NLRP3-inflammasome inhibition by MCC950 attenuates cardiac and pulmonary artery remodelling in heart failure with preserved ejection fraction.

AIMS: The purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF). MAIN METHODS: Serum inflammatory cytokines were detected in patients with heart failure. Correlation analysis was performed to investigate the relationship between serum inflammatory cytokines and left ventricular diastolic function. A 'two-hit' (metabolic stress and mechanical stress) mouse model of HFpEF was established. Furthermore, MCC950 was used to determine the role of NLRP3-inflammasome inhibition in cardiac and pulmonary artery remodelling in HFpEF mice. KEY FINDINGS: Compared with heart failure patients with reduced ejection fraction, patients with HFpEF have significantly elevated serum inflammatory cytokine levels. Serum NLRP3 and interleukin-1ß levels were positively correlated with the diastolic function of HFpEF. In the HFpEF mouse model, the inhibition of the NLRP3-inflammasome by MCC950 improved exercise intolerance, glucose intolerance, and left ventricular diastolic function, but had no significant effect on systolic function. Meanwhile, MCC950 attenuated the release of inflammatory cytokines, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, the potential protective effects of MCC950 are achieved by inhibiting activation of the NLRP3-IL-1ß pathway and cascade expansion of downstream inflammatory cytokines. Additionally, the inhibition of NLRP3-inflammasome by MCC950 reduced pulmonary artery pressure and improved pulmonary artery remodelling in HFpEF. SIGNIFICANCE: The NLRP3-inflammasome plays a considerable role in inflammation and cardiac and pulmonary artery remodelling in HFpEF by activating the cascade reaction of inflammatory cytokines. This study is the first to comprehensively elucidate the role of the NLRP3-inflammasome in HFpEF, and will provide reference for future study.

Performance improvement of GaN-based microdisk lasers by using a PEALD-SiO2 passivation layer.

Dry-etching is often utilized to shape GaN-based materials. However, it inevitably causes plenty of sidewall defects as non-radiative recombination centers and charge traps that deteriorate GaN-based device performance. In this study, the effects of dielectric films deposited by plasma-enhanced atomic layer deposition (PEALD) and plasma-enhanced chemical vapor deposition (PECVD) on GaN-based microdisk laser performance were both investigated. The results demonstrated that the PEALD-SiO2 passivation layer largely reduced the trap-state density and increased the non-radiative recombination lifetime, thus leading to the significantly decreased threshold current, notably enhanced luminescence efficiency and smaller size dependence of GaN-based microdisk lasers as compared with the PECVD-Si3N4 passivation layer.

The Efficacy and Safety of Cryoballoon Versus Radiofrequency Ablation for the Treatment of Atrial Fibrillation: A Meta-Analysis of 15 International Randomized Trials.

The purpose of this study was to evaluate the efficacy and safety of cryoballoon versus radiofrequency ablation for the treatment of atrial fibrillation (AF) by systematically reviewing randomized controlled trials (RCTs). Databases of Pubmed, Web of science, Embase, and Cochrane Library were searched for published studies up to June 31, 2022. Only RCTs comparing the efficacy and safety of cryoballoon vs radiofrequency ablation for the treatment of AF were enrolled in meta-analysis. Fifteen RCTs characterizing 2709 patients were finally included. Meta-analysis found that cryoballoon ablation was associated with a similar proportion of patients free from AF [risk ratio (RR): 1.02; 95% confidence interval (CI): 0.93 to 1.12, P = 0.65]. Acute pulmonary vein isolation rate [RR: 1.0; 95% CI: 0.98 to 1.01, P = 0.64] and fluoroscopy time (weighted mean difference: -0.03; 95% CI: -4.35 to 4.28; P = 0.99) were not statistically significant difference. The procedure time was shorter in the cryoballoon ablation (CBA) group (weighted mean difference : -18.76; 95% CI: -27.27 to -10.25; P < 0.0001). Transient phrenic nerve palsy was uniquely observed in the CBA group (RR = 6.66; 95% CI: 2.82 to 15.7, P < 0.0001) and resolved in all during the follow-up period, total complication was similar in both groups (RR = 1.24; 95% CI: 0.86 to 1.79, P = 0.24). Although the procedure time was shorter in CBA group, the efficacy and safety were similar in each group. Compared with radiofrequency ablation for the treatment of AF, patients receiving cryoballoon ablation have similar outcomes. CBA is associated with a shorter duration of procedure.

Electrically injected GaN-on-Si blue microdisk laser diodes.

III-nitride blue microdisk laser diodes are highly desirable in emerging applications, such as augmented reality, virtual reality, and visible light communication. However, the electrically pumped blue microdisk lasers have been lagging for decades owing to weak optical confinement and large internal absorption loss. In this study, the waveguide layers and cladding layers were carefully engineered to enhance the optical confinement and reduce internal absorption loss. Therefore, the first electrically injected blue microdisk laser diodes grown on Si substrates have been successfully fabricated, and exhibited a resistor-capacitance-limited bandwidth of 24.1 GHz, showing highly promising applications in high-speed and large-modulation-bandwidth visible light communication.

Therapeutic effects and safety of early use of sacubitril/valsartan after acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: infarction (AMI) can be reduced by the use of sacubitril/valsartan. However, the therapeutic effects of sacubitril/valsartan in clinical settings are inconsistent. In this paper, the related research on the application of sacubitril/valsartan in AMI was comprehensively searched, in order to explore the clinical efficacy and safety of early application of sacubitril/valsartan after AMI. METHODS: English databases, including American National Library of Medicine, Medline, and Embase, and Chinese databases, including Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), Wanfang, and VIP, were searched using a combination of the following search terms: AMI, acute ST-segment elevation myocardial infarction (STEMI), acute non-ST-segment elevation myocardial infarction (NSTEMI), sacubitril/valsartan sodium tablets, and angiotensin receptor enkephalinase inhibitors. The experimental group was given Sacubitril/Valsartan sodium tablets, while the control group was given angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB). Cochrane Handbook 5.0 risk assessment table were used for quality assessment and bias risk assessment. RESULTS: A total of 5 articles were included in the meta-analysis. The total incidence of adverse cardiovascular events in the sacubitril/valsartan group was significantly lower than that in the control group {relative risk (RR) =0.61 [95% confidence interval (CI): 0.46, 0.82], significance testing Z=3.36, and P=0.0008}. The difference between the rehospitalization rate of the sacubitril/valsartan group and control group was statistically significant [RR =0.67 (95% CI: 0.47, 0.95), significance testing Z=2.23, and P=0.03]. The difference in low blood pressure between the sacubitril/valsartan group and the control group was statistically significant [RR =1.28 (95% CI: 1.18, 1.40), significance testing Z=5.58, and P<0.00001]. The difference in left ventricular ejection fraction (LVEF) between the sacubitril/valsartan group and control group was statistically significant [mean difference (MD) =3.09 (95% CI: 1.69, 4.49), significance testing Z=4.33, and P<0.0001]. DISCUSSION: Sacubitril/valsartan was found to inhibit ventricular remodeling after AMI, improve cardiac function, and reduce the incidence of adverse cardiovascular events after myocardial infarction, the rehospitalization rate, and the mortality rate.

Atorvastatin rescues pulmonary artery hypertension via inhibiting the AKT/ERK-dependent PDGF-BB/HIF-1α axis.

BACKGROUND: To explore the role of Atorvastatin in rescuing pulmonary artery hypertension (PAH) via inhibiting the AKT/ERK-dependent PDGF-BB/HIF-1α axis. METHODS: PAH model in rats was established by MCT induction, followed by Atorvastatin intervention. Pulmonary hemodynamic measurement and pulmonary morphological evaluation in rats were conducted. Human pulmonary artery smooth muscle cells (hPASMCs) were subjected to hypoxic exposure or PDGF-BB treatment, followed by Atorvastatin induction. Relative levels of HIF-1α, p-ERK and p-Akt were detected. Viability and apoptosis were respectively determined by cell counting kit-8 (CCK-8) assay and flow cytometry. RESULTS: Atorvastatin protected PAH-induced increases in RVSP and Fulton's index in rats. Meanwhile, it inhibited vascular remodeling following PAH by downregulating HIF-1α and PDGF-BB. Hypoxia or PDGF-BB treatment in hPASMCs resulted in upregulation of p-ERK and p-Akt, and viability increase, which were partially abolished by Atorvastatin intervention. In addition, Atorvastatin triggered apoptosis in hypoxia or PDGF-BB-induced hPASMCs. CONCLUSIONS: Atorvastatin inhibits the activation of HIF-1α and proliferative ability, and triggers apoptosis in hPASMCs exposed to hypoxia or PDGF-BB treatment through inactivating the AKT/ERK pathway.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Chronic Kidney Disease: A Meta-Analysis.

OBJECTIVE: The aim of this meta-analysis was to compare the clinical outcomes of transcatheter aortic valve replacement (TAVR) with those of surgical aortic valve replacement (SAVR) in patients with chronic kidney disease (CKD). DESIGN: Meta-analysis of 10 observational studies. SETTING: Hospital. PARTICIPANTS: Patients with CKD (9,619) undergoing aortic valve replacement. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Medline, Cochrane Library, and Embase databases were searched for clinical studies published from January 2000 to October 2018. Studies that fulfilled the predefined inclusion criteria were included. The primary clinical outcomes included early all-cause mortality and postoperative stroke. Random-effects modeling was used to calculate odds ratio (OR) and 95% CI. After a literature search of the major databases, 10 observational cohort studies with a total of 9,619 patients were identified. Pooled analysis indicated that, when compared with SAVR, TAVR was associated with a lower risk of early all-cause mortality (6.1% v 10.2%; OR: 0.71; 95% CI: 0.51-0.98) and stroke (1.1% v 2.2%; OR: 0.53; 95% CI: 0.37-0.75). Although TAVR increased the risk of pacemaker implantation (OR: 2.06; 95% CI: 1.16-3.66), it reduced the risk of blood transfusion (OR: 0.50; 95% CI: 0.39-0.65), infection (OR: 0.30; 95% CI: 0.13-0.70), acute kidney injury (AKI) (OR: 0.46; 95% CI: 0.38-0.55), and AKI requiring dialysis (OR: 0.66; 95% CI: 0.58-0.75). There were not significant differences in the incidence rates of cardiac tamponade (OR: 0.60; 95% CI: 0.26-1.36) and major vascular damage (OR: 1.12; 95% CI: 0.81-1.55) between the 2 groups. CONCLUSION: Transcatheter aortic valve replacement might be a preferable approach to SAVR in patients with CKD. A large, prospective, randomized controlled trial is warranted.

[Studies on the chemical constituents of Phlomis younghusbandii].

OBJECTIVE: To study the chemical constituents of Phlomis younghusbandii. METHODS: Compounds were isolated from the ethanolic extract by silica gel column chromatography, and their structures were identified by physical and chemical evidences and spectral methods. RESULTS: Eight compounds were isolated and identified respectively as 8-acetylshanzhiside methyl ester (1), shanzhiside methyl ester (2), phlomiol (3), 2-butoxy-2-(hydroxymthyl) tetrahydro-2H-3,4,5-pyrantriol (4), sesamoside (5), pulchelloside-I (6), luteolin-7-O-beta-D-glucopyranoside (7) and daucosterol (8). CONCLUSION: All the compounds were isolated from the plant for the first time.