肠道菌群对新生儿神经发育的影响

新生儿肠道菌群的定植和建立是一个复杂的动态演变过程,且易受分娩方式、喂养方式、胎龄、抗生素暴露等多种因素的影响。肠道菌群不仅在新生儿生理发育、免疫系统成熟、抵抗病原体入侵、维护肠道屏障等方面发挥重要作用,还影响神经回路的建立、髓鞘的形成和血脑屏障的形成。早期肠道菌群失调可导致新生儿坏死性小肠结肠炎、生长发育迟缓和智力发育落后等。近年来肠道菌群通过肠-脑轴影响新生儿神经发育受到广泛关注,其主要与代谢、免疫、迷走神经和神经内分泌等途径相关。本文主要就新生儿肠道菌群特征及其影响因素和肠道菌群对神经发育的影响作一综述。     

Pole vault performance for anthropometric variability via a dynamical optimal control model

Optimal performance of a dynamical pole vault process was modeled as a constrained nonlinear optimization problem. That is, given a vaulter's anthropomorphic data and approach speed, the vaulter chose a specific take-off angle, pole stiffness and gripping height in order to yield the greatest jumping height compromised by feasible bar-crossing velocities. The optimization problem was solved by nesting a technique of searching an input-to-output mapping arising from the vaulting trajectory and a method of nonlinear sequential quadratic programming (SQP). It was suggested from the optimization results that the body's weight has an important influence on the vaulting performance beside the vaulter's height and approach speed; the less skilled vaulter should gradually adopt a longer pole to improve the performance.     

Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue

Serum leptin levels are upregulated in proportion to body fat and also increase over the short term in response to meals or insulin. To understand the mechanisms involved, we assessed leptin synthesis and secretion in samples of adipose tissue from subjects with a wide range of BMI. Tissue leptin content and relative rates of leptin biosynthesis, as determined by metabolic labeling, were highly correlated with each other and with BMI and fat cell size. To understand mechanisms regulating leptin synthesis in obesity, we used biosynthetic labeling to directly assess the effects of insulin and glucocorticoids (dexamethasone) on leptin synthesis and secretion in human adipose tissue. Chronic treatment (1-2 days in organ culture) with insulin increased relative rates of leptin biosynthesis without affecting leptin mRNA levels. In contrast, dexamethasone increased leptin mRNA and biosynthesis in parallel. Acute treatment with insulin or dexamethasone (added during 1-h preincubation and 45-min pulse labeling) did not affect relative rates of leptin biosynthesis, but pulse-chase studies showed that addition of insulin nearly doubled the release of [35S]leptin after a 1-h chase. We conclude that the higher leptin stores in adipose tissue of obese humans are maintained by chronic effects of insulin and glucocorticoids acting at pre- and posttranslational levels and that the ability of insulin to increase the release of preformed leptin may contribute to short-term variations in circulating leptin levels.     

Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line

An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in STZ-induced diabetic rats. A quantitative polymerase chain reaction (qPCR) assay was developed for the bioactivity-guided purification of the compounds within the extract that decrease PEPCK expression. The assay was based on the inhibition of dexamethasone-stimulated PEPCK upregulation in an H4IIE hepatoma cell line. Two polyphenolic compounds that inhibited PEPCK mRNA levels were isolated and identified as 6-demethoxycapillarisin and 2',4'-dihydroxy-4-methoxydihydrochalcone with IC(50) values of 43 and 61 muM, respectively. The phosphoinositide-3 kinase (PI3K) inhibitor LY-294002 showed that 6-demethoxycapillarisin exerts its effect through the activation of the PI3K pathway, similarly to insulin. The effect of 2',4'-dihydroxy-4-methoxydihydrochalcone is not regulated by PI3K and dependent on activation of AMPK pathway. These results indicate that the isolated compounds may be responsible for much of the glucose-lowering activity of the Artemisia dracunculus extract.     

Effects of chronic heat stress on immune responses of the foot-and-mouth disease DNA vaccination

The main purpose of this study was to assess the effects of chronic heat stress (CHS) on humoral and cellular responses of DNA vaccination. Mice with the CHS were exposed to a temperature set at 38 +/- 1 degrees C, 2h per day, for 35 days, and mice with thermoneutral (TN) temperature were maintained at 24 +/- 1 degrees C for the same period of time. Both groups of mice were immunized with a DNA vaccine-expressed viruscapsid protein 1 (VP1) of foot-and-mouth disease virus (FMDV), and we tested their antigen-specific humoral and cellular responses during the treatments. Compared with the TN group, titers of total Imunoglobulin G (IgG) and IgG1 and expression of interleukin 4 (IL-4) in CD4(+) cells of CHS group were not affected significantly. In contrast, the levels of IgG2a, T cell proliferations, and expression of interferon-gama (IFN-gamma) in both CD4(+) and CD8(+) cells were suppressed significantly, and cytotoxic T-lymphocyte (CTL) responses in vivo were also weakened by the CHS condition. These results indicate that the CHS treatment has negatively affected the immune responses of DNA vaccination and particularly impaired to the cell-mediated responses. It suggests that vaccination in animals is affected by the changes of ambient temperature.     

miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells

This study aimed to test the exact functions and potential mechanisms of miR-17-5p in gastric cancer. Using real-time PCR, miR-17-5p was found to be expressed more highly in gastric cancer compared with-normal tissues. Gain- and loss-of-function assays demonstrated that miR-17-5p increased the proliferation and growth of gastric cancer cells in vitro and in vivo. Through reporter gene and western blot assays, SOCS6 was shown to be a direct target of miR-17-5p, and proliferative assays confirmed that SOCS6 exerted opposing function to that of miR-17-5p in gastric cancer. In short, miR-17-5p might function as a pro-proliferative factor by repressing SOCS6 in gastric cancer.     

The epitope and neutralization mechanism of AVFluIgG01, a broad-reactive human monoclonal antibody against H5N1 influenza virus

The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus.     

Erbin-regulated sensitivity of MCF-7 breast cancer cells to TRAIL via ErbB2/AKT/NF-kappaB pathway

We have reported that Erbin expression was down-regulated in the Jurkat leukaemia T lymphocytes treated with the recombinant soluble tumour necrosis factor-related apoptosis-inducing ligand (rsTRAIL). Herein, we studied the expression and the regulation of Erbin and its binding partner, ErbB2, in the MCF-7 breast cancer cell line. We showed that the expressions of Erbin and ErbB2 were modulated by PKCdelta inhibitor, rottlerin, in the TRAIL-resistant MCF-7 cell line. The affinity of Erbin-ErbB2 interaction was reduced by ErbB2 phosphorylation. Inhibiting the expression of Erbin facilitated the sensitivity of the MCF-7 cells to TRAIL via suppressing the ErbB2/AKT/NF-kappaB signalling pathway.     

MiR-132 down-regulates high glucose-induced β-dystroglycan degradation through Matrix Metalloproteinases-9 up-regulation in primary neurons

Cognitive dysfunction is one of the complications of diabetes. Unfortunately, there is no effective methods to block its progression currently. One of the pathophysiological mechanisms is synaptic protein damage and neuronal signal disruption because of glucose metabolism disorder. Dystroglycan protein, located in the post-synaptic membrane of neurons, links the intracellular cytoskeleton with extracellular matrix. Abnormal expression of dystroglycan protein affects neuronal biological functions and leads to cognitive impairment. However, there are no relevant studies to observe the changes of β-dystroglycan protein in diabetes rat brain and in primary neurons under high glucose exposure. Our data demonstrated the alterations of cognitive abilities in the diabetic rats; β-dystroglycan protein degradation occurred in hippocampal and cortical tissues in diabetic rat brain. We further explored the mechanisms underlying of this phenomenon. When neurons are exposed to high glucose environment in long-term period, microRNA-132 (miR-132) would be down-regulated in neurons. Matrix Metalloproteinases-9 (MMP-9) mRNA, as a target of miR-132, could be up-regulated; higher expression and overlay activity of MMP-9 protein could increase β-DG protein degradation. In this way, β-DG degradation may affect structure and functions among the synapses, which related to cognition decline. It may provide some theoretical basis for elucidating the molecular mechanism of diabetes-induced cognitive dysfunction.     

First Principles Prediction of Gas-Phase Composition and Substrate Temperature for Diamond Film Growth

Abstract

A model consisting of ten hydrocarbon species and eight reactions is proposed to describe the gas-phase chemistry of diamond film growth. Based on the model, the gas-phase compositions of the chemical species were computed assuming thermodynamic equilibrium using molecular and transition-state data predicted by ab initio molecular orbital theory, and thermodynamic quantities calculated by statistical mechanics. Although the absolute compositions predicted by the model are in fair agreement with experimental data available in the literature, the model qualitatively accounts for experimentally observed changes in the concentrations of various gas-phase species with increasing addition of methane to the feed gas. The calculations also predict the pattern of temperature variance in the gas-phase close to the substrate with changes in methane concentration in the feed gas, leading to first-principles predictions of favorable conditions for diamond growth.