Search

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-β1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/β-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

In this communication, a novel compact single whip wideband antenna with an improved omnidirectional wideband antenna is proposed. First, a single whip antenna is designed on a thin flexible printed circuit (FPC) with a tapered coplanar waveguide feed line. This proposed antenna shows a wide impedance matching performance in a frequency range from 194 to 2124 MHz with a bandwidth ratio of 10:1, while a measured return loss is better than 10 dB within the desired passband. The single whip antenna has demonstrated an ultrawide bandwidth with satisfactory radiation properties in the lower frequency band. However, the omnidirectional radiation pattern deteriorated in the higher frequency band. Three whipped antennas are codesigned to form an improved omnidirectional radiation pattern. Finally, the measured performance of the fabricated antenna shows a good agreement with that obtained through simulation results.

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

Background Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment.Methods An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters.Results Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55–0.98) and cluster 1 (HR 0.54, 95% CI 0.37–0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05–1.32).Conclusion Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.

Wheat stripe rust, caused by Puccinia striiformisf. sp. tritici(Pst), is an airborne disease. In China, it frequently develops initially in central Shaanxi and southwestern Gansu, and from there, inoculum spreads to the eastern wheat production regions. Field investigations have suggested that Pstcould spread from the west to the east within central Shaanxi and that Gansu could serve as the inoculum source for central Shaanxi, but there is no direct evidence for this hypothetical dispersal route. In the current study, 321 Pstisolates collected from central Shaanxi and Gansu in the 2019-2020 and 2020-2021 winter wheat cropping seasons were genotyped using 23 pairs of KASP-SNP markers. The dispersion among subpopulations was analyzed using several approaches, and overall, the populations were found to exhibit high levels of genetic diversity. There was little genetic divergence (0.05 >Fst0) within central Shaanxi. However, significant gene flow (Nm> 4) driven by wind-oriented dispersal from west (Baoji) to east (Weinan) occurred. There was also gene flow among the 4 Gansu subpopulations of Tianshui, Longnan, Pingliang, and Qingyang. Migration of the pathogen occurred between central Shaanxi and Gansu. Migration from Gansu to central Shaanxi was major compared with that from central Shaanxi to Gansu that was minor. Genetic variation occurred among isolates, instead of among subpopulations and within isolates. Linkage disequilibrium revealed that there was strong genetic recombination in the subpopulations from Gansu and central Shaanxi. Therefore, the present study provides molecular evidence that Pstspread from west to east in central Shaanxi and showed that Gansu (especially Longnan and Tianshui) was one of the major origins of the pathogen inoculum of wheat stripe rust in central Shaanxi. The results revealed the west-to-east transmission route of wheat stripe rust in central Shaanxi, being used to guide integrated management of the disease.

Coal mining begins after coalbed methane (CBM) production which reduces CH4 concentration in coalbeds. However once CH4 concentration reaches the explosion limit, the threat of explosion accident in the coal mine will be greatly increased. Based on safety production principle, this paper analyses the feasibility of CO2 injection through CBM wells to control CH4 concentration and enhance CBM recovery at the same time during CBM production. Safe concentration of CH4 is determined according to its explosion limit and safety factor. Combined with numerical simulation, a CH4 concentration control method by CO2 injection is proposed: firstly the CO2 injection standard is calculated to ensure CH4 safe concentration, and then the optimum CO2 injection rate (14000m3/d) is determined by comparisons between different injection rates. Finally CO2 emission reduction and recycle methods are proposed to achieve effective environmental protection and high economic efficiency.

For the trends of global climate warming, it is great important to implement the Carbon capture and storage (CCS) technology. This paper describes the numerical simulation of CO2 displacement enhanced oil recovery (EOR) in M reservoir. The M reservoir is an extra-thick buried hill fractured reservoir, which use overlap alternative horizontal well pattern to produce. Considering the time-varying effects of fracture’s porosity and permeability parameters, combining the develop dynamic and the diversification of physical property parameters of fractured formation, use the dual porosity dual permeability model and the three-dimensional components simulator to simulate the develop process. By CO2 WAG orthogonal experiment design, can simulate and predict the development effect of fractured buried hill reservoir affected by factors such as: different production and injection well pattern, injection intensity, gas water slug ratio, alternating cycle and so on. The results show that in the process of CO2 WAG can significantly reduce the risk of gas breakthrough by overlap alternative horizontal well pattern, and reduce the negative impact by fracture properties, also can improve EOR and CO2 sequestration effectively. On this basis, this paper evaluates the suitability of WAG development methods to fractured buried hill reservoir with overlap alternative horizontal well pattern, also optimizes the reasonable development plan for M reservoir.

Experimental investigations were conducted on the process of combustion and explosion vent in a 200 mm (diameter)×400 mm (length) vertical cylindrical vessel. When CH4-air mixture gases were used and the vent diameter was 55 mm, conditions of Φ(equivalent ratio)=0.8, Φ=1.0 and Φ=1.3 and two ignition positions (at the cylinder center and bottom) were selected. The venting processes and the correlated factors are discussed in this paper.

Prediction of cardiovascular disease (CVD) is important in clinical practice. Machine learning (ML) may offer an improved alternative to current CVD risk stratification in individual patients. We aim to identify important predictors and compare ML models with traditional models according to their prediction performance in a large long-term follow-up cohort.

Background: We applied a network Mendelian randomization (MR) framework to determine the causal association between body mass index (BMI) and coronary heart disease (CHD) and explored whether glycated hemoglobin (HbA1c) and lipid parameters (total cholesterol, TC; low-density lipoprotein cholesterol, LDL; high-density lipoprotein cholesterol, HDL; triglycerides, TG) serve as causal mediators from BMI to CHD by integrating summary-level genome-wide association study data.Methods: Network MR analysis, an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed. Summary statistics from the GIANT consortium were used (n= 152,893) for BMI, CARDIoGRAMplusC4D consortium data were used (n= 184,305) for CHD, Global Lipids Genetics Consortium data were used (n= 108,363) for TC, LDL, HDL and TG, and MAGIC consortia data were used (n= 108,363) for HbA1c.Results: The inverse-variance-weighted-method estimate indicated that the odds ratio (95% confidence interval) for CHD was 1.562 (1.391–1.753) per 1 standard deviation (kg/m2) increase in BMI. Results were consistent in MR Egger method and weighted-median methods. MR estimate indicated that BMI was positively associated with HbA1c and TG, and negatively associated with HDL, but was not associated with TC or LDL. Moreover, HbA1c, TC, LDL, and TG were positively associated with CHD, yet there was no causal association between HDL and CHD. HbA1c was positively associated with TC, LDL, and HDL, but was not associated with TG.Conclusions: Higher BMI conferred an increased risk of CHD, which was partially mediated by HbA1c and lipid parameters. HbA1c and TG might be the main mediators in the link from BMI to CHD.