Numerical simulation of creep fracture evolution in fractured rock masses

The initiation, expansion, and penetration of microscopic cracks in rock is the macroscopic manifestation of creep. This paper investigates mechanical creep characteristics and fracture evolution processes in rock masses with different fracture angles, lengths, and rock bridge dip angles. Single fractures, dual parallel fractures, and fracture groups are considered. The approach comprises discrete element simulation based on continuum mechanics, utilizing the continuous and discontinuous software, GDEM. Single-fracture rock masses are characterized by a progressive fracture development mode dominated by tensile shear failure. The rate of creep and fracture magnitude both increase according to fracture length. With increasing fracture inclination angle, creep rate and fracture magnitude increase and decrease. The creep rate and degree of rupture are highest for fractures inclined at 30°. The dual-fracture rock mass exhibits both tensile crack failure and compressional shear failure. Creep rates are highest, and rupture effects are most apparent at rock bridge inclination angles of 90°. If the rock bridge is too long or too short, the stable creep stage is prolonged, but the creep acceleration stage intensifies due to interaction between fracture-bounded rock masses. The failure mode, in this case, involves collective failure by tension fractures and compressional shear. Creep rate and fracture magnitude increase with the number of fractures, which accelerates rock mass deformation to a certain extent. However, when the number of fractures reaches a certain threshold, a relatively stable structure may become established, slowing down the creep rate, especially during the creep acceleration stage. This study can provide a theoretical basis and reference for investigating the creep rupture law of rock mass engineering and the prevention and control of fractured rock mass geological disasters

Establishment and Application of a High Throughput Screening System Targeting the Interaction between HCV Internal Ribosome Entry Site and Human Eukaryotic Translation Initiation Factor 3

Viruses are intracellular obligate parasites and the host cellular machinery is usually recruited for their replication. Human eukaryotic translation initiation factor 3 (eIF3) could be directly recruited by the hepatitis C virus (HCV) internal ribosome entry site (IRES) to promote the translation of viral proteins. In this study, we establish a fluorescence polarization (FP) based high throughput screening (HTS) system targeting the interaction between HCV IRES and eIF3. By screening a total of 894 compounds with this HTS system, two compounds (Mucl39526 and NP39) are found to disturb the interaction between HCV IRES and eIF3. And these two compounds are further demonstrated to inhibit the HCV IRES-dependent translation in vitro. Thus, this HTS system is functional to screen the potential HCV replication inhibitors targeting human eIF3, which is helpful to overcome the problem of viral resistance. Surprisingly, one compound HP-3, a kind of oxytocin antagonist, is discovered to significantly enhance the interaction between HCV IRES and eIF3 by this HTS system. HP-3 is demonstrated to directly interact with HCV IRES and promote the HCV IRES-dependent translation both in vitro and in vivo, which strongly suggests that HP-3 has potentials to promote HCV replication. Therefore, this HTS system is also useful to screen the potential HCV replication enhancers, which is meaningful for understanding the viral replication and screening novel antiviral drugs. To our knowledge, this is the first HTS system targeting the interaction between eIF3 and HCV IRES, which could be applied to screen both potential HCV replication inhibitors and enhancers

Satellite Observed Positive Impacts of Fog on Vegetation

Fog is an important water source for many ecosystems, especially in drylands. Most fog‐vegetation studies focus on individual plant scale; the relationship between fog and vegetation function at larger spatial scales remains unclear. This hinders an accurate prediction of climate change impacts on dryland ecosystems. To this end, we examined the effect of fog on vegetation utilizing both optical and microwave remote sensing‐derived vegetation proxies and fog observations from two locations at Gobabeb and Marble Koppie within the fog‐dominated zone of the Namib Desert. Significantly positive relationships were found between fog and vegetation attributes from optical data at both locations. The positive relationship was also observed for microwave data at Gobabeb. Fog can explain about 10%–30% of variability in vegetation proxies. These findings suggested that fog impacts on vegetation can be quantitatively evaluated from space using remote sensing data, opening a new window for research on fog‐vegetation interactions

Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism

Improved chemical and electrochemical stability of perovskite oxides with less reducible cations at the surface

Segregation and phase separation of aliovalent dopants on perovskite oxide (ABO3) surfaces are detrimental to the performance of energy conversion systems such as solid oxide fuel/electrolysis cells and catalysts for thermochemical H2O and CO2 splitting. One key reason behind the instability of perovskite oxide surfaces is the electrostatic attraction of the negatively charged A-site dopants (for example, ) by the positively charged oxygen vacancies () enriched at the surface. Here we show that reducing the surface concentration improves the oxygen surface exchange kinetics and stability significantly, albeit contrary to the well-established understanding that surface oxygen vacancies facilitate reactions with O2 molecules. We take La0.8Sr0.2CoO3 (LSC) as a model perovskite oxide, and modify its surface with additive cations that are more and less reducible than Co on the B-site of LSC. By using ambient-pressure X-ray absorption and photoelectron spectroscopy, we proved that the dominant role of the less reducible cations is to suppress the enrichment and phase separation of Sr while reducing the concentration of and making the LSC more oxidized at its surface. Consequently, we found that these less reducible cations significantly improve stability, with up to 30 times faster oxygen exchange kinetics after 54 h in air at 530 °C achieved by Hf addition onto LSC. Finally, the results revealed a 'volcano' relation between the oxygen exchange kinetics and the oxygen vacancy formation enthalpy of the binary oxides of the additive cations. This volcano relation highlights the existence of an optimum surface oxygen vacancy concentration that balances the gain in oxygen exchange kinetics and the chemical stability loss

Identification and Analysis of Novel Inhibitors against NS3 Helicase and NS5B RNA-Dependent RNA Polymerase from Hepatitis C Virus 1b (Con1)

Hepatitis C virus (HCV) leads to severe liver diseases, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Non-structural protein 3 helicase (NS3h) and non-structural protein 5B RNA-dependent RNA polymerase (NS5B) are involved in the replication of HCV RNA genome, and have been proved to be excellent targets for discovery of direct-acting antivirals. In this study, two high-throughput screening systems, fluorescence polarization (FP)-based ssDNA binding assay and fluorescence intensity (FI)-based dsRNA formation assay, were constructed to identify candidate NS3h and NS5B inhibitors, respectively. A library of approximately 800 small molecules and crude extracts, derived from marine microorganisms or purchased from the National Compound Resource Center, China, were screened, with three hits selected for further study. Natural compound No.3A5, isolated from marine fungi, inhibited NS3h activity with an IC50 value of 2.8 μM. We further demonstrated that compound No.3A5 inhibited the abilities of NS3h to bind ssDNA in electrophoretic mobility shift assay and to hydrolyze ATP. The NS3h-inhibitory activity of compound No.3A5 was reversible in our dilution assay, which indicated there was no stable NS3h-No.3A5 complex formed. Additionally, compound No.3A5 exhibited no binding selectivity on NS3h or single strand binding protein of Escherichia coli. In NS5B assays, commercial compounds No.39 and No.94 previously reported as kinase inhibitors were found to disrupt dsRNA formation, and their IC50 values were 62.9 and 18.8 μM, respectively. These results highlight how identifying new uses for existing drugs is an effective method for discovering novel HCV inhibitors. To our knowledge, all inhibitors reported in this study were originally discovered with HCV anti-non-structural protein activities in vitro

Heart regeneration, stem cells, and cytokines

The human heart has limited regenerative capacity, which makes the reparative response after the cardiac infarction quite challenging. During the last decade, stem cells have become promising candidates for heart repair, owing to their potent differentiation capacity and paracrine cytokine secretion. Among the different types of stem cells, mesenchymal stem cells have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs. The paracrine cytokines play important roles in cardiac regeneration, neovascularization, anti-apoptosis, and anti-remodeling mechanisms, among others. This review summarizes the cytokines secreted by stem cells and their relative signaling pathways, which represent key mechanisms for heart regeneration and may serve as a promising future therapeutic strategy for myocardial infarction patients

Modelling and analysis of electromagnetic force, vibration, and noise in permanent magnet synchronous motor for electric vehicles under different working conditions considering current harmonics

Abstract The vibration and noise of the permanent magnet synchronous motor (PMSM) is mainly caused by its electromagnetic force. Harmonic currents affect the vibration, and noise performance of PMSM by influencing its electromagnetic force. The regularity of electromagnetic force, vibration, and noise characteristics of PMSM for electric vehicles (EVs) under different working conditions influenced by the harmonic currents is studied. Firstly, the analytical model of electromagnetic force under the action of a harmonic current is derived, and the influence of harmonic currents on the electromagnetic force of PMSM is summarised. Secondly, a multi‐physical field coupled vibration, and noise calculation model considering harmonic currents is established using the finite element method, and the vibration, and noise characteristics of PMSM under different operating conditions are analysed. The results show that the harmonic currents have different patterns of influence on the vibration, and noise of the PMSM due to the different advance angles and the saturation degree of the magnetic material under different working conditions. Finally, the validity of the theoretical analysis is verified by experiments, which has academic significance for vibration, and noise reduction of PMSMs for EVs