Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological dis...Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.展开更多
We studied the performance of AlGaN/GaN double heterojunction high electron mobility transistors （DH-HEMTs） with an AlGaN buffer layer, which leads to a higher potential barrier at the backside of the two- dimension...We studied the performance of AlGaN/GaN double heterojunction high electron mobility transistors （DH-HEMTs） with an AlGaN buffer layer, which leads to a higher potential barrier at the backside of the two- dimensional electron gas channel and better carrier confinement. This, remarkably, reduces the drain leakage current and improves the device breakdown voltage. The breakdown voltage of AlGaN/GaN double heterojunction HEMTs （-100 V） was significantly improved compared to that of conventional AlGaN/GaN HEMTs （-50 V） for the device with gate dimensions of 0.5 - 100μm and a gate-drain distance of 1μm. The DH-HEMTs also demonstrated a maximum output power of 7.78 W/mm, a maximum power-added efficiency of 62.3% and a linear gain of 23 dB at the drain supply voltage of 35 V at 4 GHz.展开更多
Chuanxiong Rhizoma(CX,the dried rhizome of Ligusticum wallichii Franch.),a well-known traditional Chinese medicine,is clinically used for treating cardiovascular,cerebrovascular and hepatobiliary diseases.Cholestatic ...Chuanxiong Rhizoma(CX,the dried rhizome of Ligusticum wallichii Franch.),a well-known traditional Chinese medicine,is clinically used for treating cardiovascular,cerebrovascular and hepatobiliary diseases.Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies.Currently,little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells(HSCs).The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous,alkaloid,phenolic acid and phthalide extracts of CX(CX_(AE),CX_(AL),CX_(PA)and CX_(PHL))and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury.The active compounds of different CX extracts were identified by UPLC-MS/MS.A cholestatic liver injury mouse model induced by bile duct ligation(BDL),and transforming growth factor-β(TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes(HIBECs)and HSC cell line(LX-2 cells)were used for in vivo and in vitro studies.Histological and other biological techniques were also applied.The results indicated that CX_(AE),CX_(AL)and CX_(PHL)significantly reduced ductular reaction(DR)and improved liver fibrosis in the BDL mice.Meanwhile,both CX_(AE)and CX_(PHL)suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β.CX_(PHL)suppressed the transcription and transfer of plasminogen activator inhibitor-1(PAI-1)and fibronectin(FN)from the‘DR-like’cholangiocytes to activated HSCs.Mechanistically,the inhibition of PAI-1 and FN by CX_(PHL)was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3,followdd by the suppression of histone 3 lysine 9 acetylation(H3K9ac)-mediated transcription in cholangiocytes.In conclusion,CX_(PHL)exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts,and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.82004045)the National High-Level Talents Special Support Program,the Fundamental Research Funds for the Central Universities(No.2023-JYB-XJSJJ009)+1 种基金the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202006)the Young Talents Promotion Project of China Association of Traditional Chinese Medicine(No.2020-QNRC2-01).
文摘Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
基金Project Supported by the National science and Technology Major Project of thc Ministry of Science and Technology of China(No. 2008ZX01002-002)the Major Program and the Key Program of the National Natural science Foundation of China(Nos.60890191, 60736033)
文摘We studied the performance of AlGaN/GaN double heterojunction high electron mobility transistors （DH-HEMTs） with an AlGaN buffer layer, which leads to a higher potential barrier at the backside of the two- dimensional electron gas channel and better carrier confinement. This, remarkably, reduces the drain leakage current and improves the device breakdown voltage. The breakdown voltage of AlGaN/GaN double heterojunction HEMTs （-100 V） was significantly improved compared to that of conventional AlGaN/GaN HEMTs （-50 V） for the device with gate dimensions of 0.5 - 100μm and a gate-drain distance of 1μm. The DH-HEMTs also demonstrated a maximum output power of 7.78 W/mm, a maximum power-added efficiency of 62.3% and a linear gain of 23 dB at the drain supply voltage of 35 V at 4 GHz.
基金the Beijing Municipal Science&Technology Commission(No.7212174)the National High-Level Talents Special Support Program to XL,the National Natural Science Foundation of China(Nos.82274186 and 82004045)+1 种基金National Key Research and Development Program on Modernization of Traditional Chinese Medicine(No.2022YFC-3502100)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202006).
文摘Chuanxiong Rhizoma(CX,the dried rhizome of Ligusticum wallichii Franch.),a well-known traditional Chinese medicine,is clinically used for treating cardiovascular,cerebrovascular and hepatobiliary diseases.Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies.Currently,little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells(HSCs).The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous,alkaloid,phenolic acid and phthalide extracts of CX(CX_(AE),CX_(AL),CX_(PA)and CX_(PHL))and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury.The active compounds of different CX extracts were identified by UPLC-MS/MS.A cholestatic liver injury mouse model induced by bile duct ligation(BDL),and transforming growth factor-β(TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes(HIBECs)and HSC cell line(LX-2 cells)were used for in vivo and in vitro studies.Histological and other biological techniques were also applied.The results indicated that CX_(AE),CX_(AL)and CX_(PHL)significantly reduced ductular reaction(DR)and improved liver fibrosis in the BDL mice.Meanwhile,both CX_(AE)and CX_(PHL)suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β.CX_(PHL)suppressed the transcription and transfer of plasminogen activator inhibitor-1(PAI-1)and fibronectin(FN)from the‘DR-like’cholangiocytes to activated HSCs.Mechanistically,the inhibition of PAI-1 and FN by CX_(PHL)was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3,followdd by the suppression of histone 3 lysine 9 acetylation(H3K9ac)-mediated transcription in cholangiocytes.In conclusion,CX_(PHL)exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts,and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.
