Abstract:Microcirculation dysfunction is regarded as one of important pathologies of senility, degeneration, immune disorder and many other diseases. Cerebral circulation insufficiency, energetic dysmetabolism, hypoxia-ischemia and metabolites accumulation in Alzheimer's disease (AD) have a close relation with microcirculation dysfunction. Here, we review microcirculation dysfunction playing an important role in hyperphosphorylation of Tau, Aβ aggregation and cognitive impairment induced by accumulation of formaldehyde and D-ribose.

Abstract:Proteasome is responsible for degradation of majority of the intracellular proteome and it could regulate almost all of the fundamental biological processes. Dysfunction of the proteolytic activity of the proteasome is associated with lots of diseases. Recently, several research groups have made important progress in clarifying high-resolution structure and regulating mechanisms of the proteasome. In this review, we focus on the structure of the proteasome and the mechanisms that regulate activity of the proteasome including transcriptional regulation, post-translational modification and assembly of subunits. These new findings in proteasome study will shed new light on development of new drugs for treatment of diseases related to dysfunction of the proteasome. An introduction of available proteasome inhibitors is also included in the present review.

Abstract:Plasmin (PLM), via activation from plasminogen (PLG), not only exerts fibrinolysis and thrombolysis effects, but also involves in extensive physical processes such as embryonic development, tissue remodeling and wound healing. Moreover, recent studies showed a tough association between PLM with inflammation, autoimmunity, malignancy and neural degeneration. Furthermore, more than ten plasminogen receptors and binding proteins have been discovered on cellular surface. Here, we review the researching progresses on the structures, signal transduction and pathogenic mechanisms of these receptors and binding proteins, so as to provide clues for better understanding on fibrinolysis system and for developing new diagnostic and therapeutic pathways.

Abstract:Deficits in communication are one of the main symptoms for individuals with autism, and studying their mode of moral reasoning might help us explain this phenomenon. Previous research has shown differences in moral reasoning between individuals with autism and normal individuals. For example, people with autism could distinguish moral violation from conventional violation, but they often judged those actors who hurt others without intention deliberately. On the other hand, they were not sensitive to the victim's emotional cues and could not understand what others felt. Such studies suggest that the ability to mind-read and to show empathy with others might be some of the key psychological mechanisms required to complete moral reasoning tasks. Furthermore, other research suggests that there is a relationship between the moral reasoning and language development of individuals with autism. People with autism often explain their moral reasoning by repeating story details and declaring concrete outcomes, but their explanations lack descriptions of abstract moral rules. Brain imaging studies show that there are significant differences between people with autism and typically-developing individuals in the activation in the orbito-frontal cortex (OFC) , amygdala, insula, inferior frontal gyrus(IFG), anterior cingulate cortex(ACC), medial prefrontal cortex(mPFC), default-mode network(DMN) and right temporo-parietal junction(RTPJ) in moral reasoning. These locations are also vital brain regions for theory of mind or empathy. Further studies have shown that when completing sentence processing tasks, people with autism also showed different activation in the verbal functional association areas by contrast with normal individuals, and this might be the internal basis for their explanation mode of moral reasoning. Future research should consider the interaction of the influence of theory of mind, empathy and verbal ability in moral reasoning for individuals with autism, and adopt more non-verbal methods. In addition, future studies could incorporate brain damage technology and hormone level analysis to examine the physiological mechanism of moral reasoning for people with autism comprehensively.

Abstract:NLRP10 is a special member of NOD-like receptors (NLRs) family that lacks the leucine-rich repeats, suggesting that NLRP10 may act as an immunity regulator rather than directly receptor recognizing intracellular pathogen products. Previous studies on NLRP10 show that NLRP10 can interact with several components of NOD1 pathway thereby enhancing NOD1-mediated innate immune responses. In particular models, NLRP10 also negatively affects the activation of NLRP3 inflammasome. It has been proposed that NLRP10 oligomers interact with ASC to form a multi-protein platform for the recruitment of caspase-1 or other signaling components. Here, we show that pyrin-like domain (PYD) degradation induce the formation of NLRP10 oligomers, which present stick-shaped and circular structure. With the NLRP10 mutant G173A made by means of site-directed mutagenesis, we successfully obtain homogeneous full-length NLRP10 preparations. Corresponding gel filtration analysis and electron microscope (EM) data further proved that the PYD domain is important in protecting NLRP10 against aggregation.

Abstract:Human papillomavirus E7 gene is the key to cancer, which expressed in most HPV-contains cervical cancers. E7 plays an important role in the induction and maintenance of cellular transformation, and it was regarded as the ideal target in cervical cancer treatment. An important development direction of cervical cancer therapy is based on HPV16 E7 antigen CTL epitope peptide vaccine design, but Short half-life in vivo and poor stimulation effect are the major therapeutic obstacles for native CTL epitope peptide. In this study, three epitope peptides were screened by molecular dynamics simulations with MM-PBSA method, associated with previous research results and polypeptide enzymolysis experiment. These predicted peptides were synthesized, examining the affinity between HLA-A2 molecule and each peptide by T2 cell line. The result showed synthesized peptides had a great improvement on enzyme-resistant ability comparing with natural HPV16 E7 CTL epitope antigen peptide, and (d)RAHYNIVTF was the most obvious epitope peptide. Meanwhile, the affinity was improved between (d)RAHYNIVTF and HLA-A2 (fluorescence indexes was 2.06). The method of structural modification in this study is expected to lay the foundation for cervical cancer therapeutic vaccine design.

Abstract:After optimizing the conditions of surface modification, sieving matrix, electric field strength of separation, injection mode, electrophoresis temperature, injection time and so on, forensic DNA samples included 15 STR loci can be separated on Brofloat glass electrophoresis chip, using electrophoresis apparatus equipped with confocal laser induced fluorescence detection system. The optimized electrophoresis system conditions were obtained and DNA samples were successfully separated within 8min. The microchip electrophoresis system has good prospects in the rapidly forensic DNA analysis.

Abstract:In this study, a novel protein submitochondia locations dataset was constructed which contained 1 293 proteins classified into four kinds of submitochondria locations. The GO information and homologous information was extracted to combine the feature vectors of proteins and the Supported Vector Machine algorithm was used to construct the classifier. As a result, by using the Jackknife Cross-Validation, an accuracy of 93.27% for four kinds of protein submitochondria locations and that of 94.73% for three kinds of protein submitochondria locations was obtained. Especially, the predictive accuracy for outer membrane of protein submitochondia locations was enhanced than previous methods. The data set of protein submitochondia locations constructed by ours has the intermembrane proteins compared to old ones. The intermembrane proteins have important functions in protein apoptosis. The integrity of data set and the improvement of prediction accuracy can help to understand the cell activity and internal biochemical process.

Abstract:The bladder cancer, which is a kind of a malignant tumor in the bladder mucosa, is the most common malignancy tumor in the urinary system. Diagnosis at an early (nonmuscle-invasive) stage is the best way to reduce the mortality rate. Tumor malignancy is closely associated with alterations of glycan expression, but glycosylation status in bladder cancer has not been well studied. Four bladder cancer cell lines (KK47, YTS1, J82, T24) and two normal bladder mucosa cell line (HCV29, HUCV1) were used in our study. We developed a kind of labeling method to derivatize the sialic acid and derivatized the reducing terminal using [¹²C₆]- or [¹³C₆]-aniline, and the derivatized glycans were quantitatively analyzed by Matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF/TOF MS). Finally, 52 N-glycans of the bladder cancer were identified. And the sialic acid as well as the fucosylated in the bladder cancer were found significantly over-expressed. At the same time, the bisecting and high-mannose glycan were also high-expressed in the bladder cancer cells. This study provides some referential significance for the future study on the glycomics of bladder cancer.

Abstract:Long non-coding RNA AFAP1-AS1 promotes cancer invasion and metastasis