Oxidative stress plays an essential role in regulating growth and death of cardiac myocytes. ClassⅡhistone deacetylases（cⅡ-HDACs） are localized primarily in the nucleus in unstimulated cardiac myocytes and negativ...Oxidative stress plays an essential role in regulating growth and death of cardiac myocytes. ClassⅡhistone deacetylases（cⅡ-HDACs） are localized primarily in the nucleus in unstimulated cardiac myocytes and negatively regulate cardiac hypertrophy by interacting with pro-hypertrophic transcription factors,including myocyte enhancer factor 2（MEF2）,calmodulin-binding transcription activator （CAMTA）,and nuclear factor activated T cells （NFATs）.Nuclear localization of cII-HDACs is regulated not only by phosphorylation but also through oxidation of conserved cysteine residues（Ago et al 2007）,suggesting that posttranslational modulation plays an important role in mediating pathological cardiac hypertrophy and heart failure. In this presentation,I will discuss how reactive oxygen species（ROS） are produced in the heart under stress and how ROS regulate the subcellular localization of cII-HDACs,thereby causing pathological hypertrophy.The NADPH oxidase family is a group of transmembrane proteins producing superoxide and hydrogen peroxide.Nox4 is localized primarily in mitochondria,endoplasmic reticulum,and nucleus, whose expression is upregulated by pressure overload and heart failure.Nox4 plays an essential role in mediating increases in ROS in the failing heart.Increased oxidative stress induces oxidation of cysteine resides in cⅡ-HDACs,such as C667 and C669 in HDAC4,which in turn causes nuclear exit of cⅡ-HDACs.The cⅡ-HDACs are further phospho-rylated by the HDAC kinases,including Ca<sup>2+</sup> calmodulin kinase and PKD,leading to prolonged cytoplasmic localization of cⅡ-HDACs and consequent cardiac hypertrophy.Thioredoxin 1（Trx1）,an anti-oxidant, reduces the critical cysteine residues in cⅡ-HDACs, thereby restoring the nuclear localization of cⅡ-HDACs and inhibiting pathological hypertrophy. Downregulation of Nox4 enhances nuclear localization of HDAC4,thereby inhibiting cardiac hypertrophy, suggesting that endogenous Nox4 mediates oxidation of HDAC4. In summary,oxidative stress plays an important role in regulating the subcellular localization of cⅡ-HDACs, critical regulators of pathological cardiac hypertrophy.Nox4 is upregulated in response to cardiac hypertrophy and heart failure,thereby playing a major role in mediating oxidative stress in the failing heart.Both Trxl and Nox4 play an essential role in regulating the oxidation status of cⅡ-HDACs, thereby critically regulating pathological hypertrophy and heart failure.I will also discuss pharmacological interventions targeting phosphorylation and/or oxidation of cⅡ-HDACs,which may be effective in treating pathological hypertrophy and heart failure in patients.展开更多
We present a study on the single event transient （SET） induced by a pulsed laser in different silicon-germanium （SiGe） heterojunction bipolar transistors （HBTs） with the structure of local oxidation of silicon ...We present a study on the single event transient （SET） induced by a pulsed laser in different silicon-germanium （SiGe） heterojunction bipolar transistors （HBTs） with the structure of local oxidation of silicon （LOCOS） and deep trench isolation （DTI）. The experimental results are discussed in detail and it is demonstrated that a SiGe HBT with the structure of LOCOS is more sensitive than the DTI SiGe HBT in the SET. Because of the limitation of the DTI structure, the charge collection of diffusion in the DTI SiGe HBT is less than that of the LOCOS SiGe HBT. The SET sensitive area of the LOCOS SiGe HBT is located in the eollector-substrate （C/S） junction, while the sensitive area of the DTI SiGe HBT is located near to the collector electrodes.展开更多
The mechanism of single-event gate-rupture in an N-channel VDMOS in a space radiation environment was analyzed. Based on the mechanism, a novel structure of VDMOS for improving single-event gate-rupture is proposed, a...The mechanism of single-event gate-rupture in an N-channel VDMOS in a space radiation environment was analyzed. Based on the mechanism, a novel structure of VDMOS for improving single-event gate-rupture is proposed, and the structure is simulated and it is demonstrated that it can improve a VDMOS SEGR threshold voltage by 120%. With this structure, the specific on-resistance value of a VDMOS is reduced by 15.5% as the breakdown voltage almost maintains the same value. As only one mask added, which is local oxidation of silicon instead of an active processing area, the new structure VDMOS it is easily fabricated. The novel structure can be widely used in high-voltage VDMOS in a space radiation environment.展开更多
文摘Oxidative stress plays an essential role in regulating growth and death of cardiac myocytes. ClassⅡhistone deacetylases（cⅡ-HDACs） are localized primarily in the nucleus in unstimulated cardiac myocytes and negatively regulate cardiac hypertrophy by interacting with pro-hypertrophic transcription factors,including myocyte enhancer factor 2（MEF2）,calmodulin-binding transcription activator （CAMTA）,and nuclear factor activated T cells （NFATs）.Nuclear localization of cII-HDACs is regulated not only by phosphorylation but also through oxidation of conserved cysteine residues（Ago et al 2007）,suggesting that posttranslational modulation plays an important role in mediating pathological cardiac hypertrophy and heart failure. In this presentation,I will discuss how reactive oxygen species（ROS） are produced in the heart under stress and how ROS regulate the subcellular localization of cII-HDACs,thereby causing pathological hypertrophy.The NADPH oxidase family is a group of transmembrane proteins producing superoxide and hydrogen peroxide.Nox4 is localized primarily in mitochondria,endoplasmic reticulum,and nucleus, whose expression is upregulated by pressure overload and heart failure.Nox4 plays an essential role in mediating increases in ROS in the failing heart.Increased oxidative stress induces oxidation of cysteine resides in cⅡ-HDACs,such as C667 and C669 in HDAC4,which in turn causes nuclear exit of cⅡ-HDACs.The cⅡ-HDACs are further phospho-rylated by the HDAC kinases,including Ca<sup>2+</sup> calmodulin kinase and PKD,leading to prolonged cytoplasmic localization of cⅡ-HDACs and consequent cardiac hypertrophy.Thioredoxin 1（Trx1）,an anti-oxidant, reduces the critical cysteine residues in cⅡ-HDACs, thereby restoring the nuclear localization of cⅡ-HDACs and inhibiting pathological hypertrophy. Downregulation of Nox4 enhances nuclear localization of HDAC4,thereby inhibiting cardiac hypertrophy, suggesting that endogenous Nox4 mediates oxidation of HDAC4. In summary,oxidative stress plays an important role in regulating the subcellular localization of cⅡ-HDACs, critical regulators of pathological cardiac hypertrophy.Nox4 is upregulated in response to cardiac hypertrophy and heart failure,thereby playing a major role in mediating oxidative stress in the failing heart.Both Trxl and Nox4 play an essential role in regulating the oxidation status of cⅡ-HDACs, thereby critically regulating pathological hypertrophy and heart failure.I will also discuss pharmacological interventions targeting phosphorylation and/or oxidation of cⅡ-HDACs,which may be effective in treating pathological hypertrophy and heart failure in patients.
基金Supported by the National Natural Science Foundation of China under Grant Nos 61274106
文摘We present a study on the single event transient （SET） induced by a pulsed laser in different silicon-germanium （SiGe） heterojunction bipolar transistors （HBTs） with the structure of local oxidation of silicon （LOCOS） and deep trench isolation （DTI）. The experimental results are discussed in detail and it is demonstrated that a SiGe HBT with the structure of LOCOS is more sensitive than the DTI SiGe HBT in the SET. Because of the limitation of the DTI structure, the charge collection of diffusion in the DTI SiGe HBT is less than that of the LOCOS SiGe HBT. The SET sensitive area of the LOCOS SiGe HBT is located in the eollector-substrate （C/S） junction, while the sensitive area of the DTI SiGe HBT is located near to the collector electrodes.
基金Project supported by the Pre-Research Foundation of China(No.51311050202)
文摘The mechanism of single-event gate-rupture in an N-channel VDMOS in a space radiation environment was analyzed. Based on the mechanism, a novel structure of VDMOS for improving single-event gate-rupture is proposed, and the structure is simulated and it is demonstrated that it can improve a VDMOS SEGR threshold voltage by 120%. With this structure, the specific on-resistance value of a VDMOS is reduced by 15.5% as the breakdown voltage almost maintains the same value. As only one mask added, which is local oxidation of silicon instead of an active processing area, the new structure VDMOS it is easily fabricated. The novel structure can be widely used in high-voltage VDMOS in a space radiation environment.
