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Evolution of sexual dimorphism in nonhuman primates.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-17 DOI: 10.1007/s11427-024-2796-3
Yuan-Ting Guo, Yijun Yang, Bolun Zhang, Hao Wu, Lei Wang, Baoguo Li, Christopher Opie, Xiao-Guang Qi
{"title":"Evolution of sexual dimorphism in nonhuman primates.","authors":"Yuan-Ting Guo, Yijun Yang, Bolun Zhang, Hao Wu, Lei Wang, Baoguo Li, Christopher Opie, Xiao-Guang Qi","doi":"10.1007/s11427-024-2796-3","DOIUrl":"https://doi.org/10.1007/s11427-024-2796-3","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic insights into the brooding reproduction and climate-driven dynamics of Pocillopora damicornis in the Anthropocene.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-17 DOI: 10.1007/s11427-024-2821-0
Jie Li, Yali Liu, Zhixin Zhang, Yu Chen, Jian Zhang, Haiyan Yu, Yingyi Zhang, Cong Liu, Zhuang Shao, David G Bourne, Meng Qu, Si Zhang, Qiang Lin
{"title":"Genomic insights into the brooding reproduction and climate-driven dynamics of Pocillopora damicornis in the Anthropocene.","authors":"Jie Li, Yali Liu, Zhixin Zhang, Yu Chen, Jian Zhang, Haiyan Yu, Yingyi Zhang, Cong Liu, Zhuang Shao, David G Bourne, Meng Qu, Si Zhang, Qiang Lin","doi":"10.1007/s11427-024-2821-0","DOIUrl":"https://doi.org/10.1007/s11427-024-2821-0","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The immuno-metabolic trade-off: a driver of metabolic disorders and aging.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-17 DOI: 10.1007/s11427-024-2881-8
Juanhong Liu, Qinlei Huang, Feng Liu
{"title":"The immuno-metabolic trade-off: a driver of metabolic disorders and aging.","authors":"Juanhong Liu, Qinlei Huang, Feng Liu","doi":"10.1007/s11427-024-2881-8","DOIUrl":"https://doi.org/10.1007/s11427-024-2881-8","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomedical data and AI.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-14 DOI: 10.1007/s11427-024-2859-1
Hao Xu, Shibo Zhou, Zefeng Zhu, Vincenzo Vitelli, Liangyi Chen, Ziwei Dai, Ning Yang, Luhua Lai, Shengyong Yang, Sergey Ovchinnikov, Zhuoran Qiao, Sirui Liu, Chen Song, Jianfeng Pei, Han Wen, Jianfeng Feng, Yaoyao Zhang, Zhengwei Xie, Yang-Yu Liu, Zhiyuan Li, Fulai Jin, Hao Li, Mohammad Lotfollahi, Xuegong Zhang, Ge Yang, Shihua Zhang, Ge Gao, Pulin Li, Qi Liu, Jing-Dong Jackie Han
{"title":"Biomedical data and AI.","authors":"Hao Xu, Shibo Zhou, Zefeng Zhu, Vincenzo Vitelli, Liangyi Chen, Ziwei Dai, Ning Yang, Luhua Lai, Shengyong Yang, Sergey Ovchinnikov, Zhuoran Qiao, Sirui Liu, Chen Song, Jianfeng Pei, Han Wen, Jianfeng Feng, Yaoyao Zhang, Zhengwei Xie, Yang-Yu Liu, Zhiyuan Li, Fulai Jin, Hao Li, Mohammad Lotfollahi, Xuegong Zhang, Ge Yang, Shihua Zhang, Ge Gao, Pulin Li, Qi Liu, Jing-Dong Jackie Han","doi":"10.1007/s11427-024-2859-1","DOIUrl":"https://doi.org/10.1007/s11427-024-2859-1","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A tango between NSUN2 and TET2: defining both the fate and origin of RNA.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-12 DOI: 10.1007/s11427-024-2862-x
Tianbao Shang, Lu Liu, Zitan Li, Yichi Xu, Yujiang Geno Shi, Li Tan
{"title":"A tango between NSUN2 and TET2: defining both the fate and origin of RNA.","authors":"Tianbao Shang, Lu Liu, Zitan Li, Yichi Xu, Yujiang Geno Shi, Li Tan","doi":"10.1007/s11427-024-2862-x","DOIUrl":"https://doi.org/10.1007/s11427-024-2862-x","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vibration mechanics involved in buzz pollination lead to size-dependent associations between bumblebees and Pedicularis flowers.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-12 DOI: 10.1007/s11427-024-2858-5
Yuanqing Xu, Bentao Wu, Mario Vallejo-Marín, Peter Bernhardt, Mark Jankauski, De-Zhu Li, Stephen Buchmann, Jianing Wu, Hong Wang

Floral traits modify pollinator behavior and shape the plant-pollinator interaction pattern at ecological and evolutionary levels. Biomechanical traits are important in mediating interactions between flowers and their pollinators in some cases, such as in buzz pollination. During buzz pollination, a bee produces vibrations using its thoracic muscles and transfers these vibrations primarily through its mandibles as it bites the flower. The interaction between buzz-pollinated flowers and their pollinators is influenced by their physical size relative to each other, but the drivers of these size-dependent associations remain unclear. Using eight beaked louseworts (Pedicularis) as a model system, we combined behavioral observations, biomechanical analyses, and pollinator network analyses to test the hypothesis that the location of where a bee bites should constrain the interaction between Pedicularis and bumblebees during buzz pollination. We found that bumblebees always chose to bite the same site at the base of the floral beak when buzzing Pedicularis, and this site is optimal for transferring vibrations from the bee to release pollen from the anthers. Bee bodies must be long enough for the mandibles to clamp onto the same optimal site on the floral beak, while its pollen-collecting abdomen is positioned at the opening of the floral beak where pollen grains are ejected. Our pollination networks showed size matching between the floral beak length of each Pedicularis species and the body length of individual bumblebees regardless of bee species. These results suggest that the optimal excitation point on the Pedicularis flower links a suite of floral traits to its pollinators' dimensions, potentially contributing to prezygotic isolation among co-flowering, sympatric Pedicularis species.

{"title":"Vibration mechanics involved in buzz pollination lead to size-dependent associations between bumblebees and Pedicularis flowers.","authors":"Yuanqing Xu, Bentao Wu, Mario Vallejo-Marín, Peter Bernhardt, Mark Jankauski, De-Zhu Li, Stephen Buchmann, Jianing Wu, Hong Wang","doi":"10.1007/s11427-024-2858-5","DOIUrl":"https://doi.org/10.1007/s11427-024-2858-5","url":null,"abstract":"<p><p>Floral traits modify pollinator behavior and shape the plant-pollinator interaction pattern at ecological and evolutionary levels. Biomechanical traits are important in mediating interactions between flowers and their pollinators in some cases, such as in buzz pollination. During buzz pollination, a bee produces vibrations using its thoracic muscles and transfers these vibrations primarily through its mandibles as it bites the flower. The interaction between buzz-pollinated flowers and their pollinators is influenced by their physical size relative to each other, but the drivers of these size-dependent associations remain unclear. Using eight beaked louseworts (Pedicularis) as a model system, we combined behavioral observations, biomechanical analyses, and pollinator network analyses to test the hypothesis that the location of where a bee bites should constrain the interaction between Pedicularis and bumblebees during buzz pollination. We found that bumblebees always chose to bite the same site at the base of the floral beak when buzzing Pedicularis, and this site is optimal for transferring vibrations from the bee to release pollen from the anthers. Bee bodies must be long enough for the mandibles to clamp onto the same optimal site on the floral beak, while its pollen-collecting abdomen is positioned at the opening of the floral beak where pollen grains are ejected. Our pollination networks showed size matching between the floral beak length of each Pedicularis species and the body length of individual bumblebees regardless of bee species. These results suggest that the optimal excitation point on the Pedicularis flower links a suite of floral traits to its pollinators' dimensions, potentially contributing to prezygotic isolation among co-flowering, sympatric Pedicularis species.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Low-dose lactate promotes neuroinflammation and induces the side effect of colitis.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-12 DOI: 10.1007/s11427-024-2879-6
Weiyan Wang, Mengdi Guo, Chuyu Wu, Bin Huang, Mei-Ling Jiang, Cun-Jin Zhang
{"title":"Low-dose lactate promotes neuroinflammation and induces the side effect of colitis.","authors":"Weiyan Wang, Mengdi Guo, Chuyu Wu, Bin Huang, Mei-Ling Jiang, Cun-Jin Zhang","doi":"10.1007/s11427-024-2879-6","DOIUrl":"https://doi.org/10.1007/s11427-024-2879-6","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic WNT signaling controls differentiation of hematopoietic progenitor cells from human pluripotent stem cells.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-11 DOI: 10.1007/s11427-024-2816-0
Mo Li, Keiichiro Suzuki, Mengge Wang, Christopher Benner, Manching Ku, Li Ma, Ladan Kobari, Na Young Kim, Nuria Montserrat, Chan-Jung Chang, Guanghui Liu, Jing Qu, Jinna Xu, Yingzi Zhang, Emi Aizawa, Jun Wu, Luc Douay, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte

Human pluripotent stem cells (hPSCs) can in theory give rise to any hematopoietic lineages, thereby offering opportunities for disease modeling, drug screening and cell therapies. However, gaps in our knowledge of the signaling requirements for the specification of human hematopoietic stem/progenitor cells (HSPCs), which lie at the apex of all hematopoietic lineages, greatly limit the potential of hPSC in hematological research and application. Transcriptomic analysis reveals aberrant regulation of WNT signaling during maturation of hPSC-derived hematopoietic progenitor cells (hPSC-HPCs), which results in higher mitochondria activity, misregulation of HOX genes, loss of self-renewal and precocious differentiation. These defects are partly due to the activation of the WNT target gene CDX2. Late-stage WNT inhibition improves the yield, self-renewal, multilineage differentiation, and transcriptional and metabolic profiles of hPSC-HPCs. Genome-wide mapping of transcription factor (TF) accessible chromatin reveals a significant overrepresentation of myeloid TF binding motifs in hPSC-HPCs, which could underlie their myeloid-biased lineage potential. Together our findings uncover a previously unappreciated dynamic requirement of the WNT signaling pathway during the specification of human HSPCs. Modulating the WNT pathway with small molecules normalizes the molecular differences between hPSC-HPCs and endogenous hematopoietic stem cells (HSCs), thereby representing a promising approach to improve the differentiation and function of hPSC-HPCs.

{"title":"Dynamic WNT signaling controls differentiation of hematopoietic progenitor cells from human pluripotent stem cells.","authors":"Mo Li, Keiichiro Suzuki, Mengge Wang, Christopher Benner, Manching Ku, Li Ma, Ladan Kobari, Na Young Kim, Nuria Montserrat, Chan-Jung Chang, Guanghui Liu, Jing Qu, Jinna Xu, Yingzi Zhang, Emi Aizawa, Jun Wu, Luc Douay, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte","doi":"10.1007/s11427-024-2816-0","DOIUrl":"https://doi.org/10.1007/s11427-024-2816-0","url":null,"abstract":"<p><p>Human pluripotent stem cells (hPSCs) can in theory give rise to any hematopoietic lineages, thereby offering opportunities for disease modeling, drug screening and cell therapies. However, gaps in our knowledge of the signaling requirements for the specification of human hematopoietic stem/progenitor cells (HSPCs), which lie at the apex of all hematopoietic lineages, greatly limit the potential of hPSC in hematological research and application. Transcriptomic analysis reveals aberrant regulation of WNT signaling during maturation of hPSC-derived hematopoietic progenitor cells (hPSC-HPCs), which results in higher mitochondria activity, misregulation of HOX genes, loss of self-renewal and precocious differentiation. These defects are partly due to the activation of the WNT target gene CDX2. Late-stage WNT inhibition improves the yield, self-renewal, multilineage differentiation, and transcriptional and metabolic profiles of hPSC-HPCs. Genome-wide mapping of transcription factor (TF) accessible chromatin reveals a significant overrepresentation of myeloid TF binding motifs in hPSC-HPCs, which could underlie their myeloid-biased lineage potential. Together our findings uncover a previously unappreciated dynamic requirement of the WNT signaling pathway during the specification of human HSPCs. Modulating the WNT pathway with small molecules normalizes the molecular differences between hPSC-HPCs and endogenous hematopoietic stem cells (HSCs), thereby representing a promising approach to improve the differentiation and function of hPSC-HPCs.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Root exudates and microbial metabolites: signals and nutrients in plant-microbe interactions.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-11 DOI: 10.1007/s11427-024-2876-0
Xiaoyan Fan, An-Hui Ge, Shanshan Qi, Yuefeng Guan, Ran Wang, Nan Yu, Ertao Wang

Plant roots meticulously select and attract particular microbial taxa from the surrounding bulk soil, thereby establishing a specialized and functionally diverse microbial community within the rhizosphere. Rhizosphere metabolites, including root exudates and microbial metabolites, function as both signals and nutrients that govern the assembly of the rhizosphere microbiome, playing crucial roles in mediating communications between plants and microbes. The environment and their feedback loops further influence these intricate interactions. However, whether and how specific metabolites shape plant-microbe interactions and facilitate diverse functions remains obscure. This review summarizes the current progress in plant-microbe communications mediated by chemical compounds and their functions in plant fitness and ecosystem functioning. Additionally, we raise some prospects on future directions for manipulating metabolite-mediated plant-microbe interactions to enhance crop productivity and health. Unveiling the biological roles of specific metabolites produced by plants and microbes will bridge the gap between fundamental research and practical applications.

植物根系从周围的大块土壤中精心选择并吸引特定的微生物类群,从而在根瘤菌圈内建立起一个专门的、功能多样的微生物群落。根圈代谢物,包括根系渗出物和微生物代谢物,既是信号也是营养物质,它们控制着根圈微生物群的组合,在植物和微生物之间的沟通中发挥着关键作用。环境及其反馈回路进一步影响着这些错综复杂的相互作用。然而,特定代谢物是否以及如何影响植物与微生物之间的相互作用并促进多种功能的发挥,目前仍不清楚。本综述总结了目前在由化合物介导的植物-微生物交流及其在植物适应性和生态系统功能中的作用方面取得的进展。此外,我们还展望了操纵代谢物介导的植物-微生物相互作用以提高作物生产力和健康的未来方向。揭示植物和微生物产生的特定代谢物的生物学作用,将在基础研究和实际应用之间架起一座桥梁。
{"title":"Root exudates and microbial metabolites: signals and nutrients in plant-microbe interactions.","authors":"Xiaoyan Fan, An-Hui Ge, Shanshan Qi, Yuefeng Guan, Ran Wang, Nan Yu, Ertao Wang","doi":"10.1007/s11427-024-2876-0","DOIUrl":"https://doi.org/10.1007/s11427-024-2876-0","url":null,"abstract":"<p><p>Plant roots meticulously select and attract particular microbial taxa from the surrounding bulk soil, thereby establishing a specialized and functionally diverse microbial community within the rhizosphere. Rhizosphere metabolites, including root exudates and microbial metabolites, function as both signals and nutrients that govern the assembly of the rhizosphere microbiome, playing crucial roles in mediating communications between plants and microbes. The environment and their feedback loops further influence these intricate interactions. However, whether and how specific metabolites shape plant-microbe interactions and facilitate diverse functions remains obscure. This review summarizes the current progress in plant-microbe communications mediated by chemical compounds and their functions in plant fitness and ecosystem functioning. Additionally, we raise some prospects on future directions for manipulating metabolite-mediated plant-microbe interactions to enhance crop productivity and health. Unveiling the biological roles of specific metabolites produced by plants and microbes will bridge the gap between fundamental research and practical applications.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel deacetylase inhibitor KLX suppresses liver fibrosis by deacetylating PPARγ through promoting ubiquitination-mediated HDAC1 degradation.
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2025-03-07 DOI: 10.1007/s11427-024-2827-y
Feng Zhang, Jinglun Song, Han Wu, Keying Lin, Chunlei Wang, Linghua Zeng, Xue Kong, Kunkun Zou, Hongtao Diao, Zhuo Wang, Wei Si, Weitao Jiang, Yang Yang, Fangting Yao, Xinyue Zhang, Yuting Xiong, Qiaoyue Zhao, Tianqi Duo, Jiaming Ju, Tengfei Pan, Baofeng Yang, Yu Bian

Liver fibrosis is a pathological response following liver injury induced by various etiologies. Herein, we present the therapeutic potential of a novel anthraquinone compound, kanglexin (KLX), in the treatment of liver fibrosis. We observed significant suppression of the inflammatory response and extracellular matrix deposition in mice with liver fibrosis induced by CCL4, by bile duct ligation, and by a methionine-choline-deficient diet. Mechanistically, through screening, we found that KLX interacts with HDAC1. Additionally, KLX facilitates binding between HDAC1 and KCTD11, promoting the ubiquitination-mediated degradation of HDAC1 and consequently reducing its protein level. Moreover, HDAC1 was found to bind to PPARγ, influencing its acetylation level. Following KLX treatment, the level of PPARγ deacetylation mediated by HDAC1 decreases, leading to increased protein expression of PPARγ. This effectively inhibited the NFκB and TGF-β/Smad2/3 signaling pathways, thereby reducing inflammation and extracellular matrix deposition. Ultimately, this intervention can halt the progression of liver fibrosis and ameliorate liver damage. In summary, our study demonstrated that KLX can effectively inhibit the progression of liver fibrosis by modulating the protein level and activity of HDAC1. These findings provide valuable insights for the development of effective drugs and treatment strategies for liver fibrosis.

{"title":"A novel deacetylase inhibitor KLX suppresses liver fibrosis by deacetylating PPARγ through promoting ubiquitination-mediated HDAC1 degradation.","authors":"Feng Zhang, Jinglun Song, Han Wu, Keying Lin, Chunlei Wang, Linghua Zeng, Xue Kong, Kunkun Zou, Hongtao Diao, Zhuo Wang, Wei Si, Weitao Jiang, Yang Yang, Fangting Yao, Xinyue Zhang, Yuting Xiong, Qiaoyue Zhao, Tianqi Duo, Jiaming Ju, Tengfei Pan, Baofeng Yang, Yu Bian","doi":"10.1007/s11427-024-2827-y","DOIUrl":"https://doi.org/10.1007/s11427-024-2827-y","url":null,"abstract":"<p><p>Liver fibrosis is a pathological response following liver injury induced by various etiologies. Herein, we present the therapeutic potential of a novel anthraquinone compound, kanglexin (KLX), in the treatment of liver fibrosis. We observed significant suppression of the inflammatory response and extracellular matrix deposition in mice with liver fibrosis induced by CCL<sub>4</sub>, by bile duct ligation, and by a methionine-choline-deficient diet. Mechanistically, through screening, we found that KLX interacts with HDAC1. Additionally, KLX facilitates binding between HDAC1 and KCTD11, promoting the ubiquitination-mediated degradation of HDAC1 and consequently reducing its protein level. Moreover, HDAC1 was found to bind to PPARγ, influencing its acetylation level. Following KLX treatment, the level of PPARγ deacetylation mediated by HDAC1 decreases, leading to increased protein expression of PPARγ. This effectively inhibited the NFκB and TGF-β/Smad2/3 signaling pathways, thereby reducing inflammation and extracellular matrix deposition. Ultimately, this intervention can halt the progression of liver fibrosis and ameliorate liver damage. In summary, our study demonstrated that KLX can effectively inhibit the progression of liver fibrosis by modulating the protein level and activity of HDAC1. These findings provide valuable insights for the development of effective drugs and treatment strategies for liver fibrosis.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":8.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Science China Life Sciences
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