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Non-alcoholic fatty liver disease (NAFLD) has become a global health problem. However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a potential drug target for treatment of NAFLD. In an attempt to screen FXR agonists, we found that cycloastragenol (CAG), a natural occurring compound in Astragali Radix, stimulated FXR transcription activity. In animal studies, we demonstrated that CAG treatment resulted in obvious reduction of high-fat diet induced lipid accumulation in liver accompanied by lowered blood glucose, serum triglyceride levels and hepatic bile acid pool size. The stimulation of FXR signalling by CAG treatment in DIO mice was confirmed via gene expression and western blot analysis. Molecular docking data further supported the interaction of CAG and FXR. In addition, CAG alleviated hepatic steatosis in methionine and choline deficient L-amino acid diet (MCD) induced non-alcoholic steatohepatitis (NASH) mice. Our data suggest that CAG ameliorates NAFLD via the enhancement of FXR signalling. [ABSTRACT FROM AUTHOR]

Abstract: Stay cables of cable-stayed bridges often experience vibrations with large amplitudes induced by wind or jointly by both wind and rain. To understand the aerodynamic characteristics of the stay cables and excitation mechanics of rain–wind-induced vibration (RWIV), an inclined and yawed circular cylinder with and without an artificial upper rivulet is studied through a series of wind tunnel tests. The impacts of upper rivulet and axial flow on the aerodynamics of the cylinder are investigated. It is found that for an inclined and yawed cylinder without rivulet there exists a non-zero lift force at large wind angle. Furthermore, the wind pressures and aerodynamic forces acting on both the cylinder and the upper rivulet are obtained, which can be used to develop more rational theoretical models for RWIV of stay cables. Results show that the upper rivulet can both enhance and depress Karman vortex shedding depending on the position of the rivulet. As a result, dramatic variations of the aerodynamic forces acting on the cylinder and the rivulet will occur, which may eventually result in RWIV. Also axial flow may have a noticeable influence on the aerodynamic characteristics of the inclined and yawed cylinder. And the presence of the rivulet can enhance such influence from the axial flow. [Copyright &y& Elsevier]

Abstract: Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness induced by autoantibodies against the acetylcholine receptor. CTLA-4 (CD152) plays an inhibitory role in the immune response and has been suggested to be involved in the pathophysiology of MG. In this study, we focused on alternative CTLA-4 mRNA expression in PBMCs from MG patients. We defined two new isoforms of CTLA-4 mRNA that arise due to alternative splicing. By semi-quantitative RT-PCR analysis, we observed a lower expression of sCTLA-4 mRNA relative to the membrane form in MG patients. In addition, the MG patients had lower levels of sCTLA-4 mRNA in PBMCs compared to healthy controls, as assessed by real-time PCR. One of the spliced isoforms (LCTLA-4) was more prevalent in MG patients compared to healthy controls. The alternative splicing was not associated with sex, thymectomy, serum levels of anti-AChR, immunosuppressive treatment or the four CTLA-4 gene polymorphisms analyzed. This study reveals an abnormal spectrum of mRNA expression of CTLA-4 in MG patients, which marks the importance of studying gene expression of alternative splicing. [Copyright &y& Elsevier]

In wind resistance research involving super high-rise buildings, most studies have concentrated on increases in the wind velocity with height, but Ekman layer effects, inducing wind veering, have rarely been considered. Therefore, the main objective of this paper is to investigate the Ekman layer effects on super high-rise buildings based on computational fluid dynamics (CFD). Numerical simulations were systematically performed on a 3D square cylinder with an aspect ratio of 9:1 using the large eddy simulation (LES) method. The simulation results for three different incident mean wind profiles, including a logarithmic profile without veering, a profile with an inflection point but without veering, and a profile with an inflection point and veering, were compared to illustrate the differences in the wind loads and flow fields with and without wind veering. The results reveal that the proposed method is capable of simulating the wind veering profiles. The local wind pressure distribution on the building is considerably affected by wind veering, especially at the upper portion of the building surface. The effects of wind veering on the mean aerodynamic forces for super high-rise buildings are mainly in the aspect of Y-axis force, X-axis and torsional moment, and the fluctuations of local wind forces and base moments decrease to various degrees. • Performed RANS simulations of wind veering profiles using a modified k - ε model. • Performed LES of wind effects on a super high-rise building considering veering. • Illustrated differences in wind loads and flow fields with and without veering. [ABSTRACT FROM AUTHOR]

Coptisine is a natural occurring isoquinoline alkaloid isolated from the traditional Chinese medicinal herb Rhizoma coptidis . Coptisine has been reported to have protective effects on reperfusion injury in cardiomyocytes, however, the underlying mechanism remains uncertain. Here, we used a hypoxia/reoxygenation (H/R)-treated H9c2 cell model to study the protective effects of coptisine on cardiomyocyte. The results showed that NaS 2 O 4 induced hypoxia/reoxygenation model increased apoptosis and up-regulated autophagy marker LC3-II and cleaved Caspase-3, Beclin1 and Sirt1 levels. Coptisine treatment increased cell survival, inhibited apoptosis, and reduced the protein level of LC3-II, cleaved Caspase-3, Beclin1 and Sirt1. Further, we showed that coptisine combined with chloroquine (CQ), the inhibitor of autolysosome, reduced LC3-II, suggesting that coptisine may inhibit autophagosome formation than induction of autolysosome in the autophagy events. Our results indicate that coptisine may protect cardiomyocyte damage by H/R through suppressing autophagy. Overall, our study provides a new mechanism for the treatment of coptisine on H/R-induced cardiomyocyte damage and death. [ABSTRACT FROM AUTHOR]

Abstract: Rice kernels of a transgenic high-amylose rice line and its wild type were examined by a high-resolution X-ray microtomography (XMT) and an environmental scanning electron microscope. Two-dimensional (2-D) cross-sectional images and 3-D objects from XMT were reconstructed and analyzed to elucidate their structural features. The lack of two isoforms of starch branching enzyme, termed SBEI and SBEIIb in high-amylose rice (HAR), resulted in a distinctly different grain inner density than wild-type rice (WTR). HAR had smaller, elongated starch granules with air spaces inside the kernels resulting in an opaque grain, whereas WTR had a tight endosperm with little air space and polygonal starch granules. XMT allowed a full 3-D characterization of the rice kernel structure and revealed that air space distribution was not uniform in the HAR kernel. [Copyright &y& Elsevier]

Abstract: In rice grains, high amylose content (AC) is correlated with poor grain quality, particularly in indica hybrid rice. To obtain indica hybrid rice with improved cooking and eating qualities, we introduced the antisense Waxy (Wx) gene into 2 elite parental lines of indica hybrid rice by using co-transformation methods. Subsequently, we selected several elite homozygous transgenic lines that did not contain the selectable marker. The expression of the endogenous Wx gene of the selected transgenic lines was significantly downregulated, resulting in low AC in the mature seeds; moreover, the AC in some lines reduced to the level observed in glutinous rice. With the decrease in AC, the gel consistency of the transgenic rice became softer, and the gelatinization temperature tended to be higher than those of the wild types, especially in the case of the Longtefu-derived transformants. We also analyzed the pasting properties of the selected transgenic low-AC lines, and we noted an improvement in the pasting properties of the transgenic rice lines. The results from a field trial indicated that the grain weights of the transgenic lines with lower AC exhibit remarkable reduction compared with those of the wild types. [Copyright &y& Elsevier]