Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H4B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers

Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells.

The outbreak of COVID-19 has remained uncontained with urgent need for robust therapeutics. We have previously reported sex difference of COVID-19 for the first time indicating male predisposition. Males are more susceptible than females, and more often to develop into severe cases with higher mortality. This predisposition is potentially linked to higher prevalence of cigarette smoking. Nonetheless, we found for the first time that cigarette smoking extract (CSE) had no effect on angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) expression in endothelial cells. The otherwise observed worse outcomes in smokers is likely linked to baseline respiratory diseases associated with chronic smoking. Instead, we hypothesized that estrogen mediated protection might underlie lower morbidity, severity and mortality of COVID-19 in females. Of note, endothelial inflammation and barrier dysfunction are major mediators of disease progression, and development of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. Therefore, we investigated potential protective effects of estrogen on endothelial cells against oxidative stress induced by interleukin-6 (IL-6) and SARS-CoV-2 spike protein (S protein). Indeed, 17β-estradiol completely reversed S protein-induced selective activation of NADPH oxidase isoform 2 (NOX2) and reactive oxygen species (ROS) production that are ACE2-dependent, as well as ACE2 upregulation and induction of pro-inflammatory gene monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to effectively attenuate endothelial dysfunction. Effects of IL-6 on activating NOX2-dependent ROS production and upregulation of MCP-1 were also completely attenuated by 17β-estradiol. Of note, co-treatment with CSE had no additional effects on S protein stimulated endothelial oxidative stress, confirming that current smoking status is likely unrelated to more severe disease in chronic smokers. These data indicate that estrogen can serve as a novel therapy for patients with COVID-19 via inhibition of initial viral responses and attenuation of cytokine storm induced endothelial dysfunction, to substantially alleviate morbidity, severity and mortality of the disease, especially in men and post-menopause women. Short-term administration of estrogen can therefore be readily applied to the clinical management of COVID-19 as a robust therapeutic option

Therapeutic application of estrogen for COVID-19: Attenuation of SARS-CoV-2 spike protein and IL-6 stimulated, ACE2-dependent NOX2 activation, ROS production and MCP-1 upregulation in endothelial cells.

The outbreak of COVID-19 has remained uncontained with urgent need for robust therapeutics. We have previously reported sex difference of COVID-19 for the first time indicating male predisposition. Males are more susceptible than females, and more often to develop into severe cases with higher mortality. This predisposition is potentially linked to higher prevalence of cigarette smoking. Nonetheless, we found for the first time that cigarette smoking extract (CSE) had no effect on angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) expression in endothelial cells. The otherwise observed worse outcomes in smokers is likely linked to baseline respiratory diseases associated with chronic smoking. Instead, we hypothesized that estrogen mediated protection might underlie lower morbidity, severity and mortality of COVID-19 in females. Of note, endothelial inflammation and barrier dysfunction are major mediators of disease progression, and development of acute respiratory distress syndrome (ARDS) and multi-organ failure in patients with COVID-19. Therefore, we investigated potential protective effects of estrogen on endothelial cells against oxidative stress induced by interleukin-6 (IL-6) and SARS-CoV-2 spike protein (S protein). Indeed, 17β-estradiol completely reversed S protein-induced selective activation of NADPH oxidase isoform 2 (NOX2) and reactive oxygen species (ROS) production that are ACE2-dependent, as well as ACE2 upregulation and induction of pro-inflammatory gene monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to effectively attenuate endothelial dysfunction. Effects of IL-6 on activating NOX2-dependent ROS production and upregulation of MCP-1 were also completely attenuated by 17β-estradiol. Of note, co-treatment with CSE had no additional effects on S protein stimulated endothelial oxidative stress, confirming that current smoking status is likely unrelated to more severe disease in chronic smokers. These data indicate that estrogen can serve as a novel therapy for patients with COVID-19 via inhibition of initial viral responses and attenuation of cytokine storm induced endothelial dysfunction, to substantially alleviate morbidity, severity and mortality of the disease, especially in men and post-menopause women. Short-term administration of estrogen can therefore be readily applied to the clinical management of COVID-19 as a robust therapeutic option

Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H4B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers

Impact and Suggestion of Column-to-Surface Vertical Correction Scheme on the Relationship between Satellite AOD and Ground-Level PM2.5 in China

As China is suffering from severe fine particle pollution from dense industrialization and urbanization, satellite-derived aerosol optical depth (AOD) has been widely used for estimating particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5). However, the correlation between satellite AOD and ground-level PM2.5 could be influenced by aerosol vertical distribution, as satellite AOD represents the entire column, rather than just ground-level concentration. Here, a new column-to-surface vertical correction scheme is proposed to improve separation of the near-surface and elevated aerosol layers, based on the ratio of the integrated extinction coefficient within 200–500 m above ground level (AGL), using the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP)) aerosol profile products. There are distinct differences in climate, meteorology, terrain, and aerosol transmission throughout China, so comparisons between vertical correction via CALIOP ratio and planetary boundary layer height (PBLH) were conducted in different regions from 2014 to 2015, combined with the original Pearson coefficient between satellite AOD and ground-level PM2.5 for reference. Furthermore, the best vertical correction scheme was suggested for different regions to achieve optimal correlation with PM2.5, based on the analysis and discussion of regional and seasonal characteristics of aerosol vertical distribution. According to our results and discussions, vertical correction via PBLH is recommended in northwestern China, where the PBLH varies dramatically, stretching or compressing the surface aerosol layer; vertical correction via the CALIOP ratio is recommended in northeastern China, southwestern China, Central China (excluding summer), North China Plain (excluding Beijing), and the spring in the southeast coast, areas that are susceptible to exogenous aerosols and exhibit the elevated aerosol layer; and original AOD without vertical correction is recommended in Beijing and the southeast coast (excluding spring), where the elevated aerosol layer rarely occurs and a large proportion of aerosol is aggregated in near-surface. Moreover, validation experiments in 2016 agreed well with our discussions and conclusions drawn from the experiments of the first two years. Furthermore, suggested vertical correction scheme was applied into linear mixed effect (LME) model, and high cross validation (CV) R2 (~85%) and relatively low root mean square errors (RMSE, ~20 μg/m3) were achieved, which demonstrated that the PM2.5 estimation agreed well with the measurements. When compared to the original situation, CV R2 values and RMSE after vertical correction both presented improvement to a certain extent, proving that the suggested vertical correction schemes could further improve the estimation accuracy of PM2.5 based on sophisticated model in China. Estimating PM2.5 with better accuracy could contribute to a more precise research of ecology and epidemiology, and provide a reliable reference for environmental policy making by governments

Real-Time Estimation of Satellite-Derived PM2.5 Based on a Semi-Physical Geographically Weighted Regression Model

The real-time estimation of ambient particulate matter with diameter no greater than 2.5 μm (PM2.5) is currently quite limited in China. A semi-physical geographically weighted regression (GWR) model was adopted to estimate PM2.5 mass concentrations at national scale using the Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth product fused by the Dark Target (DT) and Deep Blue (DB) algorithms, combined with meteorological parameters. The fitting results could explain over 80% of the variability in the corresponding PM2.5 mass concentrations, and the estimation tends to overestimate when measurement is low and tends to underestimate when measurement is high. Based on World Health Organization standards, results indicate that most regions in China suffered severe PM2.5 pollution during winter. Seasonal average mass concentrations of PM2.5 predicted by the model indicate that residential regions, namely Jing-Jin-Ji Region and Central China, were faced with challenge from fine particles. Moreover, estimation deviation caused primarily by the spatially uneven distribution of monitoring sites and the changes of elevation in a relatively small region has been discussed. In summary, real-time PM2.5 was estimated effectively by the satellite-based semi-physical GWR model, and the results could provide reasonable references for assessing health impacts and offer guidance on air quality management in China

Ground Level PM2.5 Estimates over China Using Satellite-Based Geographically Weighted Regression (GWR) Models Are Improved by Including NO2 and Enhanced Vegetation Index (EVI)

Highly accurate data on the spatial distribution of ambient fine particulate matter (<2.5 μm: PM2.5) is currently quite limited in China. By introducing NO2 and Enhanced Vegetation Index (EVI) into the Geographically Weighted Regression (GWR) model, a newly developed GWR model combined with a fused Aerosol Optical Depth (AOD) product and meteorological parameters could explain approximately 87% of the variability in the corresponding PM2.5 mass concentrations. There existed obvious increase in the estimation accuracy against the original GWR model without NO2 and EVI, where cross-validation R2 increased from 0.77 to 0.87. Both models tended to overestimate when measurement is low and underestimate when high, where the exact boundary value depended greatly on the dependent variable. There was still severe PM2.5 pollution in many residential areas until 2015; however, policy-driven energy conservation and emission reduction not only reduced the severity of PM2.5 pollution but also its spatial range, to a certain extent, from 2014 to 2015. The accuracy of satellite-derived PM2.5 still has limitations for regions with insufficient ground monitoring stations and desert areas. Generally, the use of NO2 and EVI in GWR models could more effectively estimate PM2.5 at the national scale than previous GWR models. The results in this study could provide a reasonable reference for assessing health impacts, and could be used to examine the effectiveness of emission control strategies under implementation in China

Semi-Physical Estimates of National-Scale PM10 Concentrations in China Using a Satellite-Based Geographically Weighted Regression Model

The estimation of ambient particulate matter with diameter less than 10 µm (PM10) at high spatial resolution is currently quite limited in China. In order to make the distribution of PM10 more accessible to relevant departments and scientific research institutions, a semi-physical geographically weighted regression (GWR) model was established in this study to estimate nationwide mass concentrations of PM10 using easily available MODIS AOD and NCEP Reanalysis meteorological parameters. The results demonstrated that applying physics-based corrections could remarkably improve the quality of the dataset for better model performance with the adjusted R2 between PM10 and AOD increasing from 0.08 to 0.43, and the fitted results explained approximately 81% of the variability in the corresponding PM10 mass concentrations. Annual average PM10 concentrations estimated by the semi-physical GWR model indicated that many residential regions suffer from severe particle pollution. Moreover, the deviation in estimation, which primarily results from the frequent changes in elevation, the spatially heterogeneous distribution of monitoring sites, and the limitations of AOD retrieval algorithm, was acceptable. Therefore, the semi-physical GWR model provides us with an effective and efficient method to estimate PM10 at large scale. The results could offer reasonable estimations of health impacts and provide guidance on emission control strategies in China

Enhanced CO2 Capture through SAPO-34 Impregnated with Ionic Liquid

The concurrent utilization of an adsorbent and absorbent for carbon dioxide (CO2) adsorption with synergistic effects presents a promising technique for CO2 capture. Here, 1-butyl-3-methylimidazole acetate ([Bmim][Ac]), with a high affinity for CO2, and the molecular sieve SAPO-34 were selected. The impregnation method was used to composite the hybrid samples of [Bmim][Ac]/SAPO-34, and the pore structure and surface property of prepared samples were characterized. The quantity and kinetics of the sorbed CO2 for loaded samples were measured using thermogravimetric analysis. The study revealed that SAPO-34 could retain its pristine structure after [Bmim][Ac] loading. The CO2 uptake of the loaded sample was 1.879 mmol g-1 at 303 K and 1 bar, exhibiting a 20.6% rise compared to that of the pristine SAPO-34 recording 1.558 mmol g-1. The CO2 uptake kinetics of the loaded samples were also accelerated, and the apparent mass transfer resistance for CO2 sorption was significantly reduced by 11.2% compared with that of the pure [Bmim][Ac]. The differential scanning calorimetry method revealed that the loaded sample had a lower CO2 desorption heat than that of the pure [Bmim][Ac], and the CO2 desorption heat of the loaded samples was between 30.6 and 40.8 kJ mol-1. The samples exhibited good cyclic stability. This material displays great potential for CO2 capture applications, facilitating the reduction of greenhouse gas emissions.Validerad;2024;Nivå 2;2024-05-07 (hanlid);Funder: National Natural Science Foundation of China (22327809); Post-graduate Research &amp; Practice Innovation Program of Jiangsu Province (KYCX23-1467);Full text license: CC BY</p