AIM： To study the relation between acoustic parameters and histological structure of biological tissue and to provide the basis for high-resolution image of biological tissues and quantitative ultrasonic diagnosis of...AIM： To study the relation between acoustic parameters and histological structure of biological tissue and to provide the basis for high-resolution image of biological tissues and quantitative ultrasonic diagnosis of liver disease. METHODS： Ultrasonic imaging and tissue characterization of four normal porcine liver and five cirrhotic liver tissue samples were performed using a high frequency imaging system. RESULTS： The acoustic parameters of cirrhotic liver tissue were larger than those of normal liver tissue. The sound velocity was 1577 m/s in normal liver tissue and 1631 m/s in cirrhotic liver tissue. At 35 MHz, the attenuation coefficient was 3.0 dB/mm in normal liver tissue and 4.1 dB/mm in cirrhotic liver tissue. The backscatter coefficient was 0.00431 dB/Srmm in cirrhotic liver tissue and 0.00303 dB/Srmm in normal liver tissue. The backscatter coefficient increased with the frequency. The high frequency images coincided with their histological features. CONCLUSION： The acoustic parameters, especially the sound backscatter coefficient, are sensitive to the changes of liver tissues and can be used to differentiate between the normal and pathological liver tissues. High frequency image system is a useful device for highresolution image and tissue characterization.展开更多
Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis.Here,we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arth...Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis.Here,we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis(RA).Among them,decreased expression of RNA binding motif protein 25(RBM25)was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages.Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes(including Il1b,Il6,and Cxcl10)was coupled with histone 3 lysine 9 acetylation(H3K9ac)and H3K27ac modifications as well as hypoxia inducible factor-1α(HIF-1α)activity.Furthermore,RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase(Acly)pre-mRNA,resulting in two distinct Acly isoforms,Acly Long(Acly L)and Acly Short(Acly S).In proinflammatory macrophages,Acly L was subjected to protein lactylation on lysine 918/995,whereas Acly S did not,which influenced its affinity for metabolic substrates and subsequent metabolic activity.RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform,enhancing glycolysis and acetyl-CoA production for epigenetic remodeling,macrophage overactivation and tissue inflammatory injury.Finally,macrophage-specific deletion of RBM25 led to inflammaging,including spontaneous arthritis in various joints of mice and inflammation in multiple organs,which could be relieved by pharmacological inhibition of Acly.Overall,targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.展开更多
基金Supported by the National Natural Science Foundation of China, No. 10204014
文摘AIM： To study the relation between acoustic parameters and histological structure of biological tissue and to provide the basis for high-resolution image of biological tissues and quantitative ultrasonic diagnosis of liver disease. METHODS： Ultrasonic imaging and tissue characterization of four normal porcine liver and five cirrhotic liver tissue samples were performed using a high frequency imaging system. RESULTS： The acoustic parameters of cirrhotic liver tissue were larger than those of normal liver tissue. The sound velocity was 1577 m/s in normal liver tissue and 1631 m/s in cirrhotic liver tissue. At 35 MHz, the attenuation coefficient was 3.0 dB/mm in normal liver tissue and 4.1 dB/mm in cirrhotic liver tissue. The backscatter coefficient was 0.00431 dB/Srmm in cirrhotic liver tissue and 0.00303 dB/Srmm in normal liver tissue. The backscatter coefficient increased with the frequency. The high frequency images coincided with their histological features. CONCLUSION： The acoustic parameters, especially the sound backscatter coefficient, are sensitive to the changes of liver tissues and can be used to differentiate between the normal and pathological liver tissues. High frequency image system is a useful device for highresolution image and tissue characterization.
基金supported by the National Key Research&Development Program of China(2023YFC2307302,2019YFA0801502,2023YFC2307001,2023YFC2307002)the National Natural Science Foundation of China(82071790,82070415,82271797,82341065,82371825,32400727,82201955)+1 种基金the program of Shanghai outstanding academic leader in public health subject(GWVI-11.2-XD29)the experimental animal program sponsored by the Science and Technology Commission of Shanghai Municipality(23141902300).
文摘Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis.Here,we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis(RA).Among them,decreased expression of RNA binding motif protein 25(RBM25)was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages.Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes(including Il1b,Il6,and Cxcl10)was coupled with histone 3 lysine 9 acetylation(H3K9ac)and H3K27ac modifications as well as hypoxia inducible factor-1α(HIF-1α)activity.Furthermore,RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase(Acly)pre-mRNA,resulting in two distinct Acly isoforms,Acly Long(Acly L)and Acly Short(Acly S).In proinflammatory macrophages,Acly L was subjected to protein lactylation on lysine 918/995,whereas Acly S did not,which influenced its affinity for metabolic substrates and subsequent metabolic activity.RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform,enhancing glycolysis and acetyl-CoA production for epigenetic remodeling,macrophage overactivation and tissue inflammatory injury.Finally,macrophage-specific deletion of RBM25 led to inflammaging,including spontaneous arthritis in various joints of mice and inflammation in multiple organs,which could be relieved by pharmacological inhibition of Acly.Overall,targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.
