Search

A series of N, N– disubstituted piperazines and homopiperazines were prepared and evaluated for binding to natural α4β2* and α7* neuronal nicotinic acetylcholine receptors (nAChRs) using whole brain membrane. Some compounds exhibited good selectivity for α4β2* nAChRs and did not interact with the α7* nAChRs subtype. The most potent analogs were compounds 8-19 (Ki = 10.4 μM), 8–13 (Ki = 12.0 μM), and 8–24 (Ki = 12.8 μM). Thus, linking together a pyridine π-system and a cyclic amine moiety via a homopiperazine ring affords compounds with low affinity but with good selectivity for α4β2* nAChRs. [ABSTRACT FROM AUTHOR]

We describe a sporadic amyotrophic lateral sclerosis (ALS) patient who presented rapid progress of muscle weakness and died of respiratory failure one and a half years after onset. Genetic analysis revealed a novel ALS-causing gene NEK1 nonsense mutation p.K1210* and a known pathogenic frontotemporal lobar degeneration (FTD)-causing gene GRN mutation p.C139R. It is rare for ALS patients to carry two different pathogenic mutations simultaneously. The individual only had typically motor neuron dysfunction without any related cognitive symptoms. GRN p.C139R mutation is linked to various clinical phenotypes that include FTD and Alzheimer's disease (AD). The case carrying two different gene mutations expands our understanding of ALS genetics. [ABSTRACT FROM AUTHOR]

To explore the effect of resveratrol in premature senescence and reveal its anti-premature senescence mechanisms through network pharmacology. In this study, the H2O2-induced bone marrow mesenchymal stem cells (BMMSCs) premature senescence model is applied. Cell counting kit-8 assay, β-galactosidase staining and flow cytometry are conducted to detect the proliferation, senescence and apoptosis of BMMSCs. Bioinformatics analyses are used to screen and validate molecular targets of resveratrol acting on premature senescence. Dual-luciferase reporter assay is conducted to verify the interaction between v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) and sirtuin 1 (SIRT1). RT-qPCR and western blot are adopted to detect mRNA and protein levels of RELA, SIRT1, senescence-related genes and apoptosis-related genes. First, we proved that resveratrol alleviated the H2O2-induced senescence of BMMSCs. Then, bioinformatics analysis revealed that RELA was the downstream target of resveratrol and SIRT1 was the downstream target of RELA, respectively, involved in premature aging. RELA/SIRT1 may be the potential target of resveratrol for premature senescence. Notably, rescue experiments indicated that resveratrol inhibited premature senescence partially through targeting regulation RELA/SIRT1. In our study, we confirm the functional role of the resveratrol-RELA- SIRT1 axis in the progression of premature senescence, which provides a latent target for premature senescence treatment. [ABSTRACT FROM AUTHOR]

Knowledge about fertiliser limitation to soil microbes is crucial for exploring microbial community succession and ecosystem functions. In this study, an experiment was conducted to promote ecological restoration by different treatments of organic fertiliser (OF), microbial fertiliser (MF) and non-fertiliser (CK) in a coal mine dump. We investigated microbial community structure using high-throughput sequencing. Soils under OF and MF treatment showed distinct community structures with highly bacterial α-diversity due to the variation of soil pH and organic matters (SOM). Of those, the community dissimilarity between OF and CK was higher. The DistLM analysis indicated that SOM and available nitrogen (AN) significantly influenced microbial community structure. Furthermore, functional annotation by the FAPROTAX revealed that the functional groups associating with C, N, and S cycling increased significantly under OF and MF treatment, but decreased that associated with parasites or symbionts. Compared with MF, the functional groups with OF treatment varied greatly. However, the function groups including nitrogen_fixation, hydrocarbon_degradation and methanotrophy were significantly improved under the MF treatment, which have an important implication for soil quality and microbial growth. It was concluded that MF treatment could improve microbial community structure and enhance potential ecosystem function in coal mine dump soils. [ABSTRACT FROM AUTHOR]

Ventilative drying is an essential drying method to protect natural gas pipeline from corrosion and prevent the formation of hydrate. A mathematical model describing the problem of pipelines drying with dehydrated air is developed based on the fundamental principle of mass, momentum, and species conservation in present work. To enhance the accuracy of the model, a new correlation of the evaporation rate of water in pipeline is introduced by taking interfacial resistance into account. Finite volume method (FVM) is employed to discretize the governing equations with first-order upwind scheme for mass and momentum equations and QUICK scheme for species equations. To reduce calculation load, a new solution strategy of semi-implicit method for Sm-linked equations is proposed to solve the nonlinear algebraic equations after the discretization of mathematical model. The results indicate that average absolute deviation between experimental data and the calculations are 8.8% and 8.2% for two cases, respectively. By analysis of dynamic process of the ventilative drying, it is found that the drying process takes place from the ends toward the center of the pipeline. In addition, the results also demonstrate that the nonuniform distribution of the liquid holdup may reduce the service efficiency of dehydrated air at the late period of drying process. Thus, we suggest that the drying process shifts to soak-test stage when the water vapor at the outlet reaches a minimum set value. Finally, a number of influential factors on the drying process are studied. [ABSTRACT FROM AUTHOR]

The 2Cr13/316L multilayered steel (MLS) composites were prepared by accumulative hot roll bonding and heat treatment. The element diffusion, interface bonding mechanism and interface bonding properties of the MLS composites were investigated. The microstructures of the MLS composites before and after heat treatment, are mainly composed of austenite (A), martensite (M), ferrite (F) and little M23C6 carbides. The grain refinement is achieved by accumulative hot roll bonding and heat treatment. The bonding mechanism can be divided into diffusion and recrystallization based on the difference of formation of interfacial grains. The heat treatment has opposite effects on bending strength and shear strength, it is because that softening and interface enhancement of heat treatment have different effects on corresponding bending and shear fracture behavior. [ABSTRACT FROM AUTHOR]

Nylon copolymer/clay (NC) nanocomposites were prepared using PA6/66 as a matrix and organoclay as a nanofiller through a two-step melt-compounding method. It was shown that the organoclay flakes were well exfoliated and dispersed in the PA6/66 matrix. With increasing content of organoclay, the apparent shear viscosity and the entrance pressure drop of the NC nanocomposites decreased whereas the corresponding shear activation energy increased, suggesting that the NC nanocomposites were suitable to be used in shear-flow rather than extension-flow related processes. Investigations of the crystallization behaviors of the NC nanocomposites indicated that the organoclay addition was capable of facilitating the γ-form crystal formation, which is suggested to be due to the restriction effect of the organoclay on the PA6/66 chain motion during the crystallization. Compared to the neat PA6/66, the tensile strength and elongation at break of the NC nanocomposites were both enhanced at an appropriate content of the organoclay. In addition, the NC nanocomposites exhibited enhanced barrier properties due to the high specific surface area and the homogeneous dispersion of the organoclay. [ABSTRACT FROM AUTHOR]

We reported here a high risk pregnant case in which the BoBs SP TM sp assay for chorionic villus sampling (CVS) was 22q11.2 microduplication, but it was normal in AF because of confined placental mosaicism (CPM). BACs-on-Beads™ assay for a case of trisomy 22 confined placental mosaicism The BACs-on-Beads™ (BoBs™) assay was a multiplex, bead-based suspension array using microspheres with two distinct infra-red and red fluorochromes to generate more than 100 different unique probes. [Extracted from the article]