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.     

Effects of SO2 on selective catalytic reduction of NO with NH3 over a TiO2 photocatalyst

The effect of SO₂ gas was investigated on the activity of the photo-assisted selective catalytic reduction of nitrogen monoxide (NO) with ammonia (NH₃) over a TiO₂ photocatalyst in the presence of excess oxygen (photo-SCR). The introduction of SO₂ (300 ppm) greatly decreased the activity of the photo-SCR at 373 K. The increment of the reaction temperature enhanced the resistance to SO₂ gas, and at 553 K the conversion of NO was stable for at least 300 min of the reaction. X-ray diffraction, FTIR spectroscopy, thermogravimetry and differential thermal analysis, x-ray photoelectron spectroscopy (XPS), elemental analysis and N₂ adsorption measurement revealed that the ammonium sulfate species were generated after the reaction. There was a strong negative correlation between the deposition amount of the ammonium sulfate species and the specific surface area. Based on the above relationship, we concluded that the deposition of the ammonium sulfate species decreased the specific surface area by plugging the pore structure of the catalyst, and the decrease of the specific surface area resulted in the deactivation of the catalyst.     

Combined hardware–software multi-parallel prefiltering on the Convey HC-1 for fast homology detection

Protein databases used in research are huge and still grow at a fast pace. Many comparisons need to be done when searching similar (homologous) sequences for a given query sequence in these databases. Comparing a query sequence against all sequences of a huge database using the well-known Smith–Waterman algorithm is very time-consuming. Hidden Markov Models pose an opportunity for reducing the number of entries of a database and also enable to find distantly homologous sequences. Fewer entries are achieved by clustering similar sequences in a Hidden Markov Model. Such an approach is used by the bioinformatics tool HHblits. To further reduce the runtime, HHblits uses two-level prefiltering to reduce the number of time-consuming Viterbi comparisons. Still, prefiltering is very time-consuming. Highly parallel architectures and huge bandwidth are required for processing and transferring the massive amounts of data. In this article, we present an approach exploiting the reconfigurable, hybrid computer architecture Convey HC-1 for migrating the most time-consuming part. The Convey HC-1 with four FPGAs and high memory bandwidth of up to 76.8 GB/s serves as the platform of choice. Other bioinformatics applications have already been successfully supported by the HC-1. Limited by FPGA size only, we present a design that calculates four first-level prefiltering scores per FPGA concurrently, i.e. 16 calculations in total. This score calculation for the query profile against database sequences is done by a modified Smith–Waterman scheme that is internally parallelized 128 times in contrast to the original Streaming ‘Single Instruction Multiple Data (SIMD)’ Extensions (SSE)-supported implementation where only 16-fold parallelism can be exploited and where memory bandwidth poses the limiting factor. Preloading the query profile, we are able to transform the memory-bound implementation to a compute- and resource-bound FPGA design. We tightly integrated the FPGA-based coprocessor into the hybrid computing system by employing task-parallelism for the two-level prefiltering. Despite much lower clock rates, the FPGAs outperform SSE-based execution for the calculation of the prefiltering scores by a factor of 7.9.     

CAN-BUS系统应用一例

CAN-BUS系统自问世以来,已将近30年,当代各品牌车辆纷纷采用,但大部分技术人员对CAN总线系统既熟悉又陌生。经常能听到,但具体操作又显得有些力不从心。本文通过对奇瑞A3品牌轿车CAN总线的巧妙应用,引导大家进一步理解和应用CAN总线。     

Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations

Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B₄ (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types.     

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–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial K_ATP (Sur1–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.     

Sensitivity analysis of Johnson-Cook material parameters on adiabatic shear in different directions

ABSTRACT

This study investigates the effects of strain, strain rates, and forming directions (RD-rolling direction, TD-transverse direction, and ND-normal direction) on adiabatic shear, via dynamic impact compression tests using the Split Hopkinson Pressure Bar (SHPB) apparatus. A modified Johnson-Cook (J-C) constitutive model is proposed, which used to analyse the influence of the constitutive parameters on the sensitivity of adiabatic shear, employing a finite element software. The different sensitivities of adiabatic shear under different directions are explained by combining microscopic analysis and results from mechanical responses. The results show that the sensitivity of adiabatic shear can be related to the time of stress collapse in the following trend: ND?>?TD?>?RD; the sensitivities of these constitutive parameters on adiabatic shear are calculated and compared.     

共享交通的时空轨迹检索与群体发现

为解决共享交通下的共乘用户群体发现效率低、准确率不高问题，依据R-树原理建立GeoOD-Tree索引，并在此基础上提出以最大化共乘率为目标的群体发现策略。首先，对原始时空轨迹数据进行特征提取与标定处理，挖掘有效出行起讫点（OD）轨迹；其次，针对用户起讫点轨迹的特征，建立GeoOD-Tree索引进行有效的存储管理；最后，给出以最大化共乘行程为目标的群体发现模型，并运用K最近邻（KNN）查询对搜索空间剪枝压缩，提高群体发现效率。采用西安市近12000辆出租车营运轨迹数据，选取动态时间规整（DTW）等典型算法与所提算法在查询效率与准确率上进行性能对比分析。与DTW算法相比，所提算法的准确率提高了10.12%，查询效率提高了约15倍。实验结果表明提出的群体发现策略能有效提高共乘用户群体发现的准确率和效率，可有效提升共乘出行方式的出行率。     

Investigation on phase shifting for a 4 K Stirling pulse tube cryocooler with He-3 as working fluid

He-3 is generally recognized for its ability to provide more excellent thermophysical performance than He-4, especially in the 4 K temperature range. However, this was not always the case in our preliminary experiments on a three-stage Stirling-type pulse tube cryocooler (SPTC). Our ongoing studies, as reported in this paper, demonstrate that the different working fluids also affect the performance through their phase shifting capability. This feature has been passed over in large part by researchers considering refrigerant substitution. Unlike previous theoretical analyses that focus primarily on regenerator losses, this report investigates the effects of the working fluid on the phase angle at the cold end in order to quantitatively reveal the relationship between the lowest attainable temperature and the cooling capacity. The analysis agrees well with our experimental results on a three-stage SPTC. While running with the operating parameters optimized for He-3, the lowest temperature of the SPTC decreased from 5.4 K down to 4.03 K. This is the lowest refrigeration temperature ever achieved with a three-stage SPTC.     

Slow strain rate technique for studying hydrogen induced cracking in 34CrMo4 high strength steel

Alloy hardened steels offer excellent combination of mechanical properties, hardenability and corrosion resistance. 34CrMo4 is a medium carbon, low alloy steel widely used due to a good combination of high-strength, toughness and wear resistance. However, this steel experiences hydrogen embrittlement (HE), a complex phenomenon depending on the composition and microstructure. This work estimates de loss of the mechanical properties caused by hydrogen in electrochemically H-charged specimens in absence of mechanical stress but also, at low strain rate and constant load. H-charging for 2 and 6 h induce YS losses of about 40% and 71% and UTS losses of 39% and 59%, respectively. The synergistic effect of the stress and the H-charging process leads to a higher loss, 91%, and a faster brittle fracture even though hydrogen content is similar to those firstly H-charged and then tested in air.