Abstract:RNAi (RNA interference), as a post-transcriptional regulatory mechanism, can achieve efficient gene silencing by the degradation of target mRNA. siRNA, a double strand RNA, is widely used in nucleic acid drug development due to its high efficiency and specificity based on RNAi mechanism. Currently, a variety of cationic carriers have been developed for siRNA delivery. However, due to the relatively strong rigid structure and relatively low anionic charge density, it is difficult for siRNA to form a stable and compact complex with cationic carriers. So the application of siRNA still faces many challenges, such as inefficient cellular uptake, a lack of specificity in cells and tissue, poor stability in delivery process, potential cytotoxicity and high initial immune response, etc. In recent years, nucleic acid self-assembled nanoparticles have attracted wide attention due to their flexible structures and high negative charge density, which will be very useful to achieve efficient delivery and gene silencing of siRNA drugs. This review focuses on recent progresses in the development of siRNA self-assembled nanostructures and their potential therapeutic applications.

Abstract:Poly(A) binding protein (PABP) family is commonly considered a protective barrier for the mRNA poly(A) tail. As a member of PABP family, cytoplasmic poly(A) binding protein-1(PABPC1) binds to A-rich mRNA sequences with high affinity and plays an important role in the post-transcriptional regulation. In addition, PABPC1 also participates in many metabolic pathways of mRNA, including polyadenylation/deadenylation, mRNA transport, mRNA translation, degradation and microRNA-associated regulation. Recently, numerous studies demonstrate that PABPC1 associated with the growth of germ cells, the hypertrophy of myocardium and the development of tumors, suggesting a close relationship between PABPC1 and the growth and development of cells. In this review, we will mainly summarize the structure, expression regulation, function and biological function of PABPC1.

Abstract:Autophagy is a significant protective mechanism of the body, which plays a key role in maintaining cell homeostasis and function during the process of coping with harmful stimuli. Additionally, autophagy also participates in regulating the occurrence and development of many diseases, such as malignant tumors and atherosclerosis. Cells are in a complex mechanical microenvironment and a variety of mechanical stimuli can induce autophagy. Stress can induce the autophagy of cardiomyocytes; tension regulates the autophagy of multiple cells in the motor system; and fluid shear stress activates the autophagy of vascular endothelial cells and tumor cells. The cell autophagy induced by mechanical stress relies on various signal pathways. The cytoskeleton, as an important regulatory factor, is not only involved in cell mechanotransduction, but also responsible for the specific process of autophagy. It is demonstrated that the cytoskeleton is closely related to autophagy induced by mechanical stress. In this paper, the effects of mechanical stimulation on autophagy and the underlying molecular mechanism are reviewed in combination with the recent research progress, which is expected to broaden a new prospective for studying the effects of mechanical stress on cell biological behavior and provide new strategies and molecular targets for the treatment of related diseases.

Abstract:Cross-modal learning refers to learning that involves obtaining information from multiple modalities and then integrating and utilizing it. Multisensory integration is an important basis of cross-modal learning. Although cross-modal conditions are more like the real-life environment of human learning, most studies still use single-modal stimuli, and the results of cross-modal learning are still somewhat messy and unsystematic. In order to better summarize the characteristics of cross-modal learning and its related mechanisms, the current review first introduces multisensory integration effects and the factors that influence them, as well as the experimental and theoretical researches on the modality non-specificity of primary cortexes. Then, we sum up the researches on consciousness, representation type, and transfer effect in cross-modal learning, and research progress for neural mechanism of cross-modal learning by adopting the techniques such as neuronal recording, ERP and fMRI. Finally, we summarize the current research results of cross-modal learning, and examine prospects for the potential applications of these research findings and future research issues in this area.

Abstract:With the aging of the world's population, the threat of age-related cognitive impairment is increasing. It is of great significance to study the mechanism of age-related cognitive impairment and find effective strategies to rescue it. Our previous studies have demonstrated that S-nitrosoglutathione reductase(GSNOR) was significantly increased in the hippocampus of aging mice and neuronal-specific GSNOR transgenic mice showed cognitive impairment in behavior tests. However, the mechanisms underlying this process remain unclear. Here, we found that CREB signaling was significantly decreased by GSNOR in cultured mice hippocampus neurons and GSNOR transgenic mice. Up regulation of the CREB signaling pathway by nobiletin rescued the cognitive impairment in GSNOR transgenic mice in Y-maze test. Nobiletin also showed protective effects on memory impairment in aging mice model. These results provide a new mechanism for the cognitive impairment in GSNOR transgenic mice and provide a new potential strategy to improve the cognitive function by nobiletin. GSNOR transgenic mice may be used as a screen model as age-related cognitive impairment.

Abstract:To evaluate the effect of iron-based nanozymes on the biofilm of S.typhimurium, the biofilms were detected by crystal violet staining method, biofilm integrity, biofilm biomass, bacterial activity, and the intracellular ROS levels of S.typhimurium S025. Our results showed that, after treatment with iron oxide (Fe₃O₄) nanozyme and iron sulfide (nFeS) nanozyme during biofilm formation for 48 h, the A₅₅₀ value, biofilm height, biofilm biomass, and bacteria viability were significantly decreased compared to the untreated group, but the intracellular ROS levels remarkably increased. Moreover, to determine whether there is a similar inhibitory effect on pre-formed biofilms, Fe3O4 nanozyme and nFeS nanozyme were incubated from the apical side of the biofilms for different time. As expected, both nanozymes appreciably destroyed the biofilms that had formed. Importantly, nFeS nanozyme showed better efficacy than Fe₃O₄ nanozyme in above biofilm treatment. Taken together, these findings clearly demonstrated that iron-based nanozymes, as a suitable agent, regulated intracellular ROS levels to prevent the biofilm formation of S.typhimurium and destroyed the matured biofilm, which is helpful to preventing and treating relevant diseases caused by biofilm of S.typhimurium.

Abstract:Evidence indicated that key changes in macrophage uptake of oxidized low density lipoprotein (ox-LDL) and macrophage polarization in atherosclerotic plaques are closely related to dysfunctional autophagy. Wnt5a (wingless-type MMTV integration site family member 5a) is highly expressed in the macrophage-rich region of atherosclerosis (AS) lesions. However, whether Wnt5a is involved in macrophages autophagy is not clear. In this study, we established macrophages-derived foam cell induced by ox-LDL to explore the effects of Wnt5a/PKCδ pathway on autophagy. RAW 264.7 macrophages were incubated with 60 mg/L ox-LDL for 6h. The expression of autophagy marker, LC3Ⅱ/Ⅰ was significantly increased and p62 was decreased obviously. Moreover, the expressions of Wnt5a, PCKδ and STAT3 were also elevated. Knockdown of Wnt5a reduced the expressions of LC3Ⅱ/Ⅰ and PKCδ, induced the expression of p62, inhibited cellular lipid accumulation. Furthermore, PKCδ inhibitor (Rottlerin) was downregulated the levels of LC3Ⅱ/Ⅰ and STAT3, upregulated p62 level, inhibited cellular lipid accumulation. Therefore, ox-LDL induces autophagy in macrophages may be associated with Wnt5a/PKCδ signaling pathway. The present study indicates that Wnt5a/PKCδ signaling pathway may be underlying target for autophagy and drug intervention.

Abstract:In order to complement the randomization of the Eigen model and the Crow-Kimura model, the site mutation rate in the Crow-Kimura model is treated as a Gaussian distributed random variable. The characteristics of the error threshold as well as the relationship between the extension of the error threshold and the fluctuation strength of the randomized mutation rate are investigated. It is shown that both the relative concentrations and the order parameter indicate the error threshold is no longer a phase transition point but a smooth crossover region in the presence of a sizable fluctuation of the site mutation rate. The quantitative analysis demonstrates that the relationship between the width of the crossover region and the fluctuation strength in the mutation randomized Crow-Kimura model is nonlinear. The obtained results are compared with those from the randomized Eigen model and it is found that for the two randomized models the relationship between the width and the fluctuation strength is linear for the randomized fitness and nonlinear (exponential) for the randomized site mutation rate. For the randomized Crow-Kimura model the width caused by the randomized fitness is comparable to that caused by the randomized site mutation rate. Nevertheless, for the randomized Eigen model the width is mainly caused by the randomized site mutation rate. A full picture about the randomization effects of the fitness and site mutation rate on the error threshold based of the Eigen model and the Crow-Kimura model is then outlined. The implications of the above results for anti-viral strategies, cancer therapy and breeding of animals and plants are discussed.

Abstract:We propose a high-dynamic optical angiography(HDOA) method to obtain blood flow images of a small biological specimen in vivo. High dynamic range exposure time is set to achieve high-dynamic integrated time modulation, which involves dynamic integrated effect and absorption effect. With this method, each-level vessels can be imaged with similar clarity. Moreover, the vessels in locations with different thickness and absorption coefficient can be reconstructed in the same image. Experiments on phantom and in vivo Gold Pristella Tetra were performed to demonstrate that HDOA can achieve each-level vessels imaging based on dynamic integrated effect and absorption effect.

Abstract:Type 2 diabetes is a systematic metabolic disease that involves complex interplay of multiple organs, of which adipose tissue and pancreatic islet are two key organs related to its pathogenesis. In this paper, models of fat 3D organ chip, islet 3D organ chip and their combination were established, which can be used to study the pathogenesis and to assess the mechanism of hypoglycemic agents for treatment of type 2 diabetes. A two-channel composite microfluidic chip was designed to study the effects of lipopolysaccharide (LPS) first on fat cells in one chip chamber and on islet cell in a seperate chip culture chamber. The chip channel was continuously perfused to simulate constantly changes in contents of the body fluid. The secretion of inflammatory factors such as adiponectin (ADP), interleukin-6 (IL-6) and interleukin-1β (IL-1β) from adipocytes and islet cells, the insulin secretion from islet cells, and islet cell survival rate in medium flashed with LPS or LPS/liraglutide were compared with those from cells flashed with the control medium. The results showed that LPS decreased ADP production from fat 3D organ chip, in islet 3D organ chip, and in fat/islet 3D double organ chip, LPS promoted IL-1β and IL-6 production from fat 3D organ chip and 3D fat/islet double organ chip, but not from islet 3D organ chip. Liraglutide could improve the production of ADP, and decreased IL-1β, IL-6 from fat 3D organ chip and fat/islet 3D double organ chip, but no effects on islet 3D organ chip. LPS and liraglutide separate or in combination had no effect on insulin production from islet 3D organ chip, but LPS decreased insulin production from fat/islet 3D double organ chip, liraglutide improved the decreased insulin production from fat/islet double organ chip due to LPS. The platform for the combined application of the fat organ and the islet organ based on the microfluidic chip can be applied to the multi-organ disease reaction caused by the interaction between different tissues and is expected to be a powerful tool for drug evaluation of systemic metabolic diseases such as type 2 diabetes.