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.     

Double Variational Binding—(SMILES) Conformational Analysis by Docking Mechanisms for Anti-HIV Pyrimidine Ligands

Variational quantitative binding 13;conformational analysis for a series of anti-HIV pyrimidine-based ligands is advanced at the individual molecular level. This was achieved by employing ligand-receptor docking algorithms for each molecule in the 1,3-disubstituted uracil derivative series that was studied. Such computational algorithms were employed for analyzing both genuine molecular cases and their simplified molecular input line entry system (SMILES) transformations, which were created via the controlled breaking of chemical bonds, so as to generate the longest SMILES molecular chain (LoSMoC) and Branching SMILES (BraS) conformations. The study identified the most active anti-HIV molecules, and analyzed their special and relevant bonding fragments (chemical alerts), and the recorded energetic and geometric docking results (i.e., binding and affinity energies, and the surface area and volume of bonding, respectively). Clear computational evidence was also produced concerning the ligand-receptor pocket binding efficacies of the LoSMoc and BraS conformation types, thus confirming their earlier presence (as suggested by variational quantitative structure-activity relationship, variational-QSAR) as active intermediates for the molecule-to-cell transduction process.     

PMU based voltage security assessment of power systems exploiting principal component analysis and decision trees

The need for feature selection and dimension reduction is felt as a fundamental step in security assessment of large power systems in which the number of features representing the state of power grids dramatically increases. These large amounts of attributes are not proper to be used for computational intelligence (CI) techniques as inputs, because it may lead to a time consuming procedure with insufficient results and they are not suitable for on-line purposes and updates.This paper proposes a combined method for an online voltage security assessment in which the dimension of the token data from phasor measurement units (PMUs) is reduced by principal component analysis (PCA). Then, the features with different stability indices are put into several categories and feature selection is done by correlation analysis in each category. These selected features are then given to decision trees (DTs) for classification and security assessment of power systems.The method is applied to 39-bus test system and a part of Iran power grid. It is seen from the results that the DTs with reduced data have simpler splitting rules, better performance in saving time, reasonable DT error and they are more suitable for constant updates.     

Expression of RCAS1 Correlates with Urothelial Bladder Cancer Malignancy

RCAS1 is a protein that participates in regulation of the tumor microenvironment and its immune responses, all in order to evade the immune system. The aim of this study was to analyze RCAS1 expression in urothelial bladder cancer cells (and in fibroblasts and macrophages of the tumor stroma) and its relationship with the histological pattern of malignancy. Eighty-three postcystectomy patients were enrolled. We analyzed the histological maturity (grade), progress (pT stage), tissue invasion type (TIT), nonclassic differentiation number (NDN), and the ability to metastasize (pN). The expression of RCAS1 protein was analyzed by immunohistochemistry. Indicators of histological malignancy were observed solely in association with the RCAS1 expression in cells in the border parts (BPs) of the tumor. Histological malignancy of the tumor, indicated by the pT and pN, and metastasis-free survival time, correlated significantly with RCAS1 expression in tumor neoplastic cells, whereas malignancy determined by grade, TIT, and NDN correlated with RCAS1 expression in fibroblasts and macrophages in the tumor microenvironment. These findings suggest that the increased RCAS1 expression depends on its cellular source and that RCAS1 expression itself is a component of various signaling pathways. The immune escape occurs within the tumor BPs, where the increase in the RCAS1 expression occurs within tumor cells and stromal cells in its microenvironment. We conclude that the histological pattern of tumor malignancy, indicated by grade, TIT, NDN, pT, and pN is a morphological indicator of immune escape.     

Risk factors associated with the presence of aflatoxin M1 in raw bulk milk from Argentina

The objectives of this study were to assess aflatoxin M₁ (AFM1) contamination in bulk tank milk, and to further identify the risk factors associated with the presence of AFM1 in raw milk in Argentina. The presence of AFM1 was investigated in 160 bulk tank milk samples collected from farms located in the most important milk production region in Argentina during one year (four seasons). Samples were analysed using immunoaffinity column (IAC) cleanup and UHPLC-MS/MS method for determining AFM1 at low levels of concentrations (LOQ = 0.003 μg L⁻¹). A survey about the potential factors associated with the presence of AFM1 in milk was performed directly in the field through a questionnaire applied to the farmers. Chi-square and logistic regression were performed with presence of AFM1 in milk as dependent variable, and potential risk factors as independent variables. Incidence of AFM1 in raw milk was 38.8% and, in all samples, AFM1 levels were lower than the Southern Common Market (MERCOSUR) Regulation (maximum level accepted = 0.5 μg L⁻¹). Commercial feed consumption (OR = 4.630, P = 0.001), soybean expeller consumption (>0.95 kgDM/cow) (OR = 3.542, P = 0.019), and cotton seed consumption (>1.5 kgDM/cow) (OR = 2.949, P = 0.089) were associated with the incidence of AFM1 in raw milk. Despite the incidence and the level of AFM1 in milk produced and commercialized in Argentina is not a serious problem for public health. The farm breeding intensification and the supplementation with commercial feed, soybean expeller, and cotton seed seems to be the risk factors that impacts on the AFM1 milk contamination. Therefore, Argentina should improve its monitoring program on mycotoxins in animal feed and milk and improve the management practices in farms.     

1×7-15.2/1860 MPa钢绞线用盘条优化研究

通过对1×7-15.2/1860 MPa钢绞线强度分析,对其所用原料盘条的规格、强度、拉拔道次的选择进行分析讨论,提供最优化的原料选择方案。     

Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1 13;transient receptor potential melastatin 4 (Sur1 13;Trpm4) channels and, in some cases, microglial K_ATP (Sur1 13;Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke.