{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T03:18:33Z","timestamp":1786763913382,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":"crossref","award":["32301318"],"award-info":[{"award-number":["32301318"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["3237130957"],"award-info":[{"award-number":["3237130957"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Youth Research Foundation of Qinghai University","award":["2022-QNY-1"],"award-info":[{"award-number":["2022-QNY-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Climate-change-induced thermal stress poses a significant threat to cold-adapted aquatic species, particularly fish endemic to high-altitude ecosystems such as Gymnocypris eckloni, which is native to the Qinghai-Tibetan Plateau. To elucidate the molecular and metabolic mechanisms underlying their response to elevated temperatures, we integrated RNA-seq, miRNA-seq, and LC-MS-based metabolomic analyses of liver tissue from fish exposed to chronic thermal stress (HT) versus control (CT) conditions. Although no significant differences were observed in growth parameters, histopathological examination revealed structural damage under heat stress. Transcriptomic analysis identified widespread dysregulation of genes involved in energy metabolism, with significant downregulation of pathways related to amino acid, fatty acid, glucose, and oxidative phosphorylation. In contrast, upregulated DEGs were enriched in N-glycan biosynthesis, protein processing in the endoplasmic reticulum, and phagosome. Concomitant miRNA profiling revealed differentially expressed miRNAs, including miR-196a-5p, miR-132-3p, and miR-181b-5p, which were predicted to regulate key metabolic genes such as ugt1a1, pepck, and calr. Metabolomic analysis further demonstrated significant alterations in metabolic profiles, with glutathione metabolism, tryptophan metabolism, steroid hormone biosynthesis, and pyruvate metabolism emerging as central pathways in the heat stress response. Integrated multi-omics analysis confirmed coordinated regulation of these pathways, highlighting the critical role of glutathione and tryptophan, as well as disruptions in purine and energy metabolism. The DEMiR-DEG-DEM networks involving miR-196a-5p-pepck-PEP, miR-133a-3p-gne-UDP-GlcNAc, and miR-132-3p-ugt1a1-Bilirubin may play an important role in thermal stress. This study provided a new perspective on the molecular, regulatory, and metabolic adaptations of Gymnocypris eckloni to thermal stress, identifying potential biomarkers and regulatory networks that may inform conservation strategies for cold-water fish under global warming.<\/jats:p>","DOI":"10.3390\/ani15223272","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:59:09Z","timestamp":1763027949000},"page":"3272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Physiological Responses to Thermal Stress in the Liver of Gymnocypris eckloni Revealed by Multi-Omics"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-7216","authenticated-orcid":false,"given":"Miaomiao","family":"Nie","sequence":"first","affiliation":[{"name":"State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenji","family":"Wang","sequence":"additional","affiliation":[{"name":"Fishery Environmental Monitoring Station of Qinghai Province, Xining 810012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3123-6601","authenticated-orcid":false,"given":"Qiang","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2647-3928","authenticated-orcid":false,"given":"Delin","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s13201-023-01902-9","article-title":"Are global influences of cascade dams affecting river water temperature and fish ecology?","volume":"13","author":"Soomro","year":"2023","journal-title":"Appl. Water Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/are.13049","article-title":"Effect of water temperature on the physiology of fish spermatozoon function: A brief review","volume":"48","author":"Dadras","year":"2017","journal-title":"Aquac. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Menon, S.V., Kumar, A., Middha, S.K., Paital, B., Mathur, S., Johnson, R., Kademan, A., Usha, T., Hemavathi, K.N., and Dayal, S. (2023). Water physicochemical factors and oxidative stress physiology in fish, a review. Front. Environ. Sci., 11.","DOI":"10.3389\/fenvs.2023.1240813"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110078","DOI":"10.1016\/j.fsi.2024.110078","article-title":"Effects of chronic cold stress and thermal stress on growth performance, hepatic apoptosis, oxidative stress, immune response and gut microbiota of juvenile hybrid sturgeon (Acipenser baerii Q x A. schrenkii d)","volume":"157","author":"Liu","year":"2025","journal-title":"Fish Shellfish Immunol."},{"key":"ref_5","first-page":"67","article-title":"Temperature acclimation and metabolism in ectotherms with particular reference to teleost fish","volume":"41","author":"Johnston","year":"1987","journal-title":"Symp. Soc. Exp. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1111\/jfb.15745","article-title":"Temperature-related increase in growth rate in four freshwater lake fish species","volume":"104","author":"Tien","year":"2024","journal-title":"J. Fish Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/jfb.15118","article-title":"Seasonal differences in thermal stress susceptibility of diploid and triploid brook trout, Salvelinus fontinalis (Teleostei, Pisces)","volume":"101","author":"Lahnsteiner","year":"2022","journal-title":"J. Fish Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"R\u00e9alis-Doyelle, E., Pasquet, A., De Charleroy, D., Fontaine, P., and Teletchea, F. (2016). Strong Effects of Temperature on the Early Life Stages of a Cold Stenothermal Fish Species, Brown Trout (Salmo trutta L.). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155487"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/faf.12808","article-title":"Thermal tolerance in Pacific salmon: A systematic review of species, populations, life stages and methodologies","volume":"25","author":"Mayer","year":"2024","journal-title":"Fish Fish."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11160-004-6749-0","article-title":"Effects of global climate change on marine and estuarine fishes and fisheries","volume":"14","author":"Roessig","year":"2004","journal-title":"Rev. Fish Biol. Fish."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1080\/23308249.2020.1767035","article-title":"Reservoir Fish Habitats: A perspective on coping with climate change","volume":"28","author":"Miranda","year":"2020","journal-title":"Rev. Fish. Sci. Aquac."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/fwb.13831","article-title":"Arctic freshwater biodiversity: Establishing baselines, trends, and drivers of ecological change","volume":"67","author":"Culp","year":"2022","journal-title":"Freshw. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1007\/BF01922428","article-title":"The effect of chronic heat-stress on cortisol-levels in the antarctic fish pagothenia-borchgrevinki","volume":"51","author":"Ryan","year":"1995","journal-title":"Experientia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jtherbio.2014.06.007","article-title":"Sub-lethal heat stress causes apoptosis in an Antarctic fish that lacks an inducible heat shock response","volume":"44","author":"Sleadd","year":"2014","journal-title":"J. Therm. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ygeno.2018.11.011","article-title":"Transcriptome profiling and histology changes in juvenile blunt snout bream (Megalobrama amblycephala) liver tissue in response to acute thermal stress","volume":"111","author":"Bing","year":"2019","journal-title":"Genomics"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Roh, H., Kim, A., Kim, N., Lee, Y., and Kim, D.-H. (2020). Multi-omics analysis provides novel insight into immuno-physiological pathways and development of thermal resistance in rainbow trout exposed to acute thermal stress. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239198"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7621215","DOI":"10.1155\/2023\/7621215","article-title":"Transcriptome sequencing reveals the response to acute thermal stress in the Pacific Abalone, Haliotis discus hannai","volume":"2023","author":"Wu","year":"2023","journal-title":"Aquac. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, C., Wen, H., Zheng, Y., Zhang, C., Zhang, Y., Wang, L., Sun, D., Zhang, K., Qi, X., and Li, Y. (2024). Integration of mRNA and miRNA analysis sheds new light on the muscle response to heat stress in Spotted Sea Bass (Lateolabrax maculatus). Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212098"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"740037","DOI":"10.1016\/j.aquaculture.2023.740037","article-title":"Comparative transcriptome analysis of hybrid Jinhu grouper (Epinephelus fuscoguttatus \u2640 \u00d7 Epinephelus tukula \u2642) and Epinephelus fuscoguttatus under temperature stress","volume":"578","author":"Duan","year":"2024","journal-title":"Aquaculture"},{"key":"ref_20","first-page":"308","article-title":"Global metabolic responses of the lenok (Brachymystax lenok) to thermal stress","volume":"29","author":"Liu","year":"2019","journal-title":"Comp. Biochem. Physiol. D-Genom. Proteom."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1007\/s10695-022-01128-7","article-title":"Intestinal metabolomics of juvenile lenok (Brachymystax lenok) in response to heat stress","volume":"48","author":"Chen","year":"2022","journal-title":"Fish Physiol. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101875","DOI":"10.1016\/j.aqrep.2023.101875","article-title":"Protective effect of steroidal saponins on heat stress in the liver of largemouth bass (Micropterus salmoides) revealed by metabolomic analysis","volume":"33","author":"Cheng","year":"2023","journal-title":"Aquac. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109118","DOI":"10.1016\/j.fsi.2023.109118","article-title":"Integrated metabolomic and transcriptomic responses to heat stress in a high-altitude fish, Triplophysa siluroides","volume":"142","author":"Chen","year":"2023","journal-title":"Fish Shellfish Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2021EA001973","DOI":"10.1029\/2021EA001973","article-title":"Strong warming rates in the surface and bottom layers of a boreal lake: Results from approximately six decades of measurements (1964\u20132020)","volume":"9","author":"Noori","year":"2022","journal-title":"Earth Space Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2021WR031543","DOI":"10.1029\/2021WR031543","article-title":"Six Decades of thermal change in a pristine lake situated north of the arctic circle","volume":"58","author":"Noori","year":"2022","journal-title":"Water Resour. Res."},{"key":"ref_26","unstructured":"Wu, Y.F., and Wu, C.Z. (1992). The Fishes of the Qinghai\u2014Xizang Plateau, Science and Technology Press."},{"key":"ref_27","unstructured":"Yue, P.Q. (2000). \u201cSchizothoracinae,\u201d in Fauna Sinica, Osteichthyes, Cypriniformes, Science Press. [3rd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Qi, D., Chao, Y., Wu, R., Xia, M., Chen, Q., and Zheng, Z. (2018). Transcriptome analysis provides insights into the adaptive responses to hypoxia of a Schizothoracine fish (Gymnocypris eckloni). Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01326"},{"key":"ref_29","unstructured":"Yan, S. (2016). Tudy on the Biology of Gymnocypris eckloni and the Research of Reproductive Property, Embryo and Artificial Cultivation, China West Normal University."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s10695-017-0363-2","article-title":"Study on the morphology, histology and enzymatic activity of the digestive tract of Gymnocypris eckloni Herzenstein","volume":"43","author":"Yang","year":"2017","journal-title":"Fish Physiol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.1016\/j.ygeno.2020.07.030","article-title":"Mitochondrial genome and phylogenetic relationship of Gymnocypris eckloni (Schizothoracinae) in Qaidam river basin","volume":"112","author":"Zhang","year":"2020","journal-title":"Genomics"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nie, M., Ni, W., Wang, L., Gao, Q., Liu, D., Tian, F., Wang, Z., Zhang, C., and Qi, D. (2022). Insights into mirna-mrna regulatory mechanisms of cold adaptation in Gymnocypris eckloni: Ubiquitin-mediated proteolysis is pivotal for adaptive energy metabolism. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.903995"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41597-022-01595-w","article-title":"Chromosome-level genome assembly provides insight into the evolution of chromosomes and the globin gene superfamily in Gymnocypris eckloni","volume":"9","author":"Wang","year":"2022","journal-title":"Sci. Data"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"121926","DOI":"10.1016\/j.jenvman.2024.121926","article-title":"Effect of global climate change on the sustainability of cold-water fish habitat in the alpine region: A case study on the Gymnocypris eckloni in the source region of the Yellow River","volume":"367","author":"Zhao","year":"2024","journal-title":"J. Environ. Manag."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101998","DOI":"10.1016\/j.aqrep.2024.101998","article-title":"Heat stress affects swimming performance and induces biochemical, structural, and transcriptional changes in the heart of Gymnocypris eckloni","volume":"35","author":"Li","year":"2024","journal-title":"Aquac. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Duan, Y.T., Li, H.J., Li, J.T., Bai, S.H., Fu, S.X., Zhou, Y.H., Liu, S.D., Li, R.D., Liu, H.P., and Zhou, C.W. (2024). Integrated transcriptome and 16S rDNA analyses reveal that acute heat stress induces intestinal damage in Gymnocypris eckloni. Front. Mar. Sci., 11.","DOI":"10.3389\/fmars.2024.1448313"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"741112","DOI":"10.1016\/j.aquaculture.2024.741112","article-title":"Decoding the intestinal response to heat stress in Gymnocypris eckloni: Insights from a thorough analysis of microbiome and transcriptome","volume":"591","author":"Zhou","year":"2024","journal-title":"Aquaculture"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102392","DOI":"10.1016\/j.aqrep.2024.102392","article-title":"A study on the hepatic response to heat stress in Gymnocypris eckloni through an approach combining metabolomic and transcriptomic profiling","volume":"39","author":"Zhou","year":"2024","journal-title":"Aquac. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"735329","DOI":"10.1016\/j.aquaculture.2020.735329","article-title":"Histologic examination and transcriptome analysis uncovered liver damage in largemouth bass from formulated diets","volume":"526","author":"Ma","year":"2020","journal-title":"Aquaculture"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s10695-022-01140-x","article-title":"Selenium improved mitochondrial quality and energy supply in the liver of high-fat diet-fed grass carp (Ctenopharyngodon idella) after heat stress","volume":"48","author":"Zhang","year":"2022","journal-title":"Fish Physiol. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"136940","DOI":"10.1016\/j.scitotenv.2020.136940","article-title":"Physiological responses to cold and starvation stresses in the liver of yellow drum (Nibea albiflora) revealed by LC-MS metabolomics","volume":"715","author":"Jiao","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e245","DOI":"10.1038\/emm.2016.81","article-title":"Regulation and function of AMPK in physiology and diseases","volume":"48","author":"Jeon","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nprot.2012.135","article-title":"Global metabolic profiling of animal and human tissues via UPLC-MS","volume":"8","author":"Want","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yang, Y., Yuan, H., Liu, X., Wang, Z., Li, Y., Ren, Y., Gao, C., Jiao, T., Cai, Y., and Zhao, S. (2022). Transcriptome and metabolome integration provides new insights into the regulatory networks of Tibetan pig alveolar type ii epithelial cells in response to hypoxia. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.812411"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1600-0633.2004.00052.x","article-title":"Effects of constant and cyclical thermal regimes on growth and feeding of juvenile cutthroat trout of variable sizes","volume":"13","author":"Meeuwig","year":"2004","journal-title":"Ecol. Freshw. Fish"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/jfb.14348","article-title":"Thermal variation near the thermal optimum does not affect the growth, metabolism or swimming performance in wild Atlantic salmon (Salmo salar)","volume":"98","author":"Morissette","year":"2021","journal-title":"J. Fish Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1113\/JP277091","article-title":"Fasting enhances cold resistance in fish through stimulating lipid catabolism and autophagy","volume":"597","author":"Lu","year":"2019","journal-title":"J. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/j.2040-4603.2014.tb00548.x","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"741041","DOI":"10.1016\/j.aquaculture.2024.741041","article-title":"Long-term thermal stress induces hepatic injury and alters the thermotolerance response in Hong Kong catfish (Clarias fuscus)","volume":"590","author":"Duan","year":"2024","journal-title":"Aquaculture"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2164-15-765","article-title":"Liver transcriptome analysis in gilthead sea bream upon exposure to low temperature","volume":"15","author":"Mininni","year":"2014","journal-title":"BMC Genom."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cbpb.2015.09.001","article-title":"Micromanaging metabolism\u2014A role for miRNAs in teleost energy metabolism","volume":"199","author":"Mennigen","year":"2016","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"737310","DOI":"10.1016\/j.aquaculture.2021.737310","article-title":"MicroRNAs mediated environmental stress responses and toxicity signs in teleost fish species","volume":"546","author":"Raza","year":"2022","journal-title":"Aquaculture"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"736747","DOI":"10.1016\/j.aquaculture.2021.736747","article-title":"MicroRNA roles and their potential use as selection tool to cold tolerance of domesticated teleostean species: A systematic review","volume":"540","author":"Domingues","year":"2021","journal-title":"Aquaculture"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ikert, H., and Craig, P.M. (2020). Chronic exposure to venlafaxine and increased water temperature reversibly alters microRNA in zebrafish gonads (Danio rerio). Comp. Biochem. Physiol. Part D Genom. Proteom., 33.","DOI":"10.1016\/j.cbd.2019.100634"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jtherbio.2018.02.007","article-title":"Responses of blood biochemistry, fatty acid composition and expression of microRNAs to heat stress in genetically improved farmed tilapia (Oreochromis niloticus)","volume":"73","author":"Bao","year":"2018","journal-title":"J. Therm. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.gene.2018.09.012","article-title":"Identification and characterization of microRNAs in the liver of rainbow trout in response to heat stress by high-throughput sequencing","volume":"679","author":"Huang","year":"2018","journal-title":"Gene"},{"key":"ref_57","unstructured":"Rifai, N., Horvath, A.R., and Wittwer, C.T. (2018). 13\u2014Amino acids, peptides, and proteins. Principles and Applications of Molecular Diagnostics, Elsevier."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Qaid, M.M., and Al-Garadi, M.A. (2021). Protein and amino acid metabolism in poultry during and after heat stress: A Review. Animals, 11.","DOI":"10.3390\/ani11041167"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"114366","DOI":"10.1016\/j.ecoenv.2022.114366","article-title":"Integrated biochemical, transcriptomic and metabolomic analyses provide insight into heat stress response in Yangtze sturgeon (Acipenser dabryanus)","volume":"249","author":"Chen","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10695-016-0314-3","article-title":"Effects of amino acid supplementations on metabolic and physiological parameters in Atlantic cod (Gadus morhua) under stress","volume":"43","author":"Herrera","year":"2017","journal-title":"Fish Physiol. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"656","DOI":"10.2741\/3950","article-title":"Uric acid, hyperuricemia and vascular diseases","volume":"17","author":"Jin","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cicero, A.F.G., Fogacci, F., Di Micoli, V., Angeloni, C., Giovannini, M., and Borghi, C. (2023). Purine metabolism dysfunctions: Experimental methods of detection and diagnostic potential. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087027"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jgg.2015.04.004","article-title":"Pyrimidine metabolism: Dynamic and versatile pathways in pathogens and cellular development","volume":"42","author":"Garavito","year":"2015","journal-title":"J. Genet. Genom."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1126\/science.adh2771","article-title":"Pyrimidines maintain mitochondrial pyruvate oxidation to support de novo lipogenesis","volume":"383","author":"Sahu","year":"2024","journal-title":"Science"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/22\/3272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T05:29:02Z","timestamp":1763098142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/22\/3272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":64,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ani15223272"],"URL":"https:\/\/doi.org\/10.3390\/ani15223272","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]}}}