The Ameliorative Effect of Empagliflozin in Vigabatrin-Induced Cerebellar/Neurobehavioral Deficits: Targeting mTOR/AMPK/SIRT-1 Signaling Pathways

Introduction. Vigabatrin (VGB) is an antiepileptic drug that acts to irreversibly inhibit the γ-aminobutyric acid (GABA) transaminase enzyme, elevating GABA levels. Broad studies have established that long-term treatment and/or high doses of VGB lead to variable visual defects. However, little attention has been paid to its other side effects, especially those demonstrating cerebellar involvement. Sodium glucose-linked co-transporter 2 (SGLT2) inhibitors are antidiabetic agents with protective effects far greater than expected based on their anti-hyperglycemic effect. Method. Our study herein was designed to investigate the possible ameliorative effect of empagliflozin, the SGLT2 inhibitors, in VGB-induced cerebellar toxicity. A total of 40 male Wistar rats were allocated equally into 4 groups: Group I: control group; Group II: VGB group; Group III empagliflozin treated VGB group; and Group IV: empagliflozin treated group. All groups were subjected to the detection of cerebellar messenger RNA gene expression of silent mating type information regulation 2 homolog 1 (SIRT1) and Nucleoporin p62 (P62). Mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and beclin1 levels were assessed by the ELISA technique while malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected spectrophotometrically. Immuno-histochemical studies, focusing on glial fibrillary acidic protein (GFAP) and S100 were performed, and the optical color density and the mean area percentage of GFAP positive astrocytes and the number of S 100 positive cells were also counted. Results. Following empagliflozin treatment, we documented significant upregulation of both SIRT1 and P62 mRNA gene expression. Additionally, AMPK, Beclin1 levels, and SOD activity were significantly improved, while both mTOR and MDA levels were significantly reduced. Conclusions. We concluded for the first time that empagliflozin efficiently ameliorated the VGB-induced disrupted mTOR/AMPK/SIRT-1 signaling axis with subsequent improvement of the autophagy machinery and mitigation of the oxidative and inflammatory cellular environment, paving the way for an innovative therapeutic potential in managing VGB-induced neurotoxicity.     

Cupressus sempervirens Essential Oil: Exploring the Antibacterial Multitarget Mechanisms,Chemcomputational Toxicity Prediction,and Safety Assessment in Zebrafish Embryos

Nowadays, increasing interest has recently been given to the exploration of new food preservatives to avoid foodborne outbreaks or food spoilage. Likewise, new compounds that substitute the commonly used synthetic food preservatives are required to restrain the rising problem of microbial resistance. Accordingly, the present study was conducted to examine the chemical composition and the mechanism(s) of action of the Cupressus sempervirens essential oil (CSEO) against Salmonella enterica Typhimuriumand Staphyloccocus aureus. The gas chromatography analysis revealed α-pinene (38.47%) and δ-3-carene (25.14%) are the major components of the CSEO. By using computational methods, such as quantitative structure–activity relationship (QSAR), we revealed that many CSEO components had no toxic effects. Moreover, findings indicated that α-pinene, δ-3-carene and borneol, a minor compound of CSEO, could inhibit the AcrB-TolC and MepR efflux pump activity of S. enterica Typhimurium and S. aureus, respectively. In addition, our molecular docking predictions indicated the high affinity of these three compounds with active sites of bacterial DNA and RNA polymerases, pointing to plausible impairments of the pathogenic bacteria cell replication processes. As well, the safety profile was developed through the zebrafish model. The in vivo toxicological evaluation of (CSEO) exhibited a concentration-dependent manner, with a lethal concentration (LC₅₀) equal to 6.6 µg/mL.     

Performance evaluation of a WDM/OCDM based hybrid optical switch utilizing efficient resource allocation

A hybrid optical switch （HOS） with physical layer of wavelength division multiplexing and optical code division multiplexing （WDM/OCDM） scheme is proposed. An additional feature to the HOS than optical cross connect （OXC） is that the controller can process requests for both circuit establishment and burst scheduling. In our study, the measurement criteria of HOS are the blocking probability, probability of error, and probability of outage. To simplify the analysis, no distinction is made between a circuit in progress and a burst in progress. Moreover, a minimum fit （MinF） resource allocation strategy is applied in order to increase the bandwidth efficiency and control the multiplexing interference of the OCDM. A 2D Markov model for the HOS is presented using the MinF strategy. Numerical results reveal that the code parameters and the resource allocation strategy greatly affect the performance. Certain periority can be achieved by assigning shorter codes to high periority users and longer codes to low periority users. Also, the probability of error and outage are reduced bv aonling the MinF strategy.     

UV protection filters by dielectric multilayer thin films on Glass BK-7 and Infrasil 301

The increasing use of Ultraviolet (UV) light in medicine, industrial environments, for cosmetic use, and even in consumer products necessitates that greater attention be paid to the potential hazards of this type of electromagnetic radiation. To avoid any adverse effects of exposure to this type of radiation, four suitable protection filters were produced to block three UV bands (UVA, UVB, and UVC). The design structure of the required dielectric multilayer filters was done by optical thin film technology using the absorbing property of UV radiation for the substrates and dielectric materials. The computer analyses of the multilayer filter formulas were prepared using Macleod Software for the production processes. The deposition technique was achieved on optical substrates (Glass BK-7 and Infrasil 301) by dielectric material combinations including Titanium dioxide (Ti₂O₃), Hafnium dioxide (HfO₂), and Lima (mixture of oxides SiO₂/Al₂O₃); deposition being achieved using an electron beam gun. The output results of the theoretical and experimental transmittance values for spectral band from 200 nm to 800 nm were discussed in four processes. To analyze the suitability for use in ‘real world’ applications, the test pieces were subjected to the durability tests (adhesion, abrasion resistance, and humidity) according to Military Standard MIL-C-675C and MIL-C-48497A.     

Photoluminescence and thermoluminescence properties of SnO2 nanoparticles embedded in Li20-K20-B203 with Cu-doping

Cu-doped borate glass co-doped with SnO2 nanoparticles is fabricated by melt quenching. The structure and morphology of the samples are examined by X-ray diffraction and field emission scanning electron microscopy. Up-conversion enhancement is observed in the photoluminescence （PL） and thermolumines- cence （TL） intensities of the glass. PL emission spectra are identified in the blue and green regions, and a fourfold increase in emission intensity may be observed in the presence of embedded SnO2 nanoparticles. The glow curve is recorded at 215℃, and fourfold increases in TL intensity are obtained by addition of 0.1 mol% SnO2 nanoparticles to the glass. Higher TL responses of the samples are observed in the energy range of 15-100 KeV. At energy levels greater than -0.1 MeV, however, flat responses are obtained. The activation energy and frequency factor of the second-order kinetic reaction are calculated by the peak shape method.     

Demonstration of sufficient control for two rounds of quantum error correction in a solid state ensemble quantum information processor

We report the implementation of a 3-qubit quantum error-correction code on a quantum information processor realized by the magnetic resonance of carbon nuclei in a single crystal of malonic acid. The code corrects for phase errors induced on the qubits due to imperfect decoupling of the magnetic environment represented by nearby spins, as well as unwanted evolution under the internal Hamiltonian. We also experimentally demonstrate sufficiently high-fidelity control to implement two rounds of quantum error correction. This is a demonstration of state-of-the-art control in solid state nuclear magnetic resonance, a leading test bed for the implementation of quantum algorithms.     

Improvement of sintering,nonlinear electrical,and dielectric properties of ZnO-based varistors doped with TiO_2

The effects of TiO_2 on sintering and nonlinear electrical properties of(98.5-x)ZnO–0.5MnO_2–0.5Co_2O_3-0.5Bi_2O_(3–x)TiO_2(x = 0.3,0.5,0.7,0.9 mol%) ceramic varistors prepared by the ceramic technique are investigated in this work.The optimum sintering temperature of the prepared samples is deduced by determining the firing shrinkage and water absorption percentages.The optimum sintering temperature is found to be 1200℃,at which each of the samples shows a maximum firing shrinkage and minimum water absorption.Also minimum water absorption appears in a sample of x = 0.9 mol%.Higher sintering temperature and longer sintering time give rise to a reduction in bulk density due to the increased amount of porosity between the large grains of ZnO resulting from the rapid grain growth induced by the liquid phase sintering.The crystal size of ZnO decreases with increasing TiO_2 doping.The addition of TiO_2 improves the nonlinear coefficient and attains its maximum value at x = 0.7 mol% of TiO_2,further addition negatively affects it.A decrease in capacitance consequently in the dielectric constant is recorded with increasing the frequency in a range of 30 kHz–200 kHz.The temperature and composition dependences of the dielectric constant and AC conductivity are also studied.The increase of temperature raises the dielectric constant because it increases ionic response to the field at any particular frequency.     

Elastic guided wave propagation in a periodic array of multi-layered piezoelectric plates with finite cross-sections

In this study, we present a model study of guided wave dispersion and resonance behavior of an array of piezoelectric plates with arbitrary cross-sections. The objective of this work is to analyze the influence of the geometry of an element of a 1D-array ultrasound transducer on generating multi-resonance frequency so as to increase the frequency bandwidth of the transducers. A semi-analytical finite-element (SAFE) method is used to model guided wave propagation in multi-layered 1D-array ultrasound transducers. Each element of the array is composed of LiNbO₃ piezoelectric material with rectangular or subdiced cross-section. Four-node bilinear finite-elements have been used to discretize the cross-section of the transducer. Dispersion curves showing the dependence of phase and group velocities on the frequency, and mode shapes of propagating modes were obtained for different geometry consurations. A parametric analysis was carried out to determine the effect of the aspect ratio, subdicing, inversion layer and matching layers on the vibrational behavior of 1D-array ultrasound transducers. It was found that the geometry with subdiced cross-section causes more vibration modes compared with the rectangular section. Modal analysis showed that the additional modes correspond to lateral modes of the piezoelectric subdiced section. In addition, some modes have strong normal displacements, which may influence the bandwidth and the pressure field in front of the transducer. In addition, the dispersion curves reveal strong coupling between waveguide modes due to the anisotropy of the piezoelectric crystal. The effect of the matching layers was to cluster extensional and flexural modes within a certain frequency range. Finally, inversion layer is found to have a minor effect on the dispersion curves. This analysis may provide a means to analyze and understand the dynamic response of 1D-array ultrasound transducers.     

Easy preparation,characterization and reactions of new 8-chloro-7-formyl-4-oxo-2-phenyl-4H-pyrimido[1,2-a]pyrimidine-3-carbonitrile

8-Chloro-7-formyl-4-oxo-2-phenyl-4H-pyrimido[1,2-a]pyrimidine-3-carbonitrile ( 3 ) is constructed using N-(5-cyano-6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl) acetamide ( 2 ) via Vilsmeier-Haack formylation reaction. Compound 3 reacted with 3-(triethoxysilyl)propan-1-amine under different conditions. Condensation of pyrimidopyrimidine 3 with thiosemicarbazone derivative gave Schiff base 8 , which upon treating with Vilsmeier-Haack reagent afforded pyrazole carbothioamide 9 . Cyclocondensation of compound 3 with some binucleophiles namely thiocarbohyrazide, hydrazine carbodithioic acid, benzyl hydrazinecarbodithioate and/or 2-thioxopyrimidinone was investigated. Structures of the new synthesized compounds were confirmed by their analytical and spectral data.