Abstract:The axon is a unique feature of the neurons, and its length can reach hundreds and sometimes thousands times of the diameter of the cell body. To maintain normal functions, a large amount of materials need to be transported from the soma to the axon terminals or from the axon terminals to the soma. Damage of axon transport leads to disruption of neuronal functions and eventually results in cell death. Impairment of axon transport is among the earliest symptoms of some optic neuropathies, and is therefore likely the potential target of intervention. In the animal models of glaucoma and retinal ischemia, decline in axon transport is one of the earliest signs. Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are known diseases caused by mitochondrial dysfunction. Conceivably, long distance axon transport is especially sensitive to energy metabolism and is likely affected at certain degree in the LHON and ADOA, but has not been paid enough attention. In this review, we compared the pathogenesis, clinical symptoms and therapies of the above optic neuropathies, attempt to highlight the common aspects and to reveal the relationship among optic neuropathies, energy metabolism and axon transport in order to provide new clues for the therapy.

Abstract:Alzheimer’s disease (AD) is a neurodegenerative disorders characterized by impaired memory and cognitive functions. The pathogenesis of AD is very complicated, it is extensively documented that the accumulation of β-amyloid peptide (Aβ) is a vital contributing factor in the pathology of AD. Aβ can be divided into different forms of species, such as monomer, oligomer, and fibril. Increasing evidence suggests that oligomeric Aβ, may be the main mediators which contribute to the cognitive deficits and neurodegeneration in AD. The oligomeric Aβ has different aggregation configuration, which play different roles in the process of AD. This review mainly illustrates the role and underlying mechanisms of differently aggregated components of oligomeric Aβ in the progress of AD.

Abstract:Biomolecular recognition events involving carbohydrate-protein interactions are ubiquitous in biological system and central to numerous fundamental biological phenomena, the intrinsic nature of which is multiple noncovalent weak interactions worked cooperatively. CH-π interaction occurring between CH group in carbohydrate and aromatic amino acid residue in protein is one of the most important weak interactions and plays a significant role, which has been intensively investigated over the past three decades. The fundamental understanding of CH-π interaction from several aspects of physical origin, structural features and energetic contribution have been obtained with the advance of modern analytic techniques. Therefore, comprehensive understanding on CH-π interaction paves the way to explore the application prospects in the field of recognition, detection, drug development and tissue engineering materials, which represents a challenging but also a promising research direction. In this review, we briefly summarize several characteristics of CH-π interaction based on the investigations of researchers over the years. Then, the potential application explorations based on CH-π interaction are introduced from three aspects: inhibiting effect on amyloid aggregation, artificial carbohydrate receptors, and transformation of macroscopic properties. Finally, the research prospects are briefly presented.

Abstract:Revealing the pathogenesis of arrhythmia is a key task involved in diagnosis, treatment, drug development and equipment design. Multi-scale and multi-mode models of cardiac electrophysiology from ion channel, cell, fiber, tissue, heart to torso-heart integrated various physiological and pathological data from molecular biology, biochemistry, physiology and anatomy of the heart, changed research methods based on gene mutation, protein expression, cell electrophysiology and clinical symptoms completely and created a systematic approach for studying development and transformation of arrhythmias from microscopic changes to macroscopic pathology. The most important is that the cardiac electrophysiological model, which is a powerful tool for studying the mechanisms of arrhythmia, becomes the unified method of micro and macro research. In this paper, we summarized the method of constructing cardiac electrophysiological models, discussed the role and status of the multi-scale cardiac electrophysiological model in the study of cardiac arrhythmia mechanism, and outlined important research prospects and challenges of the electrophysiological modeling and simulation of arrhythmia in the future.

Abstract:Alzheimer's disease (AD) is currently an incurable neurodegenerative disease, which is the most common cause of dementia worldwide. AD is also a progressive disorder, pathologically characterized by extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated and the density of tau tangles correlates well with regional and global aspects of AD-associated cognitive dysfunction. Furthermore, the established toxic role of tau in certain genetic forms of frontotemporal dementia strongly suggests that tau aggregation may result in a toxic gain-of-function leading to the AD-associated neurodegeneration. Thus, there is a growing interest in discovering novel compounds that will help in reducing the deleterious accumulation of tau protein tangles in the AD brain. Stem cells treatment open a gate to this which many drugs show hard to control the disease progression or enhance the patients' consideration function. hUC-MSCs (mesenchymal stem cells isolated from human Wharton's jelly of unbilical cord), emphasized by its powerful paracrine, great function of multi-directional differentiation and east to isolate, have been confirmed effective to many nervous system disease including AD. But the treatment mechanism was still unknown. Along with the studies of secreted factors by hUC-MSCs, the paracrine function of the adult stem cells attracted us to answer this treatment mechanism from those star factors. Here, we set up the AD model in vitro by okadaic acid (OA), and demonstrate that IL-6 maybe the key protein to effect the recovery function of hUC-MSCs to protect the injured cells.

Abstract:The hypoxia/reoxygenation injury model was established in rat cardiomyocytes to investigate the influence of microRNA-21 on apoptosis and autophagy in rat cardiomyocytes exposed to hypoxia/reoxygenation injury. According to RT-PCR, miR-21 was up-regulated(P < 0.05) in myocardial cells after hypoxia/reoxygenation injury. Moreover, myocardial apoptosis was aggravated according to flow cytometry. According to RT-PCR and Western blot, p62 was down-regulated whereas beclin-1 was up-regulated in cardiomyocytes (P < 0.05) after hypoxia/reoxygenation injury. These consequences inditicated that hypoxia reoxygenation induced abnormal myocardial apoptosis and autophagy. miR-21 mimic or inhibitor were transfected into cardiomyocytes via liposome. MiR-21 mimic transfection significantly enhanced myocardial apoptosis (P < 0.05), up-regulated expression of p62, and down-regulated of expression of beclin-1in myocardial cells in rat cardiomyocytes(P < 0.05), while miR-21 inhibitor transfection caused opposite effects. These data suggested that miR-21 in rat cardiomyocytes exposed to myocardial hypoxia reoxygenation injury can accelerate cell apoptosis and inhibit cell autophagy. Bioinformatics projections shown that Rab11a 3'-UTR contains a binding site for miR-21. Dual luciferase report gene assay system, coupled with the overexpression of Rab11a assay validated that Rab11a is one of miR-21 target genes. Overexpression of Rab11a significantly attenuated myocardial apoptosis，up-regulation of p62 and down-regulation of beclin-1 induced by miR-21in hypoxia/reoxygenation injury. In conclusion, miR-21 can promote myocardial apoptosis and inhibit myocardial autophagy by negative regulating Rab11a in rat cardiomyocytes exposed to hypoxia/reoxygenation injury.This research proposes a new strategy for the prevention and treatment of myocardial ischemia-reperfusion injury.

Abstract:Primate visual system is extremely efficient in extracting stable invariants from environment, despite various transformation and degradation. The timing and dynamics of invariants perception provide important constraints for theories of vision. We developed a high speed LED backlight tachistoscope capable to deliver visual stimuli with 1 ms exposure and adjust the duration in submillisecond precision, which enabled us to investigate the relative speed of processing topological, projective, affine, and Euclidean invariants in configural superiority effect paradigm by manipulating the access time to visual input and estimating the psychometric function for sensory evidence accumulation. The results suggest that topological invariant requires shortest exposure time, consistent with the prediction of global-first theory.

Abstract:Autofocusing is a fundamental step towards automated microscopic screening of Caenorhabditis elegans. Determining the optimal focus in an optical microscope is based on a clarity-evaluation function that is applied to images acquired from different focuses of the same field. The maximum value of the function is considered as the point of optimal focus. In this paper, 16 autofocus algorithms which were collected from well-known algorithms as well as the most recently proposed focusing algorithms have been evaluated. Through these evaluations, an optimal algorithm was found for C. elegants lipid droplets to set up an automatic screening system. Many features were assessed in this paper, for instance accuracy, computational time, addition of noise, and focusing curve. Our results have shown that most of the algorithms show an overall high performance for this type of image, and absolute Tenengrad algorithm will be our first choice for its best performance considering accuracy.

Abstract:The identification of risk pathogenic genes for lung cancer is helpful to understand disease pathogenesis and improve clinical practice. However, the present predicting methods of using RWR framework include the common problems of the less initial nodes, the same node transition probability, and the single information source. To further improve the performance of RWR framework, we propose a novel method named AFMFSC to identify disease-related genes, by enlarging the initial nodes and weighted fusion strategy, and use lung cancer as the test object. The AFMFSC algorithm first computes the augmented functional similarity scores between disease phenotype approximate genes based on the idea of augmenting fuzzy measure similarity, screens important genes as the expanded initial nodes together with pathogenic genes, then walks in the global PPI network separately guided by the node similarity transition matrix constructed with PPI network topological similarity properties and the correlational transition matrix constructed with the gene expression profiles, all the genes in the network are ranked by weighted fusing the above results guided by two types of transition matrices, at last the top ranked genes in the enrichment analysis as final risk pathogenic genes are determined. 73 significant genes are predicted to be the risk pathogenic genes for lung cancer, which are closely linked with the generation and development of this disease. Compared with the existing methods for prioritizing potential risk disease genes, the AFMFSC achieves a smaller average rank and less affect by degree distribution bias but bigger Top 1%，Top 5% and AUC value. In addition, the ranking performance of fusion strategy outperforms a single transfer matrix or ordinary adjacency matrix. The AFMFSC algorithm not only can accurately and effectively predict the risk pathogenic genes of lung cancer, but also can be easily extended to identify any other diseases related genes, and provide additional insights for exploring the pathogenesis of cancer.

Abstract:Patch-clamp fluorometry is a powerful biophysical method that allows the researcher to monitor conformational changes of ion channel in real time, and to correlate dynamic structural information to functional states. As a natural combination of the classic patch-clamping method and state-of-art optical methods, patch-clamp fluorometry is applicable to a wide spectrum of channel studies with unprecedent spatial-temporal resolutions. Unlike other structure-oriented methods such as X-ray crystallography and cryo-EM, patch-clamp fluorometry provides dynamic structural information of channel proteins in intact cell membrane under physiological conditions.