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。     

Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

Modeling unaccounted-for gas among residential natural gas consumers using a comprehensive fuzzy cognitive map

Residential natural gas consumption depends on several factors. Available tools and methods to identify, categorize, and validate effective factors have some limitations, making consumption modeling more complex. Once a comprehensive model of effective consumption factors is developed for residential gas consumers, it can predict consumption. In addition, such a model could be used to verify the accuracy of measuring devices in order to reduce unaccounted for gas (UFG). The key factors affecting residential gas consumption were identified based on previous studies and their mutual effects were analyzed using a fuzzy cognitive mapping (FCM) method. The most significant factors and their effects on natural gas consumption in the residential sector were determined. In this study, for the first time, the expected consumption for each consumer was estimated using a consumption index. Generally, if the estimated consumption is significantly different from the amount recorded by the meter, it could suggest a potential source of UFG. The proposed method was applied to the data collected from the residential gas consumers of a small region in Iran (Dasht-e Arjan region, Fars province), and the results demonstrate the effectiveness of the proposed method.     

Life cycle cost of conventional,battery electric,and fuel cell electric vehicles considering traffic and environmental policies in China

Electric vehicles (EVs) are considered a promising alternative to conventional vehicles (CVs) to alleviate the oil crisis and reduce urban air pollution and carbon emissions. Consumers usually focus on the tangible cost when choosing an EV or CV but overlook the time cost for restricting purchase or driving and the environmental cost from gas emissions, falling to have a comprehensive understanding of the economic competitiveness of CVs and EVs. In this study, a life cycle cost model for vehicles is conducted to express traffic and environmental policies in monetary terms, which are called intangible cost and external cost, respectively. Battery electric vehicles (BEVs), fuel cell electric vehicles (FCEVs), and CVs are compared in four first-tier, four new first-tier, and 4 s-tier and below cities in China. The comparison shows that BEVs and FCEVs in most cities are incomparable with CVs in terms of tangible cost. However, the prominent traffic and environmental policies in first-tier cities, especially in Beijing and Shanghai, greatly increase the intangible and external costs of CVs, making consumers more inclined to purchase BEVs and FCEVs. The main policy benefits of BEVs and FCEVs come from three aspects: government subsidies, purchase and driving restrictions, and environmental taxes. With the predictable reduction in government subsidies, traffic and environmental policies present important factors influencing the competitiveness of BEVs and FCEVs. In first-tier cities, BEVs and FCEVs already have a competitive foundation for large-scale promotion. In new first-tier and second-tier and below cities, stricter traffic and environmental policies need to be formulated to offset the negative impact of the reduction in government subsidies on the competitiveness of BEVs and FCEVs. Additionally, a sensitivity analysis reveals that increasing the mileage and reducing fuel prices can significantly improve the competitiveness of BEVs and FCEVs, respectively.     

金针菇多糖对微冻大黄鱼及其鱼片品质变化的影响

为研究金针菇多糖（polysaccharide from Flammulina velutipes，FVP）对微冻大黄鱼及鱼片在贮藏期间肌原纤维蛋白性质的变化及水分分布的影响，实验分别选用0.03、0.06、0.09 g/L FVP浸渍处理大黄鱼和鱼片，以无菌水处理为对照组，分析微冻贮藏期间样品的感官指标得分、总挥发性盐基氮含量、总巯基含量、Ca2＋-ATPase活性、蛋白流变学性质以及水分迁移变化规律。结果表明：FVP可有效抑制整鱼总挥发性盐基氮含量上升和感官得分的下降；减缓整鱼及鱼片在微冻过程中总巯基含量、Ca2＋-ATPase活性下降和水分流失；此外FVP还能够延缓大黄鱼因腐败而出现的蛋白凝胶能力减弱。在本实验选取的多糖浓度范围内，0.09 g/L FVP处理组保鲜效果较强。该研究结果可为FVP用于水产品贮运保鲜提供理论参考。