Background : SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear. Methods : In vascular smooth ...Background : SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear. Methods : In vascular smooth muscle cells(VSMCs), we employed gain-and loss-offunction approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2(AAV2) to validate the findings in vivo. Results : We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin Ⅱ. Conversely, in vivo overexpression of Sox6 led to a significant elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagydependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6. Conclusions : Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.展开更多
Structural design and tests on the characteristics of the SF6 gas switch with a small gap are presented. This kind of switch often works under high pressure and nanosecond pulse for getting pulse with faster risetime....Structural design and tests on the characteristics of the SF6 gas switch with a small gap are presented. This kind of switch often works under high pressure and nanosecond pulse for getting pulse with faster risetime. The breakdown voltage and breakdown delay of a number of switches with different geometries, gas pressures and pulse waveforms were investigated. Experimental results suggested that the breakdown voltage increases linearly with the gas pressure, and the breakdown delay decreases with an increase in the gas pressure and a reduction in the gap distance of the switch under the same applied pulse. By using this kind of switch with a gap of 3 mm as a peaking switch, a pulse generator can provide an output voltage with a peak voltage of 300 kV and a risetime of 3 ns on a resistance load of 150Ω.展开更多
Objectives: It is important to know what patient reported outcome measure (PROM) scores relate to a meaningful change in health status across time. The aim of this study was to investigate the minimally important diff...Objectives: It is important to know what patient reported outcome measure (PROM) scores relate to a meaningful change in health status across time. The aim of this study was to investigate the minimally important difference (MID) of the Diabetes Health Profile (DHP-18), EQ-5D and SF-6D in a Type 1 and Type 2 diabetes patient sample. Methods: A longitudinal dataset including a UK community sample of people with Type 1 and Type 2 diabetes was used for the analysis. A combination of anchor and distribution methods was used to investigate the MID. For the anchor based method, a global health change indicator was used if it correlated with the PROM scores at baseline and follow up. To calculate the anchor based MID, the change in PROM score for those reporting no change on the anchor was subtracted from those reporting small change. For the distribution based estimation, the 1 Standard Error of Measurement, 0.5 and 0.33 standard deviation methods were used. Results: The anchor was not correlated with the DHP-18 dimensions so was only used to estimate MID values for the EQ-5D and SF-6D. For the DHP-18, MID estimates for the Psychological Distress domain range from 6.99 to 10.59, the Barriers to Activity domain range from 6.48 to 9.89, and the Disinhibited Eating domain range from 7.52 to 11.39. The EQ-5D estimations range from 0.058 to 0.158, and the SF-6D estimations range from 0.038 to 0.081. The 0.5 SD and 1SEM estimations are of a similar magnitude across the three measures. Conclusions:This study has derived a range of values for each measure that may correspond to an important change in health status. The MID values may guide researchers who are using the measures as part of their assessment of both Type 1 and Type 2 patients with diabetes mellitus.展开更多
基金Beijing Nova Program,Grant/Award Number:20230484842National Natural Science Foundation of China,Grant/Award Number:82470461。
文摘Background : SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear. Methods : In vascular smooth muscle cells(VSMCs), we employed gain-and loss-offunction approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2(AAV2) to validate the findings in vivo. Results : We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin Ⅱ. Conversely, in vivo overexpression of Sox6 led to a significant elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagydependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6. Conclusions : Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.
基金supported by National Natural Science Foundation of China (No. 50437030)
文摘Structural design and tests on the characteristics of the SF6 gas switch with a small gap are presented. This kind of switch often works under high pressure and nanosecond pulse for getting pulse with faster risetime. The breakdown voltage and breakdown delay of a number of switches with different geometries, gas pressures and pulse waveforms were investigated. Experimental results suggested that the breakdown voltage increases linearly with the gas pressure, and the breakdown delay decreases with an increase in the gas pressure and a reduction in the gap distance of the switch under the same applied pulse. By using this kind of switch with a gap of 3 mm as a peaking switch, a pulse generator can provide an output voltage with a peak voltage of 300 kV and a risetime of 3 ns on a resistance load of 150Ω.
文摘Objectives: It is important to know what patient reported outcome measure (PROM) scores relate to a meaningful change in health status across time. The aim of this study was to investigate the minimally important difference (MID) of the Diabetes Health Profile (DHP-18), EQ-5D and SF-6D in a Type 1 and Type 2 diabetes patient sample. Methods: A longitudinal dataset including a UK community sample of people with Type 1 and Type 2 diabetes was used for the analysis. A combination of anchor and distribution methods was used to investigate the MID. For the anchor based method, a global health change indicator was used if it correlated with the PROM scores at baseline and follow up. To calculate the anchor based MID, the change in PROM score for those reporting no change on the anchor was subtracted from those reporting small change. For the distribution based estimation, the 1 Standard Error of Measurement, 0.5 and 0.33 standard deviation methods were used. Results: The anchor was not correlated with the DHP-18 dimensions so was only used to estimate MID values for the EQ-5D and SF-6D. For the DHP-18, MID estimates for the Psychological Distress domain range from 6.99 to 10.59, the Barriers to Activity domain range from 6.48 to 9.89, and the Disinhibited Eating domain range from 7.52 to 11.39. The EQ-5D estimations range from 0.058 to 0.158, and the SF-6D estimations range from 0.038 to 0.081. The 0.5 SD and 1SEM estimations are of a similar magnitude across the three measures. Conclusions:This study has derived a range of values for each measure that may correspond to an important change in health status. The MID values may guide researchers who are using the measures as part of their assessment of both Type 1 and Type 2 patients with diabetes mellitus.
