Search

Shahad Bawazeer,1 Maha Alshalan,2 Aziza Alkhaldi,3 Nasser AlAtwi,3 Mohammed AlBalwi,1,3,4 Abdulrahman Alswaid,2 Majid Alfadhel,1,2,4 1Developmental Medicine Department, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 2Department of Pediatrics, Genetic Division, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 3Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia; 4King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia Abstract: Tetrasomy 18p syndrome (Online Mendelian Inheritance in Man 614290) is a very rare chromosomal disorder that is caused by the presence of isochromosome 18p, which is a supernumerary marker composed of two copies of the p arm of chromosome 18. Most tetrasomy 18p cases are de novo cases; however, familial cases have also been reported. It is characterized mainly by developmental delays, cognitive impairment, hypotonia, typical dysmorphic features, and other anomalies. Herein, we report de novo tetrasomy 18p in a 9-month-old boy with dysmorphic features, microcephaly, growth delay, hypotonia, and cerebellar and renal malformations. We compared our case with previously reported ones in the literature. Clinicians should consider tetrasomy 18p in any individual with dysmorphic features and cardiac, skeletal, and renal abnormalities. To the best of our knowledge, we report for the first time an association of this syndrome with partial agenesis of cerebellar vermis. Keywords: tetrasomy 18p, chromosomal, isochromosome, 18p, dysmorphic, CGH microarray, chromosome, syndrome

Yusra A Alyafee,1,2 Manal Alaamery,1 Shahad Bawazeer,1 Mansour S Almutairi,1 Badr Alghamdi,1 Nawaf Alomran,1 Atia Sheereen,1 Maha Daghestani,2 Salam Massadeh1,3 1Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia; 2Department of Zoology/College of Science/King Saud University (KSU), Riyadh, Kingdom of Saudi Arabia; 3College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Ministry of National Guard, Health Affairs, Riyadh, Kingdom of Saudi Arabia Purpose: Anastrozole (ANS) is an aromatase inhibitor that is widely used as a treatment for breast cancer in postmenopausal women. Despite the wide use of ANS, it is associated with serious side effects due to uncontrolled delivery. In addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology-based drug delivery has the potential to enhance the efficacy of drugs and overcome undesirable side effects. In this study, we aimed to prepare novel ANS-loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response of MCF-7 cell line to both ANS and ANS-loaded NPs.Method: ANS-NPs were synthesized using double emulsion method and characterized using different methods. The apoptotic response was evaluated by assessing cell viability, morphology, and studying changes in the expression of MAPK3, MCL1, and c-MYC apoptotic genes in MCF-7 cell lines.Results: ANS was successfully encapsulated within PLA-PEG-PLA, forming monodisperse therapeutic NPs with an encapsulation efficiency of 67%, particle size of 186±27.13, and a polydispersity index of 0.26±0.11 with a sustained release profile extended over 144 hours. In addition, results for cell viability and for gene expression represent a similar apoptotic response between the free ANS and ANS-NPs.Conclusion: The synthesized ANS-NPs showed a similar therapeutic effect as the free ANS, which provides a rationale to pursue pre-clinical evaluation of ANS-NPs on animal models. Keywords: anastrozole, PLA-PEG-PLA, anti-apoptosis, gene expression, therapeutic nanoparticles

The lattice Boltzmann method (LBM) has reached maturity in many aspects for modeling incompressible, laminar flow and heat and mass transfer. However, many issues still need to be clarified. One of those is how to deal with Neumann boundary conditions (heat, momentum, and mass fluxes) at the interface between layers of different thermophysical properties, which is the topic of this work. In this work, we try to illustrate modeling of transient and steady-state heat transfer through multilayers, ensuring continuity of the flux, temperature, momentum, velocity, or species concentration at the interface, which is not a trivial issue in any of the numerical methods. Satisfying continuity conditions at the interface using the LBM needs special treatment, because the relaxation time depends on the thermophysical properties. In this work, methods to solve this issue are introduced for solving 1-D and 2-D, unsteady heat diffusion problems However, the methods can be equally applied for multilayer immiscible fluid flow and mass transfer problems. The predictions of the LBM are compared with those of the finite-volume method (FVM). [ABSTRACT FROM AUTHOR]

The notion of generalized derivations of BCC-algebras is introduced, and some related properties are investigated. Also, we consider regular generalized derivations and the D-invariant on ideals of BCC-algebras. We also characterized KerD by generalized derivations. [ABSTRACT FROM AUTHOR]

Mobile Edge Computing (MEC) is crucial for reducing latency by bringing computational resources closer to the network edge, thereby enhancing the quality of services (QoS). However, the broad deployment of cloudlets poses challenges in efficient network slicing, particularly when traffic distribution is uneven. Therefore, these challenges include managing diverse resource requirements across widely distributed cloudlets, minimizing resource conflicts and delays, and maintaining service quality amid fluctuating request rates. Addressing this requires intelligent strategies to predict request types (common or urgent), assess resource needs, and allocate resources efficiently. Emerging technologies like edge computing and 5G with network slicing can handle delay-sensitive IoT requests rapidly, but a robust mechanism for real-time resource and utility optimization remains necessary. To address these challenges, we designed an end-to-end network slicing approach that predicts common and urgent user requests through T distribution. We formulated our problem as a multi-agent Markov decision process (MDP) and introduced a multi-agent soft actor-critic (MAgSAC) algorithm. This algorithm prevents the wastage of scarce resources by intelligently activating and deactivating virtual network function (VNF) instances, thereby balancing the allocation process. Our approach aims to optimize overall utility, balancing trade-offs between revenue, energy consumption costs, and latency. We evaluated our method, MAgSAC, through simulations, comparing it with the following six benchmark schemes: MAA3C, SACT, DDPG, S2Vec, Random, and Greedy. The results demonstrate that our approach, MAgSAC, optimizes utility by 30%, minimizes energy consumption costs by 12.4%, and reduces execution time by 21.7% compared to the closest related multi-agent approach named MAA3C.

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann-Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or had a first- or second-degree relative affected by the disorder. No specific criteria were set for the age of the participants. All were between 15 and 18 weeks of gestation. Using amplicon-based next-generation sequencing (NGS), we analyzed the zygosity and variants in cffDNA extracted from maternal peripheral blood. After amplicon NGS, analysis was completed by a custom data analysis pipeline that included in-house-built data processing scripts and commonly used software packages. Importantly, the results were not disclosed to the patients. Our findings showed that in all three cases, AR cffDNA screening results were consistent with standard invasive diagnostic testing. This screening method offers several advantages: it provides critical information to families earlier in the pregnancy compared to invasive diagnostic tests, and it helps to alleviate parental anxiety. Moreover, this non-invasive method can determine pregnancy status in the first trimester for known familial variants. Future research may extend this approach to screen for known disease-causing variants in common AR conditions., Competing Interests: MA was a founder of Shomool, a company specializing in cffDNA screening for AR conditions. SL, RF, RR, YL, and YF were employed by Baylor Genetics. FX and CE were employed by Baylor College of Medicine and provide services for Baylor Genetics through a professional services agreement. One of Baylor Genetics’ many product offerings is PreSeek, a cffDNA screening for 30 genes associated with clinically significant and life-limiting AD conditions. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lau, Fawaz, Rigobello, Bawazeer, Alajaji, Faqeih, Li, Feng, Xia, Eng and Abedalthagafi.)

This research is an analysis of multiple regression models developed for predicting ketoprofen solubility in supercritical carbon dioxide under different levels of T(K) and P(bar) as input features. Solubility of the drug was correlated to pressure and temperature as major operational variables. Selected models for this study are Piecewise Polynomial Regression (PPR), Kernel Ridge Regression (KRR), and Tweedie Regression (TDR). In order to improve the performance of the models, hyperparameter tuning is executed utilizing the Water Cycle Algorithm (WCA). Among, the PPR model obtained the best performance, with an R 2 score of 0.97111, alongside an MSE of 1.6867E-09 and an MAE of 3.01040E-05. Following closely, the KRR model demonstrated a good performance with an R 2 score of 0.95044, an MSE of 2.5499E-09, and an MAE of 3.49707E-05. In contrast, the TDR model produces a lower R 2 score of 0.84413 together with an MSE of 7.4249E-09 and an MAE of 5.69159E-05., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Al Hagbani, Alshehri and Bawazeer.)

Background: Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation., Methodology: Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias., Results: We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification., Conclusion: Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Silver nanoparticles (AgNPs) are gaining increasing attention in biomedical applications due to their unique properties. Green synthesis methods are environmentally friendly and have demonstrated potential for AgNP production. This study explores the green synthesis of AgNPs using the methanolic extract of Euphorbia milii , a plant known for its medicinal properties. The primary objectives of this research were to synthesize AgNPs using E. milii extract, characterize the nanoparticles (NPs) using various techniques, and evaluate their antibacterial and enzyme inhibitory activities., Methods: E. milii plant extract was utilized for the green synthesis of AgNPs. The characterization of the NPs was performed through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy (EDX). Antibacterial activity was assessed against Staphylococcus aureus , while enzyme inhibitory assays were conducted against urease, α-glucosidase, carbonic anhydrase II, and xanthine oxidase., Results: The synthesized AgNPs exhibited significant antibacterial effects, with a remarkable 20-mm zone of inhibition against S. aureus , surpassing the efficacy of the plant extract alone. Furthermore, the AgNPs demonstrated remarkable enzyme inhibition, achieving impressive percentages of 77.98% against α-glucosidase and 88.54% against carbonic anhydrase II. Half-maximal inhibitory concentration values for enzyme inhibition were highly promising, including 78.09 ± 1.98 μM for α-glucosidase, 0.22 ± 0.10 μM for carbonic anhydrase II, and 7.11 ± 0.55 μM for xanthine oxidase., Conclusion: In this study, AgNPs were successfully synthesized using E. milii extract and characterized using various techniques. The AgNPs exhibited significant antibacterial and enzyme-inhibitory activities, showcasing their potential for biomedical applications., Competing Interests: The author declares no conflict of interest., (Copyright: © International Journal of Health Sciences.)

The Internet has become a vital source of knowledge and communication in recent times. Continuous technological advancements have changed the way businesses operate, and everyone today lives in the digital world of engineering. Because of the Internet of Things (IoT) and its applications, people's impressions of the information revolution have improved. Malware detection and categorization are becoming more of a problem in the cybersecurity world. As a result, strong security on the Internet could protect billions of internet users from harmful behavior. In malware detection and classification techniques, several types of deep learning models are used; however, they still have limitations. This study will explore malware detection and classification elements using modern machine learning (ML) approaches, including K-Nearest Neighbors (KNN), Extra Tree (ET), Random Forest (RF), Logistic Regression (LR), Decision Tree (DT), and neural network Multilayer Perceptron (nnMLP). The proposed study uses the publicly available dataset UNSWNB15. In our proposed work, we applied the feature encoding method to convert our dataset into purely numeric values. After that, we applied a feature selection method named Term Frequency-Inverse Document Frequency (TFIDF) based on entropy for the best feature selection. The dataset is then balanced and provided to the ML models for classification. The study concludes that Random Forest, out of all tested ML models, yielded the best accuracy of 97.68 %., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shaikhan Bawazeer reports financial support was provided by Arab 10.13039/100008509Open University. Shaikhan Bawazeer reports a relationship with Arab Open University, Saudi Arabia that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Non-invasive prenatal testing (NIPT) is a pioneering technique that has consistently advanced the field of prenatal testing to detect genetic abnormalities and conditions with the aim of decreasing the incidence and prevalence of inherited conditions. NIPT remains a method of choice for common autosomal aneuploidies, mostly trisomy 21, and several monogenic disorders. The advancements in gene sequencing techniques have expanded the panel of conditions where NIPT could be offered. However, basic research on the impact of several genetic conditions lags behind the methods of detection of these sequence aberrations, and the impact of the expansion of NIPT should be carefully considered based on its utility. With interest from commercial diagnostics and a lack of regulatory oversight, there remains a need for careful validation of the predictive values of different tests offered. NIPT comes with many challenges, including ethical and economic issues. The scientific evidence, technical feasibility, and clinical benefit of NIPT need to be carefully investigated before new tests and developments are translated into clinical practice. Moreover, the implementation of panel expansion of NIPT should accompany expert genetic counseling pre- and post-testing., Competing Interests: MA is a founder of Shomool, which specializes in NIPT for ARD. RF and AM are employed by Baylor Genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abedalthagafi, Bawazeer, Fawaz, Heritage, Alajaji and Faqeih.)

Mycobacterium tuberculosis , the bacterium responsible for tuberculosis, is a global health concern, affecting millions worldwide. This bacterium has earned a reputation as a formidable adversary due to its multidrug-resistant nature, allowing it to withstand many antibiotics. The development of this drug resistance in Mycobacterium tuberculosis is attributed to innate and acquired mechanisms. In the past, rifampin was considered a potent medication for treating tuberculosis infections. However, the rapid development of resistance to this drug by the bacterium underscores the pressing need for new therapeutic agents. Fortunately, several other medications previously overlooked for tuberculosis treatment are already available in the market. Moreover, several innovative drugs are under clinical investigation, offering hope for more effective treatments. To enhance the effectiveness of these drugs, it is recommended that researchers concentrate on identifying unique target sites within the bacterium during the drug development process. This strategy could potentially circumvent the issues presented by Mycobacterium drug resistance. This review primarily focuses on the characteristics of novel drug resistance mechanisms in Mycobacterium tuberculosis . It also discusses potential medications being repositioned or sourced from novel origins. The ultimate objective of this review is to discover efficacious treatments for tuberculosis that can successfully tackle the hurdles posed by Mycobacterium drug resistance., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

No effective drug treatment is available for Alzheimer disease, thus the need arise to develop efficient drugs for its treatment. Natural products have pronounced capability in treating Alzheimer disease therefore current study aimed to evaluate the neuro-protective capability of folicitin against scopolamine-induced Alzheimer disease neuropathology in mice. Experimental mice were divided into four groups i.e. control (single dose of 250 μL saline), scopolamine-administered group (1 mg/kg administered for three weeks), scopolamine plus folicitin-administered group (scopolamine 1 mg/kg administration for three weeks followed by folicitin administration for last two weeks) and folicitin-administered group (20 mg/kg administered for 5 alternate days). Results of behavioral tests and Western blot indicated that folicitin has the capability of recovering the memory against scopolamine-induced memory impairment by reducing the oxidative stress through up-regulating the endogenous antioxidant system like nuclear factor erythroid 2-related factor and Heme oxygenase-1 while prohibiting phosphorylated c-Jun N-terminal kinase. Similarly, folicitin also improved the synaptic dysfunction by up-regulating SYP and PSD95. Scopolamine-induced hyperglycemia and hyperlipidemia were abolished by folicitin as evidenced through random blood glucose test, glucose tolerance test and lipid profile test. All these results revealed that folicitin being a potent anti-oxidant is capable of improving synaptic dysfunction and reducing oxidative stress through Nrf-2/HO-1 pathway, thus plays a key role in treating Alzheimer disease as well as possess hyperglycemic and hyperlipidemic effect. Furthermore, a detailed study is suggested., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The fundamental aim of this project was to assess the sonophotocatalytic degradation of textile dyes mostly eluted from industries into wastewater. Such a pretreatment of wastewater makes the water suitable for drinking and irrigation purposes and thereby helps protect the ecosystem. The main objective of this research was to degrade real samples and laboratory-prepared samples sonophotocatalytically using a silver-impregnated ZnO photocatalyst. Reactive dyes, including Fast Yellow AB (FY AB) and Remazol Brilliant Violet-5R (RBV-5R), were degraded via this technique under optimum and enhanced conditions. The photocatalyst was synthesized through a wet impregnation process and characterized by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis, Fourier transform infrared (FTIR) spectroscopy, and UV/vis spectroscopy to examine the morphology, composition, and functional groups of the photocatalyst. Parameters including pH, dosage, dye concentration, scavengers, and effects of oxidizing agents were considered. Under optimal conditions, the degradations were 95.7 and 88.9% for RBV-5R and FY AB, respectively, in 60 min. The pH and oxidizing agents played important roles in the degradation process. Only 43.8 and 32.5% of RBV-5R and FY AB, respectively, were degraded in the absence of an oxidizing agent. With the addition of oxidizing agents, 95.7 and 88.9% of RBV-5R and FY AB degradation occurred, respectively. The optimal pH values for RBV 5-R and FY-AB were 8 and 12, respectively. A comparison between the photocatalytic and sonophotocatalytic processes revealed degradation efficiencies of 41 and 33% for RBV-5R and FY-AB, respectively, by the photocatalytic process. Therefore, results indicate the productivity of the sonophotocatalytic degradation process., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Quinoa ( Chenopodium quinoa ) is a grain-like, genetically diverse, highly complex, nutritious, and stress-tolerant food that has been used in Andean Indigenous cultures for thousands of years. Over the past several decades, numerous nutraceutical and food companies are using quinoa because of its perceived health benefits. Seeds of quinoa have a superb balance of proteins, lipids, carbohydrates, saponins, vitamins, phenolics, minerals, phytoecdysteroids, glycine betaine, and betalains. Quinoa due to its high nutritional protein contents, minerals, secondary metabolites and lack of gluten, is used as the main food source worldwide. In upcoming years, the frequency of extreme events and climatic variations is projected to increase which will have an impact on reliable and safe production of food. Quinoa due to its high nutritional quality and adaptability has been suggested as a good candidate to offer increased food security in a world with increased climatic variations. Quinoa possesses an exceptional ability to grow and adapt in varied and contrasting environments, including drought, saline soil, cold, heat UV-B radiation, and heavy metals. Adaptations in salinity and drought are the most commonly studied stresses in quinoa and their genetic diversity associated with two stresses has been extensively elucidated. Because of the traditional wide-ranging cultivation area of quinoa, different quinoa cultivars are available that are specifically adapted for specific stress and with broad genetic variability. This review will give a brief overview of the various physiological, morphological and metabolic adaptations in response to several abiotic stresses., Competing Interests: The authors declare that they have no competing interests., (© 2023 Ain et al.)

Diospyros kaki (Japanese persimmon) is cultivated specious of the Diospyros genus. D. kaki is a multi-medicinal application in the folk system for the cure of ischemic stroke, angina, atherosclerosis, muscle relaxation, internal hemorrhage, hypertension, high cough, and infectious disease. The main objective of this study was the isolated bioactive metabolites from chloroform fractions of D. kaki. The extract and fractions were then tested for various in-vitro (antioxidant and lipoxygenase) and in-vivo (muscle relaxant) activities. The repeated chromatographic separation of chloroform extract afforded compound 1. Compound 1, n -hexane, and chloroform fractions were evaluated for in vitro antioxidant, lipoxygenase inhibitory, and in vivo muscle relaxant potency. The chloroform extract has 79.54% interaction with DPPH at higher concentrations (100 μg/ml) while the compound exhibited a maximum effect of 95.09% at 100 μg/ml. Compound 1 exhibited significant lipoxygenase inhibitory activity with an IC 50 value of 36.98 μM followed by a chloroform extract of 57.09 μM. Similarly, compound 1 and chloroform extract showed excellent muscle relaxant effects at a higher dose. From this investigation, it is concluded that extracts and pure compounds exhibited promising antioxidant, lipoxygenase inhibitory, and muscle relaxant activity. This study excellently rationalizes the traditional usage of D. kaki in curing various diseases. Furthermore, the docking results indicate, that the isolated compound fits well into the active site of the lipoxygenase, and makes strong interactions with the target protein., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background: Increasing soil salinization has a detrimental effect on agricultural productivity.Therefore, strategies are needed to induce salinity-tolerance in crop species for sustainable foodproduction. γ-aminobutyric acid (GABA) plays a key role in regulating plant salinity stresstolerance. However, it remains largely unknown how mungbean plants (Vigna radiata L.) respondto exogenous GABA under salinity stress., Methods: Thus, we evaluated the effect of exogenous GABA (1.5 mM) on the growth and physiobiochemicalresponse mechanism of mungbean plants to saline stress (0-, 50-, and 100 mM [NaCland Na2SO4, at a 1:1 molar ratio])., Results: Increased saline stress adversely affected mungbean plants' growth and metabolism. Forinstance, leaf-stem-root biomass (34- and 56%, 31- and 53%, and 27- and 56% under 50- and 100mM, respectively]) and chlorophyll concentrations declined. The carotenoid level increased (10%)at 50 mM and remained unaffected at 100 mM. Hydrogen peroxide (H2O2), malondialdehyde(MDA), osmolytes (soluble sugars, soluble proteins, proline), total phenolic content, andenzymatic activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase(POD), glutathione reductase (GTR), and polyphenol oxidation (PPO) were significantlyincreased. In leaves, salinity caused a significant increase in Na+ concentration but a decrease inK+ concentration, resulting in a low K+/Na+ concentration (51- and 71% under 50- and 100- mMstress). Additionally, nitrogen concentration and the activities of nitrate reductase (NR) andglutamine synthetase (GS) decreased significantly. The reduction in glutamate synthase (GOGAT)activity was only significant (65%) at 100 mM stress. Exogenous GABA decreased Na+, H2O2,and MDA concentrations but enhanced photosynthetic pigments, K+ and K+/Na+ ratio, Nmetabolism, osmolytes, and enzymatic antioxidant activities, thus reducing salinity-associatedstress damages, resulting in improved growth and biomass., Conclusion: Exogenous GABA may have improved the salinity tolerance of mungbean plants by maintaining their morpho-physiological responses and reducing the accumulation of harmfulsubstances under salinity. Future molecular studies can contribute to a better understanding of themolecular mechanisms by which GABA regulates mungbean salinity tolerance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ullah, Ali, Noor, Zeng, Bawazeer, Eldin, Asghar, Javed, Saleem, Ullah and Ali.)

Human health is the main concern related to use of crop products irrigated with contaminated irrigation sources. Present research has been conducted to explore heavy metal status of sewage and industrial wastewater being used up for irrigation purpose in the peri-urban areas of the district Dera Ghazi Khan which has not been explored widely before. The analysis also followed heavy metal detection in the subsequent irrigated soil and vegetables/crop plants in relation to assessment of health risk to the consumer to plan the future monitoring in this area. An unremitting boost of heavy metals into the environment from wastewater irrigation has become a global issue. These heavy metals enter the food chain and pose health assumptions to consumers upon utilization. In the present study, an investigation has been conducted to determine metal concentrations in the wastewater, soil, and different plant species. For wastewater samples, pH, total dissolved solids (TDS), electrical conductivity (EC), and selected heavy metals such as Al, As, Cr, Cu, Fe, Mn, Pb, Zn, and Ni were determined. The mean values of heavy metals in the soil samples were within the WHO/FAO safe limit, while Cr and Pb were the most frequent (100%) among the metals. However, differentiating the sites, the concentration of Cr and Cu, Ni, and Fe were elevated. The metal transfer was highly effective from soil to the growing plants i.e. brinjal, red corn, wheat, tomato, and spinach than other plant species. Among the metals, Cr, Ni, Mn, and Pb in plant samples were exceeding the WHO/FAO safe limit. Health risk index (HRI) have revealed the possible potential risk of heavy metal contaminated plant species in the order of spinach (6.4) > wheat (6.4) > brinjal (5.9) > tomato (4.7) > red corn (4.5) > apple gourd (4.3) > white corn (3.8) > cabbage (3.1) > luffa (2.9). Likewise, HRI of different metals was calculated as Cu (19.6) > Zn (17.9) > Cr (2.95) > Ni (0.85) > Mn (0.48) > Fe (0.15) > Cd (0.11) > Pb (0.05) > As (0.00001). The level of HRI through the use of dietary plants revealed an elevated risk level than the acceptable limit (HRI > 1) for Cu > Zn > Cr in adults. Our findings suggest that there would be a serious health risk to the consumers due to the consumption of these plant species being irrigated with the wastewater. Therefore, a strict regulatory mechanism is proposed for the safety of food plants in the study area including monitoring and recycling of crop plants, and building water treatment plants to remove pollutants and clean wastewater., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Atta, Zehra, Dai, Ali, Naveed, Ali, Sarwar, Ali, Iqbal, Bawazeer, Abdel-Hameed and Ali.)

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, especially in Asian countries. The emergence of its drug resistance and its side effects demands alternatives, to improve prognosis. Since the majority of cancer drugs are derived from natural sources, it provides a window to look for more biocompatible alternatives. In this study, two natural compounds, costunolide (CE) and aloe emodin (AE), were isolated from the stem of Lycium shawii. The compounds were examined for their anticancer and apoptotic potentials against OSCC (CAL 27) cells, using an in vitro analysis, such as a MTT assay, scratch assay, gene, and protein expressions. Both compounds, CE and AE, were found to be cytotoxic against the cancer cells with an IC 50 value of 32 and 38 µM, respectively. Moreover, the compounds were found to be non-toxic against normal NIH-3T3 cells and comparable with the standard drug i.e., 5-fluorouracil (IC 50 = 97.76 µM). These compounds were active against normal cells at higher concentrations. Nuclear staining displayed the presence of apoptosis-associated morphological changes, i.e., karyopyknosis and karyorrhexis in the treated cancer cells. Flow cytometry results further confirmed that these compounds induce apoptosis rather than necrosis, as the majority of the cells were found in the late apoptotic phase. Gene and protein expression analyses showed an increased expression of apoptotic genes, i.e., BAK, caspase 3, 6, and 9. Moreover, the compounds significantly downregulated the expression of the anti-apoptotic (BCL-2 L1), metastatic (MMP-2), and pro-inflammatory (COX-2) genes. Both compounds have shown promising anticancer, apoptotic, and anti-migratory activities against the OSCC cell line (i.e., CAL-27). However, further in vivo studies are required to explore these compounds as anticancer agents.

Purpose: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder., Methods: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature., Results: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss., Conclusion: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities., Competing Interests: Conflict of Interest Megan Li is an employee of Invitae. Erin Torti, Amber Begtrup, and Rhonda E Schnur are employees of GeneDx, Inc. All other authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Breast cancer is the most common cancer type in women in Saudi Arabia (SA). Globally, cancer treatment has been affected by the recent COVID-19 pandemic. The present retrospective study reviews the 30-day morbidity and mortality rates of patients with breast cancer receiving anticancer systemic treatment before (group1) and during the peak of the COVID-19 (group 2) pandemic at a tertiary center, King Abdulaziz University Hospital (Jeddah, SA). There were no differences between the two groups regarding sex, age, breast cancer stage distribution, intention to treat or class of anticancer treatment received. Patients treated during the peak pandemic period received delayed treatment. No statistically significant difference was observed in the 30-day morbidity or mortality rates, although there was a trend towards higher rates of morbidity among patients treated during the peak of the pandemic period. In group 2, only 2.3% of the patients tested positive for COVID-19, and there was no significant difference in the 30-day morbidity and mortality rates between COVID-positive and COVID-negative patients receiving anticancer treatment. Individuals with breast cancer are a vulnerable group of patients that should be treated with special care during pandemics or other crises that affect the health care system., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Al-Hajeili et al.)

Amino acids (AAs) are considered as the building blocks of life. Unlike nonessential AAs, the human body cannot synthesize essential AAs and should be supplied in food or dietary supplements. The aim of the work is simultaneous HPLC-UV determination of 10 structurally related AAs without pre- or postderivatization in powdered dietary supplements (PDSs). This was challenging, especially because PDS has no standardized procedures for its quality control. HPLC-UV chromatograms of the 10 AAs were recorded using a gradient elution of the mobile phase on a CLC-C18 column at 225 nm. The elution started with 100% of phosphate buffer (pH 7.4, 10 mM) for 10 min; then, the concentration of acetonitrile increased linearly to reach 50% for another 15 min at room temperature. Good separation was achieved within a 25 min run time without pre- or postderivatization. The method was carefully validated according to the ICH guidelines over the linearity range of 100-200, 50-200, 20-150, 50-400, 20-250, 75-175, 50-250, 50-250, 50-300, and 5-100 μg/mL for l-lysine, l-threonine, l-histidine, l-valine, l-methionine, l-isoleucine, l-leucine, l-tyrosine, l-phenylalanine, and l-tryptophan, respectively, with mean recoveries ranges between 98.91 and 100.77. The method was found to be precise, and the relative standard deviation (RSD) was found to be between 0.28 and 1.92 with recoveries between 97.91 and 101.11. The method was found to be robust that resists deliberate changes in pH, flow rate, and mobile-phase percentages. It was successfully applied for the analysis of PDSs. The proposed method could be very useful for the quality control of the 10 structurally related AAs during their synthesis and for testing raw materials and pharmaceutical preparations., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Hyperlipidemia, the most common form of dyslipidemia, is the main source of cardiovascular disorders, characterized by elevated level of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) with high-density lipoprotein cholesterol (HDL-C) in peripheral blood. It is caused by a defect in lipid metabolism in the surface of Apoprotein C-II or a defect in lipoprotein lipase activity as well as reported in genetic, dietary and environmental factors. Several electronic databases were investigated as information sources, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, SpringerLink, Semantic Scholar, MEDLINE and CNKI Scholar. The current review focused on the risk factors of dyslipidemia, synthetic medication with their side effects and different types of medicinal plants having significant potential for the management of hyperlipidemia. The management of hyperlipidemia mostly involves a constant decrease in lipid level using different remedial drugs like statin, fibrate, bile acid sequestrates and niacin. However, this extensive review suggested that the consequences of these drugs are arguable, due to their numerous adverse effects. The selected parts of herb plants are used intact or their extracts containing active phytoconstituents to regulate the lipids in blood level. It was also noted that the Chinese herbal medicine and combination therapy is promising for the lowering of hyperlipidemia. This review intends to provide a scientific base for future endeavors, such as in-depth biological and chemical investigations into previously researched topics., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 3-5 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.

Juglans regia L. are nutritious fruit bearing plants mostly found in Northern areas of Pakistan. The population of walnuts was explored from district Dir and Swat Khyber Pakhtunkhwa, Pakistan for their geographical, climatic and chemical divergence. The geographical differences such as altitude, latitude and longitude whereas climatic differences viz. soil EC, soil pH, precipitations, intensity of light, temperature and soil temperature. In both districts TPC ranged from 211.2±0.6 to 227.8±0.4 mg/100g, RSA ranged from 43.32±1.5% to 52.18±0.4%, conductivity ranged from 296.43±0.6 to 312.22±0.3 S/m and elemental composition such as iron, copper, calcium, zinc and magnesium in Dir differs from 0.312±0.032, 0.209±0.13, 20.0±0.313, 0.406±0.10 and 10.2±0.030 mg/L to 0.543±0.65, 0.698±0.82, 28.7±0.234, 0.685±0.15 and 17.6±0.015 mg/L respectively. Altitude and temperature showed a correlation with total phenolics contents and radical scavenging activity while soil pH, precipitations, soil temperature, soil Ec and light intensity indicated a weak correlation with chemical traits of walnuts. Further studies of walnuts are needed to explore their therapeutically important phytochemicals to succeed naturally pharmaceutical nutrients of the maximum significance for the health of human beings.

Termites are known as social insects worldwide. Presently in China 473 species, 44 genera and 4 families of termites have been reported. Of them, 111 Reticulitermes species are widely spread in different zones of China. The dispersion flight season of these Chinese Reticulitermes species are usually started from February to June, but in some regions different species are distributed, sharing their boundaries and having overlapping flight seasons. These reasons become important sources of hybridization between two different heterospecific populations of termites. It was confirmed that the fertilized eggs and unfertilized eggs of some Reticulitermes termites have the capacity of cleavage. While the unfertilized eggs of R. aculabialis, R. chinensis and R. labralis cleaved normally and the only R. aculabialis unfertilized eggs develop in embryos. While, the R. flaviceps and R. chinensis were observed with their abnormal embryonic development, and not hatching of eggs parthenogenetically. They were reported more threatening to Chinese resources as they propagate with parthenogenesis, hybridization and sexual reproduction. Eggshell and macrophiles of eggs play important roles in species identification and control. Although, they are severe pests and cause a wide range of damages to wooden structures and products in homes, buildings, building materials, trees, crops, and forests in China's Mainland.

Germin-like proteins (GLPs) play an important role against various stresses. Vitis vinifera L. genome contains 7 GLPs; many of them are functionally unexplored. However, the computational analysis may provide important new insight into their function. Currently, physicochemical properties, subcellular localization, domain architectures, 3D structures, N-glycosylation & phosphorylation sites, and phylogeney of the VvGLPs were investigated using the latest computational tools. Their functions were predicted using the Search tool for the retrieval of interacting genes/proteins (STRING) and Blast2Go servers. Most of the VvGLPs were extracellular (43%) in nature but also showed periplasmic (29%), plasma membrane (14%), and mitochondrial- or chloroplast-specific (14%) expression. The functional analysis predicted unique enzymatic activities for these proteins including terpene synthase, isoprenoid synthase, lipoxygenase, phosphate permease, receptor kinase, and hydrolases generally mediated by Mn+ cation. VvGLPs showed similarity in the overall structure, shape, and position of the cupin domain. Functionally, VvGLPs control and regulate the production of secondary metabolites to cope with various stresses. Phylogenetically VvGLP1, -3, -4, -5, and VvGLP7 showed greater similarity due to duplication while VvGLP2 and VvGLP6 revealed a distant relationship. Promoter analysis revealed the presence of diverse cis-regulatory elements among which CAAT box, MYB, MYC, unnamed-4 were common to all of them. The analysis will help to utilize VvGLPs and their promoters in future food programs by developing resistant cultivars against various biotic (Erysiphe necator and in Powdery Mildew etc.) and abiotic (Salt, drought, heat, dehydration, etc.) stresses.

Introduction: The genus Euphorbia is known to contain diterpenoids, and several isolated compounds which exhibited biological activities including significant multidrug resistance reversal effects. This work is focused on the isolation, in vitro and in silico studies of two natural bio-active flavonoids ( 1 & 2 ) isolated from Euphorbia pulcherrima bark for the very first time. Methods: The phytochemical investigation resulted in the identification of two flavonoids: 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)-6-methoxy-4H-chromen-4-one (1) and 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6-methoxy-4H-chromen-4-one (2) , which were isolated for the first time from Euphorbia pulcherrima . Results: The chemical structures of the two isolated compounds were confirmed by 1 H NMR, 13 C NMR, and ESI-HRMS spectral data. The Bioactivity activity of these compounds was evaluated; results revealed that compounds 1 & 2 exhibit promising urease inhibitory potential with IC50 values of 15.3 ± 2.13 μM and 19.0 ± 2.43 μM, respectively, whereas the positive control thiourea had an IC 50 of 21.0 ± 0.23 μM. Similarly, these compounds were also evaluated against the tyrosinase enzyme; results showed that compound 1 displays significant inhibitory activity with an IC 50 value of 48.7 ± 2.19 μM, whereas compound 2 exhibited a moderate effect with an IC50 value of 74.8 ± 1.79 μM, when compared with the standard (alpha-kojic acid, IC 50 = 47.6 ± 0.67 μM). Additionally, compounds 1 and 2 also exhibited anti-glycation and phosphodiesterase inhibitory activities. Conclusion: Studies dealing with the drug like properties such as in silico screening (docking study) was also carried out to discover the structural features of both compounds 1 and 2 . Results indicated that the docking scores of compounds 1 and 2 are in agreement with their IC 50 values. Key messagesIsolation and characterization of two bioactive flavonoids ( 1 and 2 ) from Euphorbia pulcherrima . In silico and in vitro enzyme inhibition studies were conducted to identify the therapeutic potential of flavonoids 1 and 2 .Drug-like properties were calculated to discover important pharmacophoric features.

Bell peppers are widely considered as healthy foods that can provide people with various phytochemicals, especially phenolic compounds, which contribute to the antioxidant property of bell peppers. Nevertheless, the acknowledgment of phenolic compounds in bell peppers is still limited. Therefore, this study aimed to determine the phenolic content and the antioxidant potential in pulps and seeds of different bell peppers (green, yellow, and red) by several in vitro assays followed by the characterization and quantification of individual phenolics using liquid chromatography coupled with electrospray ionization-quadrupole-time-of-flight-mass spectrometry (LC-ESI-QTOF-MS/MS) and high-performance liquid chromatography photodiode array (HPLC-PDA) quantification, respectively. The captured results showed that the pulp of red bell peppers exhibited the highest phenolic content in the total polyphenol content (1.03 ± 0.07 mg GAE/g f.w. ), total flavonoid content (137.43 ± 6.35 μg QE/g f.w. ), and total tannin content (0.22 ± 0.01 mg CE/g f.w. ) as well as the most antioxidant potential in all antioxidant capacity estimation assays including total antioxidant capacity (3.56 ± 0.01 mg AAE/g f.w. ), 2,2'-diphenyl-1-picrylhydrazyl (0.89 ± 0.01 mg AAE/g f.w. ), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (1.36 ± 0.12 mg AAE/g f.w. ), and ferric reducing antioxidant power (0.15 ± 0.01 mg AAE/g f.w. ). LC-ESI-QTOF-MS/MS isolated and identified a total of 59 phenolic compounds, including flavonoids (21), phenolic acids (20), other phenolic compounds (12), lignans (5), and stilbenes (1) in all samples. According to HPLC-PDA quantification, the seed portions showed a significantly higher amount of phenolic compounds. These findings indicated that the waste of bell peppers can be a potential source of phenolic compounds, which can be utilized as antioxidant ingredients in foods and nutritional products., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

To prospect an isozyme-specific, effective inhibitor against the physiologically-crucial enzyme phosphodiesterase 1 (PDE1), phytochemicals from Pistacia integerrima galls were screened. The chloroform fraction of gall extract was subjected to column chromatographic which led to the isolation of compound 1 , elucidated to be 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)-4 H -chromen-4-one (a flavone). In vitro and in silico PDE1 inhibitory activity of the compound 1 was investigated. EDTA, a known PDE1 inhibitor, was used as the reference. The flavone exhibited in vitro attenuation towards snake venom PDE1. IC 50 response was superior to the standard chelator. An in silico molecular docking study was carried out using 3D structure of PDE1 to study the binding interactions of compound 1. The docking study predicted that flavone had a lower binding affinity (-7.6 kcal/mol) and total energy (-95 kcal/mol) score compared to EDTA. The minimal energy associated with the ligand-protein complex implied that isolated compound 1 can serve as a therapeutic agent against PDE1 enzyme-provoked ailments like asthma, hypertension, schizophrenia, and erectile dysfunction., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Abdur Rauf et al.)