{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T15:02:07Z","timestamp":1781967727064,"version":"3.54.5"},"reference-count":71,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372886"],"award-info":[{"award-number":["32372886"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872356"],"award-info":[{"award-number":["31872356"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021ZDZX0008"],"award-info":[{"award-number":["2021ZDZX0008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Science and Technology Program","award":["32372886"],"award-info":[{"award-number":["32372886"]}]},{"name":"Sichuan Science and Technology Program","award":["31872356"],"award-info":[{"award-number":["31872356"]}]},{"name":"Sichuan Science and Technology Program","award":["2021ZDZX0008"],"award-info":[{"award-number":["2021ZDZX0008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Artificial insemination (AI) with liquid-stored semen is the most prevalent and efficient assisted reproduction technique in the modern pork industry. Pyruvate dehydrogenase complex component X (PDHX) was demonstrated to be associated with sperm metabolism and affected the boar sperm viability, motility, and fertility. Pyruvate Dehydrogenase Kinases (PDKs) are the key metabolic enzymes that regulate pyruvate dehydrogenase complex (PDHC) activity and also the conversion from glycolysis to oxidative phosphorylation. In the present study, two PDK inhibitors, Dichloroacetate (DCA) and Phenylbutyrate (4-PBA), were added to an extender and investigated to determine their regulatory roles in liquid-stored boar sperm at 17 \u00b0C. The results indicated that PDK1 and PDK3 were predominantly located at the head and flagella of the boar sperm. The addition of 2 mM DCA and 0.5 mM 4-PBA significantly enhanced the sperm motility, plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), and ATP content. In addition, DCA and 4-PBA exerted their effects by inhibiting PDK1 and PDK3, respectively. In conclusion, DCA and 4-PBA were found to regulate the boar sperm metabolic activities via PDK1 and PDK3. These both can improve the quality parameters of liquid-stored boar sperm, which will help to improve and optimize liquid-stored boar semen after their addition in the extender.<\/jats:p>","DOI":"10.3390\/ijms242317091","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T03:40:58Z","timestamp":1701661258000},"page":"17091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phenylbutyrate and Dichloroacetate Enhance the Liquid-Stored Boar Sperm Quality via PDK1 and PDK3"],"prefix":"10.3390","volume":"24","author":[{"given":"Zhihua","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life Science, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyong","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-4551","authenticated-orcid":false,"given":"Changjun","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"},{"name":"College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611134, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.anireprosci.2017.02.007","article-title":"Long-term liquid storage and reproductive evaluation of an innovative boar semen extender (Formula12(\u00ae)) containing a non-reducing disaccharide and an enzymatic agent","volume":"180","author":"Bresciani","year":"2017","journal-title":"Anim. Reprod. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0378-4320(00)00157-3","article-title":"Storage of boar semen","volume":"62","author":"Johnson","year":"2000","journal-title":"Anim. Reprod. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cheng, Q., Li, L., Jiang, M., Liu, B., Xian, Y., Liu, S., Liu, X., Zhao, W., and Li, F. (2022). Extend the Survival of Human Sperm In Vitro in Non-Freezing Conditions: Damage Mechanisms, Preservation Technologies, and Clinical Applications. Cells, 11.","DOI":"10.3390\/cells11182845"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhsb.2006.09.021","article-title":"Fifth Metacarpal Neck Fractures: Is Follow-Up Required?","volume":"32","author":"Bansal","year":"2016","journal-title":"J. Hand Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1439-0531.2006.00738.x","article-title":"Fertility results of artificial inseminations performed with liquid boar semen stored in X-cell vs BTS extender","volume":"42","author":"Haugan","year":"2007","journal-title":"Reprod. Domest. Anim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1439-0531.2006.00765.x","article-title":"Mammalian sperm energy resources management and survival during conservation in refrigeration","volume":"41","year":"2006","journal-title":"Reprod. Domest. Anim."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.theriogenology.2015.05.005","article-title":"Current knowledge on boar sperm metabolism: Comparison with other mammalian species","volume":"85","author":"Bonet","year":"2016","journal-title":"Theriogenology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1530\/rep.0.1230579","article-title":"Differential effects of glucose and fructose on hexose metabolism in dog spermatozoa","volume":"123","author":"Rigau","year":"2002","journal-title":"Reproduction"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.theriogenology.2003.12.006","article-title":"Boar sperm storage capacity of BTS and Androhep Plus: Viability, motility, capacitation, and tyrosine phosphorylation","volume":"62","author":"Beaulieu","year":"2004","journal-title":"Theriogenology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.freeradbiomed.2019.06.018","article-title":"Negative effects of ROS generated during linear sperm motility on gene expression and ATP generation in boar sperm mitochondria","volume":"141","author":"Zhu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9688","DOI":"10.1074\/jbc.M511481200","article-title":"Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase","volume":"281","author":"Korotchkina","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.eplepsyres.2015.07.002","article-title":"Pyruvate dehydrogenase complex deficiency and its relationship with epilepsy frequency\u2014An overview","volume":"116","author":"Bhandary","year":"2015","journal-title":"Epilepsy Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1095\/biolreprod.107.066704","article-title":"Hamster sperm capacitation: Role of pyruvate dehydrogenase A and dihydrolipoamide dehydrogenase","volume":"79","author":"Kumar","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"127548","DOI":"10.1016\/j.jhazmat.2021.127548","article-title":"Multi-omics analyses reveal the mechanisms of Arsenic-induced male reproductive toxicity in mice","volume":"424","author":"Peng","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Siva, A.B., Panneerdoss, S., Sailasree, P., Singh, D.K., Kameshwari, D.B., and Shivaji, S. (2014). Inhibiting sperm pyruvate dehydrogenase complex and its E3 subunit, dihydrolipoamide dehydrogenase affects fertilization in Syrian hamsters. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097916"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Wang, W., Liang, K., Chang, Y., Ran, M., Zhang, Y., Ali, M.A., Dai, D., Qazi, I.H., Zhang, M., and Zhou, G. (2020). miR-26a is Involved in Glycometabolism and Affects Boar Sperm Viability by Targeting PDHX. Cells, 9.","DOI":"10.3390\/cells9010146"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-7075-11-10","article-title":"The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility","volume":"11","author":"Zhang","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"djx071","DOI":"10.1093\/jnci\/djx071","article-title":"Therapeutic Targeting of the Pyruvate Dehydrogenase Complex\/Pyruvate Dehydrogenase Kinase (PDC\/PDK) Axis in Cancer","volume":"109","author":"Stacpoole","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"417","DOI":"10.2174\/1381612013397915","article-title":"Current therapies and emerging targets for the treatment of diabetes","volume":"7","author":"Wagman","year":"2001","journal-title":"Curr. Pharm. Des."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/oby.2003.26","article-title":"PDK4: A factor in fatness?","volume":"11","author":"Sugden","year":"2003","journal-title":"Obes. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/cas.12085","article-title":"Cancer metabolism: Key players in metabolic reprogramming","volume":"104","author":"Soga","year":"2013","journal-title":"Cancer Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/jnr.20293","article-title":"Pyruvate dehydrogenase complex: Metabolic link to ischemic brain injury and target of oxidative stress","volume":"79","author":"Martin","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_23","first-page":"E647","article-title":"Effect of induced metabolic acidosis on human skeletal muscle metabolism during exercise","volume":"277","author":"Parolin","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"110973","DOI":"10.1016\/j.ecoenv.2020.110973","article-title":"The mechanisms of arsenic-induced ovotoxicity, ultrastructural alterations, and autophagic related paths: An enduring developmental study in folliculogenesis of mice","volume":"204","author":"Ommati","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s43032-021-00505-6","article-title":"Reprogramming of glucose metabolism of cumulus cells and oocytes and its therapeutic significance","volume":"29","author":"Imanaka","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1128312","DOI":"10.3389\/fphar.2023.1128312","article-title":"Metabolic reprogramming induced by DCA enhances cisplatin sensitivity through increasing mitochondrial oxidative stress in cholangiocarcinoma","volume":"14","author":"Qin","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_27","first-page":"617","article-title":"Dichloroacetate and cancer: New home for an orphan drug?","volume":"1846","author":"Kankotia","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1542\/peds.2005-1226","article-title":"Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children","volume":"117","author":"Stacpoole","year":"2006","journal-title":"Pediatrics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1007\/s10517-015-3039-x","article-title":"Study of Antitumor Activity of Sodium Phenylbutyrate, Histon Deacetylase Inhibitor, on Ehrlich Carcinoma Model","volume":"159","author":"Fadeev","year":"2015","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Karissa, P., Simpson, T., Dawson, S.P., Low, T.Y., Tay, S.H., Nordin, F.D.A., Zain, S.M., Lee, P.Y., and Pung, Y.-F. (2022). Comparison between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency. Br. J. Biomed. Sci., 79.","DOI":"10.3389\/bjbs.2022.10382"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175ra131","DOI":"10.1126\/scitranslmed.3004986","article-title":"Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis","volume":"5","author":"Ferriero","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1203\/01.PDR.0000057987.46622.64","article-title":"Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency","volume":"53","author":"Fouque","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s10545-014-9808-2","article-title":"Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate","volume":"38","author":"Ferriero","year":"2015","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.drudis.2015.03.012","article-title":"Development of pyruvate dehydrogenase kinase inhibitors in medicinal chemistry with particular emphasis as anticancer agents","volume":"20","author":"Zhang","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/bs.irn.2019.05.003","article-title":"Dichloroacetate-induced peripheral neuropathy","volume":"145","author":"Stacpoole","year":"2019","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, Q., Samidurai, A., Thompson, J., Hu, Y., Das, A., Willard, B., and Lesnefsky, E.J. (2020). Endoplasmic reticulum stress-mediated mitochondrial dysfunction in aged hearts. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165899"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.anireprosci.2006.12.010","article-title":"Assessment of in vitro sperm characteristics in relation to fertility in dairy bulls","volume":"103","author":"Gillan","year":"2008","journal-title":"Anim. Reprod. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.anireprosci.2013.01.010","article-title":"Assessment of in vitro sperm characteristics and their importance in the prediction of conception rate in a bovine timed-AI program","volume":"137","author":"Oliveira","year":"2013","journal-title":"Anim. Reprod. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.anireprosci.2017.02.003","article-title":"Sperm quality and oxidative status as affected by homogenization of liquid-stored boar semen diluted in short- and long-term extenders","volume":"179","author":"Menegat","year":"2017","journal-title":"Anim. Reprod. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.anireprosci.2018.03.024","article-title":"The sperm mitochondrion: Organelle of many functions","volume":"194","author":"Moraes","year":"2018","journal-title":"Anim. Reprod. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1095\/biolreprod.109.076471","article-title":"Reactive oxygen species and boar sperm function","volume":"81","author":"Awda","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1439-0531.2010.01719.x","article-title":"Effect of pre-freeze addition of cysteine hydrochloride and reduced glutathione in semen of crossbred Jersey bulls on sperm parameters and conception rates","volume":"46","author":"Perumal","year":"2011","journal-title":"Reprod. Domest. Anim."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cryobiol.2009.10.012","article-title":"Resveratrol and ascorbic acid prevent DNA damage induced by cryopreservation in human semen","volume":"60","author":"Branco","year":"2010","journal-title":"Cryobiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.freeradbiomed.2003.08.010","article-title":"In situ detection and localization of lipid peroxidation in individual bovine sperm cells","volume":"35","author":"Brouwers","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/bjc.2012.559","article-title":"Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma","volume":"108","author":"Shen","year":"2013","journal-title":"Br. J. Cancer."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1007\/s10549-014-3128-y","article-title":"Dichloroacetate enhances apoptotic cell death via oxidative damage and attenuates lactate production in metformin-treated breast cancer cells","volume":"147","author":"Haugrud","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9955","DOI":"10.1021\/acs.jmedchem.2c00640","article-title":"A Mitochondria-Targeted Phenylbutyric Acid Prodrug Confers Drastically Improved Anticancer Activities","volume":"65","author":"Huang","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5173035","DOI":"10.1155\/2021\/5173035","article-title":"DCA Protects against Oxidation Injury Attributed to Cerebral Ischemia-Reperfusion by Regulating Glycolysis through PDK2-PDH-Nrf2 Axis","volume":"2021","author":"Zhao","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e477","DOI":"10.1097\/CCM.0000000000001469","article-title":"4-Phenylbutyrate Benefits Traumatic Hemorrhagic Shock in Rats by Attenuating Oxidative Stress, Not by Attenuating Endoplasmic Reticulum Stress","volume":"44","author":"Yang","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.theriogenology.2016.03.005","article-title":"Effects of glucose metabolism pathways on sperm motility and oxidative status during long-term liquid storage of goat semen","volume":"86","author":"Qiu","year":"2016","journal-title":"Theriogenology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4103\/1008-682X.135123","article-title":"Oxidative phosphorylation versus glycolysis: What fuel do spermatozoa use?","volume":"17","author":"Agarwal","year":"2015","journal-title":"Asian J. Androl."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"121077","DOI":"10.1016\/j.lfs.2022.121077","article-title":"Novel shikonin derivatives suppress cell proliferation, migration and induce apoptosis in human triple-negative breast cancer cells via regulating PDK1\/PDHC axis","volume":"310","author":"Chen","year":"2022","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"28989","DOI":"10.1074\/jbc.270.48.28989","article-title":"Diversity of the pyruvate dehydrogenase kinase gene family in humans","volume":"270","author":"Gudi","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"25305","DOI":"10.1074\/jbc.M802249200","article-title":"Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity","volume":"283","author":"Wynn","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0079-6603(01)70013-X","article-title":"Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms","volume":"70","author":"Roche","year":"2001","journal-title":"Prog. Nucleic Acid. Res. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0065-2571(00)00020-0","article-title":"Control of pyruvate dehydrogenase kinase gene expression","volume":"41","author":"Harris","year":"2001","journal-title":"Adv. Enzyme Regul."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1042\/bj3290191","article-title":"Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex","volume":"329","author":"Davis","year":"1998","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3892\/ijo.2012.1687","article-title":"Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target","volume":"42","author":"Hur","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1158\/0008-5472.CAN-12-0979","article-title":"Inactivation of the HIF-1\u03b1\/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants","volume":"72","author":"Kluza","year":"2012","journal-title":"Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1089\/ars.2021.0083","article-title":"PDK4 Decrease Neuronal Apoptosis via Inhibiting ROS-ASK1\/P38 Pathway in Early Brain Injury After Subarachnoid Hemorrhage","volume":"36","author":"Gao","year":"2022","journal-title":"Antioxid. Redox Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.biocel.2015.01.015","article-title":"The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis","volume":"61","author":"Kolb","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1158\/1535-7163.MCT-19-0079","article-title":"Metabolic Flexibility in Cancer: Targeting the Pyruvate Dehydrogenase Kinase:Pyruvate Dehydrogenase Axis","volume":"18","author":"Woolbright","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1080\/19396368.2020.1850907","article-title":"Comparison of commercially available chamber slides for computer-aided analysis of human sperm","volume":"67","author":"Dardmeh","year":"2021","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Prochowska, S., Ni\u017ca\u0144ski, W., and Fontbonne, A. (2022). Hypo-Osmotic Swelling Test (HOST) for Feline Spermatozoa: The Simplified Procedure and the Aspect of Sperm Morphology. Animals, 12.","DOI":"10.3390\/ani12070903"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Feng, C., Zhu, Z., Bai, W., Li, R., Zheng, Y., Tian, X., Wu, D., Lu, H., Wang, Y., and Zeng, W. (2020). Proline Protects Boar Sperm against Oxidative Stress through Proline Dehydrogenase-Mediated Metabolism and the Amine Structure of Pyrrolidine. Animals, 10.","DOI":"10.3390\/ani10091549"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"skac069","DOI":"10.1093\/jas\/skac069","article-title":"Polyamines protect boar sperm from oxidative stress in vitro","volume":"100","author":"Li","year":"2022","journal-title":"J. Anim. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ran, M.X., Zhou, Y.M., Liang, K., Wang, W.C., Zhang, Y., Zhang, M., Yang, J.D., Zhou, G.B., Wu, K., and Wang, C.D. (2019). Comparative Analysis of MicroRNA and mRNA Profiles of Sperm with Different Freeze Tolerance Capacities in Boar (Susscrofa) and Giant Panda (Ailuropodamelanoleuca). Biomolecules, 9.","DOI":"10.3390\/biom9090432"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yuan, X., Ali, M.A., Qin, Z., Zhang, Y., and Zeng, C. (2021). piR-121380 Is Involved in Cryo-Capacitation and Regulates Post-Thawed Boar Sperm Quality Through Phosphorylation of ERK2 via Targeting PTPN7. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.792994"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Yuan, X., Wang, Y., Ali, M.A., Qin, Z., Guo, Z., Zhang, Y., Zhang, M., Zhou, G., Yang, J., and Chen, L. (2023). Odorant Receptor OR2C1 Is an Essential Modulator of Boar Sperm Capacitation by Binding with Heparin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021664"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/17091\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:37:13Z","timestamp":1760132233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/17091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,4]]},"references-count":71,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242317091"],"URL":"https:\/\/doi.org\/10.3390\/ijms242317091","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,4]]}}}