Abstract:The new cancer treatment research needs to be accelerated, not only because tumor types and increasing number of patients, but also because traditional therapies, surgical methods, chemotherapy and radiotherapy have certain drawbacks. Oncolytic viruses (OVs) can not only directly kill tumor cells but also activate immune system to exert better effects. However, natural OVs have some defect that limit its further application. In order to overcome its shortcomings, the OVs' vectors was constructed. With advances in molecular biology, OVs could introduced exogenous gene or reduce virulence to improve its function as vectors for treating tumors. At present, OVs such as herpes simplex virus, adenovirus, vaccinia virus, vesicular stomatitis virus, measles virus, mumps virus, and poliovirus have made certain progress in treating tumors as OVs' vectors. The current modification methods of OVs' vectors can be divided into the following types: delete genes harmful to normal cells; insert foreign genes to achieve biological regulation; insert ligand genes that specifically bind to tumor surface receptors. This article reviews modification methods and effect of the aforementioned OVs vectors.

Abstract:More and more people suffer from myopia due to keratoconus disease. Common correction methods include wearing myopia glasses, contact lenses, etc. With the progress of science and technology, the use of light for refractive correction of myopia and other ophthalmic diseases has become a common clinical method. The light can induce the cross-linking of corneal collagen, so as to treat keratoconus disease and improve the visual acuity of patients. At the same time, this method has become a novel research focus due to its merits of non-invasive and low dependence on operator ability. In this paper, the basic principle and development of light-induced corneal crosslinking are introduced, meanwhile the principles of various existing cross-linking methods and corneal detection techniques are analyzed, and the advantages and disadvantages of the existing cross-linking methods and detection methods are discussed. Finally, the latest development of light-induced corneal crosslinking and detection technology is systematically discussed, and prospected the future development trend of light-induced corneal crosslinking and detection technology.

Abstract:Deep brain stimulation (DBS) has become one of the common treatments for movement disorders such as Parkinson's disease. It is also a promising treatment for other neurological and psychiatric disorders. However, the stimulation paradigms of regular DBS are not diversified enough to meet the needs for extending its applications, because current DBS therapy usually utilizes single-channel high-frequency stimulation of electrical pulses with a constant inter-pulse-interval. According to the desynchronization mechanisms of DBS, new stimulation paradigms have been developed by designing the temporal and spatial patterns of pulse sequences to improve the therapeutic efficacy, to extend its application and to save the electric energy of impulse generator. The new paradigms include: stimulations of varying-frequency sequences (including regular varying-frequency and random varying-frequency), multi-channel asynchronous stimulations at different spatial locations, as well as the combined stimulations of varying-frequency and multi-channels. These new paradigms may improve the efficacy of DBS and reduce the energy consumption thereby showing good prospects in treating Parkinson's disease and other brain diseases such as epilepsy, obsessive-compulsive and minimally conscious state. Notably, in addition to the better acute effect during the stimulations, the efficacy of multi-channel stimulations may last for a long time after the termination of stimulations, indicating a sustained effect or an after-effect. This performance breaks the limitation of regular DBS that has only acute effects and opens out a new prospect for DBS. Based on a summary of the stimulation paradigms of regular DBS and their underlying mechanisms, this review presents the development of new DBS paradigms on the stimulations of varying-frequency and multi-channels to generate asynchronous effects, thereby providing valuable information for the development of DBS.

Abstract:Drug-induced cardiotoxicity is one of the important causes of the failure in drug development. The traditional animal models for drug evaluation have many defects such as species differences, high cost, and low efficiency. It is crucial for drug development to construct more economical and efficient toxicity evaluation models which can accurately simulate the physiological characteristics of human heart. In recent years, with the rapid development of stem cell and bioprinting technologies, the construction of in vitro cardiac tissue model has received more and more attention. In this review, the origin and development of in vitro cardiac model construction are overviewed. The cell sources of cardiomyocyte and the relative techniques and methods for model construction are comprehensively reviewed. Combining with the construction technologies such as bio-printing and microfluidics,the importance and research progress of vascularized cardiac tissue model are highlighted. Finally, the future perspectives and challenges of this field are discussed in order to provide new ideas for the research and application of in vitro cardiac tissue model in drug evaluation.

Abstract:The main functions of terminally differentiated vascular smooth muscle cells are contracting vessel, regulating vessel diameter and blood pressure, etc. Under the action of hyperphosphatemia, hyperglycemia, vitamin D₃, inflammation and other factors, vascular smooth muscle cells are transformed into osteoblast-like cells to participate in vascular calcification, which induce cardiovascular and cerebrovascular adverse events. Non-coding RNA is a general term for a variety of RNA types that transcribed from the human genome but lacking the ability to encode proteins. Non-coding RNA participates in the body's physiological and pathological processes by regulating various cell activities. Studies have shown that non-coding RNA can affect the occurrence and development of vascular calcification by regulating the osteoblast-like phenotype transformation of vascular smooth muscle cells. This article reviews the regulatory role of non-coding RNA in osteoblast-like phenotypic transformation of vascular smooth muscle and vascular calcification from the aspects of microRNA, long non-coding RNA and circular RNA, which is helpful to further understand the molecular mechanism of vascular calcification and find new targets for the prevention and treatment of vascular calcification.

Abstract:Polysaccharide is abundant in nature, but its complex anti-degradation structure limits the process of bioconversion. In recent years, with the rapid analysis of biomass polysaccharide structure and the identification of polysaccharide degrading enzyme, on the basis of different structure of substrate or product requirement, it is possible to imitate the efficient metabolic pathway of microbial polysaccharides, tailor polysaccharides degrading enzyme system, and promote the efficient conversion of biomass. In this paper, the structure composition of neutral polysaccharide (cellulose and xylan), alkaline polysaccharide (chitin and chitosan) and acidic polysaccharide (alginate) were analyzed. Then the structural characteristics and substrate binding patterns of the major degrading enzymes targeted at the three kinds of polysaccharides were summarized. Protein engineering design and customization strategies are also described. The analysis of different functional areas of enzyme molecules can provide targets for further design and modification to obtain high efficiency enzymes in industrial applications. In addition, in terms of the order of microbial extracellular degrading enzymes and their synergistic relationship, complex polysaccharides degrading enzymes can be precisely tailored based on the needs to achieve efficient and high-value degradation transformation of the biomass.

Abstract:ABC(ATP-binding cassette) transporters are members of the largest superfamily of membrane transporters which modulate the transmembrane of various substrates against a chemical gradient via the energy by ATP hydrolysis. All organisms harbor numerous ABC proteins in different cellular compartments such as the plasma membrane, vacuoles, mitochondria and peroxisomes. Typically, ABC transporters are consisted of transmembrane domains(TMDs) and nucleotide-binding domains(NBDs) to bind their substrates and ATP respectively. NBDs, as the power engine of the ABC transporters, mediate the ATP binding and hydrolysis, whileTMDs determine what ligands can be recognized. The ABC proteins, in most cases, were initially discovered during the investigation on resistance to a multitude of drugs, including PDR(pleiotropic drug resistance) and MDR (multidrug resistance). In the present article, we reviewed the research advances of the structure and transmembrane transport mechanism of ABC transporters and their roles in plant pathogenic fungi.

Abstract:Elongation factor 4 (EF4) is a non-conventional elongation factor which regulates protein synthesis in mitochondria. In this study, we explored its function in bladder urothelial carcinoma. By analyzing the expression of EF4 in bladder urothelial carcinoma and adjacent normal tissues, we found that EF4 was aberrantly elevated in multiple cohorts of bladder cancer patients. Notably, the upregulation of EF4 was positively associated with tumor progression. By manipulating EF4 expression in HTB-9 and T-24 bladder cancer cells, the effects of upregulated EF4 was investigated. Knockdown of EF4 suppressed the proliferation and colony formation in bladder cancer cells; the ability of cells to migrate in vitro was also retarded. Knockdown of EF4 down-regulated the expression of mitochondrial DNA-encoded subunits of electron transfer chain complexes, and resulted in the dysfunction of mitochondrial oxidative phosphorylation. These results define a tumor-supportive role for EF4 by maintaining the protein synthesis within the mitochondria, which may serve as a potential therapeutic target in bladder urothelial carcinoma.

Abstract:In this paper, we propose a deep learning model based on convolutional neural network and recurrent neural network, which uses genome sequence data to identify human circular RNA splicing sites. Firstly, we preprocessed the original genome sequences and designed 16 models with two network depths, eight convolution kernel sizes and three LSTM parameters; secondly, the pooling layer was further tested for average pooling and maximum pooling; and GC content was added to improve the prediction ability of the model; finally, we predicted the circRNA in human seminal plasma. The results show that the model with convolution kernel of 32 × 4, depth of 1 and LSTM parameter of 32 has the highest recognition rate of 0.9824 on training data set, and 0.95 on test data set. Also, we tested our model with a published study and the accuracy reaches 0.83. The model has good performance in the recognition of human circular RNA splicing sites.

Abstract:The retina is a layered structure, and some diseases can be clinically predicted and diagnosed based on the change in the thickness of the retinal layer. To segment the different layers of the retina quickly and accurately, this study proposes a random forest algorithm based on principal component analysis (PCA). The algorithm uses PCA to resample the normalized features collected from the retinal images and retains the feature information dimensions with significant weight, thereby eliminating the relevance between the different feature dimensions and information redundancy. After PCA, the number of features can be reduced obviously, but still retains 99% information. Random forests algorithm applies the features to learn and predict the location of retinal layer boundaries. We extract each pixels values of retinal boundaries, producing an accurate probability map for each boundary. Experimental results show that when the total number of feature dimensions decreased from 29 to 18, the training speed of the model increased by 23.20%. By contrast, when the number of feature dimensions was 14, the training speed increased by 42.38%. However, the effect on image segmentation accuracy was not obvious. Thus, it is found that this method effectively improves the efficiency of the algorithm.

Abstract:Abstract: The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols through a negative feedback mechanism. SREBP-cleavage activating protein (SCAP), and insulin-induced gene-2 (INSIG-2), 25-hydroxycholesterol (25HC) play an important role in regulating the activation, maturation, and nuclear translocation of SREBP. Recent studies have shown the structure of the SCAP-INSIG-2-25HC complex, which is important to the study of intracellular cholesterol metabolism.