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.     

Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

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.     

粉土界面恒刚度循环剪切试验研究

竖向循环荷载作用下桩土界面的作用机理是研究桩土摩擦疲劳的关键。针对循环荷载作用下桩-粉土界面的剪切性能,使用改进的剪切试验装置在恒刚度条件下进行循环剪切试验,研究循环次数、累积位移和法向刚度对其摩擦疲劳性能、循环后单调剪切性能的影响。试验结果表明,粉土在循环剪切过程中,法向应力和剪应力在初始10个循环内随循环数增加快速衰减,随着循环进行,逐渐趋于稳定;单次循环内在剪切位移方向变化时,土体呈现表现出剪缩-剪胀-剪缩交替现象,总体变形呈现剪缩的趋势;循环荷载作用下,粉土界面的法向应力和剪应力随法向刚度增大衰减速率增大,达到稳定的累积循环位移越小;粉土循环后的单调剪切、法向应力恢复的单调剪切的剪应力比小于首次单调剪切试验值,且法向应力恢复的循环后剪切试验的剪胀程度较小,表明循环剪切过程中界面处粉土颗粒棱角破碎,颗粒变得光滑。在对试验数据分析的基础上,提出了与累积位移、法向刚度和初始应力相关的无量纲累积位移,建立了法向应力和界面摩擦角随累积位移的衰减方程。     

砾岩储层精细描述中标准测井资料的应用

克拉玛依油田七区的标准测井资料是指使用标准电极系视电阻率测井、自然电位测井和井径测井,以相同的1:500深度比例尺及相同的横向比例进行测井作业所取得的资料.这种资料本来并不具备定量解释储层孔隙度和含油饱和度的能力,但这种资料占该区测井资料总量的比率高达34%.利用标准电极系视电阻率资料和岩心分析资料建立了视电阻率-岩性图版,利用自然电位减小系数α和岩心孔隙度分析资料φ建立了α-φ图版,根据综合测井资料求出标准测井视电阻率校正系数,进而确定了饱和度计算方程的参数.与相应的综合测井资料计算结果相对比,用该方法得到的孔隙度平均绝对误差及相对误差分别为1.85%和11.88%;含油饱和度平均绝对误差及相对误差分别为9.08%和24.75%.将该方法有选择地应用到该区砾岩储层精细描述研究中,弥补了缺乏综合测井资料无法进行测井储层评价及参数研究的缺陷.     

现代电子工业Cpk评价中的特殊问题

现代电子工业生产具有许多新的特点，如果不针对具体情况，均采用传统工业生产中广泛使用的常规方法计算其工序能力指数，评价生产工艺水平，将可能导致错误的结论。总结了电子工业生产中工艺参数的典型特点，并讨论了工序能力指数的正确计算方法。     

Analysis and simulations of vibrations of a beam with a slider

A model for vibrations of a beam with a slider is derived, analysed and numerically simulated. It describes a viscoelastic beam that is clamped at one end to a vibrating device, while the other end moves between two stops attached to a slider. The contact is described by the normal compliance or by the Signorini conditions. The existence of weak solutions is established using the theory of set-valued pseudomonotone operators. The model is discretized using fourth-order spatial discretization, the solutions are numerically simulated and their results presented. The dynamics of the vibrations are depicted and so are the noise characteristics of the system.     

SiGe／Si多量子阱中垂直方向红外吸收及共振色散效应

用垂直入射的中红外光束调制非掺杂SiGe/Si量子阱中光致子带间吸收，氩离子激光器作为子带间跃迁的光泵浦源在阱中产生载流子，红外调制光谱用步进式傅立叶变换光谱仪记录，实验中观察到明显的层间干涉效应与子带间跃迁有关的色散效应，理论和实验分析认为样品折射率变化造成的位相调制可以补偿吸收所造成的幅度调制。     

缺省理论的简化

缺省理论△=(D,W)中的缺省规则集D,是该理论的不确定因素.如果能去掉一些缺省规则而又不影响该理论的延伸,则就在一定程度上简化了该理论.本文证明了关于规范缺省理论的延伸的若干性质,利用这些性质,我们可以把某些规范缺省理论在一定条件下得以化简,有的甚至可以把它们化为一阶逻辑理论.