Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with the Severity of Coronary Artery Disease in Chinese Women

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) has been described as a novel adipokine, playing an important role in the development of metabolic syndrome, type 2 diabetes and atherosclerosis. In this study, we investigated the relationship between serum levels of A-FABP and the presence and severity of coronary artery disease (CAD) in Chinese subjects. METHODOLOGY/PRINCIPAL FINDINGS: Circulating A-FABP level was determined by ELISA in 341 Chinese subjects (221 men, 120 women) who underwent coronary angiography. A-FABP levels in patients with CAD were significantly higher compared with non-CAD subjects (P = 0.029 in men; P = 0.031 in women). Serum A-FABP increased significantly in multi-vessel diseased patients than in non-CAD subjects (P = 0.011 in men, P = 0.004 in women), and showed an independent correlation with coronary atherosclerosis index (standardized β = 0.173, P = 0.025). In multiple logistic regression analysis, serum A-FABP was an independent risk factor for CAD in women (OR = 5.637, 95%CI: 1.299-24.457, P = 0.021). In addition, amino terminal pro-brain natriuretic peptide (NT-proBNP) was demonstrated to be positively and independently correlated with A-FABP (standardized β = 0.135, P = 0.027). CONCLUSIONS/SIGNIFICANCE: Serum A-FABP is closely associated with the presence and severity of CAD in Chinese women

Inhibition of miR-29 by TGF-beta-Smad3 Signaling through Dual Mechanisms Promotes Transdifferentiation of Mouse Myoblasts into Myofibroblasts

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in regulating many biological processes, including myogenic differentiation and muscle development. miR-29 is a promoting factor during myogenesis but its full spectrum of impact on muscle cells has yet to be explored. Here we describe an analysis of miR-29 affected transcriptome in C2C12 muscle cells using a high throughput RNA-sequencing platform. The results reveal that miR-29 not only functions to promote myogenic differentiation but also suppresses the transdifferentiation of myoblasts into myofibroblasts. miR-29 inhibits the fibrogenic differentiation through down-regulating both extracellular matrix genes and cell adhesion genes. We further demonstrate that miR-29 is under negative regulation by TGF-beta (TGF-β)–Smad3 signaling via dual mechanisms of both inhibiting MyoD binding and enhancing Yin Yang 1 (YY1)-recruited Polycomb association. Together, these results identify miR-29 as a pleiotropic molecule in both myogenic and fibrogenic differentiation of muscle cells

Critical current density: Measurements vs. reality

Different experimental techniques are employed to evaluate the critical current density (Jc), namely transport current measurements and two different magnetisation measurements forming quasi-equilibrium and dynamic critical states. Our technique-dependent results for superconducting YBa 2Cu3O7 (YBCO) film and MgB2 bulk samples show an extremely high sensitivity of Jc and associated interpretations, such as irreversibility fields and Kramer plots, which lose meaning without a universal approach. We propose such approach for YBCO films based on their unique pinning features. This approach allows us to accurately recalculate the magnetic-field-dependent Jc obtained by any technique into the Jc behaviour, which would have been measured by any other method without performing the corresponding experiments. We also discovered low-frequency-dependent phenomena, governing flux dynamics, but contradicting the considered ones in the literature. The understanding of these phenomena, relevant to applications with moving superconductors, can clarify their dramatic impact on the electric-field criterion through flux diffusivity and corresponding measurements. © Copyright EPLA, 2013

A Novel Role for IκBζ in the Regulation of IFNγ Production

IκBζ is a novel member of the IκB family of NFκB regulators, which modulates NFκB activity in the nucleus, rather than controlling its nuclear translocation. IκBζ is specifically induced by IL-1β and several TLR ligands and positively regulates NFκB-mediated transcription of genes such as IL-6 and NGAL as an NFκB binding co-factor. We recently reported that the IL-1 family cytokines, IL-1β and IL-18, strongly synergize with TNFα for IFNγ production in KG-1 cells, whereas the same cytokines alone have minimal effects on IFNγ production. Given the striking similarities between the IL-1R and IL-18R signaling pathways we hypothesized that a common signaling event or gene product downstream of these receptors is responsible for the observed synergy. We investigated IκBζ protein expression in KG-1 cells upon stimulation with IL-1β, IL-18 and TNFα. Our results demonstrated that IL-18, as well as IL-1β, induced moderate IκBζ expression in KG-1 cells. However, TNFα synergized with IL-1β and IL-18, whereas by itself it had a minimal effect on IκBζ expression. NFκB inhibition resulted in decreased IL-1β/IL-18/TNFα-stimulated IFNγ release. Moreover, silencing of IκBζ expression led to a specific decrease in IFNγ production. Overall, our data suggests that IκBζ positively regulates NFκB-mediated IFNγ production in KG-1 cells

Verification of High-Resolution Medium-Range Precipitation Forecasts from Global Environmental Multiscale Model over China during 2009–2013

Accurate and timely precipitation forecasts are a key factor for improving hydrological forecasts. Therefore, it is fundamental to evaluate the skill of Numerical Weather Prediction (NWP) for precipitation forecasting. In this study, the Global Environmental Multi-scale (GEM) model, which is widely used around Canada, was chosen as the high-resolution medium-term prediction model. Based on the forecast precipitation with the resolution of 0.24° and taking regional differences into consideration, the study explored the forecasting skill of GEM in nine drought sub-regions around China. Spatially, GEM performs better in East and South China than in the inland areas. Temporally, the model is able to produce more precise precipitation during flood periods (summer and autumn) compared with the non-flood season (winter and spring). The forecasting skill variability differs with regions, lead time and season. For different precipitation categories, GEM for trace rainfall and little rainfall performs much better than moderate rainfall and above. Overall, compared with other prediction systems, GEM is applicable for the 0–96 h forecast, especially for the East and South China in flood season, but improvement for the prediction of heavy and storm rainfall and for the inland areas should be focused on as well

Scenario-Based LULC Dynamics Projection Using the CA–Markov Model on Upper Awash Basin (UAB), Ethiopia

Understanding the spatiotemporal changes in land use and land cover (LULC) in the watershed is crucial for maintaining the sustainability of land resources. This study intents to understand the historical (1972–2015) and future (2030–2060) spatiotemporal distribution of LULC changes in the Upper Awash Basin (UAB). The supervised Maximum Likelihood Classifier technique (MLC) was implemented for historical LULC classification. The Cellular Automata-Markov (CA–Markov) model was employed to project two scenarios of LULC, ‘business-as-usual’ (BAU) and ‘governance’ (Gov). Results from the historical LULC of the study area show that urban and cropland areas increased from 52.53 km2 (0.45%) to 354.14 km2 (3.01%) and 6040.75 km2 (51.25%) to 8472.45 km2 (71.97%), respectively. Whereas grassland, shrubland, and water bodies shrunk from 2052.08 km2 (17.41%) to 447.63 km2 (3.80%), 2462.99 km2 (20.89%) to 1399.49 km2 (11.89%) and 204.87 km2 (1.74%) to 152.44 km2 (1.29%), respectively, from 1972 to 2015. The historical LULC results indicated that the forest area was highly vulnerable and occupied by urban and cropland areas. The projected LULC under the BAU scenario shows substantial cropland and urban area expansion, increasing from 8472.45 km2 (71.97%) in 2015 to 9159.21 km2 (77.71%) in 2060 and 354.14 km2 (3.1%) in 2015, 1196.78 km2 (10.15%) in 2060, respectively, at the expense of vegetation cover. These results provide insight intothe LULC changes in the area, thus requiring urgent attention by watershed managers, policymakers, and stakeholders to provide sustainable practices for the UAB. Meanwhile, the Gov scenario indicates an increase in vegetable covers and a decrease in cropland, encouraging sustainable development compared to the BAU scenario

Enhanced Gas Production from Class II Gas Hydrate Reservoirs by the Multistage Fractured Horizontal Well

In the two test productions that have been conducted in the hydrate reservoir test development zone in the South China Sea, the gas production capacity of single wells is low and the exploitation difficulty with the cost is too high for commercial demand economically. The low permeability of the hydrate-bearing layer (HBL) acts as the major barrier for pressure propagation during depressurization. Hydraulic fracturing by the combined depressurization is considered a promising hydrate production enhancement technology that can effectively improve the seepage state in the reservoir. In this study, to evaluate the effectiveness of the development methods association with fracturing, we established an idealized Class II hydrate reservoir and studied it using a multi-stage fractured horizontal well to assist in depressurization extraction. In order to evaluate the production enhancement effect of this method, we compared the gas production results of four methods, including single vertical well, vertical fractured well, horizontal well, and multistage fractured horizontal well through numerical simulation. In order to investigate the influence of key fracture parameters on the production enhancement effect, a sensitivity analysis of the production effect of Class II hydrate reservoirs with different fracture spacing, number of fractures, fracture conductivity, and fracture length was conducted, and the results were analyzed in terms of gas production and water production behavior curves as well as physical field evolution over time. The simulation results show that the multi-stage fractured horizontal wells have the best production increase in the comparison of well types. In the analysis of fracture parameters, it can be found that the selection of proper fracture spacing and dimensionless fracture conductivity can lead to a significant increase in gas production

Quantitative Analysis of the Uncertainty of Drought Process Simulation Based on Atmospheric–Hydrological Coupling in Different Climate Zones

Droughts can lead to drought disasters, which have become one of the main natural disasters affecting the development of social economies and ecological environments around the world. Timely and effective drought process simulation and prediction based on atmospheric–hydrological coupling is crucial for drought prevention and resistance. The initial condition (IC) is one source causing uncertainty in drought process simulation and prediction, and the impacts are different with drought duration, basin size and region. Therefore, a quantitative method that measures the uncertainty caused by ICs on the drought process simulation in different climate zones is proposed in this study. In this study, the VIC (Variable Infiltration Capacity) model at a resolution of 0.05°, which is proven as an ideal model to reflect drought processes, was used as the hydrological model to obtain soil moisture. By analyzing the Soil Moisture Anomaly Percentage Index (SMAPI) error characteristics that were simulated based on different ICs, an uncertainty index for drought process simulation was constructed in different climate zones. It was found that with the development of a drought process, the uncertainty converges, and it decreases to within 10% after a drought occurs for 5 to 6 months, while it is less than 5% in the particular basin in a humid region. In climate transition zones, both the uncertainty and its decrease rate are greater than those in humid regions. Climate characteristics, as well as soil types and vegetation types, are fundamental factors that cause differences in drought process simulation and uncertainty changes. The precipitation and temperature distribution more obviously vary spatially and temporally, a greater uncertainty is caused by ICs. This quantitative method reveals the impact of ICs on drought process simulation in different climate regions and provides a basis for the further improvement of drought simulation and prediction based on atmospheric–hydrological coupling

W: Circulating adipocyte fatty acid-binding protein levels are independently associated with heart failure. Clin Sci 2013

Abstract A-FABP (adipocyte fatty acid-binding protein), one of the most abundant proteins in adipocytes, plays a key role in obesity-related insulin resistance, inflammation and atherosclerosis in animals. In the present study, we sought to investigate the association of A-FABP with HF (heart failure) in Chinese subjects. Serum A-FABP levels were measured in 252 HF patients and 261 age-, gender-and BMI (body mass index)-matched non-HF subjects. Echocardiography was performed on each patient. The severity of HF was determined by the NYHA (New York Heart Association) classification system. After adjustments for age, gender and BMI, serum A-FABP concentrations in patients with HF were significantly higher than in non-HF patients [11.17 (6.63-19.93) ng/ml compared with 5.67 (3.20-8.87) ng/ml; P < 0.001] and significantly progressed with the NYHA class (P < 0.001). In addition, NT-proBNP (N-terminal pro-brain natriuretic peptide) was independently and positively correlated with A-FABP (standardized β = 0.340, P < 0.001) after adjusting for confounding factors. Each echocardiographic parameter, especially LVEF (left ventricular ejection fraction), was independently associated with A-FABP (all P < 0.05). Multivariate logistic regression analysis demonstrated that A-FABP concentration was an independent risk factor for HF [odds ratio, 6.93 (95 % confidence interval, 2.49-19.30); P < 0.001]. Our results demonstrate that A-FABP is closely associated with HF, and raise the possibility that increased A-FABP may be causally related to the pathogenesis of heart dysfunction in humans

A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-Like Properties and Invasion in Human Bladder Cancer

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 blockade have been identified to target immune checkpoints to treat human cancers with durable clinical benefit. Several studies reveal that the response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells. However, the mechanistic pathways that regulate PD-L1 protein expression are not understood. Here, we reported that PD-L1 protein is regulated by ATG7-autophagy with an ATG7-initiated positive feedback loop in bladder cancer (BC). Mechanistic studies revealed that ATG7 overexpression elevates PD-L1 protein level mainly through promoting autophagy-mediated degradation of FOXO3a, thereby inhibiting its initiated miR-145 transcription. The lower expression of miR-145 increases pd-l1 mRNA stability due to the reduction of its direct binding to 3′-UTR of pd-l1 mRNA, in turn leading to increasing in pd-l1 mRNA stability and expression, and finally enhancing stem-like property and invasion of BC cells. Notably, overexpression of PD-L1 in ATG7 knockdown cells can reverse the defect of autophagy activation, FOXO3A degradation, and miR-145 transcription attenuation. Collectively, our results revealed a positive feedback loop to promoting PD-L1 expression in human BC cells. Our study uncovers a novel molecular mechanism for regulating pd-l1 mRNA stability and expression via ATG7/autophagy/FOXO3A/miR-145 axis and reveals the potential for using combination treatment with autophagy inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human BCs