Abstract:Circulating tumor cells (CTCs) are shed by primary or metastatic tumors, undergo the epithelial-mesenchymal transition, and enter into the peripheral blood of patients with metastatic cancers. Its critical roles in cancer research and clinical diagnostics are gradually being recognized. The presence of CTCs, especially the number in peripheral blood can not only be used for early diagnosis of cancer but also be used to assess prognosis, and monitor tumor metastasis and recurrence. Microfluidic chip as a high-throughput, miniaturized cell experimental platform has been used in CTCs sorting. In this review, we highlight recent progresses of CTCs capturing of microfluidic chip system and focus on the capture theory, chip structure and capture efficiency of various types of chips. At last, we prospect for the application foreground of microfluidic chip technology in CTCs isolation.

Abstract:Large conductance Ca²⁺ activated potassium channel (BK) is the only ion channel which is regulated by intracellular Ca²⁺ and membrane potential in the cell membrane. Recently the structure of BK determined by cryo-electron microscopy (cryo-EM) shed the first light on the assembly of the whole channel, as well as the crystal structure of the cytosolic domain by x-ray single crystal diffraction. In addition, these 3D structures corroborate many close interactions among these domains during channel gating. More recently, great advancements have been made in the research on functional regulation and gating kinetics simulation of BK channels, these contribute to understand the gating mechanism of the BK channel and the pathophysiological basis of BK-related ion channel diseases.

Abstract:Alzheimer's disease (AD) is the most common type of dementia, and has the highest incidence rate in neurodegenerative disorders. As the aged population robustly arises in China, the number of patients with AD is increasing accordingly. Studies show that decline in glucose metabolism occurs prior to amyloid deposits, and ketone bodies are the main alternative substrates for glucose in brain. Thus, the bioenergetic shift to ketone bodies is a characteristic of AD at early stage. At present, the mechanism of regulation of ketone bodies metabolism in AD pathogenesis is still unknown. In-depth understanding of ketone bodies metabolism involved in the occurrence and process of AD will lay a foundation in looking for new markers in early diagnosis and exploring prevention strategy of AD. Here we review AD-related ketone bodies metabolism and its research progress.

Abstract:Response inhibition of hand and eye-movement is to suppress the inappropriate response in hand and eye. Comparing with the classical paradigms such as Go/Nogo or Stop-signal, response inhibition of eye movement can provide more indices, and can separate from the confusion of verbal or hand movement. Response inhibition of hand and eye-movement differ in some neurological and psychiatric disorders, and the different developmental stages. Fronto-basal ganglia circuit play a similar role in eye and hand inhibition, but IFG is only key for hand response inhibition, and FEF and SC are only key for eye response inhibition. The arguments focused on the neural mechanisms, related higher cognitive activity, and the different performance and tendency in neuropsychology and developmental psychology.

Abstract:G protein coupled receptor 84(GPR84) is medium-chain fatty acid-sensing receptor(C9～C14). It plays an important role in metabolism of fatty acid and immune response, and it's also deeply involved in inflammatory immune diseases such as multiple sclerosis and endotoxemia. It may provide an effective method to treat these diseases by finding GPR84 ligands. It's important to construct a cell line stably expressing human GPR84 for screening its ligands and researching diseases. In this research, we transfected plasmids encoding GPR84 and Gα16 proteins into HEK293 cells. After selection with antibiotics, we picked out monoclones which stably expresses GPR84 to form cell lines. The permanent expression of exogenous GPR84 proteins in HEK293 cells was detected by RT-PCR, immunofluorescence staining, calcium mobilization and cAMP assay. Western blot and FACS were conducted to examine the activity of GPR84. Above all the results demonstrate that GPR84 receptor has excellent biology activity. Based on cell lines stably expressing GPR84, we conducted high-throughput assay for the screening of GPR84 ligands and found new GPR84 antagonists. We can further research on the biological functions of GPR84 and immune diseases targeted GPR84 with these antagonists.

Abstract:Using Tbx18 lineage tracer mouse model and Tbx18 conditional knockout mouse model to explore the functions of Tbx18 in the development of the structures of coronary vascular and ventricular wall. Two types of lineage tracer mouse models are established: Tbx18-Cre/Rosa26R-EYFP and Tbx18-Cre/Rosa26R-LacZ, and Tbx18:Cre/Cre gene knockout mouse model are used in the experiment. We trace the fate of Tbx18 in the formation of the vascular and myocardial structure in the cardiovascular system by immunofluorescence and X-gal staining techniques. And we compare the structure of coronary vascular and ventricular wall in Tbx18:Cre/Cre gene knockout mouse with wild-type mouse by whole-mount PECAM immunohistochemistry, HE staining, immunohistochemistry and immunofluorescence techniques. The trace of Tbx18 shows that Tbx18 contributes to the structure of the mouse coronary vessels and interventricular septum, and Tbx18 expression co-locolize with smooth muscle cells. The comparison between Tbx18:Cre/Cre gene knockout mouse and wild-type mouse shows that the knockout mouse can form normal coronary vascular system, and there is no difference between the thickness of the ventricular wall and the interventricular septum. The gene Tbx18 contributes to the heart vascular smooth muscle and interventricular septum, but it is not necessary in the formation of coronary vascular structure and the heart chamber structure.

Abstract:Glycosylation is one of the most common and important post-translational modifications of proteins. Identification of large-scale N-linked glycoprotein is a very important aspect in glycoproteomics research. The N-glycopeptide enrichment is a key step in high-throughput identification of N-glycosylation site. Lectin enrichment and hydrazide chemistry are the two widely used N-glycopeptides enrichment methods. Each method can only enrich certain types of glycopeptides. It has been reported that the two methods are highly complementary, but few studies compared overlaps of glycosties from the two methods. In this paper, using HepG2 cells, we systematically compared the performance of hydrazide chemistry and lectins enrichment methods. The results showed that although the hydrazide method with glycopeptides enrichment efficiency of 76.7%, far higher than the 54.6% lectin enrichment method, 825 glycoprotein and 1 879 N-glycosylation sites identified with the lectin method was significantly more than 522 glycoprotein and 1 014 glycosylation sites enriched by the hydrazide method. Moreover, the two methods did not show significant complementary, together, only 853 glycoproteins and 1 959 N-glycosylation sites were identified. The overlapping results of identified N-glycosylation sites and N-glycoproteins from the two methods show that lectins enrichment method was better than hydrazide chemistry method.

Abstract:Studies of the age-related positivity effect have demonstrated that older adults have a generalized preference to positive stimuli or avoidance to negative stimuli compared with younger adults. However, it remains unclear when and how this positive effect occurs in task-irrelevant affective processing in the aging brain. The present study investigated age-related emotional preference in one task-irrelevant affective stimuli processing by event-related brain potentials (ERPs) measurement with a specific focus on the time course of older adults' emotional processing and regulation. Younger and older adults completed a modified oddball task in which the deviant stimuli were affective faces. In the relatively early time window, the brain activities were not modulated by emotional valence in younger adults, yet the sad stimuli elicited a larger P3a than the happy and neutral ones in older adults. In the late time window, the sad stimuli elicited a larger positive slow wave than the happy stimuli in younger adults. Contrarily, at the later processing stage older adults' valence differences were eliminated. In general, we found time course differences in how older adults processed task-irrelevant affective stimuli compared with the young, and an age-related positivity effect occurred in the late time window, manifested as a negativity preference in younger and no preferences in older adults. These results provided evidence for supporting socioemotional selectivity theory from an ERP approach.

Abstract:Researches on the etiology and pathogenesis of prostate cancer are helpful for disease diagnosis and treatment. However, current biochemical experimental methods for prostate cancer are both costly and time-consuming, as well as networks based methods for this disease analysis limited by the nature of gene expression profiles for its incomplete, high noise and small sample size. Therefore, we proposed a dual constraint algorithm based on the confidence of one vertices belonging to the community and local modularity, named as NMCOM, to mine the candidate disease modules of prostate cancer in the present work. The NMCOM algorithm is gene expression independent method. It first integrated the concordance scores between the candidate genes and the causative phenotypes, as well as the semantic similarity scores between the candidate genes and the causative genes for prioritizing the candidate genes together, and then the starting node is selected with a sorting strategy. Finally, the candidate modules of prostate cancer are mined with dual constraint produces constructing on the confidence between node and module, as well as local modularity. 18 significant candidate disease gene modules were detected for the enrichment analysis of the obtained modules. Compared with the single scoring sorting methods and random walk with restart, the NMCOM fusion prioritizing strategy achieved a smaller MRR (Mean Rank Ratio) but bigger AUC value. The results are significantly better than other modules-based mining algorithms, and the biological explanations for these mined modules are more significant. More importantly, the NMCOM algorithm can be easily extended to mine any other diseases candidate modules.

Abstract:An Insight of D-Ribose Metabolic Imbalance in Type 2 Diabetes Mellitus