bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosan Is Necessary for the Structure of the Cell Wall, and Full Virulence of Ustilago maydis
Authors: Sánchez-Arreguin José Alejandro , Ortiz-Castellanos M. Lucila , Robledo-Briones Angélica Mariana , León-Ramírez Claudia Geraldine , Martínez-Soto Domingo , Ruiz-Herrera José
Published: August 2022

Smut fungi comprise a large group of biotrophic phytopathogens infecting important crops, such as wheat and corn. U. maydis is a plant pathogenic fungus responsible for common smut in maize and teocintle. Through our analysis of the transcriptome of the yeast-to-mycelium dimorphic transition at acid pH, we determined the number of genes encoding chitin deacetylases of the fungus, and observed that the gene encoding one of them (UMAG_11922; CDA1) was the only one up-regulated. The mutation of this gene and the analysis of the mutants revealed that they contained reduced amounts of chitosan, were severely affected in their virulence, and showed aberrant mycelial morphology when grown at acid pH. When the CDA1 gene was reinserted into the mutants by the use of an autonomous replication plasmid, virulence and chitosan levels were recovered in the retro mutant strains, indicating that the CDA1 gene was involved in these features. These data revealed that chitosan plays a crucial role in the structure and morphogenesis of the cell wall during mycelial development of the fungus, and that in its absence, the cell wall becomes altered and is unable to support the stress imposed by the defense mechanism mounted on by the plant host during the infection process.
Insulating Material Development for the Design of Standoff Insulators Fed by Hybrid Voltage
Authors: Montanari Gian Carlo , Ghosh Riddhi , Ramin Robin , Nath Debasish
Published: August 2022

Innovative electrical assets are being developed in transmission and distribution, as well as in electrified transportation, from ships to aerospace. In general, power electronics have to master the whole power supply, being the driver of high specific power, low weight and volume components, in addition to enabling flexible and highly variable power flow. In these conditions, electrical and electronic insulation systems will have to withstand new types and levels of electric stresses, while still maintaining its reliability throughout its whole design life. This paper presents a study on the interrelation between insulating material properties and surface field of standoff insulators. The aim is mainly to provide indications on material properties which can be tailored to provide a robust, reliable and optimised insulator design that will hold for any type of electrical stress the insulation will have to withstand during operation. Specifically, we focus on ac and dc supply, including voltage transients, which could feed the same insulator depending on operation, according to a hybrid asset paradigm. The challenge is, indeed, to establish a pattern to material and insulation system design which takes into account the differences between the types of electrical stress profile and magnitude when insulators are supplied either in a dc or in ac, in order to infer which type of material characteristics would be more appropriate for the sake of life and reliability. The main contribution of this paper is to show that engineering the values of bulk and surface conductivity (which can be done selecting appropriate materials or modifying them, e.g., by nano-structuration) and modelling surface discharge inception would allow the electric field profile to be stabilised whatever the shape of the applied waveform. This will enable us to reach a reliability target that not only accounts for macroscopic phenomena, but also for the likelihood of extrinsic accelerated aging mechanism occurrence as partial discharges. In such a way, optimization of conditions to improve life, reliability, design and creepage and clearance characteristics can be achieved.
Germanium Nanoparticles Prepared by Laser Ablation in Low Pressure Helium and Nitrogen Atmosphere for Biophotonic Applications
Authors: Fronya Anastasiya A. , Antonenko Sergey V. , Karpov Nikita V. , Pokryshkin Nikolay S. , Eremina Anna S. , Yakunin Valery G. , Kharin Alexander Yu. , Syuy Alexander V. , Volkov Valentin S. , Dombrovska Yaroslava , Garmash Alexander A. , Kargin Nikolay I. , Klimentov Sergey M. , Timoshenko Victor Yu. , Kabashin Andrei V.
Published: August 2022

Due to particular physico-chemical characteristics and prominent optical properties, nanostructured germanium (Ge) appears as a promising material for biomedical applications, but its use in biological systems has been limited so far due to the difficulty of preparation of Ge nanostructures in a pure, uncontaminated state. Here, we explored the fabrication of Ge nanoparticles (NPs) using methods of pulsed laser ablation in ambient gas (He or He-N2 mixtures) maintained at low residual pressures (1–5 Torr). We show that the ablated material can be deposited on a substrate (silicon wafer in our case) to form a nanostructured thin film, which can then be ground in ethanol by ultrasound to form a stable suspension of Ge NPs. It was found that these formed NPs have a wide size dispersion, with sizes between a few nm and hundreds of nm, while a subsequent centrifugation step renders possible the selection of one or another NP size fraction. Structural characterization of NPs showed that they are composed of aggregations of Ge crystals, covered by an oxide shell. Solutions of the prepared NPs exhibited largely dominating photoluminescence (PL) around 450 nm, attributed to defects in the germanium oxide shell, while a separated fraction of relatively small (5–10 nm) NPs exhibited a red-shifted PL band around 725 nm under 633 nm excitation, which could be attributed to quantum confinement effects. It was also found that the formed NPs exhibit high absorption in the visible and near-IR spectral ranges and can be strongly heated under photoexcitation in the region of relative tissue transparency, which opens access to phototherapy functionality. Combining imaging and therapy functionalities in the biological transparency window, laser-synthesized Ge NPs present a novel promising object for cancer theranostics.
A Decision Support System (DSS) for the Prediction and Selection of Optimum Operational Parameters in Pressure Die-Casting Processes
Authors: Martínez-Pastor Juan , Hernández-Ortega Juan José , Zamora Rosendo
Published: August 2022

A large number of material and process parameters affect both the part quality and the process performance in pressure die-casting (PDC) processes. The complex relations between most of these variables make PDC process optimisation a difficult issue which has been widely studied for many years. Although there are several analytical and numerical models to optimise certain process parameters, it is difficult to establish a specific operational configuration for PDC machines that ensures the joint optimisation of these variables. Therefore, in this study, some of these optimisation models have been implemented in a Decision Support System (DSS) that allows us to define an operational region that establishes a setup of machine parameters that ensures the manufacture of quality parts. By using this DSS, the user can set the values of the input variables related to the casting material, the die, or the casting machine. Then the corresponding calculations are made by the system and the results are expressed in terms of certain output variables such as the maximum filling time, maximum filling fraction, or the plunger velocity profile among others. The DSS allows the user to estimate the influence between input and output variables and find proper values for the input variables to achieve an optimum operational range. Consequently, improved process performance can be achieved taking into account productivity, part quality, and economic aspects.
Blown Composite Films of Low-Density/Linear-Low-Density Polyethylene and Silica Aerogel for Transparent Heat Retention Films and Influence of Silica Aerogel on Biaxial Properties
Authors: Yang Seong Baek , Lee Jungeon , Yeasmin Sabina , Park Jae Min , Han Myung Dong , Kwon Dong-Jun , Yeum Jeong Hyun
Published: August 2022

Blown films based on low-density polyethylene (LDPE)/linear low-density polyethylene (LLDPE) and silica aerogel (SA; 0, 0.5, 1, and 1.5 wt.%) were obtained at the pilot scale. Good particle dispersion and distribution were achieved without thermo oxidative degradation. The effects of different SA contents (0.5–1.5 wt.%) were studied to prepare transparent-heat-retention LDPE/LLDPE films with improved material properties, while maintaining the optical performance. The optical characteristics of the composite films were analyzed using methods such as ultraviolet–visible spectroscopy and electron microscopy. Their mechanical characteristics were examined along the machine and transverse directions (MD and TD, respectively). The MD film performance was better, and the 0.5% composition exhibited the highest stress at break. The crystallization kinetics of the LDPE/LLDPE blends and their composites containing different SA loadings were investigated using differential scanning calorimetry, which revealed that the crystallinity of LDPE/LLDPE was increased by 0.5 wt.% of well-dispersed SA acting as a nucleating agent and decreased by agglomerated SA (1–1.5 wt.%). The LDPE/LLDPE/SA (0.5–1.5 wt.%) films exhibited improved infrared retention without compromising the visible light transmission, proving the potential of this method for producing next-generation heat retention films. Moreover, these films were biaxially drawn at 13.72 MPa, and the introduction of SA resulted in lower draw ratios in both the MD and TD. Most of the results were explained in terms of changes in the biaxial crystallization caused by the process or the influence of particles on the process after a systematic experimental investigation. The issues were strongly related to the development of blown nanocomposites films as materials for the packaging industry.
Adsorption of Heavy Metals Ions from Mining Metallurgical Tailings Leachate Using a Shell-Based Adsorbent: Characterization, Kinetics and Isotherm Studies
Authors: Fernández Pérez Begoña , Ayala Espina Julia , Fernández González María de Los Ángeles
Published: August 2022

This study defines the optimal parameters that allow the use of waste mollusk shells (WS) to remove heavy metals from three mining and metallurgical leachates. First, the influence of parameters such as pH, contact time, initial metal concentration, adsorbent dose and the presence of co-ions in Cu2+, Cd2+, Zn2+ and Ni2+ adsorption was investigated in synthetic solutions. Metal uptake was found to be dependent on the initial pH of the solution, the removal rate increasing with the increase in pH, showing the highest affinity at pH 5–6. The removal efficiency at lower concentrations was greater than at higher values. The competitive adsorption results on bimetallic solutions showed that the adsorption capacity of the sorbent was restricted by the presence of other ions and suppressed the uptake of heavy metals compared to the single adsorption. Cu2+ was the metal that most inhibited the removal of Cd2+, Zn2+ and Ni2+. The Langmuir isotherm provided the best fit to the experimental data for Cu2+, Cd2+ and Zn2+ and the Freundlich isotherm, for Ni2+. The data showed that the maximum adsorption capacity amax for Zn2+, Cd2+ and Cu2+, was 526.32 mg g−1, 555.56 mg g−1 and 769.23 mg g−1, respectively. Sorption kinetics data best fit the pseudo-second-order kinetic model. The results obtained in the tests with three mining and metallurgical leachates showed that WS were effective in simultaneously removing several heavy metals ions such as Cu, Ni, Zn, Cd, Ni, As and Se.
Green Conversion of the Hazardous Cathode Ray Tube and Red Mud into Radiation Shielding Concrete
Authors: Sayyed M. I. , Almousa Nouf , Elsafi Mohamed
Published: August 2022

The present investigation was aimed at the utilization of alternate materials, emphasizing hazardous industrial products (red mud and cathode ray tubes), as constituents of radiation shielding concrete. The usage of these hazardous industrial products improves the sustainability and performance of the radiation shielding concrete. Five concrete blocks were cast and their density, compressive strength, gamma shielding factors, radiation absorption ratio, and transmission factor were explored. For this purpose, gamma-ray shielding measurements were done with the help of an HPGe detector. Mix-1, with zero contents of red mud and CRTs, had the lowest LAC. The LAC results demonstrated that the shielding performance of the current concretes would be better with the increase in red mud and cathode ray tube glass. The Transmission factor (TF) for the prepared concretes with a thickness of 2 cm varied between 11.9–26.1% at 0.06 MeV, while it varied between 4–13% for a thickness of 3 cm. The TF results showed that the composites with a thickness of 2, 3, or 5 cm are good shields against lower energy radiation. The radiation absorption ratio (RAR) for the prepared concretes is high at low energy, suggesting that these new composites can absorb most of the low-energy photons. The RAR results emphasize that the increase in CRTs in the new composites enhanced the radiation shielding features, and when the CRT glass is at a maximum, more attenuation was achieved.
Experimental Study on the Optimization of Coal-Based Solid Waste Filling Slurry Ratio Based on the Response Surface Method
Authors: Wei Zhen , Yang Ke , He Xiang , Zhang Jiqiang , Hu Guangcheng
Published: August 2022

The large production and low comprehensive utilization rate of solid waste from coal power base affects the efficient and coordinated development of regional resources and the ecological environment. In order to promote utilization of solid waste from coal power base, coal gangue, fly ash, and gasification slag are mixed as raw materials to prepare filling materials, and a study on the evolution law of the mechanical properties of coal-based solid waste filling body is systematically carried out. After clarifying the physical and chemical properties of the filling materials, the Box–Behnken experimental design method was used to study the effects of slurry mass fraction, coal gangue, fly ash, and gasification slag on the strength of the filling body based on the response surface-satisfaction function coupling theory. Furthermore, a multivariate nonlinear regression model was constructed for the strength of the filling body at different maintenance ages. Based on the analysis of variance (ANOVA) and the response surface function, the impact mechanism of influencing factors and their interaction on the strength of filler were revealed. The results show that the strength of the filler is affected by single factors and interactions between factors. The interaction of slurry mass fraction and gangue dosing has a significant effect on the strength of the filler in the early stage; the interaction of fly ash and gangue dosing has a significant effect on the strength of the filler in the middle stage; the interaction of slurry mass fraction and gasification slag dosing has a significant effect on the strength of the filler in the final stage. The mixed filling materials significantly affect the strength of the filler as the maintenance time is extended. The mixed filling materials are extensively interlaced with the hydration products, calcium alumina, and calcium silicate hydrate (C-S-H) gel, forming a stable three-dimensional spatial support system as the maintenance time increases. The best ratio to meet the requirements of mine filling slurry pipeline transportation and filling body strength was selected using the regression model and the proposed economic function of filling material.
New Aluminum Syntactic Foam: Synthesis and Mechanical Characterization
Authors: Sánchez de la Muela A. M. , García Cambronero L. E. , Malheiros L. F. , Ruiz-Román J. M.
Published: August 2022

Metal matrix syntactic foams (MMSF) are advanced cellular materials constituted by a system of a minimum of two phases, in which a dispersion of hollow particles is embedded by a continuous metal matrix. The incorporation of porous fillers favors the development of low-density materials with exceptional behavior for damping vibrations, impacts, and blast effects, shielding acoustic, thermal, and electromagnetic energies. There are three main techniques to produce them: infiltration casting technique (ICT), stir casting technique (SCT), and powder metallurgy technique (P/M). The first two techniques are used for embedding filler into lower melting point metallic matrices than fillers, in contrast to P/M. The present study demonstrates the feasibility of producing MMSF with components of similar melting points by ICT. The fillers were synthesized in-situ with aluminum and a natural foaming agent from wastes of Spanish white marble quarries. These novel aluminum syntactic foams (ASF) were mechanically characterized following the ISO-13314 and exhibited a porosity, plateau stress, and energy absorption capacity of 41%, 37.65 MPa, 8.62 MJ/m3 (at 35% of densification), respectively. These properties are slightly superior to equal porosity LECA ASF, making these novel ASF suitable for the same applications as LECA-ASF.
Zirconia versus Titanium Implants: 8-Year Follow-Up in a Patient Cohort Contrasted with Histological Evidence from a Preclinical Animal Model
Authors: Duncan Warwick J. , Ma Sunyoung , Siddiqi Allauddin , Osman Reham B.
Published: August 2022

Zirconia ceramic (ZC) implants are becoming more common, but comparisons between preclinical histology and long-term clinical trials are rare. This investigation comprised (1) 8-year clinical follow-up of one-piece ZC or titanium (Ti) implants supporting full overdentures and (2) histomorphometric analysis of the same implants in an animal model, comparing implants with various surface treatments. Methods: (1) Clinical trial: 24 completely edentulous participants (2 groups of N = 12) received 7 implants (one-piece ball-abutment ZC or Ti; maxilla N = 4, mandible N = 3) restored with implant overdentures. Outcomes after 8-years included survival, peri-implant bone levels, soft-tissue responses, and prosthodontic issues. (2) Preclinical trial: 10 New Zealand sheep received 4 implants bilaterally in the femoral condyle: Southern Implants ZC or Ti one-piece implants, identical to the clinical trial, and controls: Southern ITC® two-piece implants with the same surface or Nobel (NBC) anodised (TiUnite™) surface. %Bone-implant contact (%BIC) was measured after 12 weeks of unloaded healing. Results: 8 of 24 participants (33%) of an average age of 75 ± 8 years were recalled; 21% of original participants had died, and 46% could not be contacted. 80.4% of implants survived; excluding palatal sites, 87.5% of Ti and 79% of ZC implants survived. All failed implants were in the maxilla. Three ZC implants had fractured. Bone loss was similar for Ti vs. ZC; pocket depths (p = 0.04) and attachment levels (p = 0.02) were greater for Ti than ZC implants. (1.7 ± 1.6 mm vs. 1.6 ± 1.3 mm). All implants in sheep femurs survived. %BIC was not statistically different for one-piece blasted surface Ti (80 ± 19%) versus ZC (76 ± 20%) or ITC® (75 ± 16 mm); NBC had significantly higher %BIC than ITC (84 ± 17%, p = 0.4). Conclusion: Short-term preclinical results for ZC and Ti one-piece implants showed excellent bone-implant contact in unloaded femoral sites. This differed from the long-term clinical results in older-aged, edentulous participants. While ZC and Ti implants showed equivalent performance, the risks of peri-implantitis and implant loss in older, completely edentulous patients remain a significant factor.
Temperature Field Measurement of Photovoltaic Module Based on Fiber Bragg Grating Sensor Array
Authors: Li Guoli , Feng Fei , Wang Fang , Wei Bo
Published: August 2022

Studying the temperature field of photovoltaic modules is important for improving their power generation efficiency. To solve the problem of traditional sensors being unsuitable for measuring the spatial temperature field, we designed a real-time detection scheme of the photovoltaic module temperature field based on a fiber Bragg grating (FBG) sensor array. In this scheme, wavelength division multiplexing and space division multiplexing technologies were applied. The multi-channel FBG sensor strings were arranged on the surface and in the near field of the photovoltaic module. Different FBG strings were selected through optical switches, and the wavelength of the FBG string was addressed and demodulated using the tunable laser method and a peak-seeking algorithm. A measurement experiment of the photovoltaic module temperature field was carried out in an outdoor environment. The experimental results showed that the fluctuation law of the photovoltaic module surface and near-field temperature is basically consistent with that of solar radiation power. The temperature of the photovoltaic module decayed from the surface to space. Within 6 mm of the photovoltaic module surface, the temperature sharply dropped, and then the downward trend became flat. The lower the solar radiation power and the higher the wind speed, the faster the temperature decay. This method provides technical support for measuring the temperature field of a photovoltaic module and other heat source equipment.
Improved Plasma Lipids, Anti-Inflammatory Activity, and Microbiome Shifts in Overweight Participants: Two Clinical Studies on Oral Supplementation with Algal Sulfated Polysaccharide
Authors: Roach Lauren A. , Meyer Barbara J. , Fitton J. Helen , Winberg Pia
Published: August 2022

Seaweed polysaccharides in the diet may influence both inflammation and the gut microbiome. Here we describe two clinical studies with an Ulva sp. 84-derived sulfated polysaccharide—“xylorhamnoglucuronan” (SXRG84)—on metabolic markers, inflammation, and gut flora composition. The first study was a double-blind, randomized placebo-controlled trial with placebo, and either 2 g/day or 4 g/day of SXRG84 daily for six weeks in 64 overweight or obese participants (median age 55 years, median body mass index (BMI) 29 kg/m2). The second study was a randomized double-blind placebo-controlled crossover trial with 64 participants (median BMI 29 kg/m2, average age 52) on placebo for six weeks and then 2 g/day of SXRG84 treatment for six weeks, or vice versa. In Study 1, the 2 g/day dose exhibited a significant reduction in non-HDL (high-density lipoprotein) cholesterol (−10% or −0.37 mmol/L, p = 0.02) and in the atherogenic index (−50%, p = 0.05), and two-hour insulin (−12% or −4.83 mU/L) showed trends for reduction in overweight participants. CRP (C-reactive protein) was significantly reduced (−27% or −0.78 mg/L, p = 0.03) with the 4 g/day dose in overweight participants. Significant gut flora shifts included increases in Bifidobacteria, Akkermansia, Pseudobutyrivibrio, and Clostridium and a decrease in Bilophila. In Study 2, no significant differences in lipid measures were observed, but inflammatory cytokines were improved. At twelve weeks after the SXRG84 treatment, plasma cytokine concentrations were significantly lower than at six weeks post placebo for IFN-γ (3.4 vs. 7.3 pg/mL), IL-1β (16.2 vs. 23.2 pg/mL), TNF-α (9.3 vs. 12.6 pg/mL), and IL-10 (1.6 vs. 2.1 pg/mL) (p < 0.05). Gut microbiota abundance and composition did not significantly differ between groups (p > 0.05). Together, the studies illustrate improvements in plasma lipids and an anti-inflammatory effect of dietary SXRG84 that is participant specific.
Genetic Polymorphism of PTPN22 in Autoimmune Diseases: A Comprehensive Review
Authors: Tizaoui Kalthoum , Shin Jae Il , Jeong Gwang Hun , Yang Jae Won , Park Seoyeon , Kim Ji Hong , Hwang Soo Young , Park Se Jin , Koyanagi Ai , Smith Lee
Published: August 2022

It is known that the etiology and clinical outcomes of autoimmune diseases are associated with a combination of genetic and environmental factors. In the case of the genetic factor, the SNPs of the PTPN22 gene have shown strong associations with several diseases. The recent exploding numbers of genetic studies have made it possible to find these associations rapidly, and a variety of autoimmune diseases were found to be associated with PTPN22 polymorphisms. Proteins encoded by PTPN22 play a key role in the adaptative and immune systems by regulating both T and B cells. Gene variants, particularly SNPs, have been shown to significantly disrupt several immune functions. In this review, we summarize the mechanism of how PTPN22 and its genetic variants are involved in the pathophysiology of autoimmune diseases. In addition, we sum up the findings of studies reporting the genetic association of PTPN22 with different types of diseases, including type 1 diabetes mellitus, systemic lupus erythematosus, juvenile idiopathic arthritis, and several other diseases. By understanding these findings comprehensively, we can explain the complex etiology of autoimmunity and help to determine the criteria of disease diagnosis and prognosis, as well as medication developments.
Impact of Short Sleep Duration on the Incidence of Obesity and Overweight among Children and Adolescents
Authors: Han Seung-Ho , Yee Jae-Yong , Pyo Jung-Soo
Published: August 2022

Background and Objectives: The prevalence of obesity among children is increasing and is highlighting many problems. Lack of sleep is common among children and adolescents. Although several studies have investigated sleep duration and overweight and obesity from a sex perspective, data regarding age and sex effects remain limited and inconclusive. This study aimed to evaluate the risk(s) for overweight or obesity according to sleep duration among children and adolescents; to evaluate the effect of short sleep duration on the incidence of overweight/obesity among children and adolescents; and to evaluate sex differences in the risk of overweight or obesity with shorter sleep durations. Materials and Methods: The PubMed database was searched for relevant studies published up to June 30, 2021. Odds ratios for obesity/overweight were estimated for short compared with long sleep duration. Subgroup analysis based on sleep duration, sex, and study location was also performed. Results: The estimated odds ratio for combined obesity and overweight was 1.171 (95% confidence interval (CI) 1.092–1.256) according to short sleep duration. Obesity/overweight with short sleep duration was significantly prevalent in the <6 and 6–10 years’ subgroups (odds ratio 1.226 (95% CI 1.083–1.387) and 1.341 (95% CI 1.175–1.530), respectively). Among boys, short sleep duration was significantly correlated with a high occurrence of obesity/overweight (odds ratio 1.294 (95% CI 1.153–1.452)); no such correlation was found among girls. Conclusions: Short sleep duration may increase risk of obesity among children and adolescents, especially those <6 and 6–10 years of age. In the subgroup analysis, the incidence of obesity/overweight for short sleep time revealed significant results among Asians and boys.
Vibrating Flexoelectric Micro-Beams as Angular Rate Sensors
Authors: Qu Yilin , Jin Feng , Yang Jiashi
Published: August 2022

We studied flexoelectrically excited/detected bending vibrations in perpendicular directions of a micro-beam spinning about its axis. A set of one-dimensional equations was derived and used in a theoretical analysis. It is shown that the Coriolis effect associated with the spin produces an electrical output proportional to the angular rate of the spin when it is small. Thus, the beam can be used as a gyroscope for angular rate sensing. Compared to conventional piezoelectric beam gyroscopes, the flexoelectric beam proposed and analyzed has a simpler structure.
Resveratrol Effects on the Reproductive System in Ovariectomized Rats: Deciphering Possible Mechanisms
Authors: Zaychenko Ganna , Stryga Olena , Sinitsyna Oksana , Doroshenko Anna , Sulaieva Oksana , Falalyeyeva Tetyana , Kobyliak Nazarii
Published: August 2022

Phytoestrogen resveratrol (R) has been demonstrated to benefit human reproductive health. However, R bioavailability and pharmacokinetics are still problematic under oral supplementation. We used an experimental vaginal gel with R and hyaluronic acid (HA) to improve bioavailability and pharmacokinetic properties. The study aimed to assess the impact of vaginal R-HA gel on the reproductive system in ovariectomized rats. Methods: The study was carried out on Wistar female rats. It investigated the body weight, tail temperature, vaginal pH, estrogen and progesterone blood levels, and immunohistochemical biomarkers (COX2, Casp-3, Bcl-2, and VEGF). Animals were divided into control animals; ovariectomized rats (OVX); and OVX group treated with vaginal 0.5% R-HA gel (0.5%, 0.1 mL, daily 28 days). Results: The R-HA gel’s therapeutic effect was manifested by slowing weight gain by 17% (p < 0.001), less pronounced symptom of fever at the root of the tail by 9% (p < 0.001) and lowering the vaginal pH to 4.4–4.5 compared with OVX rats. The anti-inflammatory effect and the reduction of COX-2 expression in vagina were accompanied by antiapoptotic impact of RA-H on endometrium, associated with the decreased Casp-3 expression (p < 0.001) and elevated Bcl-2 score in endometrial glands (p = 0.01). Together with enhanced VEGF expression in endometrial glands (p < 0.001) and stromal cells (p = 0.007), these changes prevented endometrial atrophy (p < 0.001) after ovariectomy. Thus, this study substantiates the feasibility of developing an innovative topical drug with R and HA for treating hypoestrogenic disorders.
Molecular Basis of Inhibitory Mechanism of Naltrexone and Its Metabolites through Structural and Energetic Analyses
Authors: Bello Martiniano
Published: August 2022

Naltrexone is a potent opioid antagonist with good blood–brain barrier permeability, targeting different endogenous opioid receptors, particularly the mu-opioid receptor (MOR). Therefore, it represents a promising candidate for drug development against drug addiction. However, the details of the molecular interactions of naltrexone and its derivatives with MOR are not fully understood, hindering ligand-based drug discovery. In the present study, taking advantage of the high-resolution X-ray crystal structure of the murine MOR (mMOR), we constructed a homology model of the human MOR (hMOR). A solvated phospholipid bilayer was built around the hMOR and submitted to microsecond (µs) molecular dynamics (MD) simulations to obtain an optimized hMOR model. Naltrexone and its derivatives were docked into the optimized hMOR model and submitted to µs MD simulations in an aqueous membrane system. The MD simulation results were submitted to the molecular mechanics–generalized Born surface area (MMGBSA) binding free energy calculations and principal component analysis. Our results revealed that naltrexone and its derivatives showed differences in protein–ligand interactions; however, they shared contacts with residues at TM2, TM3, H6, and TM7. The binding free energy and principal component analysis revealed the structural and energetic effects responsible for the higher potency of naltrexone compared to its derivatives.
In Vitro Evaluation of NLS-DTX Activity in Triple-Negative Breast Cancer
Authors: Paiva Karen L. R. , Radicchi Marina A. , Báo Sônia N.
Published: August 2022

Cancer is one of the most lethal diseases in the world, and the development and improvement of treatments used in cancer therapies are extremely important for a better quality of life for patients. In view of the current problems in drug administration such as low solubility and adverse effects, the activity of a solid lipid nanoparticle containing docetaxel (SLN-DTX), a drug already used in conventional therapies, was evaluated in a cell line (MDA-MB-231) of one of the most aggressive types of breast cancer with the worst prognosis, triple-negative breast cancer. Viability tests indicated that SLN-DTX has a greater dependence on the treatment dose when compared to the free drug, which indicates a more controlled release of the drug, and both reduced viability by around 50% at a concentration of 1 µg/mL after 72 h. Transmission electron microscopy (TEM) and confocal and light microscopy analyses indicated that after treatment the cells enter a mitotic catastrophe, characteristic of antimitotic drugs that usually make cells progress to death or senescence. Cells treated with both DTX and SLN-DTX showed significant inhibition of mobility, 73.6% and 66.5% when treated with SLN-DTX and DTX, respectively, compared to the 11.4% of the control after 72 h, characteristics that are very relevant in tumor development and progression. SLN-DTX demonstrated its great potential as a nanocarrier by maintaining and improving the drug’s action in the MDA-MB-231 cell line.
The Combination of Niacinamide, Vitamin C, and PDRN Mitigates Melanogenesis by Modulating Nicotinamide Nucleotide Transhydrogenase
Authors: Park Hyun Jun , Byun Kyung-A , Oh Seyeon , Kim Hyoung Moon , Chung Moon Suk , Son Kuk Hui , Byun Kyunghee
Published: August 2022

Nicotinamide nucleotide transhydrogenase (NNT) is involved in decreasing melanogenesis through tyrosinase degradation induced by cellular redox changes. Nicotinamide is a component of coenzymes, such as NAD+, NADH, NADP+, and NADPH, and its levels are modulated by NNT. Vitamin C and polydeoxyribonucleotide (PDRN) are also known to decrease skin pigmentation. We evaluated whether a mixture of nicotinamide, vitamin C, and PDRN (NVP-mix) decreased melanogenesis by modulating mitochondrial oxidative stress and NNT expression in UV-B-irradiated animals and in an in vitro model of melanocytes treated with conditioned media (CM) from UV-B-irradiated keratinocytes. The expression of NNT, GSH/GSSG, and NADPH/NADP+ in UV-B-irradiated animal skin was significantly decreased by UV-B radiation but increased by NVP-mix treatment. The expression of NNT, GSH/GSSG, and NADPH/NADP+ ratios decreased in melanocytes after CM treatment, although they increased after NVP-mix administration. In NNT-silenced melanocytes, the GSH/GSSG and NADPH/NADP+ ratios were further decreased by CM compared with normal melanocytes. NVP-mix decreased melanogenesis signals, such as MC1R, MITF, TYRP1, and TYRP2, and decreased melanosome transfer-related signals, such as RAB32 and RAB27A, in UV-B-irradiated animal skin. NVP-mix also decreased MC1R, MITF, TYRP1, TYRP2, RAB32, and RAB27A in melanocytes treated with CM from UV-irradiated keratinocytes. The expression of MC1R and MITF in melanocytes after CM treatment was unchanged by NNT silencing. However, the expression of TYRP1, TYRP2, RAB32, and RAB27A increased in NNT-silenced melanocytes after CM treatment. NVP-mix also decreased tyrosinase activity and melanin content in UV-B-irradiated animal skin and CM-treated melanocytes. In conclusion, NVP-mix decreased mitochondrial oxidative stress by increasing NNT expression and decreased melanogenesis by decreasing MC1R/MITF, tyrosinase, TYRP1, and TYRP2.
MXenes Thin Films: From Fabrication to Their Applications
Authors: Ali Israt , Faraz Ud Din Muhammad , Gu Zhi-Gang
Published: August 2022

Two-dimensional MXenes possessed exceptional physiochemical properties such as high electrical conductivity (20,000 Scm−1), flexibility, mechanical strength (570 MPa), and hydrophilic surface functionalities that have been widely explored for energy storage, sensing, and catalysis applications. Recently, the fabrication of MXenes thin films has attracted significant attention toward electronic devices and sensor applications. This review summarizes the exciting features of MXene thin film fabrication methods such as vacuum-assisted filtration (VAF), electrodeposition techniques, spin coating, spray coating, dip-coating methods, and other physical/chemical vapor deposition methods. Furthermore, a comparison between different methods available for synthesizing a variety of MXenes films was discussed in detail. This review further summarizes fundamental aspects and advances of MXenes thin films in solar cells, batteries, electromagnetic interference shielding, sensing, etc., to date. Finally, the challenges and opportunities in terms of future research, development, and applications of MXenes-based films are discussed. A comprehensive understanding of these competitive features and challenges shall provide guidelines and inspiration for further growth in MXenes-based functional thin films and contribute to the advances in MXenes technology.
Ferromagnetic 2p-2p and 4f-2p Couplings in a Macrocycle from Two Biradicals and Two Gadolinium(III) Ions
Authors: Ito Saki , Yoshitake Toru , Ishida Takayuki
Published: August 2022

A new ground triplet biradical 2′,4′,6′-triisopropylbiphenyl-3,5-diyl bis(tert-butyl nitroxide) (iPr3BPBN) was prepared and characterized by means of room-temperature ESR spectroscopy displaying a zero-field splitting pattern together with a half-field signal. Complex formation with gadolinium(III) 1,1,1,5,5,5-hexafluoropentane-2,4-dionate (hfac) afforded a macrocycle [{Gd(hfac)3(μ-iPr3BPBN)}2]. As the X-ray crystallographic analysis clarified, the biradical serves as a bridging ligand, giving a 16-membered ring, where each nitroxide radical oxygen atom is directly bonded to a Gd3+ ion. The magnetic study revealed that the iPr3BPBN bridge behaved as a practically triplet biradical and that the Gd3+-radical magnetic coupling was weakly ferromagnetic. The exchange parameters were estimated as 2jrad-rad/kB > 300 K and 2JGd-rad/kB = 1.2 K in the H = −2J S1•S2 convention. The DFT calculation based on the atomic coordinates clarified the ground triplet nature in metal-free iPr3BPBN and the enhanced triplet character upon coordination. The calculation also suggests that ferromagnetic coupling would be favorable when the Gd-O-N-C(sp2) torsion comes around 100°. The present results are compatible with the proposed magneto-structure relationship on the nitroxide-Gd compounds.
Behaviour of True Artificial Peers
Authors: Weißkirchen Norman , Böck Ronald
Published: August 2022

Typical current assistance systems often take the form of optimised user interfaces between the user interest and the capabilities of the system. In contrast, a peer-like system should be capable of independent decision-making capabilities, which in turn require an understanding and knowledge of the current situation for performing a sensible decision-making process. We present a method for a system capable of interacting with their user to optimise their information-gathering task, while at the same time ensuring the necessary satisfaction with the system, so that the user may not be discouraged from further interaction. Based on this collected information, the system may then create and employ a specifically adapted rule-set base which is much closer to an intelligent companion than a typical technical user interface. A further aspect is the perception of the system as a trustworthy and understandable partner, allowing an empathetic understanding between the user and the system, leading to a closer integrated smart environment.
Cognitive Learning and Robotics: Innovative Teaching for Inclusivity
Authors: Oralbayeva Nurziya , Amirova Aida , CohenMiller Anna , Sandygulova Anara
Published: August 2022

We present the interdisciplinary CoWriting Kazakh project in which a social robot acts as a peer in learning the new Kazakh Latin alphabet, to which Kazakhstan is going to shift from the current Kazakh Cyrillic by 2030. We discuss the past literature on cognitive learning and script acquisition in-depth and present a theoretical framing for this study. The results of word and letter analyses from two user studies conducted between 2019 and 2020 are presented. Learning the new alphabet through Kazakh words with two or more syllables and special native letters resulted in significant learning gains. These results suggest that reciprocal Cyrillic-to-Latin script learning results in considerable cognitive benefits due to mental conversion, word choice, and handwriting practices. Overall, this system enables school-age children to practice the new Kazakh Latin script in an engaging learning scenario. The proposed theoretical framework illuminates the understanding of teaching and learning within the multimodal robot-assisted script learning scenario and beyond its scope.
Activating SIRT-1 Signalling with the Mitochondrial-CoQ10 Activator Solanesol Improves Neurobehavioral and Neurochemical Defects in Ouabain-Induced Experimental Model of Bipolar Disorder
Authors: Rajkhowa Bidisha , Mehan Sidharth , Sethi Pranshul , Prajapati Aradhana , Suri Manisha , Kumar Sumit , Bhalla Sonalika , Narula Acharan S. , Alshammari Abdulrahman , Alharbi Metab , Alkahtani Nora , Alghamdi Saeed , Kalfin Reni
Published: August 2022

Bipolar disorder (BD) is a chronic mental illness characterized by mood fluctuations that range from depressive lows to manic highs. Several studies have linked the downregulation of SIRT-1 (silent mating type information regulation-2 homologs) signaling to the onset of BD and other neurological dysfunctions. This research aimed to look into the neuroprotective potential of Solanesol (SNL) in rats given ICV-Ouabain injections, focusing on its effect on SIRT-1 signaling activation in the brain. Ouabain, found in hypothalamic and medullary neurons, is an endogenous inhibitor of brain Na+/K+ ATPase. The inhibition of brain Na+/K+ ATPase by Ouabain may also result in changes in neurotransmission within the central nervous system. SNL is a Solanaceae family active phytoconstituent produced from the plant Nicotiana tabacum. SNL is used as a precursor for the production of CoQ10 (Coenzyme Q10), a powerful antioxidant and neuroprotective compound. In the current study, lithium (Li), an important mood stabilizer drug, was used as a control. This study looked at the neuroprotective potential of SNL at dosages of 40 and 80 mg/kg in ICV-OUA injections that caused BD-like neurobehavioral and neurochemical defects in Wistar rats. Wistar rats were placed into eight groups (n = 6) and administered 1 mM/0.5 µL ICV-OUA injections for three days. Neurochemical assessments were done in rat brain homogenates, CSF, and blood plasma samples at the end of the experiment protocol schedule. Long-term SNL and lithium administration have been shown to decrease the number of rearing and crossings and reduce time spent in the center, locomotor activities, and immobility time. Solansesol treatment gradually raises the amount of Na+/K+ ATPase, limiting the severity of behavioural symptoms. These findings also revealed that SNL increases the levels of SIRT-1 in CSF, blood plasma, and brain homogenate samples. Moreover, in rat brain homogenates and blood plasma samples, SNL modulates apoptotic markers such as Caspase-3, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic). Mitochondrial-ETC complex enzymes, including complex-I, II, IV, V, and CoQ10, were also restored following long-term SNL treatment. Furthermore, SNL lowered inflammatory cytokines (TNF-α, IL-1β) levels while restoring neurotransmitter levels (serotonin, dopamine, glutamate, and acetylcholine) and decreasing oxidative stress markers. Histological examinations also validated Solanesol’s protective effect. As a result, our findings suggest that SNL, as a SIRT-1 signalling activator, may be a promising therapeutic approach for BD-like neurological dysfunctions.
Swiss Medical Devices for Autologous Regenerative Medicine: From Innovation to Clinical Validation
Authors: Gomri Farid , Vischer Solange , Turzi Antoine , Berndt Sarah
Published: August 2022

Regenerative medicine, based on the use of autologous tissues and embryonic, stem or differentiated cells, is gaining growing interest. However, their preparation, in a manner compliant with good practices and health regulations, is a technical challenge. The aim of this manuscript is to present the design of reliable CE marked medical devices for the preparation of standardized platelet-rich plasma (PRP) and other autologous biologics intended for therapeutic uses. There are numerous PRP isolation processes. Depending on the methodology used, PRP composition varies greatly in terms of platelet concentration, platelet quality, and level of contamination with red and white blood cells. This variability in PRP composition might affect the clinical outcomes. The devices presented here are based on a specific technology, patented all over the world, that allows the precise separation of blood components as a function of their density using thixotropic separator gels in closed systems. This allows the preparation, in an automated manner, of leukocyte poor PRP with a standardized composition. Production of different forms of PRP is a clinical asset to suit various therapeutic needs. Therefore, we are offering solutions to prepare PRP either in liquid or gel form, and PRP combined with hyaluronic acid. These biologics have been successfully used in many different therapeutic domains, resulting in more than 150 published clinical studies. We also developed the CuteCell technology platform for cell culture expansion for further autologous cell therapies. This technology enables the safe and rapid in vitro expansion of cells intended for therapeutic use in good manufacturing practices (GMP) and autologous conditions, using blood-derived products as culture media supplementation. We summarize in this article our 20 years’ experience of research and development for the design of PRP devices and, more recently, for PRP combined with hyaluronic acid.
Biomaterial-Mediated Protein Expression Induced by Peptide-mRNA Nanoparticles Embedded in Lyophilized Collagen Scaffolds
Authors: Oude Egberink Rik , Zegelaar Helen M. , El Boujnouni Najoua , Versteeg Elly M. M. , Daamen Willeke F. , Brock Roland
Published: August 2022

In our aging society, the number of patients suffering from poorly healing bone defects increases. Bone morphogenetic proteins (BMPs) are used in the clinic to promote bone regeneration. However, poor control of BMP delivery and thus activity necessitates high doses, resulting in adverse effects and increased costs. It has been demonstrated that messenger RNA (mRNA) provides a superior alternative to protein delivery due to local uptake and prolonged expression restricted to the site of action. Here, we present the development of porous collagen scaffolds incorporating peptide-mRNA nanoparticles (NPs). Nanoparticles were generated by simply mixing aqueous solutions of the cationic cell-penetrating peptide PepFect14 (PF14) and mRNA. Peptide-mRNA complexes were uniformly distributed throughout the scaffolds, and matrices fully preserved cell attachment and viability. There was a clear dependence of protein expression on the incorporated amount of mRNA. Importantly, after lyophilization, the mRNA formulation in the collagen scaffolds retained activity also at 4 °C over two weeks. Overall, our results demonstrate that collagen scaffolds incorporating peptide-mRNA complexes hold promise as off-the-shelf functional biomaterials for applications in regenerative medicine and constitute a viable alternative to lipid-based mRNA formulations.
The Reception and Contemporary Significance of the Hebrew Prophets and Prophetic Literature: Introduction to the Special Issue
Authors: Anderson Bradford A.
Published: August 2022

This Special Issue of Religions focuses on the reception and contemporary significance of the Hebrew prophets and the prophetic literature of the Hebrew Bible/Old Testament [...]