Abstract:Hepatitis B virus, a small DNA virus, is the prototype of the Hepadnaviridae family. Chronic infection with HBV (CHB) remains a significant public health problem in worldwide, which is a major factor resulting in fibrosis, cirrhosis, and hepatocellular. Previous HBV treatment devote to interfere the HBV genome, including nucleotide analogues (NAs) and type Ⅰ interferon (IFN). However, virus mutation and drug resistance occur during these treatments. And current therapeutic strategy tend to intervene the host factors, involvement in the entry, replication and assemble of HBV, bringing us a new venue against HBV. Thus, numerous studies spent large amount efforts to explore RNA interference (RNAi) host gene silencers, which potentially could be a novel anti-HBV therapeutics. Here, we summarized the current progression targeting the host genes for curing chronic HBV infection.

Abstract:Infectious diseases make up an important threat to human health and there is an urgent need for new treatments to reduce morbidity and mortality caused by acute viral infections such as rhinovirus and dengue virus, and chronic viral infections such as human immunodeficiency virus-1 and hepatitis B virus. With the development of molecular biology technology, gene-editing technology targeting sequence-specific loci has become a powerful tool for the treatment of infectious diseases. Among them, the regular clustered regularly interspaced short palindromic repeats (CRISPR) -CRISPR associated protein 9 (Cas9) is widely used in cell lines and animal models because of its high efficiency, convenience and high specificity, which has become a promising model for the treatment of new infectious diseases. Currently, feasibility studies of the use of viral and non-viral vectors to deliver Cas9 into cells in the form of DNA, mRNA or protein and clinical trials assessing the in vivo applicability of CRISPR-Cas9 are under way. In this review, we outline the principles of CRISPR-Cas9, the latest research advances in the treatment of infectious diseases, the challenges and possible solutions to the technology, and look further into its future direction.

Abstract:DNA methylation is a robust type of gene regulation and plays an important role in physiological processes. This review summarizes the origin of DNA methylation in bacteria, DNA methyltransferases, transcriptional and post-transcriptional regulatory mechanisms by DNA methylation, comments on research progress on DNA methylation functions as well as detection methods. The achievements will be significant for understanding bacterial epigenetic regulation and controlling bacterial infections in the future.

Abstract:The transition function impaired between goal-directed and habitual behavioral strategy are the main reasons of the formation of habitual drug-seeking behavior. Previous studies thought that the weakening ability of the prefrontal cortex to control the dorsomedial striatum, which is in charge of goal-directed system, mediated the habitual behavior. However, recent studies have found that the direct and indirect pathways of the dorsolateral striatum (DLS) can selectively regulate goal-directed and habitual systems. In addition, the projects from motor cortex to DLS can modulate the neurons’ synaptic plasticity of dopamine D1 receptor (D1DR) and D2 receptor (D2DR) bidirectional, regulating the synergistic or antagonistic effects between direct and indirect pathways. Recent studies have also revealed that the amygdala, as a key brain area for regulating emotions, can mediate the functional connection between the nucleus accumbens and DLS in the habitual drug-seeking behavior through the functional transformation between the central amygdala and the basolateral amygdala. Moreover, there is a competitive relationship for the regulation of habitual drug-seeking behavior between D1DR and D2DR neurons in the striatum. In view of these, this paper will focus on the mechanism of abnormal brain functions, which are associated with the defects of the conversion in behavioral strategies accompanying with habitual drug use, in the cell-specific and the circuit-specific ways.

Abstract:Detergent is critical for membrane protein purification, impacting the state of oligomerization, crystallization conditions and other physicochemical properties. Analytical ultracentrifugation (AUC), by characterizing the sedimentation of membrane protein-detergent complex in centrifugal fields, is able to measure various hydrodynamic and thermodynamic properties, including sedimentation coefficient, molar mass, hydrodynamic radius, binding coefficient, thus defining the homogeneity and oligomerization state of membrane protein-detergent complex. This study focuses on an ABC transporter from thermophilic bacteria, TmrAB, and utilizes AUC coupled to size-exclusion chromatography and negative staining electron microscopy to determine its homogeneity, oligomerization, and stoichiometry of membrane protein and detergent molecules. The results indicate that TmrAB complex exists as homogeneous monomer of heterodimers of TmrA and TmrB, in the condition of 8× Critical Micelle Concentration (CMC) DDM, having a ratio of DDM/TmrAB equal to 116∶1. This study suggests, AUC is a reliable method to analyze the molecular mass of membrane protein.

Abstract:Rad9 plays roles in both cell cycle checkpoint control and DNA repair. It can interact with the components of multiple DNA repair pathways and regulate their functions. Non-homologous end-joining (NHEJ) repair pathway is predominantly used in vertebrates for the repair of DNA double strand break (DSB). Proper activation of DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and DNA-dependent protein kinase catalytic subunit (DNA-PKcs), is essential for NHEJ repair. In this study, we found that Rad9 interacts with Ku70 physically and functionally. Deletion of Rad9 gene, knockdown of Rad9 expression or removal of Rad9 protein led to inefficient DNA end-joining repair. Furthermore, loss of Rad9 impaired the DNA damage-induced binding of Ku70 to the chromatin and attenuated the DNA damage-induced kinase activity of DNA-PKcs. Taken together, our data unveil a novel functional interplay between Rad9 and the NHEJ protein Ku70, indicating a role of Rad9 in NHEJ repair through modulating the activation of the DNA-PKcs/Ku70/Ku80 complex.

Abstract:Ralstonia solanacearum, a soil-borne destructive plant pathogen, has an unusually wide host range, and causes a bacterial wilt that seriously affects the production of many economically important crops in the world. Thus, investigation of physiological metabolism in R. solanacearum will be helpful to develop new ways to control the bacterial wilt. Fatty acids are compulsory components of bacteria. However, the fatty acid biosynthestic mechanism is still unclear in R. solanacearum. In this paper, we identified acyl-CoA desaturase and cyclopropane fatty acid synthase of R. solanacearum GMI1000, and characterized their functions in biosynthesis of unsaturated fatty acid or cyclopropane fatty acid. First, R. solanacearum RSc2450 (desA) complemented Shewanella oneidensis desA fabA mutant growth on LB without supplemented oleic acid and caused E. coli fabA mutant to produce unsaturated fatty acid. Furthermore, deletion of desA caused R. solanacearum grows weak on BG plate and reduces the palmitoleic acid production. The results showed though R. solanacearum RSc2450 encodes an acyl-CoA desaturase and involves in unsaturated fatty acid biosynthesis, R. solanacearum might possess a novel unsaturated fatty acid biosynthetic pathway. Next, of the two putative cyclopropane fatty acid synthases encoded genes in R. solanacearum, only cfa1 (RSc0776) restored E. coli cfa mutant YYC1257 growth in low pH medium and to produce cis-9, 10-methylene palmitic acid. And deletion cfa1 mutant was sensitive to low pH and high osmotic pressure, and lost the ability to produce cis-9, 10-methylene palmitic acid. These indicated that cfa1 involves in cyclopropane fatty acid synthesis in R. solanacearum and plays roles in adaption to low pH and high osmotic pressure. Moreover, Cfa2 (RSp1446) does not have cyclopropane fatty acid synthase activity, and its function needs further study.

Abstract:The full-field optical coherence tomography (FF-OCT) is one of the best technologies to study the morphological development of the early embryo, while its images suffer from some noises. Due to the noises, the boundaries between the different organizations in the early embryo are ambiguous, which would cause interference of organization segmentation. To solve this problem, this paper processed full-field OCT images of early embryos with the median filter, wiener filter and anisotropic diffusion algorithm, and evaluated the noise reduction effect using the signal-to-noise ratio, the mean square error, peak signal to noise ratio and edge retention index. It was shown that early embryo images after noise reduction with anisotropic diffusion algorithm kept most of the original information with relatively clear boundaries. Therefore, anisotropic diffusion algorithm is suggested to be the best denoising method for FF-OCT imaging in terms of the visual effect.