bluuebunny/crossref_metadata_2025 huggingface dataset:
Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways
Authors: Peserico Denise , Stranieri Chiara , Garbin Ulisse , Mozzini C Chiara , Danese Elisa , Cominacini Luciano , Fratta Pasini Anna M.
Published: April 2020

Background: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). Methods: Cultured cells were subjected to simulated IR with or without Ezetimibe. Results: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. Conclusions: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation.
Development of a Pyrometer That Measures the True Temperature Field of the Two-Dimensional Array
Authors: Sun Bojun , Sun Xiaogang , Luan Meisheng , Dai Jingmin , Cui Shuanglong
Published: April 2020

This paper develops a two-dimensional array pyrometer, which can measure the true temperature field of the two-dimensional array. The pyrometer consists of an optical part, a circuit part and a software part. In the optical part, the radiation energy of the two-dimensional array target is obtained by scanning with the rotating mirror. Then, the radiation signal is converted and amplified by the circuit part. The software component realizes the functions of the pyrometer calibration, signal acquisition and data processing. The data processing adopts the secondary measurement method to calculate the true temperature and uses the multi-threaded method to improve the operational efficiency. Experiments show that the uncertainty of the two-dimensional pyrometer array can reach 1.43%. Compared with the single-threaded method, the true temperature operation time of the two-dimensional pyrometer array is improved by 77%, which verifies that the software operational efficiency is greatly improved.
In Vitro and In Silico Screening of 2,4,5-Trisubstituted Imidazole Derivatives as Potential Xanthine Oxidase and Acetylcholinesterase Inhibitors, Antioxidant, and Antiproliferative Agents
Authors: Noriega-Iribe Eduardo , Díaz-Rubio Laura , Estolano-Cobián Arturo , Barajas-Carrillo Victor Wagner , Padrón José M. , Salazar-Aranda Ricardo , Díaz-Molina Raúl , García-González Victor , Chávez-Santoscoy Rocio Alejandra , Chávez Daniel , Córdova-Guerrero Iván
Published: April 2020

The employment of privileged scaffolds in medicinal chemistry supplies scientists with a solid start in the search for new and improved therapeutic molecules. One of these scaffolds is the imidazole ring, from which several derivatives have shown a wide array of biological activities. A series of 2,4,5-triphenyl imidazole derivatives were synthesized, characterized, and evaluated in vitro as antioxidant molecules using 1,1-diphenyl-2-picrylhydrazyl (DPPH.) and 2-2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS.+) assays, acetylcholinesterase (AChE) and xanthine oxidase (XO) inhibitors as well as antiproliferative agents. Additional in silico studies such as docking and determination of their absorption, distribution, metabolism, and excretion (ADME) properties were calculated. Compounds 3 and 10 were the most active antioxidants in both the DPPH and ABTS assays (EC50 of 0.141 and 0.174 mg/mL, and 0.168 and 0.162 mg/mL, respectively). In the enzymatic inhibition, compound 1 showed the best activity, inhibiting 25.8% of AChE at a concentration of 150 μg/mL, and compound 3 was the most active XO inhibitor with an IC50 of 85.8 μg/mL. Overall, against the six different evaluated cancerous cell lines, molecules 2, 10, and 11 were the most antiproliferative compounds. In silico predictions through docking point out 11, and ADME analysis to 11 and 12, as good candidates for being lead compounds for further derivations.
Analysis of Wear-Resistant Surface with Pangolin Scale Morphology by DEM Simulation
Authors: Zhang Rui , Yu Haibin , Pang Hao , Chen Guangming , Tai Weihsun
Published: April 2020

Based on the Discrete Element Method (DEM), an abrasive wear system composed of pangolin scale models and abrasive sand was established. The wear morphology of pangolin scale models under different velocities were simulated by PFC2D®. Their wear behaviors were discussed with regard to the contact bond fields, the contact force chains, the velocity fields and the displacement fields of the abrasive wear system. Moreover, the resistance of the pangolin scale models under different velocities were analyzed. In the DEM simulation, the fracture and debris locomotion on the scale model were observed at a meso-microscopic scale. The results show that the geometrical shape of the pangolin scale is helpful for decreasing the boundary stress, with the wear rate decreasing when the velocity is higher than 0.62 m·s−1. The wear rate is no more than 0.006 g/m under the abrasive sand, with a radius of 0.11–0.20 mm. The wear rates of the pangolin scale model agree with the experimental results, and the DEM provides a new way to study the abrasive wear behavior of this non-smooth biological surface.
Experimental Study of the Performance of a Novel Vertical-Axis Wind Turbine
Authors: Agbormbai James , Zhu Weidong
Published: April 2020

Basic equations for estimating the aerodynamic power captured by the Anderson vertical-axis wind turbine (AVAWT) are derived from a solution of Navier–Stokes (N–S) equations for a baroclinic inviscid flow. In a nutshell, the pressure difference across the AVAWT is derived from the Bernoulli’s equation—an upshot of the integration of the Euler’s momentum equation, which is the N–S momentum equation for a baroclinic inviscid flow. The resulting expression for the pressure difference across the AVAWT rotor is plotted as a function of the free-stream speed. Experimentally determined airstream speeds at the AVAWT inlet and outlet, coupled with corresponding free-stream speeds, are used in estimating the aerodynamic power captured. The aerodynamic power of the AVAWT is subsequently used in calculating its aerodynamic power coefficient. The actual power coefficient is calculated from the power generated by the AVAWT at various free-stream speeds and plotted as a function of the latter. Experimental results show that at all free-stream speeds and tip-speed ratios, the aerodynamic power coefficient of the AVAWT is higher than its actual power coefficient. Consequently, the power generated by the AVAWT prototype is lower than the aerodynamic power captured, given the same inflow wind conditions. Besides the foregoing, the main purpose of this experiment is to investigate the technical feasibility of the AVAWT. This proof of concept enables the inventor to commercialize the AVAWT.
System Design and Monitoring Method of Robot Grinding for Friction Stir Weld Seam
Authors: Li Mingyang , Du Zhijiang , Ma Xiaoxing , Gao Kui , Dong Wei , Di Yan , Gao Yongzhuo
Published: April 2020

In the grinding process of friction stir weld seams, excessive grinding will cause damage to the base metal and bring significant economic losses. In this paper, the authors design a robotic system for grinding the weld seam and present a monitoring method of excessive grinding. The designed system consists of an industrial robot, a line scanner for measuring the weld seam and a force-controlled grinding tool. Since the result of the measurement of the weld seam is a point cloud, the extraction method of the weld seam point cloud based on graph-cut is proposed in this paper. The extracted features are used as prior knowledge of the monitoring algorithm. On the other hand, by combining the features from the point cloud and force-position information during the processing, a monitoring method for excessive grinding based on PSO-SVM is proposed and verified by experiments. The experiments demonstrate that the proposed method can identify excessive grinding, and the accuracy of recognition is 91.5%.
A Bayesian In-Play Prediction Model for Association Football Outcomes
Authors: Zou Qingrong , Song Kai , Shi Jian
Published: April 2020

Point process models have made a significant contribution to the prediction of football association outcomes. It is conventionally the case that defence and attack capabilities have been assumed to be constant during a match and estimated against the average performance of all other teams in history. Drawing upon a Bayesian method, this paper proposes a dynamic strength model which relaxes assumption of the constant teams’ strengths and permits applying in-match performance information to calibrate them. An empirical study demonstrates that although the Bayesian model fails to achieve improvement in goal difference prediction, it registers clear achievements with regard to the prediction of the total number of goals and Win/Draw/Loss outcome prediction. When the Bayesian model bets against the SBOBet bookmaker, one of the most popular gaming companies among Asian handicaps fans, whose odds data were obtained from both the Win/Draw/Loss market and over–under market, it may obtain positive returns; this clearly contrasts with the process model with constant strengths, which fails to win money from the bookmaker.
Biostimulation in Desert Soils for Microbial-Induced Calcite Precipitation
Authors: Raveh-Amit Hadas , Tsesarsky Michael
Published: April 2020

Microbial-induced calcite precipitation (MICP) is a soil amelioration technique aiming to mitigate different environmental and engineering concerns, including desertification, soil erosion, and soil liquefaction, among others. The hydrolysis of urea, catalyzed by the microbial enzyme urease, is considered the most efficient microbial pathway for MICP. Biostimulated MICP relies on the enhancement of indigenous urea-hydrolyzing bacteria by providing an appropriate enrichment and precipitation medium, as opposed to bioaugmentation, which requires introducing large volumes of exogenous bacterial cultures into the treated soil along with a growth and precipitation medium. Biostimulated MICP in desert soils is challenging as the total carbon content and the bacterial abundance are considerably low. In this study, we examined the biostimulation potential in soils from the Negev Desert, Israel, for the purpose of mitigation of topsoil erosion in arid environments. Incubating soil samples in urea and enrichment media demonstrated effective urea hydrolysis leading to pH increase, which is necessary for calcite precipitation. Biostimulation rates were found to increase with concentrations of energy (carbon) source in the stimulation media, reaching its maximal levels within 3 to 6 days. Following stimulation, calcium carbonate precipitation was induced by spiking stimulated bacteria in precipitation (CaCl2 enriched) media. The results of our research demonstrate that biostimulated MICP is feasible in the low-carbon, mineral soils of the northern Negev Desert in Israel.
Acoustic Fabrication of Collagen–Fibronectin Composite Gels Accelerates Microtissue Formation
Authors: Norris Emma G. , Dalecki Diane , Hocking Denise C.
Published: April 2020

Ultrasound can influence biological systems through several distinct acoustic mechanisms that can be manipulated by varying reaction conditions and acoustic exposure parameters. We recently reported a new ultrasound-based fabrication technology that exploits the ability of ultrasound to generate localized mechanical forces and thermal effects to control collagen fiber microstructure non-invasively. Exposing solutions of type I collagen to ultrasound during the period of microfibril assembly produced changes in collagen fiber structure and alignment, and increased the biological activity of the resultant collagen hydrogels. In the extracellular matrix, interactions between fibronectin and collagen fibrils influence the biological activity of both proteins. Thus, in the present study, we examined how addition of fibronectin to collagen solutions prior to ultrasound exposure affects protein organization and the biological activity of the composite hydrogels. Results indicate that ultrasound can alter the distribution of fibronectin within 3D hydrogels via thermal and non-thermal mechanisms to produce composite hydrogels that support accelerated microtissue formation. The use of acoustic energy to drive changes in protein conformation to functionalize biomaterials has much potential as a unique, non-invasive technology for tissue engineering and regenerative medicine.
A Transfer Learning Method for Pneumonia Classification and Visualization
Authors: Luján-García Juan , Yáñez-Márquez Cornelio , Villuendas-Rey Yenny , Camacho-Nieto Oscar
Published: April 2020

Pneumonia is an infectious disease that affects the lungs and is one of the principal causes of death in children under five years old. The Chest X-ray images technique is one of the most used for diagnosing pneumonia. Several Machine Learning algorithms have been successfully used in order to provide computer-aided diagnosis by automatic classification of medical images. For its remarkable results, the Convolutional Neural Networks (models based on Deep Learning) that are widely used in Computer Vision tasks, such as classification of injuries and brain abnormalities, among others, stand out. In this paper, we present a transfer learning method that automatically classifies between 3883 chest X-ray images characterized as depicting pneumonia and 1349 labeled as normal. The proposed method uses the Xception Network pre-trained weights on ImageNet as an initialization. Our model is competitive with respect to state-of-the-art proposals. To make comparisons with other models, we have used four well-known performance measures, obtaining the following results: precision (0.84), recall (0.99), F1-score (0.91) and area under the ROC curve (0.97). These positive results allow us to consider our proposal as an alternative that can be useful in countries with a lack of equipment and specialized radiologists.
Surface Modification of Flax Yarns by Enzymatic Treatment and Their Interfacial Adhesion with Thermoset Matrices
Authors: Seghini Maria Carolina , Tirillò Jacopo , Bracciale Maria Paola , Touchard Fabienne , Chocinski-Arnault Laurence , Zuorro Antonio , Lavecchia Roberto , Sarasini Fabrizio
Published: April 2020

The aim of this study was to assess the effects of commercially available and relatively inexpensive enzyme preparations based on endo 1,4-β-xylanase, pectinase and xyloglucanase on the thermal (TGA), morphological (SEM), chemical (FT-IR) and mechanical (single yarn tensile tests) properties of flax yarns. The preparation based on pectinase and xyloglucanase provided the best results, resulting in the effective removal of hydrophilic components such as hemicellulose and pectin, the individualization of yarns and increased thermal stability at the expense of a reduction in mechanical properties, depending on the treatment parameters. Single yarn fragmentation tests pointed out an improved interfacial adhesion after enzymatic treatment, with reduced debonding length values of 18% for an epoxy matrix and up to 36% for a vinylester resin compared to untreated flax yarns.
Estimating the Rank of a Nonnegative Matrix Factorization Model for Automatic Music Transcription Based on Stein’s Unbiased Risk Estimator
Authors: Lee Seokjin
Published: April 2020

In this paper, methods to estimate the number of basis vectors of the nonnegative matrix factorization (NMF) of automatic music transcription (AMT) systems are proposed. Previously, studies on NMF-based AMT have demonstrated that the number of basis vectors affects the performance and that the number of note events can be a good selection as the rank of NMF. However, many NMF-based AMT methods do not provide a method to estimate the appropriate number of basis vectors; instead, the number is assumed to be given in advance, even though the number of basis vectors significantly affects the algorithm’s performance. Recently, based on Bayesian methods, certain estimation algorithms for the number of basis vectors have been proposed; however, they are not designed to be used as music transcription algorithms but are components of specific NMF methods and thus cannot be used generally as NMF-based transcription algorithms. Our proposed estimation algorithms are based on eigenvalue decomposition and Stein’s unbiased risk estimator (SURE). Because the SURE method requires variance in undesired components as a priori knowledge, the proposed algorithms estimate the value using random matrix theory and first and second onset information in the input music signal. Experiments were then conducted for the AMT task using the MIDI-aligned piano sounds (MAPS) database, and these algorithms were compared with variational NMF, gamma process NMF, and NMF with automatic relevance determination algorithms. Based on experimental results, the conventional NMF-based transcription algorithm with the proposed rank estimation algorithms demonstrated enhanced F1 score performances of 2–3% compared to the algorithms. While the performance advantages are not significantly large, the results are meaningful because the proposed algorithms are lightweight, are easy to combine with any other NMF methods that require an a priori rank parameter, and do not have setting parameters that considerably affect the performance.
Comparative Analysis of Kazakhstani and European Approaches for the Design of Shallow Foundations
Authors: Shaldykova Assel , Moon Sung-Woo , Kim Jong , Lee Deuckhang , Ku Taeseo , Zhussupbekov Askar
Published: April 2020

The design of shallow foundations is performed in accordance with different building regulations depending on geotechnical and geological conditions. This paper involves the design calculations applying Kazakhstani and European approaches. The design of shallow foundations in Nur-Sultan city in Kazakhstan was implemented by the calculation of bearing capacity and elastic settlement in accordance with the design procedures provided in SP RK 5.01-102-2013: Foundations of buildings and structures, and Eurocode 7: Geotechnical design. The calculated results of bearing capacity and elastic settlement for two types of shallow foundations, such as pad foundation and strip foundation, adhering to Kazakhstani and European approaches are relatively comparable. However, the European approach provided higher values of bearing capacity and elastic settlement for the designed shallow foundation compared to the Kazakhstani approach. The difference in the results is explained by the application of different values of partial factors of safety for the determination of bearing capacity and different methods for the calculation of the elastic settlement of shallow foundations (i.e., elasticity theory and layer summation method).
Challenges for the Implantation of Symbiotic Nanostructured Medical Devices
Authors: Alcaraz Jean-Pierre , Menassol Gauthier , Penven Géraldine , Thélu Jacques , El Ichi Sarra , Zebda Abdelkader , Cinquin Philippe , Martin Donald K.
Published: April 2020

We discuss the perspectives of designing implantable medical devices that have the criterion of being symbiotic. Our starting point was whether the implanted device is intended to have any two-way (“duplex”) communication of energy or materials with the body. Such duplex communication extends the existing concepts of a biomaterial and biocompatibility to include the notion that it is important to consider the intended functional use of the implanted medical device. This demands a biomimetic approach to design functional symbiotic implantable medical devices that can be more efficient in mimicking what is happening at the molecular and cellular levels to create stable interfaces that allow for the unfettered exchanges of molecules between an implanted device and a body. Such a duplex level of communication is considered to be a necessary characteristic of symbiotic implanted medical devices that are designed to function for long periods of time inside the body to restore and assist the function of the body. We illustrate these perspectives with experience gained from implanting functional enzymatic biofuel cells.
Thermal Infrared Imaging-Based Affective Computing and Its Application to Facilitate Human Robot Interaction: A Review
Authors: Filippini Chiara , Perpetuini David , Cardone Daniela , Chiarelli Antonio Maria , Merla Arcangelo
Published: April 2020

Over recent years, robots are increasingly being employed in several aspects of modern society. Among others, social robots have the potential to benefit education, healthcare, and tourism. To achieve this purpose, robots should be able to engage humans, recognize users’ emotions, and to some extent properly react and "behave" in a natural interaction. Most robotics applications primarily use visual information for emotion recognition, which is often based on facial expressions. However, the display of emotional states through facial expression is inherently a voluntary controlled process that is typical of human–human interaction. In fact, humans have not yet learned to use this channel when communicating with a robotic technology. Hence, there is an urgent need to exploit emotion information channels not directly controlled by humans, such as those that can be ascribed to physiological modulations. Thermal infrared imaging-based affective computing has the potential to be the solution to such an issue. It is a validated technology that allows the non-obtrusive monitoring of physiological parameters and from which it might be possible to infer affective states. This review is aimed to outline the advantages and the current research challenges of thermal imaging-based affective computing for human–robot interaction.
Optimized Erosion Prediction with MAGA Algorithm Based on BP Neural Network for Submerged Low-Pressure Water Jet
Authors: Chen Yanzhen , Hu Yihuai , Zhang Shenglong , Mei Xiaojun , Shi Qingguo
Published: April 2020

In order to accurately predict the erosion effect of underwater cleaning with an angle nozzle under different working conditions, this paper uses refractory bricks to simulate marine fouling as the erosion target, and studies the optimized erosion prediction model by erosion test based on the submerged low-pressure water jet. The erosion test is conducted by orthogonal experimental design, and experimental data are used for the prediction model. By combining with statistical range and variance analysis methods, the jet pressure, impact time and jet angle are determined as three inputs of the prediction model, and erosion depth is the output index of the prediction model. A virtual data generation method is used to increase the amount of input data for the prediction model. This paper also proposes a Mind-evolved Advanced Genetic Algorithm (MAGA), which has a reliable optimization effect in the verification of four stand test functions. Then, the improved back-propagating (BP) neural network prediction models are established by respectively using Genetic Algorithm (GA) and MAGA optimization algorithms to optimize the initial thresholds and weights of the BP neural network. Compared to the prediction results of the BP and GA-BP models, the R2 of the MAGA-BP model is the highest, reaching 0.9954; the total error is reduced by 47.31% and 35.01%; the root mean square error decreases by 51.05% and 31.80%; and the maximum absolute percentage error decreases by 65.79% and 64.01%, respectively. The average prediction accuracy of the MAGA-BP model is controlled within 3%, which has been significantly improved. The results show that the prediction accuracy of the MAGA-BP prediction model is higher and more reliable, and the MAGA algorithm has a good optimization effect. This optimized erosion prediction method is feasible.
Partitioning Waves and Eddies in Stably Stratified Turbulence
Authors: Lam Henri , Delache Alexandre , Godeferd Fabien S
Published: April 2020

We consider the separation of motion related to internal gravity waves and eddy dynamics in stably stratified flows obtained by direct numerical simulations. The waves’ dispersion relation links their angle of propagation to the vertical θ , to their frequency ω , so that two methods are used for characterizing wave-related motion: (a) the concentration of kinetic energy density in the ( θ , ω ) map along the dispersion relation curve; and (b) a direct computation of two-point two-time velocity correlations via a four-dimensional Fourier transform, permitting to extract wave-related space-time coherence. The second method is more computationally demanding than the first. In canonical flows with linear kinematics produced by space-localized harmonic forcing, we observe the pattern of the waves in physical space and the corresponding concentration curve of energy in the ( θ , ω ) plane. We show from a simple laminar flow that the curve characterizing the presence of waves is distorted differently in the presence of a background convective mean velocity, either uniform or varying in space, and also when the forcing source is moving. By generalizing the observation from laminar flow to turbulent flow, this permits categorizing the energy concentration pattern of the waves in complex flows, thus enabling the identification of wave-related motion in a general turbulent flow with stable stratification. The advanced method (b) is finally used to compute the wave-eddy partition in the velocity–buoyancy fields of direct numerical simulations of stably stratified turbulence. In particular, we use this splitting in statistics as varied as horizontal and vertical kinetic energy, as well as two-point velocity and buoyancy spectra.
A Budget-Based Turbulence Length Scale Diagnostic
Authors: Bašták Ďurán Ivan , Schmidli Juerg , Bhattacharya Ritthik
Published: April 2020

The most frequently used boundary-layer turbulence parameterization in numerical weather prediction (NWP) models are turbulence kinetic energy (TKE) based-based schemes. However, these parameterizations suffer from a potential weakness, namely the strong dependence on an ad-hoc quantity, the so-called turbulence length scale. The physical interpretation of the turbulence length scale is difficult and hence it cannot be directly related to measurements or large eddy simulation (LES) data. Consequently, formulations for the turbulence length scale in basically all TKE schemes are based on simplified assumptions and are model-dependent. A good reference for the independent evaluation of the turbulence length scale expression for NWP modeling is missing. Here we propose a new turbulence length scale diagnostic which can be used in the gray zone of turbulence without modifying the underlying TKE turbulence scheme. The new diagnostic is based on the TKE budget: The core idea is to encapsulate the sum of the molecular dissipation and the cross-scale TKE transfer into an effective dissipation, and associate it with the new turbulence length scale. This effective dissipation can then be calculated as a residuum in the TKE budget equation (for horizontal sub-domains of different sizes) using LES data. Estimation of the scale dependence of the diagnosed turbulence length scale using this novel method is presented for several idealized cases.
Integral Representation of Coherent Lower Previsions by Super-Additive Integrals
Authors: Doria Serena , Mesiar Radko , Šeliga Adam
Published: April 2020

Coherent lower previsions generalize the expected values and they are defined on the class of all real random variables on a finite non-empty set. Well known construction of coherent lower previsions by means of lower probabilities, or by means of super-modular capacities-based Choquet integrals, do not cover this important class of functionals on real random variables. In this paper, a new approach to the construction of coherent lower previsions acting on a finite space is proposed, exemplified and studied. It is based on special decomposition integrals recently introduced by Even and Lehrer, in our case the considered decomposition systems being single collections and thus called collection integrals. In special case when these integrals, defined for non-negative random variables only, are shift-invariant, we extend them to the class of all real random variables, thus obtaining so called super-additive integrals. Our proposed construction can be seen then as a normalized super-additive integral. We discuss and exemplify several particular cases, for example, when collections determine a coherent lower prevision for any monotone set function. For some particular collections, only particular set functions can be considered for our construction. Conjugated coherent upper previsions are also considered.
Clinical Effectiveness of a Combination of Black Elder Berries, Violet Herb, and Calendula Flowers in Chronic Obstructive Pulmonary Disease: The Results of a Double-Blinded Placebo-Controlled Study
Authors: Kirichenko Tatiana V. , Sobenin Igor A. , Markina Yuliya V. , Gerasimova Elena V. , Grechko Andrey V. , Kashirskikh Dmitry A. , Romanenko Elena B. , Wu Wei-Kai , Orekhov Alexander N.
Published: April 2020

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease, in which systemic inflammation plays a key role. This 6-month randomized double-blinded placebo-controlled study evaluates the possible effect of natural preparation Inflaminat on clinical symptoms of COPD, indicators of respiratory function, and exacerbation frequency in 60 patients with moderate severity of COPD. Inflaminat is a combination of natural ingredients black elder (Sambucus nigra L.) berries, violet (Viola tricolor L.) herb, and calendula (Calendula officinalis L.) flowers. The preparation has been previously demonstrated to possess anticytokine and anti-inflammatory effects in experimental studies. In present study, COPD dynamics were evaluated by means of BCSS (Breathlessness, Cough, and Sputum Scale) and spirometry tests. It was shown that 6-months Inflaminat administration led to significant decrease of BCSS points from 3.0 ± 0.6 to 1.9 ± 0.7, (p = 0.002) as well as significant increase of FEV1 from 66 ± 18% to 73 ± 17%, (p = 0.042); there were no beneficial dynamics in placebo group. Side effects associated with preparation administration were not identified. The results of the study suggest that Inflaminat may be employed in treatment of patients with moderate severity of COPD, since it has a positive effect on COPD symptoms according BCSS and indicators of respiratory function FEV1.
The Impact of Insurance and Marital Status on Survival in Patients with Nasopharyngeal Carcinoma
Authors: Wang Chih-Chun , Yang Ching-Chieh , Yeh Shyh-An , Huang Chung-I , Hwang Tzer-Zen , Yang Chuan-Chien , Su Yu-Chieh
Published: April 2020

Objective: This study aimed to explore the influence of social support on the survival outcomes of patients with nasopharyngeal carcinoma (NPC). We examined whether the combined proxy influenced whether patients were more likely to receive radiotherapy. Methodology: data were collected from the 18 registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. The association between both insurance status and marital status and disease-specific survival rates were evaluated with a multivariate Cox proportional-hazards regression model to calculate the hazard ratios and associated confidence intervals. Odds ratio (OR) computed by logistic regression was also used to examine the relationship between the receipt of radiotherapy and insurance and marital status. Results: insured and uninsured patients differed significantly in T-stage, N-stage, M-stage, radiotherapy use, race, and marital status. The uninsured-non-married patients showed the lowest 5-year disease-specific survival rates. We further found unmarried patients with either Medicaid (OR, 0.40), or no insurance (OR, 0.24) had lower odds of receiving radiotherapy than those with insurance at diagnosis. Conclusions: uninsured-unmarried NPC patients had a significantly higher risk of distant metastasis at diagnosis, poorer 5-year disease-specific survival, and were less likely to receive radiotherapy than insured-married patients.
Structural and Functional Peculiarities of α-Crystallin
Authors: Selivanova Olga M. , Galzitskaya Oxana V.
Published: April 2020

α-Crystallin is the major protein of the eye lens and a member of the family of small heat-shock proteins. Its concentration in the human eye lens is extremely high (about 450 mg/mL). Three-dimensional structure of native α-crystallin is unknown. First of all, this is the result of the highly heterogeneous nature of α-crystallin, which hampers obtaining it in a crystalline form. The modeling based on the electron microscopy (EM) analysis of α-crystallin preparations shows that the main population of the α-crystallin polydisperse complex is represented by oligomeric particles of rounded, slightly ellipsoidal shape with the diameter of about 13.5 nm. These complexes have molecular mass of about 700 kDa. In our opinion, the heterogeneity of the α-crystallin complex makes it impossible to obtain a reliable 3D model. In the literature, there is evidence of an enhanced chaperone function of α-crystallin during its dissociation into smaller components. This may indirectly indicate that the formation of heterogeneous complexes is probably necessary to preserve α-crystallin in a state inactive before stressful conditions. Then, not only the heterogeneity of the α-crystallin complex is an evolutionary adaptation that protects α-crystallin from crystallization but also the enhancement of the function of α-crystallin during its dissociation is also an evolutionary acquisition. An analysis of the literature on the study of α-crystallin in vitro led us to the assumption that, of the two α-crystallin isoforms (αA- and αB-crystallins), it is αA-crystallin that plays the role of a special chaperone for αB-crystallin. In addition, our data on X-ray diffraction analysis of α-crystallin at the sample concentration of about 170–190 mg/mL allowed us to assume that, at a high concentration, the eye lens α-crystallin can be in a gel-like stage. Finally, we conclude that, since all the accumulated data on structural-functional studies of α-crystallin were carried out under conditions far from native, they cannot adequately reflect the features of the functioning of α-crystallin in vivo.
Src/NF-κB-Targeted Anti-Inflammatory Effects of Potentilla glabra var. Mandshurica (Maxim.) Hand.-Mazz. Ethanol Extract
Authors: Kim Haeyeop , Shin Kon Kuk , Kim Han Gyung , Jo Minkyeong , Kim Jin Kyeong , Lee Jong Sub , Choung Eui Su , Li Wan Yi , Lee Sang Woo , Kim Kyung-Hee , Yoo Byong Chul , Cho Jae Youl
Published: April 2020

Inflammation is a complex protective response of body tissues to harmful stimuli. Acute inflammation can progress to chronic inflammation, which can lead to severe disease. Therefore, this research focuses on the development of anti-inflammatory drugs, and natural extracts have been explored as potential agents. No study has yet examined the inflammation-associated pharmacological activity of Potentilla glabra Var. mandshurica (Maxim.) Hand.-Mazz ethanol extract (Pg-EE). To examine the mechanisms by which Pg-EE exerts anti-inflammatory effects, we studied its activities in lipopolysaccharide (LPS)-treated murine macrophage RAW264.7 cells and an HCl/EtOH-induced gastritis model. LPS-triggered nitric oxide (NO) release and mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in RAW264.7 cells were suppressed by Pg-EE in a dose-dependent manner. Using a luciferase assay and western blot assay, we found that the NF-κB pathway was inhibited by Pg-EE, particularly by the decreased level of phosphorylated proteins of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunits (p65 and p50), inhibitor of kappa B alpha (IκBα), p85, and Src. Using an overexpression strategy, cellular thermal shift assay, and immunoprecipitation analysis, we determined that the anti-inflammatory effect of Pg-EE was mediated by the inhibition of Src. Pg-EE further showed anti-inflammatory effects in vivo in the HCl/EtOH-induced gastritis mouse model. In conclusion, Pg-EE exerts anti-inflammatory activities by targeting Src in the NF-κB pathway, and these results suggest that Pg-EE could be used as an anti-inflammatory herbal medicine.
Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning
Authors: Petushkova Anastasiia I. , Zamyatnin Andrey A.
Published: April 2020

Proteolytic enzymes play a crucial role in metabolic processes, providing the cell with amino acids through the hydrolysis of multiple endogenous and exogenous proteins. In addition to this function, proteases are involved in numerous protein cascades to maintain cellular and extracellular homeostasis. The redox regulation of proteolysis provides a flexible dose-dependent mechanism for proteolytic activity control. The excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) in living organisms indicate pathological conditions, so redox-sensitive proteases can swiftly induce pro-survival responses or regulated cell death (RCD). At the same time, severe protein oxidation can lead to the dysregulation of proteolysis, which induces either protein aggregation or superfluous protein hydrolysis. Therefore, oxidative stress contributes to the onset of age-related dysfunction. In the present review, we consider the post-translational modifications (PTMs) of proteolytic enzymes and their impact on homeostasis.
Trajectories of Immediate and Delayed Verbal Memory in the Spanish General Population of Middle-aged and Older Adults
Authors: Bayes-Marin Ivet , Fernández Daniel , Lara Elvira , Martín-María Natalia , Miret Marta , Moreno-Agostino Darío , Ayuso-Mateos José Luis , Sanchez-Niubo Albert , Haro Josep Maria , Olaya Beatriz
Published: April 2020

(1) Cognitive decline differs among individuals and cognition function domains. We sought to identify distinct groups of immediate and delayed verbal memory in two age subsamples (50–64, 65+ years), and to analyze associated factors. (2) Latent class mixed models were used to identify verbal memory trajectories in a sample of Spanish community-dwelling individuals over 8 years’ follow up. Chi-square and Kruskal–Wallis tests were used to assess differences among trajectories. (3) Different trajectories were identified. In the case of immediate verbal memory, these were: very low/decline (6.3%), low/stable (38.2%), medium/slow decline (43.4%), and high/slow decline (12.2%) in the middle-aged group, and low/decline (20.4%), medium/slow decline (60.4%), and high/slow decline (19.2%) in the older subsample. In delayed verbal memory, more distinct patterns were found: very low/decline (12.4%), low/stable (51.4%), medium/accelerated decline (24.7%), and high/slow increase (11.4%) in the younger group, and low/slow decline (34.4%), medium/decline (52.7%), and high/slow decline (12.9%) in the older group. (4) Overall, low initial performance and decline were associated with older age, lower education, and higher diabetes/stroke prevalence. Differences found suggests heterogeneity in cognitive ageing. The high prevalence of cardiovascular diseases in those with worse cognition suggests that early interventions to prevent those conditions should be targeted in midlife to delay cognitive decline.
Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy
Authors: Liu Wai Nam , Fong Shin Yie , Tan Wilson Wei Sheng , Tan Sue Yee , Liu Min , Cheng Jia Ying , Lim Sherlly , Suteja Lisda , Huang Edwin Kunxiang , Chan Jerry Kok Yen , Iyer Narayanan Gopalakrishna , Yeong Joe Poh Sheng , Lim Darren Wan-Teck , Chen Qingfeng
Published: April 2020

Immune checkpoint blockade (ICB) monotherapy shows early promise for the treatment of nasopharyngeal carcinoma (NPC) in patients. Nevertheless, limited representative NPC models hamper preclinical studies to evaluate the efficacy of novel ICB and combination regimens. In the present study, we engrafted NPC biopsies in non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain-null (NSG) mice and established humanized mouse NPC-patient-derived xenograft (NPC-PDX) model successfully. Epstein–Barr virus was detected in the NPC in both NSG and humanized mice as revealed by Epstein–Barr virus-encoded small RNA (EBER) in situ hybridization (ISH) and immunohistochemical (IHC) staining. In the NPC-bearing humanized mice, the percentage of tumor-infiltrating CD8+ cytotoxic T cells was lowered, and the T cells expressed higher levels of various inhibitory receptors, such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) than those in blood. The mice were then treated with nivolumab and ipilimumab, and the anti-tumor efficacy of combination immunotherapy was examined. In line with paired clinical data, the NPC-PDX did not respond to the treatment in terms of tumor burden, whilst an immunomodulatory response was elicited in the humanized mice. From our results, human proinflammatory cytokines, such as interferon-gamma (IFN-γ) and interleukin-6 (IL-6) were significantly upregulated in plasma. After treatment, there was a decrease in CD4/CD8 ratio in the NPC-PDX, which also simulated the modulation of intratumoral CD4/CD8 profile from the corresponding donor. In addition, tumor-infiltrating T cells were re-activated and secreted more IFN-γ towards ex vivo stimulation, suggesting that other factors, including soluble mediators and metabolic milieu in tumor microenvironment may counteract the effect of ICB treatment and contribute to the tumor progression in the mice. Taken together, we have established and characterized a novel humanized mouse NPC-PDX model, which plausibly serves as a robust platform to test for the efficacy of immunotherapy and may predict clinical outcomes in NPC patients.
Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease
Authors: Zhou Xiang , Flüchter Patricia , Nickel Katharina , Meckel Katharina , Messerschmidt Janin , Böckle David , Knorz Sebastian , Steinhardt Maximilian Johannes , Krummenast Franziska , Danhof Sophia , Einsele Hermann , Kortüm K. Martin , Rasche Leo
Published: April 2020

Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.
Positive Impact of Natural Deep Eutectic Solvents on the Biocatalytic Performance of 5-Hydroxymethyl-Furfural Oxidase
Authors: de Gonzalo Gonzalo , Martin Caterina , Fraaije Marco W.
Published: April 2020

Deep eutectic solvents (DESs) have been applied as cosolvents in various biocatalytic processes during recent years. However, their use in combination with redox enzymes has been limited. In this study, we have explored the beneficial effects of several DES as cosolvents on the performance of 5-hydroxymethylfurfural oxidase (HMFO), a valuable oxidative enzyme for the preparation of furan-2,5-dicarboxylic acid (FDCA), and other compounds, such as carbonyl compounds and carboxylic acids. The use of natural DESs, based on glucose and fructose, was found to have a positive effect. Higher conversions are obtained for the synthesis of several oxidized compounds, including FDCA. Depending on the type of DES, the stability of HMFO could be significantly improved. As the use of DES increases the solubility of many substrates while they only mildly affect dioxygen solubility, this study demonstrates that biocatalysis based on HMFO and other redox biocatalysts can benefit from a carefully selected DES.
C–H Bond Activation of Silyl-Substituted Pyridines with Bis(Phenolate)Yttrium Catalysts as a Facile Tool towards Hydroxyl-Terminated Michael-Type Polymers
Authors: Pehl Thomas M. , Kränzlein Moritz , Adams Friederike , Schaffer Andreas , Rieger Bernhard
Published: April 2020

Herein, silicon-protected, ortho-methylated hydroxy-pyridines were reported as initiators in 2-aminoalkoxy-bis(phenolate)yttrium complexes for rare earth metal-mediated group-transfer polymerization (REM-GTP) of Michael-type monomers. To introduce these initiators, C−H bond activation was performed by reacting [(ONOO)tBuY(X)(thf)] (X = CH2TMS, thf = tetrahydrofuran) with tert-butyl-dimethyl-silyl-functionalized α-methylpyridine to obtain the complex [(ONOOtBuY(X)(thf)] (X = 4-(4′-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-2,6-di-methylpyridine). These initiators served as functional end-groups in polymers produced via REM-GTP. In this contribution, homopolymers of 2-vinylpyridine (2VP) and diethyl vinyl phosphonate (DEVP) were produced. Activity studies and end-group analysis via mass spectrometry, size-exclusion chromatography (SEC) and NMR spectroscopy were performed to reveal the initiator efficiency, the catalyst activity towards both monomers as well as the initiation mechanism of this initiator in contrast to commonly used alkyl initiators. In addition, 2D NMR studies were used to further confirm the end-group integrity of the polymers. For all polymers, different deprotection routes were evaluated to obtain hydroxyl-terminated poly(2-vinylpyridine) (P2VP) and poly(diethyl vinyl phosphonate) (PDEVP). Such hydroxyl groups bear the potential to act as anchoring points for small bioactive molecules, for post-polymerization functionalization or as macroinitiators for further polymerizations.