{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:20:22Z","timestamp":1776795622084,"version":"3.51.2"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["2021YFD1200403"],"award-info":[{"award-number":["2021YFD1200403"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guizhou Province Mutton Sheep Genetic Improvement and Innovative Utilization Science and Technology Innovation Talent Team Project","award":["Qian Kehe Platform Talent-CXTD[2023]025"],"award-info":[{"award-number":["Qian Kehe Platform Talent-CXTD[2023]025"]}]},{"name":"Guizhou Province High-level Innovative \u201cHundred\u201d Level Talent Project","award":["GCC[2022]021-1"],"award-info":[{"award-number":["GCC[2022]021-1"]}]},{"name":"Key Core Technology Research and Development Project of Mountain Agriculture in Guizhou Province","award":["GZNY GJHX-2023006"],"award-info":[{"award-number":["GZNY GJHX-2023006"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The Maguan hornless goat is a valuable indigenous goat breed in Yunnan Province, China. As a rare and endangered genetic resource, its population protection and breeding are challenged by numerous challenges, particularly during artificial insemination procedures. During chilled storage, sperm generate excessive levels of reactive oxygen species (ROS), which disrupt the integrity of the sperm plasma membrane, damage the celluar structures, and lead to a decline in semen quality. This study investigated the effects of different concentrations (0, 5, 7, 9 mM) of N-acetylcysteine (NAC) on the chilled storage of semen collected from Maguan hornless goats. Semen was collected from four healthy rams with normal reproductive performance. The different concentrations of NAC were added to the semen diluent, and the samples were diluted 10-fold prior to storage at 4 \u00b0C for up to 72 h. After defining storage intervals, sperm kinetics, antioxidant gene transcription, and oxidative stress\u2013related enzymatic activity were analyzed. Results showed that sperm samples extended in diluent supplemented with 7 mM NAC and subjected to 72 h of chilled storage at 4 \u2103 exhibited improved antioxidant levels. This approach also reduced sperm apoptosis, enhanced membrane integrity and mitochondrial membrane potential, and suppressed the expression of pro-apoptotic genes (\n                    <jats:italic>BAX, Caspase 3<\/jats:italic>\n                    ) while upregulating that of antioxidant genes (\n                    <jats:italic>GPX4, GPX1<\/jats:italic>\n                    ). The results suggest NAC supports semen chilled storage in endangered species by enhancing antioxidant capacity and inhibiting cell death-related pathways. This study provides insights into the application of reproductive biotechnology in small ruminants.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0347756","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:28:14Z","timestamp":1776792494000},"page":"e0347756","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of N-acetyl-L-cysteine on sperm quality during chilled storage of Maguan hornless goat semen"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1459-0303","authenticated-orcid":true,"given":"Haoran","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maosheng","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghong","family":"Ju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingji","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6495-6851","authenticated-orcid":true,"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"issue":"2","key":"pone.0347756.ref001","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11250-024-03930-2","article-title":"Effects of different extenders, storage temperatures, and antioxidant supplementation on chilled semen quality: a review","volume":"56","author":"N Hameed","year":"2024","journal-title":"Trop Anim Health Prod"},{"issue":"7","key":"pone.0347756.ref002","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.3390\/antiox10071096","article-title":"Role of Antioxidants in Cooled Liquid Storage of Mammal Spermatozoa","volume":"10","author":"MA Silvestre","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"pone.0347756.ref003","doi-asserted-by":"crossref","first-page":"106822","DOI":"10.1016\/j.anireprosci.2021.106822","article-title":"Cooled storage of semen from livestock animals (part I): boar, bull, and stallion","volume":"246","author":"M Wiebke","year":"2022","journal-title":"Anim Reprod Sci"},{"key":"pone.0347756.ref004","doi-asserted-by":"crossref","first-page":"764750","DOI":"10.3389\/fvets.2021.764750","article-title":"Evaluation of Chilled Dog Semen Extended With Sperm Activator","volume":"8","author":"M Mart\u00ednez-Barbitta","year":"2022","journal-title":"Front Vet Sci"},{"issue":"5","key":"pone.0347756.ref005","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s40263-022-00907-3","article-title":"The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders","volume":"36","author":"RCJ Bradlow","year":"2022","journal-title":"CNS Drugs"},{"issue":"8","key":"pone.0347756.ref006","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1007\/s11095-016-1941-1","article-title":"N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders","volume":"33","author":"Y Ma","year":"2016","journal-title":"Pharm Res"},{"key":"pone.0347756.ref007","doi-asserted-by":"crossref","first-page":"106801","DOI":"10.1016\/j.anireprosci.2021.106801","article-title":"N-acetyl-cysteine and the control of oxidative stress during in vitro ovarian follicle growth, oocyte maturation, embryo development and cryopreservation","volume":"231","author":"LG Barrozo","year":"2021","journal-title":"Anim Reprod Sci"},{"issue":"12","key":"pone.0347756.ref008","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0226696","article-title":"N-acetyl cysteine attenuates oxidative stress and glutathione-dependent redox imbalance caused by high glucose\/high palmitic acid treatment in pancreatic Rin-5F cells","volume":"14","author":"A Alnahdi","year":"2019","journal-title":"PLoS One"},{"key":"pone.0347756.ref009","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.theriogenology.2024.12.009","article-title":"Effects of different concentrations of N-acetylcysteine on the sperm quality, antioxidant enzyme activity, and antioxidant gene expression of cryopreserved goat semen","volume":"234","author":"X Wang","year":"2025","journal-title":"Theriogenology"},{"issue":"2","key":"pone.0347756.ref010","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.repbio.2015.03.001","article-title":"Effects of N-acetyl-L-cysteine and catalase on the viability and motility of chicken sperm during liquid storage","volume":"15","author":"A Partyka","year":"2015","journal-title":"Reprod Biol"},{"issue":"6","key":"pone.0347756.ref011","first-page":"493","article-title":"Role of sperm apoptosis and oxidative stress in male infertility: A narrative review","volume":"19","author":"A Asadi","year":"2021","journal-title":"Int J Reprod Biomed"},{"key":"pone.0347756.ref012","doi-asserted-by":"crossref","first-page":"1554771","DOI":"10.3389\/fvets.2025.1554771","article-title":"Extender development for optimal cryopreservation of buck sperm to increase reproductive efficiency of goats","volume":"12","author":"M Bodu","year":"2025","journal-title":"Front Vet Sci"},{"issue":"11","key":"pone.0347756.ref013","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.14202\/vetworld.2019.1784-1789","article-title":"Addition of L-arginine in skim milk extender maintains goat spermatozoa quality in chilled temperature for five days","volume":"12","author":"S Susilowati","year":"2019","journal-title":"Vet World"},{"key":"pone.0347756.ref014","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cryobiol.2022.09.008","article-title":"Effects of water-soluble curcuminoid-rich extract in a solid dispersion form (CRE-SD) on the sperm characteristics, longevity and casein kinase II catalytic subunit alpha protein stability in chilled goat semen","volume":"109","author":"N Kupthammasan","year":"2022","journal-title":"Cryobiology"},{"issue":"3","key":"pone.0347756.ref015","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3390\/ani12030352","article-title":"Practical Method for Freezing Buck Semen","volume":"12","author":"JM Morrell","year":"2022","journal-title":"Animals (Basel)"},{"key":"pone.0347756.ref016","article-title":"Dietary resveratrol improves semen quality by promoting mitochondrial function-related genes expression in aging boars","volume":"103","author":"J Lv","year":"2025","journal-title":"J Anim Sci"},{"issue":"1","key":"pone.0347756.ref017","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1186\/s12967-022-03811-y","article-title":"Effects of Malate Ringer\u2019s solution on myocardial injury in sepsis and enforcement effects of TPP@PAMAM-MR","volume":"20","author":"L Tan","year":"2022","journal-title":"J Transl Med"},{"issue":"9","key":"pone.0347756.ref018","doi-asserted-by":"crossref","DOI":"10.1002\/cpz1.531","article-title":"Evaluation of Human Spermatozoa Mitochondrial Membrane Potential Using the JC-1 Dye","volume":"2","author":"DF Carrageta","year":"2022","journal-title":"Curr Protoc"},{"issue":"22","key":"pone.0347756.ref019","article-title":"Correction Notice: Microscopy and Plate Reader-based Methods for Monitoring the Interaction of Platelets and Tumor Cells in vitro","volume":"13","author":"V Toragall","year":"2023","journal-title":"Bio Protoc"},{"issue":"9","key":"pone.0347756.ref020","doi-asserted-by":"crossref","DOI":"10.1111\/rda.70118","article-title":"Beneficial Effects of the Mitochondria-Targeted Antioxidant MitoQ on Bull Semen Post Cryopreservation Quality Characteristics","volume":"60","author":"SA Nazari","year":"2025","journal-title":"Reprod Domest Anim"},{"issue":"3","key":"pone.0347756.ref021","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3390\/microorganisms9030520","article-title":"Coordinated Expression of HPV-6 Genes with Predominant E4 and E5 Expression in Laryngeal Papilloma","volume":"9","author":"T Ikegami","year":"2021","journal-title":"Microorganisms"},{"key":"pone.0347756.ref022","doi-asserted-by":"crossref","first-page":"107088","DOI":"10.1016\/j.anireprosci.2022.107088","article-title":"Liquid storage of stallion spermatozoa - Past, present and future","volume":"247","author":"J Clulow","year":"2022","journal-title":"Anim Reprod Sci"},{"issue":"7","key":"pone.0347756.ref023","first-page":"658","article-title":"Sperm membrane stability: in-depth analysis from structural basis to functional regulation","volume":"12","author":"SH Xue","year":"2025","journal-title":"Vet Sci"},{"issue":"6","key":"pone.0347756.ref024","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1111\/andr.12883","article-title":"Sperm morphology: What implications on the assisted reproductive outcomes?","volume":"8","author":"G Cito","year":"2020","journal-title":"Andrology"},{"key":"pone.0347756.ref025","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.theriogenology.2023.12.030","article-title":"Protective effects of l-cysteine and N-acetyl-l-cysteine on boar sperm quality during hypothermic liquid storage with bovine serum albumin as a protectant","volume":"216","author":"D Yang","year":"2024","journal-title":"Theriogenology"},{"issue":"6","key":"pone.0347756.ref026","doi-asserted-by":"crossref","first-page":"101093","DOI":"10.1016\/j.psj.2021.101093","article-title":"Research Note: Evaluation of two methods for adding cryoprotectant to semen and effects of bovine serum albumin on quality characteristics of cryopreserved rooster spermatozoa","volume":"100","author":"A Behnamifar","year":"2021","journal-title":"Poult Sci"},{"key":"pone.0347756.ref027","doi-asserted-by":"crossref","first-page":"1520835","DOI":"10.3389\/fendo.2025.1520835","article-title":"Mechanisms of oxidative stress-induced sperm dysfunction","volume":"16","author":"Y Wang","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"pone.0347756.ref028","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1186\/s12967-023-04361-7","article-title":"Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease","volume":"21","author":"Q Yan","year":"2023","journal-title":"J Transl Med"},{"issue":"11","key":"pone.0347756.ref029","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.3390\/antiox12111953","article-title":"The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates","volume":"12","author":"SK Georgiou-Siafis","year":"2023","journal-title":"Antioxidants (Basel)"},{"issue":"1","key":"pone.0347756.ref030","article-title":"Non-canonical Glutamate-Cysteine Ligase Activity Protects against Ferroptosis","volume":"33","author":"YP Kang","year":"2021","journal-title":"Cell Metab"},{"issue":"13","key":"pone.0347756.ref031","doi-asserted-by":"crossref","first-page":"10978","DOI":"10.3390\/ijms241310978","article-title":"Total Antioxidant Capacity: Biochemical Aspects and Clinical Significance","volume":"24","author":"A Silvestrini","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"10","key":"pone.0347756.ref032","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1093\/humrep\/deaa159","article-title":"DNA fragmentation of sperm: a radical examination of the contribution of oxidative stress and age in 16\u2009945 semen samples","volume":"35","author":"DA Vaughan","year":"2020","journal-title":"Hum Reprod"},{"key":"pone.0347756.ref033","doi-asserted-by":"crossref","first-page":"107384","DOI":"10.1016\/j.anireprosci.2023.107384","article-title":"L-cysteine improves boar semen motility at 5 \u00baC but does not affect the oxidative status","volume":"260","author":"G Dos Santos","year":"2024","journal-title":"Anim Reprod Sci"},{"key":"pone.0347756.ref034","doi-asserted-by":"crossref","first-page":"1150951","DOI":"10.3389\/fendo.2023.1150951","article-title":"High sperm DNA fragmentation: do we have robust evidence to support antioxidants and testicular sperm extraction to improve fertility outcomes? a narrative review","volume":"14","author":"M Romano","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0347756.ref035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2017.07.010","article-title":"Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center","volume":"112","author":"G Cozza","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"pone.0347756.ref036","doi-asserted-by":"crossref","first-page":"7211485","DOI":"10.1155\/2022\/7211485","article-title":"Singlet Oxygen, Photodynamic Therapy, and Mechanisms of Cancer Cell Death","volume":"2022","author":"PS Maharjan","year":"2022","journal-title":"J Oncol"},{"issue":"4","key":"pone.0347756.ref037","first-page":"685","article-title":"Comparing the effects of Cyperus esculentus hydroethanolic extract and Euterpe oleracea on reproductive efficacy against cadmium-induced testicular toxicity in male rats","volume":"10","author":"SS Khafaji","year":"2023","journal-title":"J Adv Vet Anim Res"},{"issue":"6","key":"pone.0347756.ref038","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/rda.13023","article-title":"Antioxidants protect proteins\u2019 anchorage to the bilayer by improving plasma membrane integrity of ram spermatozoa during liquid preservation in a soya lecithin-based diluent","volume":"52","author":"RK Paul","year":"2017","journal-title":"Reprod Domest Anim"},{"issue":"9","key":"pone.0347756.ref039","doi-asserted-by":"crossref","first-page":"102014","DOI":"10.1016\/j.psj.2022.102014","article-title":"Sperm flow cytometric parameters, antioxidant status, and testicular histomorphology in roosters fed diets supplemented with camphor","volume":"101","author":"H Raei","year":"2022","journal-title":"Poult Sci"},{"issue":"11","key":"pone.0347756.ref040","first-page":"1135","article-title":"Ability of the ISAS3Fun Method to Detect Sperm Acrosome Integrity and Its Potential to Discriminate between High and Low Field Fertility Bulls","volume":"10","author":"JL Y\u00e1niz","year":"2021","journal-title":"Biology (Basel)"},{"key":"pone.0347756.ref041","doi-asserted-by":"crossref","first-page":"1345016","DOI":"10.3389\/fvets.2023.1345016","article-title":"Alpha-lipoic acid improves the quality of ram spermatozoa stored at 4\u00b0C by reducing oxidative stress and increasing mitochondrial potential","volume":"10","author":"X Sun","year":"2024","journal-title":"Front Vet Sci"},{"issue":"6","key":"pone.0347756.ref042","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1007\/s00204-023-03476-6","article-title":"ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis","volume":"97","author":"B Wang","year":"2023","journal-title":"Arch Toxicol"},{"key":"pone.0347756.ref043","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.theriogenology.2022.12.041","article-title":"Schisandrin B protects boar spermatozoa against oxidative damage and increases their fertilization ability during in vitro storage","volume":"198","author":"C Li","year":"2023","journal-title":"Theriogenology"},{"issue":"10","key":"pone.0347756.ref044","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/s41580-023-00629-4","article-title":"Mechanisms of BCL-2 family proteins in mitochondrial apoptosis","volume":"24","author":"PE Czabotar","year":"2023","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"8","key":"pone.0347756.ref045","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.3390\/cells9081843","article-title":"Brain-specific serine-47 modification of cytochrome c regulates cytochrome c oxidase activity attenuating ROS production and cell death: implications for ischemia\/reperfusion injury and Akt signaling","volume":"9","author":"HA Kalpage","year":"2020","journal-title":"Cells-Basel"},{"issue":"14","key":"pone.0347756.ref046","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.3390\/cells11142157","article-title":"Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer","volume":"11","author":"J Manils","year":"2022","journal-title":"Cells"},{"key":"pone.0347756.ref047","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cryobiol.2020.10.018","article-title":"Supplementation of ram\u2019s semen extender with Mito-TEMPO I: Improvement in quality parameters and reproductive performance of cooled-stored semen","volume":"98","author":"F Zarei","year":"2021","journal-title":"Cryobiology"},{"issue":"4","key":"pone.0347756.ref048","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1089\/bio.2021.0128","article-title":"Antioxidant Effect of Melatonin on Proliferation, Apoptosis, and Oxidative Stress Variables in Frozen-Thawed Neonatal Mice Spermatogonial Stem Cells","volume":"20","author":"T Nazeri","year":"2022","journal-title":"Biopreserv Biobank"},{"issue":"9","key":"pone.0347756.ref049","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3390\/biomedicines9091086","article-title":"The Role of Curcumin in Cancer Treatment","volume":"9","author":"V Zoi","year":"2021","journal-title":"Biomedicines"},{"key":"pone.0347756.ref050","doi-asserted-by":"crossref","first-page":"102497","DOI":"10.1016\/j.redox.2022.102497","article-title":"NAC, NAC, Knockin\u2019 on Heaven\u2019s door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells","volume":"57","author":"B Kalyanaraman","year":"2022","journal-title":"Redox Biol"},{"issue":"2","key":"pone.0347756.ref051","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3390\/antiox10020175","article-title":"Activation of NRF2 and ATF4 Signaling by the Pro-Glutathione Molecule I-152, a Co-Drug of N-Acetyl-Cysteine and Cysteamine","volume":"10","author":"R Crinelli","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"pone.0347756.ref052","doi-asserted-by":"crossref","first-page":"111114","DOI":"10.1016\/j.fsi.2026.111114","article-title":"Activation of the Nrf2-Keap1 pathway is associated with NAC-mediated alleviation of nitrite-induced oxidative and endoplasmic reticulum stress and apoptosis in Marsupenaeus japonicus","volume":"170","author":"Y Lei","year":"2026","journal-title":"Fish Shellfish Immunol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:28:21Z","timestamp":1776792501000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347756"}},"subtitle":[],"editor":[{"given":"Sameh","family":"Abdelnour","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347756","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}