Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

AbstractCurcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation

HECT, UBA and WWE domain containing 1 represses cholesterol efflux during CD4+ T cell activation in Sjögren’s syndrome

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction, leading to loss of salivary function. Histological analysis of salivary glands from SS patients reveals a high infiltration of immune cells, particularly activated CD4+ T cells. Thus, interventions targeting abnormal activation of CD4+ T cells may provide promising therapeutic strategies for SS. Here, we demonstrate that Hect, uba, and wwe domain containing 1 (HUWE1), a member of the eukaryotic Hect E3 ubiquitin ligase family, plays a critical role in CD4+ T-cell activation and SS pathophysiology.Methods: In the context of HUWE1 inhibition, we investigated the impact of the HUWE1 inhibitor BI8626 and sh-Huwe1 on CD4+ T cells in mice, focusing on the assessment of activation levels, proliferation capacity, and cholesterol abundance. Furthermore, we examined the therapeutic potential of BI8626 in NOD/ShiLtj mice and evaluated its efficacy as a treatment strategy.Results: Inhibition of HUWE1 reduces ABCA1 ubiquitination and promotes cholesterol efflux, decreasing intracellular cholesterol and reducing the expression of phosphorylated ZAP-70, CD25, and other activation markers, culminating in the suppressed proliferation of CD4+ T cells. Moreover, pharmacological inhibition of HUWE1 significantly reduces CD4+ T-cell infiltration in the submandibular glands and improves salivary flow rate in NOD/ShiLtj mice.Conclusion: These findings suggest that HUWE1 may regulate CD4+ T-cell activation and SS development by modulating ABCA1-mediated cholesterol efflux and presents a promising target for SS treatment

Aerodynamic Characteristics of a Ducted Fan Hovering and Transition in Ground Effect

Ducted fans installed on vertical takeoff and landing vehicles experience significant ground effect during takeoff and landing. The aerodynamic characteristics of a ducted fan hovering and transitioning in the ground effect are studied using numerical simulations in this paper. The flowfields are obtained by solving Reynolds Averaged Navier–Stokes equations with the Multiple Reference Frame approach. When a ducted fan hovers in the ground effect, the blade thrust increases due to the combined effect of the increase in the effective angle of attack of the blade and the increase in ambient pressure; the duct thrust decreases due to the combined effect of the decrease in the effective angle of attack of the duct and the increase in ambient pressure. Stall occurs at a certain advance ratio and angle of attack when transitioning in the ground effect. The ground effect delays the occurrence of stall at some advance ratios. The ground effect is hardly detectable at angles of attack less than 30° even if the height drops to 0.5 times the duct exit diameter. At this height and high angles of attack, the different positions and influence regions of the ground vortex at different advance ratios contribute to the different variation trends in the ducted fan performance

Analysis and simulation on two types of thrust reversers in an aircraft engine

With rapid development of new composite material and manufacturing, innovative engineering solutions are supplied to the advanced nacelle, such as integrated propulsion system(IPS), carbon-fiber composite inner skin by single-piece molding process，which offers a reduction in fuel burn and less noise produced by engines. The advanced nacelle has an O-duct thrust reverser demonstrator whose composite structure is in the form of an “O” as opposed to the traditional “D-duct”. A comparative study is to be conducted to investigate the differences between the latest O-duct and conventional D-duct in numerical approaches. To focus on the quantitative analysis of thrust reverser’s operation, this paper mainly uses CATIA/Digital Mock Up(DMU) to simulate under deployment and stowed conditions of two different thrust reverser. After comparing the structural weight, the design models of blocker door are built for kinematic analysis of relevant mechanism and simulation. The results show that simplified design and elimination of multiple interfaces generates weight saving, O-duct improves airflows within the engine, meanwhile D-duct has excellent cost effective and maintainability

Optimization of Hydraulic Fine Blanking Press Control System Based on System Identification

Fine-blanking is a molding process based on the common blanking process, which obtains hydrostatic stress through blank holder reverse jacking, in order to increase material plasticity. It requires special equipment, namely a fine-blanking press, to complete the fine-blanking process. In this paper, the problem of the speed of the slide block fluctuation found in the actual use of a 12,000 kN hydraulic fine-blanking press after multi-stage pressure source optimization is studied. Firstly, the mathematical model of the motion of the slide block in the blanking stage of the hydraulic fine blanking press is established, and the accurate mathematical model in the blanking stage of the hydraulic fine-blanking press is obtained through the least square method system identification experiment. Aiming at the complex working situation of the fine-blanking press, a phased PID control strategy is creatively proposed. The optimal PID control parameters are obtained by a genetic algorithm, and established a fuzzy PID controller for the blanking stage to accurately control the movement speed of the slide block. The results show that the new control strategy is very effective in improving the movement accuracy of the slide block, effectively improving the machining accuracy and reducing the impact vibration of the hydraulic system

Aktivni nadzor vibracij pri mehanski visokohitrostni servostiskalnici za natančno štancanje

The fine-blanking process as an advanced sheet metal forming process has been widely applied in industry. However, specially designed equipment is required for this process. In this paper, a novel mechanical servo high-speed fine-blanking press with the capacity of 3200 kN is proposed, and the vibration control for this machine is researched to achieve the requirement of fine-blanked parts of high dimensional accuracy, since the vibration of the fine-blanking machine will cause the machining displacement error and reduce the machining accuracy. Self-adaptive feed-forward control is used to simulate the active vibration control of the mechanical fine-blanking machine. The vibration control principle of the fine-blanking machine is described, and the control algorithm is established. At the same time, the mechanical vibration model of the fine-blanking machine as the controlled object is established, and the parameters of the excitation input and the mechanical model are obtained by the fine-blanking finite element simulation and the experiments of the vibration measurement of the press. Finally, the numerical simulation and analysis of active vibration control based on MATLAB are carried out. The results show that the control effect is good, and the vibration response is effectively reduced, thus greatly increasing the processing accuracy, saving a significant amount of energy, and reducing the energy consumption and defective rate

An Evaluation of Immobilized Poly-(<i>S</i>)-<i>N</i>-(1-phenylethyl)acrylamide Chiral Stationary Phases

In this study, brush type and polymer type stationary phases were prepared based on (S)-N-(1-phenylethyl) acrylamide, and the polymeric stationary phase demonstrated superior chiral recognition ability. The two polymeric stationary phases were synthesized by two strategies, one was the “grafting from” method, which obtained polymer CSP by initiating monomer polymerization on the surface of 3-methacrylatepropyl silica gel, and the other was “grafting to”, which fixed the copolymer of (S)-N-(1-phenylethyl) acrylamide and trimethoxysilylpropyl methacrylate on silica gel. A comparison of these two bonding modes revealed that the stationary phase produced by “grafting to” had higher chiral recognition ability. Further improvement can be achieved by the end-capping of silanol groups with trimethylchlorosilane to reduce non-enantioselective retention caused by residual silanol groups and improve the peak shape of enantiomers. Chiral separation in subcritical fluid chromatography was also studied. Similar enantioselectivity results with higher resolution were observed due to the improvement of peak shape

Recent Advances in Marine Geodesy of China

The ocean accounts for approximately 71% of the total area of the Earth. Whether it is studying the shape of the Earth itself through geodesy or the future development of earth system science, strengthening the construction of ocean geodesy disciplines and innovating ocean geodetic observation technologies have evident theoretical and practical significance. In recent years, the discipline of ocean geodesy in China has been continuously developing and growing, and notable breakthroughs have been made in ocean satellite geodesy and seafloor geodetic observation technology. Research on ocean geodetic observation models and algorithms has also made great progress

<i>Bifidobacterium animalis</i> subsp. <i>lactis</i> A6 Enhances Fatty Acid β-Oxidation of Adipose Tissue to Ameliorate the Development of Obesity in Mice

Fatty acid β-oxidation (FAO) is confirmed to be impaired in obesity, especially in adipose tissues. We previously proved that Bifidobacterium animalis subsp. lactis A6 (BAA6) had protective effects against diet-induced obesity. However, whether BAA6 enhances FAO to ameliorate the development of obesity has not been explored. After being fed with high-fat diet (HFD) for 9 weeks, male C57BL/6J mice were fed HFD or BAA6 for 8 weeks. In vitro study was carried out using 3T3-L1 adipocytes to determine the effect of BAA6 culture supernatant (BAA6-CM). Here, we showed that administration of BAA6 to mice fed with HFD decreased body weight gain (by 5.03 g) and significantly up-regulated FAO in epididymal adipose tissues. In parallel, FAO in 3T3-L1 cells was increased after BAA6-CM treatment. Acetate was identified as a constituent of BAA6-CM that showed a similar effect to BAA6-CM. Furthermore, acetate treatment activated the GPR43-PPARα signaling, thereby promoting FAO in 3T3-L1 cells. The levels of acetate were also elevated in serum and feces (by 1.92- and 2.27-fold) of HFD-fed mice following BAA6 administration. The expression levels of GPR43 and PPARα were increased by 55.45% and 69.84% after BAA6 supplement in the epididymal fat of mice. Together, these data reveal that BAA6 promotes FAO of adipose tissues through the GPR43-PPARα signaling, mainly by increasing acetate levels, leading to alleviating the development of obesity

A polyacrylamide-based silica stationary phase for the separation of carbohydrates using alcohols as the weak eluent in hydrophilic interaction liquid chromatography

A hydrophilic interaction liquid chromatography (HILIC) stationary phase was prepared by a two-step synthesis method, immobilizing polyacrylamide on silica sphere particles. The stationary phase (named PA, 5 mu m dia) was evaluated using a mixture of carbohydrates in HILIC mode and the column efficiency reached 121,000 N m(-1). The retention behavior of carbohydrates on PA stationary phase was investigated with three different organic solvents (acetonitrile, ethanol and methanol) employed as the weak eluent. The strongest hydrophilicity of PA stationary phase was observed in both acetonitrile and methanol as the weak eluent, when compared with another two amide stationary phases. Attributing to its high hydrophilicity, three oligosaccharides (xylooligosaccharide, fructooligosaccharide and chitooligosaccharides) presented good retention on PA stationary phase using alcohols/water as mobile phase. Finally, PA stationary phase was successfully applied for the purification of galactooligosaccharides and saponins of Paris polyphylla. It is feasible to use safer and cheaper alcohols to replace acetonitrile as the weak eluent for green analysis and purification of polar compounds on PA stationary phase. (C) 2017 Published by Elsevier B.V