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2篇 您的检索式:作者名="Xiuting Lan"
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1Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease显示文摘Metabolic-associated fatty liver disease(MAFLD),which is previously known as non-alcoholic fatty liver disease(NAFLD),represents a major health concern worldwide with limited therapy.Here,we provide evidence that ferroptosis,a novel form of regulated cell death characterized by iron-driven lipid peroxidation,was comprehensively activated in liver tissues from MAFLD patients.The canonical-GPX4(cGPX4),which is the most important negative controller of ferroptosis,is downregulated at protein but not mRNA level.Interestingly,a non-canonical GPX4 transcript-variant is induced(inducible-GPX4,iGPX4)in MAFLD condition.The high fat-fructose/sucrose diet(HFFD)and methionine/choline-deficient diet(MCD)-induced MAFLD pathologies,including hepatocellular ballooning,steatohepatitis andfibrosis,were attenuated and aggravated,respectively,in cGPX4-and iGPX4-knockin mice.cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes.Knockdown of iGPX4 by siRNA alleviated lipid stress,ferroptosis and cell injury.Mechanistically,the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress,and thus promotes ferroptosis.Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4.Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis,and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.Jie Tong Dongjie Li Hongbo Meng Diyang Sun Xiuting Lan Min Ni Jiawei Ma Feiyan Zeng Sijia Sun Jiangtao Fu Guoqiang Li Qingxin Ji Guoyan Zhang Qirui Shen Yuanyuan Wang Jiahui Zhu Yi Zhao Xujie Wang Yi Liu Shenxi Ouyang Chunquan Sheng Fuming Shen Pei Wang 2022Acta Pharmaceutica Sinica B2022,12,9:3
2A near-complete genome assembly of the allotetrapolyploid Cenchrus fungigraminus(JUJUNCAO)provides insights into its evolution and C4 photosynthesis显示文摘JUJUNCAO(Cenchrus fungigraminus;2n=4x=28)is a Cenchrus grass with the highest biomass production among cultivated plants,and it can be used for mushroom cultivation,animal feed,and biofuel production.Here,we report a nearly complete genome assembly of JUJUNCAO and reveal that JUJUNCAO is an allopolyploid that originated2.7 million years ago(mya).Its genome consists of two subgenomes,and subgenome A shares high collinear synteny with pearl millet.We also investigated the genome evolution of JUJUNCAO and suggest that the ancestral karyotype of Cenchrus split into the A and B ancestral karyotypes of JUJUNCAO.Comparative transcriptome and DNA methylome analyses revealed functional divergence of homeologous gene pairs between the two subgenomes,which was a further indication of asymmetric DNA methylation.The three types of centromeric repeat in the JUJUNCAO genome(CEN137,CEN148,and CEN156)may have evolved independently within each subgenome,with some introgressions of CEN156 from the B to the A subgenome.We investigated the photosynthetic characteristics of JUJUNCAO,revealing its typical C4 Kranz anatomy and high photosynthetic efficiency.NADP-ME and PEPCK appear to cooperate in the major C4 decarboxylation reaction of JUJUNCAO,which is different from other C4 photosynthetic subtypes and may contribute to its high photosynthetic efficiency and biomass yield.Taken together,our results provide insights into the highly efficient photosynthetic mechanism of JUJUNCAO and provide a valuable reference genome for future genetic and evolutionary studies,as well as genetic improvement of Cenchrus grasses.Huakun Zheng Baiyu Wang Xiuting Hua Ruiting Gao Yuhao Wang Zixin Zhang Yixing Zhang Jing Mei Yongji Huang Yumin Huang Hui Lin Xingtan Zhang Dongmei Lin Siren Lan Zhongjian Liu Guodong Lu Zonghua Wang Ray Ming Jisen Zhang Zhanxi Lin 2023Plant Communications2023,4,5:1
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