Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

Thermomechanical stability and inelastic energy dissipation as durability criteria for fuel cell gas diffusion media with pre-assembly effects

In this article, pre-assembly hot-press pressure and thermal expansion effects in gas-diffusion layers (GDLs) are addressed to explore the practicalities of the constitutive model reported in the companion article. A facile technique is proposed to include deformation history dependent residual strain effects. The model is implemented in the numerical environment and compared with widely followed conventional models such as isotropic and orthotropic material models. With the normal and accelerated thermal expansion effects no significant variation in stresses or strains is reported with the compressible GDL model in contrast to the conventional incompressible form of the GDL model. The present work identifies the critical differences with advanced and extended variants of the model along with conventional GDL material models in terms of planar stress/strain distribution and the membrane response. Finally, the model is simulated for micro-cyclic stress loads of varying amplitudes that imitate the real working conditions of fuel cell. The inelastic energy dissipation in GDLs is predicted using the proposed model, which is utilized further to distinguish the safe (elastic) and unsafe (inelastic shakedown) operating limits. The inelastic collapse of GDLs is shown to be a active function of high amplitude micro-cyclic load with high initial clamping load.     

Finite-time adaptive fuzzy control for a class of output constrained nonlinear systems with dead-zone

The article investigates the finite-time adaptive fuzzy control for a class of nonlinear systems with output constraint and input dead-zone. First, by skillfully combining the barrier Lyapunov function, backstepping design method, and finite-time control theory, a novel adaptive state-feedback tracking controller is constructed, and the output constraint of the nonlinear system is not violated. Second, the fuzzy logic system is used to approximate unknown function in the nonlinear system. Third, the finite-time command filter is introduced to avoid the problem of “complexity explosion” caused by repeated differentiations of the virtual control signal in conventional backstepping control schemes. Meanwhile, a new saturation function is added in the compensating signal for filter error to improve control accuracy. Finally, based on Lyapunov stability analysis, all the signals of the closed-loop are proved to be semi-globally uniformly ultimately bounded, and the tracking error converges to a small neighborhood region of the origin in a finite time. A simulation example is presented to demonstrate the effectiveness for the proposed control scheme.     

PID Control of Planar Nonlinear Uncertain Systems in the Presence of Actuator Saturation

This paper investigates PID control design for a class of planar nonlinear uncertain systems in the presence of actuator saturation. Based on the bounds on the growth rates of the nonlinear uncertain function in the system model, the system is placed in a linear differential inclusion. Each vertex system of the linear differential inclusion is a linear system subject to actuator saturation. By placing the saturated PID control into a convex hull formed by the PID controller and an auxiliary linear feedback law, we establish conditions under which an ellipsoid is contractively invariant and hence is an estimate of the domain of attraction of the equilibrium point of the closed-loop system. The equilibrium point corresponds to the desired set point for the system output. Thus, the location of the equilibrium point and the size of the domain of attraction determine, respectively, the set point that the output can achieve and the range of initial conditions from which this set point can be reached. Based on these conditions, the feasible set points can be determined and the design of the PID control law that stabilizes the nonlinear uncertain system at a feasible set point with a large domain of attraction can then be formulated and solved as a constrained optimization problem with constraints in the form of linear matrix inequalities (LMIs). Application of the proposed design to a magnetic suspension system illustrates the design process and the performance of the resulting PID control law.      

纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

Generation,validation and application of dynamic load profiles in flow measurement using cavitating Herschel–Venturi nozzles

Today, utility meters for water are tested for measurement behavior at stable operating conditions at specified flow rates as part of the approval process. The measurement error that occurs during start and stop or when changing between flow rates may not be taken into account. In addition, there are new technologies whose measuring behavior under real-world conditions is only known to a limited extend. To take these facts into account, a new method has been developed and tested to determine the measurement behavior of water meters under dynamic load profiles as they occur in the real application. For this purpose, a test rig for flow rate measurement was extended by a cavitation nozzle apparatus and the generation of dynamic load profiles was validated. For the cavitation nozzles used, possible factors influencing the flow rate, such as temperature and purity of the water as well as the upstream pressure were investigated. Using different types of domestic water meters, the applicability of the dynamic test procedure was demonstrated and the measurement behavior of the meters was characterised.     

基于特征建模的TDD系统大气波导干扰控制体系研究

大气波导干扰是特定气象条件下发生的时分双工（time-division duplex，TDD）系统内干扰，是TDD移动通信系统大规模组网面临的顽疾。在总结分析大气波导干扰成因和分类等的基础上，对大气波导干扰进行建模和表征，验证了海量干扰源在时域和频域的功率集总特征，并结合大量4G/5G现网实测数据给出了典型条件下内陆波导和海面波导的量化干扰信号传播模型，对于干扰的预测和预防具有重要意义。基于干扰特征，给出了TDD系统预防大气波导干扰的帧结构与组网的4项设计原则，5G现网数据表明干扰控制方案有效，上行干扰下降10 dB以上，相关原则对于6G系统的设计也具有指导意义。     

Analysis and proposition of limiting current density measurement protocol

Limiting current density at different temperatures, backpressures, and balance gases can be used to separate molecular diffusion resistance, Knudsen diffusion resistance and local transport resistance of membrane electrode assembly (MEA). However, the measurement of limiting current density has no unified protocol. The diverse choices in the literature, either in the control of current or voltage or in the atmosphere like relative humidity and O₂ concentrations, make it difficult to compare the results and identify the true bottleneck hindering the mass transport. In this work, the current-voltage curves obtained by current scanning/stepping and voltage scanning/stepping methods under dilute O₂ of different concentrations and a wide range of relative humidity were measured and analyzed systematically. It is found that the voltage stepping method is superior to the other three ways of control for the reliable determination of the limiting current density. Aided with simultaneous electrochemical impedance spectroscopy measurement, the limiting current density can be determined with pinpoint accuracy. When the limiting current density is just used to qualitatively evaluate different MEA, the voltage scanning method can be used instead for its high time efficiency. The selection of the atmosphere also plays an important role in suppressing the distortion from excessive water and reducing the spurious contribution from proton conduction resistance. It is found that O₂ concentrations at 0.5 vol% and relative humidity at 90% can give the best estimation of O₂ transport resistance in membrane electrode assembly.