Therapeutic efficacy of novel memantine nitrate MN‐08 in animal models of Alzheimer’s disease

Alzheimer''s disease (AD) is a leading cause of dementia in elderly individuals and therapeutic options for AD are very limited. Over‐activation of N‐methyl‐D‐aspartate (NMDA) receptors, amyloid β (Aβ) aggregation, a decrease in cerebral blood flow (CBF), and downstream pathological events play important roles in the disease progression of AD. In the present study, MN‐08, a novel memantine nitrate, was found to inhibit Aβ accumulation, prevent neuronal and dendritic spine loss, and consequently attenuate cognitive deficits in 2‐month‐old APP/PS1 transgenic mice (for a 6‐month preventative course) and in the 8‐month‐old triple‐transgenic (3×Tg‐AD) mice (for a 4‐month therapeutic course). In vitro, MN‐08 could bind to and antagonize NMDA receptors, inhibit the calcium influx, and reverse the dysregulations of ERK and PI3K/Akt/GSK3β pathway, subsequently preventing glutamate‐induced neuronal loss. In addition, MN‐08 had favorable pharmacokinetics, blood‐brain barrier penetration, and safety profiles in rats and beagle dogs. These findings suggest that the novel memantine nitrate MN‐08 may be a useful therapeutic agent for AD.     

Eremophilane Sesquiterpenes and Benzene Derivatives from the Endophyte Microdiplodia sp. WGHS5

Three new eremophilane sesquiterpenes phomadecalins G−I ( 1 – 3 ) and two new benzene derivatives microdiplzenes A and B ( 12 and 13 ), together with nine known eremophilane sesquiterpenes ( 4 – 11 and 14 ) were isolated from an endophytic fungus, Microdiplodia sp. WGHS5. Their structures were elucidated by the interpretation of HR-ESI-MS and NMR data; meanwhile, the absolute configurations of new compounds were determined on the base of ECD calculations. All compounds were evaluated for the antimicrobial activities and antiproliferative effect on human gastric cancer cell lines (BGC-823).     

Protective effects of acetylcholine on hypoxia-induced endothelial-to-mesenchymal transition in human cardiac microvascular endothelial cells

Molecular and Cellular Biochemistry - Nutritional supplements are traditionally employed for overall health and for managing some health conditions, although controversies are found concerning the...     

Tunable emission,energy transfer and charge compensation in SrMoO4:Sm3+,Tb3+,Na+ phosphor

A series of SrMoO₄:Sm³⁺,Tb³⁺,Na⁺ phosphors was synthesized using a high‐temperature solid‐state reaction method in air. On excitation at 290 nm, SrMoO₄:Sm³⁺,Tb³⁺ phosphor emitted light that varied systematically from green to reddish‐orange on changing the Sm³⁺ and Tb³⁺ ion concentrations. The emission intensities of SrMoO₄:Sm³⁺ and SrMoO₄:Sm³⁺,Tb³⁺ phosphors were increased two to four times due to charge compensation when Na⁺ was added as a charge compensator. The luminescence mechanism and energy transfer could be explained using energy‐level diagrams of the MoO₄^2– group, Sm³⁺ and Tb³⁺ ions. SrMoO₄:Sm³⁺,Tb³⁺,Na⁺ could be used as reddish‐orange phosphor in white light‐emitting diodes (LEDs) based on an ~ 405 nm near‐UV LED chip. This research is helpful in adjusting and improving the luminescence properties of other phosphors. Copyright © 2015 John Wiley & Sons, Ltd.     

Experimental and Natural Infections of Goats with Severe Fever with Thrombocytopenia Syndrome Virus: Evidence for Ticks as Viral Vector

Background

Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent for the fatal life-threatening infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was first identified in the central and eastern regions of China. Although the viral RNA was detected in free-living and parasitic ticks, the vector for SFTSV remains unsettled.

Methodology/Principal Findings

Firstly, an experimental infection study in goats was conducted in a bio-safety level-2 (BSL-2) facility to investigate virus transmission between animals. The results showed that infected animals did not shed virus to the outside through respiratory or digestive tract route, and the control animals did not get infected. Then, a natural infection study was carried out in the SFTSV endemic region. A cohort of naïve goats was used as sentinel animals in the study site. A variety of daily samples including goat sera, ticks and mosquitoes were collected for viral RNA and antibody (from serum only) detection, and virus isolation. We detected viral RNA from free-living and parasitic ticks rather than mosquitoes, and from goats after ticks’ infestation. We also observed sero-conversion in all members of the animal cohort subsequently. The S segment sequences of the two recovered viral isolates from one infected goat and its parasitic ticks showed a 100% homology at the nucleic acid level.

Conclusions/Significance

In our natural infection study, close contact between goats does not appear to transmit SFTSV, however, the naïve animals were infected after ticks’ infestation and two viral isolates derived from an infected goat and its parasitic ticks shared 100% of sequence identity. These data demonstrate that the etiologic agent for goat cohort’s natural infection comes from environmental factors. Of these, ticks, especially the predominant species Haemaphysalis longicornis, probably act as vector for this pathogen. The findings in this study may help local health authorities formulate and focus preventive measures to contain this infection.     

桂西南岩溶区八种适生植物光合性状的变异与关联

为探究岩溶植物的光合生理适应机制，采用Li-6400XT便携式光合作用测量系统，对广西平果市岩溶区8种适生植物的叶片净光合速率(P_n)、气孔导度(G_s)、胞间CO₂浓度(C_i)、蒸腾速率(T_r)、水分利用效率(WUE)和气孔限制值(L_s)等光合特征参数进行了测定分析。结果表明：(1)6个光合特征参数在种内和种间均存在不同程度的变异，并且种内变异均大于种间变异。(2)G_s和T_r的变化主要来源于种间变异(46.72%～49.76%),而P_n、C_i、WUE和L_s变化主要来源于种内变异(48.66%～64.50%)。在生活型水平上，P_n、G_s和T_r的种内变异表现为常绿植物小于落叶植物，而C_i、WUE和L_s则相反。(3)各参数的种间变异均表现为落叶植...     

Properties of an LNA-modified ricin RNA aptamer

'Locked nucleic acids' (LNAs) are sugar modified nucleic acids containing the 2'-O-4'C-methylene-β-D-ribofuranoses. The substitution of RNAs with LNAs leads to an enhanced thermostability. Aptamers are nucleic acids, which are selected for specific target binding from a large library pool by the 'SELEX' method. Introduction of modified nucleic acids into aptamers can improve their stability. The stem region of a ricin A chain RNA aptamer was substituted by locked nucleic acids. Different constructs of the LNA-substituted aptamers were examined for their thermostability, binding activity, folding and RNase sensitivity as compared to the natural RNA counterpart. The LNA-modified aptamers were active in target binding, while the loop regions and the adjacent stem nucleotides remained unsubstituted. The thermostability and RNase resistance of LNA substituted aptamers were enhanced as compared to the native RNA aptamer. This study supports the approach to substitute the aptamer stem region by LNAs and to leave the loop region unmodified, which is responsible for ligand binding. Thus, LNAs possess an encouraging potential for the development of new stabilized nucleic acids and will promote future diagnostic and therapeutic applications.     

Metagenomic insights into the fibrolytic microbiome in yak rumen

The rumen hosts one of the most efficient microbial systems for degrading plant cell walls, yet the predominant cellulolytic proteins and fibrolytic mechanism(s) remain elusive. Here we investigated the cellulolytic microbiome of the yak rumen by using a combination of metagenome-based and bacterial artificial chromosome (BAC)-based functional screening approaches. Totally 223 fibrolytic BAC clones were pyrosequenced and 10,070 ORFs were identified. Among them 150 were annotated as the glycoside hydrolase (GH) genes for fibrolytic proteins, and the majority (69%) of them were clustered or linked with genes encoding related functions. Among the 35 fibrolytic contigs of >10 Kb in length, 25 were derived from Bacteroidetes and four from Firmicutes. Coverage analysis indicated that the fibrolytic genes on most Bacteroidetes-contigs were abundantly represented in the metagenomic sequences, and they were frequently linked with genes encoding SusC/SusD-type outer-membrane proteins. GH5, GH9, and GH10 cellulase/hemicellulase genes were predominant, but no GH48 exocellulase gene was found. Most (85%) of the cellulase and hemicellulase proteins possessed a signal peptide; only a few carried carbohydrate-binding modules, and no cellulosomal domains were detected. These findings suggest that the SucC/SucD-involving mechanism, instead of one based on cellulosomes or the free-enzyme system, serves a major role in lignocellulose degradation in yak rumen. Genes encoding an endoglucanase of a novel GH5 subfamily occurred frequently in the metagenome, and the recombinant proteins encoded by the genes displayed moderate Avicelase in addition to endoglucanase activities, suggesting their important contribution to lignocellulose degradation in the exocellulase-scarce rumen.