The fate of RNA and RNA binding proteins in Sindbis virus infection

RNA binding proteins (RBPs) accompany RNA throughout its whole life cycle. Therefore, the interaction of RBPs and target RNAs is particularly essential for post-transcriptional regulation. Not only can RBPs affect the RNA’s expression, they can also control the localization, degradation, translation, and other activities of RNA. Capitalizing on recent advances in high-throughput sequencing, this thesis describes the use of transcriptomic and proteomic technologies to systematically study the interplay of RNA and RBPs under the context of viral infection. In brief, we infect the human cell line HEK293 with the Sindbis RNA virus, with the aim of demonstrating how the viral infection remodels the host transcriptome and proteome. While it is commonly accepted that RBPs play a role in the regulation of gene expression, their contributions are still poorly understood. By using RNA interactome capture to track dynamic changes in RNA-binding proteome along the course of viral infection of Sindbis virus in human cells, we aim to assess the global impact of Sindbis virus infection on host transcriptome and proteome, and to identify host RBPs that interact with the Sindbis virus during its reproduction. This thesis reviewed the interplay dynamics between RNA and RBPs in human HEK293 cell line at three different viral infection stages. We observed a remodelling of binding activities of RBPs and the subsequent activation of the immune responses in the host cell. To our surprise, most RBPs demonstrating altered RNA binding did not show protein-level changes. Besides using statistical methods to evaluate the relative effects of different RNA processes, we also demonstrated that RNA degradation pathways had the biggest contribution to changes in RNA abundance change in SINV infected cells. Similar machinery may also apply to other alphaviruses, such as Chikungunya and Mayaro viruses, and thus we hope this study may contribute for the development of drugs to help solving public health problems caused by similar viruses in around the world

Research on the Competitiveness and Trade Potential of China-India Pharmaceutical Trade under the One Belt and One Road Initiative

The implementation of One Belt And One Road initiative brings both opportunities and challenges for China to strengthen the pharmaceutical trade cooperation with India. Based on the data of pharmaceutical products trade from 2001 to 2018, this paper examines the pharmaceutical trade competition between China and India, establishes an expanded trade gravity model between China and countries along the One Belt And One Road Initiative, and measures the export potential of Chinese pharmaceutical products to India. The results show that China\u27s pharmaceutical trade volume to India is positively affected by GDP of the two countries, Indian population and language, and negatively affected by distance. China\u27s pharmaceutical export trade potential to India as a whole belongs to potential reshape type. It is urgent need for the two countries to further strengthen trade cooperation in pharmaceutical products in the context of the global spread of Covid-19 pandemic. Finally, the countermeasures and suggestions to promote the development of China-India pharmaceutical trade are put forward

The level of IL-35 in the circulation of patients with Graves’ disease

Introduction: The aim of this study was to explore the potential role of IL-35 in Graves’ disease (GD). Material and methods: A total of 142 GD patients including 80 newly onset patients, 52 refractory patients and 10 remission patients and 70 normal controls (NCs) were recruited. The messenger RNA (mRNA) expressions of P35 and Epstein-Barr-virus-induced gene 3 (Ebi3) were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serum level of IL-35 was measured by enzyme-linked immunosorbent assay (ELISA). Results: The expression of IL-35mRNA in new onset GD and refractory GD were both significantly higher than NC. Comparison between remission GD and NC showed no significant difference (p > 0.05). A significant increase of Ebi3mRNA expression was observed in new onset GD compared with remission GD (p = 0.030). The new onset GD showed a tendency for increased expression of serum IL-35 but without significant difference. No correlation between IL-35 expression and clinic parameters was found. Conclusions: Our preliminary observations indicate that IL-35 and CD4+P35+Ebi3+T cells may be involved in the pathogenesis of GD

A Context-Aware Adaptive Streaming Media Distribution System in a Heterogeneous Network with Multiple Terminals

We consider the problem of streaming media transmission in a heterogeneous network from a multisource server to home multiple terminals. In wired network, the transmission performance is limited by network state (e.g., the bandwidth variation, jitter, and packet loss). In wireless network, the multiple user terminals can cause bandwidth competition. Thus, the streaming media distribution in a heterogeneous network becomes a severe challenge which is critical for QoS guarantee. In this paper, we propose a context-aware adaptive streaming media distribution system (CAASS), which implements the context-aware module to perceive the environment parameters and use the strategy analysis (SA) module to deduce the most suitable service level. This approach is able to improve the video quality for guarantying streaming QoS. We formulate the optimization problem of QoS relationship with the environment parameters based on the QoS testing algorithm for IPTV in ITU-T G.1070. We evaluate the performance of the proposed CAASS through 12 types of experimental environments using a prototype system. Experimental results show that CAASS can dynamically adjust the service level according to the environment variation (e.g., network state and terminal performances) and outperforms the existing streaming approaches in adaptive streaming media distribution according to peak signal-to-noise ratio (PSNR)

A van der Waals pn heterojunction with organic/inorganic semiconductors

van der Waals (vdW) heterojunctions formed by two-dimensional (2D) materials have attracted tremendous attention due to their excellent electrical/optical properties and device applications. However, current 2D heterojunctions are largely limited to atomic crystals, and hybrid organic/inorganic structures are rarely explored. Here, we fabricate hybrid 2D heterostructures with p-type dioctylbenzothienobenzothiophene (C8-BTBT) and n-type MoS2. We find that few-layer C8-BTBT molecular crystals can be grown on monolayer MoS2 by vdW epitaxy, with pristine interface and controllable thickness down to monolayer. The operation of the C8-BTBT/MoS2 vertical heterojunction devices is highly tunable by bias and gate voltages between three different regimes: interfacial recombination, tunneling and blocking. The pn junction shows diode-like behavior with rectifying ratio up to 105 at the room temperature. Our devices also exhibit photovoltaic responses with power conversion efficiency of 0.31% and photoresponsivity of 22mA/W. With wide material combinations, such hybrid 2D structures will offer possibilities for opto-electronic devices that are not possible from individual constituents.Comment: 16 pages, 4 figure

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone tissue engineering application, however, the great hydrophobicity limits its broad application. In this study, the hybrid amphiphilic poly(ethylene glycol) (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with regular and continuous fibers compared to corresponding blank PLA fiber mats. The prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment and proliferation by providing an interconnected porous extracellular environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the interstitial pores and integrate well with the surrounding fibers, which is very important for favorable application in tissue engineering. More importantly, the electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate into bone-associated cells by comprehensively evaluating the representative markers of the osteogenic procedure with messenger ribonucleic acid quantitation and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better differentiation potential with higher messenger ribonucleic acid expression of the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I. The significantly higher alkaline phosphatase activity of the PEG/PLA fibrous scaffolds indicated that these can enhance the differentiation of MSCs into osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level of the late osteogenic differentiation markers OCN (osteocalcin) and OPN (osteopontin), accompanied by the positive Alizarin red S staining, showed better maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the mineralization stage of differentiation. After transplantation into the thigh muscle pouches of rats, and evaluating the inflammatory cells surrounding the scaffolds and the physiological characteristics of the surrounding tissues, the PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular response and excellent osteogenic potential in vitro, as well as the biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA fibrous scaffolds could be one of the most promising candidates in bone tissue engineering

Manufacturability, mechanical properties, mass-transport properties and biocompatibility of Triply Periodic Minimal Surface (TPMS) scaffolds fabricated by selective laser melting

Selective laser melting is a promising additive manufacturing technology for manufacturing porous metallic bone scaffolds. Bone repair requires scaffolds that meet various mechanical and biological requirements. This paper addresses this challenge by comprehensively studying the performance of porous scaffolds. The main novelty is exploring scaffolds with different porosities, verifying various aspects of their performance and revealing the effect of their permeability on cell growth. This study evaluates the manufacturability, mechanical behaviour, permeability and biocompatibility of gyroid scaffolds. In simulations, mechanical behaviour and permeability exhibited up to 56% and 73% accuracy, respectively, compared to the experimental data. The compression and permeability experiments showed that the elastic modulus and the permeability of the scaffolds were both in the range of human bones. The morphological experiment showed that manufacturing accuracy increased with greater designed porosity, while the in vitro experiments revealed that permeability played the main role in cell proliferation. The significance of this work is improving the understanding of the effect of design parameters on the mechanical properties, permeability and cell growth of the scaffolds, which will enable the design of porous bone scaffolds with better bone-repair effects

Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma

Background: Dysregulation of immune checkpoint molecules leads to immune evasion in human tumours but has become a viable target for tumour therapy. Here, we examined expression of Herpes virus entry mediator (HVEM), an immune checkpoint molecule, in human glioblastoma (GBM) to assess its potential as a molecular target for treatment. Methods: Molecular and clinical data from publicly available genomic databases containing WHO grade II-IV human glioma cases (n = 1866) were analyzed. Immunohistochemistry was applied to assess HVEM protein levels in primary tumour sections. Statistical analysis was performed using Matlab and R language. Findings: HVEM was found to be elevated in aggressive gliomas, particularly in the mesenchymal and isocitrate dehydrogenase (IDH) wild-type molecular subtypes of GBM. HVEMhigh tumours tended to be associated with amplification of EGFR and loss of PTEN, while HVEMlow tumours harbored mutations in IDH1 (93%). HVEM exhibited potential as a prognostic marker based on Cox regression and nomogram models. HVEM displayed intra-tumour heterogeneity and was more highly expressed in peri-necrotic and microvascular regions. Gene ontology and pathway analysis revealed enrichment of HVEM in multiple immune regulatory processes, such as suppression of T cell mediated immunity in GBM. Finally, in cell lineage analysis, HVEM was found to be tightly associated with several infiltrating immune and stromal cell types which localized to the tumour microenvironment. Interpretation: Our data highlights the importance of HVEM in the development of GBM and as a potential molecular target in combination with current immune checkpoint blockades for treatment of GBM.publishedVersio