A Good Man Is Hard to Find is a famous fiction which attracts many scholars to analyze the characters of the protagonists. According to Booth's rhetorical theory, it tries to analyze how the rhetorical skills infl...A Good Man Is Hard to Find is a famous fiction which attracts many scholars to analyze the characters of the protagonists. According to Booth's rhetorical theory, it tries to analyze how the rhetorical skills influence the readers'interpretation to the work by analyzing the application of narrative visual conversion, irony and foreshadowing. It will help readers understand the full fiction better.展开更多
Tumor metabolism often interferes with the immune microenvironment.Although natural killer(NK)cells play pivotal roles in antitumor immunity,the connection between NK cells and tumor metabolism remains unclear.Our sys...Tumor metabolism often interferes with the immune microenvironment.Although natural killer(NK)cells play pivotal roles in antitumor immunity,the connection between NK cells and tumor metabolism remains unclear.Our systematic analysis of multiomics data and survival data from colorectal cancer(CRC)patients uncovered a novel association between mitochondrial acetyl-CoA acetyltransferase 1(ACAT1)and NK cell infiltration that influences disease progression.ACAT1,a metabolic enzyme involved in reversible conversion of acetoacetyl-CoA to two molecules of acetyl-CoA,exhibits nuclear protein acetylation activity through its translocation.Under immune stimulation,mitochondrial ACAT1 can be phosphorylated at serine 60(S60)and enters the nucleus;however,this process is hindered in nutrient-poor tumor microenvironments.Nuclear ACAT1 directly acetylates lysine 146 of p50(NFKB1),attenuating its DNA binding and transcriptional repression activity and thereby increasing the expression of immune-related factors,which in turn promotes NK cell recruitment and activation to suppress colorectal cancer growth.Furthermore,significant associations are found among low nuclear ACAT1 levels,decreased S60 phosphorylation,and reduced NK cell infiltration,as well as poor prognosis in CRC.Our findings reveal an unexpected function of ACAT1 as a nuclear acetyltransferase and elucidate its role in NK cell-dependent antitumor immunity through p50 acetylation.展开更多
文摘A Good Man Is Hard to Find is a famous fiction which attracts many scholars to analyze the characters of the protagonists. According to Booth's rhetorical theory, it tries to analyze how the rhetorical skills influence the readers'interpretation to the work by analyzing the application of narrative visual conversion, irony and foreshadowing. It will help readers understand the full fiction better.
基金supported by the National Key R&D Program of China(2023YFC3402100)National Natural Science Foundation of China(82273241,82303224,82372826)+2 种基金Guangdong Basic and Applied Basic Research Foundation(SL2023A04J01630)Sanming Project of Medicine in Shenzhen(SZSM202211017)Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004).
文摘Tumor metabolism often interferes with the immune microenvironment.Although natural killer(NK)cells play pivotal roles in antitumor immunity,the connection between NK cells and tumor metabolism remains unclear.Our systematic analysis of multiomics data and survival data from colorectal cancer(CRC)patients uncovered a novel association between mitochondrial acetyl-CoA acetyltransferase 1(ACAT1)and NK cell infiltration that influences disease progression.ACAT1,a metabolic enzyme involved in reversible conversion of acetoacetyl-CoA to two molecules of acetyl-CoA,exhibits nuclear protein acetylation activity through its translocation.Under immune stimulation,mitochondrial ACAT1 can be phosphorylated at serine 60(S60)and enters the nucleus;however,this process is hindered in nutrient-poor tumor microenvironments.Nuclear ACAT1 directly acetylates lysine 146 of p50(NFKB1),attenuating its DNA binding and transcriptional repression activity and thereby increasing the expression of immune-related factors,which in turn promotes NK cell recruitment and activation to suppress colorectal cancer growth.Furthermore,significant associations are found among low nuclear ACAT1 levels,decreased S60 phosphorylation,and reduced NK cell infiltration,as well as poor prognosis in CRC.Our findings reveal an unexpected function of ACAT1 as a nuclear acetyltransferase and elucidate its role in NK cell-dependent antitumor immunity through p50 acetylation.
