bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure Development and Properties of the Two-Component Melt-Spun Ni55Fe20Cu5P10B10 Alloy at Elevated Temperatures
Authors: Ziewiec Krzysztof , Wojciechowska Mirosława , Jankowska-Sumara Irena , Ziewiec Aneta , Kąc Sławomir
Published: April 2021

The aim of this work was to investigate the features of microstructure, phase composition, mechanical properties, and thermal stability of the two-component melt-spun Ni55Fe20Cu5P10B10 alloy. The development of the microstructure after heating to elevated temperatures was studied using scanning electron microscope and in situ high temperature X-ray diffraction. The high-temperature behavior of the two-component melt-spun Ni55Fe20Cu5P10B10 alloy and Ni40Fe40B20, Ni70Cu10P20, and Ni55Fe20Cu5P10B10 alloys melt-spun from single-chamber crucible was investigated using differential scanning calorymetry at different heating rates and by dynamic mechanical thermal analysis. The results show that band-like microstructure of the composite alloy is stable even at 800 K, although coarsening of bands forming the microstructure of the ribbons is observed above 550 K. Plastic deformation is observed in the composite previously heated to temperatures of 600–650 K. The properties of the composite alloy are generally different than the properties obtained for the melt-spun alloy of the same average nominal composition produced traditionally. Additionally, the mechanical and the thermal properties in this composite are inherited from the amorphous state of alloys that are precursors for two-component melt spinning (TCMS) processing.
Flat-Top Cylinder Indenter for Mechanical Characterization: A Report of Industrial Applications
Authors: Montanari Roberto , Varone Alessandra
Published: April 2021

FIMEC (flat-top cylinder indenter for mechanical characterisation) is an instrumented indentation test employing a cylindrical punch. It has been used to determine the mechanical properties of metallic materials in several applications of industrial interest. This work briefly describes the technique and the theory of indentation with a flat-ended punch. The flat indentation of metals has been investigated through experimental tests, and an equation has been derived to calculate the yield stress from the experimental data in deep indentation. The approach is supported by many data on various metals and alloys. Some selected case studies are presented in the paper: (i) crank manufacturing through pin squeeze casting; (ii) the evaluation of the local mechanical properties in a carter of complex geometry; (iii) the qualification of Al billets for extrusion; (iv) stress–relaxation tests on CuCrZr heat sinks; (v) the characterization of thick W coatings on CuCrZr alloy; (vi) the measure of the local mechanical properties of the molten-zone (MZ) and the heat-affected zone (HAZ) in welded joints. The case studies demonstrate the great versatility of the FIMEC test which provides information not available by employing conventional experimental techniques such as tensile, bending, and hardness tests. On the basis of theoretical knowledge and large amount of experimental data, FIMEC has become a mature technique for application on a large scale in industrial practice.
Extra-Soft Tactile Sensor for Sensitive Force/Displacement Measurement with High Linearity Based on a Uniform Strength Beam
Authors: Ni Na , Xue Xiaomin , Li Dongbo
Published: April 2021

The soft sensing system has drawn huge enthusiasm for the application of soft robots and healthcare recently. Most of them possess thin-film structures that are beneficial to monitoring strain and pressure, but are unfavorable for measuring normal displacement with high linearity. Here we propose soft tactile sensors based on uniform-strength cantilever beams that can be utilized to measure the normal displacement and force of soft objects simultaneously. First, the theoretical model of the sensors is constructed, on the basis of which, the sensors are fabricated for testing their sensing characteristics. Next, the test results validate the constructed model, and demonstrate that the sensors can measure the force as well as the displacement. Besides, the self-fabricated sensor can have such prominent superiorities as follows—it is ultra-soft, and its equivalent stiffness is only 0.31 N·m−1 (approximately 0.4% of fat); it has prominent sensing performance with excellent linearity (R2 = 0.999), high sensitivity of 0.533 pF·mm−1 and 1.66 pF·mN−1 for measuring displacement and force; its detection limit is as low as 70 μm and 20 μN that is only one-tenth of the touch of a female fingertip. The presented sensor highlights a new idea for measuring the force and displacement of the soft objects with broad application prospects in mechanical and medical fields.
Optimization of Two Steps in Scale-Up Synthesis of Nannocystin A
Authors: Zhang Tingrong , Miao Shaojie , Zhang Mingxiao , Liu Wenjie , Wang Liang , Chen Yue
Published: April 2021

We have accomplished a 10-step (longest linear) total synthesis of nannocystin A on a four hundred milligram scale. The previously reported Kobayashi vinylogous Mukaiyama aldol reaction to connect C4 and C5 was unreproducible during the scaling up process. A more convenient and cost-efficient Keck asymmetric vinylogous aldol reaction was employed to improve this transformation.
Evaluation of Obstructive Sleep Apnea Phenotypes Treatment Effectiveness
Authors: Charčiūnaitė Karolina , Gauronskaitė Rasa , Šlekytė Goda , Danila Edvardas , Zablockis Rolandas
Published: April 2021

Background and Objective: Obstructive sleep apnea (OSA) is a heterogeneous chronic sleep associated disorder. A common apnea-hypopnea index (AHI)-focused approach to OSA severity evaluation is not sufficient enough to capture the extent of OSA related risks, it limits our understanding of disease pathogenesis and may contribute to a modest response to conventional treatment. In order to resolve the heterogeneity issue, OSA patients can be divided into more homogenous therapeutically and prognostically significant groups–phenotypes. An improved understanding of OSA phenotype relationship to treatment effectiveness is required. Thus, in this study several clinical OSA phenotypes are identified and compared by their treatment effectiveness. Methods and materials: Retrospective data analysis of 233 adult patients with OSA treated with continuous positive airway pressure (CPAP) was performed. Statistical analysis of data relating to demographic and anthropometric characteristics, symptoms, arterial blood gas test results, polysomnografic and respiratory polygraphic tests and treatment, treatment results was performed. Results: 3 phenotypes have been identified: “Position dependent (supine) OSA” (Positional OSA), “Severe OSA in obese patients” (Severe OSA) and “OSA and periodic limb movements (PLM)” (OSA and PLM). The highest count of responders to treatment with CPAP was in the OSA and PLM phenotype, followed by the Positional OSA phenotype. Treatment with CPAP, despite the highest mean pressure administered was the least effective among Severe OSA phenotype. Conclusions: Different OSA phenotypes vary significantly and lead to differences in response to treatment. Thus, treatment effectiveness depends on OSA phenotypes and treatment techniques other than CPAP may be needed. This emphasizes the importance of a more individualized approach when treating OSA.
Influence of HPT and Accumulative High-Pressure Torsion on the Structure and Hv of a Zirconium Alloy
Authors: Gunderov Dmitry , Stotskiy Andrey , Lebedev Yuri , Mukaeva Veta
Published: April 2021

The authors previously used the accumulative high-pressure torsion (ACC HPT) method for the first time on steel 316, β-Ti alloy, and bulk metallic glass vit105. On low-alloyed alloys, in particular, the zirconium alloy Zr-1%Nb, the new method was not used. This alloy has a tendency to α → ω phase transformations at using simple HPT. When using ACC HPT, the α → ω transformation can be influenced to a greater extent. This article studies the sliding effect and accumulation of shear strain in Zr-1%Nb alloy at various stages of high-pressure torsion (HPT). The degree of shear deformation at different stages of HPT was estimated. The influence of various high-pressure torsion conditions on the micro-hardness and phase composition by X-ray diffraction (XRD) of Zr-1%Nb was analyzed. It is shown that at high-pressure torsion revolutions of n = 2, anvils and the specimen significantly slip, which is a result of material strengthening. It was found that despite sliding, regular high-pressure torsion resulted in the high strengthening of Zr-1%Nb alloy (micro-hardness more than doubled), and after high-pressure torsion n = 10, up to 97% of the high-pressure ω-phase was formed in it (as in papers of other researchers). Accumulative high-pressure torsion deformation leads to the strongest transformation of the Zr-1%Nb structure and Hv and, therefore, to a higher real strain of the material due to composition by upsetting and torsion in strain cycles.
Development of an Electrostatic Comb-Driven MEMS Scanning Mirror for Two-Dimensional Raster Scanning
Authors: Wang Qiang , Wang Weimin , Zhuang Xuye , Zhou Chongxi , Fan Bin
Published: April 2021

Microelectromechanical System (MEMS)-based scanning mirrors are important optical devices that have been employed in many fields as a low-cost and miniaturized solution. In recent years, the rapid development of Light Detection and Ranging (LiDAR) has led to opportunities and challenges for MEMS scanners. In this work, we propose a 2D electrostatically actuated micro raster scanner with relatively large aperture. The 2D scanner combines a resonant scanning axis driven by an in-plane comb and a quasistatic scanning axis driven by a vertical comb, which is achieved by raising the moving comb finger above the fixed comb finger through the residual stress gradient. The analytic formula for the resonant axis frequency, based on the mechanical coupling of two oscillation modes, is derived and compared with finite element simulation. A prototype is designed, fabricated, and tested, and an overall optical Field-of-View (FoV) of about 60° × 4° is achieved. Finally, some possibilities for further improvement or optimization are discussed.
A Novel Method for Estimating and Balancing the Second Harmonic Error of Cylindrical Fused Silica Resonators
Authors: Tao Yunfeng , Pan Yao , Liu Jianping , Jia Yonglei , Yang Kaiyong , Luo Hui
Published: April 2021

The cylindrical resonator gyroscope (CRG) is a type of Coriolis vibratory gyroscope which measures the angular velocity or angle through the precession of the elastic wave of the cylindrical resonator. The cylindrical fused silica resonator is an essential component of the CRG, the symmetry of which determines the bias drift and vibration stability of the gyroscope. The manufacturing errors breaking the symmetry of the resonator are usually described by Fourier series, and most studies are only focusing on analyzing and reducing the fourth harmonic error, the main error source of bias drift. The second harmonic error also is one of the obstacles for CRG towards high precision. Therefore, this paper provides a chemical method to evaluate and balance the second harmonic error of cylindrical fused silica resonators. The relation between the frequency split of the n = 1 mode and the second harmonic error of the resonator is obtained. Simulations are performed to analyze the effects of the first three harmonic errors on the frequency splits. The relation between the location of the low-frequency axis of n = 1 mode and the heavy axis of the second harmonic error is also analyzed by simulation. Chemical balancing experiments on two fused silica resonators demonstrate the feasibility of this balancing procedure, and show good consistency with theoretical and simulation analysis. The second harmonic error of the two resonators is reduced by 86.6% and 79.8%, respectively.
A Resonant Pressure Microsensor with a Wide Pressure Measurement Range
Authors: Xiang Chao , Lu Yulan , Cheng Chao , Wang Junbo , Chen Deyong , Chen Jian
Published: April 2021

This paper presents a resonant pressure microsensor with a wide range of pressure measurements. The developed microsensor is mainly composed of a silicon-on-insulator (SOI) wafer to form pressure-sensing elements, and a silicon-on-glass (SOG) cap to form vacuum encapsulation. To realize a wide range of pressure measurements, silicon islands were deployed on the device layer of the SOI wafer to enhance equivalent stiffness and structural stability of the pressure-sensitive diaphragm. Moreover, a cylindrical vacuum cavity was deployed on the SOG cap with the purpose to decrease the stresses generated during the silicon-to-glass contact during pressure measurements. The fabrication processes mainly contained photolithography, deep reactive ion etching (DRIE), chemical mechanical planarization (CMP) and anodic bonding. According to the characterization experiments, the quality factors of the resonators were higher than 15,000 with pressure sensitivities of 0.51 Hz/kPa (resonator I), −1.75 Hz/kPa (resonator II) and temperature coefficients of frequency of 1.92 Hz/°C (resonator I), 1.98 Hz/°C (resonator II). Following temperature compensation, the fitting error of the microsensor was within the range of 0.006% FS and the measurement accuracy was as high as 0.017% FS in the pressure range of 200 ~ 7000 kPa and the temperature range of −40 °C to 80 °C.
Group Theory Analysis to Study Phase Transitions of Quasi-2D Sr3Hf2O7
Authors: da Silva Estelina Lora , Gerami Adeleh Mokhles , Lekshmi P. Neenu , Marcondes Michel L. , Assali Lucy V. C. , Petrilli Helena M. , Correia Joao Guilherme , Lopes Armandina M. L. , Araújo João P.
Published: April 2021

We present an ab-initio study performed in the framework of density functional theory, group-subgroup symmetry analysis and lattice dynamics, to probe the octahedral distortions, which occur during the structural phase transitions of the quasi-2D layered perovskite Sr3Hf2O7 compound. Such a system is characterized by a high-temperature I4/mmm centrosymmetric structure and a ground-state Cmc21 ferroelectric phase. We have probed potential candidate polymorphs that may form the I4/mmm → Cmc21 transition pathways, namely Fmm2, Ccce, Cmca and Cmcm. We found that the band gap widths increase as the symmetry decreases, with the ground-state structure presenting the largest gap width (∼5.95 eV). By probing the Partial Density of States, we observe a direct relation regarding the tilts and rotations of the oxygen perovskite cages as the transition occurs; these show large variations mostly of the O p-states which contribute mostly to the valence band maximum. Moreover, by analyzing the hyperfine parameters, namely the Electric Field Gradients and asymmetric parameters, we observe variations as the transition occurs, from which it is possible to identify the most plausible intermediate phases. We have also computed the macroscopic polarization and confirm that the Cmc21 phase is ferroelectric with a value of spontaneous polarization of 0.0478 C/m2. The ferroelectricity of the ground-state Cmc21 system arises due to a second order parameter related to the coupling of the rotation and tilts of the O perovskite cages together with the Sr displacements.
Structuring of ZnTiO3/TiO2 Adsorbents for the Removal of Methylene Blue, Using Zeolite Precursor Clays as Natural Additives
Authors: Jaramillo-Fierro Ximena , González Silvia , Montesdeoca-Mendoza Fernando , Medina Francesc
Published: April 2021

Adsorption is an effective method of removing harmful pollutants from air and water. In the present study, zeolites prepared by sol-gel method from two Ecuadorian clays were combined with precursor clays and the ZnTiO3/TiO2 semiconductor for adsorbing methylene blue (MB) as a water contaminant. The synthesized compounds were characterized using powder X-ray diffraction, X-ray fluorescence, scanning electron microscopy, energy dispersive X-ray, and surface area measurement. These compounds were combined to form cylindrical extrudates of 0.2 cm (diameter) and 1.0 cm (length). The adsorption characteristics of the composites were measured using batch sorption studies as a function of pH, initial concentration, and contact time. The pseudo-second-order model and the Langmuir isotherm model were better suited to the adsorption process. The equilibrium state was achieved around 180 min of adsorption, and a pH of 7 was established as the optimal operating condition. The maximum adsorption values of the dye were obtained with the composites derived from G-Clay, whose average adsorption capacity was 46.36 mg g−1, in contrast with composites derived from R-Clay, whose average adsorption value was 36.24 mg g−1. The results reflect that synthesized composites could be used potentially for the removal of cationic dye from wastewater.
Interactive Effects of Biosynthesized Nanocomposites and Their Antimicrobial and Cytotoxic Potentials
Authors: El-Kahky Dina , Attia Magdy , Easa Saadia M. , Awad Nemat M. , Helmy Eman A.
Published: April 2021

The present study investigated the biosynthesis of silver (AgNPs), zinc oxide (ZnONPs) and titanium dioxide (TiO2NPs) nanoparticles using Aspergillusoryzae, Aspergillusterreus and Fusariumoxysporum. Nanocomposites (NCs) were successfully synthesized by mixing nanoparticles using a Sonic Vibra-Cell VC/VCX processor. A number of analytical techniques were used to characterize the synthesized biological metal nanoparticles. Several experiments tested biologically synthesized metal nanoparticles and nanocomposites against two types of human pathogenic bacteria, including Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative Escherichia coli and Pseudomonasaeruginosa. Additionally, the antitumor activity in HCT-116 cells (colonic carcinoma) was also evaluated. Significant antimicrobial effects of various synthesized forms of nanoparticles and nanocomposites against E. coli and P. aeruginosa bacteria were detected. Various synthesized biogenic forms of nanoparticles and nanocomposite (9.0 to 29 mm in diameter) had high antibacterial activity and high antitumor activity against HCT-116 cells (colonic carcinoma) with IC50 values of 0.7–100 µg/mL. Biosynthesized NPs are considered an alternative to large-scale biosynthesized metallic nanoparticles and nanocomposites, are simple and cost effective, and provide stable nanomaterials.
Early-Life Metabolic and Hormonal Markers in Blood and Growth until Age 2 Years: Results from a Randomized Controlled Trial in Healthy Infants Fed a Modified Low-Protein Infant Formula
Authors: Kouwenhoven Stefanie M. P. , Fleddermann Manja , Finken Martijn J. J. , Twisk Jos W. R. , van der Beek Eline M. , Abrahamse-Berkeveld Marieke , van de Heijning Bert J. M. , van Harskamp Dewi , van Goudoever Johannes B. , Koletzko Berthold V.
Published: April 2021

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age.
Effects of a Mediterranean Diet, Dairy, and Meat Products on Different Phenotypes of Dyslipidemia: A Preliminary Retrospective Analysis
Authors: Formisano Elena , Pasta Andrea , Cremonini Anna Laura , Di Lorenzo Ilaria , Sukkar Samir Giuseppe , Pisciotta Livia
Published: April 2021

Background: Dyslipidemia is one of the major causes of atherosclerotic cardiovascular disease (ASCVD) and a Mediterranean Diet (MD) is recommended for its prevention. The objectives of this study were to evaluate adherence to an MD at baseline and follow-up, in a cohort of dyslipidemic patients, and to evaluate how different food intakes can influence lipid profile, especially how different sources of saturated fatty acids impact lipid phenotype. Methods: A retrospective analysis was conducted on 106 dyslipidemic patients. Clinical characteristics, lipid profile, and food habits data were collected at baseline and after three months of follow-up with counseling. Adherence to an MD was evaluated with a validated food-frequency questionnaire (MEDI-LITE score). Results: The cross-sectional analysis showed that higher consumption of dairy products correlated independently with higher levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) and with lower triglycerides (TG) levels. Instead, lower HDL-C and TG levels and higher TC levels were independently associated with higher consumption of meat products. Adherence to an MD significantly improved after the follow-up period, from a mean value of 10 ± 3 (median 10, IQR 8–12) to 13 ± 2 (median 14, IQR 12–15), p < 0.0001. Conclusions: Dyslipidemic patients benefit from counseling for improving their adherence to an MD. The high intake of dairy products was associated with less atherogenic hyperlipidemia, which was characterized by higher levels of TC and HDL-C as compared withs the intake of an excessive amount of meat products, which was associated with higher levels of TC and TG and lower levels of HDL-C.
Gut Dysbiosis and Western Diet in the Pathogenesis of Essential Arterial Hypertension: A Narrative Review
Authors: Canale Maria Paola , Noce Annalisa , Di Lauro Manuela , Marrone Giulia , Cantelmo Maria , Cardillo Carmine , Federici Massimo , Di Daniele Nicola , Tesauro Manfredi
Published: April 2021

Metabolic syndrome is a cluster of the most dangerous cardiovascular (CV) risk factors including visceral obesity, insulin resistance, hyperglycemia, alterations in lipid metabolism and arterial hypertension (AH). In particular, AH plays a key role in the complications associated with metabolic syndrome. High salt intake is a well-known risk factor for AH and CV diseases. Vasoconstriction, impaired vasodilation, extracellular volume expansion, inflammation, and an increased sympathetic nervous system (SNS) activity are the mechanisms involved in the pathogenesis of AH, induced by Western diet. Gut dysbiosis in AH is associated with reduction of short chain fatty acid-producing bacteria: acetate, butyrate and propionate, which activate different pathways, causing vasoconstriction, impaired vasodilation, salt and water retention and a consequent high blood pressure. Moreover, increased trimethylamine N-oxide and lipopolysaccharides trigger chronic inflammation, which contributes to endothelial dysfunction and target organs damage. Additionally, a high salt-intake diet impacts negatively on gut microbiota composition. A bidirectional neuronal pathway determines the “brain–gut” axis, which, in turn, influences blood pressure levels. Then, we discuss the possible adjuvant novel treatments related to gut microbiota modulation for AH control.
Dietary Olive Oil Intake Improves Running Endurance with Intramuscular Triacylglycerol Accumulation in Mice
Authors: Komiya Yusuke , Sugiyama Makoto , Ochiai Masaru , Osawa Nanako , Adachi Yuto , Iseki Shugo , Arihara Keizo
Published: April 2021

Olive oil is a functional food shown to have a variety of bioactive effects. Therefore, we expect it to be a novel functional food with an exercise-mimetic effect on skeletal muscles. This study aimed to investigate the effect of olive oil on the endurance capacity and muscle metabolism in mice. Mice fed a 7% (w/w) olive oil diet for eight weeks showed improved treadmill running endurance and increased intramuscular triacylglycerol (IMTG) accumulation in the gastrocnemius muscle compared to soybean oil diet-fed controls. The increase in running endurance with olive oil intake was independent of the muscle fiber type. To elucidate underlying the mechanism of elevated IMTG levels, we examined the expression levels of the genes related to lipid metabolism. We found that the expression of diacylglycerol O-acyltransferase1 (DGAT1) was significantly upregulated in the muscle of olive oil diet-fed mice. In addition, the olive oil diet-fed mice showed no metabolic impairment or differences in growth profiles compared to the controls. These results suggest that dietary olive oil intake affects muscle metabolism and muscle endurance by increasing energy accumulation.
Consequences of the COVID-19 Syndemic for Nutritional Health: A Systematic Review
Authors: Neira Cristian , Godinho Rejane , Rincón Fabio , Mardones Rodrigo , Pedroso Janari
Published: April 2021

Confinement at home, quarantine, and social distancing are some measures adopted worldwide to prevent the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2), which has been generating an important alteration in the routines and qualities of life of people. The impact on health is still being evaluated, and consequences in the nutritional field are not entirely clear. The study objective was to evaluate the current evidence about the impact that preventive measures of physical contact restriction causes in healthy nutrition. A systematic review was carried out according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” PRISMA Group and Cochrane method for rapid systematic reviews. Searching was performed in six electronic databases and evaluated articles published between 2010 and 2020, including among their participants adult subjects who had been exposed to the preventive measures of physical contact restriction. Seven studies met the selection criteria and reported an overall increase in food consumption, weight, Body Mass Index (BMI), and a change in eating style. Findings suggest that healthy nutrition is affected by preventive measures to restrict physical contact as a result of the COVID-19 syndemic.
The Effectiveness of Probiotic Lactobacillus rhamnosus and Lactobacillus casei Strains in Children with Atopic Dermatitis and Cow’s Milk Protein Allergy: A Multicenter, Randomized, Double Blind, Placebo Controlled Study
Authors: Cukrowska Bożena , Ceregra Aldona , Maciorkowska Elżbieta , Surowska Barbara , Zegadło-Mylik Maria Agnieszka , Konopka Ewa , Trojanowska Ilona , Zakrzewska Magdalena , Bierła Joanna Beata , Zakrzewski Mateusz , Kanarek Ewelina , Motyl Ilona
Published: April 2021

Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this multicenter randomized placebo-controlled trial was to evaluate the effectiveness of a probiotic preparation comprising Lactobacillus rhamnosus ŁOCK 0900, Lactobacillus rhamnosus ŁOCK 0908, and Lactobacillus casei ŁOCK 0918 in children under 2 years of age with AD and a cow’s milk protein (CMP) allergy. The study enrolled 151 children, who—apart from being treated with a CMP elimination diet—were randomized to receive the probiotic preparation at a daily dose of 109 bacteria or a placebo for three months, with a subsequent nine-month follow-up. The primary outcomes included changes in AD symptom severity assessed with the scoring AD (SCORAD) index and in the proportion of children with symptom improvement (a SCORAD score decreased by at least 30% in comparison with that at baseline). After the three-month intervention, both the probiotic and placebo groups showed a significant (p < 0.0001) decrease in SCORAD scores, which was maintained nine months later. The percentage of children who showed improvement was significantly higher in the probiotic than in the placebo group (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.13–5.8; p = 0.012) after three months. Probiotics induced SCORAD improvement mainly in allergen sensitized patients (OR 6.03; 95% CI 1.85–19.67, p = 0.001), but this positive effect was not observed after nine months. The results showed that the mixture of probiotic ŁOCK strains offers benefits for children with AD and CMP allergy. Further research is necessary to assess the effect of probiotic supplementation on the development of immune tolerance (NCT04738565).
Assessing the Impact of Salt Reduction Initiatives on the Chronic Disease Burden of Singapore
Authors: Tan Ken Wei , Quaye Sharon Esi Duoduwa , Koo Joel Ruihan , Lim Jue Tao , Cook Alex R. , Dickens Borame L.
Published: April 2021

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.
Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Treatment of Viral Diseases
Authors: Harrell Carl , Popovska Jovicic Biljana , Djonov Valentin , Volarevic Vladislav
Published: April 2021

Mesenchymal stem cells (MSCs) are adult, immunomodulatory stem cells which reside in almost all postnatal tissues. Viral antigens and damage-associated molecular patterns released from injured and infected cells activate MSCs, which elicit strong antiviral immune response. MSC-sourced interferons and inflammatory cytokines modulate the cytotoxicity of NK cells and CTLs, enhance the antigen-presentation properties of DCs and macrophages, regulate cytokine synthesis in CD4+ T helper cells and promote antibody production in B cells. After the elimination of viral pathogens, MSCs produce immunoregulatory cytokines and trophic factors, prevent the over-activation of immune cells and promote tissue repair and regeneration. In this review article, we summarize the current knowledge on the molecular mechanisms that are responsible for the MSC-dependent elimination of virus-infected cells, and we emphasize the therapeutic potential of MSCs and their secretomes in the treatment of viral diseases.
Home Management of Patients with Moderate or Severe Respiratory Failure Secondary to COVID-19, Using Remote Monitoring and Oxygen with or without HFNC
Authors: Annunziata Anna , Coppola Antonietta , Carannante Novella , Simioli Francesca , Lanza Maurizia , Di Micco Pierpaolo , Fiorentino Giuseppe
Published: April 2021

Background: Home treatment of patients affected by COVID-19 is still a matter of daily debate. During the clinical evolution of the disease, there are high risks of lung failure, which requires oxygen therapy. Here, we report our clinical experience with at-home treatment using high-flow nasal cannula in non-hospitalised patients with confirmed COVID-19. Patients and methods: In this study, 18 patients with moderate-to-severe respiratory failure secondary to COVID-19 were monitored at home daily for temperature and SpO2 measurements. Other parameters such as saturation of peripheral oxygen (SpO2), SpO2/FiO2 (fraction of inspired oxygen), temperature, and lung performance were monitored periodically. Depending on oxygen requirements, the patients also received either standard oxygen via a face mask or, if higher FiO2 required, high-flow nasal cannula (HFNC). Results: All 18 patients had favourable outcomes and recovered from COVID-19. No death was recorded in this group. Conclusion: Our clinical experience proves that high-flow nasal cannula oxygen therapy may be considered for at-home treatment of COVID-19 patients with moderate lung failure. This could be useful for further treatment during the pandemic and may also be considered in future epidemics.
Mild Cognitive Impairment and Mild Dementia: The Role of Ginkgo biloba (EGb 761®)
Authors: Tomino Carlo , Ilari Sara , Solfrizzi Vincenzo , Malafoglia Valentina , Zilio Guglielmo , Russo Patrizia , Proietti Stefania , Marcolongo Federica , Scapagnini Giovanni , Muscoli Carolina , Rossini Paolo Maria
Published: April 2021

Mild cognitive impairment (MCI) and dementia are clinically prevalent in the elderly. There is a high risk of cognitive decline in patients diagnosed with MCI or dementia. This review describes the effectiveness of Ginkgo biloba leaf special extract EGb 761® for the treatment of dementia syndromes and EGb 761® combination therapy with other medications for symptomatic dementia. This drug has shown convincing results, improving cognitive function, neuropsychiatric symptoms and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild to moderate dementia. Currently, there is little evidence to support the combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb 761® in mixed therapy.
Novel Mechanism for Memantine in Attenuating Diabetic Neuropathic Pain in Mice via Downregulating the Spinal HMGB1/TRL4/NF-kB Inflammatory Axis
Authors: Alomar Suliman Y. , Gheit Rehab E. Abo El , Enan Eman T. , El-Bayoumi Khaled S. , Shoaeir Mohamed Z. , Elkazaz Amany Y. , Al Thagfan Sultan S. , Zaitone Sawsan A. , El-Sayed Rehab M.
Published: April 2021

Diabetic neuropathic pain (DNP) is a common diabetic complication that currently lacks an efficient therapy. The aim of the current work was to uncover the anti-allodynic and neuroprotective effects of memantine in a model of mouse diabetic neuropathy and its ameliorative effect on the high-mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-k B (NF-kB) inflammatory axis. Diabetes was prompted by an alloxan injection (180 mg/kg) to albino mice. On the ninth week after diabetes induction, DNP was confirmed. Diabetic mice were randomly allocated to two groups (six mice each); a diabetes mellitus (DM) group and DM+memantine group (10 mg/kg, daily) for five weeks. DNP-related behaviors were assessed in terms of thermal hyperalgesia and mechanical allodynia by hot-plate and von Frey filaments. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the spinal glutamate, interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α). The spinal levels of N-methyl-D-aspartate type 1 receptor (NMDAR1), HMGB1, TLR4, and phosphorylated NF-kB were assessed using Western blotting. Histopathological investigation of the spinal cord and sciatic nerves, together with the spinal cord ultrastructure, was employed for assessment of the neuroprotective effect. Memantine alleviated pain indicators in diabetic mice and suppressed excessive NMDAR1 activation, glutamate, and pro-inflammatory cytokine release in the spinal cord. The current study validated the ability of memantine to combat the HMGB1/TLR4/NF-kB axis and modulate overactive glutamate spinal transmission, corroborating memantine as an appealing therapeutic target in DNP.
Identification of Anti-Inflammatory and Anti-Proliferative Neolignanamides from Warburgia ugandensis Employing Multi-Target Affinity Ultrafiltration and LC-MS
Authors: Zhuang Xiao-Cui , Zhang Yong-Li , Chen Gui-Lin , Liu Ye , Hu Xiao-Lan , Li Na , Wu Jian-Lin , Guo Ming-Quan
Published: April 2021

Previous reports have illustrated that the incidence and mortality of cancer are increasing year by year worldwide. In addition, the occurrence, development, recurrence and metastasis of cancer are closely related to inflammation, which is a kind of defensive response of human body to various stimuli. As an important medicinal plant in Africa, Warburgia ugandensis has been reported to have certain anti-inflammatory and anti-proliferative activities, but its specific components and mechanisms of action remain elusive. To tackle this challenge, affinity ultrafiltration with drug targets of interest coupled to high-performance liquid chromatography-mass spectrometry (AUF-HPLC-MS/MS) could be utilized to quickly screen out bioactive constituents as ligands against target enzymes from complex extracts of this plant. AUF-HPLC-MS/MS with four drug targets, i.e., cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), topoisomerase I (Top I) and topoisomerase II (Top II) were used to rapidly screen and characterize the anti-inflammatory and anti-proliferative natural ligands from W. ugandensis, and the resulting potential active compounds as ligands with specific binding affinity to COX-2, 5-LOX, Top I and Top II, were isolated with modern separation and purification techniques and identified with spectroscopic method like NMR, and then their antiinflammatory and anti-proliferative activities were tested to verify the screening results from AUF-HPLC-MS/MS. Compounds 1 and 2, which screened out and identified from W. ugandensis showed remarkable binding affinity to COX-2, 5-LOX, Top I and Top II with AUF-HPLC-MS/MS. In addition, 1 new compound (compound 3), together with 5 known compounds were also isolated and identified from W. ugandensis. The structure of compound 3 was elucidated by extensive 1D, 2D NMR data and UPLC-QTOF-MS/MS. Furthermore, compounds 1 and 2 were further proved to possess both anti-inflammatory and anti-proliferative activities which are in good agreement with the screening results using AUF-HPLC-MS/MS. This work showcased an efficient method for quickly screening out bioactive components with anti-inflammatory and anti-proliferative activity from complex medicinal plant extracts using AUF-HPLC-MS/MS with target enzymes of interest, and also demonstrated that neolignanamides (compounds 1 and 2) from W. ugandensis would be the active components responsible for its anti-inflammatory and anti-proliferative activity with the potential to treat cancer and inflammation.
Extracellular Vesicles and Their Potential Significance in the Pathogenesis and Treatment of Osteoarthritis
Authors: Mustonen Anne-Mari , Nieminen Petteri
Published: April 2021

Osteoarthritis (OA) is a chronic joint disease characterized by inflammation, gradual destruction of articular cartilage, joint pain, and functional limitations that eventually lead to disability. Join tissues, including synovium and articular cartilage, release extracellular vesicles (EVs) that have been proposed to sustain joint homeostasis as well as to contribute to OA pathogenesis. EVs transport biologically active molecules, and OA can be characterized by altered EV counts and composition in synovial fluid. Of EV cargo, specific non-coding RNAs could have future potential as diagnostic biomarkers for early OA. EVs may contribute to the propagation of inflammation and cartilage destruction by transporting and enhancing the production of inflammatory mediators and cartilage-degrading proteinases. In addition to inducing OA-related gene expression patterns in synoviocytes and articular chondrocytes, EVs can induce anti-OA effects, including increased extracellular matrix deposition and cartilage protection. Especially mesenchymal stem cell-derived EVs can alleviate intra-articular inflammation and relieve OA pain. In addition, surgically- or chemically-induced cartilage defects have been repaired with EV therapies in animal models. While human clinical trials are still in the future, the potential of actual cures to OA by EV products is very promising.
Green Nanotechnology in the Formulation of a Novel Solid Dispersed Multilayered Core-Sheath Raloxifene-Loaded Nanofibrous Buccal Film; In Vitro and In Vivo Characterization
Authors: Nageeb El-Helaly Sara , Abd-Elrasheed Eman , Salim Samar A. , Fahmy Rania H. , Salah Salwa , EL-Ashmoony Manal M.
Published: April 2021

Green nanotechnology utilizes the principles of green chemistry to formulate eco-friendly nanocarrier systems to mitigate patients and environment hazards. Raloxifene (RLX) demonstrates poor aqueous solubility (BCS class II) and low bioavailability, only 2% (extensive first-pass metabolism). The aim of this study is to enhance RLX solubility and bioavailability via development of novel solid dispersed multilayered core-sheath RLX-loaded nanofibers (RLX-NFs) without the involvement of organic solvents. A modified emulsion electrospinning technique was developed. Electrospinning of an RLX-nanoemulsion (RLX-NE) with polymer solution (poly vinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and chitosan (CS) in different volume ratios (1:9, 2:8, and 4:6) using D-optimal response surface methodology was adopted. In vitro characterization of RLX-loaded NFs was performed; scanning electron microscope (SEM), thermal analysis, drug content, release studies, and bioadhesion potential. The optimum NFs formula was evaluated for morphology using high-resolution transmission electron microscopy (HRTEM), and ex vivo drug permeation. The superiority of E2 (comprising RLX-NE and PVA (2:8)) over other NF formulae was statistically observed with respect to Q60 (56.048%), Q240 (94.612%), fiber size (594.678 nm), mucoadhesion time 24 h, flux (5.51 µg/cm2/h), and enhancement ratio (2.12). RLX pharmacokinetics parameters were evaluated in rabbits following buccal application of NF formula E2, relative to RLX oral dispersion. E2 showed significantly higher Cmax (53.18 ± 4.56 ng/mL), and relative bioavailability (≈2.29-fold).
Pharmacokinetic Changes According to Single or Multiple Oral Administrations of Socheongryong-Tang to Rats: Presented as a Typical Example of Changes in the Pharmacokinetics Following Multiple Exposures to Herbal Medicines
Authors: Jeong Seung-Hyun , Jang Ji-Hun , Jung Da-Hwa , Lee Guk-Yeo , Lee Yong-Bok
Published: April 2021

The purpose of this study was to investigate the pharmacokinetic properties of ephedrine, paeoniflorin, and cinnamic acid after single or multiple doses of Socheongryong-tang (SCRT) were administered to rats, and to present an example of the pharmacokinetic changes following multiple doses of an herbal medicine. SCRT is a traditional herbal medicine that has been used clinically for a long time, and its main ingredients include ephedrine, paeoniflorin, and cinnamic acid. However, studies on the pharmacokinetic properties of SCRT are insufficient, and particularly, no pharmacokinetic information has been reported for multiple doses. In this study, SCRT was administered orally to rats once or multiple times, and plasma sampled at different times was quantitatively analyzed for ephedrine, paeoniflorin, and cinnamic acid using ultra-high-performance liquid chromatography-tandem mass spectrometry. There was a difference between the pharmacokinetic parameter values of each component (especially in paeoniflorin and cinnamic acid) obtained after single or multiple doses of SCRT. The actual observed values of each component obtained after multiple doses of SCRT were clearly different from the predicted results of multiple-dose simulations based on the pharmacokinetic profiles obtained after a single dose. The results confirmed that the plasma concentrations and, thus, exposures to paeoniflorin and cinnamic acid were significantly increased when SCRT was administered multiple times, whereas that of ephedrine was not. The results of this study are expected to provide useful pharmacokinetic data for the safety and efficacy evaluation of SCRT in the future and demonstrate the necessity of pharmacokinetic comparison studies according to single or multiple oral administrations of herbal medicines.
Biomimetic Approaches to the Synthesis of Natural Disesquiterpenoids: An Update
Authors: Caprioglio Diego , Salamone Stefano , Pollastro Federica , Minassi Alberto
Published: April 2021

Natural disesquiterpenoids represent a small group of secondary metabolites characterized by complex molecular scaffolds and interesting pharmacological profiles. In the last decade, more than 400 new disesquiterpenoids have been discovered and fully characterized, pointing out once more the “magic touch” of nature in the design of new compounds. The perfect blend of complex and unique architectures and biological activity has made sesquiterpene dimers an attractive and challenging synthetic target, inspiring organic chemists to find new and biomimetic approaches to replicate the efficiency and the selectivity of natural processes under laboratory conditions. In this work, we present a review covering the literature from 2010 to 2020 reporting all the efforts made in the total synthesis of complex natural disesquiterpenoids.