Abstract:Membrane proteins (MPs) play a crucial role in the life activities of humans and other species, which account for about 30% in all sequenced genomes. Drug targeting sites, cell-to-cell signaling, and detection of the environment mainly depends on specific membrane receptor proteins. MPs have significant theoretical and practical value in industrial, environmental, national defense and other research areas. Olfactory receptor (OR) protein is one kind of typical MPs, belonging to G protein-coupled receptor (GPCR) family. ORs regulate the organism to hunt for food, escape from risks and search for spouses. ORs are mainly distributed in the vertebrate nasal cavity or insect antennae. A series of reactions will be stimulated when the odorants bind with osmoceptors. The stimulus signal will be converted into an electrical signal. Eventually pass to the nervous system and to make the appropriate instructions. It is tough to extract MPs directly from tissues. Heterologous expression of MPs makes it difficult to integrate proteins into membranes, which brings great challenges to the study of structure and function. Cell-free protein synthesis system(CFPS) is an efficient strategy to express proteins in vitro on account of the open system and independence of cell lives. CFPS puts forward new ideas for synthesis and assemblage of MPs. It will be a major breakthrough for the study of structures and functions of MPs when the self-assembly and dimer formation can be accomplished in vitro. Here, we summarize latest progress in using CFPS to express ORs and other MPs.

Abstract:The neural network of our brain processes all kinds of information through excitatory and inhibitory synapses. Although there are less inhibitory neurons in the brain, they are extremely important in regulating information processing and neuronal plasticity. Further more, various of brain dysfunctions are related to the disfunction of inhibitory system. Inter-cortical inhibition, which includes feedforward and feedback projections, mediates the inhibitory effects between different brain areas. Intra-cortical inhibition, or mutual inhibition, mediates inhibitory interactions between neurons nearby but with different preferences. In this review, we introduced the behavioral performance of two kinds of inbitiory mechanisms, using center-surround suppression and motion repulsion paradigm as examples. Then we related the changes of cortical inhibition to aging and two typical mental disorders.

Abstract:Humans’ perception of time has been observed to be distorted by emotions．Subjective distortion of time is typically modulated through experienced emotions and anticipated emotions．In this review, we distinguished the effects of experienced emotions and anticipated emotions on timing from the perspective of the ways that emotions take effect and cognitive mechanisms. According to the scalar expectancy theory, we proposed a new cognitive model to explain how emotions modulate the time perception in different time processing stages．Finally, we summarized the evidence of neurophysiology basis and brain mechanisms about emotional modulation of interval timing．Future researches are advised to further investigate and extend our understanding on the roles of anticipated emotions in driving emotion-induced temporal distortions, to find out the interactions of attention, arousal and valence, and to explore the neuropsychological mechanisms of emotional temporal distortions.

Abstract:Neural control technology (NCT) could activate the function of the nervous system, alleviate neurological disease and improve the quality of life by importing electrical, magnetic, optical, acoustic and other physical factors to the neural circuits. The technology has been widely used in the research of life science and clinical diagnosis and treatment. Especially, low intensity focused ultrasound (LIFU) has the advantages of nondestructive, high penetration ability and spatial resolution, which is more suitable for the neural regulation as a safety physical stimulating factor. At the moment, research of LIFU in neural control has attracted much attention of scientific community. A large number of animal and human researches in neural control have been carried out and achieved gratifying results. In this paper, we review the progress of the LIFU regulation in central nervous system in the animals and human. Besides, the biophysical mechanism, security issues and future applications are also discussed. We hope this paper will provide a new insight to the research and application of neural regulation of LIFU.

Abstract:Deep brain stimulation (DBS) has shown great potential for treating various neurological disorders in clinic. However, the mechanisms of DBS are not clear yet. Regular DBS uses high frequency stimulation (HFS) of pulse sequences. The narrow pulses facilitate the activation of axon fibers most readily among all elements of a neuronal structure. Through the projection of axons, the effects of HFS can spread to downstream neurons. Therefore, to explore the mechanisms of DBS, we investigated the effects of axonal HFS on the downstream neurons in hippocampus, as it has been an important target for treating diseases such as epilepsy and dementia. One-minute HFS at 100 Hz was applied to the afferent fibers of hippocampal CA1 region (i.e., the Schaffer collaterals) in anesthetized rats. Single unit spikes of pyramidal cells and interneurons in the downstream CA1 region were recorded and analyzed. Firing rates of spikes, phase-locking values (PLV) between spikes and stimulation pulses, as well as spike latencies were calculated to quantify the changes of neuronal action potential firing during the HFS periods. Results showed that during the initial period of HFS, synchronized action potentials (i.e., population spikes, PS) generated in the population of neurons. During the late period of HFS (after the disappearance of PS events), both types of neurons continued to fire unit spikes with stable rates. However, the phase-locking relationship between spikes and stimulation pulses decreased gradually, while the latencies of spikes increased gradually. In addition, compared to interneurons, the unit spikes of pyramidal cells had smaller phase-locking values and longer latencies. These results indicate that prolonged axonal HFS can generate asynchronous activity in the downstream neurons. Partial block in axon conduction induced by high-frequency pulse stimulation might be one major cause underlying the phenomena. The present study provides important information for revealing the mechanisms of DBS.

Abstract:Protein tyrosine phosphatase 1B (PTP1B) is one of the targets of type Ⅱ diabetes, screening PTP1B inhibitors is of great significance. Structure-based virtual screening against a library of natural products containing 42 296 molecules was conducted to determine the occurrence of PTP1B inhibitors by molecular docking method. Firstly, the active sites of PTP1B complex crystal structure (PDB code: 1XBO) were analyzed and 7 amino acid residues, Arg254，Gln262，Tyr46，Asp181，Ser216，Phe182，and Arg221, were identified as the active pocket. Before docking, all the molecules were filtered according to the Lipinski’s Rule of Five. Then, the screening was carried out based on the LibDock module and CDOCKER module, and 11 top-scored compounds were screened out as virtual hits. Of which 3 molecules, namely para-benzoquinone compound 7, isocoumarins derivative 10 and Clavepictine analogue 11, were determined with low toxicity ultimately according to the predictive ADME simulation and predictive toxic simulation. Binding model analysis revealed that these 3 candidate compounds are all good drug-like PTP1B inhibitors, of which the PTP1B inhibitory activity of compound 10 and 11 haven’t been reported before, of which in vitro PTP1B enzyme inhibition of compound 10 was tested with IC₅₀ values of (74.58±1.23) μmol/L, which is potential for the treatment of type Ⅱ diabete.

Abstract:The identification of DNA-binding proteins (DBPs) plays an important role in functional annotation of genes and proteins of prokaryote and eukaryote organisms. This study, for the first time, combined the gapped-dipeptide composition (GapDPC) and recursive feature elimination (RFE) to identify DBPs. The position specific scoring matrix (PSSM) of each tested amino acid sequence was obtained. Based on the PSSM, their GapDPC features of the amino acid sequences were extracted, and then the optimal features were selected using the RFE method. Subsequently, the support vector machine (SVM) was chosen as a classifier and the datasets PDB396 and LB1068 were tested using the jackknife cross validation test. The result showed that the values of accuracy, Matthews correlation coefficient, sensitivity, and specificity for the identification of DBPs were 93.43%, 0.86, 89.04% and 96%, and 86.33%, 0.73, 86.49% and 86.18% for the datasets PDB396 and LB1068, respectively, which were obviously superior to the methods reported previously in the literature. The new model established in this study improved the identification methods of DBPs.

Abstract:Despite progresses achieved in the therapy of tumors, the prognosis of patients is still limited by reccurence of residual tumor cells. Cancer cell dormancy plays a pivotal role in cancer relapse and drug resistance. In recent years, tumor cells undergoing EMT(epithelial-mesenchymal transition), CSCs(cancer stem cells) and CTCs(circulating tumor cells) are proved to share some common characteristics and show a cell cycle arrest phenotype. Thus, understanding the dormant stage of tumor cells could facilitate us in discovering ways to accelerate the development of tumor therapy and prevent its reccurence. In this review, we summarize the specific process of tumor cell dormancy induced by pharmacotherapy, and consider that dormancy is an initiative response rather than a passive defense to cytotoxicity. Besides, we probe into the mechanisms of tumor cell dormancy-mediated drug resistance, anticipating paving a way to target dormant tumor cells and result in better clinical outcomes.

Abstract:Human NAP1L5 is a member of the nucleosome assembly protein (NAP-1) family, until now its function has been completely unknown. In liver cancer, Nap1l5 was suggested as a tumor suppressor gene, and might inhibit cell proliferation. However, it’s reported that many NAP-1 family members promote cell cycle progression. Whether human NAP1L5 promotes or inhibits cell proliferation has been undetermined yet. Here, we found that the proliferation of 293T cells was promoted by Nap1l5 overexpression, and inhibited by knockdown of its expression. Cell cycle analysis showed that compared with control groups, Nap1l5-overexpressed cells had higher percentage of cells in G2-phase, and lower percentage in G1-phase; instead, knockdown of Nap1l5 expression increased the percentage of cells in G1-phase, and decreased the percentage in G2-phase. Our study demonstrated that human NAP1L5 could promote cell proliferation as well as accelerate cell cycle progression, and suggested that the original postulation of Nap1l5 as a tumor suppressor gene was incorrect.