Abstract:The new coronavirus SARS-CoV-2 has a strong transmission ability and has been confirmed to be transmissible from person to person. Asymptomatic carriers can also be a source of transmission. Rapid and accurate diagnosis of the new coronavirus is particularly important to control the outbreak. Based on the relevant research progress at home and abroad, this paper analyzes and combs the four major detection technologies of new coronaviruses such as fluorescent PCR, isothermal amplification, Cas enzyme technology and immunoassay, in order to provide references and ideas for the diagnosis, prevention and control of new coronaviruses and other epidemic viruses.

Abstract:CRISPR/Cas-based gene editing system is one of the newly-developed and promising biotechnologies. It shows broad application prospects for gene editing, DNA and RNA imaging, regulation of gene transcription, gene detection and disease diagnosis, establishing animal disease models, and improving crop, etc. In this review, we overviewed the background and development history of CRISPR / Cas systems, discussed recently-investigated delivery methods including various nanocarriers, summarize the preclinical and clinical advances of CRISPR/Cas-based therapeutics, and introduced other application areas besides gene editing. Finally, we made an outlook on the challenges we need pay attention to, and the future application prospects of CRISPR/Cas technologies.

Abstract:RNA polymerase is responsible for RNA biosynthesis and is an important regulatory machine for maintaining cell growth and organ development. Eukaryotes mainly transcribe genes through three kinds of multi-subunit RNA polymerase (RNAPⅠ, RNAPⅡ and RNAPⅢ). RNA polymeraseⅡ consists of 10 core subunits, the molecular size of which is about 520 ku. Structure and function of RNA polymerases have been clarified, but their assembly process are not clear. RNA polymerase subunits can not be completely self-assembled in vitro, indicating that this process in cells needs the help of assembly factors. RNA polymerase assembly is a complex biological process. In recent years, the identification and functional analysis of assembly factors have made RNA polymerase assembly a hot spot. The assembly factors found in Saccharomyces cerevisiae are Rba50, Bud27 and GPN protein family. Among them, GPN protein family is an important GTPase family, which exists in archaea, yeast and higher eukaryotes, and is highly conserved. Recent studies have found that Rba50 homologous proteins (IYO and RPAP1) in plants and animals are related to cell differentiation and tissue development. Mutations in assembly factors such as GPNs are closely related to cell development and cancer development. This article reviews the latest progress of RNA polymerase assembly in eukaryotes, with a view to provide a basis for the final elucidation of RNA polymerase assembly mechanism and its association with disease occurrence.

Abstract:Lysosomal dysfunction caused by abnormal lysosomal ion channels is an important factor leading to neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Lysosomes ion channels regulate lysosomal ion homeostasis, lysosomal membrane voltage, and lysosomal acidity. Structural or functional defects of lysosomal ion channels will cause lysosomal degradation dysfunction, leading to the occurrence and development of neurodegenerative diseases. In this review, The role and mechanisms of various lysosome ion channels in regulating lysosomal function were summarized.The underlying mechanism of the deficits of the ion channels in neurodegenerative diseases were also introduced. Regulating ion channels to improve lysosomal function and promote the clearance of abnormal aggregated proteins are underlying targets for the treatments of neurodegenerative diseases.

Abstract:Posttraumatic stress disorder (PTSD) can impair cognitive functions such as memory, attention, and executive control, and induce the abnormality of brain activity and functional connectivity between brain regions. Although pharmacotherapy and psychotherapy can achieve a certain degree of therapeutic effects, there are problems such as side effects and delayed onset of action. Transcranial magnetic stimulation (TMS) has attracted more and more attention as a new intervention method for posttraumatic stress disorder. Here we systematically review the studies of the effects of TMS in the intervention of PTSD and the regulation of cognitive function and brain activity. The issues of TMS in the intervention of PTSD were discussed, including the stimulation pattern, the stimulation target and the efficacy evaluation. In the future, the intervention programs with long-term clinical improvement can be explored by applying more effective techniques for precise targeting, establishing integrative and effective evaluation systems, and combining new memory theories.

Abstract:Ubiquitination is an important post-translational modification that controls nearly every facet of a cell’s life and death. Only ubiquitin ligases E3 can specifically recognize substrates during ubiquitination, so E3 plays a pivotal role in ubiquitination and degradation of substrate proteins. Human apoptosis-resistant E3 ubiquitin protein Ligase 1 (AREL1) belongs to the Homology to E6AP C-Terminus(HECT) ubiquitin ligase family, and it inhibits apoptosis through ubiquitinating mitochondrial proapoptotic proteins such as SMAC, HtrA2, and ARTS, which are degraded by the 26 S proteasome. Here, the crystal structure of the HECT domain of AREL1 (AREL1^HECT) at 3.2 ? resolution is reported, and structural comparisons of AREL1^HECT against different HECT E3 ligases are conducted. Size Exclusion Chromatography (SEC) and Small Angle X-ray Scattering (SAXS) indicate that there are diverse oligomeric states of AREL1^HECT in solution, and the SAXS 3D model further suggests that AREL1^HECT can dimerize in solution. These findings offer a structural basis for studying the complex of AREL1^HECT and ubiquitin, and provide insights into molecular mechanisms of substrate ubiquitination by AREL1.

Abstract:Hepatocellular carcinoma (HCC) is one of the malignancies with high morbidity and mortality in the world. The purpose of our study was to search for HCC related miRNA prognostic biomarkers to predict the risk degree and survival time of HCC patients and provide effective prognostic information for HCC patients. Four methods were used to identify differentially expressed miRNAs (DEMs) from The Cancer Genome Atlas(TCGA). Kaplan-Meier survival curve, univariate and multivariable Cox regression analysis were used to identify prognostic miRNAs of HCC from DEMs. Four prognostic miRNAs biomarkers (hsa-miR-132-3p, hsa-miR-139-5p, hsa-miR-3677-3p, hsa-miR-500a-3p) of HCC were identified at last, and combined into a risk score model. There was no experimental evidence that hsa-mir-3677-3p is related to HCC, and it was a newly discovered miRNA in this study. The evaluation results of various bioinformatics methods, including survival curve, ROC curve, chi-square test, et al.. All indicated that the risk score calculated by the model can effectively predict the risk degree of patients(P<0.000, hazard ratio=2.551, 95% confidence interval=1.751-3.717). 1-5 year survival rates of HCC patients in the low risk group had 20%-30% higher than in the high risk group. Through the clinical data analysis, it was found that the combined biomarkers have a better prognostic effect than other clinical indicators, and can also be used as an independent prognostic factor. Target genes of four miRNAs were predicted, including AGO2, FOXO1, ROCK2, RAP1B, CYLD, et al., and enriched in biological processes such as cell proliferation, migration, apoptosis and immune response.