Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes.

Aims/hypothesisWhile genome-wide association studies (GWASs) have been successful in identifying novel variants associated with various diseases, it has been much more difficult to determine the biological mechanisms underlying these associations. Expression quantitative trait loci (eQTL) provide another dimension to these data by associating single nucleotide polymorphisms (SNPs) with gene expression. We hypothesised that integrating SNPs known to be associated with type 2 diabetes with eQTLs and coexpression networks would enable the discovery of novel candidate genes for type 2 diabetes.MethodsWe selected 32 SNPs associated with type 2 diabetes in two or more independent GWASs. We used previously described eQTLs mapped from genotype and gene expression data collected from 1,008 morbidly obese patients to find genes with expression associated with these SNPs. We linked these genes to coexpression modules, and ranked the other genes in these modules using an inverse sum score.ResultsWe found 62 genes with expression associated with type 2 diabetes SNPs. We validated our method by linking highly ranked genes in the coexpression modules back to SNPs through a combined eQTL dataset. We showed that the eQTLs highlighted by this method are significantly enriched for association with type 2 diabetes in data from the Wellcome Trust Case Control Consortium (WTCCC, p = 0.026) and the Gene Environment Association Studies (GENEVA, p = 0.042), validating our approach. Many of the highly ranked genes are also involved in the regulation or metabolism of insulin, glucose or lipids.Conclusions/interpretationWe have devised a novel method, involving the integration of datasets of different modalities, to discover novel candidate genes for type 2 diabetes

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV(1)/forced vital capacity (FVC) ≤70% and FEV(1) less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction

A study on the effect of resveratrol on lipid metabolism in hyperlipidemic mice

Background: The content of resveratrol is relatively high in Polygonum cuspidatum Sieb. et Zucc., and the resveratrol has the effect of blood vessel dilating, microcirculation improving, platelet aggregation inhibiting and anti-cancer. The objective of this paper was to study the effect of resveratrol on lipid metabolism in hyperlipidemia mice.Materials andMethods: Through the establishment of an experimental mouse model of hyperlipidemia, the effect of resveratrol on change in total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) levels in mouse serum were determined.Results: Resveratrol group can apparently reduce TC, TG, LDL-c and AI of hyperlipidemic mice in a dose effect manner.Conclusion: We concluded that resveratrol can effectively reduce blood lipid levels of hyperlipidemic mice.Keywords: Resveratrol; hyperlipidemia; TC; TG; HDL-c; LDL-

The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases

Rheumatoid arthritis (RA) is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF). The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insufficient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specific antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specificity (98%) for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody), can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA

Model-based assessment of chromate reduction and nitrate effect in a methane-based membrane biofilm reactor

© 2019 Zhejiang University Chromate contamination can pose a high risk to both the environment and public health. Previous studies have shown that CH4-based membrane biofilm reactor (MBfR) is a promising method for chromate removal. In this study, we developed a multispecies biofilm model to study chromate reduction and its interaction with nitrate reduction in a CH4-based MBfR. The model-simulated results were consistent with the experimental data reported in the literature. The model showed that the presence of nitrate in the influent promoted the growth of heterotrophs, while suppressing methanotrophs and chromate reducers. Moreover, it indicated that a biofilm thickness of 150 μm and an influent dissolved oxygen concentration of 0.5 mg O2/L could improve the reactor performance by increasing the chromate removal efficiency under the simulated conditions

ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma.

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions

Experimental and Theoretical Investigation of Macro-Periodic and Micro-Random Nanostructures with Simultaneously Spatial Translational Symmetry and Long-Range Order Breaking

Photonic and plasmonic quasicrystals, comprising well-designed and regularly-arranged patterns but lacking spatial translational symmetry, show sharp diffraction patterns resulting from their long-range order in spatial domain. Here we demonstrate that plasmonic structure, which is macroscopically arranged with spatial periodicity and microscopically constructed by random metal nanostructures, can also exhibit the diffraction effect experimentally, despite both of the translational symmetry and long-range order are broken in spatial domain simultaneously. With strategically pre-formed metal nano-seeds, the tunable macroscopically periodic (macro-periodic) pattern composed from microscopically random (micro-random) nanoplate-based silver structures are fabricated chemically through photon driven growth using simple light source with low photon energy and low optical power density. The geometry of the micro-structure can be further modified through simple thermal annealing. While the random metal nanostructures suppress high-order Floquet spectra of the spatial distribution of refractive indices, the maintained low-order Floquet spectra after the ensemble averaging are responsible for the observed diffraction effect. A theoretical approach has also been established to describe and understand the macro-periodic and micro-random structures with different micro-geometries. The easy fabrication and comprehensive understanding of this metal structure will be beneficial for its application in plasmonics, photonics and optoelectronics.published_or_final_versio

Optical Waveplates Based on Birefringence of Anisotropic Two-Dimensional Layered Materials

Birefringence is an inherent optical property of anisotropic materials introduced by the anisotropic confinement in their crystal structures. It enables manipulation of light propagation properties (e.g., phase velocity, reflection, and refrac- tion) for various photonic and optoelectronic applications, including waveplates and liquid crystal displays. Two-dimensional (2D) layered materials with high anisotropy are currently gaining an increasing interest for polarization-integrated nano- device applications, which advances the research on birefringent materials. In this article, we investigate the optical birefrin- gence of three anisotropic 2D layered materials (black phosphorus (BP), rhenium disulfide (ReS2), and rhenium diselenide (ReSe2)). We demonstrate that the birefringence in BP (~0.245) is ~ 6 times larger than that of ReS2 (~0.037) and ReSe2 (~0.047) at 520 nm and is comparable to the current state of the art bulk materials (e.g., CaCO3). We use these 2D materials to fabricate atomically-thin optical waveplates and investigate their performance. In particular, for BP, we observe a polarization-plane rotation of ~0.05° per atomic layer at 520 nm. Our results show that the relatively large birefringence of anisotropic 2D layered materials can enable accurate manipulation of light polarization with atomically controlled device thickness for various applications where integrated, nanoscale polarization-controllers are required

A RISC-V Vector Processor With Simultaneous-Switching Switched-Capacitor DC-DC Converters in 28 nm FDSOI

This work demonstrates a RISC-V vector microprocessor implemented in 28 nm FDSOI with fully integrated simultaneous-switching switched-capacitor DC-DC (SC DC-DC) converters and adaptive clocking that generates four on-chip voltages between 0.45 and 1 V using only 1.0 V core and 1.8 V IO voltage inputs. The converters achieve high efficiency at the system level by switching simultaneously to avoid charge-sharing losses and by using an adaptive clock to maximize performance for the resulting voltage ripple. Details about the implementation of the DC-DC switches, DC-DC controller, and adaptive clock are provided, and the sources of conversion loss are analyzed based on measured results. This system pushes the capabilities of dynamic voltage scaling by enabling fast transitions (20 ns), simple packaging (no off-chip passives), low area overhead (16%), high conversion efficiency (80%-86%), and high energy efficiency (26.2 DP GFLOPS/W) for mobile devices