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.     

Density functional theory study of the hydrogen evolution reaction in haeckelite boron nitride quantum dots

To satisfy arising energy needs and to handle the forthcoming worldwide climate transformation, the major research attention has been drawn to environmentally friendly, renewable and abundant energy resources. Hydrogen plays an ideal and significant role is such resources, due to its non-carbon based energy and production through clean energy. In this work, we have explored catalytic activity of a newly predicted haeckelite boron nitride quantum dot (haeck-BNQD), constructed from the infinite BN sheet, for its utilization in hydrogen production. Density functional theory calculations are employed to investigate geometry optimization, electronic and adsorption mechanism of haeck-BNQD using Gaussian16 package, employing the hybrid B3LYP and wB97XD functionals, along with 6–31G(d,p) basis set. A number of physical quantities such as HOMO/LUMO energies, density of states, hydrogen atom adsorption energies, Mulliken populations, Gibbs free energy, work functions, overpotentials, etc., have been computed and analysed in the context of the catalytic performance of haeck-BNQD for the hydrogen-evolution reaction (HER). Based on our calculations, we predict that the best catalytic performance will be obtained for H adsorption on top of the squares or the octagons of haeck-BNQD. We hope that our prediction of most active catalytic sites on haeck-BNQD for HER will be put to test in future experiments.     

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.      

Inhibitory effects of curcumin and piperine on fluorescent advanced glycation end products formation in a bovine serum albumin–fructose model

This study investigated the inhibitory effects of curcumin and piperine on fluorescent advanced glycation end products (fAGEs) formation in a bovine serum albumin (BSA)–fructose model. Model systems of BSA and fructose were prepared, and curcumin or piperine was added. fAGEs and BSA oxidation product (dityrosine, kynurenine and N'-formylkynurenine) contents were determined. The results showed that fAGEs content decreased with increasing concentration of curcumin and piperine (P < 0.05). Addition of curcumin and piperine at 160 µg mL⁻¹ could inhibit fluorescent AGEs by 100% and 93% respectively. Dityrosine and N'-formylkynurenine contents decreased as curcumin and piperine concentration increased (P < 0.05). Furthermore, the result of principal component analysis indicated that curcumin and piperine markedly impeded BSA oxidation, resulting in a lower level of fAGEs in model systems. Therefore, adding curcumin and piperine may facilitate reduced fAGEs levels in BSA–fructose model.     

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。     

Experimental investigation on the invert stability of operating railway tunnels with different drainage systems using 3D printing technology

In recent years, the invert anomalies of operating railway tunnels in water-rich areas occur frequently, which greatly affect the transportation capacity of the railway lines. Tunnel drainage system is a crucial factor to ensure the invert stability by regulating the external water pressure (EWP). By means of a three-dimensional (3D) printing model, this paper experimentally investigates the deformation behavior of the invert for the tunnels with the traditional drainage system (TDS) widely used in China and its optimized drainage system (ODS) with bottom drainage function. Six test groups with a total of 110 test conditions were designed to consider the design factors and environmental factors in engineering practice, including layout of the drainage system, blockage of the drainage system and groundwater level fluctuation. It was found that there are significant differences in the water discharge, EWP and invert stability for the tunnels with the two drainage systems. Even with a dense arrangement of the external blind tubes, TDS was still difficult to eliminate the excessive EWP below the invert, which is the main cause for the invert instability. Blockage of drainage system further increased the invert uplift and aggravated the track irregularity, especially when the blockage degree is more than 50%. However, ODS can prevent these invert anomalies by reasonably controlling the EWP at tunnel bottom. Even when the groundwater level reached 60 m and the blind tubes were fully blocked, the invert stability can still be maintained and the railway track experienced a settlement of only 1.8 mm. Meanwhile, the on-site monitoring under several rainstorms further showed that the average EWP of the invert was controlled within 84 kPa, while the maximum settlement of the track slab was only 0.92 mm, which also was in good agreement with the results of model test.