Analysis of Effect of Schisandra in the Treatment of Myocardial Infarction Based on Three-Mode Gene Ontology Network

Schisandra chinensis is a commonly used traditional Chinese medicine, which has been widely used in the treatment of acute myocardial infarction in China. However, it has been difficult to systematically clarify the major pharmacological effect of Schisandra, due to its multi-component complex mechanism. In order to solve this problem, a comprehensive network analysis method was established based-on “component–gene ontology–effect” interactions. Through the network analysis, reduction of cardiac preload and myocardial contractility was shown to be the major effect of Schisandra components, which was further experimentally validated. In addition, the expression of NCOR2 and NFAT in myocyte were experimentally confirmed to be associated with Schisandra in the treatment of AMI, which may be responsible for the preservation effect of myocardial contractility. In conclusion, the three-mode gene ontology network can be an effective network analysis workflow to evaluate the pharmacological effects of a multi-drug complex system

Efficient induction of CD25- iTreg by co-immunization requires strongly antigenic epitopes for T cells

Background: We previously showed that co-immunization with a protein antigen and a DNA vaccine coding for the same antigen induces CD40(low) IL-10(high) tolerogenic DCs, which in turn stimulates the expansion of antigenspecific CD4(+)CD25(-)Foxp3(+) regulatory T cells (CD25(-) iTreg). However, it was unclear how to choose the antigen sequence to maximize tolerogenic antigen presentation and, consequently, CD25(-) iTreg induction. Results: In the present study, we demonstrated the requirement of highly antigenic epitopes for CD25(-) iTreg induction. Firstly, we showed that the induction of CD25(-) iTreg by tolerogenic DC can be blocked by anti-MHC-II antibody. Next, both the number and the suppressive activity of CD25(-) iTreg correlated positively with the overt antigenicity of an epitope to activate T cells. Finally, in a mouse model of dermatitis, highly antigenic epitopes derived from a flea allergen not only induced more CD25(-) iTreg, but also more effectively prevented allergenic reaction to the allergen than did weakly antigenic epitopes. Conclusions: Our data thus indicate that efficient induction of CD25- iTreg requires highly antigenic peptide epitopes. This finding suggests that highly antigenic epitopes should be used for efficient induction of CD25- iTreg for clinical applications such as flea allergic dermatitis

Coherent control of a high-orbital hole in a semiconductor quantum dot

Coherently driven semiconductor quantum dots are one of the most promising platforms for non-classical light sources and quantum logic gates which form the foundation of photonic quantum technologies. However, to date, coherent manipulation of single charge carriers in quantum dots is limited mainly to their lowest orbital states. Ultrafast coherent control of high-orbital states is obstructed by the demand for tunable terahertz pulses. To break this constraint, we demonstrate an all-optical method to control high-orbital states of a hole via stimulated Auger process. The coherent nature of the Auger process is proved by Rabi oscillation and Ramsey interference. Harnessing this coherence further enables the investigation of single-hole relaxation mechanism. A hole relaxation time of 161 ps is observed and attributed to the phonon bottleneck effect. Our work opens new possibilities for understanding the fundamental properties of high-orbital states in quantum emitters and developing new types of orbital-based quantum photonic devices.Comment: Manuscript with 14 pages and 6 figures plus supplementary Information comprising 15 pages and 14 figure

MicroRNA-1224 Inhibits Tumor Metastasis in Intestinal-Type Gastric Cancer by Directly Targeting FAK

Intestinal-type gastric cancer (GC) of the Lauren classification system has specific epidemiological characteristics and carcinogenesis patterns. MicroRNAs (miRNAs) have prognostic significance, and some can be used as prognostic biomarkers in GC. In this study, we identified miR-1224 as a potential survival-related miRNA in intestinal-type GC patients by The Cancer Genome Atlas (TCGA) analysis. Using quantitative real-time PCR (qRT-PCR), we showed that the relative expression of miR-1224 was significantly decreased in intestinal-type GC tissues compared to matched adjacent normal mucosa tissues (p < 0.01). We found that high miR-1224 expression was associated with no lymph-node metastasis (p < 0.05) and good prognosis (p = 0.028) in 90 intestinal-type GC tissues. Transfection of intestinal-type GC cells with miR-1224 mimics showed that miR-1224 suppressed cell migration in vitro (wound healing assay and Transwell migration assay), whereas the transfection of cells with miR-1224 inhibitor promoted cell migration in vitro. miR-1224 also suppressed intestinal-type GC cell metastasis in a xenograft mouse model. Furthermore, bioinformatics, luciferase reporter, Western blotting, and immunohistochemistry (IHC) studies demonstrated that miR-1224 directly bound to the focal adhesion kinase (FAK) gene, and downregulated its expression, which decreased STAT3 and NF-κB signaling and subsequent the epithelial-to-mesenchymal transition (EMT). Repression of FAK is required for the miR-1224-mediated inhibition of cell migration in intestinal-type GC. The present study demonstrated that miR-1224 is downregulated in intestinal-type GC. miR-1224 inhibits the metastasis of intestinal-type GC by suppressing FAK-mediated activation of the STAT3 and NF-κB pathways, and subsequent EMT. miR-1224 could represent an important prognostic factor in intestinal-type GC

Identification and Characterization of Paramyosin from Cyst Wall of Metacercariae Implicated Protective Efficacy against Clonorchis sinensis Infection

Human clonorchiasis has been increasingly prevalent in recent years and results in a threat to the public health in epidemic regions, motivating current strategies of vaccines to combat Clonorchis sinensis (C. sinensis). In this study, we identified C. sinensis paramyosin (CsPmy) from the cyst wall proteins of metacercariae by proteomic approaches and characterized the expressed recombinant pET-26b-CsPmy protein (101 kDa). Bioinformatics analysis indicated that full-length sequences of paramyosin are conserved in helminthes and numerous B-cell/T-cell epitopes were predicted in amino acid sequence of CsPmy. Western blot analysis showed that CsPmy was expressed at four life stages of C. sinensis, both cyst wall proteins and soluble tegumental components could be probed by anti-CsPmy serum. Moreover, immunolocalization results revealed that CsPmy was specifically localized at cyst wall and excretory bladder of metacercaria, as well as the tegument, oral sucker and vitellarium of adult worm. Both immunoblot and immunolocalization results demonstrated that CsPmy was highly expressed at the stage of adult worm, metacercariae and cercaria, which could be supported by real-time PCR analysis. Both recombinant protein and nucleic acid of CsPmy showed strong immunogenicity in rats and induced combined Th1/Th2 immune responses, which were reflected by continuous high level of antibody titers and increased level of IgG1/IgG2a subtypes in serum. In vaccine trials, comparing with control groups, both CsPmy protein and DNA vaccine exhibited protective effect with significant worm reduction rate of 54.3% (p<0.05) and 36.1% (p<0.05), respectively. In consistence with immune responses in sera, elevated level of cytokines IFN-γ and IL-4 in splenocytes suggested that CsPmy could induce combined cellular immunity and humoral immunity in host. Taken together, CsPmy could be a promising vaccine candidate in the prevention of C. sinensis regarding its high immunogenicity and surface localization

A Study on the Spatial Correlation Effects of Digital Economy Development in China from a Non-Linear Perspective

Accurate analysis of the spatial correlation effects, spatial aggregation patterns, and critical factors in the development of China&rsquo;s digital economy is of great significance to the high-quality development of China&rsquo;s economy. Based on the monthly data of &ldquo;The Tencent Internet Plus&rdquo; digital economy index for 31 provinces in China from 2018 to 2020, the non-linear Granger causality test and social network analysis were applied to reveal the spatial correlation effects of China&rsquo;s digital economy. The quadratic assignment procedure (QAP) was used to empirically examine the factors influencing the formation of non-linear spatial association networks. The results show that the spatially linked relationships of the digital economy in 31 Chinese provinces exhibit a significant non-linear spatially correlated network structure. Block model analysis reveals that the development of the digital economy between the four major sectors is closely linked, and the national linkage effect is significant. The results of the secondary assignment procedure indicate that capital stock, information infrastructure, and geographical proximity have a significant positive impact on the formation of spatial linkages in the digital economy. In contrast, technological innovation has a significant negative impact

Discrimination of Rice with Different Pretreatment Methods by Using a Voltammetric Electronic Tongue

In this study, an application of a voltammetric electronic tongue for discrimination and prediction of different varieties of rice was investigated. Different pretreatment methods were selected, which were subsequently used for the discrimination of different varieties of rice and prediction of unknown rice samples. To this aim, a voltammetric array of sensors based on metallic electrodes was used as the sensing part. The different samples were analyzed by cyclic voltammetry with two sample-pretreatment methods. Discriminant Factorial Analysis was used to visualize the different categories of rice samples; however, radial basis function (RBF) artificial neural network with leave-one-out cross-validation method was employed for prediction modeling. The collected signal data were first compressed employing fast Fourier transform (FFT) and then significant features were extracted from the voltammetric signals. The experimental results indicated that the sample solutions obtained by the non-crushed pretreatment method could efficiently meet the effect of discrimination and recognition. The satisfactory prediction results of voltammetric electronic tongue based on RBF artificial neural network were obtained with less than five-fold dilution of the sample solution. The main objective of this study was to develop primary research on the application of an electronic tongue system for the discrimination and prediction of solid foods and provide an objective assessment tool for the food industry

Assessment of Taste Attributes of Peanut Meal Enzymatic-Hydrolysis Hydrolysates Using an Electronic Tongue

Peanut meal is the byproduct of high-temperature peanut oil extraction; it is mainly composed of proteins, which have complex tastes after enzymatic hydrolysis to free amino acids and small peptides. The enzymatic hydrolysis method was adopted by using two compound proteases of trypsin and flavorzyme to hydrolyze peanut meal aiming to provide a flavor base. Hence, it is necessary to assess the taste attributes and assign definite taste scores of peanut meal double enzymatic hydrolysis hydrolysates (DEH). Conventionally, sensory analysis is used to assess taste intensity in DEH. However, it has disadvantages because it is expensive and laborious. Hence, in this study, both taste attributes and taste scores of peanut meal DEH were evaluated using an electronic tongue. In this regard, the response characteristics of the electronic tongue to the DEH samples and standard five taste samples were researched to qualitatively assess the taste attributes using PCA and DFA. PLS and RBF neural network (RBFNN) quantitative prediction models were employed to compare predictive abilities and to correlate results obtained from the electronic tongue and sensory analysis, respectively. The results showed that all prediction models had good correlations between the predicted scores from electronic tongue and those obtained from sensory analysis. The PLS and RBFNN prediction models constructed using the voltage response values from the sensors exhibited higher correlation and prediction ability than that of principal components. As compared with the taste performance by PLS model, that of RBFNN models was better. This study exhibits potential advantages and a concise objective taste assessment tool using the electronic tongue in the assessment of DEH taste attributes in the food industry

A Herpesvirus Virulence Factor Inhibits Dendritic Cell Maturation through Protein Phosphatase 1 and IκB Kinase▿

Dendritic cells are sentinels in innate and adaptive immunity. Upon virus infection, a complex program is in operation, which activates IκB kinase (IKK), a key regulator of inflammatory cytokines and costimulatory molecules. Here we show that the γ134.5 protein, a virulence factor of herpes simplex viruses, blocks Toll-like receptor-mediated dendritic cell maturation. While the wild-type virus inhibits the induction of major histocompatibility complex (MHC) class II, CD86, interleukin-6 (IL-6), and IL-12, the γ134.5-null mutant does not. Notably, γ134.5 works in the absence of any other viral proteins. When expressed in mammalian cells, including dendritic cells, γ134.5 associates with IKKα/β and inhibits NF-κB activation. This is mirrored by the inhibition of IKKα/β phosphorylation, p65/RelA phosphorylation, and nuclear translocation in response to lipopolysaccharide or poly(I:C) stimulation. Importantly, γ134.5 recruits both IKKα/β and protein phosphatase 1, forming a complex that dephosphorylates two serine residues within the catalytic domains of IκB kinase. The amino-terminal domain of γ134.5 interacts with IKKα/β, whereas the carboxyl-terminal domain binds to protein phosphatase 1. Deletions or mutations in either domain abolish the activity of γ134.5. These results suggest that the control of IκB kinase dephosphorylation by γ134.5 represents a critical viral mechanism to disrupt dendritic cell functions