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.     

Experimental study and model predictions on helium release in an enclosure with single or multiple vents

This paper presents experiments performed at Canadian Nuclear Laboratories (CNL) to examine the dispersion behaviour of helium in a polycarbonate enclosure that was representative of a residential parking garage. The purpose was to gain a better understanding of the effect of buoyancy- or wind-driven natural ventilation on hydrogen dispersion behaviour. Although hydrogen dispersion studies have been reported extensively in the literature, gaps still exist in predictive methods for hazard analysis. Helium, a simulant for hydrogen, was injected near the centre of the floor with a flow rate ranging from 5 to 75 standard litres per minute through an upward-facing nozzle, resulting in an injection Richardson number ranging between 10^?1 and 10². The location of the nozzle varied from the bottom of the enclosure to near the ceiling to examine the impact of the nozzle elevation on the development of a stratified layer in the upper region of the enclosure. When the injection nozzle was placed at a sufficiently low elevation, the vertical helium profile always consisted of a homogenous layer at the top overlaying a stratified layer at the bottom. To simulate outdoor environmental conditions, a fan was placed in front of each vent to examine the effect of opposing or assisting wind on the dispersion. The helium transients in the uniform layer predicted with analytical models were in good agreement with the measured transients for most tests. Model improvements are required for adequately predicting transients with primarily stratified profiles or strong opposing wind.     

基于多通道的ICU脑血管疾病死亡风险预测模型

死亡风险预测指根据病人临床体征监测数据来预测未来一段时间的死亡风险。对于ICU病患，通过死亡风险预测可以有针对性地对病人做出临床诊断，以及合理安排有限的医疗资源。基于临床使用的MEWS和Glasgow昏迷评分量表，针对ICU病人临床监测的17项生理参数，提出一种基于多通道的ICU脑血管疾病死亡风险预测模型。引入多通道概念应用于BiLSTM模型，用于突出每个生理参数对死亡风险预测的作用。采用Attention机制用于提高模型预测精度。实验数据来自MIMIC [Ⅲ]数据库，从中提取3?080位脑血管疾病患者的16?260条记录用于此次研究，除了六组超参数实验之外，将所提模型与LSTM、Multichannel-BiLSTM、逻辑回归（logistic regression）和支持向量机（support vector machine, SVM）四种模型进行了对比分析，准确率Accuracy、灵敏度Sensitive、特异性Specificity、AUC-ROC和AUC-PRC作为评价指标，实验结果表明，所提模型性能优于其他模型，AUC值达到94.3%。     

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).     

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。