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IntroductionAlzheimer’s disease (AD) is a neurodegenerative disorder that significantly impacts the cognitive function and memory of a person. Despite the significant research efforts, the ability to completely prevent or effectively treat AD and its related dementias remains limited. Protein kinases are integral to AD pathology and represent promising targets for therapeutic intervention.MethodsA series of pyrimidine-based compounds 4-(4-(arylsulfonyl)piperazin-1-yl)-6-(thiophen-3-yl)pyrimidine derivatives (8-14) were synthesized and characterised. ATPase inhibition was carried out against the MARK4 enzyme. Molecular docking and molecular dynamics (MD) simulation at 500 ns was carried out against MARK4 (PDB: 5ES1). The drug-likeness feature and toxicity of the molecules were evaluated using QikProp and other tools.ResultsCompounds were synthesized following a multi-step approach and characterized using multi-nuclear magnetic resonance (1H/13C-NMR) and mass spectrometry. ATPase inhibition assay of the compounds against MARK4 showed an IC50 value in the micromolar (μM) range. The results of the docking studies were consistent with the in-vitro experiments and identified (9) and (14) as the candidates with the highest affinity towards MARK4. MD simulation further supported these results, showing that the binding of ligands stabilises the target protein.ConclusionUsing experimental and theoretical approaches, we demonstrated that the reported class of pyrimidine derivatives are an excellent starting point for developing the next-generation anti-AD drugs.

In the present work, we report the synthesis, characterization and anionic dye adsorption application of a polyethyleneimine (PEI) functionalized (5,10,15,20 tetraphenyl porphyrinato) tin(IV) dichloride Sn(TPP)(Cl2). The adsorbent [Sn(TPP)(Cl2)]-PEI was prepared via a swift protocol and characterized extensively using multi-nuclear spectroscopic techniques including the 1H NMR, FT-IR and UV–Vis spectroscopic techniques. X-ray diffraction (XRD) data confirmed that the addition of PEI to the Sn-porphyrin complex did not affect its crystallinity. On the other hand, scanning electron microscopy (SEM) analysis indicated that the morphological characteristics of Sn(TPP)Cl2 and [Sn(TPP)(Cl2)]-PEI were different. The prepared material was tested for its ability to adsorb Acid Blue 25, an anionic dye, from water. The adsorption results showed a significant enhancement in the adsorption capacity of the resulting material. Under optimized conditions (pH = 5, time = 60 min., and T = 295.15 K), the adsorption capacity of [Sn(TPP)(Cl2)]-PEI was 208 mg/g while it was 14 mg/g for [Sn(TPP)(Cl2)]. The fitting of the adsorption data indicated that the process followed pseudo-second-order and Langmuir equations. Overall, we reported a simple and cost-effective method for efficient adsorbent for removing anionic dyes from contaminated water.

Coronavirus spread in Wuhan, China, in December 2019. A few weeks later, the virus was present in over 100 countries around the globe. Governments have adopted extreme measures to contain the spreading virus. Quarantine is considered the most effective way to control the spreading speed of COVID-19. In this study, a mathematical model is developed to explore the influence of quarantine and the latent period on the spatial spread of COVID-19. We use the mathematical model with quarantine, and delay to predict the spreading speed of the virus. In particular, we transform the model to a single integral equation and then apply the Laplace transform to find implicit equations for the spreading speeds. The basic reproduction number of COVID-19 is also found and calculated. Numerical simulations are performed to confirm our theoretical results. To validate the proposed model, we compare our outcomes with the actual reported data published by the National Health Commission of China and the Health Commission of local governments. The model demonstrates good qualitative agreement with the actual data reported. The results show that delay and quarantine highly influence the spreading speeds of COVID-19. Also, we can only contain the disease if we quarantine $ 75 \% $ of the infected people.

Background: Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions. Methods: Human serum albumin (HSA) was glycated with 0.05 M α-D-glucose alone or in the presence of Zingiber officinale Roscoe (ginger) extract (0.781–100 μg/mL) for 10 weeks, and biochemical, biophysical, and computational analyses were carried out. Results: HSA glycated for 10 weeks (G-HSA-10W) resulted in significant production of ketoamines, carbonyl compounds, and AGE pentosidine. Notable structural alterations were observed in G-HSA-10W, ascertained by ultraviolet (UV), fluorescence, and circular dichroism (CD) studies. Antioxidant, anti-glycating, AGEs inhibitory, and antibacterial effects of ginger extracts were observed and attributed to the presence of various phytochemicals. Molecular docking studies suggested that the compounds 8-shagaol and gingerol exhibited strong and multiple interactions with HSA. Molecular simulation analysis suggests HSA attains a high degree of conformational stability with the compounds gingerol and 8-shogaol. Conclusions: These findings showed that ginger extract has an antioxidant function and can prevent glycation-induced biochemical and biophysical alterations in HSA. Thus, aqueous ginger extract can be utilized to combat glycation and AGE-related health issues, especially diabetes, neurological disorders, inflammatory diseases, etc.

In the current work, chloro(meso-tetrakis(phenyl)porphyrin) manganese(III) [Mn(TPP)Cl] was synthesized following two steps: the preparation of meso-tetraphenylporphyrin (H⁠2TPP) and the insertion of manganese into the free porphyrin H2TPP. The compounds were characterized using SEM, FT-IR, UV, TGA/DTA, and XRD analyses. Manganese(III) meso-porphyrins exhibited hyper-type electronic spectra with a half-vacant metal orbital with symmetry, such as [dπ:dxz and dyz]. The thermal behavior of [Mn(TPP)(Cl)] changed (three-step degradation process) compared to the initial H2TPP (one-step degradation process), confirming the insertion of manganese into the core of the free porphyrin H2TPP. Furthermore, [Mn(TPP)Cl] was used to degrade calmagite (an azo dye) using H2O2 as an oxidant. The effects of dye concentration, reaction time, H2O2 dose, and temperature were investigated. The azo dye solution was completely degraded in the presence of [Mn(TPP)(Cl)]/H2O2 at pH = 6, temperature = 20 °C, C0 = 30 mg/L, and H2O2 = 40 mL/L. The computed low activation energy (Ea = 10.55 Kj/mol) demonstrated the efficiency of the proposed catalytic system for the azo dye degradation. Overall, based on the synthesis process and the excellent catalytic results, the prepared [Mn(TPP)Cl] could be used as an effective catalyst for the treatment of calmagite-contaminated effluents.

ZnO nanoparticles (NPs) were prepared by green synthesis using plant leaf extraction of Ochradenus baccatus and characterized by XRD, FESEM, HRTEM, and Raman spectroscopy techniques. Since elevated CO levels have been associated with inflammatory conditions, cardiovascular diseases, and respiratory disorders and the methane gas primarily produced by gut microbiota and linked to gastrointestinal disorders and other abnormal methane levels in breath samples, the nanoparticles were applied for gas sensor fabrication. Thus, the gas sensors fabricated using ZnO nanoparticles were investigated for CH4, H2, CO, and NO2 gases. The gas sensing was performed for the fabricated sensors at various operating temperatures and gas concentrations. Interestingly, leaf-extracted green synthesized ZnO NPs were more sensitive to CH4, CO, and NO2 gases than to H2. The results of sensing studies revealed that the nanoparticles exhibit a selectivity toward gas depending on the gas type. The sensor response was also studied against the humidity. These findings bridge between the laboratory and industry sectors for future gas sensors development, which can be used for exhaled breath analysis and serve as potential diagnostic tools for highly sensitive contagious diseases.

We derive a reaction–diffusion model with time-delayed nonlocal effects to study an epidemic’s spatial spread numerically. The model describes infected individuals in the latent period using a structured model with diffusion. The epidemic model assumes that infectious individuals are subject to containment measures. To simulate the model in two-dimensional space, we use the continuous Runge–Kutta method of the fourth order and the discrete Runge–Kutta method of the third order with six stages. The numerical results admit the existence of traveling wave solutions for the proposed model. We use the COVID-19 epidemic to conduct numerical experiments and investigate the minimal speed of spread of the traveling wave front. The minimal spreading speeds of COVID-19 are found and discussed. Also, we assess the power of containment measures to contain the epidemic. The results depict a clear drop in the spreading speed of the traveling wave front after applying containment measures to at-risk populations.

Background: Dates palm (Phoenix dactylifera L.) fruits are among the most widely used fruits in the Middle East and African nations. Numerous researchers confirmed the presence of phytochemicals in P. dactylifera L. fruit and its by-products with broad-ranging biological activities.Objectives: In the present work, phytochemical and biological assessments of two different cultivars of date fruit (ShishiM1 and MajdoolM2 grown in the Ha’il region of Saudi Arabia) have been carried out.Methods: Date fruits were extracted and analyzed by gas chromatography-mass spectrometry (GS-MS),liquid chromatography-mass spectrometry (LC-MS) and Fourier-transform infrared spectroscopy (FT-IR)techniques. The lyophilized methanolic extracts were analyzed for their in-vitro antiproliferative andcytotoxicity against colon cancer (HCT116) cell line. To identify the possible constituents responsible for the bioactivity, in-silico molecular docking and molecular dynamics (MD) simulation studies were carried out.Results: Both cultivars exhibited in-vitro anticancer activity (IC50 = 591.3 μg/mL and 449.9 μg/mL for M1 and M2, respectively) against colon cancer HCT-116 cells. The computational analysis results indicated procyanidin B2 and luteolin-7-O-rutinoside as the active constituents.Conclusion: Based on these results, we conclude that these cultivars could be a valuable source for developing health promoter phytochemicals, leading to the development of the Ha’il region, Saudi Arabia.

The global significance of English law continues, particularly in Saudi as it is the most frequently chosen insurance policy law. Both jurisdictions provide consumer protections in insurance markets including the Consumer Insurance (Disclosure and) Act and the 2015 Insurance Act and the Insurance Consumer Protection Principles 2014 in Saudi Arabia. This study aims to analyse the current reform impact on the interpretation of these doctrines between the UK and Saudi jurisdictions. In the last few years British insurance law has been significantly reviewed and modified and the most recent amendments, as per the Insurance Act 2015, are of the greatest significance and will be given due consideration within this paper. However, both the rationale for the reforms and the reform process will be reviewed as well as the UK perspective of the increasing rivalries between countries on account of legal business.

Generally, the treated wastewater must at least achieve the minimum safety standards for the purpose of the treatment process. The main target of this work is the combination of the features of surfactants, nanoparticles, and silica gel in one system for Cu(II) removal from the aqueous solution. To achieve this goal, the attempt would be made by the fabrication of nanocomposite based on 4-amino-N-tetradecyl pyridinium bromide (C14) coated silver nanoparticles and silica gel. The fabricated nanocomposite (C14-Ag-SG) was characterized using different techniques such as FTIR, XRD, XRF, SEM, and TEM. We examined the adsorption of Cu(II) ions onto the fabricated nanocomposite using batch adsorption. The effect of the contact time, pH of the solution, and mass of the adsorbent on the efficiency of adsorption was evaluated. The adsorption capacity of Cu(II) increased by increasing of the contact time with a neutral pH. The maximum removal of Cu(II) ions (98.57 %) was found using 0.4 g of the (C14-Ag-SG) nanocomposite. The fabricated nanocomposite showed high adsorption efficiency which clarifies the effect of the surfactant compound (C14) and silver nanoparticles in improving the adsorption efficiency. The results in this work suggest that the fabricated nanocomposite has high efficiency in the removal of Cu(II).

The oxidation of chlorobenzene (CB) was studied by electrochemical electrolysis using boron-doped diamond (BDD), PbO2 or platine (Pt) as anode and graphite bar as cathode. The effect of applied current density, supporting electrolyte and initial pH value were also studied. The results demonstrated that BDD anode had the best effectiveness and accomplishment of electrochemical degradation of CB compared to PbO2 and Pt anodes. For a current density of 20 mA/cm2 and at pH = 3, the elimination of COD and TOC were about 97% and 98%, respectively, after 360 min of electrolysis with the BDD anode. Pseudo-first order kinetics appears to be the most appropriate to describe the degradation of chlorobenzene. The electrochemical mechanism of chlorobenzene on BDD was proposed based on the identified intermediates.

Trialkyl and triaryl phosphines are important classes of ligands in the field of catalysis and materials research. The wide usability of these low-valent phosphines has led to the design and development of new synthesis routes for a variety of phosphines. In the present work, we report the synthesis and characterization of some mixed arylalkyl tertiary phosphines via the Grignard approach. A new asymmetric phosphine is characterized extensively by multi-spectroscopic techniques. IR and UV–Vis spectra of some selected compounds are also compared and discussed. Density functional theory (DFT)-calculated results support the formation of the new compounds.

In this study, the influence of substrate temperature of the RF (Radio frequency) deposition system under a high vacuum on the characteristics of the deposited niobium oxide (Nb2O5) thin films was investigated. The X-Ray diffraction (XRD) measurements showed a polycrystalline orthorhombic structure for the pure Nb2O5 phase. The crystallinity was enhanced and the crystalline size was enlarged with the deposition temperature causing to a reduction in the lattice strain. The surface morphology investigated by scanning electron microscope (FE-SEM) shows the uniformity of the prepared thin films over the entire surface. Increasing the deposition temperature causes an increase in the oxidizing degree. The process might reduce the electron vacancies. The optical properties show that the band edges become sharper with an increase in the substrate temperature. The energy bandgap values increased with the deposition temperature. The response of the prepared gas sensor is highly affected by working temperature, particle size, surface roughness, and oxygen vacancies. The maximum sensitivity appeared at 250 °C working temperature is 118.2 against H2S gas for the sample prepared at room temperature (RT) at 160 W RF power. [ABSTRACT FROM AUTHOR]

In the current work, chloro(meso-tetrakis(phenyl)porphyrin) manganese(III) [Mn(TPP)Cl] was synthesized following two steps: the preparation of meso-tetraphenylporphyrin (H⁠2TPP) and the insertion of manganese into the free porphyrin H2TPP. The compounds were characterized using SEM, FT-IR, UV, TGA/DTA, and XRD analyses. Manganese(III) meso-porphyrins exhibited hyper-type electronic spectra with a half-vacant metal orbital with symmetry, such as [dπ:dxz and dyz]. The thermal behavior of [Mn(TPP)(Cl)] changed (three-step degradation process) compared to the initial H2TPP (one-step degradation process), confirming the insertion of manganese into the core of the free porphyrin H2TPP. Furthermore, [Mn(TPP)Cl] was used to degrade calmagite (an azo dye) using H2O2 as an oxidant. The effects of dye concentration, reaction time, H2O2 dose, and temperature were investigated. The azo dye solution was completely degraded in the presence of [Mn(TPP)(Cl)]/H2O2 at pH = 6, temperature = 20 °C, C0 = 30 mg/L, and H2O2 = 40 mL/L. The computed low activation energy (Ea = 10.55 Kj/mol) demonstrated the efficiency of the proposed catalytic system for the azo dye degradation. Overall, based on the synthesis process and the excellent catalytic results, the prepared [Mn(TPP)Cl] could be used as an effective catalyst for the treatment of calmagite-contaminated effluents. [ABSTRACT FROM AUTHOR]

Background: Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions. Methods: Human serum albumin (HSA) was glycated with 0.05 M α-D-glucose alone or in the presence of Zingiber officinale Roscoe (ginger) extract (0.781–100 μg/mL) for 10 weeks, and biochemical, biophysical, and computational analyses were carried out. Results: HSA glycated for 10 weeks (G-HSA-10W) resulted in significant production of ketoamines, carbonyl compounds, and AGE pentosidine. Notable structural alterations were observed in G-HSA-10W, ascertained by ultraviolet (UV), fluorescence, and circular dichroism (CD) studies. Antioxidant, anti-glycating, AGEs inhibitory, and antibacterial effects of ginger extracts were observed and attributed to the presence of various phytochemicals. Molecular docking studies suggested that the compounds 8-shagaol and gingerol exhibited strong and multiple interactions with HSA. Molecular simulation analysis suggests HSA attains a high degree of conformational stability with the compounds gingerol and 8-shogaol. Conclusions: These findings showed that ginger extract has an antioxidant function and can prevent glycation-induced biochemical and biophysical alterations in HSA. Thus, aqueous ginger extract can be utilized to combat glycation and AGE-related health issues, especially diabetes, neurological disorders, inflammatory diseases, etc. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative condition that leads to the gradual decline of neuronal cells. Despite significant interest and investment, complete prevention or treatment for AD and related dementia is still limited. The human acetylcholinesterase (hAChE) enzyme is a promising target for combating AD as it plays a crucial role in metabolising the neurotransmitter acetylcholine, which is essential for cognitive function and memory. The present study employed a multi-step approach, beginning with molecular docking to virtually screen 73 531 compounds from the PubChem library. Subsequently, we used Glide extra precision molecular docking to narrow down the list to three compounds (PubChem CID: 73058259, 141100002, and 44285707). The pharmacological and ADMET properties of the top three compounds were determined using multiple tools. The molecular dynamics (MD) simulation study at 500 ns revealed that all the ligands formed stable complexes with AChE. The trajectories of the ligands were stable, similar/better to the reference compound (donepezil), and identified compounds have drug-like features. This study presents the unique findings of structural and molecular features of new hAChE inhibitors and their dynamics, which have not been studied before. These insights could pave the way for developing more effective treatments for neurological conditions. [ABSTRACT FROM AUTHOR]