Abstract:The mitochondrial antiviral signaling adaptor, MAVS, also known as Cardif, VISA or IPS1, is critical for host defenses against viral infection by inducing expression of type-1 interferons (IFN-Ⅰ). The sensors of antiviral immunity, RIG-Ⅰ and melanoma differentiation-associated gene 5 (MDA5), detect the invasion pathogens, and pass the signal to MAVS, which is anchored to the mitochondrial membrane. MAVS then stimulates TBK1 and IKK complex and activates the transcription factors of IRF3/7 and NF-κB, which lead to the expression of interferon and activate antiviral innate immunity. MAVS was recently found to localize in both peroxisome and mitochondrial membrane. The peroxisomal MAVS is required for the rapid induction of antiviral effectors, whereas the mitochondrial MAVS is required for a sustained antiviral immunity response. This review focused on the discovery, domain structure and cellular localization of MAVS with an emphasis on the regulatory mechanisms of MAVS in modulating the antiviral innate immunity.

Abstract:Innate immune response plays important roles in the lesion initiation and progression of atherosclerosis (As). Innate immune cells, including monocyte/macrophages, mast cells, natural killer cells, neutrophilic granulocytes and dendritic cells, represent the first line of defense against pathogens and foreign agents. These cells have extensive effects involved in foam cell formation, extracellular matrix degradation, cell apoptosis, angiogenesis and As plaque rupture. Pattern recognition receptors, including Toll-like and NOD-like receptors, could mediate innate immune response by recognize pathogen-associated molecular patterns or some endogenous components. TLRs are differentially expressed by the various cell types in atherosclerosis, and have different roles. TLR2 and TLR4 accelerate the progress of atherosclerosis, but the TLR3 induces protection of the atherosclerosis development. NLRP3 inflammasome is related to early arterial wall damages. Further researchs on the roles of the innate immune cells and pattern recognition receptors in atherogenesis help to understanding the formation of atherosclerosis, and also provide novel potential therapeutic and diagnostic targets in the future treatment of cardiovascular disease.

Abstract:Human cases infected by H7N9 subtype influenza virus that is a novel bird flu were reported in 2013, subtype H7N9 is discovered a influenza virus never occurred previously in human and only in wild birds existence and propagation. The virus belongs to subtype H7 that subtype H7 viruses are globally divided into two lineage (namely the North American sublineage and the Eurasian sublineage). Influenza subtype circulated in human are mainly H7N7, H7N3, H7N2 subtypes and so on. In order to further learn about the H7 subtype, we review the host distribution of A subtype influenza virus, the history and property of human infection caused by subtype H7,and focus of future research.

Abstract:Proximity and similarity organization are two extremely important kinds of perceptual organization. In this study, a patient with anterior-temporal lobe damage CXY took part in our proximity and similarity experiments. In this study, compound stimuli that a global figure made up of local figures were used to investigate the interference of global and local in the proximity and similarity perceptual organization. In the global-local experiment, we found that, normal subjects showed stronger global interference than local interference in the proximity perceptual organization. Such effect, however, disappeared in CXY, suggesting there was an obstacle in his automatic processing of the proximity organization; in similarity organization, there was no difference between CXY and normal subjects. In the uniform connectedness experiment, we also found the obstacle in CXY's automatic processing of the proximity organization. These results indicated that the anterior-temporal lobe plays an important role in proximity organization, global organization and uniform connectedness.

Abstract:In order to establish a polycistronic plasmid delivery system that reprogram human adipose stem cells (ASCs) into induced pluripotency stem cells(iPSCs), a polycistronic plasmid vector was constructed in which defined factors were fused in-frame into a single open reading frame via self-cleaving 2A sequences. The iPSCs were generated at 3～4 weeks after ASCs have been transiently transfected with the polycistronic plasmid. Then, the iPSCs were identified subsequently via the morphological observation, immunofluorescence with specific antigen, embryoid body formation in vitro and teratoma formation in vivo. The results demonstrated that the characteristics of these generated iPSCs resembled embryonic stem cells (ESCs) in terms of the expression of pluripotent markers, and the ability to differentiate into the three embryonic germ layers in vitro by embryoid body generation together with in vivo by teratoma formation after injection into immunodeficient mice. Remarkably, Southern bolt revealed that the human iPSCs were not integrated with plasmid DNA sequence. Therefore, hASCs derived iPSCs has the pluripotency using polycistronic plasmid method, which provides a useful platform for the further study of hereditary or degenerative disease therapies with the potential to bypass both the insertional mutagenesis and immune rejection barriers.

Abstract:Caveolae and caveolin-1 participate in the transportation of cholesterol and cell signal transduction. Our previous studies showed that the inhibitory effect of calcitonin gene-related peptide (CGRP) on the vascular smooth muscle cells (VSMCs) was related to decreasing the activity of extracellular signal-regulated kinase (ERK)_1/2 and increasing the expression of caveolin-1. In the present study, we investigated the role of caveolae and caveolin-1 in proliferation of VSMCs and whether there are interaction between the caveolin-1 and ERK_1/2 in the inhibitory effect of CGRP signal pathway. VSMCs were prepared from thoracic aorta of male Sprague-Dawley rat by the classic explants method, the passage 3 ~ 10 VSMCs were used for the present study. 10% fetal bovine serum (FBS) was employed as a stimulus for the proliferation of VSMCs. β-Cyclodextrin or filipin was used to deplete cholesterol in the caveolae. Proliferation of VSMCs was estimated by methylthiazoletrazolium (MTT) assay and Flow Cytometry. Western blotting and co-immunoprecipitation were used to determine interaction of p-ERK_1/2 or caveolin-1. Results showed that CGRP significantly inhibited VSMC proliferation and down-regulated phosphorylation of ERK_1/2. Incubation of VSMCs with β-cyclodextrin or filipin promoted cells proliferation, up-regulated phosphorylation of ERK_1/2, attenuated the inhibitory action of CGRP on VSMC proliferation and decreased caveolin-1 expression. Pretreatment with CGRP increased the direct binding of cavolin-1 with phosphorylated(p-) ERK_1/2 but not non-phosphorylated ERK_1/2 in the presence of 10?S. Our results revealed that caveolae and caveolin-1 may contribute to the inhibitory effect of CGRP on the VSMC proliferation, and the mechanism may be related to the deceased nuclei translocation of p-ERK_1/2 because of the increased binding of caveolin-1 with p-ERK_1/2.

Abstract:CD1d-restricted natural killer T cell (NKT) is a subset of T cells and plays an important role in the regulation of diverse immune responses. MicroRNA-mediated RNA interference is emerging as a crucial regulatory mechanism in the control of NKT cell development and function. Yet, roles of specific microRNA in the development and function of NKT cells is not completely understood. In this study, miR-150 knockout (miR-150KO) mice were adopted and the quantities of thymic and peripheral NKT cells were detected by flow cytometry. Cytokine production was detected by intracellular staining and ELISA. We found that miR-150 deletion resulted in the decreased number of thymic NKT cells, while peripheral NKT cells did not change in mice. However, activated NKT cells in miR-150KO mice produced more IFN-γ than that of wild type control (WT) mice. In addition, using B16BL6 melanoma mouse model, we found that miR-150 deletion enhanced the inhibitory effect of α-Galcer on the lung metastasis of melanoma cells. Our data provide new clues for the specific role of miR-150 in the development and function of NKT cells.

Abstract:The goal of this study was to screen bioactive peptides to identify an efficient antagonist of multiple pro-inflammatory chemokines that inhibits the pathological process of inflammatory diseases. A phage display library was sequentially screened by binding phages. The binding properties of individual phage clones to LPS-activated PBMCs were determined using cell-based ELISAs. The positive clones were selected and determined by chemotaxis assays. A high-activity peptide was determined to inhibit carrageenan-induced paw oedema and formaldehyde-induced arthritis in Wistar rats in vivo. A possible mechanism of inflammation inhibition involving chemokine mRNA by the peptide was determined by analyzing mRNA expression levels of chemokines and tristetraprolin (TTP) by SqRT-PCR.Nineteen phage clones were selected after four rounds of biopanning with a cut-off of 3-fold higher binding to LPS-activated PBMCs than to normal PBMCs. Nine of the phage clones inhibited IL-8, MCP-1, and MIP-1β production in vitro. Five clones displayed the same peptide(CI-S5)most robustly inhibited the chemotactic activity in vitro and reduced paw oedema and arthritis in Wistar rats in vivo. SqRT-PCR results indicated that mRNA expression of IL-8, MCP-1, and MIP-1β were reduced and TTP mRNA expression was increased in the CI-S5 treatment group. Our data demonstrate that CI-S5 is a broad-spectrum antagonist of pro-inflammatory chemokines as it enhances the expression of TTP to reduce chemokine mRNA expression. This study provides a basis for the development of new peptide-based therapies for the treatment of inflammatory diseases.

Abstract:The definition of perceptual objects is one of the most central but still controversial questions in cognitive science. By using the motion-induced blindness (MIB) paradigm, we found that: a. when two targets were connected, enclosed, or contained the same number of holes, they intended to be grouped together and co-disappeared; b. the targets and background figures with different topological properties significantly weakened MIB effects; c. once observers lost awareness of the targets, the topological changes of the target compared with the non-topological changes, lead it return to awareness much quickly. These results revealed an important role of the topological invariants in the MIB, and provided further support for the topological definition of perceptual objects. Furthermore, current study suggested that the representation of the perceptual new object could be processed in the absence of visual awareness.

Abstract:MicroRNAs (miRNAs) are a class of short, endogenous, non-coding small RNAs. The regulation function accompanies with the cell growth, differentiation, proliferation and apoptosis. The miRNAs expression is closely related with the development of cancer and has been considered as a potential biomarker. The analysis of the miRNAs expression profile is a critical part in the studying of miRNAs. Usually, miRNAs in biological samples require fraction, labeling and purification before applied to most assays. This is the most time-consuming, labor-intensive and the highest cost in the assay process. The assay results would be affected for the initial ratio of the sample target miRNAs which may have been changed due to the application of enzymes and complicated steps in this preprocess. The main purpose of this work is to develop a new microRNA microarray platform that free of the sample labeling. It is named the stacking hybridization-based universal tag (SHUT) assay for it takes advantage of stacking hybridization interaction and involves a universal tag (UT)——an 8mers oligonucleotide labeled previously. This article focuses on the optimization of the experimental procedures in the SHUT assay and the evaluation of its properties, such as the sensitivity and the specificity. The results show that the microarray has the advantage of high sensitivity, that even 2 fmol/L input miRNAs can be detected. The miRNAs microarray has perfect selectivity simultaneously. It can distinguish the target miRNAs from other family members with only one base mismatched. In particularly, the pri-miRNA and pre-miRNA can be easily discriminated from mature-miRNAs, which enables as little as 100 ng total RNAs to be analyzed directly and rapidly. All these results have shown that the application of this new microarray platform approach is a rapid and ideal platform for the detection as well as analysis of miRNAs and other small nucleic acid molecules.