Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model

IntroductionAngiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension.MethodsDahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696.Results and discussionThe study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment

Facile synthesis of a nickel sulfide (NiS) hierarchical flower for the electrochemical oxidation of H2O2 and the methanol oxidation reaction (MOR).

The synthesis of a novel hierarchical flower-like NiS via a solvothermal method for the electrochemcial oxidation of H2O2 on a carbon paste electrode with high catalytic activity for the (MOR) in an alkaline medium has been reported. Novel nickel sulfide (NiS) hierarchical flower-like structures were characterized by X-ray diffraction, scanning electron microscope, and transmission electron microscopy. A carbon paste electrode was modified with the as-prepared hierarchical flower-like NiS, resulting in a high electrocatalytic activity toward the oxidation of H2O2. The NiS-modified electrode was used for H2O2 sensing, which was achieved over a wide linear range from 0.5 μMto1.37mM(I/μA =-0.19025 + 0.06094 C/mM) with a low limit of detection (LOD) of 0.3 μM and a limit of quantitation (LOQ) of 0.8 μM. The hierarchical flower-like NiS also exhibited a high electrocatalytic activity for the methanol oxidation reaction (MOR) in an alkaline medium with a high tolerance toward the catalyst-poisoning species generated during the MOR. The MOR proceeded via the direct electrooxidation of methanol on the oxidized NiS surface layer because the oxidation peak potential of the MOR was more positive than that of the oxidation of NiS

Energy waste in buildings due to occupant behaviour

Occupants’ behaviour has a significant impact on the energy performance of buildings. A good understanding of how occupants use a building provides a possibility of promoting the building’s energy efficiency through changing occupant behaviour. Building simulation has been adopted as a useful method by building engineers for quantifying the effects of changing occupant behaviour on the building’s energy consumption and indoor environment. However, due to the lack of real measured data with respect to how occupants use the building, such simulation work has relied on assumed behavioural patterns, which significantly reduces the reliability of the predicted results. This paper describes a longitudinal study monitoring occupants’ heating, window opening and cooling behaviour in an office building throughout summer, transitional and winter periods. These behavioural data were then used to drive dynamic building performance simulation to predict the energy saving potential of changing behaviour. Comparison with predicted results by assumed behavioural patterns reflected that improperly assumed behavioural patterns may either overestimate or underestimate the energy saving potential of changing behaviour, especially for unextreme behaviours

Observed variability of intertropical convergence zone over 1998-2018

The intertropical convergence zone (ITCZ) accounts for more than 30% of the global precipitation and its variability has a great effect on the people living in the tropical area. It is the manifestation of the Hadley circulation, tropical dynamic and thermodynamic coupling and the air-sea interaction. Therefore, it is essential to understand the changes and variability of the ITCZ, including its position and intensity. Using observed precipitation from GPCP and TRMM 3B43, as well as the ERA5 reanalysis data, we examine the ITCZ variations over the global and seven regions from 1998-2018. These data sets show consistent ITCZ climatology and inter-annual variability. Except over Atlantic and eastern Pacific where ITCZ stays in the northern hemisphere, the ITCZ crosses the equator after equinoxes over other sections. There is no overall significant shift of annual mean ITCZ position over the globe and seven regions, except over the America section where the GPCP data show a significant increase trend of 0.8°decade-1 and over the western Pacific section where ERA5 data show a significant decrease trend of -1.2°decade-1. The ITCZ positions over the globe and Africa are related to both ENSO and NAO, while ITCZ position over eastern Pacific is significantly affected by ENSO and the Atlantic ITCZ is mainly related to NAO. Except for the western Pacific, all other sections are significantly related to local meridional surface temperature gradient, particularly over America, Atlantic and eastern Pacific. The meridional gradient variation of the vertically integrated moist static energy has generally good agreement with the shift of the intertropical convergence zone, particularly for the seasonal climatology over the Africa region. The relationship between ITCZ position and intensity shows complicated patterns, with positive correlation over the globe, but different correlations over different sections. The two observed data sets are more or less consistent, but ERA5 shows discrepancies over some sections. It is also found that the local meridional temperature gradient has more influences on the ITCZ positions than the global on

MicroRNA-323a-3p Promotes Pressure Overload-Induced Cardiac Fibrosis by Targeting TIMP3

Background/Aims: Cardiac fibrosis is a major cause of diverse cardiovascular diseases. MicroRNAs have recently been proven a novel class of regulators of cardiac fibrosis. In this study, we sought to investigate the role of miR-323a-3p and its mechanisms in regulating cardiac fibrosis. Methods: The transverse aortic constriction (TAC) mice model was induced and neonatal cardiac fibroblasts (CFs) were cultured. MTT (3- [4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay was used to detect the cell viability. Echocardiography was used to evaluate cardiac function. Masson’s Trichrome stain was used to evaluate the development of fibrosis. Luciferase activity assay was performed to confirm the miRNA’s binding site. Real-time PCR and Western blot were used to evaluate the level of mRNA and protein. Results: MiR-323a-3p was found up-regulated in myocardial tissues subjected to TAC and in CFs cultured with Angiotensin Ⅱ (Ang Ⅱ). Overexpression of miR-323a-3p significantly increased the mRNA levels of collagen Ⅰ, collagen Ⅲ, MMP2 and MMP9, while inhibition of miR-323a-3p prevented the proliferation, collagen production and the protein level of transforming growth factor (TGF-β) in rat neonatal CFs. Strikingly, injection of antagomiR-323a-3p elevated cardiac function and inhibited the expression of TGF-β in the TAC mice. TIMP3 was a direct target of miR-323a-3p, as the overexpression of miR-323a-3p decreased the protein and mRNA levels of TIMP3. In the CFs with pre-treatment of Ang Ⅱ, siRNA-TIMP abolished the effects of AMO-323a-3p on the inhibition of the proliferation of CFs, the down-regulation of collagen Ⅰ and collagen Ⅲ, and the expression of TGF-β. Conclusion: Our findings provide evidence that miR-323a-3p promotes cardiac fibrosis via miR-323a-3p-TIMP3-TGF-β pathway. miR-323a-3p may be a new marker for cardiac fibrosis progression and that inhibition of miR-323a-3p may be a promising therapeutic target for the treatment of cardiac fibrosis

DeePMD-kit v2: A software package for Deep Potential models

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials (MLP) known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, Deep Potential - Range Correction (DPRc), Deep Potential Long Range (DPLR), GPU support for customized operators, model compression, non-von Neumann molecular dynamics (NVNMD), and improved usability, including documentation, compiled binary packages, graphical user interfaces (GUI), and application programming interfaces (API). This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, the article benchmarks the accuracy and efficiency of different models and discusses ongoing developments.Comment: 51 pages, 2 figure

The Tianlai Cylinder Pathfinder array: System functions and basic performance analysis

The Tianlai Cylinder Pathfinder is a radio interferometer array designed to test techniques for 21 cm intensity mapping in the post-reionization Universe, with the ultimate aim of mapping the large scale structure and measuring cosmological parameters such as the dark energy equation of state. Each of its three parallel cylinder reflectors is oriented in the north-south direction, and the array has a large field of view. As the Earth rotates, the northern sky is observed by drift scanning. The array is located in Hongliuxia, a radio-quiet site in Xinjiang, and saw its first light in September 2016. In this first data analysis paper for the Tianlai cylinder array, we discuss the sub-system qualification tests, and present basic system performance obtained from preliminary analysis of the commissioning observations during 2016-2018. We show typical interferometric visibility data, from which we derive the actual beam profile in the east-west direction and the frequency band-pass response. We describe also the calibration process to determine the complex gains for the array elements, either using bright astronomical point sources, or an artificial on site calibrator source, and discuss the instrument response stability, crucial for transit interferometry. Based on this analysis, we find a system temperature of about 90 K, and we also estimate the sensitivity of the array