Normal-weight central obesity: implications for diabetes mellitus

BackgroundCurrent guidelines for obesity prevention and control focus on body mass index (BMI) and rarely address central obesity. Few studies have been conducted on the association between normal-weight central obesity and the risk of diabetes mellitus (DM).Methods26,825 participants from the National Health and Nutrition Examination Survey (NHANES) were included in our study. A weighted multivariate logistic regression model was used to analyze the relationship between different obesity patterns and the risk of DM.ResultsOur results suggest that normal-weight central obesity is associated with an increased risk of DM (OR: 2.37, 95% CI: 1.75–3.23) compared with normal-weight participants without central obesity. When stratified by sex, men with normal-weight central obesity, obesity and central obesity were found to have a similar risk of DM (OR: 3.83, 95% CI: 2.10–5.97; OR: 4.20, 95% CI: 3.48–5.08, respectively) and a higher risk than all other types of obesity, including men who were overweight with no central obesity (OR: 1.21, 95% CI: 0.96–1.51) and obese with no central obesity (OR: 0.53, 95% CI: 0.30–0.91).ConclusionOur results highlight the need for more attention in people with central obesity, even if they have a normal BMI

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity

Genome-Wide Profiling Identified a Set of miRNAs that Are Differentially Expressed in Glioblastoma Stem Cells and Normal Neural Stem Cells

A major challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, we compared microRNA (miRNA) expression profiles in human glioblastoma stem cells and normal neural stem cells using combined microarray and deep sequencing analyses. These studies allowed us to identify a set of 10 miRNAs that are considerably up-regulated or down-regulated in glioblastoma stem cells. Among them, 5 miRNAs were further confirmed to have altered expression in three independent lines of glioblastoma stem cells by real-time RT-PCR analysis. Moreover, two of the miRNAs with increased expression in glioblastoma stem cells also exhibited elevated expression in glioblastoma patient tissues examined, while two miRNAs with decreased expression in glioblastoma stem cells displayed reduced expression in tumor tissues. Furthermore, we identified two oncogenes, NRAS and PIM3, as downstream targets of miR-124, one of the down-regulated miRNAs; and a tumor suppressor, CSMD1, as a downstream target of miR-10a and miR-10b, two of the up-regulated miRNAs. In summary, this study led to the identification of a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells may lead to the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10⁻⁵). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/articles/srep2124

Characterization of Pore Structures and Implications for Flow Transport Property of Tight Reservoirs: A Case Study of the Lucaogou Formation, Jimsar Sag, Junggar Basin, Northwestern China

Quantitate characterization of pore structures is fundamental to elucidate fluid flow in the porous media. Pore structures of the Lucaogou Formation in the Jimsar Sag were investigated using petrography, mercury intrusion capillary porosimetry (MICP) and X-ray computed tomography (X-ray μ-CT). MICP analyses demonstrate that the pore topological structure is characterized by segmented fractal dimensions. Fractal dimension of small pores (r &lt; Rapex) ranges from 2.05 to 2.37, whereas fractal dimension of large pores (r &gt; Rapex) varies from 2.91 to 5.44, indicating that fractal theory is inappropriate for the topological characterization of large pores using MICP. Pore volume of tight reservoirs ranges over nine orders of magnitude (10−1–108 μm3), which follows a power-law distribution. Fractal dimensions of pores larger than a lower bound vary from 1.66 to 2.32. Their consistence with MICP results suggests that it is an appropriate indicator for the complex and heterogeneous pore network. Larger connected pores are primary conductive pathways regardless of lithologies. The storage capacity depends largely on pore complexity and heterogeneity, which is negatively correlated with fractal dimension of pore network. The less heterogeneous the pore network is, the higher storage capability it would have; however, the effect of pore network heterogeneity on the transport capability is much more complicated

Protective effects of astragaloside IV against amyloid beta1-42 neurotoxicity by inhibiting the mitochondrial permeability transition pore opening.

Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial permeability transition pore (mPTP) opening is involved in Aβ-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aβ1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD

Diagenesis and porosity-permeability evolution of low permeability reservoirs: A case study of Jurassic Sangonghe Formation in Block 1, central Junggar Basin, NW China

Based on core observation, thin section examination, cathode luminescence analysis, scanning electron microscopy, fluid inclusions, carbon and oxygen isotope, mercury penetration, porosity-permeability test and other analytical methods, combined with the histories of burial evolution, organic matter thermal evolution and hydrocarbon charge, the diagenesis and porosity-permeability evolution are studied of low-permeability reservoirs of Jurassic Sangonghe Formation in Block 1 of central Junggar Basin. The matching relation between reservoir porosity-permeability evolution and hydrocarbon accumulation history is analyzed. The diagenetic environment evolution of the reservoir in the study area is early alkaline, interim acid and late alkaline, forming the diagenetic sequence of chlorite membrane precipitation, early calcite cementation, feldspar dissolution accompanied by quartz overgrowth and authigenic kaolinite precipitation, anhydrite cementation, late period ferrocalcite and ankerite cementation, a small amount of pyrite cementation. Generally, compaction occurs throughout the whole burial process. According to the matching relation between reservoir porosity-permeability evolution and hydrocarbon accumulation history, the Jurassic Sangonghe Formation has three genetic types of low permeability reservoirs: densification after hydrocarbon accumulation, with the best exploration potential; densification during the hydrocarbon accumulation, with medium exploration potential; densification before the hydrocarbon accumulation, with the poorest exploration potential. Key words: low permeability reservoir, diagenesis, porosity-permeability evolution, hydrocarbon accumulation history, Junggar Basi

AS-IV attenuates Aβ1-42-induced increase of ROS generation in SK-N-SH cells.

<p>A. Confocal fluorescence images of intracellular ROS stained with DCFH-DA. Mitochondria were counterstained with Mitotracker Red (red fluorescence). (a) vehicle; (b) 50 µM AS-IV; (c) 5 µM Aβ1-42; (d, e, f) 10, 25, 50 µM AS-IV+ 5 µM Aβ1-42, respectively. B. Quantification analysis for DCFH-DA fluorescence intensity. ^#<i>P</i><0.01 <i>vs</i> vehicle; ^*<i>P</i><0.01 <i>vs</i> Aβ1-42 (n = 8). C. Confocal fluorescence images of mitochondrial superoxide stained with MitoSOX Red. Mitochondria were counterstained with Mitotracker Green (green fluorescence). (a) vehicle; (b) 50 µM AS-IV; (c) 5 µ µM Aβ1-42; (d, e, f) 10, 25, 50 µM AS-IV+ 5 µM Aβ1-42, respectively. D. Quantification analysis for MitoSOX Red fluorescence intensity ^#<i>P</i><0.01 <i>vs</i> vehicle; ^*<i>P</i><0.01 <i>vs</i> Aβ1-42 (n = 8). Scale bar = 10 µm.</p