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This paper addresses the enhancement of multiple Unmanned Aerial Vehicle (UAV) swarm formation control in challenging terrains through the novel fractional memetic computing approach known as fractional-order velocity-pausing particle swarm optimization (FO-VPPSO). Existing particle swarm optimization (PSO) algorithms often suffer from premature convergence and an imbalanced exploration–exploitation trade-off, which limits their effectiveness in complex optimization problems such as UAV swarm control in rugged terrains. To overcome these limitations, FO-VPPSO introduces an adaptive fractional order β and a velocity pausing mechanism, which collectively enhance the algorithm's adaptability and robustness. This study leverages the advantages of a meta-heuristic computing approach; specifically, fractional-order velocity-pausing particle swarm optimization is utilized to optimize the flying path length, mitigate the mountain terrain costs, and prevent collisions within the UAV swarm. Leveraging fractional-order dynamics, the proposed hybrid algorithm exhibits accelerated convergence rates and improved solution optimality compared to traditional PSO methods. The methodology involves integrating terrain considerations and diverse UAV control parameters. Simulations under varying conditions, including complex terrains and dynamic threats, substantiate the effectiveness of the approach, resulting in superior fitness functions for multi-UAV swarms. To validate the performance and efficiency of the proposed optimizer, it was also applied to 13 benchmark functions, including uni- and multimodal functions in terms of the mean average fitness value over 100 independent trials, and furthermore, an improvement at percentages of 29.05% and 2.26% is also obtained against PSO and VPPSO in the case of the minimum flight length, as well as 16.46% and 1.60% in mountain terrain costs and 55.88% and 31.63% in collision avoidance. This study contributes valuable insights to the optimization challenges in UAV swarm-formation control, particularly in demanding terrains. The FO-VPPSO algorithm showcases potential advancements in swarm intelligence for real-world applications. [ABSTRACT FROM AUTHOR]

The proper coordination of directional overcurrent relays (DOCRs) is crucial in electrical power systems. The coordination of DOCRs in a multi-loop power system is expressed as an optimization problem. The aim of this study focuses on improving the protection system's performance by minimizing the total operating time of DOCRs via effective coordination with main and backup DOCRs while keeping the coordination constraints within allowable limits. The coordination problem of DOCRs is solved by developing a new application strategy called Fractional Order Derivative Moth Flame Optimizer (FODMFO). This approach involves incorporating the ideas of fractional calculus (FC) into the mathematical model of the conventional moth flame algorithm to improve the characteristics of the optimizer. The FODMFO approach is then tested on the coordination problem of DOCRs in standard power systems, specifically the IEEE 3, 8, and 15 bus systems as well as in 11 benchmark functions including uni- and multimodal functions. The results obtained from the proposed method, as well as its comparison with other recently developed algorithms, demonstrate that the combination of FOD and MFO improves the overall efficiency of the optimizer by utilizing the individual strengths of these tools and identifying the globally optimal solution and minimize the total operating time of DOCRs up to an optimal value. The reliability, strength, and dependability of FODMFO are supported by a thorough statistics study using the box-plot, histograms, empirical cumulative distribution function demonstrations, and the minimal fitness evolution seen in each distinct simulation. Based on these data, it is evident that FODMFO outperforms other modern nature-inspired and conventional algorithms. [ABSTRACT FROM AUTHOR]

This research utilizes the innovative fractional-order Archimedean spiral moth–flame optimization (FO-AMFO) technique to address the issues of the optimal reactive power dispatch (ORPD) problem. The formulated fitness function aims to minimize power losses and determine the ideal flow of reactive power for the IEEE 30- and 57-bus test systems. The extensive functions of the fractional evolutionary computing strategy are utilized to address the minimization problem of ORPD. This involves determining the control variables, such as VAR compensators, bus voltages, and the tap setting of the transformers. The effective incorporation of reactive compensation devices into traditional power grids has greatly reduced power losses; however, it has resulted in an increase in the complexity of optimization problems. A comparison of the findings indicates that swarming fractional intelligence using FO-AMFO surpassed the state-of-the-art competitors in terms of minimizing power losses. [ABSTRACT FROM AUTHOR]

Recently, the concept of the microgrid (MG) has been developed to assist the penetration of large numbers of distributed energy resources (DERs) into distribution networks. However, the integration of DERs in the form of MGs disturbs the operating codes of traditional distribution networks. Consequently, traditional protection strategies cannot be applied to MG against short-circuit faults. This paper presents a novel intelligent protection strategy (NIPS) for MGs based on empirical wavelet transform (EWT) and long short-term memory (LSTM) networks. In the proposed NIPS, firstly, the three-phase current signals measured by protective relays are decomposed into empirical modes (EMs). Then, various statistical features are extracted from the obtained EMs. Afterwards, the extracted features along with the three-phase current measurement are input to three different LSTM network to obtain exact fault type, phase, and location information. Finally, a trip signal based on the obtained fault information is generated to disconnect the faulty portion from the rest of the MG. The significant feature of the proposed NIPS is that it does not need adaptive relaying and communication networks. Moreover, it is independent of the operating scenario and hence fault current magnitude. To evaluate the efficacy of the proposed NIPS, exhaustive simulations are performed on an international electro-technical commission (IEC) MG. The simulation results confirm the efficiency of the proposed NIPs in terms of accuracy, dependability, and security. Moreover, comparisons with existing intelligent protection schemes validate that the proposed NIPS is highly accurate, secure, and dependable. [ABSTRACT FROM AUTHOR]

The optimal allocation of protective devices is a serious issue in an electrical power system; in order to reduce the possibility of faults, the protection devices should be optimally placed. The paper presents a continuous genetic algorithm (CGA) for the optimal allocation of directional relays for the efficient energy minimization in a radial distribution system (DG). The algorithm is flexible to use for the changes and improvements in the optimal location for a DG unit and can optimize the energy consumption in the radial distribution system. The proposed algorithm has been implemented on IEEE 33 and 69-bus system using MATLAB (R2014b, MathWorks). Low energy consumption is a common design objective in an energy-constrained distribution system. Engineers, power utilities, and network operators can profit from the proposed methodology to enhance the use of DG in distribution networks. [ABSTRACT FROM AUTHOR]

Electrophoretic deposition (EPD) is a powerful technique to assemble metals, polymer, ceramics, and composite materials into 2D, 3D, and intricately shaped implants. Polymers, proteins, and peptides can be deposited via EPD at room temperature without affecting their chemical structures. Furthermore, EPD is being used to deposit multifunctional coatings (i.e., bioactive, antibacterial, and biocompatible coatings). Recently, EPD was used to architect multi-structured coatings to improve mechanical and biological properties along with the controlled release of drugs/metallic ions. The key characteristics of EPD coatings in terms of inorganic bioactivity and their angiogenic potential coupled with antibacterial properties are the key elements enabling advanced applications of EPD in orthopedic applications. In the emerging field of EPD coatings for hard tissue and soft tissue engineering, an overview of such applications will be presented. The progress in the development of EPD-based polymeric or composite coatings, including their application in orthopedic and targeted drug delivery approaches, will be discussed, with a focus on the effect of different biologically active ions/drugs released from EPD deposits. The literature under discussion involves EPD coatings consisting of chitosan (Chi), zein, polyetheretherketone (PEEK), and their composites. Moreover, in vitro and in vivo investigations of EPD coatings will be discussed in relation to the current main challenge of orthopedic implants, namely that the biomaterial must provide good bone-binding ability and mechanical compatibility. [ABSTRACT FROM AUTHOR]

Background: Suicide is a serious public health concern all over the world including Bangladesh. About 9% of the patients admitted with suicidal ideation (SI) or suicide attempt (SA) later complete suicide. To understand and prevent suicide, the study of SI and SA is necessary but research in this area is scanty in Bangladesh. Therefore, we studied suicidality (SI and SA) among married adults in Rajshahi City, Bangladesh. Methods: This was a household cross-sectional study. A total of 708 married adults were selected for this study using a multi-stage random sampling. Suicidality was measured based on two factors: (i) suicidal ideation, and (ii) suicide attempt. Frequency distribution, Chi-square test and multiple binary logistic regression model were used in this study according to our objectives. Results: The prevalence of suicidal ideation, suicide attempt, and suicidality was 5.8%, 3.4%, and 8.3% respectively among married adults. A multiple binary logistic regression model provided the following risk factors of suicidality: (i) joint family (AOR = 0.310, p<0.01), (ii) ≥26 years of age at the first marriage (AOR = 0.379, p<0.05), (iii) twice or more marriage (AOR = 0.214, p<0.01), (iv) conjugal life of ≥16 years (AOR = 0.410, p<0.05), (v) having no child (AOR = 6.343, p<0.01) and (vi) having 1–2 children (AOR = 6.190, p<0.01), (vii) medical comorbidity (AOR = 0.421, p<0.01), (viii) mental comorbidity (AOR = 0.253, p<0.01), (ix) stress-anxiety (AOR = 0.311, p<0.01), (x) family history of mental disorders (AOR = 0.059, p<0.01), (xi) family history of suicide/suicide attempt (AOR = 0.009, p<0.01), (xii) substance abuse (AOR = 0.065, p<0.01), (xiii) poor relationship with spouse (AOR = 0.209, p<0.01), and (xiv) poor relationship with other family members (AOR = 0.347, p<0.05). Conclusion: The prevalence of suicidality is remarkable in Rajshahi city, Bangladesh. The government and non-government agencies can use the findings of this study to identify the vulnerable groups and undertake measures for preventing and reducing suicidality. [ABSTRACT FROM AUTHOR]

Microalgae are a sustainable raw material for biodiesel production that earned a lot of consideration. Biodiesel from the conventional transesterification (liquid acid based) process of microalgae oil needs pre-treatment before its use as fuel. Moreover, the oil extraction process is energy extensive. In this study, room temperature assisted in situ transesterification method is reported using a solid acid catalyst obtained from sulfonated rice husk (RHS). The RHS catalyst was synthesized by microwave acid treatment of rice husk. The surface characterization of RHS by XRD, FT-IR, Raman, and XPS confirms the presence of −SO3H, while the pore anatomy and pore structure analysis by FE-SEM and BET substantiate the presence of porous structure and high surface area. Furthermore, the RHS catalyst was successfully employed for the in situ transesterification of the microalgae (Parachlorella kessleri) biomass. Various experimental conditions influencing the in situ transesterification were evaluated. The optimization of catalyst dose revealed that 30 mg RHS produce highest FAME yield after 30-min reaction time at room temperature (25 °C). Performance of the catalyst was compared with rice husk-derived fluorocarbon (RHFC) and conventional acid catalyst (H2SO4). Moreover, in the proposed approach, there is no need for oil extraction step and pre-treatment of biodiesel after the reaction. RHS is very effective at room temperature compared with conventional transesterification. [ABSTRACT FROM AUTHOR]

Development of hard materials for structural and bearing applications is a challenging task due to complexities in materials processing. Nickel-based intermetallics are a choice for the wear resistance applications. In this study, in order to examine the effects of Ni and Cr addition on the wear performance of Ni-rich alloys, 60Ni, 55Ni-5Cr, 50Ni-5Cr, and 50Ni-10Cr (at.%) alloys were developed through arc melting technique. The aim was to conduct a microstructural and phase analysis study and their effects on hardness and wear behavior. Samples were solution treated at 900 °C for 5 h under vacuum followed by equilibrium cooling. Microstructural and phase analysis revealed the presence of B2 cubic NiTi austenite along with Ni-rich hexagonal Ni3Ti and Cr-rich tetragonal Cr3Ni2 phases throughout the microstructure of alloys. The Cr developed phase was not present in binary composition because of Cr absence. Ternary compositions possessed higher hardness and wear resistance than the binary alloy. Hardness and wear resistance of 50Ni-5Cr and 50Ni-10Cr were comparable with tool steels and conventional 440C martensitic stainless steel bearing material; this high hardness and wear resistance was attributed to the strong solid solution strengthening and precipitation hardening effects of Cr along with the combined effect of Ni-rich Ni3Ti and NiTi austenite phases. Improvement in hardness and wear resistance were correlated with the Cr addition in the developed alloys. [ABSTRACT FROM AUTHOR]

Highlights • This paper proposes two controlling methods for SVC in smart grid with connected EV charger. • SMC, ASRFC with a HVC are separately applied in the grid. • This paper presents usage of proposed methods for decreasing size of capacitor and value of apparent power loss. • The proposed scheme is validated through computer simulations of a 22.9-kV grid. Abstract Electric Vehicles (EVs) play a pivotal role in reducing the emissions of greenhouse gases in the world. Currently demand for EVs has abruptly increased for transportation and other applications. Using more EVs causes an increasing load on the power system. Random EV charging yields voltage distortion, which results in an unbalanced grid. In a distributed system, the connection of EVs to the grid may diminish the power factor, which increases the apparent power loss. The Static VAR Compensator (SVC), which is a FACTS device, is applied to the power system to compensate the voltage distortions and apparent power loss. In this paper, two controlling methods are contemplated and tested in a SVC to reduce the apparent power loss and minimize the capacitor size of the SVC in comparison with the conventional control method in a SVC. Proposed methods are also compared with the conventional control method used for SVC. The Slide Mode Controller (SMC) and Asymmetric Synchronous Reference Frame Controller (ASRFC) with a Harmonic Voltage Compensator (HVC) are separately applied in the grid. This paper presents usage of SMC and ASRFC methods for decreasing size of capacitor and value of apparent power loss through computer simulations of a 22.9-kV grid. With application of new controllers, apparent power loss of grid will be reduced as compared with conventional method of SVC controller. Moreover, the size of SVC capacitor can also be reduced. [ABSTRACT FROM AUTHOR]

Urease is known to be one of the major causes of diseases induced by Helicobacter pylori , thus allow them to survive at low pH inside the stomach and thereby, play an important role in the pathogenesis of gastric and peptic ulcer, apart from cancer as well. Keeping in view the great importance of urease inhibitors, here in this study we have synthesized piperazine derivatives ( 1 – 15 ) and evaluated for their urease inhibitory activity. All analogs showed excellent inhibitory potential with IC 50 values ranging between 1.1 ± 0.01 and 33.40 ± 1.50 µM when compared with the standard inhibitor thiourea (IC 50  = 21.30 ± 1.10 µM). Structure activity relationship has been established for all compounds which are mainly based upon the substitution on phenyl ring. Molecular docking study was performed in order to understand the binding interaction of the compounds in the active site of enzyme. [ABSTRACT FROM AUTHOR]

In the recent decades, the interest on glycosidases has dramatically increased, mainly because these enzymes play a vital role in many biological processes. Based on the biological potential associated to these enzymes, several glycosidase inhibitors have been developed. In this review, the most important inhibitors targeting these enzymes, including the disaccharides, iminosugars, monocyclic iminosugars, bicyclic iminosugars, thiosugars and carbasugars will be discussed and special attention will be given to the ones that are currently used clinically. This review summarizes and characterizes the current knowledge regarding the classes of glycosidase inhibitors that have therapeutic potential in a wide range of diseases. It highlights the patents, relevant research and patent applications filed in the past years in the field. Since the glycosidase inhibitors are involved in several chronic diseases and possibly pandemic, the pharmaceutical research towards developing new generations of these molecules is very important to public health. Most of the glycosidase inhibitors mimics the structures of monosaccharides or oligosaccharides and are well accepted by the organisms since they benefit from privileged drug-like properties. Disaccharides, iminosugars, carbasugars and thiosugars derivatives are the most popular inhibitors among the glycosidase inhibitors. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (pneumococcus) is a Gram-positive bacterium. Humans are the major target for the pneumococcus. The pneumococcus is a common etiological agent of many different diseases such as bacterial meningitis, pneumonia, otitis media (OM), sinusitis, and conjunctivitis. According to the WHO, the pneumococcus is responsible for causing 1 million deaths each year. In 2000, over 14 million children worldwide under the age of 5 years were diagnosed with a pneumococcal disease, with the highest incidence seen in Africa. The human population most susceptible to pneumococcal infections is that of children due to their immature immune system. A sensational increase in antibiotic resistance among S. pneumoniae has been witnessed in different parts of the world since 1980s. The increase of resistance of S. pneumoniae to antibiotics is of major concern throughout the world. Worldwide, there are concerns about rising levels of antibiotic resistance and fears that the efficacy of antimicrobial therapy may be compromised, resulting in treatment failure and reduced utility of older antibiotics, a comparatively novel method has been used to defeat the resistant pathogens since last decade. The computational subtractive genomics approach is one of them, in which the bacterial pathogen complete proteins is gradually rock-bottom to a small number of likely drug targets. In this approach the steps which are used to find human non-homologs targets, proteins that are essential to the disease causing agent and participation of the selected proteins in pathogen metabolic pathways which are necessary for the survival of bacteria. We used computational subtractive genomics on consummate proteins of the of S . pneumonia strain JJA in this study and concluded with 2 proteins that can be used as potent drug targets against which new dynamic molecules can be planned to make better the action to treat the disease which is related with pathogen. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) has emerged as a rapidly spreading epidemic throughout the tropical and subtropical regions around the globe. No suitable drug has been designed yet to fight against DENV, therefore, the need for safe and effective antiviral drug has become imperative. The envelope protein of DENV is responsible for mediating the fusion process between viral and host membranes. This work reports an in silico approach to target B and T cell epitopes for dengue envelope protein inhibition. A conserved region “QHGTI” in B and T cell epitopes of dengue envelope glycoprotein was confirmed to be valid for targeting by visualizing its interactions with the host cell membrane TIM-1 protein which acts as a receptor for serotype 2 and 3. A reverse pharmacophore mapping approach was used to generate a seven featured pharmacophore model on the basis of predicted epitope. This pharmacophore model as a 3D query was used to virtually screen a chemical compounds dataset “Chembridge”. A total of 1010 compounds mapped on the developed pharmacophore model. These retrieved hits were subjected to filtering via Lipinski’s rule of five, as a result 442 molecules were shortlisted for further assessment using molecular docking. Finally, 14 hits of different structural properties having interactions with the active site residues of dengue envelope glycoprotein were selected as lead candidates. These structurally diverse lead candidates have strong likelihood to act as further starting structures in the development of novel and potential drugs for the treatment of dengue fever. [ABSTRACT FROM AUTHOR]

Context:Malaria remains one of the prevalent infectious diseases worldwide.Plasmodium falciparum1-deoxy-d-xylulose-5-phosphate reductoisomerase (PfDXR) plays a role in isoprenoid biosynthesis in the malaria parasite, making this parasite enzyme an attractive target for antimalarial drug design. Fosmidomycin is a promising DXR inhibitor, which showed safety as well as efficacy againstPlasmodium falciparummalaria in clinical trials. However, due to its poor oral bioavailability and non-drug-like properties, the focus of medicinal chemists is to develop inhibitors with improved pharmacological properties. Objective:This study described the computational design of new and potent inhibitors for deoxyxylulose 5-phosphate reductoisomerase and the prediction of their pharmacokinetic and pharmacodynamic properties. Material and methods:A complex-based pharmacophore model was generated from the complex X-ray crystallographic structure ofPfDXRusing MOE (Molecular Operating Environment). Furthermore, MOE-Dock was used as docking software to predict the binding modes of hits and target enzyme. Results:Finally, 14 compounds were selected as new and potent inhibitors ofPfDXRon the basis of pharmacophore mapping, docking score, binding energy and binding interactions with the active site residues of the target protein. The predicted pharmacokinetic properties showed improved permeability by efficiently crossing blood–brain barrier. While,in silicopromiscuity binding data revealed that these hits also have the ability to bind with otherP. falciparumdrug targets. Discussion and conclusion:In conclusion, innovative scaffolds with novel modes of action, improved efficacy and acceptable physiochemical/pharmacokinetic properties were computationally identified. [ABSTRACT FROM AUTHOR]

The PIM kinases are a family of serine/threonine kinases that catalyze the ATP dependent phosphorylation. These kinases were identified to be overexpressed in a variety of malignancies and tumors and hence can be taken a therapeutic drug target. Pharmacophore-based virtual screening, were employed to identify lead compounds for PIM kinases. A seven featured pharmacophore model was developed on the basis of tricyclic benzothienopyrimidinone, a triple inhibitor of PIM kinases. The validated pharmacophore model was used to screen ZINC database. As a result, 1028 compounds were mapped on the pharmacophore model. These initial hits, were subjected to filtering via Lipinski's rule of five to predict drug like molecules. 1028 drug like hits were selected for evaluation using docking simulation. Finally, 22 hits having different structural properties and binding modes with all the three PIM kinases were selected as lead candidates for triple inhibitors. These candidates having different scaffolds have a strong likelihood to act as further starting points in the development of new and potential PIM kinases inhibitors. [ABSTRACT FROM AUTHOR]

Shape memory alloys remember their shape due to thermoelastic martensitic phase transformation. These alloys have advantages in terms of large recoverable strain and these alloys can exert continuous force during use. Equiatomic NiTi, also known as nitinol, has a great potential for use as a biomaterial as compared to other conventional materials due to its shape memory and superelastic properties. In this paper, an overview of recent research and development related to NiTi based shape memory alloys is presented. Applications and uses of NiTi based shape memory alloys as biomaterials are discussed. Biocompatibility issues of nitinol and researchers’ approach to overcome this problem are also briefly discussed. [ABSTRACT FROM AUTHOR]

The hybridization of PSO for the Optimal Coordination of Directional Overcurrent Protection Relays (DOPR) of the IEEE bus system proposes a new method for coordinating directional overcurrent protection relays in power systems. The method combines the hybrid particle swarm optimization (HPSO) algorithm and a heuristic PSO algorithm to find the minimum total operating time of the directional overcurrent protection relays with speed and accuracy. The proposed method is tested on the IEEE 4-bus, 6-bus, and 8-bus systems, and the results are compared with those obtained using traditional coordination methods. The collected findings suggest that the proposed method may produce better coordination and faster operation of DOPRs than the previous methods, with an increase of up to 74.9% above the traditional technique. The hybridization of the PSO algorithm and heuristic PSO algorithm offers a promising approach to optimize power system protection. [ABSTRACT FROM AUTHOR]

Context: The three Pim serine/threonine kinases (Pim-1, Pim-2, and Pim-3) belong to a small family of kinases that regulate numerous signaling pathways fundamental to the development of tumors. Pim kinases' overexpression has been reported in numerous solid and hematological tumors and, in particular, prostate cancer (Pim-1). Objectives: This study investigated the binding modes of benzofuran-2-carboxlic acids against Pim-1 kinase, hence providing useful information for the active inhibition of it. Materials and methods: In present study, molecular docking approach via MOE-Dock program was applied to predict the binding interactions of some known Pim-1 kinase inhibitors. First validation of the docking protocol was carried out by calculating RMSD for the co-crystallized and docked ligands. Using the same protocol, all the compounds were docked into the active site of Pim-1 kinase. Results: All the compounds showed significant interactions and good correlation with the experimental data. The results illustrate that compounds with optimum basicity and relevant distance between the acidic and basic groups showed optimum interactions with the active site residues of Pim-1 kinase. Conclusion: We hope that this study will be helpful in designing new, structurally diverse and more potent compounds for the active treatment of prostate cancer and other related diseases caused by deregulation of Pim-1 kinase. [ABSTRACT FROM AUTHOR]

Abstract: Equiatomic TiPt exhibits very high transformation temperatures (~1300K) from B2 to B19 orthorhombic martensitic phase. However TiPt exhibits negligible (~0–11%) shape memory effect and low strength (~450MPa) in martensite and very low strength (~20MPa) in B2 phase region. Then in this study, we compared the high temperature strength and shape memory properties of Ti–50Pt by partial substitution of Platinum (Pt) belonging to group 10 of periodic table with Cobalt (Co) belonging to group 9 and Ruthenium (Ru) belonging to group 8 of periodic table respectively. Partial substitution of Pt with Co and Ru was found effective in improving the high temperature strength and shape memory properties of Ti–50Pt alloy. However partial substitution of Pt with Ru was found more effective than Co due to more effective solid solution strengthening effect. Ti–45Pt–5Co and Ti–45Pt–5Ru alloys have potential for high temperature shape memory materials applications. [Copyright &y& Elsevier]

Hepatitis C virus (HCV) infection is an alarming and growing threat to public health. The present treatment gives limited efficacy and is poorly tolerated, recommending the urgent medical demand for novel therapeutics. NS3/4A protease is a significant emerging target for the treatment of HCV infection. This work reports the complex-based pharmacophore modeling to find out the important pharmacophoric features essential for the inhibition of both protease and helicase activity of NS3/4A protein of HCV. A seven featured pharmacophore model of HCV NS3/4A protease was developed from the crystal structure of NS3/4A protease in complex with a macrocyclic inhibitor interacting with both protease and helicase sites residues via MOE pharmacophore constructing tool. It consists of four hydrogen bond acceptors (Acc), one hydrophobic (Hyd), one for lone pair or active hydrogen (Atom L) and a heavy atom feature (Atom Q). The generated pharmacophore model was validated by a test database of seventy known inhibitors containing 55 active and 15 inactive/least active compounds. The validated pharmacophore model was used to virtually screen the ChemBridge database. As a result of screening 1009 hits were retrieved and were subjected to filtering by Lipinski’s rule of five on the basis of which 786 hits were selected for further assessment using molecular docking studies. Finally, 15 hits of different scaffolds having interactions with important active site residues were predicted as lead candidates. These candidates having unique scaffolds have a strong likelihood to act as further starting points in the development of novel and potent NS3/4A protease inhibitors. [ABSTRACT FROM AUTHOR]

Abstract: Plasmodium falciparum causes the most fatal form of malaria and accounts for over 1 million deaths annually, yet currently used drug therapies are compromised by resistance. The malaria parasite cannot salvage pyrimidines and relies on de novo biosynthesis for survival. The enzyme dihydrooratate dehydrogenase (DHODH), a mitochondrial flavoenzyme, catalyzes the rate-limiting step of this pathway and is therefore an attractive anti-malarial chemotherapeutic target. In an effort to design new and potential anti-malarials, structure-based pharmacophore mapping, molecular docking, binding energy calculations and binding affinity predictions were employed in a virtual screening strategy to design new and potent P. falciparum dihydrooratate dehydrogenase (PfDHODH) inhibitors. A structure-based pharmacophore model was generated which consist of important interactions as observed in co-crystal of PfDHODH enzyme. The developed model was used to retrieve molecules from ChemBridge database, a freely available commercial database. A total of 87 molecules mapped on the modeled pharmacophore from the database. The retrieved hits were further screened by docking simulation, binding energy calculations and biding affinity predictions using genetic optimization for ligand docking (GOLD) and MOE. Based on these results, finally 26 chemo-types molecules were predicted as new, potential and structurally diverse PfDHODH inhibitors. [Copyright &y& Elsevier]

Membrane fusion is the central molecular event during the entry of enveloped viruses into cells. The critical agents of this process are viral surface proteins, primed to facilitate cell bilayer fusion. The important role of Dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN) in Dengue virus transmission makes it an attractive target to interfere with Dengue virus Propagation. Receptor mediated endocytosis allows the entry of virions due to the presence of endosomal membranes and low pH-induced fusion of the virus. DC-SIGN is the best characterized molecule among the candidate protein receptors and is able to mediate infection with the four serotypes of dengue virus (DENV). Unrestrained pair wise docking was used for the interaction of dengue envelope protein with DC-SIGN and monoclonal antibody 2G12. Pre-processed the PDB coordinates of dengue envelope glycoprotein and other candidate proteins were prepared and energy minimized through AMBER99 force field distributed in MOE software. Protein-protein interaction server, ZDOCK was used to find molecular interaction among the candidate proteins. Based on these interactions it was found that antibody successfully blocks the glycosylation site ASN 67 and other conserved residues present at DC-SIGN-Den-E complex interface. In order to know for certain, the exact location of the antibody in the envelope protein, co-crystallize of the envelope protein with these compounds is needed so that their exact docking locations can be identified with respect to our results. [ABSTRACT FROM AUTHOR]

Phased array ultrasonic testing (PAUT) has widely emerged as an innovative and improved method of assessing critical flaws in safety critical equipments of industrial plants. The technology gives a clear advantage over a conventional ultrasonic testing (UT). The utilization of advanced form of UT however has associated disadvantages and pitfalls. An attempt has been made to address some of the challenges that are associated to PAUT techniques in characterization of defects in 27 mm Al 6061-O curvilinear welds made from friction stir welding process (FSW). Three distinct defect parameters, i.e., (a) defect length, (b) defect height, and (c) defect position was estimated using PAUT. Quality of results are significantly dependent on important factors. These factors affect the probability of detection (POD). X-ray radiography was carried as a complimentary technique for defect identification. Defect sizing results of PAUT has been assessed and compared against macro-examination results. While PAUT has a proven record of exhibiting better POD, incorrect selection of parameters like probe selection, operator competency, scanning method and defect orientation can result in inconsistent results. [ABSTRACT FROM AUTHOR]

This article has employed a computational method to evaluate the dynamic response of Carbon fiber reinforced polymers composite material. Three Dimensional, Computational Shell and Two Dimensional modelling of a protective system has been conducted by the authors using Finite Element Method. In order to simulate the influence of space debris impacts on carbon epoxy composites, velocity variation in high and hyper speed range has been conducted. Rigid elements were utilized to model the projectile, while three dimensional stress elements, Continuum Shell elements and Plane stress elements were used for three dimensional, Continuum Shell and two dimensional modelling of the plate. The computational results indicated a good convergence with the available experimental results with variation less than 10%. It was observed that the generated stresses, energy absorbed, damaged area as well as the computation time of the models increased with the subsequent increase in impacting velocity. An increase of 75% in the energy absorbed, 86% increase in the generated stress and 93% increase in the deformation was observed against an increase in the impact velocity from 150 m/s to 1674 m/s. A maximum increase of 12% in the overall damage area, 41% increase in delamination of plies and 95% enhanced computation time was also observed against the above mentioned velocity variation. • Finite Element Analysis (FEA). • Dynamic characterization of composites. • Crash Analysis of Composite based Space structures. • Experimental and Numerical validation. • Computer Aided Engineering (CAE) using Three Dimensional (3D), Continuum Shell (CS) and Two dimensional (2D) elements [ABSTRACT FROM AUTHOR]

In addition to catalytic action, snake venom phospholipase A2 induces several pharmacological effects including neurotoxicity, cardiotoxicity as well as anti-coagulant and anti-platelet aggregation effects. Therefore, strategy to identify dual inhibitor for this enzyme will be of much importance in medical research. In this paper, structure-based pharmacophore mapping, molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions were employed in a virtual screening strategy to identify new hits for dual inhibition of anti-coagulation and inflammation of phospholipase A2. A structure-based pharmacophore map was modeled which comprised of important interactions as observed in co-crystal of phospholipase A2 and its dual inhibitor indomethacin. The generated model was used to retrieve molecules from ChemBridge, a free database of commercially available compounds. A total of 381 molecules mapped on the developed pharmacophore model from ChemBridge database. The hits retrieved were further screened by molecular docking, protein-ligand interaction fingerprints, binding energy calculations, and binding affinity predictions using Genetic Optimization for Ligand Docking and moe. Based on these results, 32 chemo-types molecules were predicted as potential lead scaffolds for developing novel, potent and structurally diverse dual inhibitor of phospholipase A2. [ABSTRACT FROM AUTHOR]

Abstract: A pharmacophore model was developed based on three structurally diverse urease inhibitors by using the GASP program. This model comprises the positions and tolerance for two acceptor atoms (AA1 and AA2), one donor atom (DA1), and one hydrophobic center (HYP1). This derived phamacophore model was employed to screen an in-house database of organic compounds. Hits obtained were evaluated by molecular docking using GOLD software. On the basis of ligand- and structural-based predictions, an in vitro testing of short-listed compounds was conducted and a novel class of urease inhibitors (2-aminothiophines) was identified. The potent in vitro activity and selectivity of these compounds, along with their non-toxic nature against the plant cells indicated that they can serve as leads for solving urease-associated health and agriculture problems. [Copyright &y& Elsevier]

Urease (EC 3.5.1.5) serves as a virulence factor in pathogens that are responsible for the development of many diseases in humans and animals. Urease allows soil microorganisms to use urea as a source of nitrogen and aid in the rapid break down of urea-based fertilizers resulting in phytopathicity. It has been well established that hydroxamic acids are the potent inhibitors of urease activity. The 3D-QSAR studies on thirty five hydroxamic acid derivatives as known urease inhibitors were performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods to determine the factors required for the activity of these compounds. The CoMFA model produced statistically significant results with cross-validated (q 2) 0.532 and conventional (r 2) correlation coefficients 0.969.The model indicated that the steric field (70.0%) has greater influence on hydroxamic acid inhibitors than the electrostatic field (30.0%). Furthermore, five different fields: steric, electrostatic, hydrophobic, H-bond donor and H-bond acceptor assumed to generate the CoMSIA model, which gave q 2 0.665 and r 2 0.976.This model showed that steric (43.0%), electrostatic (26.4%) and hydrophobic (20.3%) properties played a major role in urease inhibition. The analysis of CoMFA and CoMSIA contour maps provided insight into the possible modification of the hydroxamic acid derivatives for improved activity. [ABSTRACT FROM AUTHOR]

In continuation of our previous study on the urease inhibition by a number of chalcones, 2,3-dihydro-1,5-benzothiazepines and 2,3,4,5-tetrahydro-1,5-benzothiazepines, FlexX docking has been exploited to get a deeper insight into the mechanism of their inhibitory action. A comparison of the IC50 values of the active compounds reveals that, of the three classes of compounds studied, 2,3-dihydro-1,5-benzothiazepines were the most potent urease inhibitors. An in silico examination of these compounds showed that the activity is related to the interaction of ligand with the nickel metallocentre, its interaction with two amino acid residues, Asp224 and Cys322, in addition to the orientation of rings A and B in the catalytic core of the enzyme. The most active compound 2,3-dihydro-1,5-benzothiazepine (4) anchor tightly through a network of interactions with Ni701 and Ni702. This includes a number of hydrogen bonds and hydrophobic contacts with the amino acid residues in its vicinity. For their reduced analogs, the difference in the activity of different diastereomers has been observed to be configuration-dependent. This may be ascribed mainly to the difference in the orientation of ring B of the two stereoisomers and the extent of their interaction with Asp224 and Cys322 present in the catalytic core of the enzyme. [ABSTRACT FROM AUTHOR]

The relay coordination problem is of dire importance as it is critical to isolate the faulty portion in a timely way and thus ensure electrical network security and reliability. Meanwhile a relay protection optimization problem is highly constraint and complicated problem to be addressed. To fulfill this purpose, Harris Hawk Optimization (HHO) is adapted to solve the optimization problem for Directional Over-current Relays (DOCRs) and numerical relays. As it is inspired by the intelligent and collegial chasing and preying behavior of hawks for capturing the prey, it shows quite an impressive result for finding the global optimum values. Two decision variables; Time Dial Settings (TDS) and Plug Settings (PS) are chosen as the decision variables for minimization of overall operating time of relays. The proposed algorithm is implemented on three IEEE test systems. In comparison to other state-of-the-art nature inspired and traditional algorithms, the results demonstrate the superiority of HHO. [ABSTRACT FROM AUTHOR]

Protein design is central to nearly all protein engineering problems, as it can enable the creation of proteins with new biological functions, such as improving the catalytic efficiency of enzymes. One key facet of protein design, fixed-backbone protein sequence design, seeks to design new sequences that will conform to a prescribed protein backbone structure. Nonetheless, existing sequence design methods present limitations, such as low sequence diversity and shortcomings in experimental validation of the designed functional proteins. These inadequacies obstruct the goal of functional protein design. To improve these limitations, we initially developed the Graphormer-based Protein Design (GPD) model. This model utilizes the Transformer on a graph-based representation of three-dimensional protein structures and incorporates Gaussian noise and a sequence random masks to node features, thereby enhancing sequence recovery and diversity. The performance of the GPD model was significantly better than that of the state-of-the-art ProteinMPNN model on multiple independent tests, especially for sequence diversity. We employed GPD to design CalB hydrolase and generated nine artificially designed CalB proteins. The results show a 1.7-fold increase in catalytic activity compared to that of the wild-type CalB and strong substrate selectivity on p -nitrophenyl acetate with different carbon chain lengths (C2–C16). Thus, the GPD method could be used for the de novo design of industrial enzymes and protein drugs. The code was released at https://github.com/decodermu/GPD. [ABSTRACT FROM AUTHOR]

The use of a directional overcurrent protection relay (DOPR) to protect an electrical power system is a crucial instrument for keeping the system dynamic and avoiding undue interruption. The coordination of a DOPR's primary and backup relays is modelled as a highly constrained optimization problem. The goal is to determine an ideal value that will reduce the overall working time of all primary relays. The coordination is accomplished by the use of particle swarm optimization hybridization (HPSO). Comprehensive simulation experiments are carried out to evaluate the efficacy of the proposed HPSO by employing the time multiplier setting (TMS) and plug setting (PS) as an optimization variable and constant, respectively. The HPSO has been examined satisfactorily utilizing certain IEEE benchmark test systems (9-bus and 14-bus). The outcomes are contrasted with earlier heuristics and evolutionary approaches. Based on the acquired findings, it is clear that the obtained results exceed the other conventional and state of the art procedures in terms of total DOPR operation and the computing time necessary to achieve the global optimal solution. [ABSTRACT FROM AUTHOR]

Lung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12–14% of non-small cell lung cancers are caused by mutations in KRASG12C. The KRASG12C is one of the most prevalent mutants in lung cancer patients. KRAS was first considered undruggable. The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development is a challenging, expensive, and time-consuming process. Recently, machine-learning-based virtual screening are used for the development of new drugs. In this study, we performed machine-learning-based virtual screening followed by molecular docking, all atoms molecular dynamics simulation, and binding energy calculations for the identifications of new inhibitors against the KRASG12C mutant. In this study, four machine learning models including, random forest, k-nearest neighbors, Gaussian naïve Bayes, and support vector machine were used. By using an external dataset and 5-fold cross-validation, the developed models were validated. Among all the models the performance of the random forest (RF) model was best on the train/test dataset and external dataset. The random forest model was further used for the virtual screening of the ZINC15 database, in-house database, Pakistani phytochemicals, and South African Natural Products database. A total of 100 ns MD simulation was performed for the four best docking score complexes as well as the standard compound in complex with KRASG12C. Furthermore, the top four hits revealed greater stability and greater binding affinities for KRASG12C compared to the standard drug. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at (https://github.com/Amar-Ajmal/Datasets-for-KRAS). [ABSTRACT FROM AUTHOR]

In power systems protection, the optimal coordination of directional overcurrent relays (DOCRs) is of paramount importance. The coordination of DOCRs in a multi-loop power system is formulated as an optimization problem. The main objective of this paper is to develop the whale optimization algorithm (WOA) for the optimal coordination of DOCRs and minimize the sum of the operating times of all primary relays. The WOA is inspired by the bubble-net hunting strategy of humpback whales which leads toward global minima. The proposed algorithm has been applied to six IEEE test systems including the IEEE three-bus, eight-bus, nine-bus, 14-bus, 15-bus, and 30-bus test systems. Furthermore, the results obtained using the proposed WOA are compared with those obtained by other up-to-date algorithms. The obtained results show the effectiveness of the proposed WOA to minimize the relay operating time for the optimal coordination of DOCRs. [ABSTRACT FROM AUTHOR]

This descriptive study aimed to investigate causes and impact of part-time employment on the academic performance of students at secondary level. It was conducted in 105 High and Higher Secondary schools of district Peshawar. The part-time employed 378 students were taken from schools as sample. Questionnaire was designed to get the opinions of the students. The collected data was analyzed by using percentages. The analysis of data revealed that that most of the students started their paid part-time employment at secondary level at adolescence age with their parents, family members and others. More than seventy percent students were engaged in their part-time employment for 5 to 8 hours after their school hours. Burden of work at work place, absence of father/brother or boss from the work place were reasons for missing their school. The students had no time for completing their class room assignment, performing their class room activities easily and for participating in co-curricular activities. Although the students did not repeat any grade but only few students got 1st division with their part-time employment. Majority of the students believed that their part-time employment would be beneficial for them in future. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has significantly contributed to the treatment of various types of cancers mainly by targeting immune checkpoint inhibitors (ICI). Among them, V-domain immunoglobulin suppressor of T cell activation (VISTA) has been explored as a promising therapeutic target. Besides, histone deacetylase 6 (HDAC6) has been demonstrated to be efficacious target for several cancers. The current theoretical work was performed to explore the virtual repurposing of the FDA-approved drugs as inhibitors against these two (VISTA and HDAC6) cancers therapeutic targets. The crystal structure of the two proteins were downloaded from PDB and subjected to virtual screening by DrugRep webserver while using FDA-approved drugs library as ligands database. Our study revealed that Oxymorphone and Bexarotene are the top-ranked inhibitors of VISTA and HDAC6, respectively. The docking score of Bexarotene was predicted as − 10 kcal/mol while the docking score of Oxymorphone was predicted as − 6.2 kcal/mol. Furthermore, a total of 100 ns MD simulation revealed that the two drugs Oxymorphone and Bexarotene formed stable complexes with VISTA and HDAC6 drug targets. As compared to the standard drug the two drugs Oxymorphone and Bexarotene revealed great stability during the whole 100 ns MD simulation. The binding free energy calculation further supported the Root Mean Square Deviation (RMSD) result which stated that as compared to the ref/HDAC6 (− 18.0253 ± 2.6218) the binding free energy score of the Bexarotene/HDAC6 was good (− 51.9698 ± 3.1572 kcal/mol). The binding free energy score of Oxymorphone/VISTA and Ref/VISTA were calculated as − 36.8323 ± 3.4565, and − 21.5611 ± 4.8581 respectively. In conclusion, the two drugs deserve further consideration as cancer treatment option. [ABSTRACT FROM AUTHOR]

A novel spirooxindole‐pyrrolidine clubbed thiochromene and pyrazole motifs were synthesized by [3+2] cycloaddition (32CA) reactions in one step process starting from the ethylene‐based thiochromene and pyrazole scaffolds with the secondary amino‐acids and substituted isatins in high yield. The 32CA reaction of AY 10 with ethylene derivative 6 has also been studied with Molecular Electron Density Theory. The high nucleophilic character of AY 10, N = 4.39 eV, allows explaining that the most favorable TS‐on is 13.9 kcal mol−1 below the separated reagent. This 32CA, which takes place through a non‐concerted one‐step mechanism, presents a total ortho regio‐ and endo stereoselectivity, which is controlled by the formation of two intramolecular H...O hydrogen bonds. The design of spirooxindole‐pyrrolidines engrafted thiochromene and pyrazole was tested for alpha‐amylase inhibition and show a high efficacy in nanoscale range of reactivity. The key interaction between the most active hybrids and the receptor was studied by molecular docking. The physiochemical properties of the designed spirooxindole‐pyrrolidines were carried out by in silico ADMET prediction. The newly synthesized most potent hybrid could be considered as a lead compound for drug discovery development for type 2 diabetes mellitus (T2DM). [ABSTRACT FROM AUTHOR]

This review presents an overview of published studies for a better understanding of the anti-mutagenic potential of medicinal plants and the precise indications for the utilization of natural compounds as chemo-preventive agents. Reports on the anti-mutagenic potential of medicinal plants published from 1997 to 2019 were searched through different scientific databases using the following keywords: medicinal plants and mutagens, carcinogens, the anti-mutagenic potential of medicinal plants. The data relevant to the anti-mutagenic potential of some common medicinal plants is summarized in this mini-review. These medicinal plants include Carum carvi, Withania somnifera, Panax ginseng, Mentha spicata, Curcuma zedoaria, Cassia angustifolia, Cymbopogon citrates, Ipomoea batatas, Glycyrrhiza glabra, Citrullus colocynthis, Capsicum annuum and Asparagus racemosus. An overview of the identified molecules or enzymes being targeted is also presented, with a focus on anti-carcinogenic and/or anti-mutagenic activity. The recent advancements in the research on medicinal plants pave the way for the better understanding and future prospects of the use of natural components as chemo-preventive and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

In an electrical power system, the coordination of the overcurrent relays plays an important role in protecting the electrical system by providing primary as well as backup protection. To reduce power outages, the coordination between these relays should be kept at the optimum value to minimize the total operating time and ensure that the least damage occurs under fault conditions. It is also imperative to ensure that the relay setting does not create an unintentional operation and consecutive sympathy trips. In a power system protection coordination problem, the objective function to be optimized is the sum of the total operating time of all main relays. In this paper, the coordination of overcurrent relays in a ring fed distribution system is formulated as an optimization problem. Coordination is performed using proposed continuous particle swarm optimization. In order to enhance and improve the quality of this solution a local search algorithm (LSA) is implanted into the original particle swarm algorithm (PSO) and, in addition to the constraints, these are amalgamated into the fitness function via the penalty method. The results achieved from the continuous particle swarm optimization algorithm (CPSO) are compared with other evolutionary optimization algorithms (EA) and this comparison showed that the proposed scheme is competent in dealing with the relevant problems. From further analyzing the obtained results, it was found that the continuous particle swarm approach provides the most globally optimum solution. [ABSTRACT FROM AUTHOR]

Copper(II) complexes with a general formula [Cu2(3,4-F2C6H3CH2COO)4(L)2], where L = 2-methylpyridine (1) and 3-methylpyridine (2), are reported here. The FTIR spectra of the complexes confirmed the bridging bidentate coordination mode of the carboxylate ligand. The low (475 and 449 cm−1) and strong (727 & 725 cm−1) intensity bands in the FTIR spectra, due to Cu-N stretches and pyridyl ring vibrations, confirmed coordination of the 2-/3-methyl pyridine co-ligands in complexes 1 and 2, respectively. A binuclear paddlewheel structural arrangement with a square pyramidal geometry was confirmed for copper atoms in the complexes via single-crystal X-ray analysis. The DPPH, •OH radical, and α-amylase enzyme inhibition assays showed higher activities for the complexes than for the free ligand acid. The binding constant (Kb = 1.32 × 105 for 1 and 5.33 × 105 for 2) calculated via UV-VIS absorption measurements and docking scores (−6.59 for 1 and −7.43 for 2) calculated via molecular docking showed higher SS-DNA binding potential for 2 compared to 1. Viscosity measurement also reflected higher DNA binding ability for 2 than 1. Both complexes 1 and 2 (docking scores of −7.43 and −6.95, respectively) were found to be more active inhibitors than the free ligand acid (docking score of −5.5159) against the target α-amylase protein. This in silico study has shown that the herein reported compounds follow the rules of drug-likeness and exhibit good potential for bioavailability. [ABSTRACT FROM AUTHOR]

With the growing cyber-infrastructure of smart grids, the threat of cyber-attacks has intensified, posing an increased risk of compromised communication links. Of particular concern is the false data injection (FDI) attack, which has emerged as a highly dangerous cyber-attack targeting smart grids. This paper addresses the limitations of the variable dummy value model proposed in the authors previous work and presents a novel defense methodology called the nonlinear function-based variable dummy value model for the AC power flow network. The proposed model is evaluated using the IEEE 14-bus test system, demonstrating its effectiveness in detecting FDI attacks. It has been shown that previous detection techniques are unable to detect FDI attacks, whereas the proposed method is shown to be successful in the detection of such attacks, guaranteeing the security of the smart grid's measurement infrastructure. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has significantly contributed to the treatment of various types of cancers mainly by targeting immune checkpoint inhibitors (ICI). Among them, V-domain immunoglobulin suppressor of T cell activation (VISTA) has been explored as a promising therapeutic target. Besides, histone deacetylase 6 (HDAC6) has been demonstrated to be efficacious target for several cancers. The current theoretical work was performed to explore the virtual repurposing of the FDA-approved drugs as inhibitors against these two (VISTA and HDAC6) cancers therapeutic targets. The crystal structure of the two proteins were downloaded from PDB and subjected to virtual screening by DrugRep webserver while using FDA-approved drugs library as ligands database. Our study revealed that Oxymorphone and Bexarotene are the top-ranked inhibitors of VISTA and HDAC6, respectively. The docking score of Bexarotene was predicted as − 10 kcal/mol while the docking score of Oxymorphone was predicted as − 6.2 kcal/mol. Furthermore, a total of 100 ns MD simulation revealed that the two drugs Oxymorphone and Bexarotene formed stable complexes with VISTA and HDAC6 drug targets. As compared to the standard drug the two drugs Oxymorphone and Bexarotene revealed great stability during the whole 100 ns MD simulation. The binding free energy calculation further supported the Root Mean Square Deviation (RMSD) result which stated that as compared to the ref/HDAC6 (− 18.0253 ± 2.6218) the binding free energy score of the Bexarotene/HDAC6 was good (− 51.9698 ± 3.1572 kcal/mol). The binding free energy score of Oxymorphone/VISTA and Ref/VISTA were calculated as − 36.8323 ± 3.4565, and − 21.5611 ± 4.8581 respectively. In conclusion, the two drugs deserve further consideration as cancer treatment option. [ABSTRACT FROM AUTHOR]

In search of potent inhibitors of cholinesterase enzymes and antioxidant agents, synthetic derivatives of dihydroquinazolin-4(1H)-one (1-38) were evaluated as potential anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitions and radical (DPPH and ABTS) scavenging activities. The structure-activity relationship (SAR) was mainly based on the different substituents at the aryl part which showed a significant effect on the inhibitory potential of enzymes and radical scavenging activities. The kinetic studies of most active compounds showed a noncompetitive mode of inhibition for AChE and a competitive mode of inhibition for the BChE enzyme. Additionally, molecular modelling studies were carried out to investigate the possible binding interactions of quinazolinone derivatives with the active site of both enzymes. [ABSTRACT FROM AUTHOR]

Abstract Lightweight aluminium matrix composites find wide applications in automobile and aerospace sector. Aluminium alloy composites with graphene nanoplatelets (GNPs) were prepared by powder metallurgy route containing four different loadings, i.e. 0.1 wt%, 0.5 wt%, 1 wt% and 3 wt%. Two methods for exfoliation of GNPs were employed to achieve uniform dispersion in Al6061 matrix. Pressureless consolidation followed by sintering was carried out to obtain near-theoretical densities. Comparison of the fabricated thermal condition and artificially aged T6 samples was carried out to investigate the contribution of GNPs in the strengthening of Al6061 matrix. Microstructure evolution was confirmed by X-ray diffraction, optical and scanning electron microscopy. Electrical conductivity increased with increasing content of GNPs up to 1 wt% due to conductive network around the matrix grains. Mechanical properties were found to increase 93%, 61% and 92% in hardness, compression strength and flexural strength up till 1 wt% GNPs in matrix alloy. Agglomeration at 3 wt% GNPs resulted in deterioration of properties. The fractured surfaces were examined to determine the change in fracture morphology, associated strengthening mechanism and behaviour of GNPs. Highlights • Dual dispersion technique for dispersion of GNPs is utilised. • GNPs are incorporated in fabricated and artificially aged Al6061 matrices. • GNPs contribution in ductile and hardened matrices is established for the first time. • A mathematical model for predicting the contribution of GNPs is proposed. • An illustrative model of GNPs and crack propagation is developed. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Phytosterols including beta-sitosterol and stigmasterol were isolated from Polygonum hydropiper L. • Structures were confirmed via NMR and Mass analysis. • Phytosterols were evaluated against HeLa, MCF-7 and NIH/3T3 cell lines using MTT assays. • Compounds were docked against Tyrosine kinase an important enzyme in the cancer drug targets. Abstract Based on our previous studies on cytotoxic potentials of Polygonum hydropiper L, two steroidal compounds beta-sitosterol and stigmasterol were isolated from the most active fraction and were subjected to cell lines cytotoxicity. Isolated compounds were tested against HeLa, MCF-7 and NIH/3T3 cell lines following MTT assay. Furthermore, the compounds were also docked against tyrosine kinase enzyme to predict the binding mode of phytosterols in the active sites of the enzyme. Beta-sitosterol exhibited considerable cytotoxicity against NIH/3T3, HeLa and MCF-7 cell with 67.05 ± 2.08, 79.63 ± 2.34 and 71.50 ± 1.57% lethality respectively at 1 mg/ml concentration. Median inhibitory concentrations calculated from dose response curve against NIH/3T3, HeLa and MCF-7 cells were 440, 170 and 200 µg/ml respectively. Stigmasterol was more effective against MCF-7 and NIH/3T3 cells by killing 87.50 and 81.45% cancerous cells respectively at 1 mg/ml concentration. Stigmasterol showed 77.25% cyctotoxicity against HeLA cells at 1 mg/ml concentration in MTT assay. The IC 50 values for HeLA, MCF-7 and NIH/3T3 cells were 170, 60 and 140 µg/ml respectively. In docking studies, the docking score for beta-sitosterol and stigmasterol were −7.266 and −4.89 respectively. The binding energies for beta-sitosterol and stigmasterol were −41.21 and −41.04 respectively. Such lower binding energies indicate that the compounds fit into the active site more strongly. Binding affinities for both compounds were −7.76 and −7.68 respectively. Both phytosterols possess significant anticancer potentials and can be effective in the prevention and treatment of several malignancies. [ABSTRACT FROM AUTHOR]

Dengue Virus (DENV) is a serious threat to human life worldwide and is one of the most dangerous vector-borne diseases, causing thousands of deaths annually. We constructed a comprehensive PPI map of DENV with its host Homo sapiens and performed various bioinformatics analyses. We found 1195 interactions between 858 human and 10 DENV proteins. Pathway enrichment analysis was performed on the two sets of gene products, and the top 5 human proteins with the maximum number of interactions with dengue viral proteins revealed noticeable results. The non-structural protein NS1 in DENV had the maximum number of interactions with the host protein, followed by NS5 and NS3. Among the human proteins, HBA1 and UBE2I were associated with 7 viral proteins, and 3 human proteins (CSNK2A1, RRP12, and HSP90AB1) were found to interact with 6 viral proteins. Pharmacophore-based virtual screening of millions of compounds in the public databases was performed to identify potential DENV-NS1 inhibitors. The lead compounds were selected based on RMSD values, docking scores, and strong binding affinities. The top ten hit compounds were subjected to ADME profiling which identified compounds C2 (MolPort-044-180-163) and C6 (MolPort-001-742-737) as lead inhibitors against DENV-NS1. Molecular dynamics trajectory analysis and intermolecular interactions between NS1 and the ligands displayed the molecular stability of the complexes in the cellular environment. The in-silico approaches used in this study could pave the way for the development of potential specie-specific drugs and help in eliminating deadly viral infections. Therefore, experimental and clinical assays are required to validate the results of this study. [ABSTRACT FROM AUTHOR]

Herein, we present an experimental and theoretical drug–drug interaction study between nitazoxanide (NTZ) and azithromycin (AZT) in an aqueous solution. Interaction was studied by using UV/Vis, fluorescence, attenuated total reflectance‐fourier transform infrared (ATR‐FTIR), and circular dichroism (CD) spectroscopy, while molecular docking studies were performed to establish the interaction computationally. A bright yellow color was observed when the two drugs interacted, giving a hyperchromic band at 420 nm. The rate of absorbance was linearly increased by increasing drug concentrations and in a time‐dependent manner. Stability of the interaction complex (i.e., NTZ: AZT) was measured at variable temperatures (25–80°C), pH (5.0–10.0) and ionic strength (0.05–2.0 M NaCl), and not only proved stable but also retained antimicrobial potential with reduced cellular toxicity. Mole ratio and Job's method of continuous variations were used to establish the binding stoichiometry and found to be 2:1. The calculated binding constant (kb = 8,400 M−1) and Gibb's free energy (ΔG° = −22.4 KJ/mol) also suggested an energetically favorable interaction. FTIR spectra of NTZ: AZT complex in comparison with two drugs alone revealed significant interaction which was nicely complemented by molecular docking studies. Interaction was also successfully demonstrated in presence of carrier protein HSA and by spiking the two drugs in real samples of human plasma and urine. [ABSTRACT FROM AUTHOR]

Hospitals are the most prominent places for the growth and spread of bacteria which are resistant to the available antibiotics. This antibiotic resistance is due to the over and misuse of antibiotic dosages of a high-density of patient population which are in frequent interaction with inanimate items of the hospitals and the consequent risk of cross infection. Out of 1010 samples of the current study, 510 (50.49%) were culture positive of which 329 (64.5%) were Gram-positive while 181 (35.49%) Gram negative. The Gram positive bacterial isolates in the current study were; S. aureus and S. epidermidis while Gram negative were; Citrobacter , P. aeruginosa , Provedencia , E. coli , Proteus , Klebsiella , Shigella and Serratia . In the current study, 50 ESBL and 10 MBL producing isolates were obtained from inanimate objects. The ESBL positive isolates were highly resistant to MEM. Out of 50 ESBL, 2 isolates were resistant to DO, SXT and FEP while 1 was resistant to TZP and CN. The BlaTEM gene was detected in 22 and BlaCTX was detected in 19 ESBL producing isolates. Six of the MBL producing isolates were NDM positive while all of the isolates were AmpC negative. Most of the isolates had more than two resistant genes. Several classes of inhibitors have been reported for β-lactamase TEM, Metallo-β-lactamase and β-lactamase proteins. Complex-base pharmacophore models were generated on the bases of co-crystalline ligands attached in the 3-D structures of the proteins. The validated pharmacophore models were used for the screening of ZINC drug like database. As a screening results 571 structurally diverse hits of Ethyl Boronic Acid, 866 on L-Captopril and 1020 of Nacubactam were mapped and filtered via Lipinski’s rule of five. In conclusion, 30 hits (10 to each protein) having diverse structure and binding modes with all the three proteins active sites were selected as leading novel inhibitors. These selected novel inhibitors have different scaffolds and a strong possibility to act as an additional starting opinion in the development of new and potential inhibitors. [ABSTRACT FROM AUTHOR]

New zinc(II) carboxylate complexes [Zn(3-F-C 6 H 4 CH 2 COO) 2 ] n ( 1 ), [Zn 3 (3-F-C 6 H 4 CH 2 COO) 6 (Phen) 2 ] ( 2 ) and [Zn 3 (3-F-C 6 H 4 CH 2 COO) 6 (bipy) 2 ] ( 3 ) were synthesized and characterized by atomic absorption, single crystal structural analysis and IR studies. Complex 1 crystallizes as a coordination polymer constituting a web of μ − η 1 ,η 1 carboxylate bridged tetrahedral zinc centers. Complexes 2 and 3 comprise trinuclear zinc centers with two terminal fivefold coordinated slightly distorted square-pyramidal and central sixfold coordinated octahedral zinc centers. The complexes were also assessed for their DNA binding ability by UV/− Vis spectroscopy and their behavior rationalized theoretically by molecular docking studies. A DNA binding study has shown groove binding interactions with the complexes. [ABSTRACT FROM AUTHOR]

Globally, novel coronavirus (nCoV19) outbreak is a great concern to humanity owing to the unavailability of effective medication or vaccine to date. Therefore, the development of drugs having anti-COVID-19 potential is a need of time. In this milieu, in-silico studies have proven to be rapid, inexpensive and effective as compared to other experimental studies. Evidently, natural products have shown significant potential in drug development to curtail different ailments, which have opened a new horizon in the screening of anti-COVID-19 agents. In this study, in-silico analysis were performed on derivatives of amentoflavone (4′, 4′′′-Dimethylamentoflavone, 4′′′, 7-Di-O-Methylamentoflavone, 4′′′′′′-methylamentoflavone, 4′-Monomethylamentoflavone, 7,4′-Dimethylamentoflavone, 7′-O-Methylamentoflavone, 7-O-methylamentoflavone, Heveaflavone, kayaflavone, and Sciadopitysin) and FDA approved anti-viral drug (camostatmesylate). All the derivatives of amentoflavone and FDA-approved anti-viral drugs were docked against SARS-CoV2 main protease (MPRO). The ten derivatives of amentoflavone showed strong interactions with the MPRO protein. In all cases, derivatives of amentoflavone showed good interaction with the targeted protein and better binding/docking score (–9.0351, –8.8566, –8.8509, –8.7746, –8.6192, –8.2537, –8.0876, –7.9501, –7.6429, and –7.6248 respectively) than FDA approved anti-viral drug. Therefore, derivatives of amentoflavone may be potent leads in drug discovery to combat HCoVs, such as SARS-CoV2. Moreover, to support the outcomes of this study further in-vivo investigations are required. [ABSTRACT FROM AUTHOR]