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Traumatic injuries to the inferior vena cava (IVC) are rare and among the most dreadful injuries encountered in evaluation of both penetrating and blunt traumatic settings. Clinical outcome of IVC injury is multifactorial with injuries being classically managed surgically. In this report, we present a case of 52 years old male patient with successfully treated blunt retrohepatic IVC injury utilizing arterial stent graft and anticoagulation regime without short-term complications. Evidence based standardized approach for endovascular management of IVC injury is not yet available. We hope that our report can contribute to worldwide procedure and postprocedural anticoagulation standardization.

In this work, the capture of carbon dioxide using a dense hollow fiber membrane was studied experimentally and theoretically. The factors affecting the flux and recovery of carbon dioxide were studied using a lab-scale system. Experiments were conducted using a mixture of methane and carbon dioxide to simulate natural gas. The effect of changing the CO2 concentration from 2 to 10 mol%, the feed pressure from 2.5 to 7.5 bar, and the feed temperature from 20 to 40 °C, was investigated. Depending on the solution diffusion mechanism, coupled with the Dual sorption model, a comprehensive model was implemented to predict the CO2 flux through the membrane, based on resistance in the series model. Subsequently, a 2D axisymmetric model of a multilayer HFM was proposed to simulate the axial and radial diffusion of carbon dioxide in a membrane. In the three domains of fiber, the CFD technique was used to solve the equations for the transfer of momentum and mass transfer by using the COMSOL 5.6. Modeling results were validated with 27 experiments, and there was a good agreement between the simulation results and the experimental data. The experimental results show the effect of operational factors, such as the fact that temperature was directly on both gas diffusivity and mass transfer coefficient. Meanwhile, the effect of pressure was exactly the opposite, and the concentration of CO2 had almost no effect on both the diffusivity and the mass transfer coefficient. In addition, the CO2 recovery changed from 9% at a pressure equal to 2.5 bar, temperature equal to 20 °C, and a concentration of CO2 equal to 2 mol%, to 30.3% at a pressure equal to 7.5 bar, temperature equal to 30 °C, and concentration of CO2 equal 10 mol%; these conditions are the optimal operating point. The results also manifested that the operational factors that directly affect the flux are pressure and CO2 concentration, while there was no clear effect of temperature. This modeling offers valuable data about the feasibility studies and economic evaluation of a gas separation unit operation as a helpful unit in the industry.

Eluxadoline (ELD), a recently approved drug, exhibits potential therapeutic effects in the management and treatment of IBS-D. However, its applications have been limited due to poor aqueous solubility, leading to a low dissolution rate and oral bioavailability. The current study’s goals are to prepare ELD-loaded eudragit (EG) nanoparticles (ENPs) and to investigate the anti-diarrheal activity on rats. The prepared ELD-loaded EG-NPs (ENP1-ENP14) were optimized with the help of Box–Behnken Design Expert software. The developed formulation (ENP2) was optimized based on the particle size (286 ± 3.67 nm), PDI (0.263 ± 0.01), and zeta potential (31.8 ± 3.18 mV). The optimized formulation (ENP2) exhibited a sustained release behavior with maximum drug release and followed the Higuchi model. The chronic restraint stress (CRS) was successfully used to develop the IBS-D rat model, which led to increased defecation frequency. The in vivo studies revealed a significant reduction in defecation frequency and disease activity index by ENP2 compared with pure ELD. Thus, the results demonstrated that the developed eudragit-based polymeric nanoparticles can act as a potential approach for the effective delivery of eluxadoline through oral administration for irritable bowel syndrome diarrhea treatment.

Commercial pure Mg specimens were processed through equal channel angular pressing (ECAP) using two dies with die angles of 90° and 120°. Mg billets were processed up to four passes via different route types. Machine learning (ML) techniques were adopted to estimate the ECAP parameters and verify the experimental findings. Several ML techniques were employed to estimate the effect ECAP parameters of pure Mg on microstructural evolution, Vicker’s microhardness (HV), and tensile properties for ECAP billets and their as-annealed (AA) counterparts. Electron back-scatter diffraction (EBSD) was applied to determine the structural evolution and crystallographic texture both prior to and following the ECAP process for the Mg billets. EBSD analysis showed that route Bc is the most effective route in grain refinement, and four passes of route Bc experienced a significant refinement of 86% compared to the AA condition. Furthermore, the crystallographic texture showed that four passes of route Bc produced the most robust texture that was greater than 26.21 times random. ML findings revealed that the grain size demonstrated a strong correlation of −0.67 with rising number of passes, while ϕ affected the grain size strongly with 0.83. When adopting a 90°-die to accumulate the plastic strain up to 4Bc, the subsequent HV was indeed 111% higher than that of the AA equivalent. From ML findings it was clear that the number of passes was the most significant parameter on the Mg HV values, while ECAP channel angle (ϕ) revealed high correlation factor with HV values as well. Furthermore, four passes of route Bc with ϕ = 90° and 120° led to a significant increase of the tensile strength by 44.7%% and 35.7%, respectively, compared to the AA counterpart. ML findings revealed that the tensile strength was affected by the increasing number of passes with a strong correlation of 0.81, while affecting ductility moderately with 0.47.

Gelatin (bovine/porcine)-based edible films are considered as an excellent carrier for essential oils (EOs) to preserve food quality and extend their shelf life. Spearmint essential oil (SEO) is known for its potential antioxidant and antimicrobial effects; nevertheless, its food applications are limited due to the volatile nature of its active components. Thus, edible films loaded with essential oil can be an alternative to synthetic preservatives to improve their food applications. In the present study, the effect of SEO addition was investigated on the physicochemical properties of bovine and porcine gelatin films, and antioxidant activity was assessed. GCMS (Gas chromatography mass spectrometry) analysis revealed the presence of carvone (55%) and limonene (25.3%) as major components. The incorporation of SEO into the films decreased the opacity, moisture content, water solubility, and elongation at break of bovine and porcine gelatin films. However, with the addition of EO, the thickness and water vapor permeability of bovine and porcine-based gelatin films increased. Moreover, the addition of SEO increased the tensile strength (TS) of the porcine-based film, whereas bovine samples demonstrated a decrease in tensile strength. XRD (X-ray diffraction) findings revealed a decrease in the percentage crystallinity of both types of gelatin films. SEM (scanning electron microscope) results showed the changes in the morphology of films after the addition of SEO. Antioxidant properties significantly (p < 0.05) increased with the incorporation of EO when compared with control films. Therefore, the addition of SEO to gelatin-based edible films could be an effective approach to prepare an active food packaging material to prevent food oxidation.

The peel aqueous extract of Punica granatum was utilized to fabricate zinc oxide nanoparticles (ZnO-NPs) as a green approach. The synthesized NPs were characterized by UV-Vis spectroscopy, Fourier transform infrared (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy, which was attached to an energy dispersive X-ray (SEM-EDX). Spherical, well arranged, and crystallographic structures of ZnO-NPs were formed with sizes of 10–45 nm. The biological activities of ZnO-NPs, including antimicrobial and catalytic activity for methylene blue dye, were assessed. Data analysis showed that the antimicrobial activity against pathogenic Gram-positive and Gram-negative bacteria, as well as unicellular fungi, was observed to occur in a dose-dependent manner, displaying varied inhibition zones and low minimum inhibitory concentration (MIC) values in the ranges of 6.25–12.5 µg mL–1. The degradation efficacy of methylene blue (MB) using ZnO-NPs is dependent on nano-catalyst concentration, contact time, and incubation condition (UV-light emission). The maximum MB degradation percentages of 93.4 ± 0.2% was attained at 20 µg mL−1 after 210 min in presence of UV-light. Data analysis showed that there is no significant difference between the degradation percentages after 210, 1440, and 1800 min. Moreover, the nano-catalyst showed high stability and efficacy to degrade MB for five cycles with decreasing values of 4%. Overall, P. granatum-based ZnO-NPs are promising tools to inhibit the growth of pathogenic microbes and degradation of MB in the presence of UV-light emission.

Euphorbia plants have a significant place in traditional medicine due to their numerous therapeutic properties, including their anti-tumor effects, which have been observed in several species. In the current study, a phytochemical investigation of Euphorbia saudiarabica methanolic extract led to the isolation and characterization of four secondary metabolites from the chloroform (CHCl3) and ethyl acetate (EtOAc) fractions, which are reported for the first time in this species. One of the constituents, saudiarabicain F (2), is a rare C-19 oxidized ingol-type diterpenoid that has not been previously reported. The structures of these compounds were determined by extensive spectroscopic (HR-ESI-MS, 1D and 2D NMR) analyses. The anticancer properties of the E. saudiarabica crude extract, its fractions and its isolated compounds were examined against several cancer cells. The active fractions were evaluated for their effects on cell-cycle progression and apoptosis induction using flow cytometry. Furthermore, RT-PCR was employed to estimate the gene-expression levels of the apoptosis-related genes. It was demonstrated that the E. saudiarabica CHCl3 and EtOAc fractions suppressed the proliferation of the cancer cells. The MCF-7 cells were the most sensitive to both fractions, with IC50 values of 22.6 and 23.2 µg/mL, respectively. Notably, both fractions caused cell-cycle arrest in the G2/M phase of the treated MCF-7 cells. The inhibition of the MCF-7 cells’ proliferation was also linked with apoptosis induction by flow-cytometry analysis. Additionally, the activation of apoptosis by both fractions was demonstrated by an increase in the ratio of Bax to Bcl-2, with an increase in the expression of caspase-7. Among the isolated compounds, glutinol (1) showed potent activity against the MCF-7 cell line, with an IC50 value of 9.83 µg/mL. Our findings suggest that E. saudiarabica has apoptosis-inducing effects and shows promise as a potential source of new chemotherapeutic drugs.

In recent years, the popularity of copaiba oil-resin has increased worldwide due to its medicinal value and wide applications in industry. Despite its popularity, the oil has not been standardized by industry or regulatory agencies. Product adulteration in order to maximize profits has become a problem. To address these issues, the current study describes the chemical and chemometric characterization of forty copaiba oil-resin samples by GC/MS. The results demonstrated, with the exception of commercial samples, that all sample groups contained six characteristic compounds (β-caryophyllene, α-copaene, trans-α-bergamotene, α-humulene, γ-muurolene, and β-bisabolene) in varying concentrations. Furthermore, compositional patterns were observed in individual groups which corresponded to sample origin. Within the commercial group, two samples did not contain or contained only one of the characteristic compounds. Principal component analysis (PCA) revealed distinct groups which largely corresponded to sample origin. Moreover, commercial samples were detected by PCA as outliers, and formed a group far removed from the other samples. These samples were further subjected to analysis using a SFC/MS method. Product adulteration with soybean oil was clearly detected, with each individual triglyceride in soybean oil being unambiguously identified. By combining these analytical techniques, the overall quality of copaiba oil-resin can be assessed.

The aim of this study was to examine the effect of Sage (Salvia sclarea) essential oil (SEO) on the physiochemical and antioxidant properties of sodium alginate (SA) and casein (CA) based films. Thermal, mechanical, optical, structural, chemical, crystalline, and barrier properties were examined using TGA, texture analyzer, colorimeter, SEM, FTIR, and XRD. Chemical compounds of the SEO were identified via GC–MS, the most important of which were linalyl acetate (43.32%) and linalool (28.51%). The results showed that incorporating SEO caused a significant decrease in tensile strength (1.022–0.140 Mpa), elongation at break (28.2–14.6%), moisture content (25.04–14.7%) and transparency (86.1–56.2%); however, WVP (0.427–0.667 × 10−12 g·cm/cm2·s·Pa) increased. SEM analysis showed that the incorporation of SEO increased the homogeneousness of films. TGA analysis showed that SEO-loaded films showed better thermal stability than others. FTIR analysis revealed the compatibility between the components of the films. Furthermore, increasing the concentration of SEO increased the antioxidant activity of the films. Thus, the present film shows a potential application in the food packaging industry.

A pharmaceutical formulation with favorable pharmacokinetic parameters is more likely to be efficacious and safe to overcome the failures of the drug resulting from lack of efficacy, poor bioavailability, and toxicity. In this view, we aimed to evaluate the pharmacokinetic functionalities and safety margin of an optimized CS-SS nanoformulation (F40) by in vitro/in vivo methods. The everted sac technique was used to evaluate the improved absorption of a simvastatin formulation. In vitro protein binding in bovine serum and mice plasma was performed. The formulation’s liver and intestinal CYP3A4 activity and metabolic pathways were investigated by the qRT-PCR technique. The excretion of cholesterol and bile acids was measured to demonstrate the formulation’s cholesterol depletion effect. Safety margins were determined by histopathology as well as fiber typing studies. In vitro protein binding results revealed the existence of a high percentage of free drugs (22.31 ± 3.1%, 18.20 ± 1.9%, and 16.9 ± 2.2%, respectively) compared to the standard formulation. The controlled metabolism in the liver was demonstrated from CYP3A4 activity. The formulation showed enhanced PK parameters in rabbits such as a lower Cmax, clearance, and a higher Tmax, AUC, Vd, and t1/2. qRT-PCR screening further proved the different metabolic pathways followed by simvastatin (SREBP-2) and chitosan (PPAR-γ pathway) in the formulation. The results from qRT-PCR and histopathology confirmed the toxicity level. Hence, this pharmacokinetic profile of the nanoformulation proved it has a unique synergistic hypolipidemic modality.

This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.

This study aimed to maximize the dependent variables [total phenolic content (TPC), antioxidant (DPPH and ABTS), and anticancer activities (against HepG2 and MCF-7 cells)] from P. schimperi aerial parts by optimizing three independent variables (extraction temperature, extraction time, and liquid-to-solid ratio) of ultrasound-assisted extraction (UAE) using the Box–Behnken design (BBD) of response surface methodology (RSM). For each of the dependent variables, the projected quadratic models were found to be very significant (p < 0.001). The extraction temperature and extraction time had a significant impact on the TPC extraction, antioxidant, and anticancer properties (p < 0.05). The best conditions were identified as an extraction temperature of 54.4 °C, extraction time of 48 min, and liquid-to-solid ratios of 20.72 mL/g for the simultaneous extraction of the TPC, antioxidant, and anticancer properties of P. schimperi. The experimental results and the expected values agreed under these circumstances. Regarding the high extraction effectiveness and antioxidant and anticancer effects at comparably low extraction temperature and duration, UAE demonstrated considerable benefits over conventional solvent extraction (CSE). This improved UAE approach has shown a potential use for effective polyphenolic antioxidant extraction from P. schimperi aerial parts in the nutraceutical sectors.

In the world, brain tumor (BT) is considered the major cause of death related to cancer, which requires early and accurate detection for patient survival. In the early detection of BT, computer-aided diagnosis (CAD) plays a significant role, the medical experts receive a second opinion through CAD during image examination. Several researchers proposed different methods based on traditional machine learning (TML) and deep learning (DL). The TML requires hand-crafted features engineering, which is a time-consuming process to select an optimal features extractor and requires domain experts to have enough knowledge of optimal features selection. The DL methods outperform the TML due to the end-to-end automatic, high-level, and robust feature extraction mechanism. In BT classification, the deep learning methods have a great potential to capture local features by convolution operation, but the ability of global features extraction to keep Long-range dependencies is relatively weak. A self-attention mechanism in Vision Transformer (ViT) has the ability to model long-range dependencies which is very important for precise BT classification. Therefore, we employ a hybrid transformer-enhanced convolutional neural network (TECNN)-based model for BT classification, where the CNN is used for local feature extraction and the transformer employs an attention mechanism to extract global features. Experiments are performed on two public datasets that are BraTS 2018 and Figshare. The experimental results of our model using BraTS 2018 and Figshare datasets achieves an average accuracy of 96.75% and 99.10%, respectively. In the experiments, the proposed model outperforms several state-of-the-art methods using BraTS 2018 and Figshare datasets by achieving 3.06% and 1.06% accuracy, respectively.

Abstract Background Myoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE). Case presentation We here in report a twenty months old Saudi boy who presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up. Conclusions Our patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.

ABSTRACTObjectives: Evaluation of urinary neutrophil gelatinase-associated lipocalin (UNGAL) and kidney injury molecule 1 (UKIM-1) as early predictors of development of acute kidney injury (AKI) in patients admitted to surgical ICU.Patients & Methods: 188 ICU patients were clinically evaluated and gave blood samples for estimation of at admission (T0) serum creatinine (SCr) and urine samples for estimation of urinary creatinine (UCr), UNGAL and UKIM-1 and their values were adjusted to UCr level. At 48-hr after admission SCr levels were re-estimated and AKI was diagnosed and staged according to the Acute Kidney Injury Network criteria. Study outcomes included the ability of estimated markers for prediction of possible AKI development.Results: At 48-hr after ICU admission, 73 patients (38.8%) developed AKI; 42, 21 and 10 mild, moderate and severe AKI, respectively. At T0, UNGAL and UKIM1, and their UCr ratios showed progressive increase with increased AKI grade. Calculated ∆SCr was positively correlated with clinical data and estimated levels of urinary markers. Regression analysis defined elevated BMI, TISS-28 score, UNGAL and UKIM-1 as early significant predictors for AKI. ROC curve analysis defined UNGAL and UKIM-1 and their ratios to UCr as the significant predictors for AKI development.Conclusion: Development of AKI in ICU patients was related to severity of surgical trauma. High UNGAL and UKIM-1 at time of ICU admission can predict upcoming AKI and its AUC after adjustment to UCr levels had superior predictive value for AKI. A high uKIM-1/UCr ratio can be considered the most significant early predictor for AKI.

This paper proposes an efficient encryption technique based on Dynamic and Secure Substitution Box (DS2B) design suitable for IoT and resource-constrained platforms. The DS2B has the advantages of simple structure and good encryption performance. A different number of strong S-boxes could be generated with minor variations in the DS2B parameters. Performance analyses of the DS2B, including differential/linear cryptanalysis, bijective, nonlinearity, strict avalanche criterion (SAC), and bit independence criterion (BIC) have been presented where high $nonlinearity$ , and low differential uniformity are achieved. Besides, a comparison with recent S-boxes is introduced which shows the robustness of the DS2B. To verify the DS2B, a speech encryption engine was realized on FPGA. Various security analyses were evaluated including the National Institute of Standards & Technology (NIST) statistical test suite, number of samples changes rate NSCR, mean square error (MSE), correlation, histogram, and spectrogram. In this work, the silence periods are encrypted in a way that makes them much harder to detect using the DS2B. The proposed encryption scheme achieved a throughput of 9.87 G bit/s, which is higher than previous work. A Xilinx Nexys 4 FPGA evaluation board was used for implementing and verifying the design.

This paper presents a novel cross-coupling capacitor processing unit (C3PU) that supports analog-mixed signal in-memory computing to perform multiply-and-accumulate (MAC) operations. The C3PU consists of a capacitive unit, a CMOS transistor, and a voltage-to-time converter (VTC). The capacitive unit serves as a computational element that holds the multiplier operand and performs multiplication once the multiplicand is applied at the terminal. The multiplicand is the input voltage that is converted to a pulse width signal using a low power VTC. The transistor transfers this multiplication where a voltage level is generated. A demonstrator of $5 \times 4$ C3PU array that is capable of implementing 4 MAC units is presented. The design has been verified using Monte Carlo simulation in 65 nm technology. The $5 \times 4$ C3PU consumed energy of 66.4 fJ/MAC at 0.3 V voltage supply with an error of 5.7%. The proposed unit achieves lower energy and occupies a smaller area by $3.4\times $ and $3.6\times $ , respectively, with similar error value when compared to a digital-based $8 \times 4$ -bit fixed point MAC unit. The C3PU has been utilized through an iris flower classification utilizing an artificial neural network which achieved a 90% classification accuracy compared to ideal accuracy of 96.67% using MATLAB.

Tadalafil (TDL) is a phosphodiesterase-5 inhibitor (PDE5I), indicated for erectile dysfunction (ED). However, TDL exhibits poor aqueous solubility and dissolution rate, which may limit its application. This study aims to prepare amorphous solid dispersion (ASD) by spray-drying, using glycyrrhizin-a natural drug carrier. Particle and physicochemical characterizations were performed by particle size, polydispersity index measurement, yield, drug content estimation, Fourier Transformed Infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and dissolution study. In order to evaluate the aphrodisiac activity of the prepared ASD, sexual behavior study was performed in male rats. It is further considered for the stability study. Our results revealed that TDL-GLZ spray-dried dispersion was a successful drug-carrier binary mixture. XRD and SEM showed that ASD of TDL with GLZ presented in the amorphous state and dented-spherical shape, unlike the drug indicating crystalline and spiked shaped. The optimized ASD3 formulation with particle size (1.92 µm), PDI (0.32), yield (97.78%) and drug content (85.00%) showed 4.07 folds’ increase in dissolution rate compared to pure TDL. The results obtained from the in vivo study exhibit significantly improved aphrodisiac activity with ASD3. The stability study revealed that the prepared ASD3 did not show any remarkable changes in the dissolution and drug content for 1 month storage at room temperature.

The objective of the present study was to improve the dissolution rate and aphrodisiac activity of tadalafil by using hydrophilic polymers. Solid dispersions were prepared by solvent evaporation-Rota evaporator using Koliphore 188, Kollidon® VA64, and Kollidon® 30 polymers in a 1:1 ratio. Prepared tadalafil-solid dispersions (SDs) evaluated for yield, drug content, micromeritics properties, physicochemical characterizations, and aphrodisiac activity assessment. The optimized SDs TK188 showed size (2.175 ± 0.24 µm), percentage of content (98.89 ± 1.23%), yield (87.27 ± 3.13%), bulk density (0.496 ± 0.005 g/cm3), true density (0.646 ± 0.003 g/cm3), Carr’s index (23.25 ± 0.81), Hausner ratio (1.303 ± 0.003) and angle of repose (

Summary: Nanopore sensing is an emerging technology that has many biosensing applications ranging from DNA sequencing using biological pores to biomolecular analysis using solid-state pores. Solid-state nanopores that are more stable are an attractive choice for biosensing applications. Still, biomolecule interactions with the nanopore surface reduce nanopore stability and increase usage costs. In this study, we investigated the biosensing capability for 102 quartz glass nanopores with a diameter of 11–18 nm that were fabricated using laser-assisted capillary pulling. Nanopores were assembled into multiple microfluidic chips that were repeatedly used for up to 19 weeks. We find that using vacuum storage combined with minimal washing steps improved the number of use cycles for nanopores. The single-molecule biosensing capability over repeated use cycles was demonstrated by quantitative analysis of a DNA carrier designed for detection of short single-stranded DNA oligonucleotides.

The presence of Origami patterns in the anatomy of many biological species compels a thorough understanding of their underlying mechanics and possible utilization in man-made systems. Along this line, the past decade has witnessed an increased interest in Origami inspired engineering, where it was shown that foldable and spatially-expandable structures with rich kinematics and unconventional Poisson’s ratio can be created using different Origami patterns. Among those, the Kresling Origami pattern has inspired the design of springs with nonconventional properties. Here, we develop a representative shell-based finite element model for predicting the quasi-static mechanical behavior of a class of 3D printed Kresling Origami springs. We validate the model against experimental data, then use it to generate maps that demarcate regions in the design parameter space into qualitatively different behaviors of the springs. We show that, depending on their design parameters, the springs can exhibit a linear elastic behavior; a nonlinear elastic softening/hardening mono-stable behavior; quasi-zero stiffness behavior; or even a bi-stable behavior. The modularity of these springs, their tunability, and the ability to combine them permits architecturing metamaterials with tunable constitutive laws, which could potentially revolutionize the design of shock absorbers and cushion materials.

ObjectivesThere are limited data on the efficacy and safety of favipiravir antiviral in coronavirus disease 2019 (COVID-19), particularly in the more progressed disease phase. This study aims to evaluate the favipiravir effect on reducing the length of hospital stay and in-hospital mortality among moderate and severe hospitalized COVID-19 patients.MethodsA prospective, multicenter observational study was conducted that included moderate and severe hospitalized adult COVID-19 patients in four major regions (Riyadh (Riyadh), Eastern (Dammam), Al-Qassem (Buraydah), and Macca (Jeddah) of Saudi Arabia. For the primary outcome of all-cause mortality, a Cox proportional hazard analysis was performed. While the association between favipiravir use and length of hospital stay was determined using adjusted generalized linear model. This study was approved by the Central Institutional Review Board in The Saudi Ministry of Health (MoH) with the approval number IRB # 20-85-M.ResultsThis study included 598 moderate and severe COVID-19 patients, of whom 156 (26%) received favipiravir. Favipiravir treatment was associated with more extended hospital stays (14 vs. 10 median days, P = 0.034) and higher mortality rate (aHR 3.63; 95% CI 1.06–12.45) compared to no favipiravir regimen. Despite lack of effectiveness, favipiravir use was only associated with higher diarrhea adverse effects (12 vs. 5%, P = 0.002), but it did not affect the renal and liver profiles of patients.ConclusionFavipiravir was ineffective in reducing the length of hospital stay and in-hospital mortality in patients with moderate and severe COVID-19.

The present study assesses RO stations at four sites in Al-Mahalabea area – Nineveh governorate, Iraq during the summer of 2013. The performance of RO stations are ranked by two methods: the Simple Additive Weight (SAW) and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). Two groups of samples were collected from feed and permeate water for two periods (at zero time of operation and after ten weeks of operation) with eleven parameters for each sample were analysed. The highest overall rejection R efficiency appeared with the first set of parameters more than 90% (SO4, TDS, NO3, TH, and turbidity), while the second set was the least (Cl, Na, and total alkalinity – TA) ranged between 65 and 85%. It is observed that both the SAW and the TOPSIS methods are accurate to predict the performance efficiency.

This paper introduces an intensive discussion for the dynamical model of the love triangle in both integer and fractional-order domains. Three different types of nonlinearities soft, hard, and mixed between soft and hard, are used in this study. MATLAB numerical simulations for the different three categories are presented. Also, a discussion for how the kind of personalities affects the behavior of chaotic attractors is introduced. This paper suggests some explanations for the complex love relationships depending on the impact of memory (IoM) principle. Lyapunov exponents, Kaplan-Yorke dimension, and bifurcation diagrams for three different integer-order cases show a significant dependency on system parameters. Hardware digital realization of the system is done using the Xilinx Artix-7 XC7A100T FPGA kit. Version 14.7 from the Xilinx ISE platform is used in both Verilog simulation and hardware implementation stages. The digital approach of such a system opens the door to predict the love relation after sensing the human personality. Also, this study will help in justifying more human emotions like happiness, panic, and fear accurately. Perhaps shortly, this study may combine with artificial intelligence to demonstrate Human-Computer interaction products.

Abstract The drillstring used in the oil and gas exploration is a complex structure due to the different forces acting on it. One of the primary sources of drillstring vibrations is the cutting forces caused by the drill bit contact with the rock formation. In some drilling applications, such as hole enlargement and underreaming, the source of the cutting action originates from the drill bit as well as the reamer which increases the dynamic complexity of the drillstring. This paper’s objective is to investigate the torsional vibration behaviors of the bottom hole assembly (BHA) under simultaneous drilling and reaming. More specifically, it addresses the effect of the reamer interaction with the wellbore during drilling operations on the overall torsional vibrations of the BHA. The BHA was modeled as a torsional shaft subjected to a localized external force due to the reamer cutting action, and a point load external force due to the drill bit interaction with the formation. The equation of motion was obtained using Hamilton’s principle, and modal expansion was used to solve the equation of motion. The results showed that the location of the reamer within the BHA plays an important role in vibrations response. It was found that vibration modes that exhibit symmetry within the reamer location show a negligible effect on the overall BHA torsional response. Reamers with aggressive cutters cause higher vibration response when compared with a drill bit with the same cutter aggressiveness. The simplified model reveals the significance of properly matching the drill bit and the reamer to reduce the overall BHA torsional vibrations.

A 67-year-old woman presented with upper respiratory symptoms and was diagnosed with coronavirus disease-2019 (COVID-19). She was found to have a large hemorrhagic pericardial effusion with echocardiographic signs of tamponade and mild left ventricular impairment. Clinical course was complicated by development of takotsubo cardiomyopathy. She was treated with pericardiocentesis, colchicine, corticosteroids, and hydroxychloroquine, with improvement in symptoms. (Level of Difficulty: Intermediate.)

There is a continuous need to assess Groundwater Quality (GWQ) for human beneficial uses especially in areas suffering a shortage of nearby surface water. This study aims to assess GWQ of 56 wells located at Al-Shekhan area for drinking, irrigation, and livestock purposes. Analytical Hierarchical Process (AHP) technique is used to extract weights of parameters that are needed in the calculation of Simple Additive Weighting (SAW) technique. Maps are created using Geographical Information Systems (GIS), and these maps shows the classes of suitable areas for each purpose depending upon the calculated indices which are extracted from SAW technique. The results show that the final map classifi es the suitable parts according to the drinking, irrigation and livestock purposes, and it shows that the north eastern part of the studied area is suitable for irrigation and livestock only. A model of GIS and AHP is built to assess the suitability of GWQ in Al-Shekhan area, and can be a raw model to be applied to assess GWQ in any other area after inserting the values of their parameters.

Active herbal or natural compounds have high chemical diversity and specificity than synthetic drugs. Recently, we have validated the hypoglycemic salutation of Oncocalyx glabratus in rodent model, and demonstrated the activation of PPARα/γ by its newly ioslated flavan derivative Oncoglabrinol C (5,3′-Dihydroxyflavan 7-4′-O-digallate) in liver cells (HepG2). Here we evaluated the potential of Oncoglabrinol C against Dichlorofluorescin (DCFH) and Methylglyoxal (MGO) induced endothelial cells (HUVEC) oxidative and apoptotic damage, including activation of PXR-mediated hepatic CYP3A4. Our MTT assay showed protection of ~57% and ~63.5% HUVEC cells by 10 and 20 μg/ml doses of Oncoglabrinol C, respectively through attenuating DCFH triggered free-radicals. Also, the two doses effectively protected ~53% and ~65.5% cells, respectively by reversing MGO toxicity. In DCFH and MGO treated cells, Oncoglabrinol C (20 μg/ml) effectively downregulated caspase 3/7 activity by ~33% and ~43.5%, respectively. Moreover, in reporter gene (dual-luciferase) assay, Oncoglabrinol C (20 μg/ml) moderately activated hepatic CYP3A4. Molecular docking of Oncoglabrinol C indicated its strong interactions with cellular caspase 3/7, PPARα/γ and PXR proteins, which supported its anti-apoptotic (antagonistic) as well as pro-hypoglycemic and PXR/CYP activating (agonistic) activities. Taken together, our findings demonstrated the potential of Oncoglabrinol C in reversing the endothelial oxidative and apoptotic damage as well as in the activation of hepatic CYP3A4. This warrants further evaluations of Oncoglabrinol C and related compounds towards developing effective and safe drugs against diabetes associated cardiovascular disorders.

AIM: To assess the changes in the anterior chamber parameters using Pentacam following four different lines of treatment of primary angle-closure glaucoma (PACG). METHODS: A retrospective comparative study included 126 patients (126 eye) presented within 24-48h after acute angle-closure glaucoma (AACG). Patients were divided into 2 groups: group A (68 eyes) with controlled intraocular pressure (IOP) ≤21 mm Hg, which included subgroup A1 (34 eyes) with clear lens underwent Nd:YAG laser peripheral iridotomy (LPI) and subgroup A2 (34 eyes) with cataract underwent standard phacoemulsification; and group B (58 eyes) with uncontrolled IOP, which included subgroup B1 (30 eyes) with clear lens underwent trabeculectomy and subgroup B2 (28 eyes) with cataract underwent combined phacoemulsification and trabeculectomy. Patients were followed up for at least 3mo. Primary outcomes were Pentacam anterior segment measurements [anterior chamber angle (ACA) and depth (ACD)]. Secondary outcomes were changes in IOP, visual acuity (VA) and recorded complications. RESULTS: At the 3rd month, there was significant increase in the ACA values in all studied groups compared to preoperative values (P

Binary convolutional neural networks (BCNN) have been proposed in the literature for resource-constrained IoTs nodes and mobile computing devices. Such computing platforms have strict constraints on the power budget, system performance, processing and memory capabilities. Nonetheless, the platforms are still required to efficiently perform classification and matching tasks needed in various applications. The memristor device has shown promising results when utilized for in-memory computing architectures, due to its ability to perform storage and computation using the same physical element. This is in addition to their nonlinear dynamic characteristics that can be used for various applications. Emulating the memristor operation through FPGAs implementation provides flexibility for rapid prototyping and exploration of the design space. In this paper, a FPGA-based memristor emulator circuit is implemented using a multi-bit XNOR gate as the main block for binary convolution which is followed by a memristor-based pooling layer. The BCNN layer is realized by bitwise XNOR-cell followed by wide NOR gate. The implementation has been successfully synthesized and verified using Xilinx Nexys4 FPGA with less than 1% utilization and 144.9 MHz frequency of operation. In order to test the functionality of the proposed cores, a digital implementation for the circuit was realized and verified experimentally. The experimental results show similar performance when compared to software simulation.

Internet of Things (IoT) has been the driving force for many smart city applications. The huge volume of IoT data generated from these applications require efficient processing to get the insight, which poses significant difficulty. Data mining and machine learning (DM) algorithms are used to minimize such difficulty. However, it is still very challenging to select a particular DM algorithm that can process a dynamic IoT dataset based on some application-specific goals to achieve better accuracy. This paper proposes a knowledge-driven framework that considers the knowledge of datasets, available DM algorithms, and application goals to select the suitable DM algorithm for performing a target data processing task. This work considers data from cultural domain, health domain, and transportation domain in the experiment. The results show that the proposed approach dynamically selects the best-suited DM algorithms for the available datasets and target goals that exhibits satisfactory performance in obtaining accurate results compared to the existing work. The proposed approach not only provides flexibility in conducting dynamic IoT data mining tasks, but also reduces the complexity that would otherwise be necessary while adopting the traditional data mining approaches.

Objective: To evaluate a novel polyherbal formulation (BSVT) containing the standardized extracts from the leaves of Boerhavia diffusa, Solidago virgaurea, Vitex negundo, and thymoquinone in CCl4 induced hepatorenal toxicity in rats. Methods: A total of 36 rats were divided into six groups including normal control, CCl4 (2 mL/kg, i.p.), CCl4 (2 mL/kg, i.p.) + Cystone® (750 mg/kgp.o.), CCl4 (2 mL/kg, i.p.) + BSVT (25 mg/ kg, p.o.), CCl4 (2 mL/kg, i.p.) + BSVT (50 mg/kg, p.o.), and CCl4 (2 mL/kg, i.p.) + BSVT (100 mg/kg,p.o.). All treatments were given for four weeks. Serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, total protein, serum urea, blood urea nitrogen and creatinine were assessed. Superoxide dismutase, malondialdehyde, and glutathione peroxidase were evaluated in tissue homogenate. The histopathological study of liver and kidney tissues was also done. Results: Aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, serum urea, blood urea nitrogen and creatinine were significantly elevated (P

Context: Nonneoplastic and neoplastic lesions of the nasal cavity are common conditions in routine clinical practice among almost all age group of people. Aims: This study examines the clinicopathological and radiological profiles of the unilateral nasal mass in an Ear, Nose, and Throat (ENT) clinic of AlHada Armed Forces Hospital. Settings and Design: The study design involves an ENT clinic of AlHada Armed Forces Hospital, Taif, Saudi Arabia. Subjects and Methods: A retrospective examination of patients' records was done to investigate the clinicopathological and radiological profiles of unilateral nasal masses between 2016 and 2018. Statistical Analysis Used: Descriptive statistics included mean, standard deviation, frequencies, and percentages, and inferential statistics such as independent t-test and Chi-square were carried out using the Statistical Package for the Social Sciences software (Version 20.0 IBM SPSS Corp., Armonk, NY, USA). Results: Nasal polyps were the most common diagnosis seen in seven (35%) cases, and the most common symptom was nasal obstruction (N: 12; 60%). Histopathological examination revealed that inflammatory lesions were more common (N: 13; 65%) than that of nonneoplastic masses (N: 7; 35%). In two patients with nasal polyps (n = 7), the radiological diagnosis was not correlated with the histopathological findings. Conclusions: Most of our cases of unilateral nasal mass were inflammatory nasal polyps followed by allergic fungal sinusitis. Clinicians should use caution in relying on radiological findings, and all lesions should undergo a pathological examination.

Abstract With the increased attention toward nanotechnology and their innovative use for different industries including but not limited to food, biomedical, electronics, materials, etc, the application of nanotechnology or nanoparticles in the oil and gas industry is a subject undergoing intense study by major oil companies, which is reflected through the huge amount of funds invested on the research and development, with respect to the nanotechnology. Nanotechnology has been recently investigated extensively for different applications in the oil and gas industry such as drilling fluids and enhanced oil recovery in addition to other applications including cementing and well stimulation. In this paper, comprehensive literature was conducted to review the different applications of nanotechnology in the oil and gas industry. A summary of all nanoparticles used along with a detailed analysis of their performance in improving the targeted parameters is comprehensively presented. The main objective of this review was to provide a comprehensive summary of the different successful applications of nanotechnology and its associated challenges, which could be very helpful for future researches and applications.

Herein, the metabolites secreted by brown algae, Cystoseira crinita, were used as biocatalyst for green synthesis of magnesium oxide nanoparticles (MgO-NPs). The fabricated MgO-NPs were characterized using UV-vis spectroscopy, Fourier transforms infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy linked with energy-dispersive X-ray (SEM-EDX), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Data showed successful formation of crystallographic and spherical MgO-NPs with sizes of 3–18 nm at a maximum surface plasmon resonance of 320 nm. Moreover, EDX analysis confirms the presence of Mg and O in the sample with weight percentages of 54.1% and 20.6%, respectively. Phyco-fabricated MgO-NPs showed promising activities against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans with MIC values ranging between 12.5 and 50 μg mL−1. The IC50 value of MgO-NPs against cancer cell lines (Caco-2) was 113.4 μg mL−1, whereas it was 141.2 μg mL−1 for normal cell lines (Vero cell). Interestingly, the green synthesized MgO-NPs exhibited significant larvicidal and pupicidal activity against Musca domestica. At 10 μg mL−1 MgO-NPs, the highest mortality percentages were 99.0%, 95.0%, 92.2%, and 81.0% for I, II, III instars’ larvae, and pupa of M. domestica, respectively, with LC50 values (3.08, 3.49, and 4.46 μg mL−1), and LC90 values (7.46, 8.89, and 10.43 μg mL−1), respectively. Also, MgO-NPs showed repellence activity for adults of M. domestica at 10 μg mL−1 with 63.0%, 77.9%, 84.9%, and 96.8% after 12, 24, 48, and 72 h, respectively.

Background Renal transplantation is the definitive treatment for patients with end-stage renal disease (ESRD). It is associated with better quality of life and patient survival. Nevertheless, these benefits come with rising concerns about weight gain and metabolic abnormalities, which adversely impact transplant outcomes. Objective The objective of this study is to estimate the incidence of weight gain in the first year post-renal transplant in addition to the assessment of potential risk factors and the resulting outcome of the graft. Methods We conducted a single-center retrospective cohort study of all 295 patients who underwent kidney transplantation at King Abdulaziz Medical City (KAMC) between January 2016 and December 2019. Clinical and laboratory variables were collected from electronic records. Continuous variables were reported as mean ± standard deviation. Comparison between groups was assessed by unpaired t-test or Mann-Whitney U test while follow-up data were compared using paired t-test and repeated measures ANOVA. Association between the potential risk factors and the weight gain was assessed by means of binary logistic regression analysis. Results Significant weight gain was observed in 161 (54.6%) patients. Females were 119 (40.30%) of the cohort. The mean age was 45.3±15.1 years. The prevalence of diabetes was 234 (79.6%), while hypertensives constituted 77 (26.3%). The comparison between patients who gained weight significantly and patients with stable weight showed a numerical higher prevalence of female gender in patients who had more weight gain (44.1% vs. 35.8%), higher diabetes, higher rate of a living donor, and statistically significant lower dialysis duration before transplant. Other clinical and laboratory variables were comparable between the two groups. Conclusion Our study showed a high incidence of clinically significant weight gain among patients post-renal transplantation. Patients with lower dialysis duration, a living kidney donor and those who are obese at baseline were at higher risk of gaining weight. Patients who underwent kidney transplantation should be monitored closely for weight gain and further studies are needed to determine the risk factors and appropriate interventions.

The development of resistance in microbes against antibiotics and limited choice for the use of chemical preservatives in food lead the urgent need to search for an alternative to antibiotics. The enzymes are catalytic proteins that catalyze digestion of bacterial cell walls and protein requirements for the survival of the cell. To study methyltransferase as antibiotics against foodborne pathogen, the methyltransferase enzyme sequence was modeled and its interactions were analyzed against a membrane protein of the gram-positive and gram-negative bacteria through in silico protein–protein interactions. The methyltransferase interaction with cellular protein was found to be maximum, due to the maximum PatchDock Score (15808), which was followed by colicin (12864) and amoxicillin (4122). The modeled protein has found to be interact more significantly to inhibit the indicator bacteria than the tested antibiotics and antimicrobial colicin protein. Thus, model enzyme methyltransferase could be used as enzymobiotics. Moreover, peptide sequences similar to this enzyme sequence need to be designed and evaluated against the microbial pathogen.

BackgroundAlthough genetic diseases are rare, children with such conditions who get infected with COVID-19 tend to have a severe illness requiring hospitalization. Osteogenesis imperfecta (OI) is a rare genetic disorder of collagen resulting in fractures and skeletal deformities. Kyphoscoliosis, restrictive lung disease, and pneumonia worsen the prognosis of patients with OI. The use of bisphosphonate improves bone mineral density (BMD) and reduces fractures in OI. There is no literature describing the impact of COVID-19 in patients with OI.MethodologyA retrospective multi-center study was performed in three hospitals in Jeddah and Riyadh, Saudi Arabia, from March 1st, 2020, until August 31st, 2021, aiming to evaluate the outcome of COVID-19 in patients with OI. Demographics, vaccination status, underlying kyphoscoliosis, functional status, use of bisphosphonate, BMD, and COVID-19 severity, and course were recorded for all patients.ResultsTwelve cases of confirmed COVID-19 were identified among 146 patients with OI. 9 (75%) of patients were less than 18 years, 6 (50%) were male, 5 (41%) had kyphoscoliosis, and 5 (41%) were wheelchair-bound. 6 (50%) received bisphosphonate, and 7(58%) had normal BMD. All patients had mild disease and did not require hospitalization. None of OI the patients with COVID-19 were fully vaccinated before the infection, and some were ineligible for vaccination.ConclusionPatients with OI and COVID-19 in our study recovered without complications, unlike patients with other genetic diseases. Young age and mild illness contributed to the favorable outcome. Half of the patients received bisphosphonate and had normal BMD.

Several physics-based models have been utilized in material design for the simulation and prediction of material properties. In this study, several machine-learning (ML) approaches were used to construct a prediction model to analyze the influence of equal-channel angular pressing (ECAP) parameters on the microstructural, corrosion and mechanical behavior of the biodegradable magnesium alloy ZK30. The ML approaches employed were linear regression, the Gaussian process, and support vector regression. For the optimization of the alloy’s performance, experiments were conducted on ZK30 billets using different ECAP routes, channel angles, and number of passes. The adopted ML model is an adequate predictive model which agreed with the experimental results. ECAP die angles had an insignificant effect on grain refinement, compared to the route type. ECAP via four passes of route Bc (rotating the sample 90° on its longitudinal axis after each pass in the same direction) was the most effective condition producing homogenous ultrafine grain distribution of 1.92 µm. Processing via 4-Bc and 90° die angle produced the highest hardness (97-HV) coupled with the highest tensile strength (344 MPa). The optimum corrosion rate of 0.140 mils penetration per year (mpy) and the optimum corrosion resistance of 1101 Ω·cm2 resulted from processing through 1-pass using the 120°-die. Grain refinement resulted in reducing the corrosion rates and increased corrosion resistance, which agreed with the ML findings.

Although Cs(I) and Sr(II) are not strategic and hazardous metal ions, their recovery from aqueous solutions is of great concern for the nuclear industry. The objective of this work consists of designing a new sorbent for the simultaneous recovery of these metals with selectivity against other metals. The strategy is based on the functionalization of algal/polyethyleneimine hydrogel beads by phosphonation. The materials are characterized by textural, thermo-degradation, FTIR, elemental, titration, and SEM-EDX analyses to confirm the chemical modification. To evaluate the validity of this modification, the sorption of Cs(I) and Sr(II) is compared with pristine support under different operating conditions: the pH effect, kinetics, and isotherms are investigated in mono-component and binary solutions, before investigating the selectivity (against competitor metals) and the possibility to reuse the sorbent. The functionalized sorbent shows a preference for Sr(II), enhanced sorption capacities, a higher stability at recycling, and greater selectivity against alkali, alkaline-earth, and heavy metal ions. Finally, the sorption properties are compared for Cs(I) and Sr(II) removal in a complex solution (seawater sample). The combination of these results confirms the superiority of phosphonated sorbent over pristine support with promising performances to be further evaluated with effluents containing radionuclides.

The wound-healing process is complex and prone to interruption or failure, which can result in the development of chronic wounds that never heal. This can be overcome by seeking prompt medical attention, which will reduce the likelihood of complications and speed up the healing of the cutaneous wound. It has been established that functionalized engineered biomaterials are a possible strategy for starting skin wound care. The purpose of the current study is to develop a diosmin (DSM)-loaded nanoemulsion (NE)-based gel formulation and to investigate its wound healing and anti-inflammatory activity on rats. The DSM-loaded NEs (F1-F17) were developed and optimized with the help of Box–Behnken Design Expert. The DSM-Nes were developed using lauroglycol 90 (LG90®) as oil, Tween-80 as surfactant and transcutol-HP (THP) as co-surfactant. The optimized Nes showed globule size (41 ± 0.07 nm), polydispersity index (PDI) (0.073 ± 0.008) and percentage of entrapment efficiency (%EE) (87 ± 0.81%). This optimized DSM-loaded NEs (F1) was further evaluated and incorporated into 1% carbopol 940 gel. F1-loaded gel was then characterized for drug content, spreadability, in vitro release, wound healing, and anti-inflammatory studies. The developed gel of DSM was found to show significantly better (p < 0.05) wound-healing and anti-inflammatory activity.

Diabetic nephropathy is the primary cause of morbidity in type 2 diabetes mellitus (T2DM) patients. New data indicate that hypertension, a common comorbidity in T2DM, can worsen outcomes of diabetic nephropathy. While metformin is a commonly prescribed drug for treating type 2 diabetes, its blood pressure regulating ability is not well documented. The aim of this study was to investigate the effect of metformin on normalizing blood pressure in salt-loaded hypertensive diabetic db/db mice. Sixteen-week-old male and female diabetic db/db mice were individually placed in metabolic cages and then randomized to a control vehicle (saline) or metformin treatment group. We evaluated the blood pressure reducing ability of metformin in salt-induced hypertension and progression of nephropathy in db/db mice. We observed that metformin- normalized systolic blood pressure in hypertensive diabetic mice. Mechanistically, metformin treatment reduced renal cathepsin B expression. Low cathepsin B expression was associated with reduced expression and activity of the epithelial sodium channel (ENaC), sodium retention, and thus control of hypertension. In addition, we identified that urinary extracellular vesicles (EVs) from the diabetic mice are enriched in cathepsin B. Compared to treatment with urinary EVs of vehicle-treated hypertensive diabetic mice, the amiloride-sensitive transepithelial current was significantly attenuated upon exposure of renal collecting duct cells to urinary EVs isolated from metformin-treated db/db mice or cathepsin B knockout mice. Collectively, our study identifies a novel blood pressure reducing role of metformin in diabetic nephropathy by regulating the cathepsin B-ENaC axis.

The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood–brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals.

In the present work, ginger essential oil (GEO) loaded chitosan (CS) based films incorporated with varying concentrations of gelatin (GE) were fabricated and dried at different conditions (25 °C and 45 °C). The physio-chemical, mechanical and antioxidant potential of the films were determined. Films dried at 45 °C showed better physical attributes and less thickness, swelling degree (SD), moisture content, water vapor permeability (WVP), more transparency, and better mechanical characteristics. Fourier transform infrared spectroscopy (FTIR) revealed the chemical composition and interaction between the functional groups of the film components. X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) findings revealed that samples dried at 45 °C had more crystalline structure, were thermally stable, and smoother. Antioxidant results showed that films dried at low temperature showed comparatively more (p < 0.0001) antioxidant activity. Additionally, an increase in gelatin concentration improved the tensile strength and swelling factor (p < 0.05), however, had no significant impact on other parameters. The overall results suggested better characteristics of GEO-loaded CS-GE based edible films when dried at 45 °C.

The main challenge for researchers in the biomedical sectors concerns the development of new active compounds through cost-effectiveness, rapid, simple, and ecofriendly methods to overcome antibiotic resistance to pathogenic microbes. Herein, gold nanoparticles (AuNPs) were fabricated by a green approach through the reduction of chloroauric acid (HAuCl4) by harnessing the metabolites present in the aqueous extract of Zingiber officinale rhizome. UV-Vis spectroscopy, FT-IR, XRD, TEM, DLS, and zeta potential were used to characterize phytosynthesized AuNPs. In addition, the antimicrobial effect was investigated against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus), Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), unicellular fungi (Candida albicans), and multicellular fungi (Aspergillus brasiliensis). Antioxidant and in vitro cytotoxic activities were assessed. TEM and XRD showed the successful formation of spherical and crystalline structures, with sizes in the range of 5–53 nm (average size: 15.11 ± 8.5 nm). The zeta potential value (i.e., –28.8 mV) explains the high stability of synthesized AuNPs. AuNPs exhibit promising activity against prokaryotic and eukaryotic microorganisms with variable inhibition zones and low MIC values in the range of 25–6.25 µg mL−1. Phytosynthesized AuNPs exhibit DPPH scavenging activity with percentages of 87.6 ± 0.5% at a maximum concentration (1000 µg mL−1), which can be compared with ascorbic acid (97.3 ± 0.2%). Moreover, the AuNPs displayed a target-oriented effect for cancer cell lines HepG2 and MCF7 at low IC50 concentrations of 131.9 ± 9.34 and 288.23 ± 31.39 µg mL−1 compared to the normal oral epithelial OEC cell line (487.612 ± 3.53 µg mL−1). Overall, the phytosynthesized AuNPs show wide activities that enable their use in various biomedical and biotechnological applications.

In the current study, diosmin (DSM)-loaded beta-cyclodextrin (β-CD)-based nanosponges (NSPs) using diphenylcarbonate (DPC) as a cross-linker were prepared. Four different DSM-loaded NSPs (D-NSP1-NSP4) were developed by varying the molar ratio of β-CD: DCP (1:15–1:6). Based on preliminary evaluations, NSPs (D-NSP3) were optimized for size (412 ± 6.1 nm), polydispersity index (PDI) (0.259), zeta potential (ZP) (−10.8 ± 4.3 mV), and drug loading (DL) (88.7 ± 8.5%), and were further evaluated by in vitro release, scanning electron microscopy (SEM), and in vitro antioxidant studies. The NSPs (D-NSP3) exhibited improved free radical scavenging activity (85.58% at 100 g/mL) compared to pure DSM. Dissolution efficiency (%DE) was enhanced to 71.50% (D-NSP3) from plain DSM (58.59%). The D-NSP3 formulation followed the Korsmeyer–Peppas kinetic model and had an n value of 0.529 indicating a non-Fickian and controlled release by diffusion and relaxation. The D-NSP3 showed cytotoxic activity against MCF-7 breast cancer, as evidenced by caspase 3, 9, and p53 activities. According to the findings, DSM-loaded NSPs might be a promising therapy option for breast cancer.

The objective was to implement CI under national tuberculosis programmatic conditions and to advocate for its scaling up. Contact investigation was implemented in 150 Basic Management Units identified across eight countries. The target populations (children

Hypertension may develop before or after the onset of diabetes and it is known to increase the risk of developing diabetic nephropathy. Alpha-1 antitrypsin (AAT) is a multi-functional protein with beneficial effects in various diseases but its role in reducing blood pressure in the diabetic kidney has not been thoroughly studied. Like blood pressure, epithelial sodium channels (ENaC) and its adaptor protein myristoylated alanine-rich C-kinase substrate (MARCKS) are regulated by circadian rhythms. Our hypothesis is that administration of human AAT (hAAT) reduces blood pressure in hypertensive diabetic mice by attenuating membrane expression of ENaC and its association with the actin cytoskeleton. First, we show hAAT administration results in reduced blood pressure in diabetic db/db mice compared to vehicle treatment in both the inactive and active cycles. Western blotting and immunohistochemistry analyses showed a reduction of ENaC and the actin cytoskeleton protein, MARCKS in the kidneys of diabetic db/db mice treated with hAAT compared to vehicle. hAAT treatment resulted in elevated amounts of extracellular vesicles present in the urine of diabetic db/db mice compared to vehicle treatment both in the inactive and active cycles. Multiple hexosylceramides, among other lipid classes increased in urinary EVs released from hAAT treated hypertensive diabetic mice compared to vehicle treated mice. Taken together, these data suggest hAAT treatment could normalize blood pressure in the diabetic kidney in a mechanism involving attenuation of renal ENaC and MARCKS protein expression and possibly ceramide metabolism to hexosylceramide in kidney cells.

The current study aimed to prepare a topical gel containing solid lipid nanoparticles (SLNs) encapsulating fluoxetine for diabetic wound healing effects. Fluoxetine (FX) was loaded into SLNs by employing an emulsion solvent evaporation technique using stearic acid as a lipid, and soya lecithin as a surfactant. SLNs were then evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), percent entrapment efficiency (%EE), percent drug loading (%DL), and in vitro drug release. The optimized SLN (FS3) composed of FX (100 mg), SA (150 mg), and SA (100 mg) displayed mean particle size (467.3 ± 2.2nm), PDI (0.435 ± 0.02), ZP (−32.2 ± 4.47mV), EE (95.8 ± 3.38%), and DL (16.4 ± 2.4%). FTIR and DSC studies denote drug-polymer compatibility and the amorphous nature of FX in the SLNs. The drug release at 24 h was found to be (98.89 ± 2.57%) which followed the fickian diffusion mechanism. SLN (FS3) was further loaded into carbopol gel and tested for pH, spreadability, and extrudability of pharmaceutical parameters. In-vitro release of FX from the SLN gel and plain gel was compared, diabetic wound healing gel (DWH) showed sustained drug delivery. An in vivo study was also performed for DWH gel in streptozotocin-induced diabetic rats. Histopathological examination exhibited DWH gel-treated wounds have increased hydroxyproline, cellular proliferation, a rise in the number of blood vessels, and the level of collagen synthesis. Thus, DWH gel-loaded SLN encapsulated with FX could be a potential carrier for the effective treatment and management of diabetic wounds.