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Recently, the vascular protective effect of anti-diabetic agents has been receiving much attention. Sodium glucose cotransporter 2 (SGLT2) inhibitors had demonstrated reductions in cardiovascular (CV) events. However, the therapeutic effect of dapagliflozin on angiogenesis in peripheral arterial disease was unclear. This study aimed to explore the effect and mechanism of dapagliflozin on angiogenesis after hindlimb ischemia. We first evaluated the effect of dapagliflozin on post-ischemic angiogenesis in the hindlimbs of rats. Laser doppler imaging was used to detect the hindlimb blood perfusion. In addition, we used immunohistochemistry to detect the density of new capillaries after ischemia. The relevant signaling pathways of dapagliflozin affecting post-ischemic angiogenesis were screened through phosphoproteomic detection, and then the mechanism of dapagliflozin affecting post-ischemic angiogenesis was verified at the level of human umbilical vein endothelial cells (HUVECs). After subjection to excision of the left femoral artery, all rats were randomly distributed into two groups: the dapagliflozin group (left femoral artery resection, receiving intragastric feeding with dapagliflozin (1 mg/kg/d), for 21 consecutive days) and the model group, that is, the positive control group (left femoral artery resection, receiving intragastric feeding with citric acid–sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days). In addition, the control group, that is the negative control group (without left femoral artery resection, receiving intragastric feeding with citric acid–sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days) was added. At day 21 post-surgery, the dapagliflozin-treatment group had the greatest blood perfusion, accompanied by elevated capillary density. The results showed that dapagliflozin could promote angiogenesis after hindlimb ischemia. Then, the ischemic hindlimb adductor-muscle tissue samples from three rats of model group and dapagliflozin group were taken for phosphoproteomic testing. The results showed that the PI3K-Akt-eNOS signaling pathway was closely related to the effect of dapagliflozin on post-ischemic angiogenesis. Our study intended to verify this mechanism from the perspective of endothelial cells. In vitro, dapagliflozin enhanced the tube formation, migration, and proliferation of HUVECs under ischemic and hypoxic conditions. Additionally, the dapagliflozin administration upregulated the expression of angiogenic factors phosphorylated Akt (p-Akt) and phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor A (VEGFA), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. dapagliflozin could promote angiogenesis after ischemia. This effect might be achieved by promoting the activation of the PI3K-Akt-eNOS signaling pathway. This study provided a new perspective, new ideas, and a theoretical basis for the treatment of peripheral arterial disease. [ABSTRACT FROM AUTHOR]

Crocin is a unique water-soluble carotenoid found in crocus and gardenia flowers. Crocin has been shown to have a variety of pharmacological activities, such as antioxidant, anti-cancer, memory improvement, antidepressant, anti-ischemia, blood pressure lowering and aphrodisiac, gene protection and detoxification activities. Due to their amphiphilicity, crocin molecules form concentration-dependent self-associates (micelles) in a water solution. In the present study, using various NMR techniques (T2 relaxation and selective gradient NOESY), we have demonstrated that crocin forms mixed micelles with water-soluble drug delivery system glycyrrhizin and linoleic acid molecules. Note, that the spin–spin T2 relaxation time and NOESY spectroscopy are very sensitive to intermolecular interactions and molecular diffusion mobility. The second purpose of this work was the elucidation of the interaction of crocin with a model lipid membrane using NMR techniques and a molecular dynamics simulation and its effects on lipid oxidation. It was shown that the crocin molecule is located near the surface of the lipid bilayer and effectively protects lipids from oxidation by peroxyl radicals. The role of glycyrrhizin and vitamin C in metal-induced lipid oxidation was also elucidated. The results of this study may be useful for expanding the field of application of crocin in medicine and in the food industry. [ABSTRACT FROM AUTHOR]

Natural bioactive compounds have recently emerged as a current strategy for Alzheimer's disease treatment. Carotenoids, including astaxanthin, lycopene, lutein, fucoxanthin, crocin and others are natural pigments and antioxidants, and can be used to treat a variety of diseases, including Alzheimer's disease. However, carotenoids, as oil-soluble substances with additional unsaturated groups, suffer from low solubility, poor stability and poor bioavailability. Therefore, the preparation of various nano-drug delivery systems from carotenoids is a current measure to achieve efficient application of carotenoids. Different carotenoid delivery systems can improve the solubility, stability, permeability and bioavailability of carotenoids to a certain extent to achieve Alzheimer's disease efficacy. This review summarizes recent data on different carotenoid nano-drug delivery systems for the treatment of Alzheimer's disease, including polymer, lipid, inorganic and hybrid nano-drug delivery systems. These drug delivery systems have been shown to have a beneficial therapeutic effect on Alzheimer's disease to a certain extent. [ABSTRACT FROM AUTHOR]

Analyzing vertical distribution characters of air pollutants is conducive to study the mechanisms under polluted atmospheric conditions. Nitrous acid (HONO) is a kind of crucial species in photochemical cycles. Exploring the influence and sources of HONO in air pollution at different altitudes offers some insights into the research of tropospheric oxidation chemistry processes. Ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements were conducted in Shanghai, China, from December 2017 to March 2018 to investigate vertical distributions and diurnal variations of trace gases (NO2, HONO, HCHO, SO2, and water vapor) and aerosol extinction coefficient in the boundary layer. Aerosol and NO2 showed decreasing profile exponentially, SO2 and HCHO concentrations were observed relatively high values in the middle layer. SO2 was caused by industrial emissions, while HCHO was from secondary sources. As for HONO, below 0.82 km, the heterogeneous reactions of NO2 impacted on forming HONO, while in the upper layers, vertical diffusion might be the dominant source. The contribution of OH production from HONO photolysis at different altitudes was mainly controlled by the concentration of HONO. MAX-DOAS measurements characterize the vertical structure of air pollutants in Shanghai and provide further understanding for HONO formation, which can help deploy advanced measurement platforms of regional air pollution over eastern China. [ABSTRACT FROM AUTHOR]

Recently, the occurrence of fog and haze over China has increased. The retrieval of trace gases from the multi-axis differential optical absorption spectroscopy (MAX-DOAS) is challenging under these conditions. In this study, various reported retrieval settings for formaldehyde (HCHO) and sulfur dioxide (SO2) are compared to evaluate the performance of these settings under different meteorological conditions (clear day, haze, and fog). The dataset from 1st December 2019 to 31st March 2020 over Nanjing, China, is used in this study. The results indicated that for HCHO, the optimal settings were in the 324.5–359 nm wavelength window with a polynomial order of five. At these settings, the fitting and root mean squared (RMS) errors for column density were considerably improved for haze and fog conditions, and the differential slant column densities (DSCDs) showed more accurate values compared to the DSCDs between 336.5 and 359 nm. For SO2, the optimal settings for retrieval were found to be at 307–328 nm with a polynomial order of five. Here, root mean square (RMS) and fitting errors were significantly lower under all conditions. The observed HCHO and SO2 vertical column densities were significantly lower on fog days compared to clear days, reflecting a decreased chemical production of HCHO and aqueous phase oxidation of SO2 in fog droplets. [ABSTRACT FROM AUTHOR]

Air quality is strongly influenced by both local emissions and regional transport. Atmospheric chemical transport models can distinguish between emissions and regional transport sources in air pollutant concentrations. However, quantifying model inventories is challenging due to emission changes caused by the recent strict control measures taken by the Chinese government. In this study, we use NO2 column observations from the Tropospheric Monitoring Instrument to retrieve top-down nitrogen oxide (NOX) emissions and quantify the contributions of local emissions and regional transport to NOx in Beijing (BJ), from 1 November 2018 to 28 February 2019 (W_2018) and 1 November 2019 to 29 February 2020 (W_2019). In W_2018 and W_2019, the BJ bottom-up NOX emissions from the multi-resolution emission inventory for China in 2017 were overestimated by 11.8% and 40.5%, respectively, and the input of NOX from other cities to BJ was overestimated by 10.9% and 51.6%, respectively. The simulation using our adjusted inventory exhibited a much higher spatial agreement (slope = 1.0, R2 = 0.79) and reduced a mean relative error by 45% compared to those of bottom-up NOX emissions. The top-down inventory indicated that (1) city boundary transport contributes approximately 40% of the NOX concentration in BJ; (2) in W_2019, NOX emissions and transport in BJ decreased by 20.4% and 17.2%, respectively, compared to those of W_2018; (3) in W_2019, NOX influx substantially decreased (−699 g/s) in BJ compared to that of W_2018 despite negative meteorological conditions that should have increased NOx influx by +503 g/s. Overall, the contribution of intercity input to NOx in BJ has declined with decreasing emissions in the surrounding cities due to regional cooperative control measures, and the role of local emissions in BJ NOx levels was more prominent. Our findings indicate that local emissions may play vital roles in regional center city air quality. [ABSTRACT FROM AUTHOR]

Restrictions on human activities remarkably reduced emissions of air pollutants in China during the COVID-19 lockdown periods. However, distinct responses of O3 concentrations were observed across China. In the Beijing–Tianjin–Hebei (BTH) and Yangtze River Delta (YRD) regions, O3 concentrations were enhanced by 90.21 and 71.79% from pre-lockdown to lockdown periods in 2020, significantly greater than the equivalent concentrations for the same periods over 2015–2019 (69.99 and 43.62%, p < 0.001). In contrast, a decline was detected (−1.1%) in the Pearl River Delta (PRD) region. To better understand the underlying causes for these inconsistent responses across China, we adopted the least absolute shrinkage and selection operator (Lasso) and ordinary linear squares (OLS) methods in this study. Statistical analysis indicated that a sharp decline in nitrogen dioxide (NO2) was the major driver of enhanced O3 in the BTH region as it is a NOx-saturated region. In the YRD region, season-shift induced changes in the temperature/shortwave radiative flux, while lockdown induced declines in NO2, attributable to the rise in O3. In the PRD region, the slight drop in O3 is attributed to the decreased intensity of radiation. The distinct regimes of the O3 response to the COVID-19 lockdown in China offer important insights into different O3 control strategies across China. [ABSTRACT FROM AUTHOR]

In this paper, we present the Hefei EMI Cloud Retrieval Algorithm (HECORA), which uses information from the O2-O2 absorption band around 477 nm to retrieve effective cloud fraction and effective cloud pressure from satellite observations. The retrieved cloud information intends to improve the atmospheric trace gas products based on the Environment Monitoring Instrument (EMI) spectrometer. The HECORA method builds on OMCLDO2 and presents some evolutions. The Vector Linearized Discrete Ordinate Radiative Transfer (VLIDORT) model has been used to produce the Top of the Atmosphere (TOA) reflectance Look-up Tables (LUT) as a function of the cloud fraction and cloud pressure. Applying the Differential Optical Absorption Spectroscopy (DOAS) technique to the synthetic reflectance LUT, the reflectance spectra can be associated with O2-O2 geometrical vertical column densities (VCDgeo) and continuum reflectance. This is the core of the retrieval method, since there is a one-to-one relationship between O2-O2 VCDgeo and continuum reflectance, on the one hand, and effective cloud fraction and effective cloud pressure, on the other hand, for a given illumination and observing geometry and given surface height and surface albedo. We first used the VLIDORT synthetic spectra to verify the HECORA algorithm and obtained good results in both the Lambertian cloud model and the scattering cloud model. Secondly, HECORA is applied to OMI and TROPOMI and compared with OMCLDO2, FRESCO+, and OCRA/ROCINN cloud products. Later, the cloud pressure results from TROPOMI observations obtained using HECORA and FRESCO+ are compared with the CALIOP Cloud Layer product. HECORA is closer to the CALIOP results under low cloud conditions, while FRESCO+ is closer to high clouds due to the higher sensitivity of the O2 A-band to cloud vertical information. Finally, HECORA is applied to the TROPOMI NO2 retrieval. Validation of the tropospheric NO2 VCD with ground-based MAX-DOAS measurements shows that choosing HECORA cloud products to correct for photon path variations on the TROPOMI tropospheric NO2 VCD retrievals has better performance than using FRESCO+ under low cloud conditions. In conclusion, this paper shows that the HECORA cloud products are in good agreement with the well-established cloud products and that they are suitable for correcting the effect of cloud in trace gas retrievals. Therefore, HECORA has the potential to be applied to EMI. [ABSTRACT FROM AUTHOR]