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.     

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。     

基于示范城市创建的食品安全治理体系研究

食品安全示范城市创建是食品安全治理体系的重要载体。本文系统性回顾食品安全治理体系相关研究,从“党政同责”、政府监管、市场主体、社会共治等四个治理主体,构建生产规范、产业转型升级等27个评价指标的治理标准,利用层次分析法实证分析了浙江省食品安全示范城市创建情况。结果表明:采用暗查暗访、现场检查、体系评估、示范引领答辩等形式,按照一定的评价流程、评价标准的食品安全示范城市创建,是实现食品安全现代化目标的重要载体。食品安全治理体系包括“治理载体—治理主体—治理标准—治理目标”。食品安全治理成效与跟踪评价、群众满意度以及体系评估高度关联。     

Heterometallic sulfide cluster [Ag6Sn6S20]10 −: Solvothermal syntheses and characterizations of silver thiostannates with lanthanide complex counter cations

Novel organic hybrid silver thiostannates [Hen]₄[Ln(en)₄]₂[Ag₆Sn₆S₂₀]·3en (Ln = Er, 1; Tm, 2; Yb, 3) were prepared by the reactions of Ln₂O₃, Ag, Sn and S in ethylenediamine (en) under solvothermal conditions. Six SnS₄ tetrahedra and six AgS₃ triangles are connected into the heterometallic sulfide cluster [Ag₆Sn₆S₂₀]^10 − via edge-sharing. In the [Ag₆Sn₆S₂₀]^10 − cluster, a hexanuclear Ag₆S₆ core is enclosed by two Sn₃S₁₀ fragments. The Ag₆S₆ core is the first As–S cluster stabilized by inorganic SnS₄ ligands. In 1–3, all Ln^3 + ions are in 8-fold coordination environments that involved four bidentate en ligands, forming bicapped trigonal prisms. Compounds 1–3 show well-defined absorption edges with band gaps in the range of 2.18–2.47 eV.     

In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury.     

Resistive switching characteristics of ZnO–graphene quantum dots and their use as an active component of an organic memory cell with one diode-one resistor architecture

We investigated the resistive switching characteristics of a polystyrene:ZnO–graphene quantum dots system and its potential application in a one diode-one resistor architecture of an organic memory cell. The log–log I–V plot and the temperature-variable I–V measurements revealed that the switching mechanism in a low-current state is closely related to thermally activated transport. The turn-on process was induced by a space-charge-limited current mechanism resulted from the ZnO–graphene quantum dots acting as charge trap sites, and charge transfer through filamentary path. The memory device with a diode presented a ∼10³ I_ON/I_OFF ratio, stable endurance cycles (10² cycles) and retention times (10⁴ s), and uniform cell-to-cell switching. The one diode-one resistor architecture can effectively reduce cross-talk issue and realize a cross bar array as large as ∼3 kbit in the readout margin estimation. Furthermore, a specific word was encoded using the standard ASCII character code.     

A methodology for the estimation of transverse failure strength of an oxidized lamina from isothermal aging studies

Surface oxidation and ensuing damage substantially decrease the service life of High Temperature Polymer Matrix Composite (HTPMC) structures. Oxidative degradation behavior of composites is strongly dependent on the coupling between chemical and mechanical responses of the material. In a composite lamina, the onset of damage and subsequent coupled acceleration of both damage and oxidation are controlled by the transverse failure strength of the oxidized regions. The direct measurement of this strength from experimentation is challenging and cumbersome. A model-based methodology for estimating the mean transverse failure strength of the oxidized regions of a unidirectional composite is described in this paper. As the strength of the oxidized region is expected to show a high-degree of spatial variability, the estimated mean is shown to be relatively insensitive to the effect of strength variance. The developed methodology is illustrated with isothermal aging data available for a typical high-temperature composite system.