Abstract:Alzheimer"s disease (AD) is the most common neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques and the formation of hyperphosphorylated tau-containing neurofibrillary tangles. Unfortunately, the current clinical drugs for the treatment of AD can only temporarily improve cognition, and cannot prevent and/ or reverse the pathological process. More and more studies have confirmed that long-term moderate aerobic exercise, as a healthy and feasible form of exercise, can eliminate Aβ deposition and reduce hyperphosphorylated Tau protein as well as alleviate AD symptoms of neural plasticity, inflammatory response, oxidative stress and energy metabolism. Therefore, aerobic exercise is considered as an effective strategy to prevent or delay AD. This article elucidates the pathological mechanism of aerobic exercise ameliorates AD and in the hope of providing a new strategy to prevent and treat AD.

Abstract:In recent years, the abuse of antibiotics has caused the emergence of drug-resistant bacteria, which is now widely spread around the world. It is currently a critical issue that seriously threats to human health due to the lack of effective clinical drugs to treat the multidrug-resistant bacterial infections. With such a serious shortage of drugs and means for clinical treatment against multidrug-resistant bacterial infections, it is urgently needed to develop new antibacterial drugs, especially those molecules possessing new mechanisms of action to combat the drug-resistant bacteria. Filamenting temperature-sensitive mutant Z（FtsZ）is an essential protein for bacterial division and has been one of the most popular targets for new drug discovery. FtsZ is a highly conserved protein and it plays a key role in cell division in most prokaryotic cells. In this article, we reviewed the structural characteristics and biological functions of bacterial cell division proteins and the recent research progress on antibacterial drugs development targeting FtsZ.

Abstract:Lipoproteins are a kind of cell membrane anchoring proteins widely found in Gram-negative bacteria and Gram-positive bacteria, which possess many biological functions. Lipoproteins are not only as virulence factors, but also can recognize and elicit the host's immune system, which becomes one of the most popular research targets for the prevention and treatment of bacterial infection. This paper reviews the research progress of lipoprotein functions, and their application as vaccine candidates or drug targets in Streptococci. The prospect and suggestion are provided for the future research on Streptococci lipoprotein, which will expand research ideas for lipoprotein in Streptococci.

Abstract:In this paper, 38 ancestry informative insertion-deletion (InDel) polymorphism markers, with allele frequency differences between three major continental population groups (East Asian, European, and African) were selected from the related literatures and dbSNP database. The Amelogenin locus and a Y chromosomal STR (DYS439) locus were integrated to aid in the sex determination of an unknown sample. All markers were designed and amplified in a single-tube direct amplification assay based on the PCR-CE technology for inferring ancestry of three continental populations. This assay was integrated with a microfluidic system for automatic amplification and InDel genotyping using DNA samples in 1.7 hours. The genotypes of 1607 individuals obtained from the 1000 Genomes Phase III panel were used to assess the differentiation capacity of this 38-plex InDels assay. Then, this assay was validated by sensitivity, genotyping accuracy, and direct PCR ability. 779 samples from 5 populations and 215 direct amplification from saliva and blood samples were genotyped by this assay, then using the structure cluster analysis and principal component analysis to infer ancestral origins and evaluate the accuracy of the system. The results indicate that the 38-plex InDels assay can provide an accurate genotyping, with a sensitivity of 157 pg, and enable the direct amplification of DNA from saliva and blood on filter paper without sample purification. In addition, this assay is sufficient to distinguish between three continental populations and the admixture of Eurasian populations and also, accurately infer the ancestry origins of testing DNA samples. The integration of cell lysis into the microfluidic system is possible to yield ‘sample-in-profile-out’ results of InDel genotyping in 2 hours.

Abstract:The risk of post-operative paralysis is high in patients with eloquent area gliomas and without apparent limb motor dysfunction preoperatively. This study aims to evaluate the risk of postoperative paralysis via task-based and resting state fMRI. 24 patients with eloquent area gliomas who had no obvious limb dysfunction and 8 patients with non-eloquent area gliomas were admitted. All patients underwent task-based and resting state fMRI. Lateralization index (LI) of M1 activation was calculated. The regions-of-interest (ROIs) within motor network were selected. Functional connectivity (FC) between bilateral M1 and other ROIs were calculated. Occurrences of postoperative paralysis were recorded three months after operations. Receiver operating characteristic (ROC) analysis was performed to determine the optimum LI thresholds for prediction of paralysis. Compared with non-eloquent gliomas group, LI of M1 increased significantly (P=0.001) in eloquent gliomas group. Compared with patients without paralysis, LI of M1 in patients with paralysis increased significantly (P=0.011). ROC analysis showed the area under the curve (AUC) was 0.867. The best cut-off value for LI in the prediction of postoperative paralysis is 0.31 with sensitivity of 87.5%, specificity of 87.5%. Patients were then divided into groups of high and low risk of operation by LI ≥ 0.31. In patients with high-risk of operation, the tumors caused more damages to FC than in patients with low-risk of operation. Task-based and resting state fMRI can be combined together to better evaluate the risk of surgery and to clarify the mechanism of functional damage and its compensation.

Abstract:Multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains are spreading globally, and thus, new antituberculosis drugs are urgently needed. The M. tuberculosis L,D-transpeptidase LdtMt2 is directly involved in peptidoglycan formation, bacterial virulence and β-lactam resistance. This enzyme is a potential antituberculosis target that can be inhibited by carbapenems, FDA-approved drugs that are used in the treatment of tuberculosis. Two different intermediate states, states I and II, have been reported for LdtMt2 interacting with carbapenems, such as ertapenem, imipenem and meropenem. State I was proposed as an initial adduct formation state, whereas state II was proposed as a stable protein-ligand interaction state accompanied by local conformational arrangements of both carbapenem and the protein. Here, we report a new LdMt2-ertapenem interaction state, I-plus, with the same carbapenem conformation as state II and a similar local protein conformation to state I. This new state was proposed as an intermediate state for the transition from state I to state II, in which the ertapenem molecule, but not the protein, undergoes a conformational change. Our work helps elucidate the changes that occur after carbapenem acts on LdtMt2 and, together with the other reported state, demonstrates how the L,D-transpeptidase interacts with carbapenems.

Abstract:Steady state visual evoked potential (SSVEP) is widely used in the study of brain perception and cognition. At present, the mechanism of SSVEP subharmonic is ambiguous. The induced factors and power variation of the SSVEP subharmonics is studied by a visual cortex network model in this paper. Further, the SSVEP of 20 subjects’ head surface is tested to verify the simulation results. The simulation and experimental results show that the stimulus frequency, stimulus intensity and noise intensity are three important parameters that affect the 1/2 subharmonic induction and power change of SSVEP. Subharmonic is induced by the synergistic action of three parameters: (1) when the stimulus frequency and noise intensity are same, the curve of 1/2 subharmonic power with stimulus intensity is similar to sigma function, and there are non-induction region, linear growth region and saturation region: in non-induction region, 1/2 subharmonic power is approximately 0; in linear growth region, 1/2 subharmonic power is proportional to stimulus intensity; in saturation region, 1/2 subharmonic power is proportional to stimulus intensity; when the noise intensity is same, the stimulus parameters area that can induce the 1/2 subharmonic obviously is similar with arnold tongue in nonlinear synchronization, that is, the effective stimulus frequency range widen with the increase of stimulus intensity; (3) when the stimulus parameter is same, the noise intensity determines the 1/2 subharmonic energy ; the higher the noise intensity is, the stronger restraining effect of inducing 1/2 subharmonic and power is. The experiment and simulation results in this paper are basically consistent, which shows the feasibility of model simulation. The research results provide theoretical and experimental basis for understanding the generation mechanism and effective application of SSVEP subharmonics.