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Abstract Computer-aided drug design has been employed to get the medicinal effects against Corona virus from different pyridine derivatives after synthesizing the new compounds. Additionally, various computational studies are also employed between the newly prepared pyridine derivatives and three controls against three proteins (6Y2E, 6M71 and 6M3M). Different methods were employed to synthesize new pyridine derivatives according to the literature using different reaction mediums. MTT was performed for cytotoxicity study and IC50 for inhibitory concentration. Additionally, in-silico studies including DFT, molecular docking, molecular dynamics, MMPBSA, ADME, pharmacokinetics and Lipinski rules were evaluated. The chemical structures of all new compounds were elucidated based on spectroscopic investigation. A molecular docking study demonstrated that compounds 5, 11, and 12 have the best binders of the SARS-CoV-2 main protease enzyme, with energy scores of − 7.5 kcal/mol, − 7.2 kcal/mol, and − 7.9 kcal/mol, respectively. The net binding energy values of the 11-Mpro, 12-Mpro, and 5-Mpro complexes revealed their highly stable nature in terms of both intermolecular interactions and docked conformation across the simulation time. ADME properties, besides the pharmacokinetics and Lipinski rules, showed that all seven newly synthesized compounds follow Lipinski rules with high GI absorption. The In Vitro antiviral study against SARS-CoV-2 using MTT methods confirms that compound 5 has more potential and is safer than other tested compounds. The study shows that the newly synthesized pyridine derivatives have medicinal properties against SARS-CoV-2 without violating Lipinski rules. Compounds 5, 11, and 12, particularly compound 5, may serve as promising potential candidate for COVID-19.

Isoquinoline and its derivatives, which constitute an important category of heterocyclic compounds and are found in a variety of naturally occurring alkaloids, serve a variety of biological purposes such as a potent agonist for human melatonin receptors 1. This research was conducted in an attempt to develop new dihydroisoquinoline molecules (III and IV). Single-crystal X-ray crystallography study validated their structures. The Hirshfeld surface analysis identifies intermolecular interactions by using a 2-D fingerprint map to recognize each type's relative contribution H⋅⋅⋅H connections are discovered to be dominating. The interaction energies between chemical pairs in crystal structures were found using an energy framework analysis. The DFT investigation demonstrates the electronic stability and reactivity of the compounds using the HOMO-LUMO and global reactivity descriptors, indicating that IV has higher chemical reactivity than III. The derived polarizability (αo) and hyperpolarizability (βo) values were used to calculate the optical and nonlinear optical characteristics of III and IV. The IV's significant βo value (488.94 au) indicates that it has good optical and NLO qualities. Molecular docking simulation using human melatonin receptors 1 was used to better understand the binding interaction mechanism of the title compounds. In addition, ADMET evaluations were performed to establish the therapeutic potential of III and IV.

Carbohydrates derivatives played an important and vital role in a large part to design new potential drug against various pathogens, in medicinal chemistry. Also, monosaccharide derivatives are very useful in biological chemistry because monosaccharide binding agents were shown to possess antiviral, antibacterial, and antifungal activity towards HIV, Dengue coronaviruses, and many members of the family Enterobacteriaceae, including strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, Shigella flexneri, and Enterobacter aerogenes. The present study was therefore interesting in identifying the binding affinity of a series of monosaccharides previously synthesized through their physicochemical and pharmacokinetic properties. These monosaccharides are derivatives of methyl-β-D-galactopyranoside (MGP) coupled to the protein deacetoxycephalosporin C synthase (DAOCS) of Streptomyces clavuligerus (1RXF). Molecular docking study against DAOCS proteins (PDB ID: 1RXF) was performed assess the antimicrobial activities of these derivatives along with antiviral prediction. The results of molecular docking studies showed that derivatives 8 and 10 both presented the highest score (-7.2 kcal/mol), reflecting their good binding affinity toward the active pocket of the pathogen S. clavuligerus (1RXF). They are found to be potent antimicrobial agents. These findings were further validated in dynamics (200 ns) milieu and intermolecular stability was evaluated via highly acceptable Molecular Mechanics Poisson-Boltzmann Surface Area (MMPB)/Molecular Mechanics/Generalized Born Surface Area (GBSA) binding free energies estimation methods. The dynamics of the complexes are highly stable with the strengthening of docked interactions as highlighted by MMPB/GBSA method (net binding energy < −40 kcal/mol). Density functional theory (DFT) calculations were carried out on the derivatives of MGP in order to determine the partial atomic charges, electronic energies, enthalpies, entropies and polarizability, at the B3LYP/3-21G level. The in silico ADMET prediction carried out provided access to the bioactivity and toxicity parameters which established that most of the different ligands designed are safe to use as drugs. This in silico study provided an overall view of the possible pharmacological and therapeutic profile of MGP derivatives. It therefore, paved the way for the discovery of promising next-generation drugs against pathogenic microbes.

The black fungus is a SARS-CoV-2-associated fungal co-infection. Mechanisms by which antifungal drugs act against Mucormycosis are by inhibition of enzymes implicated in ergosterol biosynthesis or cell wall formation or the drug interaction directly with ergosterol. Since it has been shown that the reduction of ergosterol biosynthesis prevents this infection, we carried out a virtual screening with molecular docking analysis and tested a dataset of 880 molecules for its effects on an enzyme involved in ergosterol biosynthesis (CYP51) and fungal infection (lipase), as well as ADMET and toxicity properties of the studied molecules. We calculated the stability of the complex’s inhibitor-enzyme throughout the time using molecular dynamics simulations. From this, initial screening indicated that 600 out of a total of 880 compounds have a good affinity towards sterol 14α-demethylase. The two compounds ZINC95486139 and ZINC33833639 were determined as safe and have good drug-likeness properties, and have binding energies of −75.07 and −83.89 kcal/mol, respectively by MMGBSA and create strong and stable interactions with the residues of the active site of the enzyme. To the best of our knowledge, ZINC95486139 and ZINC33833639 have not yet been described in the literature as anti-sterol 14α-demethylase inhibitors or evaluated for their anti-fungal activity.

Abstract The cobalt (II) complexes have been synthesized from the reaction of the cationic entities (3,4-dimethylaniline (1) and histamine (2)) with metallic salt CoCl2⋅6H2O and thiocyanate ion (SCN−) as a ligand in H2O/ethanolic solution and processing by the evaporation crystal growth method at room temperature to get crystals. The synthesized complex has been fully characterized by single-crystal X-ray diffraction. UV–Visible, FTIR spectroscopy, TGA analysis, and DFT circulations were also performed. The crystal structural analysis reveals that the solid (1) {[Co(SCN)4] (C8H12N)3}·Cl crystallizes in the monoclinic system with the space group P21/n and the solid (2) {[Co(SCN)4](C5H11N3)2}·2Cl crystallizes in the monoclinic space group P21/m. Metal cations are joined into corrugated chains parallel to the b-axis direction in (1) and (2) by four thiocyanate anions. The crystal structures of (1) and (2) were calculated using XRPD data, indicating that they are closely connected to the DRX mono-crystal results. Different interactions pack the system into a ring formed by N–H⋯Cl and N–H⋯S hydrogen bonds. C–H⋯π and the π⋯π stacking of anilinuim ring for (1) and N–H⋯S intermolecular interactions for (1) and (2) increase the crystals' robustness. Hirshfeld surface analysis cum 2D fingerprint plots visualize the main intermolecular interactions with their contributions in the solid-state phase. The molecular geometries of both complexes obtained from the crystal structure were used for quantum chemical calculation. Here, frontier orbital analysis and electrostatic potential illustrate the chemical reactivities of metal–organic complexes. QTAIM and NCI analysis reveal the strength of interactions at the electronic level.

An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.

The present study elaborates on the synthesis, crystal structure, and computational studies of two new ionic liquids. In the crystal structure, [C5H12N][C21H14ClN2O2S] (4a), the anions form chains along the a-axis direction through C—H···π(ring) interactions. These are connected into layers that run approximately parallel to the ac plane by a variety of hydrogen bonds. In the compound structure, [C5H12N][C18H15N2O2S] (4b), the two ions are primarily associated by an N—H···N hydrogen bond. In the crystal structure, layers parallel to the bc plane are formed by pairs of C—H···O and N—H···S hydrogen bonds and by C—H···π(ring) interactions. A theoretical study reveals that 4a has lower energy than 4b and is more stable. The NBO and DOS studies further confine the liquids’ structural reactivity and electronic properties. The quantum theory of atoms in a molecule (QTAIM) analysis reveals the important non-covalent interactions among the fragments and charge transfer. The global reactivity descriptors indicate their molecular reactivity relationship with the presence of functional groups. The remarkable polarizability (αo) and hyperpolarizability (βo) values indicate their optical and nonlinear optical (NLO) properties. Furthermore, the analysis performed by CrystalExplorer shows the intermolecular interactions and reactive sites between cations and anions in ionic liquids. The 2D fingerprint plots and Hirshfeld surfaces indicate the major interactions of crystals with neighboring elements in crystal packing. For both compounds, the H···H interactions are significantly higher than the other element interactions.

Despite extensive genetic and biochemical characterization, the molecular genetic basis underlying the biosynthesis of β-diketones remains largely unexplored. β-Diketones and their complexes find broad applications as biologically active compounds. In this study, in silico molecular docking results revealed that two β-diketone derivatives, namely 2-(2-(4-fluorophenyl)hydrazono)-5,5-dimethylcyclohexane-1,3-dione and 5,5-dimethyl-2-(2-(2-(trifluoromethyl)phenyl)hydrazono)cyclohexane-1,3-dione, exhibit anti-COX-2 activities. However, recent docking results indicated that the relative anti-COX-2 activity of these two studied β-diketones was influenced by the employed docking programs. For improved design of COX-2 inhibitors from β-diketones, we conducted molecular dynamics simulations, density functional theory (DFT) calculations, Hirshfeld surface analysis, energy framework, and ADMET studies. The goal was to understand the interaction mechanisms and evaluate the inhibitory characteristics. The results indicate that 5,5-dimethyl-2-(2-(2-(trifluoromethyl)phenyl)hydrazono)cyclohexane-1,3-dione shows greater anti-COX-2 activity compared to 2-(2-(4-fluorophenyl)hydrazono)-5,5-dimethylcyclohexane-1,3-dione.

In the present work, we describe the synthesis of new tetrahydroisoquinoline derivatives and the crystal structures of two of them. Density functional theory (DFT) investigations at the B3LYP/6-31+G(d,p) level provided their structural reactivity and nonlinear optical properties. The low HOMO-LUMO gaps (EH-L) suggest a soft nature and higher reactivity, while calculated global reactivity descriptors provide assessments of their reactivity and electronic stability. The calculated natural bonding molecular orbital (NBO) charges show excellent charge separation (charge transfer) and identify the donor and acceptor parts of the molecules. Density of states (DOS) analyses show the newly generated energy states and reduced band gaps, which impart higher conductive properties. For surface reactivity, 3D MESP surfaces are plotted and show electron-rich sites near the nitrogen atoms of the tetrahydroisoquinoline rings. Nonlinear optical (NLO) properties of the crystals are predicted from calculated polarizability (αo) and hyperpolarizability (βo) values. For IVb, the αo and βo values are 415.53 and 1003.44 au. The remarkable value (1003.44 au) of the hyperpolarizability (βo) shows IVb has excellent NLO properties. Structural activity relationship analysis suggests that nitric oxide synthases are better targets for both compounds, and they were further subjected to molecular docking simulations to understand the binding efficiency. In addition, ADMET analyses were carried out to understand the potential activity of the molecules as drug candidates.

# Background Malaria is a significant cause of morbidity, mortality, and economic burden among the Tanzanian population. An effective form of personal protection against malaria is the insecticide-treated bed net (ITN). Although Tanzania has made great efforts to implement ITNs in the general population, gaps in use, access, coverage, and ownership remain. We conducted a systematic review of the available data on the barriers and facilitators to the implementation of ITNs in Tanzania. # Methods A comprehensive search was conducted in four databases: OVID Medline, OVID Embase, EBSCO CINAHL, and Web of Science. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to present the review and analysis. Eligible studies were appraised to determine the quality of evidence. Various content data were extracted, including study locations, years of publication, study objectives, and barriers and facilitators to ITNs. The Consolidated Framework for Implementation Research (CFIR) facilitated a thematic analysis of the barriers and facilitators. # Results Seven mixed-methods and three qualitative studies met this review's inclusion criteria. Seven regions and ten districts within Tanzania were represented in this review, most notably the Morogoro region and its respective districts, Kilombero and Ulanga. Study dates ranged from 1995 to 2020. Facilitators of ITN implementation included cost, voucher schemes, involving locals, planning for distribution, and social marketing and communication campaigns. Similarly, barriers to ITN implementation included cost, knowledge and beliefs, a poorly developed private sector, and inadequate distribution methods. # Conclusions A systematic review of studies on the implementation of ITNs in Tanzania highlights vital areas in the development of successful implementation that include: (i) the cost of ITNs, (ii) knowledge and beliefs about ITNs among potential users, and (iii) planning for the execution of ITN distribution programs. ITN implementation can be enhanced if national stakeholders invest further in processes that promote ITN procurement, such as voucher schemes, providing education sessions, integrating distribution methods that cater to locals' preferences, and initiating the promotion of ITN months in advance of their distribution. # Registration PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=222128)

Objective: While psychological issues in epilepsy patients have been studied extensively, the phenomena of self-concept and self-security have not been adequately addressed in such patients. Therefore, the aim of the current study is to assess the levels of psychological self-security and self-concept among Saudi epilepsy patients. Methods: A case-control study was conducted on adult patients with epilepsy from the Epilepsy Monitoring Unit at King Fahad Medical City in Riyadh, Saudi Arabia. Healthy controls were obtained from the community. Demographic data including age, gender and education level were collected. Self-concept and self-security were assessed using validated scales. Descriptive statistics were obtained, and inferential testing was conducted. Results: Data from 145 subjects was entered in the final analysis, including 100 patients with epilepsy and 45 controls (females = 32%). A significantly higher level of psychological insecurity was found in PWE (people with epilepsy) compared to controls. No significant difference was noticed on self-concept level between PWE versus controls. Education level was significantly lower in PWE than in controls. Those with higher education levels scored lower on psychological insecurity, although this effect disappeared when the data were split by health status. Conclusion: Level of psychological self-security was higher in PWE than controls, while no difference in self-concept was observed. This study highlights the areas of focus needed in epilepsy-related social services in order to improve the psychological wellbeing of patients with epilepsy.

A new triazolopyrimidine derivative, namely, 6-hydroxy-7-phenyl-6,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one (HPTP) was synthesized. Its corrosion inhibition performance on mild steel in 1 M HCl solution was researched through weight loss, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and scanning electron microscope (SEM) approaches. The experimental results show that the inhibition efficiency of HPTP increases with the increase of concentrations, whereas decreases as the temperature rises. PDP data reveal that the HPTP acts as a mixed type inhibitor. EIS results imply that the HPTP molecules form an antiseptic layer at the steel/solution interface. The adsorption of the inhibitor molecules on the steel surface follows Langmuir's adsorption isotherm. In addition, density functional theory (DFT) calculations were also employed to gain further insight into the adsorption behavior and inhibition mechanism.

The multicomponent reaction of 4-nitrobenzaldehyde with acetophenone and urea in the presence of HCl was investigated, and, as a result, 4,5-bis(4-nitrophenyl)-8a-phenyl-decahydro-[1,3]diazino[4,5-d]pyrimidine-2,7-dione was synthesized. The structure of the synthesized compound was confirmed by the X-ray method. We performed Hirshfeld surfaces (HS) analysis and two-dimensional (2D) fingerprint plots for the studied compound to obtain surface reactivity and intermolecular interactions. The H∙∙∙H interactions were found to be higher, up to 32.2%, while the percentage C∙∙∙O contact was found to be the lowest among the reported interactions for single crystal packing. The energy framework analysis shows the strength of interaction energy within fragments of a single crystal at 3.08 A distances. The DFT study shows structural reactivity and a reduced HOMO-LUMO gap up to 4.0 eV. The NPA study reveals the reactivity and excellent charge transfer within the structure. The TD-DFT study reveals the absorbance in the UV region and excited state parameters during crucial transitions (transitions with maximum oscillator strength). The investigated compound shows excellent optical and nonlinear optical (NLO) properties, as indicated by its polarizability (αo) and hyperpolarizability (βo) values.

Nucleoside analogs are frequently used in the control of viral infections and neoplastic diseases. However, relatively few studies have shown that nucleoside analogs have antibacterial and antifungal activities. In this study, a fused pyrimidine molecule, uridine, was modified with various aliphatic chains and aromatic groups to produce new derivatives as antimicrobial agents. All newly synthesized uridine derivatives were analyzed by spectral (NMR, FTIR, mass spectrometry), elemental, and physicochemical analyses. Prediction of activity spectra for substances (PASS) and in vitro biological evaluation against bacteria and fungi indicated promising antimicrobial capability of these uridine derivatives. The tested compounds were more effective against fungal phytopathogens than bacterial strains, as determined by their in vitro antimicrobial activity. Cytotoxicity testing indicated that the compounds were less toxic. In addition, antiproliferative activity against Ehrlich ascites carcinoma (EAC) cells was investigated, and compound 6 (2′,3′-di-O-cinnamoyl-5′-O-palmitoyluridine) demonstrated promising anticancer activity. Their molecular docking against Escherichia coli (1RXF) and Salmonella typhi (3000) revealed notable binding affinities and nonbonding interactions in support of this finding. Stable conformation and binding patterns/energy were found in a stimulating 400 ns molecular dynamics (MD) simulation. Structure–activity relationship (SAR) investigation indicated that acyl chains, CH3(CH2)10CO-, (C6H5)3C-, and C2H5C6H4CO-, combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. Pharmacokinetic predictions were examined to determine their ADMET characteristics, and the results in silico were intriguing. Finally, the synthesized uridine derivatives demonstrated increased medicinal activity and high potential for future antimicrobial/anticancer agent(s).

The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is one of the optimum targets for antiviral drug design and development. The hydroxyl groups of cytidine structures were modified with different aliphatic and aromatic groups to obtain 5´-O-acyl and 2´,3´-di-O-acyl derivatives, and then, these derivatives were employed in molecular modeling, antiviral prediction, molecular docking, molecular dynamics, pharmacological and POM studies. Density functional theory (DFT) at the B3LYP/6-31G++ level analyzed biochemical behavior and molecular electrostatic potential (MESP) of the modified cytidine derivatives. The antiviral parameters of the mutated derivatives revealed promising drug properties compared with those of standard antiviral drugs. Molecular docking has determined binding affinities and interactions between the cytidine derivatives and SARS-CoV-2 RdRp. The modified derivatives strongly interacted with prime Pro620 and Lys621 residues. The binding conformation and interactions stability were investigated by 200 ns of molecular dynamics simulations and predicted the compounds to firmly dock inside the RdRp binding pocket. Interestingly, the binding residues of the derivatives were revealed in high equilibrium showing an enhanced binding affinity for the molecules. Intermolecular interactions are dominated by both Van der Waals and electrostatic energies. Finally, the pharmacokinetic characterization of the optimized inhibitors confirmed the safety of derivatives due to their improved kinetic properties. The selected cytidine derivatives can be suggested as potential inhibitors against SARS-CoV-2. The POM Theory supports the hypothesis above by confirming the existence of an antiviral (Oδ-—O’δ-) pharmacophore site of Hits.

In this conference paper, an optimal control method is designed for a variable speed wind turbine system. Due to the inherent nonlinearity of the wind turbine arising from the aerodynamic torque, a linearized model is derived to handle the system's nonlinearities. An online update cost function is created based on the resulting linearized model. The critic neural network weight vector is updated with the steepest decent algorithm to design an optimal control able to minimize the given cost function. To validate the effectiveness of the optimal control based on reinforcement learning, simulation results with varying wind speed profile for different values of learning parameters are presented.

This study examines a nonlinear control technique based on fractional-order sliding mode theory to track the highest power point of a wind energy conversion system. The proposed method achieves chatter-free fractional sliding-mode control by using a continuous control strategy. The main advantages of the proposed fractional-order SMC law are accurate reference tracking, elimination of the chattering problem and minimization of overshoot. To demonstrate the boundedness and convergence characteristics of the closed-loop signals, Lyapunov's stability theory is used. Extensive simulations results are presented to evaluate the robustness and effectiveness of the proposed control under various uncertainty.

V-domain Ig suppressor of T cell activation (VISTA) is an immune checkpoint and is a type I transmembrane protein. VISTA is linked to immunotherapy resistance, and it is a potential immune therapeutic target, especially for triple-negative breast cancer. It expresses at a high concentration in regulatory T cells and myeloid-derived suppressor cells, and its functional blockade is found to delay tumor growth. A useful medicinal plant database for drug designing (MPD3), which is a collection of phytochemicals from diverse plant families, was employed in virtual screening against VISTA to prioritize natural inhibitors against VISTA. Three compounds, Paratocarpin K (PubChem ID: 14187087), 3-(1H-Indol-3-yl)-2-(trimethylazaniumyl)propanoate (PubChem ID: 3861164), and 2-[(5-Benzyl-4-ethyl-1,2,4-triazol-3-yl)sulfanylmethyl]-5-methyl-1,3,4-oxadiazole (PubChem ID: 6494266), having binding energies stronger than −6 kcal/mol were found to have two common hydrogen bond interactions with VISTA active site residues: Arg54 and Arg127. The dynamics of the compound–VISTA complexes were further explored to infer binding stability of the systems. Results revealed that the compound 14187087 and 6494266 systems are highly stable with an average RMSD of 1.31 Å. Further affirmation on the results was achieved by running MM-GBSA on the MD simulation trajectories, which re-ranked 14187087 as the top-binder with a net binding energy value of −33.33 kcal/mol. In conclusion, the present study successfully predicted natural compounds that have the potential to block the function of VISTA and therefore can be utilized further in experimental studies to validate their real anti-VISTA activity.

In the title molecule, C13H16N4O3, the mean planes of the phenyl and triazole rings are nearly perpendicular to one another as a result of the intramolecular C—H...O and C—H...π(ring) interactions. In the crystal, layers parallel to (101) are generated by O—H...N, N—H...O and N—H...N hydrogen bonds. The layers are connected by inversion-related pairs of C—H...O hydrogen bonds. The experimental molecular structure is close to the gas-phase geometry-optimized structure calculated by DFT methods. Hirshfeld surface analysis indicates that the most important interaction involving hydrogen in the title compound is the H...H contact. The contribution of the H...O, H...N, and H...H contacts are 13.6, 16.1, and 54.6%, respectively.

In the title molecule, C17H23NO2, the dihydroindole portion is planar (r.m.s. deviation = 0.0157 Å) and the nonyl substituent is in an `extended' conformation. In the crystal, the nonyl chains intercalate and the dihydroindoledione units are associated through C—H...O hydrogen bonds to form micellar blocks. Based on the Hirshfeld surface analysis, the most important intermolecular interaction is the H...H interaction.

The chemistry and biochemistry of carbohydrate esters are essential parts of biochemical and medicinal research. A group of methyl β-d-galactopyranoside (β-MGP, 1) derivatives was acylated with 3-bromobenzoyl chloride and 4-bromobenzoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to obtain 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl derivatives with different aliphatic and aromatic substituents. Spectroscopic and elemental data exploration of these derivatives confirmed their chemical structures. In vitro biological experiments against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed ascending antifungal and antibacterial activities compared with their antiviral activities. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were performed for two derivatives, 3 and 9, based on their antibacterial activities. Most of these derivatives showed >780% inhibition of fungal mycelial growth. Density functional theory (DFT) was used to calculate the chemical descriptors and thermodynamic properties, whereas molecular docking was performed against antibacterial drug targets, including PDB: 4QDI, 5A5E, 7D27, 1ZJI, 3K8E, and 2MRW, and antifungal drug targets, such as PDB: 1EA1 and 1AI9, to identify potential drug candidates for microbial pathogens. A 100 ns molecular dynamics simulation study revealed stable conformation and binding patterns in a stimulating environment by their uniform RMSD, RMSF, SASA, H-bond, and RoG profiles. In silico pharmacokinetic and quantitative structure–activity relationship (QSAR) calculations (pIC50 values 3.67~8.15) suggested that all the designed β-MGP derivatives exhibited promising results due to their improved kinetic properties with low aquatic and non-aquatic toxicities. These biological, structure–activity relationship (SAR) [lauroyl-(CH3(CH2)10CO-) group was found to have potential], and in silico computational studies revealed that the newly synthesized MGP derivatives are potential antibacterial/antifungal candidates and can serve as therapeutic targets for human and plant pathogens.

BackgroundOral rehydration therapy (ORT) is an effective and cheap treatment for diarrheal disease; globally, one of the leading causes of death in children under five. The World Health Organization launched a global campaign to improve ORT coverage in 1978, with activities such as educational campaigns, training health workers and the creation of designate programming. Despite these efforts, ORT coverage remains relatively low. The objective of this systematic review is to identify the barriers and facilitators to the implementation of oral rehydration therapy in low and middle-income countries.MethodsA comprehensive search strategy comprised of relevant subject headings and keywords was executed in 5 databases including OVID Medline, OVID Embase, OVID HealthStar, Web of Science and Scopus. Eligible studies underwent quality assessment, and a directed content analysis approach to data extraction was conducted and aligned to the Consolidated Framework for Implementation Research (CFIR) to facilitate narrative synthesis.ResultsThe search identified 1570 citations and following removal of duplicates as well as screening according to our inclusion/exclusion criteria, 55 articles were eligible for inclusion in the review. Twenty-three countries were represented in this review, with India, Bangladesh, Egypt, Nigeria, and South Africa having the most representation of available studies. Study dates ranged from 1981 to 2020. Overarching thematic areas spanning the barriers and facilitators that were identified included: availability and accessibility, knowledge, partnership engagement, and design and acceptability.ConclusionA systematic review of studies on implementation of ORT in low- and middle-income countries (LMICs) highlights key activities that facilitate the development of successful implementation that include: (1) availability and accessibility of ORT, (2) awareness and education among communities, (3) strong partnership engagement strategies, and (4) adaptable design to enhance acceptability. The barriers and facilitators identified under the CIFR domains can be used to build knowledge on how to adapt ORT to national and local settings and contribute to a better understanding on the implementation and use of ORT in LMICs. The prospects for scaling and sustaining ORT (after years of low use) will increase if implementation research informs local applications, and implementers engage appropriate stakeholders and test assumptions around localized theories of change from interventions to expected outcomes.RegistrationA protocol for this systematic review was developed and uploaded onto the PROSPERO international prospective register of systematic reviews database (Registration number: CRD420201695).

Objectives: Consuming raw vegetables presents a considerable risk to the public and is the chief mode of transmission of intestinal parasites. We sought to assess the degree of parasitic contaminations on selected vegetables in the UAE. Methods: A total of 218 fresh vegetable samples were collected randomly from different farms and local supermarkets between February 2017 and January 2018. After washing and centrifugation, the sediment was examined microscopically for parasitic forms. Results: Protozoa cysts and helminths eggs were detected in 15.1% (33/218) of samples. The most detected parasites were Entamoebacomplex(E. histolytica/E. dispar/E. moshkovskii) (30.3%), Entamoeba coli (18.2%), Trichuris trichiura (12.1%), Strongyloides stercoralis (12.1%), Ascaris lumbricoides egg (9.1%), Endolimax nana cyst and Enterobius vermicularis egg (6.1% each), and Giardia lamblia and Hymenolepis nana (3.0% each). We found no significant association between the vegetable type and the parasite occurrence (p > 0.050). Moreover, parasite incidence was independent of the vegetable type (p > 0.050). Conclusions: The study highlights the potential of raw produce serving as a major source of foodborne disease outbreaks and its role in the transmission of intestinal parasitic infections. Public education on the safe handling of raw vegetables is recommended.

In the title molecule, C21H25N3O, the 1-decyl substituents are in an extended conformation and intercalate in the crystal packing to form hydrophobic bands. The packing is further organized by π–π-stacking interactions between pyrrole and phenyl rings [centroid–centroid distance = 3.6178 (11) Å] and a C=O...π(pyrrole) interaction [3.447 (2) Å]. Hirshfeld surface analysis indicates that the H...N/N...H interactions make the highest contribution (17.4%) to the crystal packing.

The asymmetric unit of the title compound, C14H11N3O3, consists of two independent molecules having very similar conformations in which the indazole moieties are planar. The independent molecules are distinguished by small differences in the rotational orientations of the nitro groups. In the crystal, N—H...O and C—H...O hydrogen bonds form zigzag chains along the b-axis direction. Additional C—H...O hydrogen bonds link the chains into layers parallel to (10\overline{1}). These are connected by slipped π-stacking and C—H...π(ring) interactions.

Abstract Background Identifying the optimal type and amount of activity for the maintenance of function in older adults has proved challenging. On the one hand, Masters Athletes have been proposed as the ideal model of successful aging but most of this research has focused on physical functioning. On the other hand, the importance of cognitive engagement has been emphasized, which may be more strongly related to activities such as playing chess. The current study aimed to compare physical health outcomes (i.e., prevalence of physical injury and chronic disease) among older athletes and chess players. Masters Athletes and chess players were recruited from track and field and chess competitions within the province of Ontario. In addition to these primary groups, moderately active and inactive older adults from Canadian Community Health Survey were also included for comparison. Results Masters Athletes had significantly higher rates of injury with the lowest rates of chronic disease, compared to all other activity groups. In contrast, chess players reported lower rates of injury compared to Masters Athletes as well as lower prevalence of chronic diseases compared to the moderately active and inactive groups. The normative groups reported the lowest rate of injury, but increased prevalence of chronic diseases compared to Masters Athletes and chess players. Conclusions Findings from this study indicate that both athletic and cognitive engagement may be positively related to the physical health of older adults, since Masters Athletes and chess players reported a lower prevalence of chronic disease. Importantly, the results expand our current understanding of health by providing evidence for physical health outcomes associated with an activity that is primarily associated with cognitive health.