Abstract:In recent years, genome editing technology has been well developed, which have major implications for basic biology research, medicine, and biotechnology. As a new member of CRISPR system, Cpf1 greatly expands the choice of target sites for genome editing and has significant advantages in multiple gene editing. In addition, its shorter RNA sequences (crRNAs) make it closer for the application via industrial direct synthesis. Here we summarized the structure, gene editing characteristics, application progress, current limitations and future prospects of Cpf1 system.

Abstract:Stimuli responsive nanocarriers as nano-intelligent drug delivery system could make corresponding change in structure and physicochemical properties for response to external stimulus．Take the advantages of avoiding premature drug release and improving the drug concentration in the lesion, they have become a focus in diagnosis and treatment of cancer and were widely used to control drug delivery and release．Based on the temperature, magnetic field, ultrasonic, light, pH and other endogenous and endogenous stimulus, we reviewed the recent research development of stimuli responsive nanocarriers in the field of tumor diagnosis and treatment in this paper.

Abstract:Circular RNAs (circRNAs) are endogenous non-coding RNAs that widely exist in eukaryotic transcriptomes. Unlike linear RNAs, circRNAs are not easily degraded for having a more stable structure. By acting as microRNA (miRNA) sponges, RNA-binding protein sponges, regulating transcription, or translating to proteins, circRNAs regulate gene expression at transcriptional or post-transcriptional levels. Recent studies have found that circRNAs play important roles in regulating cell proliferation, migration and invasion of tumor cells. Gastrointestinal tumors are common malignant tumors with high mortality in China. Researchers found a large number of abnormally expressed circRNAs (such as hsa_circ_0014717, hsa_circ_0001017, hsa_circ_0061276, hsa_circ_0125965, hsa_circ_0000181, hsa_circ_002059, hsa_circ_0000190, hsa_circ_0000096, hsa_circ_0014717, and hsa_circ_KLDHC10) in gastrointestinal tumors. This paper firstly describes the formation mechanisms and biological functions of circRNAs. Then, combining with the latest research progresses of gastrointestinal tumor-associated circRNAs and our group’s related research results, we review the mechanisms of circRNAs affecting gastrointestinal tumorigenesis and hope to provide a new theory for the diagnosis and treatment of gastrointestinal tumors.

Abstract:WRAP53 beta, a protein with a WD40 domain, plays an essential role in the maintenance of Cajal body stability, RNA splicing, and telomere elongation. WRAP53 β dysfunction is related to dyskeratosis congenita, tumor, progressive spinal muscular atrophy, premature aging and other diseases. Recent studies have found that WRAP53 β is an important scaffold protein essential for DNA double strand break repair (DSBs). It can be recruited to DNA damage sites in a H2AX, ATM and MDC1-dependent manner and phosphorylated by ATM. Then the phosphorylated WRAP53 β recruits ubiquitin E3 ligase RNF8 through its WD40 domain leading to histone H2AX ubiquitination, and further aggregation of downstream repair factors for DNA damage repair. In this review, we summarize the recent advances in the specific role and underlying mechanisms of WRAP53 β in the repair of DNA damages.

Abstract:The competition between cells can influence cells’ growth, survival, as well as their functions．In tumor micro-environment, there also exists a fierce competition between tumor cells and non-tumor cells．Because different cells have different nutritional conditions and energy metabolism phenotypes, the state of cells has a closed relationship with energy metabolism．The growth of tumor cells is very fast, and the invasion and metastasis are easy to occur．All of these are based on the support of their own energy．Tumor cells mostly depend on the way of glycolysis to gain their energy, glucose can be converted to pyruvate by glycolysis when it enters into cells．The rate of glycolysis is related to the amount of glucose flowing into the cell, the activity of coenzyme and other related enzymes．Succinate dehydrogenase(SDH) is the essence of the tricarboxylic acid cycle which locates in the inner membrane of mitochondria．Mutations in the SDH gene are involved in many cancers, such as renal cell carcinoma, wild-type gastrointestinal stromal tumors (WT GISTs) and hereditary paraganglioma, pheochromocytoma．The mitochondrial succinate dehydrogenase complex is composed of multiple subunits, including SDHA, SDHB, SDHC, and SDHD．Among them, SDHA plays an important role, and SDHA mutation can cause the loss of enzyme activity in SDH tumor tissues．Immunohistochemistry and transcriptome analysis shows that the SDHA mutation can cause hypoxia, this may lead to increased angiogenesis and other SDHx mutations．The mitochondrial succinate dehydrogenase subunit A (SDHA) provides electrons for the mitochondrial electron transport chain．The abnormal expression of SDHA plays a key role in tumorigenesis．In this paper, SDHA is reviewed on the basis of the effect of SDHA on energy metabolism in tumor cells.

Abstract:Since the inverse relationship between the levels of apoA-Ⅰ in plasma and the risk of cardiovascular disease is derived from the atherosclerosis (AS). Lipid apoA-Ⅰ formation of high-density lipoprotein(HDL), which by promoting reverse cholesterol transport(RCT) helps cholesterol efflux. α-Helix plays an important role in cholesterol efflux, it’s the acceptor of lipid on apoA-Ⅰ. The mimic peptides of apoA-Ⅰ have similar structure with α-helix, and they can inhibit the development of AS by different ways. This review focuses on the effects of α-helix of apoA-Ⅰ in cholesterol efflux, in order to further explore the structure of apoA-Ⅰ influence on cholesterol efflux, aims at providing the new thought and therapy targeting for AS.

Abstract:Alzheimer’s disease (AD) is a complex multifactorial disease, characterized by progressive cognitive impairments and loss of memory. At present, there is no effective treatment for AD. The neurons differentiated from induced pluripotent stem cells (iPSCs) which are derived from AD patients have the relevant pathological manifestations of AD. Thus iPSCs is one of models for the study of the pathogenesis of AD and for finding the underlying drug target for AD. iPSCs can differentiate into different types of nerve cells to improve the symptoms of AD. The study of iPSCs in AD became an important issue. The advantages of iPSCs as a model in the pathological study of AD and the role of iPSCs in AD treatment were summarized in this article.

Abstract:Rapid point-of-care (POC) detection of influenza A virus is critical for timely and effective flu prevention and control. In this study, we developed a hybridization chain reaction (HCR)-based assay, through coupling HCR reaction with fluorescence quenching by graphene oxide (GO), for the rapid detection of influenza A virus. The target is detected as it triggers HCR, which results in the extension of short DNA chains, protecting the 6-carboxy-fluorescein amidite (FAM) group from GO quenching. The results demonstrate that it could specifically recognize target nucleic acid fragment of influenza A virus from other pathogen, and even from single-base mismatched oligonucleotides. A good linear correlation between fluorescence intensity and the target concentrations ranging from 10 to 40 nmol/L was achieved, with a detection limit of 5 nmol/L. Its detection performance was verified on nasopharyngeal swab samples, which is the first clinical application of HCR-based influenza assay. This HCR-based method shows many advantages including the enzyme-free amplification of nucleic acids, simple reaction system and convenient protocols, suggesting its availability for POC detection.

Abstract:In reptiles with temperature-dependent sex determination(TSD), the individual’s gender depends completely on the incubation temperature of the eggs. The molecular mechanism underlying temperature- dependent sex determination has been a long-standing mystery, in particular, the factors responsible for triggering the differentiation of biopotential gonads either into a testis or an ovary are unknown. In this study, the regulatory role of Sox9 on male gonadal differentiation in Trachemys scripta was investigated through expression analysis and gene-modulating approach, providing important reference for the study of sexual differentiation and gonadal development mechanism of reptiles with TSD and an effective molecular techniques for controlling the sex of animals. Real-time PCR showed that the MPT-specific expression of Sox9 in embryonic gonads initiated early at stage 17, preceding the onset of gonadal differentiation, however, the FPT embryonic gonads exhibited extremely low expression level of Sox9 throughout the embryogenesis. Immunofluorescence further confirmed the SOX9 protein was abundantly expressed and mainly localized in the nuclei of precursor Sertoli cells in MPT gonads. The temperature shifts experiments showed that the expression of Sox9 in MPT→FPT (which was shifted at stage 16) gonads was significantly reduced from the stage 17, indicating that Sox9 can respond rapidly to the new temperature. Meanwhile, the expression of Sox9 was also down-regulated rapidly in the MPT gonads treated with estrogen. Loss-of-function analysis showed that 90.9% MPT embryos with Sox9 knockdown exhibited male to female sex reversal, characterized by obvious feminization gonads with well organized outer cortex and degradated medullary area. These above results indicate that Sox9 is required for testicular differentiation in a TSD system.

Abstract:To investigate whether dihydromyricetin(DHM)inhibits high glucose induced PC12 cell apoptosis by downregulating JNK signaling. The cell viabilities of PC12 cells were assessed by MTT assay. The apoptotic rates of PC12 cells were measured after Annexin-V/PI (propidium iodide) staining by flow cytometry (FCM). Hoechst 33258 staining was used to detect the morphology of apoptotic PC12 cells. The expression of apoptosis-related proteins (Bax, Bcl-2, cleaved-Caspase-3) and the level of p-JNK in PC12 cells were detected by Western blotting assay. After PC12 cells were treated with different concentrations of glucose (4.5, 9, 13.5, 18 g/L) at 24, 48, 72 and 96 h respectively, the results showed that 13.5 g/L high glucose treatment for 72 h could significantly change the cell morphology, reduce cell viability, increase the apoptosis rate, at the same time, the expression of pro-apoptotic protein (Bax, Caspase-3) was increased and anti-apoptotic protein Bcl-2 was decreased, indicating that long-term high glucose treatment induced PC12 cell apoptosis. However, pretreatment with DHM (15 μmol/l) could significantly improve high glucose induced PC12 cell apoptosis and decrease the expression of JNK and p-JNK high glucose induced PC12 cell. Further treatment with JNK agonists (Anisomycin), which could eliminate the protective effect of DHM on apoptosis induced by high glucose in PC12 cells. In conclusion, DHM antagonizes high glucose-induced PC12 cell apoptosis by down-regulating JNK signaling.

Abstract:The important factors in secondary structures of mRNA influencing on protein folding rates are found during our previous research, and there are kinds of complex loop structures in secondary structures of mRNA. Do these complex loop structures have important influences on protein folding rate? Do different loop structures have similar effects on protein folding rate? Based on this idea, a data set that contains both the information of internal loops, hairpin loops, bulge loops, multi-branch loops and protein folding rates was constructed. For each protein in the data set, the secondary structures of mRNA were predicted followed by calculations of the parameters of mRNA secondary structures, including the base content of each loop structure, the content of base pairs, and the base content of the single strand. Analyses of the relationship between the protein folding rates and each parameter of loop structures of mRNA reveal that the protein folding rate has a significant positive correlation with the content of each kind of the four loop structures, it means that the loop structures of mRNA act as a kind of influential factors for the protein folding rate. Given the proteins in the data set were classed into different folding types and different secondary structural types, the relationship analyses reveal that for proteins in different types, the effects of loop structures on protein folding rate are significantly different. This work will provide the theoretical basis for the future study of mRNA and protein folding rate.