Global burden of stroke attributable to high systolic blood pressure in 204 countries and territories, 1990-2019.

Background: High systolic blood pressure (HSBP) is severely related to stroke, although the global burden of stroke associated with HSBP needs to be understood. Materials and methods: Data derived from the Global Burden of Disease, Injuries, and Risk Factors Study were used to analyze deaths, disability-adjusted life years (DALYs), age-standardized rates of mortality (ASMR), age-standardized rates of DALY (ASDR), and estimated annual percentage change (EAPC). Results: Globally, 52.57% of deaths and 55.54% of DALYs from stroke were attributable to HSBP in 2019, with higher levels in men; the ASMRs and ASDRs in 1990-2019 experienced a decline of 34.89% and 31.71%, respectively, with the highest ASMR- and ASDR-related EAPCs in women. The middle socio-demographic index (SDI) regions showed the most numbers of deaths and DALYs in 2019 and 1990, with a decline in ASMR and ASDR; East Asia shared over 33% of global deaths and DALYs; Central Asia shared the highest ASMR and ASDR; high-income Asia Pacific experienced the highest decline in the ASMR- and ASDR-related EAPCs. Central and Southeast Asia had the highest percentages for deaths and DALYs, respectively, with more ASMR in high-middle SDI; the SDI and human development index were negatively associated with ASMR/ASDR and ASMR/ASDR-related EAPCs in 2019. Conclusion: Global deaths and DALYs of stroke attributable to HSBP but none of their age-standardized rates have been on the rise over the past three decades; its disease burden focused especially on men aged 70 years and older in East, Central, and Southeast Asia, and the middle to high SDI regions.

Associations of cognitive impairment and longitudinal change in cognitive function with the risk of fatal stroke in middle-aged to older Chinese.

It is unclear whether cognitive impairment and the longitudinal change in cognition are associated with the risk of fatal stroke in aging populations. Based on the Guangzhou Biobank Cohort Study data a sum of 26,064 participants at baseline and all deaths caused by stroke in a mean follow-up of 14.3 years (standard deviation = 3.2) were included, and the Cox proportional hazard regression was used in this prospective cohort study. Cognitive impairment was respectively associated with an increased risk of fatal strokes (the adjusted hazard ratio (aHR) = 1.38, 95% CI1.16-1.64, P < 0.001) and fatal ischaemic stroke (aHR = 1.39, 95% CI1.10-1.77, P = 0.007), compared to median cognition; the Delayed Word Recall Test (DWRT) score was associated with a decreasing trend for the risk of fatal strokes in a restricted cubic spline analysis; the longitudinal DWRT score decline was associated with the increased risks of fatal strokes (aHR = 1.42, 95% CI 1.11-1.82, P = 0.006) and fatal haemorrhagic stroke (aHR = 1.75, 95% CI 1.10-2.78, P = 0.02), compared to the longitudinal DWRT score rise. In summary, cognitive impairment and the longitudinal decline in DWRT scores were associated with the increased risk of fatal strokes; early screening of cognitive function should be conducive to predictive intervention in fatal stroke among relatively healthy middle-aged to older populations.

Trends in deaths and disability-adjusted life-years of stroke attributable to low physical activity worldwide, 1990-2019.

BACKGROUND: Low physical activity (LPA) is linked to the risk of stroke, but the disease burden of stroke attributable to LPA needs to be understood to develop effective preventive strategies. We aim to assess spatiotemporal trends in the global burden of stroke attributable to LPA from 1990 to 2019. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study, our research examined deaths, the Disability-Adjusted Life Years (DALYs), the Age-Standardized Mortality Rate (ASMR), the Age-Standardized DALY Rate (ASDR), and the Estimated Annual Percentage Change (EAPC) for stroke attributable to LPA. RESULTS: Deaths and DALYs were on the rise worldwide from 1990 to 2019, with increases of 72.72% for the former and 67.41% for the latter; ASMR and ASDR decreased, with the ASMR-related EAPC of -1.61 (95% CI:-1.71--1.5) and ASDR-related EAPC of -1.35 (95% CI:-1.43--1.27); females had more numbers of deaths and DALYs, and the majorities of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by North Africa, the Middle East, and Tropical Latin America; the ASMR-related EAPC was associated with the ASMR in 1990 (R = -0.26, P < 0.001) and the Socio-Demographic Index (SDI) across different countries in 2019 (R = -0.61, P < 0.001), respectively, and such patterns were similar to what ASDR and the ASDR-related EAPC had; the Human Development Index (HDI) in 2019 was associated with the ASMR-related EAPC (R = 0.63, P < 0.001) and the ASDR-related EAPC across different countries (R = -0.62, P < 0.001), respectively. CONCLUSIONS: Globally, deaths and DALYs of stroke attributable to LPA were on the rise, although their age-standardized rates presented downward over the past three decades; the burden of stroke attributable to LPA showed upward trends especially in those aged ≥ 70 and females in the regions of East Asia, North Africa, and the Middle East, which need more attention to the effects of physical activity on health interventions.

Trends in deaths and disability-adjusted life-years of stroke attributable to high body-mass index worldwide, 1990-2019.

Background: High body mass index (HBMI) is an independent risk factor for stroke. Previous studies on the incremental burden of the rapid growth of stroke attributable to HBMI are incomplete and lag behind. We aim to assess the global burden of stroke attributable to HBMI based on a public database online. Materials and methods: Study data were taken from the Global Burden of Disease, Injuries, and Risk Factors Study; deaths, the Disability-Adjusted Life-Years (DALYs), and their age-standardized rates were screened. The join point regression was used, wherein age-standardized rates were referred to as temporal trends in disease burden. Results: Deaths from stroke attributable to HBMI worldwide were on the rise during 1990-2019, with an increase of 88.75%. Age-standardized DALYs were on the rise during 1990-2003 but declined during 2003-2013, with a turning point in 2013 and an increasing trend since then [the Annual Percentage Change (APC) = 0.30%, p < 0.05]. China, India, Indonesia, the Russian Federation, and the United States of America shared in sequence the rate of leading deaths and DALYs in 2019. The Socio-Demographic Index (SDI) was associated with an increasing trend in age-standardized deaths (R = -0.24, p < 0.001) and age-standardized DALYs (R = -0.22, p = 0.0018). Conclusion: A range of indicators for the global burden of stroke attributable to HBMI have been on the rise for the past three decades. Tremendous efforts worldwide should be in place to control and treat stroke attributable to HBMI, especially in regions with high-middle and middle SDIs and among middle-aged and aged populations.

Free-standing graphene aerogel with improved through-plane thermal conductivity after being annealed at high temperature.

Both high through-plane thermal conductivity and low elastic modulus can reduce thermal interface resistance, which is important for thermal interface materials. The internal porous structure of graphene aerogel (GA) makes it to have a low elastic modulus, which results in its good compressibility. Also, the network structure of GA provides thermal conducting paths, which improve the through-plane thermal conductivity of GA. Annealing GA at 3000 °C helps to remove oxygen-containing functional groups and reduces defects. This greatly improves its crystallinity, which further leads to the improvement of its through-plane thermal conductivity and it has a low modulus of 1.37Mpa. The through-plane thermal conductivity of GA annealed at 3000 °C (GA-3000) was improved as the pressure increased and got to 2.93 W/ m K at a pressure of 1.13 MPa, which is 30 times higher than other graphene-based thermal interface materials (TIMs). These discoveries offer a novel approach for preparing excellent TIMs.

Impact of Ionic Liquids on Effectiveness of Tuning the Emissivity of Multilayer Graphene.

Multilayer graphene has been employed as a functional material for tuning the emissivity in mid- and long-infrared range, which shows great potential for various applications, such as radiative cooling and thermal camouflage. However, the stability of the multilayer graphene is not sufficient for practical applications yet. Even though it is reported that the integrity of the multilayer graphene is compromised by ion intercalation, the detailed mechanism is rather unclear. Here, a set of ionic liquids is deployed as sources of electronic charges for tuning the emissivity of multilayer graphene. It is found that the emissivity modulator using 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([EMIm]NTf2) as the ionic liquid provides a modulation depth of about 0.52 (i.e., about 21% larger than the best-reported value) while maintaining a reasonable device lifetime. The microscopic structures of the multilayer graphene in an operational and failure modulator are investigated by scanning electron microscopy, Raman spectroscopy, X-ray diffraction. The results indicate that the modulation depth of emissivity is negatively correlated with the initial voltage, which represents the reaction potential between the ionic liquid and graphene. Furthermore, not only the chemical reactivity but also the size of both anion and cation in the ionic liquids play important roles in maintaining stability of the modulator. Therefore, a set of criteria (e.g., low initial voltage and small size of anion and cation) is proposed to select proper ionic liquids for emissivity modulation. This not only sheds light on the underlying physics of the modulator but also promotes its practical applications.

Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice.

Farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has emerged as a potential therapy for nonalcoholic fatty liver disease (NAFLD). However, the side effects of OCA may limit its application in clinics. We identified previously that isotschimgine (ITG) is a non-steroidal FXR selective agonist and has potent therapeutic effects on NAFLD in mice. Here, we aimed to evaluate the therapeutic effects of ITG on nonalcoholic steatohepatitis (NASH) and fibrosis in mice. We used methionine and choline deficient (MCD) diet-induced NASH mice, bile duct ligation (BDL), and carbon tetrachloride (CCl4 )-treated hepatic fibrosis mice to investigate the effects of ITG on NASH, fibrosis, and cholestatic liver injury. Our results showed that ITG improved steatosis and inflammation in the liver of MCD diet-fed mice, as well as alleviated fibrosis and inflammation in the liver of CCl4 -treated mice. Furthermore, ITG attenuated serum bile acid levels, and reduced vacuolization, inflammatory infiltration, hepatic parenchymal necrosis, and collagen accumulation in the liver of BDL mice. Mechanistically, ITG increased the expression of FXR target genes. These data suggest that ITG is an FXR agonist and may be developed as a novel therapy for NASH, hepatic fibrosis, or primary biliary cholangitis.

Protopanaxadiol alleviates obesity in high-fat diet-fed mice via activation of energy-sensing neuron in the paraventricular nucleus of hypothalamus.

Obesity is one of the most important health problems worldwide. Panax ginseng has been reported to exert anti-obesity effect. However, the active constituents and the underlying mechanism remained uncertain. This study uncovered the anti-obesity effect of protopanaxadiol (PPD) and its potential mechanism. To investigate the anti-obesity effect of PPD, high-fat diet induced obesity (DIO) C57BL/6 mice were treated with PPD by both intraperitoneal injection (i.p.) and oral administration. Body weight and food intake were recorded. Energy expenditure was measured by CLAMS metabolic cages. For mechanism study, C-Fos in the hypothalamus of the mice was stained following the intracerebroventricular (i.c.v.) injection of PPD. Our results showed that with both injection and feeding, PPD reduced body weight, inhibited food intake, increased energy expenditure and improved liver damage in DIO mice. Mechanistically, i.c.v. injection of PPD inhibited feeding and increased C-Fos expression in paraventricular nucleus of the hypothalamus (PVH). The results suggest that PPD may reduce body weight of DIO mice via the activation of PVH neurons and PPD is a potential therapeutic candidate for the treatment of obesity.

Enantioselective resolution of Rac-terbutaline and evaluation of optically pure R-terbutaline hydrochloride as an efficient anti-asthmatic drug.

Terbutaline is a ß2 -adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R-isomer was found to be the potent enantiomer in generating therapeutic effect, while S-isomer has been reported to show side effects. In this study, R-terbutaline hydrochloride (R-TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac-TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R-TBH 6 nebulized solution was prepared in half dosage of Bricanyl®, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti-asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R-TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti-asthmatic effect with Bricanyl®.

Resolution of Rac-Bambuterol via Diastereoisomeric Salt Formation with o-Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles.

In this study an enantioseparation method for rac-bambuterol (5-(2-(tert-butylamino)-1-hydroxyethyl)-1,3-phenylene bis(dimethylcarbamate)) via diastereoisomeric salt formation with o-chloromandelic acid was developed. The enantiomeric excess (ee) values and chemical purities of the desired products were confirmed by high-performance liquid chromatography (HPLC) using chiral stationary phase and reverse-phase HPLC analyses, respectively. The ee values and the chemical purities both exceeded 99%. Animal experiments showed that (R)-bambuterol was a potent inhibitor for histamine-induced asthma reactions. (S)-bambuterol was ineffective in relaxing the airways. Both enantiomers increased heart rates in beagles. Therefore, replacing rac-bambuterol with (R)-bambuterol could be beneficial for asthma patients.