Activation of M3 Muscarinic Acetylcholine Receptors Delayed Cardiac Aging by Inhibiting the Caspase-1/IL-1β Signaling Pathway

Background/Aims: Because the prevalence of age-related cardiac impairment increases as the human lifespan increases, it is important to combat the effects of aging. Recently, the cardiac M3 muscarinic acetylcholine receptor (M3-mAChR) has been demonstrated to play important roles in cardiac development and in the pathogenesis of cardiac diseases. However, the role of M3-mAChR in aging remains largely unknown. Therefore, the aim of this study was to investigate the involvement of M3-mAChR in the progression of cardiac aging. Methods: We established a cardiac aging model in mice through subcutaneous injection with D-galactose at a dose of 100 mg/kg/day for 6 weeks. D-galactose was also used to induce aging in primary cultured neonatal mouse cardiomyocytes. The myocardium from mice was stained with hematoxylin and eosin for histological analysis. The protein expression levels of p53 and p21 were determined using western blotting. The mRNA and protein expression levels of M3-mAChR, caspase-1, and interleukin (IL)-1β were determined using real-time PCR, immunohistochemical staining, and western blotting. Results: The expression of M3-mAChR was down-regulated in the myocardium from aged mice and D-galactose-treated mice, while the expression levels of caspase-1 and its downstream molecule IL-1β were significantly increased. The M3-mAChR agonist choline reduced the increase in caspase-1 in cardiomyocytes induced by D-galactose, which was reversed by the M3-mAChR antagonist 4-DAMP. Moreover, 4-DAMP promoted D-galactose-induced cardiomyocyte aging, which was attenuated by a caspase-1 inhibitor. Conclusion: Activation of M3-mAChR delayed cardiac aging by inhibiting the caspase-1/IL-1β signaling pathway

Hepatitis B Virus X Protein Drives Multiple Cross-Talk Cascade Loops Involving NF-κB, 5-LOX, OPN and Capn4 to Promote Cell Migration

Hepatitis B virus X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). However, the mechanism remains unclear. Recently, we have reported that HBx promotes hepatoma cell migration through the upregulation of calpain small subunit 1 (Capn4). In addition, several reports have revealed that osteopontin (OPN) plays important roles in tumor cell migration. In this study, we investigated the signaling pathways involving the promotion of cell migration mediated by HBx. We report that HBx stimulates several factors in a network manner to promote hepatoma cell migration. We showed that HBx was able to upregulate the expression of osteopontin (OPN) through 5-lipoxygenase (5-LOX) in HepG2-X/H7402-X (stable HBx-transfected cells) cells. Furthermore, we identified that HBx could increase the expression of 5-LOX through nuclear factor-κB (NF-κB). We also found that OPN could upregulate Capn4 through NF-κB. Interestingly, we showed that Capn4 was able to upregulate OPN through NF-κB in a positive feedback manner, suggesting that the OPN and Capn4 proteins involving cell migration affect each other in a network through NF-κB. Importantly, NF-κB plays a crucial role in the regulation of 5-LOX, OPN and Capn4. Thus, we conclude that HBx drives multiple cross-talk cascade loops involving NF-κB, 5-LOX, OPN and Capn4 to promote cell migration. This finding provides new insight into the mechanism involving the promotion of cell migration by HBx

Empirical Research on E-commerce to Increase the Scale of Agricultural Products Trade: Taking Guangxi Hezhou Zhengfeng Modern Agriculture Co., Ltd. as an Example

Agriculture is the foundation of the national economy. The periodicity of agricultural product output and prices, the asymmetry of information between buyers and sellers, and the inherent characteristics of small scale, high cost, and low profit have caused slow sales, which greatly hurt the enthusiasm of farmers to develop production and endanger social stability. Constructing an informationized and commercialized trading platform and an information sharing platform through e-commerce and establishing related systems and supervision mechanisms will help to promote the rapid growth of agricultural product sales. Research has shown that in the field of agricultural circulation, e-commerce has a significant effect on increasing the scale of agricultural trade

Microstructural Modeling and Strengthening Mechanism of TiB/Ti-6Al-4V Discontinuously-Reinforced Titanium Matrix Composite

A novel modeling method was proposed to provide an improved representation of the actual microstructure of TiB/Ti-6Al-4V discontinuously-reinforced titanium matrix composite (DRTMC). Based on the Thiessen polygon structure, the representative volume element (RVE) containing the complex microstructures of the DRTMC was first generated. Thereafter, by using multiple user-defined subroutines in the commercial finite element software ABAQUS, the application of asymmetric mesh periodic boundary conditions on the RVE was realized, and the equivalent elastic modulus of the DRTMC was determined according to the homogenization method. Through error analyses on the experimental and calculated results regarding the equivalent elastic parameters of the DRTMC, the rationality of generating the DRTMC finite element model by using the present method was validated. Finally, simulations based on four types of network-like models revealed that the present simplifications to the particle shape of the reinforcement phase had less of an influence on the overall composite strength. Moreover, the present study demonstrates that the DRTMC enhancement is mainly attributed to the matrix strengthening, rather than the load-transferring mechanism. The strengthening influences of the distribution forms of the reinforcement phases, including their distribution density and orientation, were studied further. It was found that both the higher distribution density and limited distribution orientation of the particles would increase the probability of overlapping and merging between particles, and; therefore, higher strength could be yielded when the volume fraction of the reinforcement phase reached a certain threshold. Owing to the versatility of the developed methods and programs, this work can provide a useful reference for the characterization of the mechanical properties of other composites types

Experimental Study of Imbibition Characteristics of Silica Sol in Coal-Measure Mudstone Matrix

Coal-measure mudstone is a typical dual-porosity media, and grouting in a matrix system is dominantly controlled by the imbibition effect for silica sol. This paper studies the imbibition effect using mudstone in the Huaibei mining area and silica sol as grouting material as an example. Groutability, driving force, and diffusion difficulty affecting the imbibition effect were tested by a mercury porosimeter, nanoparticle size analyzer, optical contact-angle measuring device, surface tension meter, and rotary viscosity meter. After finely grinding a mudstone sample, a pressureless imbibition process was conducted through nuclear magnetic resonance equipment for 216 h to study colloid spontaneous migration and phase characteristics. Results show that silica sol absorption rate follows a power function and that the spectrograms of T2 are distributed in a triple peak pattern, with a tendency to move to the right of vertex time. The paper lays a theoretical and experimental foundation for field grouting in the coal mine

Long-Term Mechanical Behavior of Nano Silica Sol Grouting

The longevity of grouting has a significant effect on the safe and sustainable operation of many engineering projects. A 500-day experiment was carried out to study the long-term mechanical behavior of nano silica sol grouting. The nano silica sol was activated with different proportions of a NaCl catalyst and cured under fluctuating temperature and humidity conditions. The mechanical parameters of the grout samples were tested using an electrohydraulic uniaxial compression tester and an improved Vicat instrument. Scanning electron microscope, X-ray diffraction, and ultrasonic velocity tests were carried out to analyze the strength change micro-mechanism. Tests showed that as the catalyst dosage in the grout mix is decreased, the curves on the graphs showing changes in the weight and geometric parameters of the samples over time could be divided into three stages, a shrinkage stage, a stable stage, and a second shrinkage stage. The catalyst improved the stability of the samples and reduced moisture loss. Temperature rise was also a driving force for moisture loss. Uniaxial compressive stress-strain curves for all of the samples were elastoplastic. The curves for uniaxial compression strength and secant modulus plotted against time could be divided into three stages. Sample brittleness increased with time and the brittleness index increased with higher catalyst dosages in the latter part of the curing time. Plastic strength-time curves exhibit allometric scaling. Curing conditions mainly affect the compactness, and then affect the strength

Spatiotemporal patterns and drivers of methane uptake across a climate transect in Inner Mongolia Steppe

Steppe soils are important biological sinks for atmospheric methane (CH4), but the strength of CH4 uptake remains uncertain due to large spatiotemporal variation and the lack of in situ measurements at regional scale. Here, we report the seasonal and spatial patterns of CH4 uptake across a 1200 km transect in arid and semi-arid steppe ecosystems in Inner Mongolia, ranging from meadow steppe in the east plain to typical and desert steppes on the west plateau. In general, seasonal patterns of CH4 uptake were site specific, with unimodal seasonal curves in meadow and typical steppes and a decreasing seasonal trend in desert steppe. Soil moisture was the dominant factor explaining the seasonal patterns of CH4 uptake, and CH4 uptake rate decreased with an increase in soil moisture. Across the transect, CH4 uptake showed a skewed unimodal spatial pattern, with the peak rate observed in the typical steppe sites and with generally higher uptake rates in the west plateau than in the east plain. Soil moisture, together with soil temperature, soil total carbon, and aboveground plant biomass, were the main drivers of the regional patterns of CH4 uptake rate. These findings are important for model development to more precisely estimate the soil CH4 sink capacity in arid and semi-arid regions. (C) 2020 Elsevier B.V. All rights reserved