The protective effect of PL 1-3 on D-galactose-induced aging mice

The aging population has become an issue that cannot be ignored, and research on aging is receiving increasing attention. PL 1-3 possesses diverse pharmacological properties including anti-oxidative stress, inhibits inflammatory responses and anti-apoptosis. This study showed that PL 1-3 could protect mice, especially the brain, against the aging caused by D-galactose (D-gal). D-gal could cause oxidative stress, inflammation, apoptosis and tissue pathological injury and so on in aging mice. The treatment of PL 1-3 could increase the anti-oxidative stress ability in the serum, liver, kidney and brain of aging mice, via increasing the total antioxidant capacity and the levels of anti-oxidative defense enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and reducing the end product of lipid peroxidation (malondialdehyde). In the brain, in addition to the enhanced anti-oxidative stress via upregulating the level of the nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, PL 1-3 could improve the dysfunction of the cholinergic system via reducing the active of acetylcholinesterase so as to increase the level of acetylcholine, increase the anti-inflammatory and anti-apoptosis activities via downregulating the expressions of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and pro-apoptosis proteins (Bcl-2 associated X protein and Caspase-3) in the D-gal-induced aging mice, to enhance the anti-aging ability via upregulating the expression of sirtuin 1 and downregulating the expressions of p53, p21, and p16. Besides, PL 1-3 could reverse the liver, kidney and spleen damages induced by D-gal in aging mice. These results suggested that PL 1-3 may be developed as an anti-aging drug for the prevention and intervention of age-related diseases

Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells

Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem (ES) cells. The recent demonstration that 5-methylcytosine (5-mC) may be further modified to 5-hydroxymethylcytosine (5-hmC) in ES cells has revealed a novel regulatory paradigm to modulate the epigenetic landscape of pluripotency. To understand the role of 5-hmC in the epigenomic landscape of pluripotent cells, here we profile the genome-wide 5-hmC distribution and correlate it with the genomic profiles of 11 diverse histone modifications and six transcription factors in human ES cells. By integrating genomic 5-hmC signals with maps of histone enrichment, we link particular pluripotency-associated chromatin contexts with 5-hmC. Intriguingly, through additional correlations with defined chromatin signatures at promoter and enhancer subtypes, we show distinct enrichment of 5-hmC at enhancers marked with H3K4me1 and H3K27ac. These results suggest potential role(s) for 5-hmC in the regulation of specific promoters and enhancers. In addition, our results provide a detailed epigenomic map of 5-hmC from which to pursue future functional studies on the diverse regulatory roles associated with 5-hmC

Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis

VARYING INDEX COEFFICIENT MODELS

It has been a long history of utilizing interactions in regression analysis to investigate interactive effects of covariates on response variables. In this paper we aim to address two kinds of new challenges resulted from the inclusion of such high-order effects in the regression model for complex data. The first kind arises from a situation where interaction effects of individual covariates are weak but those of combined covariates are strong, and the other kind pertains to the presence of nonlinear interactive effects. Generalizing the single index coefficient regression model (Xia and Li, 1999), we propose a new class of semiparametric models with varying index coefficients, which enables us to model and assess nonlinear interaction effects between grouped covariates on the response variable. As a result, most of the existing semiparametric regression models are special cases of our proposed models. We develop a numerically stable and computationally fast estimation procedure utilizing both profile least squares method and local fitting. We establish both estimation consistency and asymptotic normality for the proposed estimators of index coefficients as well as the oracle property for the nonparametric function estimator. In addition, a generalized likelihood ratio test is provided to test for the existence of interaction effects or the existence of nonlinear interaction effects. Our models and estimation methods are illustrated by both simulation studies and an analysis of body fat dataset

Modeling and Design of Graphene GaAs Junction Solar Cell

Graphene based GaAs junction solar cell is modeled and investigated by Silvaco TCAD tools. The photovoltaic behaviors have been investigated considering structure and process parameters such as substrate thickness, dependence between graphene work function and transmittance, and n-type doping concentration in GaAs. The results show that the most effective region for photo photogenerated carriers locates very close to the interface under light illumination. Comprehensive technological design for junction yields a significant improvement of power conversion efficiency from 0.772% to 2.218%. These results are in good agreement with the reported experimental work

Alterations in brain activation in response to prolonged morphine withdrawal-induced behavioral inflexibility in rats

The inability to stop a repetitive maladaptive behavior is a main problem in addictive disorders. Neuroadaptations that are associated with behavioral inflexibility may be involved in compulsive drug use. The aim of the present study was to investigate the pattern of behavioral inflexibility during morphine withdrawal and map brain activation that is linked to alterations in flexibility. We first analyzed the effects of chronic morphine exposure on reversal learning after 2-week (short-term) and 6-week (prolonged) morphine withdrawal. We then compared the level of neuronal activation using cFos immunohistochemistry in 15 brain areas between rats that underwent morphine withdrawal and saline-control rats after a test of reversal learning. Only prolonged morphine withdrawal impaired reversal learning. Rats that exhibited impairments in reversal learning presented a significant decrease in cFos expression in the orbitofrontal cortex (OFC), including the medial, lateral, and ventral OFC. cFos expression significantly increased in the dorsomedial striatum and major subregions of the medial prefrontal cortex (mPFC) in the morphine group. Rats that underwent prolonged morphine withdrawal exhibited no significant changes in cFos expression in the dorsolateral striatum, nucleus accumbens, amygdala, paraventricular thalamic nucleus, or motor cortex. The rats that underwent short-term withdrawal did not present any changes in cFos expression in any of these brain regions. Altogether, these data suggest that alterations in the function of the frontal cortex and its striatal connections during the late morphine withdrawal phase may underlie the disruption of inhibitory control in opioid dependence.</p

Copper Doped Hollow Structured Manganese Oxide Mesocrystals with Controlled Phase Structure and Morphology as Anode Materials for Lithium Ion Battery with Improved Electrochemical Performance

We develop a facile synthesis route to prepare Cu doped hollow structured manganese oxide mesocrystals with controlled phase structure and morphology using manganese carbonate as the reactant template. It is shown that Cu dopant is homogeneously distributed among the hollow manganese oxide microspherical samples, and it is embedded in the lattice of manganese oxide by substituting Mn³⁺ in the presence of Cu²⁺. The crystal structure of manganese oxide products can be modulated to bixbyite Mn₂O₃ and tetragonal Mn₃O₄ in the presence of annealing gas of air and nitrogen, respectively. The incorporation of Cu into Mn₂O₃ and Mn₃O₄ induces a great microstructure evolution from core–shell structure for pure Mn₂O₃ and Mn₃O₄ samples to hollow porous spherical Cu-doped Mn₂O₃ and Mn₃O₄ samples with a larger surface area, respectively. The Cu-doped hollow spherical Mn₂O₃ sample displays a higher specific capacity of 642 mAhg^–1 at a current density of 100 mA g^–1 after 100 cycles, which is about 1.78 times improvement compared to that of 361 mA h g^–1 for the pure Mn₂O₃ sample, displaying a Coulombic efficiency of up to 99.5%. The great enhancement of the electrochemical lithium storage performance can be attributed to the improvement of the electronic conductivity and lithium diffusivity of electrodes. The present results have verified the ability of Cu doping to improve electrochemical lithium storage performances of manganese oxides