Abstract:The development of broad-spectrum antiviral agents has recently become a major thrust area in the field of virology, and received enormous attention in the pharmaceutical industry worldwide. Much progress has been made to substantially extend the limitations of current antiviral therapy drugs, which are mostly pathogen-specific. Breakthroughs were made in establishing fundamental understanding of the underlying biochemical mechanisms. Part of the research results have been implemented for practical applications. The present review addresses the state-of-the-art knowledge, prospective applications, and challenges for the development of broad-spectrum antiviral agents. Detailed models of agent targets to virus entry and infection, and host cell defense are given. Finally, future research needs and opportunities are discussed.

Abstract:Altruistic punishment is very common in human life, which is an effective mechanism enforcing group cooperation and social norm. From perceiving the transgressions to administering costly punishment, potential punishing requires a series of cognitive and affective processes, including fairness judgment, reward processing, self-control, mentalizing, etc., and their underlying neurophysiological mechanisms. Cognitive neuroscience provides alternative perspective and paradigm for understanding human punishment behavior. Based on the latest findings, the neurophysiological mechanisms of altruistic punishment are reviewed and discussed in this article.

Abstract:As one of the epigenetic regulation mechanisms, ATP-dependent chromatin remodeling participates in various critical biological processes, including stem cell maintenance and differentiation, individual development, and other physiological and pathological processes in higher plants and animals. Recently, studies on chromatin remodeling have become one of hot fields in epigenetics. In this review, based on the recent progresses in the field of chromatin remodeling in higher plants and animals, we summarized the mechanisms of chromatin remodeling, and analyzed the diversity of the compositions and biological functions of chromatin remodeling complexes in higher plants and animals. Significantly, the function of SWI/SNF chromatin remodeling complexes in plant development under normal and environmental stress was emphatically summarized. This review will be helpful to understand the molecular mechanisms of the chromatin remodeling in plants.

Abstract:Cholesterol efflux is indispensable for maintaining the structure and function of cells, while it's function in regulating angiogenesis is not clear still. Recently an issue published on Nature(2013,498:118-122) by researchers from Department of Medicine, University of California, USA found that apoA-Ⅰ binding protein (AIBP) can mediate cholesterol efflux and plays a key role in the control of angiogenesis. Based on the ex vivo aortic ring of mice and zebrafish, the researchers have found that AIBP together with HDL can facilitate cholesterol efflux so as to inhibit angiogenesis induced by vascular endothelial growth factor(VEGF).

Abstract:In 1815, the French chemist Michel Eug?ne Chevreul (1786-1889) discovered that the sweetness in the urine of diabetics comes from grape sugar or D-glucose. Diabetes mellitus (DM) is considered as a group of metabolic diseases characterized by hyperglycemia (high concentration of blood D-glucose) resulting from defects in insulin secretion, insulin action, or both. On the other hand, D-ribose as an energetic enhancer was found to decrease the concentration of blood D-glucose, and thus "Oral administration of D-ribose in diabetes mellitus" was ever described by Steinberg and colleagues (1970). As described previously in this laboratory, D-ribose rapidly glycates proteins, such as BSA, neuronal Tau and α-synuclein, producing advanced glycation end products (AGEs) with severe cytotoxicity, leading to dysfunction and cell death, in vitro and in vivo. Intraperitoneal injection of D-ribose into mice significantly increases their glycated serum protein and blood AGEs though the concentration of D-glucose became slightly decreased, suggesting that D-ribose is much easier to produce AGEs than D-glucose in vivo. Here, using 4-(3-Methyl-5-oxo-2-pyrazolin-1-yl) benzoic acid (MOPBA) coupled with HPLC, we determined the concentration of uric D-ribose of type 2 diabetic patients (n=30) and the age-matched healthy controls (n=30). The results show that the yield of the derivative of MOPBA-ribose is linearly correlated with the concentration of D-ribose (r²=0.999) with a recovery of 99%. The isolated fractions of D-ribose and D-glucose from urine of type 2 diabetic patients through HPLC were analyzed by mass spectrometry, and the results showed that the fractions contained 569.19 u compound (C₂₇H₂₉N₄O₁₀, D-ribose), and 599.20 u compound (C₂₈H₃₁N₄O₁₁, D-glucose) respectively. The concentration of uric D-ribose of Type 2 diabetics (male (134.28±35.09) μmol/L, female (97.33±23.68) μmol/L) was significantly (P < 0.001) higher than that of the age-matched healthy control (male (35.99±5.64) μmol/L, female (33.72±6.27) μmol/L). Under the experimental conditions, the uric D-glucose level of the patients was also markedly (P < 0.001) higher than the control. Further analyses showed a marked increase in the level of uric D-ribose from either male (P < 0.001) or female (P < 0.001), but a significant difference of the uric levels between male and female could not be observed (P > 0.05). The high levels of uric D-ribose and D-glucose of the patients suggest that type 2 diabetic patients are not only suffered from D-glucose metabolism disorders, but also from D-ribose metabolism disorders.

Abstract:The structural connectivity patterns of human brain are the underlying basis of functional connectivity. Abnormal functional connectivity in default mode network (DMN) has been uncovered in electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies, which suggests that the abnormality might be related to the cognitive mental impairment and unconsciousness during absence seizures. However, so far, little is known about the structural connectivity in DMN about childhood absence epilepsy (CAE). In the present study, we hypothesize that the structural connectivity in DMN should be disrupted to respond to the altered brain function in CAE. To test the hypothesis, 11 patients with CAE and 12 age- and gender- matched healthy controls were recruited. We utilized diffusion tensor imaging tractography to map the anatomical structural connectivity of DMN. The fiber bundles among regions of DMN were built for each subject. Then, mean length, fractional anisotropic (FA), mean diffusivity (MD) and connection strength on fibers linking two brain regions were calculated. Further, these parameters were executed two-sample t-test between CAE group and health control group. Finally, we used Pearson's correlation coefficient to evaluate the relationship between these parameters and epilepsy duration (year). Both CAE and healthy control groups showed similar structural connectivity patterns in DMN. Among these fiber bundles, three were identified in all subjects, with one linking posterior cingulate cortex/precuneus to medial prefrontal cortex, and another two linking posterior cingulate cortex/precuneus to bilateral medial temporal lobes. Furthermore, the significantly decreased FA and connection strength, and increased MD in fiber bundles linking posterior cingulated cortex/precuneus to medial prefrontal cortex, were found in patients compared with the cases in healthy controls (P < 0.05，Bonferroni corrected). Predominantly, the FA values in fiber bundles linking posterior cingulated cortex/precuneus to medial prefrontal cortex were negatively correlated with the epilepsy duration (P=0.006). These findings might reflect the structural basis of the altered functional connectivity in DMN about absence epilepsy. Given that functional connectivity abnormality in our previous work, it is implied that the abnormal fiber connectivity from posterior cingulated cortex/precuneus to medial prefrontal cortex plays an important role in absence epilepsy. This may open up new avenues to understand the pathophysiological mechanisms of absence epilepsy.

Abstract:The effects of glycoprotein (GP) Ⅱb/Ⅲa inhibitors on the development of the atherosclerotic process has received scant attention. To investigate whether GP Ⅱb/Ⅲa blockade influences atherosclerosis lesion and HMGB-1/TLR4 signaling, we compared plaque formation in ApoE^-/- mice: control group (n=10); IgG group (n=10, 50 μg) and GP Ⅱb/Ⅲa mAb group (n=10, 50 μg). All mice were fed on a Western diet (10% fat and 1.25% cholesterol) for 10 weeks. GP Ⅱb/Ⅲa blockade significantly decreased the atherosclerotic lesion and platelet adhesion to the vessel wall. Immunohistochemistry analysis showed that blocking GP Ⅱb/Ⅲa diminished MOMA-2 and VCAM-1 expression in aortic plaque in ApoE-/- mice. Western blot results indicated that HMGB-1, TLR4, and NF-κB levels were markedly reduced in arteries of ApoE^-/- mice treated with GP Ⅱb/Ⅲa mAb (P < 0.05). Moreover, GP Ⅱb/Ⅲa mAb decreased plasma HMGB-1, IL-1β, TNF-α and MCP-1 concentrations. Our findings demonstrated that GP Ⅱb/Ⅲa mAb significantly decreased atherosclerotic lesions and HMGB-1, TLR4 and NF-κB expression in ApoE^-/- mice (P < 0.05). The present study has suggested a possibility that GP Ⅱb/Ⅲa blockade attenuates atherosclerosis by inhibiting the HMGB-1/TLR4 pathway.

Abstract:F-box proteins are widely present in eukaryotes, and their biological functions are diverse in animals. In this study, the full-length coding sequence of an unnamed gene LOC416151 (GenBank accession XM_414482) was cloned from the chicken abdominal adipose tissue by reverse transcriptase (RT)-PCR, and the sequence analysis showed that the acquired sequence (GenBank accession. JX290204) is one of the transcript variants of chicken FBXO38, which was designated as gFBXO38t1. Real-time RT-PCR analysis showed that gFBXO38t1 was widely expressed in various chicken tissues, with a relatively higher expression level in the pancreas, ileum and abdominal fat tissue. In addition, gFBXO38t1 was expressed in all the chicken abdominal fat tissues used in the present study, and at 3 and 4 weeks of age, the gFBXO38t1 expression in lean males was significantly greater than that in fat males (P < 0.05) and no significant difference was observed at the other ages (P > 0.05). The gFBXO38t1 expression decreased followed by the differentiation of chicken preadipocytes induced by oleate, and gFBXO38t1 expressed more highly in chicken preadipocytes than in mature adipocytes (P < 0.05), suggesting that gFBXO38t1 might play a negative role in the chicken adipogenesis. Additionally, The luciferase reporter assay showed that gFBXO38t1 overexpression inhibited the promoter activities of chicken CCAAT/enhancer-binding protein α (C/EBPα), lipoprotein lipase (LPL), fatty acid synthase (FASN) and fatty acid-binding protein 4 (FABP4). The combined overexpression of gKLF7 and gFBXO38t1 did not lead to an enhanced ability for gFBXO38t1 to regulate the promoter activities of chicken LPL, FABP4 and FASN, indicating that gFBXO38t1 may regulate promoter activities of these genes through a KLF7-independent manner. The current study provides evidence that the gFBXO38t1 is involved in chicken adipogenesis.

Abstract:Bone marrow stroma stem cells (BMSSCs) have shown promising future in repairing injured myocardium. However, few studies have explored the potential mechanism of BMSSCs transplantation for dilated cardiomyopathy (DCM). In this study we aimed to examine whether BMSSCs transplantation can improves the cardiac function of dilated cardiomyopathy of rats and investigate the possible mechanism of BMSSCs transplantation improving the cardiac function of dilated cardiomyopathy according to investigate the collagen fiber deposition, capillary density, VEGF and its receptor expression. Global heart failure in Wistar rats was induced by means of adriamycin administration, after labeled with DAPI, BMSSCs were transplanted into the myocardium of rats which were divided into transplantation group and control group. At 1w, 2w, 3w, 4w after transplantation, heart function was measured by hemodynamic, the deposition of collagen fiber, expressions of VEGF and its receptor and capillary density were checked by immunochemistry and RT-PCR. Immunofluorescence microscopy revealed that the transplanted BMSSCs were visible at four weeks after transplantation. Compared with the control group, the transplantation group had a significantly higher maximum rate of rise and decline (?dp/dt) of left ventricular pressure and left ventricular systolic pressure (P < 0.05), as well as a significantly lower rate of left ventricular diastolic pressure (P < 0.05). The deposition of collagen fibers in the myocardium of transplantation group was reduced, according to A value in transplant group is less than control group (P < 0.05). The expression of VEGF and its receptor were significantly higher than those of control group, and the upregulation of VEGF and its receptors was unsynchronized, the capillary density is higher in transplantation group than control group after four weeks. Taken together, our results suggest that BMSSCs transplantation can improve dilated cardiomyopathy's heart function of rats, we found that BMSSCs transplantation prevented the fusion of collagen fibers to some extent, decrease the deposition of collagen fiber and maintained the orderly structural arrangement of myocardial tissue. BMSSCs transplantation can also promote the angiogenesis, in our study we found that capillary density increased, BMSSCs transplantation not only upregulated the expression of VEGF, but also upregulated the expression of VEGF receptors. Unsynchronized upregulation of VEGF and its receptors was observed which may promote angiogenesis continuously and steadily.

Abstract:Research on the protective effect and mechanism of rosiglitazone on learning and memory impairment of AD-like mice induced by streptozotocin (STZ) intracerebroventricular (i.c.v.) injection. STZ i.c.v. injection was used to establish AD mice model and the treatment mice were administered orally with rosiglitazone for 30 days. Morris water maze was applied to detect the learning and memory ability of mice and Western blot and immunofluorescence to analyze the phosphorylation levels of Tau，the expression levels of phosphorylation and glycosylation of neurofilaments (NFs) protein, the expression levels of JNK and ERK. The microtubule binding assay was used to detect the assembly function of Tau binding with microtubule. The degenerative neurons were labeled by Fluoro -Jade B (FJB). Compared with the control group, the escape latency and path length were increased of the model group with less number of crossing hidden platform, and the Tau and NFs proteins were hyperphosphorylated and the glycosylation of NFs protein were lower. But compared with the model group, the rosiglitazone significantly improved the learning and memory ability of mice and decreased the hyperphosphorylated levels of Tau and NFs proteins, increased the glycosylation of NFs protein, and increased the microtubule-binding of Tau in treated-mice. The phosphorylated expression levels of JNK of model group were higher than the other two groups, while ERK1 were lower, but there was no significant difference of ERK2 in three groups. And the numbers of FJB-degenerative neurons of model group were much more than the other two groups. Rosiglitazone could protect learning and memory impairment of AD-like mice induced by STZ i.c.v. injection, which may be related to ameliorate the insulin signal pathway, decrease the hyperphosphorylation of Tau and NFs proteins, and protect from the neural degeneration.

Abstract:Nucleophosmin (NPM1 or B23.1) is a ubiquitously expressed nuclear phosphoprotein that plays key role in several cellular processes, including ribosome biogenesis, centrosome duplication, cell cycle progression, cell growth, and transformation. NPM1 is one of the most frequently mutated genes in AML. EDAG is a hematopoietic tissue-specific transcription regulator that plays a key role in maintaining the homeostasis of hematopoietic lineage commitment. In AML patients, the high expression level of EDAG is associated with poor prognosis. Our previous study suggest that EDAG is a physiological binding partner of NPM1 and regulates NPM1 protein stability, however, whether EDAG regulates NPM1 in AML patients and whether EDAG regulates NPM1 mutations remain unknown. In the present study, we found that in bone marrow CD34⁺ cells from AML patients, silencing of EDAG led to decreased protein stability of NPM1 protein and increased cell sensitivity to daunorubicin. Although EDAG failed to interact with NPMc⁺ and regulate its protein stability in normal culture condition, with leptomycin B treatment, EDAG overexpression enhanced the protein stability of NPMc⁺. In AML patients with NPMc⁺, the CD34⁺ cells were more responsive to daunorubicin treatment than the cells from AML with wild type NPM1, and silencing of EDAG weakly increased the sensitivity to daunorubicin. These results suggested a potential role of EDAG in chemotherapy of AML and the "escape" of NPMc⁺ protein from EDAG stabilization might contribute to the favorable prognosis of AML with NPMc⁺.