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.     

Precipitous weakening of quartz at the α–β phase inversion

Crystalline quartz has long been identified as among the weakest of abundant crustal minerals. This weakness is particularly evident around the α–β phase inversion at 573°C, in which Si–O bonds undergo a displacive structural transformation from trigonal to hexagonal symmetry. Here we present data using indentation testing methodologies that highlight the precipitous extent of the transformational weakening. Although the indentations are localized over relatively small specimen contact areas, the data quantify the essential deformation and fracture properties of quartz in a predominantly (but not exclusively) compressive stress field, at temperatures and pressures pertinent to conditions in the earth's crust.     

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.     

Learning shape and texture progression for young child face aging

Face aging (FA) for young faces refers to rendering the aging faces at target age for an individual, generally under 20s, which is an important topic of facial age analysis. Unlike traditional FA for adults, it is challenging to age children with one deep learning-based FA network, since there are deformations of facial shapes and variations of textural details. To alleviate the deficiency, a unified FA framework for young faces is proposed, which consists of two decoupled networks to apply aging image translation. It explicitly models transformations of geometry and appearance using two components: GD-GAN, which simulates the Geometric Deformation using Generative Adversarial Network; TV-GAN, which simulates the Textural Variations guided by the age-related saliency map. Extensive experiments demonstrate that our method has advantages over the state-of-the-art methods in terms of synthesizing visually plausible images for young faces, as well as preserving the personalized features.     

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.     

深部松软煤层钻孔孔周煤体变形产渣特征研究

针对煤矿井下高瓦斯软煤顺层长钻孔排渣困难、成孔率低、施工困难等问题,通过数值模拟实验研究了井下深部软煤体变形破坏特征,分析了顺层长钻孔孔周松软煤体变形特征及应力变化,以揭示顺层长钻孔孔周松软煤体变形产渣规律。研究表明:深部高瓦斯软煤顺层钻孔孔周煤体的应力平衡临界条件破坏后将发生大体积突然垮落;钻孔水平最大变形位移为1.22mm,垂直方向最大变形位移为10.7mm;径向孔周煤体垂向变形呈现逐渐减小趋势,且垂向变形明显大于钻孔水平变形。在水平方向上,钻孔孔周煤体应力分布呈现先增大再逐渐减小的变化规律,径向距离对水平应力分布的影响逐渐减小;随着径向距离的增加,钻孔孔周煤体应力分布逐渐降低,钻孔孔壁处煤体的应力出现最大值,且垂直方向处应力值最大。     

RESERVOIR PROPERTIES OF BARREMIAN – APTIAN URGONIAN LIMESTONES,SE FRANCE,PART 1: INFLUENCE OF STRUCTURAL HISTORY ON POROSITY-PERMEABILITY VARIATIONS

Upper Barremian – Lower Aptian inner platform “Urgonian” limestones in the Mont de Vaucluse region, SE France, consist of alternating metre-scale microporous and tight intervals. This paper focuses on the influence of structural deformation on the reservoir properties of the Urgonian limestone succession in a study area near the town of Rustrel. Petrographic, petrophysical and structural data were recovered from five fully-cored boreholes, from the walls of a 100 m long underground tunnel, and from a 50 m long transect at a nearby outcrop. The data allowed reservoir property variations in the Urgonian limestones to be studied from core to reservoir scale. Eleven Reservoir Rock Types (RRTs) were identified based on petrographic features (texture, grain size), reservoir properties (porosity, permeability), and the frequency of structural discontinuities such as fractures, faults and stylolites. Tight and microporous reservoir rock types were distinguished. Tight reservoir rock types were characterised by early cementation of intergranular pore spaces and by the presence of frequent structural discontinuities. By contrast microporous reservoir rock types contained preserved intragranular microporosity and matrix permeability, but had very few structural discontinuities. Observed vertical alternations of microporous and tight rock types are interpreted to have been controlled by the early diagenesis of the Urgonian carbonates. Deformation associated with regional-scale tectonic phases, including Albian – Cenomanian “Durancian” uplift (∼105 to 96 Ma) and Pyrenean compression (∼55 to 25 Ma), resulted in the modification of the initial petrophysical properties of the Urgonian limestones. An early diagenetic imprint conditioned both the intensity of structural deformations and the associated circulations of diagenetic and meteoric fluids. Evolution of the Reservoir Rock Types is therefore linked both to the depositional conditions and to subsequent phases of structural deformation.     

Towards a Better Prediction of Cell Settling on Nanostructure Arrays—Simple Means to Complicated Ends

Vertical arrays of nanostructures (NSs) are emerging as promising platforms for probing and manipulating live mammalian cells. The broad range of applications requires different types of interfaces, but cell settling on NS arrays is not yet fully controlled and understood. Cells are both seen to deform completely into NS arrays and to stay suspended like tiny fakirs, which have hitherto been explained with differences in NS spacing or density. Here, a better understanding of this phenomenon is provided by using a model that takes into account the extreme membrane deformation needed for a cell to settle into a NS array. It is shown that, in addition to the NS density, cell settling depends strongly on the dimensions of the single NS, and that the settling can be predicted for a given NS array geometry. The predictive power of the model is confirmed by experiments and good agreement with cases from the literature. Furthermore, the influence of cell‐related parameters is evaluated theoretically and a generic method of tuning cell settling through surface coating is demonstrated experimentally. These findings allow a more rational design of NS arrays for the numerous exciting biological applications where the mode of cell settling is crucial.     

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.     

积分中值屈服准则解析厚板轧制椭圆速度场

为解决非线性Mises比塑性功率积分困难以及由此导致的轧制功率解析式难以获得的问题,本文通过建立并利用线性比塑性功率表达式对提出的椭圆速度场进行能量分析,得到了轧制力能参数的解析解.文中通过对变角度屈服函数求积分中值,构建了一个新的屈服准则,它是主应力分量的线性组合,在π平面上的轨迹是逼近Mises圆的等边非等角的十二边形,其基于Lode参数表达式的理论结果也与实验数据吻合较好.同时,根据厚板轧制时金属流动速度从入口到出口逐渐增大的特点,提出了水平速度分量满足椭圆方程的速度场,该速度场满足运动许可条件.通过相应的轧制能量分析,获得了基于线性屈服准则的内部变形功率以及基于应变矢量内积法上的摩擦功率与剪切功率.在此之上,通过泛函的极值变分导出了轧制力矩、轧制力以及应力状态系数的解析解,并与现场实测数据进行了对比,结果表明利用本文提出的屈服准则与速度场所建立的轧制力矩与轧制力模型与实测值吻合较好,其中轧制力误差小于5.3%,轧制力矩误差在6%左右.