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Emerging preclinical data suggest that glucagon-like peptide-1 receptor agonist (GLP1RA) possesses cardioprotective properties against the pathophysiology of hypertension (HT). We sought to unravel the potential therapeutic application of GLP1RA in a clinically relevant large animal model of hypertensive cardiomyopathy (hCMP). A combination of angiotensin II (Ang II) and deoxycorticosterone acetate (DOCA) pellets were used to induce sustained HT status and establish hCMP in porcine model. Changes in cardiac echocardiography, invasive hemodynamic parameters, neurohumoral biomarkers and inflammation-related cytokines were investigated in 23 adult pigs, among which 6 were serving as control, 9 were induced with HT, and the remaining 8 were HT-induced with GLP1RA treatment. Eight weeks after the study initiated, HT pigs have developed sustained high blood pressure (BP) at both systole and diastole. Phenotype of hCMP has also become significant as impairment in systolic/diastolic function, left ventricular remodeling and cardiac hypertrophy was determined by echocardiogram and invasive hemodynamics. Additionally, blood norepinephrine (NE) content, venoarterial NE gradient and pro-inflammatory cytokines in HT pigs were increased. GLP1RA treatment halted the elevation in BP, left ventricular remodeling and cardiac hypertrophy development; preserved the left ventricular systolic/diastolic function; reduced the venoarterial NE gradient as well as the pro-inflammatory cytokines at 18 weeks in pigs with hCMP. Our results demonstrate that GLP1RA treatment has a remarkable effect on BP decrease, inflammation suppression and left ventricular function improvement. Thus, we provide novel insight into the therapeutic potential of GLP1RA in HT-induced heart failure in a large animal model of hCMP.

Adipose tissue macrophage (ATM) has been shown to play a key role in the pathogenesis of obesity-associated adipose tissue inflammation and metabolic diseases. However, the upstream factors that integrate the environmental signals to control ATM activation and adipose inflammation in obesity remain elusive. Here, we identify BAF60a, a subunit of the SWI/SNF chromatin remodeling complexes, as the central checkpoint regulator of obesity-induced ATM activation, adipose tissue inflammation and systemic metabolic impairment. BAF60a expression was robustly downregulated in the adipose tissue stromal vascular fractions (SVFs) in type 2 diabetic mice. Myeloid-specific BAF60a ablation (BaMKO) promotes ATM pro-inflammatory activation, exacerbating diet-induced obesity, insulin resistance and metabolic dysfunction. Conversely, myeloid-specific overexpression of BAF60a in mice attenuates macrophage pro-inflammatory activation. Mechanistically, transcriptome and chromatin landscape analyses demonstrate that BAF60a inactivation triggers the expression of pro-inflammatory gene program through chromatin remodeling. Moreover, motif analysis of ATAC-Seq and CUT&Tag-Seq data identifies the transcription factor Atf3 that physically interacts with BAF60a to suppress the pro-inflammatory gene expression, thereby controlling ATM activation and metabolic inflammation in obesity. Consistently, myeloid-specific Atf3 deficiency also promotes the pro-inflammatory activation of macrophage. Together, this work uncovers BAF60a/Atf3 axis as the key regulator in obesity-associated ATM activation, adipose tissue inflammation and metabolic diseases.

Pancreatic β-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes (T2D). Recent clinical and experimental studies have suggested that the functional capacity of β-cells, particularly in the first phase of insulin secretion, is a primary contributor to the progression of T2D and its associated complications. Pancreatic β-cells undergo dynamic compensation and decompensation processes during the development of T2D, in which metabolic stresses such as endoplasmic reticulum stress, oxidative stress, and inflammatory signals are key regulators of β-cell dynamics. Dietary and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D, especially in the early stages. Whilst the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague, accumulating evidence has implicated the improvement of β-cell functional capacity. In this review, we summarize recent advances in the understanding of the dynamic adaptations of β-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions on β-cell dysfunction in T2D. This review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D, and more importantly, it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.

Implementation of a critical care pathway (CCP) for acute coronary syndrome (ACS) has been shown to improve early compliance to guideline-directed therapies and reduce early mortality. Nevertheless its long-term impact on the compliance with medications or clinical outcomes remains unknown. Between 2004 and 2015, 2023 consecutive patients were admitted to our coronary care unit with ACS. We retrospectively compared the outcomes of 628 versus 1059 patients (mean age 66.1 ± 13.3 years, 74% male) managed before and after full implementation of a CCP. Compared with standard care, implementation of the CCP significantly increased coronary revascularization and long-term compliance with guideline-directed medical therapy (both P

The prognostic implication of early ventricular tachyarrhythmias (VTs) after acute coronary syndrome (ACS) remains unclear.We sought to investigate the clinical outcomes of early monomorphic and non-monomorphic VTs that occur within 48 hours in patients after ACS.We retrospectively reviewed the clinical outcomes of 2033 [mean age 67.0 ± 13.4 years; 1486 (73.1%) men] consecutive patients who presented with ACS from 2004 to 2015.A total of 67 (3.3%) and 90 (4.4%) patients developed early monomorphic or non-monomorphic VT, respectively. Killip class IV (odds ratio [OR] 3.05; 95% confidence interval [CI] 1.47-6.36; P.01), creatine kinase level (OR 1.01; 95% CI 1.00-1.02 per 100 IU/L; P = .01), and left ventricular ejection fraction (OR 0.96; 95% CI 0.94-0.99; P.01) were independently associated with early monomorphic VT, whereas age (OR 0.98; 95% CI 0.97-0.99; P = .04), ST elevated myocardial infarction (OR 3.53; 95% CI 1.71-7.27; P.01), Killip class IV (OR 4.91; 95% CI 2.76-8.74; P.01), diabetes mellitus (OR 0.48; 95% CI 0.28-0.81; P.01), and left ventricular ejection fraction (OR 0.97; 95% CI 0.95-0.99; P.01) were independently associated with early non-monomorphic VT. More patients with early monomorphic VT (n = 22 [32.8%]) died in hospital than those with non-monomorphic VT (n = 16 [17.8%]) or without early VT (n = 133 [7.1%]; P.01). After a mean follow-up of 67.8 ± 43.2 months, 21 patients with early monomorphic VT (46.7%), 22 patients with early non-monomorphic VT (29.7%), and 552 patients without early VT (31.7%) died. Both early monomorphic and non-monomorphic VTs were associated with a long-term increase in sudden arrhythmic deaths and recurrent VTs. Nevertheless, only early monomorphic VT was shown to independently predict overall survival (hazard ratio 1.62; 95% CI 1.03-2.55; P = .04).Early monomorphic VT, but not early non-monomorphic VT, independently predicted all-cause mortality in patients with ACS who survived to hospital discharge.

The overvoltage during hard switching limits the full utilization of devices due to higher blocking voltage requirement. The faster switching speed of SiC MOSFET worsens the trade-off, and the understanding of the overvoltage’s mechanism is crucial for the better utilization. In this paper, experimental characterizations on the influence of circuit parasitic parameters and gate resistances on overvoltage are performed. Furthermore, a SPICE-based device behavioral model is built and found to able to accurately predict the overvoltage. The same method could be applied to device rating selection in converter design.

This paper evaluates potential benefits of high voltage (HV) SiC devices in medium voltage (MV) distribution grids. The MV microgrid, that HV SiC devices can benefit most, is selected as the “killer application” and focused in this paper. The design and simulation are carried out to compare Si-and SiC-based grid interface converters for the quantitative benefit assessment both at converter level and system level. The SiC-based converter has significant benefits in weight and size, and shows enhanced performance and functionality on power quality, system stability and low voltage ride through (LVRT) as well.

A new tetranuclear pyrophosphate-bridged Cu(II) complex with 4,4′-bipyridine and 1,10-phenanthroline [Cu4(phen)4(bpy)2(P2O7)2]·10H2O (1) has been hydrothermal synthesized and characterized by single-crystal X-ray analysis, element analysis, IR spectroscopy, TG analysis, and UV–vis spectra. Variable-temperature magnetic susceptibility measurements show the occurrence of antiferromagnetic interactions between the neighbor Cu(II) centers in 1. The analysis of the magnetic data in the whole temperature range allows the determination of the value of the intramolecular magnetic coupling (J = − 13.16 cm− 1).

The analysis and calculation of the settlement of the clay core rockfill dam is decided by the constitutive relation of the dam material. In this paper, the settlement of the clay core rockfill dam of Luding Hydropower Station under different working conditions is analyzed and calculated by using Duncan E-v and double yield surface elastic-plastic model. E-v model is quite sensitive to Poisson’s ratio, and the small changes of parameters G, D and F may lead to great differences in the deformation calculation results of the model, while the elastic-plastic model with double yield surface is not very sensitive, and its settlement calculation results under different working conditions are relatively stable.

A new organically templated molybdenum oxides compound Zn2(bpe)Mo2O8 (bpe = 1,2-bis(4-pyridyl)ethane) has been hydrothermal synthesized and characterized by single X-ray analysis, element analysis, IR spectroscopy, TG analysis, diffuse reflectance UV–Vis spectra. Compound 1 shows a three-dimensional net-like structure, where the bimetallic oxide layers {ZnMoO4} were knitted together with the bpe ligands. The optical band gap for 1 was 2.5 eV, which is comparable to that of TiO2. Moreover, the photoluminescent properties of 1 have been investigated at room temperature.

The post evaluation of Water Project in Xiasha district is taken as the object of study.The social influence of the project is evaluated from different parts according to the fuzzy analytic hierarchy process. Subjective and objective weights are combined to form the combined weight,taking the minimum information entropy as a tool.The fuzzy AHP comprehensive evaluation model of Water Project social influence in XiashaDistrict, which is based on entropy weight, is set up.The calculation result shows that the method is effective because the analysis result of the model, the project construction and environment characteristics achieve the basic agreement.

Monitoring of PM2.5 is the emphasis of atmospheric environment management, and the first thing to do is the choice of monitoring sites. In this paper, we took Beijing as an example for its more serious PM2.5 pollution. Priority analysis on monitoring sites of PM2.5 was proceeded with the algorithm TOPSIS, and the 30 basic monitoring points was optimized into 11 effective and representative monitoring points. The model been used is simple, scientific and practical and there is a great sense of promotion. Keywords: PM2.5, monitoring sites, Priority Analysis, TOPSIS algorithm.