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| Research Progress on Metabolism Mechanism and Preliminary Application of Bile Acid in Transition Dairy Cow (Bos taurus) |
| WU Ying1, ZHANG Xia2, YAO Jun-Hu1, ZHANG Jun1,3,* |
1 College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China;
2 College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China;
3 National Center of Technology Innovation for Dairy, Hohhot 010100, China |
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Abstract The transition period is a critical phase in the lactation cycle of dairy cows (Bos taurus), characterized by profound physiological adaptations associated with pregnancy, parturition, and lactation. These changes often lead to immune dysfunction and disruptions in glucose and lipid metabolism, predisposing cows to metabolic disorders such as fatty liver, and ketosis. Bile acids, synthesized from cholesterol in the liver, not only facilitate fat emulsification and absorption in the intestine but also act as signaling molecules that regulate glucose-lipid metabolism and immune responses via downstream receptor activation. This review systematically summarizes current knowledge regarding changes in bile acid synthesis, transport, and signaling pathways in dairy cows during the periparturient period, with a focus on their roles as metabolic regulators. Particular emphasis is placed on the mechanisms by which bile acids contribute to the maintenance of glucose stability, lipid metabolic balance, and immune responses, thereby supporting overall metabolic homeostasis in transition dairy cows. Furthermore, the potential applications of bile acid-related findings in dietary formulation, prevention of metabolic diseases, and development of metabolic and health monitoring indicators are discussed, aiming to provide a theoretical basis and practical insights for improving metabolic health and production efficiency in dairy cows.
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Received: 03 November 2025
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Corresponding Authors:
*jzhang0701@nwafu.edu.cn
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[1] 岑蒙莎, 郑霞, 戴宁, 等. 2021. 肠道菌群, 胆汁酸及其交互作用对炎症性肠病的影响及临床应用进展[J]. 中华炎性肠病杂志, 05(3): 242-245.
(Cen M S, Zheng X, Dai N, et al.2021. The influence of bile acid, microbiota and their interaction on inflammatory bowel disease and the related progress in clinical application[J]. Chinese Journal of Inflammatory Bowel Diseases, 05(3): 242-245.)
[2] 丁宝隆, 伏东宝, 赵洪喜. 2024. 酮病奶牛血清脂代谢和肝功能相关指标的变化[J]. 中国兽医杂志, 60(06): 80-85.
(Ding B L, Fu D B, Zhao H X.2024. Changes in serum lipid metabolism and liver function-related indexes in ketotic dairy cows[J]. Chinese Journal of Veterinary Medicine, 60(06): 80-85.)
[3] 高畅鸿. 2023. FXR对脂肪肝奶牛肝脂代谢调控机制研究[D]. 硕士学位论文, 黑龙江八一农垦大学, 导师: 杨威, pp. 58-60.
(Gao C H.2023. Regulation mechanism of liver fat metabolism by FXR in dairy cows with fatty liver[D]. Thesis for M. S., Heilongjiang Bayi Agricultural University, Supervisor: Yang W, pp. 58-60.)
[4] 黄岩. 2021. NEFA介导PERK-eIF2α信号通路调控奶牛肝脂代谢的机制研究[D]. 硕士学位论文, 西北农林科技大学, 导师: 王建国, pp. 11-17.
(Huang Y.2021. The mechanism of NEFA-induced PERK-eIF2α signaling pathway to regulate lipid metabolism in bovine hepatocytes[D]. Thesis for M. S., Northwest A&F University, Supervisor: Wang J G, pp. 11-17.)
[5] 贾宗菲, 石建朋, 韩一超, 等. 2010. 奶牛亚临床酮病血液生化指标消长规律的研究[J]. 畜牧兽医学报, 41(11): 1490-1496.
(Jia Z F, Shi J P, Han Y C, et al.2010. Study on changes of blood biochemical metabolites for subclinical ketosis in dairy cows[J]. Acta Veterinaria et Zootechnica Sinica, 41(11): 1490-1496.)
[6] 姜茜, 彭军, 刘率男, 等. 2015. 法尼醇X受体与糖脂代谢[J]. 药学学报, 50(03): 245-251.
(Jiang X, Peng J, Liu S N, et al.2015. Farnesoid X receptor regulates glucose and lipid metabolisms[J]. Acta Pharmaceutica Sinica, 50(03): 245-251.)
[7] 寇慧娟, 朱怡静, 张继安, 等. 2024. 围产期奶牛的营养需求与饲养管理策略[J]. 畜牧业环境, (13): 138-139.
(Kou H J, ZhuY J, Zhang J A, et al. 2024. Nutritional requirements and feeding management strategies for perinatal cows[J]. Animal Industry and Environment, (13): 138-139.)
[8] 李磊. 2025. 补充胆汁酸对围产期奶牛生产性能、乳品质和健康状况的影响[D]. 硕士学位论文, 西北农林科技大学, 导师: 张俊, pp. 38-44.
(Li L.2025. Effect of supplementing bile acids on the production performance, milk quality, and health status in transition dairy cows[D]. Thesis for M. S., Northwest A&F University, Supervisor: Zhang J, pp. 38-44.)
[9] 李磊, 姚军虎, 杨景, 等. 2024. 胰岛素通路对围产期奶牛糖代谢、脂代谢、健康状况和生产性能影响的研究进展[J]. 动物营养学报, 36(3): 1436-1445.
(Li L, Yao J H, Yang J, et al.2024. Research progress on effects of insulin pathway on glucose metabolism, lipid metabolism, health status and production performance of transition dairy cows[J]. Chinese Journal of Animal Nutrition, 36(3): 1436-1445.)
[10] 李胜利, 郝阳毅, 王蔚, 等. 2020. 围产期奶牛糖脂代谢与健康养殖研究进展[J]. 动物营养学报, 32(10): 4708-4715.
(Li S L, Hao Y Y, Wang W, et al.2020. Research progress on glucose-lipid metabolism and healthy feeding in transition dairy cows[J]. Chinese Journal of Animal Nutrition, 32(10): 4708-4715.)
[11] 刘乐, 何丽丽, 马楠, 等. 2024. 围产期饲粮中添加蛋氨酸羟基类似物异丙酯和N-氨甲酰谷氨酸对奶牛产奶性能和血浆代谢组的影响[J]. 动物营养学报, 36(07): 4375-4387.
(Liu L, He L L, Ma N, et al.2024. Effects of dietary 2-hydroxy-4-methionine isopropyl and N-carbamylglutamate during perinatal period on milk production performance and plasma metabolome of dairy cows[J]. Chinese Journal of Animal Nutrition, 36(7): 4375-4387.)
[12] 刘潇怡, 王迪铭, 孙会增, 等. 2024. 泌乳盛期奶牛肝脏脂肪变性影响生产性能的代谢机制[J]. 浙江大学学报(农业与生命科学版), 50(5): 805-816.
(Liu X Y, Wang D M, Sun H Z, et al.2024. Metabolic mechanism of hepatic steatosis affecting production performance of dairy cows during peak lactation[J]. Journal of Zhejiang University(Agriculture and Life Sciences), 50(5): 805-816)
[13] 刘鑫, 黎力之, 关玮琨, 等. 2020. 肠道菌群介导动物胆汁酸FXR/TGR5信号通路的研究进展[J]. 中国畜牧杂志, 56(12): 13-19.
(Liu X, Li L Z, Guang W K, et al.2020. Research progress on intestinal microflora mediated animal bile acid FXR/TGR5 signaling pathway[J]. Chinese Journal of Animal Science, 56(12): 13-19.)
[14] 聂源. 2022. 基于肠道菌-肝胆汁酸轴探究熊果酸抑制肝纤维化的作用机制[D]. 博士学位论文, 南昌大学, 导师: 朱萱, pp. 108-130.
(Nie Y.2022. Exploring the mechanism of ursolic acid inhibit liver fibrosis based on intestinal bacteria-liver bile acids axis[D]. Thesis for Ph.D., Nanchang University, Supervisor: Zhu X, pp. 108-130.)
[15] 孙博非, 余超, 曹阳春, 等. 2018. 过瘤胃蛋氨酸对围产期奶牛代谢及健康的调控作用及机理[J]. 动物营养学报, 30(03): 829-836.
(Sun B F, Yu C, Cao Y C, et al.2018. Methionine regulates the metabolism and health of transition dairy cows and its mechanism[J]. Chinese Journal of Animal Nutrition, 30(3): 829-836.)
[16] 孙菲菲, 曹阳春, 李生祥, 等. 2014. 胆碱对奶牛围产期代谢的调控[J]. 动物营养学报, 26(01): 26-33.
(Sun F F, Cao Y C, Li S X, et al.2014. Regulation of choline on nutrient metabolism in periparturient dairy cows: A review[J]. Chinese Journal of Animal Nutrition, 26(1): 26-33.)
[17] 王建东, 梁小军. 2023. 代谢组学技术在母牛围产期营养代谢病研究中的应用[J]. 宁夏农林科技, 64(11): 70-73.
(Wang J D, Liang X J.2023. Application of metabolomics techniques in the study of perinatal nutritional metabolic diseases in cows[J]. Journal of Ningxia Agriculture and Forestry Science and Technology, 64(11): 70-73.)
[18] 王朋, 林森, 吴德, 等. 2019. 胆汁酸的营养生理作用及代谢调控研究进展[J]. 动物营养学报, 31(05): 2002-2011.
(Wang P, Lin S, Wu D, et al.2019. Recent Progress in nutrition physiology role and metabolism regulation of bile acids[J]. Chinese Journal of Animal Nutrition, 31(5): 2002-2011.)
[19] 王馨怡, 姚军虎, 张霞, 等. 2025. 胆汁酸调控动物肠道健康的作用及机制研究进展[J]. 畜牧兽医学报, 56(3): 1006-1018.
(Wang X Y, Yao J H, Zhang X, et al.2025. Advances in effect and mechanism of bile acids regulating animal intestinal health[J]. Acta Veterinaria et Zootechnica Sinica, 56(3): 1006-1018.)
[20] 岳晓岩, 张瑞霞. 2023. 肠道菌群-胆汁酸通路与2型糖尿病的关系[J]. 临床医学进展, 13(12): 19851-19856.
(Yue X Y, Zhang R X.Correlation between intestinal flora-bile acid related pathway and type 2 diabetes[J]. Advances in Clinical Medicine, 13(12): 19851-19856.)
[21] 张毕红, 刘耀权, 黄岩, 等. 2023. 饲粮营养调控对维持围产期奶牛糖脂代谢稳态的研究进展[J]. 动物医学进展, 44(11): 101-106.
(Zhang B H, Liu Y Q, Huang Y, et al.2023. Progress on maintenance of glycolipid metabolism homeostasis in periparturient dairy cows by dietary nutrition regulation and control[J]. Animal Husbandry & Veterinary Medicine, 44(11): 101-106.)
[22] 周晓静. 2019. 酮病奶牛血浆GH的动态变化及BHBA对肝细胞氧化应激的影响[D]. 硕士学位论文, 广西大学, 导师: 何宝祥, pp. 27-47.
(Zhou X J.2019. Dynamic changes of plasma GH in ketosis cows and effects of BHBA on hepatic oxidative stress[D]. Thesis for M. S., Guangxi University, Supervisor: He B X, pp. 27-47.)
[23] 周莹, 刘军彤, 宁顺宇, 等. 2023. 胆汁酸代谢与2型糖尿病研究进展[J].辽宁中医药大学学报, 25(03): 142-146.
(Zhou Y, Liu J T, Ning S Y, et al.2023. Research progress on bile acid metabolism and type 2 diabetes[J]. Journal of Liaoning University of Traditional, 25(03): 142-146.)
[24] Badiee S A, Isu U H, Khodadadi E, et al.2023. The alternating access mechanism in mammalian multidrug resistance transporters and their bacterial homologs[J]. Membranes (Basel), 13(6): 568-599.
[25] Baumgard L H, Collier R J, Bauman D E.2017. A 100-year review: Regulation of nutrient partitioning to support lactation[J]. Journal of Dairy Science, 100(12): 10353-10366.
[26] Berg R D.1999. Bacterial translocation from the gastrointestinal tract[J]. Advances in Experimental Medicine and Biology, 473: 11-30.
[27] Che Y, Xu W, Ding C, et al.2023. Bile acids target mitofusin 2 to differentially regulate innate immunity in physiological versus cholestatic conditions[J]. Dynamic Cell Reprogramming, 42(1): 112011.
[28] Chen Y, Yuan C, Yang T, et al.2024. Effects of bile acid supplementation on lactation performance,nutrient intake, antioxidative status, and serum biochemistry in mid-lactation dairy cows[J]. Animals(Basel), 14(2): 290-301.
[29] Dai L, Liu Z, Guo L, et al.2023. Multi-tissue transcriptome study of innate immune gene expression profiling reveals negative energy balance altered the defense and promoted system inflammation of dairy cows[J]. Veterinary Sciences, 10(2): 107-124.
[30] Dicks L, Schuh-Von Graevenitz K, Prehn C, et al.2024a. Bile acid profiles and messenger RNA expression of bile acid-related genes in the liver of dairy cows with high versus normal body condition[J]. Journal of Dairy Science, 107(10): 8688-8708.
[31] Dicks L, Schuh-Von Graevenitz K, Prehn C, et al.2024b. Bile acid profiles and mRNA abundance of bile acid-related genes in adipose tissue of dairy cows with high versus normal body condition[J]. Journal of Dairy Science, 107(8): 6288-6307.
[32] Dong C, Liu S X, Zou B, et al.2025. Duodenal fluid analysis is an excellent differential diagnosis method of diseases with enterohepatic circulation disturbance[J]. Medicine (Baltimore), 104(7): e41469.
[33] Dong X, Qi M, Cai C, et al.2024. Farnesoid X receptor mediates macrophage-intrinsic responses to suppress colitis-induced colon cancer progression[J]. Journal of Clinical Investigation Insight, 9(2): e170428.
[34] Dowling R H.1973. The enterohepatic circulation of bile acids as they relate to lipid disorders[J]. Journal of Clinical Pathology (Association of Clinical Pathologists), 5: 59-67.
[35] Du Z, Luo Z, Huang Y, et al.2024. Screening for potential warning biomarkers in cows with ketosis based on host-microbiota co-metabolism analysis[J]. Frontiers in Cellular and Infection Microbiology, 15: 1373402.
[36] Fan F X, Wu F C, Guo Z Y, et al.2025. Supplementation with ursodeoxycholic acid and bile salt benefits lactation performance, health, and rumen and fecal microbiota of transition dairy cows[J]. Journal of Dairy Science, 108(6): 5982-5996.
[37] Fiorucci S, Marchianò S, Urbani G, et al.2024. Immunology of bile acids regulated receptors[J]. Progress in Lipid Research, 95: 101291.
[38] Francis M B, Allen C A, Shrestha R, et al.2013. Bile acid recognition by the clostridium difficile germinant receptor, CspC, is important for establishing infection[J]. Public Library of Science Pathogens, 9(5): e1003356.
[39] Geng W, Lin J.2016. Bacterial bile salt hydrolase: an intestinal microbiome target for enhanced animal health[J]. Animal Health Research Reviews, 17(2): 148-158.
[40] Gong T, Liu L, Jiang W, et al.2020. DAMP-sensing receptors in sterile inflammation and inflammatory diseases[J]. Nature Reviews Immunology, 20(2): 95-112.
[41] Guban J, Korver D R, Allison G E, et al.2006. Relationship of dietary antimicrobial drug administration with broiler performance, decreased population levels of Lactobacillus salivarius, and reduced bile salt deconjugation in the ileum of broiler chickens[J]. Poultry Science, 85(12): 2186-2194.
[42] Gu F, Zhu S, Tang Y, et al.2023. Gut microbiome is linked to functions of peripheral immune cells in transition cows during excessive lipolysis[J]. Microbiome, 11(1): 40-56.
[43] Guo C, Xie S, Chi Z, et al.2016. Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome[J]. Immunity, 45(4): 802-816.
[44] Hang S, Paik D, Yao L, et al.2019. Bile acid metabolites control T(H)17 and T(reg) cell differentiation[J]. Nature, 576(7785): 143-148.
[45] Hernández S B, Cota I, Ducret A, et al.2012. Adaptation and preadaptation of Salmonella enterica to Bile[J]. Public Library of Science Genetics, 8(1): e1002459.
[46] Hollenback D, Hambruch E, Fink G, et al.2024. Development of cilofexor, an intestinally-biased farnesoid X receptor agonist, for the treatment of fatty liver disease[J]. Journal of Pharmacology and Experimental Therapeutics, 389(1): 61-75.
[47] Joyce S A, O'malley D.2024. Regional and conditional variability of FXR: New lessons on ileal inflammation and gut barrier functions[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 327(5): G626-G628.
[48] Joyce S A, Shanahan F, Hill C, et al.2014. Bacterial bile salt hydrolase in host metabolism: Potential for influencing gastrointestinal microbe-host crosstalk[J]. Gut Microbes, 5(5): 669-674.
[49] Kong F, Wang S, Zhang Y, et al.2025. Alanine derived from Ruminococcus_E bovis alleviates energy metabolic disorders during the Peripartum Period by providing glucogenic precursors[J]. Research (Wash D C), 8: 0682-0698.
[50] Kreuder A J, Schleining J A, Yaeger M, et al.2017. RNAseq reveals complex response of Campylobacter jejuni to ovine bile and in vivo gallbladder environment[J]. Frontiers in Cellular and Infection Microbiology, 8: 940-959.
[51] Lam J H, Baumgarth N.2023. Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses[J]. Nature Communications, 14(1): 3979-3993.
[52] Li L, Li J, Liu Z, et al.2025. Effects of supplementing bile acids on the production performance, fatty acid and bile acid composition, and gut microbiota in transition dairy cows[J]. Journal of Animal Science and Biotechnology, 16(1): 83-101.
[53] Lin L, Lai Z, Yang H, et al.2023. Genome-centric investigation of bile acid metabolizing microbiota of dairy cows and associated diet-induced functional implications[J]. International Society for Microbial Ecology, 17(1): 172-184.
[54] Lun W, Yan Q, Guo X, et al.2024. Mechanism of action of the bile acid receptor TGR5 in obesity[J]. Acta Pharmaceutica Sinica B, 14(2): 468-491.
[55] Malik-Kale P, Parker C T, Konkel M E.2008. Culture of Campylobacter jejuni with sodium deoxycholate induces virulence gene expression[J]. Journal of Bacteriology, 190(7): 2286-2297.
[56] Mohammed T A, Zalzala M H.2025. Impact of nuclear receptors on the control of bile acid metabolism and synthesis: A comprehensive review[J]. Current Pharmacology Reports, 11(1): 25-33.
[57] Pabst O, Hornef M W, Schaap F G, et al.2023. Gut-liver axis: Barriers and functional circuits[J]. Nature Reviews Gastroenterology & Hepatology, 20(7): 447-461.
[58] Paul S, Alegre K O, Holdsworth S R, et al.2014. A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress[J]. Molecular Microbiology, 92(4): 872-884.
[59] Perino A, Velázquez-Villegas L A, Bresciani N, et al.2021. Central anorexigenic actions of bile acids are mediated by TGR5[J]. Nature Metabolism, 3(5): 595-603.
[60] Rivera-Cancel G, Orth K.2017. Biochemical basis for activation of virulence genes by bile salts in Vibrio parahaemolyticus[J]. Gut Microbes, 8(4): 366-373.
[61] Ridlon J M, Harris S C, Bhowmik S, et al.2016. Consequences of bile salt biotransformations by intestinal bacteria[J]. Gut Microbes, 7(1): 22-39.
[62] Ridlon J M, Kang D J, Hylemon P B.2006. Bile salt biotransformations by human intestinal bacteria[J]. Journal of Lipid Research, 47(2): 241-259.
[63] Sannasiddappa T H, Lund P A, Clarke S R.2017. In vitro antibacterial activity of unconjugated and conjugated bile salts on staphylococcus aureus[J]. Frontiers in Cellular and Infection Microbiology, 8: 1581-1592.
[64] Sawado R, Osawa R, Sobajima H, et al.2024. Analysis of the relationship between energy balance and properties of rumen fermentation of primiparous dairy cows during the perinatal period[J]. Animal Science Journal, 95(1): e13988.
[65] Sayin S I, Wahlström A, Felin J, et al.2013. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist[J]. Cell Metabolism, 17(2): 225-235.
[66] Setchell K D, Heubi J E, Shah S, et al.2013. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency[J]. Gastroenterology, 144(5): 945-955.
[67] Staniek J, Rizzi M.2025. Signaling activation and modulation in extrafollicular B cell responses[J]. Immunological Reviews, 330(1): e70004.
[68] Sun X, Zhu S, Tonnessen T I, et al.2021. Bile is a promising gut nutrient that inhibits intestinal bacterial translocation and promotes gut motility via an interleukin-6-related pathway in an animal model of endotoxemia[J]. Nutrition, 84: 111064.
[69] Thomas C, Gioiello A, Noriega L, et al.2009. TGR5-mediated bile acid sensing controls glucose homeostasis[J]. Cell Metabolism, 10(3): 167-177.
[70] Tomioka I, Ota C, Tanahashi Y, et al.2024. Loss of the DNA-binding domain of the farnesoid X receptor gene causes severe liver and kidney injuries[J]. Biochemical and Biophysical Research Communications, 721: 150125.
[71] Tschuck J, Theilacker L, Rothenaigner I, et al.2023. Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis[J]. Nature Communications, 14(1): 6908-6921.
[72] Wei M, Cao W B, Zhao R D, et al.2023. Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy[J]. World Journal of Gastroenterology, 29(21): 3280-3291.
[73] Winston J A, Theriot C M.2020. Diversification of host bile acids by members of the gut microbiota[J]. Gut Microbes, 11(2): 158-171.
[74] Won T H, Arifuzzaman M, Parkhurst C N, et al.2025. Host metabolism balances microbial regulation of bile acid signaling[J]. Nature, 638(8049): 216-624.
[75] Ye D, He J, He X.2024. The role of bile acid receptor TGR5 in regulating inflammatory signaling[J]. Scandinavian Journal of Immunology, 99(4): e13361.
[76] Zhang J, Gaowa N, Wang Y, et al.2023. Complementary hepatic metabolomics and proteomics reveal the adaptive mechanisms of dairy cows to the transition period[J]. Journal of Dairy Science, 106(3): 2071-2088.
[77] Zhang J, Zhang X, Liu H, et al.2024. Altered bile acid and correlations with gut microbiome in transition dairy cows with different glucose and lipid metabolism status[J]. Journal of Dairy Science, 107(11): 9915-9933.
[78] Zheng X, Chen T, Jiang R, et al.2021. Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism[J]. Cell Metabolism, 33(4): 791-803. e7.
[79] Zhang Y, Kast-Woelbern H R, Edwards P A.2003. Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation[J]. Journal of Biological Chemistry, 278(1): 104-110.
[80] Zhao H, Li L, Tan J, et al.2024. Multi-omics reveals disrupted immunometabolic homeostasis and oxidative stress in adipose tissue of dairy cows with subclinical ketosis: A sphingolipid-centric perspective[J]. Antioxidants (Basel), 13(5): 614-641.
[81] Zou A J, Kinch L, Chimalapati S, et al.2023. Molecular determinants for differential activation of the bile acid receptor from the pathogen Vibrio parahaemolyticus[J]. Journal of Biological Chemistry, 299(4): 104591. |
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