bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data
Authors: Lobo João , Gillis Ad J.M. , van den Berg Annette , Dorssers Lambert C.J. , Belge Gafanzer , Dieckmann Klaus-Peter , Roest Henk P. , van der Laan Luc J.W. , Gietema Jourik , Hamilton Robert J. , Jerónimo Carmen , Henrique Rui , Salvatori Daniela , Looijenga Leendert H.J.
Published: December 2019

Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim to explore issues impeding this transition, in the setting of germ cell tumors, for which novel biomarkers are needed. We describe a model for identifying and validating clinically relevant microRNAs for germ cell tumor patients, using both in vitro, in vivo (mouse model) and patient-derived data. Initial wide screening of candidate microRNAs is performed, followed by targeted profiling of potentially relevant biomarkers. We demonstrate the relevance of appropriate (negative) controls, experimental conditions (proliferation), and issues related to sample origin (serum, plasma, cerebral spinal fluid) and pre-analytical variables (hemolysis, contaminants, temperature), all of which could interfere with liquid biopsy-based studies and their conclusions. Finally, we show the value of our identification model in a specific scenario, contradicting the presumed role of miR-375 as marker of teratoma histology in liquid biopsy setting. Our findings indicate other putative microRNAs (miR-885-5p, miR-448 and miR-197-3p) fulfilling this clinical need. The identification model is informative to identify the best candidate microRNAs to pursue in a clinical setting.
Non-Coding RNAs in IGF-1R Signaling Regulation: The Underlying Pathophysiological Link between Diabetes and Cancer
Authors: Chen Baoqing , Li Junyan , Chi Dongmei , Sahnoune Iman , Calin Steliana , Girnita Leonard , Calin George A.
Published: December 2019

The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM has been associated with several hormone-dependent malignancies, including breast, pancreatic, and colorectal cancer (CRC). Insulin resistance, hyperglycemia, and inflammation are the main pathophysiological mechanisms linking DM to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are widely appreciated as pervasive regulators of gene expression, governing the evolution of metabolic disorders, including DM and cancer. The ways ncRNAs affect the development of DM complicated with cancer have only started to be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator of pathophysiological processes directing DM and cancer. In this review, we briefly summarize a number of well-known miRNAs and lncRNAs that regulate the IGF-1R in DM and cancer, respectively, and further discuss the potential underlying molecular pathogenesis of this disease association.
Copresentation of BMP-6 and RGD Ligands Enhances Cell Adhesion and BMP-Mediated Signaling
Authors: Posa Francesca , Grab Anna Luise , Martin Volker , Hose Dirk , Seckinger Anja , Mori Giorgio , Vukicevic Slobodan , Cavalcanti-Adam Elisabetta Ada
Published: December 2019

We report on the covalent immobilization of bone morphogenetic protein 6 (BMP-6) and its co-presentation with integrin ligands on a nanopatterned platform to study cell adhesion and signaling responses which regulate the transdifferentiation of myoblasts into osteogenic cells. To immobilize BMP-6, the heterobifunctional linker MU-NHS is coupled to amine residues of the growth factor; this prevents its internalization while ensuring that its biological activity is maintained. Additionally, to allow cells to adhere to such platform and study signaling events arising from the contact to the surface, we used click-chemistry to immobilize cyclic-RGD carrying an azido group reacting with PEG-alkyne spacers via copper-catalyzed 1,3-dipolar cycloaddition. We show that the copresentation of BMP-6 and RGD favors focal adhesion formation and promotes Smad 1/5/8 phosphorylation. When presented in low amounts, BMP-6 added to culture media of cells adhering to the RGD ligands is less effective than BMP-6 immobilized on the surfaces in inducing Smad complex activation and in inhibiting myotube formation. Our results suggest that a local control of ligand density and cell signaling is crucial for modulating cell response.
Uptake of Pb(II) Ions from Simulated Aqueous Solution via Nanochitosan
Authors: Zareie Camellia , Kholghi Eshkalak Saeideh , Najafpour Darzi Ghasem , Sharifzadeh Baei Mazyar , Younesi Habibollah , Ramakrishna Seeram
Published: December 2019

In this work, nanochitosan (NC) was prepared through ionic gelation using low molecular weight chitosan and maleic acid (MA). The synthesized NC was characterized by atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During preparation, the particle size of the material depended on parameters such as concentration of chitosan and pH of the aqueous solution. After controlling the mentioned parameters, NC smaller than 100 nm was prepared. The chitosan and prepared NC were employed for the adsorption of Pb(II) from an aqueous solution in the form of a batch system. Among the sorption parameters, pH showed the strongest effect on the sorption process and removal of the maximum number of Pb(II) ions was obtained at pH value of 6. Pseudo-first-order and pseudo-second-order models were used to track the kinetics of the adsorption process. Langmuir and Freundlich’s isotherms were subjected to the absorption data to evaluate absorption capacity. NC proved to be an excellent adsorbent with a remarkable capacity to eliminate Pb(II) ions from aqueous solutions at multiple concentrations. The NC also showed better performance with a comparatively easier preparation process than in other reported work.
Alterations of Cardiovascular Complexity during Acute Exposure to High Altitude: A Multiscale Entropy Approach
Authors: Faini Andrea , Caravita Sergio , Parati Gianfranco , Castiglioni Paolo
Published: December 2019

Stays at high altitude induce alterations in cardiovascular control and are a model of specific pathological cardiovascular derangements at sea level. However, high-altitude alterations of the complex cardiovascular dynamics remain an almost unexplored issue. Therefore, our aim is to describe the altered cardiovascular complexity at high altitude with a multiscale entropy (MSE) approach. We recorded the beat-by-beat series of systolic and diastolic blood pressure and heart rate in 20 participants for 15 min twice, at sea level and after arrival at 4554 m a.s.l. We estimated Sample Entropy and MSE at scales of up to 64 beats, deriving average MSE values over the scales corresponding to the high-frequency (MSEHF) and low-frequency (MSELF) bands of heart-rate variability. We found a significant loss of complexity at heart-rate and blood-pressure scales complementary to each other, with the decrease with high altitude being concentrated at Sample Entropy and at MSEHF for heart rate and at MSELF for blood pressure. These changes can be ascribed to the acutely increased chemoreflex sensitivity in hypoxia that causes sympathetic activation and hyperventilation. Considering high altitude as a model of pathological states like heart failure, our results suggest new ways for monitoring treatments and rehabilitation protocols.
Entropy of the Multi-Channel EEG Recordings Identifies the Distributed Signatures of Negative, Neutral and Positive Affect in Whole-Brain Variability
Authors: Keshmiri Soheil , Shiomi Masahiro , Ishiguro Hiroshi
Published: December 2019

Individuals’ ability to express their subjective experiences in terms of such attributes as pleasant/unpleasant or positive/negative feelings forms a fundamental property of their affect and emotion. However, neuroscientific findings on the underlying neural substrates of the affect appear to be inconclusive with some reporting the presence of distinct and independent brain systems and others identifying flexible and distributed brain regions. A common theme among these studies is the focus on the change in brain activation. As a result, they do not take into account the findings that indicate the brain activation and its information content does not necessarily modulate and that the stimuli with equivalent sensory and behavioural processing demands may not necessarily result in differential brain activation. In this article, we take a different stance on the analysis of the differential effect of the negative, neutral and positive affect on the brain functioning in which we look into the whole-brain variability: that is the change in the brain information processing measured in multiple distributed regions. For this purpose, we compute the entropy of individuals’ muti-channel EEG recordings who watched movie clips with differing affect. Our results suggest that the whole-brain variability significantly differentiates between the negative, neutral and positive affect. They also indicate that although some brain regions contribute more to such differences, it is the whole-brain variational pattern that results in their significantly above chance level prediction. These results imply that although the underlying brain substrates for negative, neutral and positive affect exhibit quantitatively differing degrees of variability, their differences are rather subtly encoded in the whole-brain variational patterns that are distributed across its entire activity.
A New Approach to Fuzzy TOPSIS Method Based on Entropy Measure under Spherical Fuzzy Information
Authors: Barukab Omar , Abdullah Saleem , Ashraf Shahzaib , Arif Muhammad , Khan Sher Afzal
Published: December 2019

Spherical fuzzy set (SFS) is one of the most important and extensive concept to accommodate more uncertainties than existing fuzzy set structures. In this article, we will describe a novel enhanced TOPSIS-based procedure for tackling multi attribute group decision making (MAGDM) issues under spherical fuzzy setting, in which the weights of both decision-makers (DMs) and criteria are totally unknown. First, we study the notion of SFSs, the score and accuracy functions of SFSs and their basic operating laws. In addition, defined the generalized distance measure for SFSs based on spherical fuzzy entropy measure to compute the unknown weights information. Secondly, the spherical fuzzy information-based decision-making technique for MAGDM is presented. Lastly, an illustrative example is delivered with robot selection to reveal the efficiency of the proposed spherical fuzzy decision support approach, along with the discussion of comparative results, to prove that their results are feasible and credible.
Detecting Causality in Multivariate Time Series via Non-Uniform Embedding
Authors: Jia Ziyu , Lin Youfang , Jiao Zehui , Ma Yan , Wang Jing
Published: December 2019

Causal analysis based on non-uniform embedding schemes is an important way to detect the underlying interactions between dynamic systems. However, there are still some obstacles to estimating high-dimensional conditional mutual information and forming optimal mixed embedding vector in traditional non-uniform embedding schemes. In this study, we present a new non-uniform embedding method framed in information theory to detect causality for multivariate time series, named LM-PMIME, which integrates the low-dimensional approximation of conditional mutual information and the mixed search strategy for the construction of the mixed embedding vector. We apply the proposed method to simulations of linear stochastic, nonlinear stochastic, and chaotic systems, demonstrating its superiority over partial conditional mutual information from mixed embedding (PMIME) method. Moreover, the proposed method works well for multivariate time series with weak coupling strengths, especially for chaotic systems. In the actual application, we show its applicability to epilepsy multichannel electrocorticographic recordings.
Causal Random Forests Model Using Instrumental Variable Quantile Regression
Authors: Chen Jau-er , Hsiang Chen-Wei
Published: December 2019

We propose an econometric procedure based mainly on the generalized random forests method. Not only does this process estimate the quantile treatment effect nonparametrically, but our procedure yields a measure of variable importance in terms of heterogeneity among control variables. We also apply the proposed procedure to reinvestigate the distributional effect of 401(k) participation on net financial assets, and the quantile earnings effect of participating in a job training program.
Runner Lifting-Up during Load Rejection Transients of a Kaplan Turbine: Flow Mechanism and Solution
Authors: Liu Ke , Yang Feng , Yang Zhiyan , Zhu Yunxian , Cheng Yongguang
Published: December 2019

Dangerous runner lifting-up (RLU) accidents regarding Kaplan turbines, which are widely used in low-head hydropower stations, were frequently reported. Three-dimensional (3D) computational fluid dynamics (CFD) was used to simulate the load rejection transients with guide-vane closing to predict the RLU possibility of the fixed-blade Kaplan turbine in an under-construction hydropower station. It was found that using any linear closing rule, the upward axial water force on the runner was larger than the weight of rotating parts that started before the guide-vanes were closed, which indicated a RLU possibility. It was the pumping effect that caused the imbalance, during which the high rotational speed runner propels water downstream with a low discharge. We proposed a piecewise closing rule based on this finding. By keeping the opening unchanged in a period in the closing process, the rotational speed can be reduced by using the braking effect, and the concurrence of high speed and low discharge can be prevented. Simulations verified this effective measure and accepted by the manufacturer. Although this study used a fixed-blade Kaplan turbine, the revealed mechanism and verified solution to the RLU problem have reference value for all of the Kaplan turbines.
Profitability Analysis and Capital Cost Estimation of a Thermochemical Energy Storage System Utilizing Fluidized Bed Reactors and the Reaction System MgO/Mg(OH)2
Authors: Flegkas Stylianos , Birkelbach Felix , Winter Franz , Groenewold Hans , Werner Andreas
Published: December 2019

The storage of industrial waste heat through thermochemical energy storage (TCES) shows high potential to reduce the dependency on fossil fuels. In this paper the capital cost investment of a TCES system utilizing fluidized bed reactors and the reaction system MgO/Mg(OH) 2 is estimated and a profitability analysis is performed. The study estimate is based on a simulation study that considers the mass and energy balance of the proposed preliminary heat storage and release processes utilizing fluidized bed reactors. Furthermore, transport, operation and maintenance as well as utility costs were estimated in order to evaluate the profitability of the system. It is concluded that for the selected boundary conditions, the specific investment costs per kW stored heat are approximately 900 €/kW and that the systems should not be installed at sites where less than around 5 MW of waste heat are available. Finally, a sensitivity analysis was conducted, to identify the key process and economic parameters critical for a positive net present value.
Formation of Conductive Oxide Scale on 33NK and 47ND Interconnector Alloys for Solid Oxide Fuel Cells
Authors: Eremin V.A. , Solodyankin A.A. , Belyakov S.A. , Khodimchuk A.V. , Farlenkov A.S. , Krainova D.A. , Saetova N.S. , Kuzmin A.V. , Artamonov A.S. , Steinberger-Wilckens R. , Ananyev M.V.
Published: December 2019

: Two grades of chromium-free alloys were studied in order to apply them as interconnectors for solid oxide fuel cells. The surface modification methods were proposed for each alloy with the purpose of forming of oxide scales considering the required physicochemical properties. Investigations of the structure and properties of the obtained oxide scales were performed and the efficiency of the chosen surface modification methods was approved. The samples with the surface modification exhibited higher conductivity values in comparison with the nonmodified samples. A compatibility study of samples with surface modification and glass sealant of chosen composition was accomplished. The modified samples demonstrated good adhesion during testing and electrical resistance less than 40 mOhm/cm2 at 850 °C in air, which allowed us to recommend these alloys with respective modified oxide scales as interconnectors for SOFC.
Analysis and Introduction of Effective Permeability with Additional Air-Gaps on Wireless Power Transfer Coils for Electric Vehicle Based on SAE J2954 Recommended Practice
Authors: Kim Dongwook , Kim Hongseok , Huang Anfeng , He Qiusen , Zhang Hanyu , Ahn Seungyoung , Zhu Yuyu , Fan Jun
Published: December 2019

The wireless power transfer (WPT) method for electric vehicles (EVs) is becoming more popular, and to ensure the interoperability of WPT systems, the Society of Automotive Engineers (SAE) established the J2954 recommended practice (RP). It includes powering frequency, electrical parameters, specifications, testing procedures, and other contents for EV WPT. Specifically, it describes the ranges of self-inductances of the transmitting coil, the receiving coil, and coupling coefficient (k), as well as the impedance matching values of the WPT system. Following the electrical parameters listed in SAE J2954 RP is crucial to ensure the EV wireless charging system is interoperable. This paper introduces a method for adjusting the effective permeability of the ferrite blocks in the standard model, to tune the self-inductance of the coils as well as the coupling coefficient. To guarantee the given values of the self-inductance of the coil and coupling coefficient matched those in the standard, we slightly modified the air-gap between the ferrite tiles in a specific region. Based on this method, it was possible to successfully tune the self-inductance of the transmitting coil and receiving coil as well as the coupling coefficient. The proposed method was verified by simulation and experimental measurements.
Multifunctional Distributed MPPT Controller for 3P4W Grid-Connected PV Systems in Distribution Network with Unbalanced Loads
Authors: Ahmed Emad M. , Aly Mokhtar , Elmelegi Ahmed , Alharbi Abdullah G. , Ali Ziad M.
Published: December 2019

The integration of photovoltaic (PV) systems with three-phase four-wire (3P4W) distribution networks has imposed several challenges related to existing unbalanced loads, reactive power generation and harmonics content. In this paper, a multifunctional distributed maximum power point (MPPT) controller for grid integration of PV systems is proposed. The proposed distributed MPPT controller is developed based on employing a four-leg three-level T-type multilevel inverter. The proposed inverter performs multifunctionalities, including distributed MPPT, neutral current compensation for the unbalanced loads, supplying reactive power into the grid and the grid integration. Moreover, the proposed inverter overcomes the stochastic behavior of both the PV generation with partial shading problems and its operation with unbalanced loads as well. Furthermore, the new proposed controller injects sinusoidal output currents with decreased levels of total harmonic distortion (THD) into the grid. The tested case study is investigated for the various operating scenarios of PV generation and load demands. The results and tabulated performance comparisons have proven the superior performance of the proposed multifunctional PV generation system. The results show the ability of the proposed controller to efficiently extract distributed MPPT for all PV modules at all the tested scenarios. Additional improvement of the energy efficiency is achieved through the elimination of the neutral current due to existing unbalanced loads.
The Impact of Economic Growth, FDI and Energy Intensity on China’s Manufacturing Industry’s CO2 Emissions: An Empirical Study Based on the Fixed-Effect Panel Quantile Regression Model
Authors: Ma Chao-Qun , Liu Jiang-Long , Ren Yi-Shuai , Jiang Yong
Published: December 2019

Since the reform and opening-up, China’s CO2 emissions have increased dramatically, and it has become the world’s largest CO2 emission and primary energy consumption country. The manufacturing industry is one of the biggest contributors to CO2 emission, and determining the drivers of CO2 emissions are essential for effective environmental policy. China is also a vast transition economy with great regional differences. Therefore, based on the data of China’s provincial panel from 2000 to 2013 and the improved STIRPAT model, this paper studies the impact of economic growth, foreign direct investment (FDI) and energy intensity on China’s manufacturing carbon emissions through the fixed-effect panel quantile regression model. The results show that the effects of economic growth, FDI and energy intensity on carbon emissions of the manufacturing industry are different in different levels and regions, and they have apparent heterogeneity. In particular, economic growth plays a decisive role in the CO2 emissions of the manufacturing industry. Economic growth has a positive impact on the carbon emissions of the manufacturing industry; specifically, a higher impact on high carbon emission provinces. Besides, FDI has a significant positive effect on the upper emission provinces of the manufacturing industry, which proves that there is a pollution paradise hypothesis in China’s manufacturing industry, but no halo effect hypothesis. The reduction of energy intensity does not have a positive effect on the reduction of carbon emissions. The higher impact of the energy intensity of upper emission provinces on carbon emissions from their manufacturing industry, shows that there is an energy rebound effect in China’s manufacturing industry. Finally, our study confirms that China’s manufacturing industry has considerable space for emission reduction. The results also provide policy recommendations for policymakers.
Assessing the Impact of Ozone on Forest Trees in An Integrative Perspective: Are Foliar Visible Symptoms Suitable Predictors for Growth Reduction? A Critical Review
Authors: Marzuoli Riccardo , Gerosa Giacomo , Bussotti Filippo , Pollastrini Martina
Published: December 2019

Plant growth reduction (GR) is the most widely accepted damage parameter to assess the sensitivity of trees to tropospheric ozone (O3) pollution since it integrates different physiological processes leading to loss of photosynthetic activity and distraction of metabolic resources from growth to defense, repair, and recovery pathways. Because of the intrinsic difficulty to assess the actual O3 risk assessment for forests in field conditions, foliar visible symptoms (FVS) induced by O3 have been proposed as a proxy to estimate possible GR in forest trees. The rationale for this assumption is that the onset of FVS implies a reduction of the photosynthetic capacity of plants. In this review, we show that GR and FVS can be the consequences of independent physiological pathways involving different response mechanisms that can cause both FVS without GR and GR without FVS. The onset of FVS may not lead necessarily to significant GR at plant level for several reasons, including the rise of compensatory photosynthesis, the time lag between growth processes and the accumulation of critical O3 dose, and the negligible effect of a modest amount of injured leaves. Plant GR, on the other hand, may be induced by different physiological mechanisms not necessarily related to FVS, such as stomatal closure (i.e., carbon starvation) to avoid or reduce O3 uptake, and the increase of respiratory processes for the production of metabolic defense compounds. Growth reduction and FVS can be interpreted as different strategies for the acclimation of plants to a stressful environment, and do not mean necessarily damage. Growth reduction (without FVS) seems to prevail in species adapted to limiting environmental conditions, that avoid loss and replacement of injured leaves because of the high metabolic cost of their production; conversely, FVS manifestation (without GR) and the replacement of injured leaves is more common in species adapted to environments with low-stress levels, since they can benefit from a rapid foliar turnover to compensate for the decreased rate of photosynthesis of the whole plant.
Dependable and Secure Voting Mechanism in Edge Computing
Authors: Costa Pedro A.R.S. , Beko Marko
Published: December 2019

Edge computing is a distributed computing paradigm that encompasses data computing and storage and is performed close to the user, efficiently guaranteeing faster response time. This paradigm plays a pivotal role in the world of the Internet of Things (IoT). Moreover, the concept of the distributed edge cloud raises several interesting open issues, e.g., failure recovery and security. In this paper, we propose a system composed of edge nodes and multiple cloud instances, as well as a voting mechanism. The multi-cloud environment aims to perform centralized computations, and edge nodes behave as a middle layer between edge devices and the cloud. Moreover, we present a voting mechanism that leverages the edge network to validate the performed computation that occurred in the centralized environment.
Transcriptome Profiling, Biochemical and Physiological Analyses Provide New Insights towards Drought Tolerance in Nicotiana tabacum L.
Authors: Khan Rayyan , Zhou Peilu , Ma Xinghua , Zhou Lei , Wu Yuanhua , Ullah Zia , Wang Shusheng
Published: December 2019

Drought stress is one of the main factors limiting crop production, which provokes a number of changes in plants at physiological, anatomical, biochemical and molecular level. To unravel the various mechanisms underpinning tobacco (Nicotiana tabacum L.) drought stress tolerance, we conducted a comprehensive physiological, anatomical, biochemical and transcriptome analyses of three tobacco cultivars (i.e., HongHuaDaJinYuan (H), NC55 (N) and Yun Yan-100 (Y)) seedlings that had been exposed to drought stress. As a result, H maintained higher growth in term of less reduction in plant fresh weight, dry weight and chlorophyll content as compared with N and Y. Anatomical studies unveiled that drought stress had little effect on H by maintaining proper leaf anatomy while there were significant changes in the leaf anatomy of N and Y. Similarly, H among the three varieties was the least affected variety under drought stress, with more proline content accumulation and a powerful antioxidant defense system, which mitigates the negative impacts of reactive oxygen species. The transcriptomic analysis showed that the differential genes expression between HongHuaDaJinYuan, NC55 and Yun Yan-100 were enriched in the functions of plant hormone signal transduction, starch and sucrose metabolism, and arginine and proline metabolism. Compared to N and Y, the differentially expressed genes of H displayed enhanced expression in the corresponding pathways under drought stress. Together, our findings offer insights that H was more tolerant than the other two varieties, as evidenced at physiological, biochemical, anatomical and molecular level. These findings can help us to enhance our understanding of the molecular mechanisms through the networks of various metabolic pathways mediating drought stress adaptation in tobacco.
Rock Mass Behavior under Tunnel Widening in Asymmetric and Symmetric Modes Considering Different Shapes and Parametric Conditions
Authors: Khan Babar , Jamil Syed Muhammad , Kim Jung Joo , Jafri Turab H. , Kim Jonguk
Published: December 2019

To accommodate traffic volume on roads due to ever-increasing population growth, the widening of highways and motorways is in high demand. Nevertheless, the widening of tunnels on these road networks is quite complex due to the presence of numerous rock types, in situ stress, and different widening modes. To overcome these complexities, eight different tunnel shapes were simulated under varying support conditions for asymmetric and symmetric widening. It was found that the tunnels with a round shape, such as horseshoe and semicircular with flatbed, are more effective for asymmetric widening, whereas the provision of a rounded invert in these shapes can reverse the widening option to symmetric. Furthermore, an insignificant effect of the difference in asymmetric and symmetric widening of regular tunnel shapes, such as box, rectangular, and semi-elliptical, was found. A full factorial design statistical analysis confirmed the decrease in tunnel deformation by using various tunnel support systems and showed a significant deformation difference according to monitoring locations at the tunnel periphery. The deformation difference in the case of both tunnel widening modes was also analyzed according to different design parameters. This study provides a comprehensive understanding of rock mass behavior when the widening of any underground opening is carried out.
Associations of Residential Greenness with Diabetes Mellitus in Chinese Uyghur Adults
Authors: Fan Shujun , Xue Zhenxiang , Yuan Jun , Zhou Ziyan , Wang Yuzhong , Yang Zhicong , Yang Boyi , Dong Guanghui , Zhang Zhoubin
Published: December 2019

Greenness exposure is nominated as a potential beneficial factor for health, but evidence is limited on its diabetes effects. We conducted a cross-sectional study between May and September 2016 in rural areas of northwestern China, including 4670 Uyghur adults, to explore the associations between residential greenness and fasting glucose levels and diabetes prevalence. Fasting glucose levels were determined, and information on covariates was collected by questionnaire. Normalized difference vegetation index (NDVI) and soil-adjusted vegetation index (SAVI) were calculated to assess greenness levels. Generalized linear mixed models were applied to evaluate the associations of greenness with fasting glucose levels and diabetes prevalence. The prevalence of diabetes was 11.6%. We found that living in rural areas characterized by increased amounts of greenness was associated with reduced diabetes prevalence (e.g., NDVI1000m: OR, 0.92; 95% CI, 0.86, 0.99). Stratified analyses showed that the protective effects of greenness on diabetes prevalence were found only in women (NDVI1000m: OR, 0.90; 95% CI, 0.82, 0.99). However, none of the interaction was statistically significant. Our study suggests that greater residential greenness levels were associated with a lower odds ratio of diabetes prevalence in Xinjiang Uyghur adults. Further well-designed longitudinal studies are needed to confirm our findings.
Numerical Simulation of Flow and Temperature Fields in a Deep Stratified Reservoir Using Water-Separating Curtain
Authors: Zhang Lifang , Zhang Jianmin , Peng Yong , Pan Jiangyang , Peng Zhongxian
Published: December 2019

In this work, the flow and temperature fields of a thermally stratified reservoir under different settings of a water-separating curtain are simulated by using the standard k-ε turbulence model. In the simulation, two different equations of state including Boussinesq approximation and the density-temperature function have been used and compared. This study shows that Boussinesq approximation is more time-saving, and the density-temperature function has higher computational accuracy. Thus, the standard k-ε turbulence model with two equations of state is applied to study the effect of adding a water-separating curtain in the stratified reservoir on the Discharged Water Temperature (DWT). It is found that adding the Water-Separating Curtain (WSC) can effectively increase the discharged water temperature. Moreover, the different arrangements of WSC have obvious effects on the discharged water temperature. For example, the increased temperature by adding a WSC with full sealing is 1 °C higher than that by using the WSC with a bottom opening height of 2 m. However, the maximum pressure difference acting on the WSC for the former WSC is 100 Pa higher than that for the latter WSC. In addition, this study shows that the different equations of state have little effect on the simulation results. Considering the calculation efficiency, equations of state using the Boussinesq approximation can be recommended to save the calculation time.
Altered Metabolic Profile and Adipocyte Insulin Resistance Mark Severe Liver Fibrosis in Patients with Chronic Liver Disease
Authors: Gaggini Melania , Carli Fabrizia , Rosso Chiara , Younes Ramy , D’Aurizio Romina , Bugianesi Elisabetta , Gastaldelli Amalia
Published: December 2019

Metabolomics/lipidomics are important tools to identify novel biomarkers associated with liver damage. Patients with chronic liver disease (CLD) and hepatitis C virus (HCV) infection often have alterations in glucose, lipid and protein metabolism. The aim of this study was to evaluate if dysfunctional lipid and amino acid metabolism was associated with fibrosis severity and insulin resistance in CLD/HCV patients. We analyzed the baseline sera of 75 subjects with CLD/HCV infection HCV genotype-1, with proven liver biopsy prior to antiviral treatment. We measured amino acid (AA) and lipid concentration by gas and liquid chromatography-mass spectrometry respectively. Alterations in peripheral glucose metabolism due to insulin resistance (IR) were assesed by HOMA-IR (Glucose x Insulin/22.5), while adipose tissue IR was estimated as (Adipo-IR = Free Fatty Acids x Insulin). Baseline HOMA-IR and Adipo-IR were related to the degree of liver fibrosis. Reduction in ceramides 18:1/22:0, 18:1/24:0, diacylglycerol 42:6 and increased phosphocholine 40:6 were associated with higher fibrosis. Adipo-IR was related to lower levels of lysophosphatidylcholine 14:0 and 18:2 and with higher levels of sphingomyelin 18:2/24:0 and 18:2/24:1. Almost all AA were positively associated with Adipo-IR but not with HOMA-IR. We further confirmed the potential use of metabolomics and lipidomics in CLD/HCV subjects finding novel biomarkers of hepatic fibrosis and show that the adipose tissue IR is associated with more severe liver disease and is an important marker not only of altered lipid but also AA metabolism.
Inducible Nitric Oxide Synthase (iNOS) Mediates Vascular Endothelial Cell Apoptosis in Grass Carp Reovirus (GCRV)-Induced Hemorrhage
Authors: Liang Bo , Su Jianguo
Published: December 2019

Hemorrhage is one of the most obvious pathological phenomena in grass carp reovirus (GCRV) infection. The etiology of GCRV-induced hemorrhage is unclear. We found inducible nitric oxide synthase (iNOS) may relate to viral hemorrhage according to the previous studies, which is expressed at high levels after GCRV infection and is related to apoptosis. In this study, we aimed to investigate the mechanism of iNOS on apoptosis and hemorrhage at the cell level and individual level on subjects who were infected with GCRV and treated with S-methylisothiourea sulfate (SMT), an iNOS inhibitor. Cell structure, apoptosis rate, and hemorrhage were evaluated through fluorescence microscopy, Annexin V-FITC staining, and H&E staining, respectively. Cell samples and muscle tissues were collected for Western blotting, NO concentration measure, caspase activity assay, and qRT-PCR. iNOS-induced cell apoptosis and H&E staining showed that the vascular wall was broken after GCRV infection in vivo. When the function of iNOS was inhibited, NO content, apoptosis rate, caspase activity, and hemorrhage were reduced. Collectively, these results suggested iNOS plays a key role in apoptosis of vascular endothelial cells in GCRV-induced hemorrhage. This study is the first to elucidate the relationship between iNOS-induced cell apoptosis and GCRV-induced hemorrhage, which lays the foundation for further mechanistic research of virus-induced hemorrhage.
The Puzzling Role of Neuron-Specific PMCA Isoforms in the Aging Process
Authors: Boczek Tomasz , Radzik Tomasz , Ferenc Bozena , Zylinska Ludmila
Published: December 2019

The aging process is a physiological phenomenon associated with progressive changes in metabolism, genes expression, and cellular resistance to stress. In neurons, one of the hallmarks of senescence is a disturbance of calcium homeostasis that may have far-reaching detrimental consequences on neuronal physiology and function. Among several proteins involved in calcium handling, plasma membrane Ca2+-ATPase (PMCA) is the most sensitive calcium detector controlling calcium homeostasis. PMCA exists in four main isoforms and PMCA2 and PMCA3 are highly expressed in the brain. The overall effects of impaired calcium extrusion due to age-dependent decline of PMCA function seem to accumulate with age, increasing the susceptibility to neurotoxic insults. To analyze the PMCA role in neuronal cells, we have developed stable transfected differentiated PC12 lines with down-regulated PMCA2 or PMCA3 isoforms to mimic age-related changes. The resting Ca2+ increased in both PMCA-deficient lines affecting the expression of several Ca2+-associated proteins, i.e., sarco/endoplasmic Ca2+-ATPase (SERCA), calmodulin, calcineurin, GAP43, CCR5, IP3Rs, and certain types of voltage-gated Ca2+ channels (VGCCs). Functional studies also demonstrated profound changes in intracellular pH regulation and mitochondrial metabolism. Moreover, modification of PMCAs membrane composition triggered some adaptive processes to counterbalance calcium overload, but the reduction of PMCA2 appeared to be more detrimental to the cells than PMCA3.
Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle
Authors: Gatien Julie , Mermillod Pascal , Tsikis Guillaume , Bernardi Ophélie , Janati Idrissi Sarah , Uzbekov Rustem , Le Bourhis Daniel , Salvetti Pascal , Almiñana Carmen , Saint-Dizier Marie
Published: December 2019

Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts ipsilateral and contralateral to ovulation at four stages of the estrous cycle (post-ovulatory stage, early and late luteal phases, and pre-ovulatory stage). The metabolomic profiling of EVs was performed by proton nuclear magnetic resonance spectroscopy (NMR). NMR identified 22 metabolites in oEVs, among which 15 were quantified. Lactate, myoinositol, and glycine were the most abundant metabolites throughout the estrous cycle. The side relative to ovulation had no effect on the oEVs’ metabolite concentrations. However, levels of glucose-1-phosphate and maltose were greatly affected by the cycle stage, showing up to 100-fold higher levels at the luteal phase than at the peri-ovulatory phases. In contrast, levels of methionine were significantly higher at peri-ovulatory phases than at the late-luteal phase. Quantitative enrichment analyses of oEV-metabolites across the cycle evidenced several significantly regulated metabolic pathways related to sucrose, glucose, and lactose metabolism. This study provides the first metabolomic characterization of oEVs, increasing our understanding of the potential role of oEVs in promoting fertilization and early embryo development.
Genetic and Physiological Dissection of Photosynthesis in Barley Exposed to Drought Stress
Authors: Daszkowska-Golec Agata , Collin Anna , Sitko Krzysztof , Janiak Agnieszka , Kalaji Hazem M. , Szarejko Iwona
Published: December 2019

Balanced photosynthesis under drought is essential for better survival and for agricultural benefits in terms of biomass and yield. Given the current attempts to improve the photosynthetic efficiency for greater crop yield, the explanation of the genetic basis of that process, together with the phenotypic analysis, is significant in terms of both basic studies and potential agricultural application. Therefore, the main objective of this study was to uncover the molecular basis of the photosynthesis process under drought stress in barley. To address that goal, we conducted transcriptomic examination together with detailed photosynthesis analysis using the JIP-test. Using this approach, we indicated that photosynthesis is a process that is very early affected in barley seedlings treated with severe drought stress. Rather than focusing on individual genes, our strategy was pointed to the identification of groups of genes with similar expression patterns. As such, we identified and annotated almost 150 barley genes as crucial core-components of photosystems, electron transport components, and Calvin cycle enzymes. Moreover, we designated 17 possible regulatory interactions between photosynthesis-related genes and transcription factors in barley. Summarizing, our results provide a list of candidate genes for future genetic research and improvement of barley drought tolerance by targeting photosynthesis.
The Roles of Auxin Biosynthesis YUCCA Gene Family in Plants
Authors: Cao Xu , Yang Honglei , Shang Chunqiong , Ma Sang , Liu Li , Cheng Jialing
Published: December 2019

Auxin plays essential roles in plant normal growth and development. The auxin signaling pathway relies on the auxin gradient within tissues and cells, which is facilitated by both local auxin biosynthesis and polar auxin transport (PAT). The TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAA)/YUCCA (YUC) pathway is the most important and well-characterized pathway that plants deploy to produce auxin. YUCs function as flavin-containing monooxygenases (FMO) catalyzing the rate-limiting irreversible oxidative decarboxylation of indole-3-pyruvate acid (IPyA) to form indole-3-acetic acid (IAA). The spatiotemporal dynamic expression of different YUC gene members finely tunes the local auxin biosynthesis in plants, which contributes to plant development as well as environmental responses. In this review, the recent advances in the identification, evolution, molecular structures, and functions in plant development and stress response regarding the YUC gene family are addressed.
Preventive Effects of Pyungwi-san against Dextran Sulfate Sodium- and Clostridium difficile-Induced Inflammatory Bowel Disease in Mice
Authors: Yang Meng , Bose Shambhunath , Lim Soo-Kyoung , Kim Hojun
Published: December 2019

Several lines of evidence indicate that inflammatory bowel disease (IBD) is associated with Clostridium difficile (CD) infection as a consequence of gut dysbiosis. Currently available treatments of IBD are either not very effective or have adverse effects. Pyungwi-san (PWS), a traditional Chinese herbal formulation, has long been used to treat gastrointestinal disorders. The present study was conducted to investigate the efficacy of PWS against dextran sulfate sodium (DSS) + CD-induced IBD in mice. The animals received DSS in drinking water for seven days to produce DSS-induced acute colitis. In the DSS + CD group, the DSS-fed animals were orally administered with CD spores twice during the DSS treatment period. We observed that exposure of DSS + CD-treated animals to PWS significantly decreased the disease activity index; prevented the shortening of colonic length and increases in spleen size and weight; restored colonic histological parameters by significantly increasing mucus thickness, crypt depth, and goblet cell numbers; protected the tight junction proteins; improved the profiles of pro-inflammatory and anti-inflammatory cytokines; and normalized the abundance ratio of the Firmicutes/Bacteroidetes in the gut. Thus, PWS exerted a number of protective effects on DSS + CD-induced colitis, which might be mediated via restoration of a balance in gut microbial communities.
Integrated Transcriptomics, Metabolomics, and Lipidomics Profiling in Rat Lung, Blood, and Serum for Assessment of Laser Printer-Emitted Nanoparticle Inhalation Exposure-Induced Disease Risks
Authors: Guo Nancy Lan , Poh Tuang Yeow , Pirela Sandra , Farcas Mariana T. , Chotirmall Sanjay H. , Tham Wai Kin , Adav Sunil S. , Ye Qing , Wei Yongyue , Shen Sipeng , Christiani David C. , Ng Kee Woei , Thomas Treye , Qian Yong , Demokritou Philip
Published: December 2019

Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently reported exposure to PEPs induces adverse cardiovascular responses including hypertension and arrythmia via monitoring left ventricular pressure and electrocardiogram in rats. This study employed genome-wide mRNA and miRNA profiling in rat lung and blood integrated with metabolomics and lipidomics profiling in rat serum to identify biomarkers for assessing PEPs-induced disease risks. Whole-body inhalation of PEPs perturbed transcriptional activities associated with cardiovascular dysfunction, metabolic syndrome, and neural disorders at every observed time point in both rat lung and blood during the 21 days of exposure. Furthermore, the systematic analysis revealed PEPs-induced transcriptomic changes linking to other disease risks in rats, including diabetes, congenital defects, auto-recessive disorders, physical deformation, and carcinogenesis. The results were also confirmed with global metabolomics profiling in rat serum. Among the validated metabolites and lipids, linoleic acid, arachidonic acid, docosahexanoic acid, and histidine showed significant variation in PEPs-exposed rat serum. Overall, the identified PEPs-induced dysregulated genes, molecular pathways and functions, and miRNA-mediated transcriptional activities provide important insights into the disease mechanisms. The discovered important mRNAs, miRNAs, lipids and metabolites may serve as candidate biomarkers for future occupational and medical surveillance studies. To the best of our knowledge, this is the first study systematically integrating in vivo, transcriptomics, metabolomics, and lipidomics to assess PEPs inhalation exposure-induced disease risks using a rat model.
Novel Aspects of CPAP Treatment and Interventions to Improve CPAP Adherence
Authors: Weaver Terri E.
Published: December 2019

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea. However, the success of this treatment is hampered by nonadherence in half of the treated patients. Moreover, in clinical trials, poor adherence reduces adequate exposure required to determine its true effect. There is growing evidence that behavioral interventions, in addition to education, are a promising approach to improving adherence. Behavioral interventions include the use of cognitive behavioral therapy and motivational enhancement therapy designed to elevate a patient’s self-efficacy. The abundance of data obtained by CPAP tracking systems enables daily surveillance of use, and this telemonitoring along with telehealth allows the provider to quickly intervene when nightly CPAP use falls below thresholds or mask leaks are present. Telehealth reaches a large number of patients who may not be able to regularly attend a clinic, providing support and reinforcement. Peer support may also be useful in improving adherence. Not all obstructive sleep apnea patients present with the same phenotype, and can, therefore, be clustered into several groupings. Which intervention is most successful with a given phenotype or cluster remains unexplored. Comprehensive adherence management requires a team approach with the unique contribution of different professionals.