Abstract:As an important part of functional genomics, gene expression profiling plays an important role in many fields, such as biology, medicine and drug discovery. With the advent of precision medicine, integration of multi-omics data for personalized health care is becoming the trend of future medicine. In this review, Relevant databases of gene expression profile were introduced first. And then three general methods for gene expression profile analysis, i.e., connectivity map method, gene regulatory network method and multi-omics data integration methods were focused. The latest usage of these methods in drug discovery, especially in cancer drug development was reviewed. This review would serve as a guide for transcriptome-based drug discovery.

Abstract:Monoclonal antibody (mAb) technology has become a powerful tool in the field of tumor-targeted diagnosis and therapy due to its antigen-binding specificity and capacity. However, the drawbacks of mAbs include weak tumor penetration, poor solubility and long retention time in vivo, thus limiting its clinical applications. Recently, single domain antigen-binding fragments known as “nanobodies” or as VHH were cloned from the naturally occurring heavy-chain-only antibodies in Camelid. The beneficial features such as small size, high solubility and stability, robust specificity, and good expression in microorganisms enable the nanobody technology to be used in a broad range of applications in fundamental research, biotechnology, disease diagnosis and therapy. In this review, we outline the current status of nanobody research including 1) the similarities and differences of nanobodies compared with conventional antibody fragments, 2) the framework of VHH production from camel immunization, VHH repertoire construction, VHH biopanning, and purification of recombinant VHH, and 3) the competitive advantages of nanobody-based delivery systems in molecular imaging and tumor-targeted cancer treatment over the conventional antibody usage.

Abstract:Fast neurotransmitter release plays an important role in neuron communications. The membrane fusion process mediated by SNAREs can be significantly influenced by proteins related to neurodegeneration. In order to understand the molecular mechanism, a series of single molecule biophysical assays have been developed for observing content mixing rather than (or in addition to) lipid mixing at the single-vesicle level. Based on proteoliposomes reconstituted with v- or t-SNARE proteins, people have developed single vesicle-vesicle fusion assays that monitor lipid or content mixing and both lipid and content of individual vesicle-vesicle pairs. By simultaneously observing lipid and content mixing indicators of single vesicle pairs, these assays provide a foundation to investigate the influence of other regulation factors on SNARE-mediated membrane fusion. Furthermore, these single vesicle-vesicle fusion assays have been applied for systematically characterizing proteins related to neurodegeneration (CSPα, α-Syn, and Aβ) during different stages (docking, hemifusion, and full fusion) of SNARE-mediated membrane fusion.

Abstract:Toxin-antitoxin (TA) loci encode two-component genetic elements: a stable “toxin” protein and an unstable “antitoxin” (a protein or a regulatory RNA) that neutralizes the toxin action. A lot of researches have been done on the cellular targets of toxins, the molecular structures and biological functions, and the mechanisms of antitoxin actions. The studies not only discovered a multitude of physiology roles of TA systems, but also led to a number of applications for various purposes. Currently, five TA systems have been discovered in countless bacteria and archaea. The antitoxins in type Ⅰ systems are regulatory RNAs which can employ several different modes to counteract toxin proteins and their special RNA regulatory strategies have made type Ⅰ TA systems become a focus of TA researches. Within this review, we will summarize our current knowledge on type Ⅰ TA system and look into the future of their potential applications.

Abstract:Sialic acid which often terminated in the carbohydrate chain of glycoconjugates, is closely related to organs development and various disease progression. Sialic acids may regulate the biological functions of glycoconjugates through removing the sialic acid on them and changing their conformation. Up to date, four sialidases have been found in mammalian cells, and the research on sialidase 1 (Neu1)is more widely. The hydrolysis substrates of Neu1 are varied, and strongly linked to the structure and function of cell surface receptors. Recent evidence indicates that Neu1 has recently emerged as a central target in sialidase-mediated regulation of diseases development, and plays a much more profound role in human diseases than previously expected. This paper summarized current progress of functional research on Neu1 in recent years, and the interacting mechanism between Neu1 and cell surface receptors.

Abstract:Lytic polysaccharide monooxygenases (LPMOs) are newly discovered copper-dependent oxidases usually with diverse modular combinations, and can decompose biomass polysaccharides through an oxidative mechanism. The catalytic domains of LPMOs share a β-sandwich structure, and their active sites contain a single copper ion. Their catalytic reaction process is more complicated than that of glycoside hydrolases. After binding the substrate, electrons provided by the electron donor are transferred to Cu[Ⅱ] in the active site of LPMOs via electron transport chain, then Cu[Ⅱ] is reduced to Cu[Ⅰ] which bind and activate oxygen, finally LPMOs break down the glycosidic bond of polysaccharides via oxidative cleavage, generating oxidized and non-oxidized products. Recent studies demonstrate that LPMOs can significantly enhance the efficiency of lignocellulolytic enzymes in degrading crystaline cellulose. Further investigation of LPMOs can expand the understanding of their efficient degradation mechanism and provide theoretical guidance for recomposing high-efficiency degradation enzymes to lower the cost in industrial application. This review addresses the recent research progress of LPMOs and analyzes perspective of potential research fields and practical applications.

Abstract:Chronic active Epstein Barr virus infection(CAEBV) is subcategorized as EBV⁺ T/NK lymphoproliferative diseases (EBV⁺ T/NK-cell LPD) and characterized by recurrent or chronic symptoms of infectious mononucleosis and clonal expansion of EBV⁺ T/NK cells and with high morbidity and mortality in clinic. It remains unclear what is the cause of CAEBV due to its complexity among different cases. Clinically, it is of importance to give accurate classification of EBV⁺ T/NK-cell LPD for appropriate therapeutic strategy, however, the standards for classification are still unsettled and the treatments are less than satisfactory. To explore some clues for further study, the current understanding of the pathogenesis of CAEBV will be summarized from several aspects such as the clonal expansion of EBV infected cells, EBV related virological factors, defects in host immune system in this review.

Abstract:Heat shock protein gp96 is overexpressed in many kinds of tumors including hepatic tumors, and its overexpression is significantly correlated with tumor malignant degree and poor prognosis in patients. The mechanisms of heat shock protein gp96 in the development of tumors need to be further investigated. The effects of gp96 3′UTR as a ceRNA (competing endogenous RNA) on miR-642a and DOHH expression was studied through bioinformatics prediction, luciferase reporter assay, Western blotting, real-time PCR, RNA interference. MiR-642a specifically targets gp96 3′UTR. The wild type but not the mutant gp96 3′UTR in miR-642a binding site could sequester and downregulate miR-642a levels, which led to increased expression of the miR-642a target DOHH. Further studies showed that regulation of DOHH expression by gp96 3′UTR was miR-642a dependent. It was also found that DOHH does not affect the expression of gp96. Heat shock protein gp96 promotes DOHH expression via its 3′UTR as a ceRNA, providing new insights into the role of gp96 on the development of hepatic tumors and other tumors.

Abstract:Single molecule fluorescence resonance energy transfer (smFRET) is a technique used to study the conformational change of a molecule by detecting the transfer efficiency of fluorescence energy between donor and acceptor fluorescence inside a single molecule. However, to obtain the information of these biological macromolecules, the statistical analysis of a large number of single molecular signals is required. Manual analysis is time-consuming and laborious and lacks objectivity and reproducibility. Therefore, the wavelet transform and rolling ball algorithms are applied to smFRET images to analyze single molecule signals. Based on the accurate detection of single molecule signals, we analyzed the linearity of the images processed by the rolling ball and wavelet transform algorithms. The results show that the two methods can not only remove the background noise of smFRET images but also maintain the linearity of single molecule fluorescence signals. At the end of this paper, we draw a statistics histogram of 15 bp DNA FRET efficiency and calculated the FRET efficiency value using rolling ball algorithm processing.

Abstract:3-ketoacyl ACP synthase Ⅲ (FabH) catalyzes the initial reaction in bacterial fatty acid synthesis. Gram-positive bacterial FabHs are able to utilize branched chain acyl-CoA as a primer, and are essential for the synthesis of branched chain fatty acids (BCFAs). However, some Gram-negative bacteria also synthesize BCFAs through a mechanism that is poorly understood. To compare the features of different bacterial FabHs, we selected four homologous Gram-positive bacterial fabH genes (Bacillus subtilis BsfabH1 and BsfabH2, Staphylococcus aureus SafabH and Streptomyces coelicolor ScofabH), and three homologous Gram-negative bacterial fabH genes (Escherichia coli EcfabH, Ralstonia solanacearum RsfabH, and Xanthomonas oryzae pv. oryzae XoofabH) for further study. Expression of each of the seven fabH genes restored the growth of the R. solanacearum fabH mutant RsmH in the absence of octanoic acid, indicating that all encoded FabHs have 3-ketoacyl ACP synthase Ⅲ activity. Furthermore, fatty acid profiling showed that complementation with the four Gram-positive bacterial fabH genes or the Gram-negative XoofabH rendered the R. solanacearum fabH mutant able to produce a large quantity of BCFAs, while the RsmH mutant harbouring EcfabH or RsfabH could only synthesize straight chain fatty acids, suggesting XooFabH performs a role different from EcFabH or RsFabH in BCFA sysnthesis. In vitro analysis showed that, similar to the four Gram-postive FabHs, XooFabH has a preferance for using branched chain acyl-CoAs as primers. XooFabH also displayed a strong activity towards short or medium chain acyl-CoAs (~C4-C10), unlike other Gram-positive FabHs. These results confirmed that FabH from different bacteria have different biological characteristics, and display a preferance for branched chain acyl-CoAs, which are essential for BCFAs synthesis.

Abstract:Milk: new transmission route of hepatitis e virus