The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, ...Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. In non-IBC, the cysteine protease cathepsin B (CTSB) is known to be involved in cancer progression and invasion; ...however, very little is known about its role in IBC.
In this study, we enrolled 23 IBC and 27 non-IBC patients. All patient tissues used for analysis were from untreated patients. Using immunohistochemistry and immunoblotting, we assessed the levels of expression of CTSB in IBC versus non-IBC patient tissues. Previously, we found that CTSB is localized to caveolar membrane microdomains in cancer cell lines including IBC, and therefore, we also examined the expression of caveolin-1 (cav-1), a structural protein of caveolae in IBC versus non-IBC tissues. In addition, we tested the correlation between the expression of CTSB and cav-1 and the number of positive metastatic lymph nodes in both patient groups.
Our results revealed that CTSB and cav-1 were overexpressed in IBC as compared to non-IBC tissues. Moreover, there was a significant positive correlation between the expression of CTSB and the number of positive metastatic lymph nodes in IBC.
CTSB may initiate proteolytic pathways crucial for IBC invasion. Thus, our data demonstrate that CTSB may be a potential prognostic marker for lymph node metastasis in IBC.
Metals are extensively used in a variety of applications in the medical field for internal support and biological tissue replacements, such as joint replacements, dental roots, orthopedic fixation, ...and stents. The metals and alloys that are primarily used in biomedical applications are stainless steels, Co alloys, and Ti alloys. The service period of a metallic biomaterial is determined by its abrasion and wear resistance. A reduction in the wear resistance of the implant results in the release of incompatible metal ions into the body that loosen the implant. In addition, several reactions may occur because of the deposition of wear debris in tissue. Therefore, developing biomaterials with high wear resistance is critical to ensuring a long life for the biomaterial. The aim of this work is to review the current state of knowledge of the wear of metallic biomaterials and how wear is affected by the material properties and conditions in terms of the type of alloys developed and fabrication processes. We also present a brief evaluation of various experimental test techniques and wear characterization techniques that are used to determine the tribological performance of metallic biomaterials.
Silver nanoparticles (AgNPs) have been widely produced for different industrial purposes. Recently, biogenic synthesis of AgNPs has emerged although the extent of effects from exposure, oral exposure ...in particular, to nanomaterials synthesized in such a manner remains elusive. The main objective of this study was to evaluate the effects of oral administration of a dose of 50 mg/Kg body weight AgNPs biosynthesized in baker’s yeast (
Saccharomyces cerevisiae
) over a period of eight weeks on the reproductive performance and the possibility of a protective effect through co-administration of morin. Forty-eight male Sprague-Dawley rats were used in four experimental groups (control, morin-treated group, AgNP-treated, and AgNP + morin co-treatment). AgNPs produced no significant alteration in daily food intake or body weight. Both the absolute and relative testicular weights were significantly reduced but not the epididymal weight. Also, serum levels of urea, creatinine, uric acid, and liver enzymes were significantly elevated. Furthermore, AgNPs significantly downregulated the hypothalamic–pituitary–gonadal axis. This corresponds to lower motility and viability percent, reduced sperm concentration, and a higher abnormality ratio as well as a prominent alteration in the blood–testis barrier (BTB) and testicular histology and induction of testicular apoptosis and oxidative stress. The supplementation of morin evidently restored most of the reproductive characters to its physiological range. We can conclude that exposure to the biologically synthesized AgNPs for an extended period of time has proven to be a health risk that can be ameliorated via oral administration of some bioactive agents including morin.
Unlike a traditional virtual machine (VM), a container is an emerging lightweight virtualization technology that operates at the operating system level to encapsulate a task and its library ...dependencies for execution. The Container as a Service (CaaS) strategy is gaining in popularity and is likely to become a prominent type of cloud service model. Placing container instances on virtual machine instances is a classical scheduling problem. Previous research has focused separately on either virtual machine placement on physical machines (PMs) or container, or only tasks without containerization, placement on virtual machines. However, this approach leads to underutilized or overutilized PMs as well as underutilized or overutilized VMs. Thus, there is a growing research interest in developing a container placement algorithm that considers the utilization of both instantiated VMs and used PMs simultaneously.
The goal of this study is to improve resource utilization, in terms of number of CPU cores and memory size for both VMs and PMs, and to minimize the number of instantiated VMs and active PMs in a cloud environment. The proposed placement architecture employs scheduling heuristics, namely, Best Fit (BF) and Max Fit (MF), based on a fitness function that simultaneously evaluates the remaining resource waste of both PMs and VMs. In addition, another meta-heuristic placement algorithm is proposed that uses Ant Colony Optimization based on Best Fit (ACO-BF) with the proposed fitness function. Experimental results show that the proposed ACO-BF placement algorithm outperforms the BF and MF heuristics and maintains significant improvement of the resource utilization of both VMs and PMs.
Foodborne pathogens can be found in various foods, and it is important to detect foodborne pathogens to provide a safe food supply and to prevent foodborne diseases. The nucleic acid base detection ...method is one of the most rapid and widely used methods in the detection of foodborne pathogens; it depends on hybridizing the target nucleic acid sequence to a synthetic oligonucleotide (probes or primers) that is complementary to the target sequence. Designing primers and probes for this method is a preliminary and critical step. However, new bioinformatics tools are needed to automate, specific and improve the design sets to be used in the nucleic acid‒base method. Thus, we developed foodborne pathogen primer probe design (FBPP), an open-source, user-friendly graphical interface Python-based application supported by the SQL database for foodborne pathogen virulence factors, for (i) designing primers/probes for detection purposes, (ii) PCR and gel electrophoresis photo simulation, and (iii) checking the specificity of primers/probes.
Iron deficiency anaemia (IDA) is a major health issues and common type of nutritional deficiency worldwide. For IDA treatment, intravenous (IV) iron is a useful therapy. To determine the efficacy and ...cost-effectiveness (CE) of intravenous (IV) Ferric Carboxymaltose (FCM) versus IV Iron Sucrose (IS) in treating IDA. Electronic medical record i.e. Cerner.sup.® system. IV Ferric Carboxymaltose versus IV Iron Sucrose. With regard to responses to treatment i.e., efficacy of treatment with FCM & IS in IDA patients, hemoglobin (Hgb), ferritin, and transferrin saturation (TSAT) levels were the primary outcomes. Additionally, the researchers also collected levels of iron, platelet, white blood cell (WBC), red blood cell (RBC), mean corpuscular hemoglobin (MCH), and mean corpuscular volume (MCV). The costs i.e. resources consumed (obtained from NCCCR-HMC) and the CE of FCM versus IS were the secondary outcomes. There was a significant improvement in Hgb, RBC and MCH levels in the IS group than the FCM group. The overall cost of IS therapy was significantly higher than FCM. The medication cost for FCM was approximately 6.5 times higher than IS, nonetheless, it is cheaper in terms of bed cost and nursing cost. The cost effectiveness (CE) ratio illustrated that FCM and IS were significantly different in terms of Hgb, ferritin and MCH levels. Further, Incremental Cost Effectiveness Ratio (ICER) indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes. Not applicable. The higher cost of FCM versus IS can be offset by savings in healthcare personnel time and bed space. ICER indicated that further justifications and decisions need to be made for FCM when using Hgb, iron, TSAT, MCH and MCV levels as surrogate outcomes.
The interaction between the tumor suppressor protein p53 and its negative regulator, the MDM2 oncogenic protein, has gained significant attention in cancer drug discovery. In this study, 120 lignans ...reported from Ferula sinkiangensis and Justicia procumbens were assessed for docking simulations on the active pocket of the MDM2 crystal structure bound to Nutlin-3a. The docking analysis identified nine compounds with higher docking scores than the co-crystallized reference. Subsequent AMDET profiling revealed satisfactory pharmacokinetic and safety parameters for these natural products. Three compounds, namely, justin A, 6-hydroxy justicidin A, and 6′-hydroxy justicidin B, were selected for further investigation due to their strong binding affinities of −7.526 kcal/mol, −7.438 kcal/mol, and −7.240 kcal/mol, respectively, which surpassed the binding affinity of the reference inhibitor Nutlin-3a (−6.830 kcal/mol). To assess the stability and reliability of the binding of the candidate hits, a molecular dynamics simulation was performed over a duration of 100 ns. Remarkably, the thorough analysis demonstrated that all the hits exhibited stable molecular dynamics profiles. Based on their effective binding to MDM2, favorable pharmacokinetic properties, and molecular dynamics behavior, these compounds represent a promising starting point for further refinement. Nevertheless, it is essential to synthesize the suggested compounds and evaluate their activity through in vitro and in vivo experiments.
A series of novel compounds carrying pyrazino1,2-aindol-1(2H)-one scaffold (5a-g) and their reaction intermediates, indole-2-carboxamides, (3a-g) were synthesized and evaluated for their ability to ...inhibit reactive oxygen species (ROS) generation, antioxidant activity and anticancer activity against a panel of cancer cell lines using MTT assay. The results showed that these compounds can inhibit ROS generation during the metabolic phase of phagocytosis in a dose-dependent manner where compounds 5d and 5e were the most potent samples with higher inhibitory activities (IC50 values 3.3 and 1.4 μM, respectively) than that of the reference acetylsalicylic acid (IC50 = 9.7 μM). Results for the determination of potential antioxidant properties of the synthesized compounds showed that compounds 5d and 5e containing pyrazino1,2-aindol-1-one backbone were the most acive and even comparable to Trolox. Compounds 3d-f and 5d-f with the least IC50 values in MTT assay were tested against three known anticancer targets EGFR, BRAF and Tubulin. Histopathological and immunohistochemical study were performed to determine the consequence of exposure to chronic low dose of chlorpyrifos on the testis of male mice and results revealed that these effects can be ameliorated by co-treatment with the most active antioxidant compounds 5d and 5e. Finally, molecular docking studies were performed to explore the binding mode of the most active compounds against EGFR and BRAF kinases.
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•Two series of pyrazino1,2-aindol-1(2H)-one closed system and open indole derivatives have been synthesized.•The new compounds were evaluated for their anticancer and antioxidant activities.•The most active anticancer compounds were tested against EGFR, BRAF and Tubulin.•Histopathological and immunohistochemical studies of most potent derivatives were performed.•Docking study of the active compounds was done against EGFR and BRAF kinases.
Nano-ZnO and Co–ZnO supported algae (
Sargassum
species) were synthesized as a novel composite of promising photocatalytic activities in decolorization of malachite green dye under a visible light ...source. The composites were characterized by different analytical techniques, and the results confirmed the loading process and the formation of composites of low band gap energies for ZnO/algae composite (2.45 eV) and Co–ZnO/algae composite (2.32 eV). The composites were used as photocatalysts for the rapid degradation of malachite green dye (MG) within the visible light zone. The synthetic catalysts showed stunning photocatalytic activities reflected in the complete degradation of 5 mg/L of MG after 10 min using 0.06 g of ZnO/algae and 0.05 g of Co–ZnO/algae at pH 7. Also, the studied composites showed high efficiency in the degradation of higher MG concentration (10 mg/L and 15 mg/L). The photocatalytic performances were enhanced by 58% for ZnO/algae and about 75% for Co–ZnO/algae as compared to pure ZnO without support. Moreover, they have high reusability properties and are applied effectively in seven cycles of MG degradation reusing tests. The active species trapping tests reflected the dominance of the electron–hole pairs in the visible light degradation of MG by ZnO/algae. For Co–ZnO/algae composite, the degradation mechanism appears to be controlled by both the electron–hole pairs and hydroxyl radicals with a similar effect.
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