":"262","author":"Tian","year":"2026","journal-title":"J. Steroid Biochem. Mol.\nBiol."},{"key":"2026090311494487700_cit7","doi-asserted-by":"publisher","first-page":"28126","DOI":"10.1021\/acs.jafc.5c09896","article-title":"Nrf2 Promotes\nBhba-Induced Pyroptosis in Bovine Endometrial\nEpithelial Cells by Modulating Autophagy Mediated through Oxidative\nStress","volume":"73","author":"Mu","year":"2025","journal-title":"J. Agric. 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Heart J."},{"key":"2026090311494487700_cit19","doi-asserted-by":"publisher","DOI":"10.3390\/antiox14121513","article-title":"Lycopene Protects\nDeoxynivalenol-Induced Intestinal Barrier Dysfunction and Nlrp3 Inflammasome\nActivation by Targeting the Erk Pathway","volume":"14","author":"Cai","year":"2025","journal-title":"Antioxidants"},{"key":"2026090311494487700_cit20","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2713511","article-title":"Lycopene:\nFood Sources, Biological\nActivities, and Human Health Benefits","volume":"2021","author":"Khan","year":"2021","journal-title":"Oxid.\nMed. Cell. Longevity"},{"key":"2026090311494487700_cit21","doi-asserted-by":"publisher","first-page":"4032","DOI":"10.1002\/ptr.7127","article-title":"Activation\nof Autophagy Contributes to the Protective Effects of Lycopene against\nOxidative Stress-Induced Apoptosis in Rat Chondrocytes","volume":"35","author":"Wu","year":"2021","journal-title":"Phytother. Res."},{"key":"2026090311494487700_cit22","doi-asserted-by":"publisher","first-page":"6276","DOI":"10.1039\/C9FO01922G","article-title":"Lycopene\nalleviates H2O2-Induced Oxidative Stress, Inflammation and Apoptosis\nin Bovine Mammary Epithelial Cells Via the Nfe2l2 Signaling Pathway","volume":"10","author":"Sun","year":"2019","journal-title":"Food Funct."},{"key":"2026090311494487700_cit23","doi-asserted-by":"publisher","first-page":"7278","DOI":"10.1021\/acs.jafc.2c07494","article-title":"Mitochondrial Calcium\nUniporter Regulator 1 (Mcur1) Relieves Mitochondrial Damage Induced\nby Lipopolysaccharide by Mediating Mitochondrial Ca(2+) Homeostasis\nin Bovine Mammary Epithelial Cells","volume":"71","author":"Sun","year":"2023","journal-title":"J. Agric.\nFood Chem."},{"key":"2026090311494487700_cit24","doi-asserted-by":"publisher","first-page":"6909","DOI":"10.3168\/jds.2020-19964","article-title":"Enhanced Mitochondrial Dysfunction and Oxidative Stress\nin the Mammary Gland of Cows with Clinical Ketosis","volume":"104","author":"Song","year":"2021","journal-title":"J. Dairy Sci."},{"key":"2026090311494487700_cit25","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.14202\/vetworld.2021.1492-1503","article-title":"Ketone Bodies\n- Causes and Effects of Their Increased Presence in Cows\u2019 Body\nFluids: A Review","volume":"14","author":"Gulin\u0301ski","year":"2021","journal-title":"Vet. 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Neuropharmacol."},{"key":"2026090311494487700_cit28","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115253","article-title":"Paeoniflorin\nAlleviates Angii-Induced\nCardiac Hypertrophy in H9c2 Cells by Regulating Oxidative Stress and\nNrf2 Signaling Pathway","volume":"165","author":"Ren","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"2026090311494487700_cit29","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1093\/humrep\/dez161","article-title":"Mitochondria-Targeted\nTherapy Rescues\nDevelopment and Quality of Embryos Derived from Oocytes Matured under\nOxidative Stress Conditions: A Bovine in Vitro Model","volume":"34","author":"Marei","year":"2019","journal-title":"Hum. 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Food Chem."},{"key":"2026090311494487700_cit31","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.123452","article-title":"Lycopene Inhibits\nDoxorubicin-Induced Heart Failure by Inhibiting Ferroptosis through\nthe Nrf2 Signaling Pathway","volume":"365","author":"Huang","year":"2025","journal-title":"Life Sci."},{"key":"2026090311494487700_cit32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25052472","article-title":"Endotoxin Inflammatory\nAction on Cells by Dysregulated-Immunological-Barrier-Linked\nRos-Apoptosis Mechanisms in Gut-Liver Axis","volume":"25","author":"Dumitru","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"2026090311494487700_cit33","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102494","article-title":"Lycopene Attenuates the Inflammation\nand Apoptosis in Aristolochic Acid Nephropathy by Targeting the Nrf2\nAntioxidant System","volume":"57","author":"Wang","year":"2022","journal-title":"Redox Biol."},{"key":"2026090311494487700_cit34","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2025.05.424","article-title":"Hinokitiol\nProtects Rpe Cells from Oxidative and Autophagic\nDysfunction: Implications for Amd Therapy","volume":"237","author":"Huang","year":"2025","journal-title":"Free\nRadicals Biol. Med."},{"key":"2026090311494487700_cit35","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"Mtor: A Pharmacologic\nTarget for Autophagy Regulation","volume":"125","author":"Kim","year":"2015","journal-title":"J. Clin. 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Dairy Sci."},{"key":"2026090311494487700_cit37","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine Inhibits\nAutophagic Flux by Decreasing\nAutophagosome-Lysosome Fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"2026090311494487700_cit38","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1080\/15548627.2015.1068489","article-title":"Pharmacological\nInhibition of Lysosomes Activates the Mtorc1 Signaling Pathway in\nChondrocytes in an Autophagy-Independent Manner","volume":"11","author":"Newton","year":"2015","journal-title":"Autophagy"},{"key":"2026090311494487700_cit39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2213670120","article-title":"A Small-Molecule Drug Inhibits Autophagy\nGene Expression through the Central Regulator Tfeb","volume":"120","author":"Lin","year":"2023","journal-title":"Proc. Natl. Acad. Sci. 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Toxicol."},{"key":"2026090311494487700_cit44","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1042\/BCJ20190596","article-title":"A Lysosome\nIndependent Role for Tfeb in Activating\nDNA Repair and Inhibiting Apoptosis in Breast Cancer Cells","volume":"477","author":"Slade","year":"2020","journal-title":"Biochem. J."},{"key":"2026090311494487700_cit45","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1016\/j.jia.2024.12.023","article-title":"Free Fatty Acids Induce Apoptosis in Mammary Epithelial Cells from\nKetotic Dairy Cows Via Endoplasmic Reticulum Stress","volume":"25","author":"Chang","year":"2026","journal-title":"J. Integr. Agric."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c05011","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/34\/27111\/67018757\/acs.jafc.6c05011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/34\/27111\/67018757\/acs.jafc.6c05011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:23:51Z","timestamp":1788452631000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/34\/27111\/5288838\/Lycopene-Alleviates-Fatty-Acid-Induced-Oxidative"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":45,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,21]]},"published-print":{"date-parts":[[2026,9,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c05011","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}