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Introduction: The main enzymes that hydrolyses nucleotides at the cell surface are nucleoside triphosphate diphosphohydrolases (NTPDases), ecto-nucleotide pyrophosphatases/phosphodiesterases (ENPPs), alkaline phosphatases (APs) and ecto-5'-nucleotidase (e5'NT, CD73) and by regulating the concentration of nucleotides at the cell surface, these enzymes have the potential to affect various conditions such as fibrosis, cancer metastasis, pruritus, inflammation, and autoimmune diseases. Thus, they represent a prospective therapeutic target., Area Covered: A number of molecules, including nucleoside/nucleotide and non-nucleoside analogues, and bicyclic compounds, have shown strong potential as ectonucleotidase inhibitors. This review covers the chemistry and clinical uses of ectonucleotidase inhibitors patented between 2017 and 2023., Expert Opinion: By binding to their specific P1 and P2 receptors at the cell surface, nucleosides and nucleotides regulate a number of pathophysiological events such as inflammation, fibrosis, cancer and autoimmune diseases. Interestingly, these nucleotides can be hydrolyzed to nucleosides by several cell surface enzymes named ectonucleotidases. The development of small molecules that modulate ectonucleotidase activity is, therefore, of therapeutic value. This review provides valuable insights into recent advancements, including combination therapy and enhanced selectivity, which are poised to shape the future of ectonucleotidase inhibition through a comprehensive analysis of patents.

Urease catalyzes the hydrolysis of urea, leading to an increase in stomach pH and supporting Helicobacter pylori survival, which is linked to several gastrointestinal disorders. In this study, thiazine-based Schiff bases were explored as promising urease inhibitors. Various spectroscopic techniques characterized the synthetic library of thiazine Schiff bases 2-36 and also evaluated for their inhibitory activities against urease. The derivatives demonstrated significant inhibitory potential with IC 50 values ranging from 0.14 ± 0.08 to 3.66 ± 0.21 μM, outperforming the standard inhibitor thiourea (IC 50  = 19.43 ± 0.18 μM). Structure-activity relationship (SAR) studies revealed that specific substitutions (type and positions) on the aryl ring significantly affect the inhibition potential. The most potent derivative, compound 7, possessed 2-methoxy-5-trifluoromethyl substitutions and exhibited an IC 50 of 0.14 ± 0.08 μM. Enzyme kinetics studies revealed that the most potent derivatives function as competitive inhibitors. Additionally, molecular docking studies provided insights into the binding interactions between the molecule and the urease active site, highlighting key residues involved in inhibitor binding. These findings highlight the therapeutic potential of thiazine-based Schiff bases as urease inhibitors and provide insights for the development of new anti-ulcer agents., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise. No writing assistance was utilized in the production of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A sustainable approach was proposed to address environmental pollution, carbon footprint and economic efficiency challenges in Electrical Discharge Machining (EDM). This approach involved the use of Bio-dielectric such as biodiesel and Bio fuel (distilled water with 10% ethanol). The EDM process performance was further optimized by experimenting with both electrodes' rotation (i.e., in same direction, opposite direction, no rotation) and the use of treated tools (no treatment, heat treatment, cryogenic treatment). Biodiesel as a bio-dielectric showed promise by delivering the highest Material Removal Rate (MRR) and the lowest Tool Wear Rate (TWR). Bio-fuel (distilled water with 10% ethanol) resulted in the lowest Surface Roughness (SR) and cleaner machined surface with least carbon deposition. Additionally, electrode rotation improved flushing and enhanced performance parameters, with opposite direction rotation yielding the highest MRR and the lowest SR. However, no rotation of electrodes resulted in the lowest TWR. The use of treated tools, specifically heat-treated and cryogenically treated tools, also improved performance and reduced energy consumption, with cryogenic treatment providing the highest MRR, heat treatment giving least SR, and no treatment providing least TWR. Certain interactions between factors significantly impacted performance parameters. Grey relational analysis revealed that using distilled water with 10% ethanol as a dielectric, employing cryogenically treated copper tools, and having no rotation of both electrodes yielded the best performance parameters., (© 2024. The Author(s).)

The pressing global issue of organic pollutants, particularly phenolic compounds derived primarily from industrial wastes, poses a significant threat to the environment. Although progress has been made in the development of low-cost materials for phenolic compound removal, their effectiveness remains limited. Thus, there is an urgent need for novel technologies to comprehensively address this issue. In this context, MXenes, known for their exceptional physicochemical properties, have emerged as highly promising candidates for the remediation of phenolic pollutants. This review aims to provide a comprehensive and critical evaluation of MXene-based technologies for the removal of phenolic pollutants, focusing on the following key aspects: (1) The classification and categorization of phenolic pollutants, highlighting their adverse environmental impacts, and emphasizing the crucial need for their removal. (2) An in-depth discussion on the synthesis methods and properties of MXene-based composites, emphasizing their suitability for environmental remediation. (3) A detailed analysis of MXene-based adsorption, catalysis, photocatalysis, and hybrid processes, showcasing current advancements in MXene modification and functionalization to enhance removal efficiency. (4) A thorough examination of the removal mechanisms and stability of MXene-based technologies, elucidating their operating conditions and stability in pollutant removal scenarios. (5) Finally, this review concludes by outlining future challenges and opportunities for MXene-based technologies in water treatment, facilitating their potential applications. This comprehensive review provides valuable insights and innovative ideas for the development of versatile MXene-based technologies tailored to combat water pollution effectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Existing healthcare systems are struggling to cope with the rapid increase in mental health diseases. Wearable devices such as smartwatches introduce a new opportunity in this regard. The realisation of this opportunity depends on the engagement of the community in sharing their lived experience data. A health data marketplace is introduced in this regard, where individuals can monetise their wearable device-derived lived experience data by selling it to consumers such as researchers, medical practitioners, and artificial intelligence service providers.

Introduction: The pandemic caused by SARS-CoV-2 significantly impacted human life around the globe. Numerous unexpected modifications of the SARS-CoV-2 genome have resulted in the emergence of new types and have caused great concern globally., Method: Inhibitory effects of bioactive phytochemicals derived from natural and synthetic sources are promising for pathogenic viruses. in vitro and in silico techniques were used in the current study to identify novel inhibitors of coumarin clubbed thiazolo[3,2-b][1,2,4]triazoles against the SARS-CoV-2 spike protein., Result: Interestingly, all the tested molecules demonstrated substantial inhibition of spike protein with 91.81-57.90% inhibition. The spike protein was remarkably inhibited by compounds 6k (91.83%), 6j (89.75%), 6m (87.69%),6i (86.60%), 6l (85.40%), 6h (84.70%), 6l (84.70%), 6g (83.40%), 6b (82.60%), 6f (81.90%), while compounds 6d 6a, 6c, and 6e exhibited significant activity against spike protein with 79.60%, 77.10%, 75.30%, and 57.90% inhibition, respectively. The binding mechanism of these novel inhibitors with spike protein was deduced in silico, which reflects that the active molecules firmly bind with the receptor binding domain (RBD) of spike protein, thereby inhibiting its function., Conclusion: The combined in vitro and in silico investigations unfold the therapeutic potential of coumarin-thiazolotriazole scaffolds in the treatment of SARS-CoV-2 infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

An estimated 2000 plant species have been employed for pest control worldwide. The use of these botanical derivatives is thought to be one of the most cost-effective and sustainable options for pest management in stored grain. The present study was designed to assess the efficacy of five plant extracts viz; Nicotiana tabacum L., Nicotiana rustica L., Azadirachta indica A. Juss., Thuja orientalis L., and Melia azedarach L. against Callosobruchus maculatus L. Plant species extracts were applied at six different concentrations, i.e., 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0% in four replications. The phytochemical analyses of ethanolic extracts of five plant species showed variable amounts of phytochemicals i.e., alkaloids, flavonoids, saponins, diterpenes, phytosterol, and phenols. Total phenolic and flavonoid compounds were also observed. The efficacy of A. indica was highest, characterized by the lowest infestation rate (16.65%), host seed weight loss (7.85%), mean oviposition (84.54), and adult emergence (58.40%). In contrast, T. orientalis was found to be the least effective against C. maculatus , with the highest infestation rate of 25.60%, host seed weight loss of 26.73%, mean oviposition of 117.17, and adult emergence rate of 82.01%. Probit analysis was performed by estimating LC 50 and LC 90 . The toxicity percentages of N. tabacum (LC 50 = 0.69%, LC 90 = 14.59%), N. rustica (LC 50 = 0.98%, LC 90 = 22.06%), and A. indica (LC 50 = 1.09%, LC 90 = 68.52%) were notable in terms of the lower LC 50 and LC 90 values after the 96-h exposure period against C. maculatus . Repellency was assessed by using the area preference and filter paper method. The repellency of C. maculatus on plant extracts increased with the increasing dose and time, such that it was the highest after 48 h. Likewise, at a 3% concentration, A. indica demonstrated 100.00% (Class-V) repellency followed by N. tabacum (96.00%, Class-V), N. rustica (74%, Class-IV), M. azedarach (70.00%, Class-IV), and T. orientalis (68.00%, Class-IV). Based on the findings of this study, we recommend integrating N. rustica , N. tabacum , A. indica , and M. azedarach for effective management of C. maculatus and highlight the potential of these plant species in the formulation of new biocidal agents.

Depletion of oil and gas resources is a major concern for researchers and the global community. Researchers are trying to develop a way to overcome these issues using the Fischer-Tropsch synthesis (FTS) process. The FTS reaction converts a mixture of hydrogen and carbon monoxide gases into a liquid fuel. The reactions are performed in the reactor and in the presence of a catalyst. A series of catalysts, such as iron, cobalt, nickel, and ruthenium, have been used for the FTS process. In iron-based catalysts, the Fe 5 C phase is the active phase that produces C 5+ hydrocarbons. At higher conversion rates, the presence of water in the products is a problem for cobalt catalysts because it can trigger catalyst deactivation mechanisms. Ni-based catalysts play key roles as base catalysts, promoters, and photothermal catalysts in FTS reactions to produce different useful hydrocarbons. Ruthenium catalysts offer not only high activity but also selectivity toward long-chain hydrocarbons. Moreover, depending on the Ru particle size and interaction with the oxide support, the catalyst properties can be tuned to enhance the catalytic activity during FTS. The detailed reaction pathways based on catalyst properties are explained in this article. This review article describes the issues and challenges associated with catalysts used for the FTS process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Amin, Usman, Kella, Khan, Khan and Hoon Lee.)

Silver nanoparticles (Ag NPs) have accumulated significant interest due to their exceptional physicochemical properties and remarkable applications in biomedicine, electronics, and catalysis sensing. This comprehensive review provides an in-depth study of synthetic approaches such as biological synthesis, chemical synthesis, and physical synthesis with a detailed overview of their sub-methodologies, highlighting advantages and disadvantages. Additionally, structural properties affected by synthesis methods are discussed in detail by examining the dimensions and surface morphology. The review explores the distinctive properties of Ag NPs, including optical, electrical, catalytic, and antimicrobial properties, which render them beneficial for a range of applications. Furthermore, this review describes the diverse applications in several fields, such as medicine, environmental science, electronics, and optoelectronics. However, with numerous applications, several kinds of issues still exist. Future attempts need to address difficulties regarding synthetic techniques, environmental friendliness, and affordability. In order to ensure the secure utilization of Ag NPs, it is necessary to establish sustainability in synthetic techniques and eco-friendly production methods. This review aims to give a comprehensive overview of the synthesis, structural analysis, properties, and multifaceted applications of Ag NPs.

In the area of flexible electronics, pressure sensors are a widely utilized variety of flexible electronics that are both indispensable and prevalent. The importance of pressure sensors in various fields is currently increasing, leading to the exploration of materials with unique structural and piezoelectric properties. Perovskite-based materials are ideal for use as flexible pressure sensors (FPSs) due to their flexibility, chemical composition, strain tolerance, high piezoelectric and piezoresistive properties, and potential integration with other technologies. This article presents a comprehensive study of perovskite-based materials used in FPSs and discusses their components, performance, and applications in detecting human movement, electronic skin, and wireless monitoring. This work also discusses challenges like material instability, durability, and toxicity, the limited widespread application due to environmental factors and toxicity concerns, and complex fabrication and future directions for perovskite-based FPSs, providing valuable insights for researchers in structural health monitoring, physical health monitoring, and industrial applications.

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment., (© 2024. The Author(s).)

In China, achieving financial agglomeration necessitates both the gathering of financial resources and the reduction of carbon emissions and the interrelation between these two goals is significant. In this research, sophisticated econometric models are applied to examine the correlation between financial agglomeration and per capita carbon emissions in China, such as spatial econometric, mixed OLS, and stationary panel models. The research sample is composed of data from 30 provinces and cities in China from 2010 to 2020 and examines both temporal and spatial distributions of these two factors and how they influence each other. The direct effect of financial agglomeration on carbon emission is analyzed through spatial panel model, while indirect effect is analyzed by examining the role of industrial structure upgrading as a mediating variable through mediating effect model. This study also looks at how these effects vary regionally, both directly and indirectly. Generally, the study discovered that financial agglomeration and per capita carbon emissions have significantly positive spatial autocorrelation coefficient in all provinces and cities in China, indicating path dependence and spatial spillover. In terms of distribution trends, financial agglomeration shows an upward trend over time, while per capita carbon emissions grew faster in the early stage, but gradually achieves a steady decrease in recent years. In terms of the impact of financial agglomeration on carbon emissions, the relationship between financial agglomeration and per capita carbon emissions is in the form of "inverted U-shaped." Financial agglomeration indirectly influences the intensity of per capita carbon emissions through the advanced industrial structure, which acts as a mediator. In the test of industrial structure serving as a mediating variable, different regions exhibit different impacts due to regional heterogeneity, with a clear distinction between the central region and the eastern and western regions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Hyperlipidemia is the major cardiovascular morbidity and mortality risk factor. Statins are the first-line treatment for hyperlipidemia. Statin-associated muscle symptoms (SAMS) are the main reason for the discontinuation of statins among patients. The purpose of this review is to guide clinicians to recognize the difference between self-limited and autoimmune statin myopathy in addition to the factors that potentiate them. Finally, treatment strategies will be discussed. This review mostly focuses on new data in the past 3 years., Recent Findings: Recent findings suggest that SAMS is a complex and multifactorial condition that involves mitochondrial dysfunction, oxidative stress, and immune-mediated mechanisms. Effective management of SAMS requires a thorough evaluation of the patient's symptoms, risk factors, and medication history, as well as consideration of alternative treatment options. While statins are effective in reducing the risk of cardiovascular events, their use is associated with a range of adverse effects, including SAMS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A series of sulfonate and sulfamate derivatives bearing benzofuran or benzothiophene scaffold exhibited potent inhibitory effect on urease enzyme. Most of the derivatives exhibited significantly higher potency than thiourea, the standard inhibitor. Compound 1s was identified as the most potent urease inhibitor with an IC 50 value of 0.42 ± 0.08 μM, which is 53-fold more potent than thiourea, positive control (IC 50  = 22.3 ± 0.031 μM). The docking results further revealed the binding interactions towards the urease active site. Phenotypic screening revealed that compounds 1c, 1d, 1e, 1f, 1j, 1n, and 1t exhibit high potency against H. pylori with MIC values ranging from 0.00625 to 0.05 mM and IC 50 values ranging from 0.0031 to 0.0095 mM, much more potent than the positive control, acetohydroxamic acid (MIC and IC 50 values were 12.5 and 7.38 mM, respectively). Additional studies were performed to investigate the toxicity of these compounds against the gastric epithelial cell line (AGS) and their selectivity profile against E. coli, and five Lactobacillus species representative of the gut microflora. Permeability characteristics of the most promising derivatives were investigated in Caco-2 cell line. The results indicate that the compounds could be targeted in the GIT only without systemic side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neurodegenerative diseases with progressive cellular loss of the central nervous system and elusive disease etiology provide a continuous impetus to explore drug discovery programmes aiming at identifying robust and effective inhibitors of cholinesterase and monoamine oxidase enzymes. We herein present a concise library of anthranilamide derivatives involving a palladium-catalyzed Suzuki-Miyaura cross-coupling reaction to install the diverse structural diversity required for the desired biological action. Using Ellman's method, cholinesterase inhibitory activity was performed against AChE and BuChE enzymes. In vitro assay results demonstrated that anthranilamides are potent inhibitors with remarkable potency. Compound 6k emerged as the lead candidate and dual inhibitor of both enzymes with IC 50 values of 0.12 ± 0.01 and 0.49 ± 0.02 μM against AChE and BuChE, respectively. Several other compounds were found as highly potent and selective inhibitors. Anthranilamide derivatives were also tested against monoamine oxidase (A and B) enzymes using fluorometric method. In vitro data revealed compound 6h as the most potent inhibitor against MAO-A, showing an IC 50 value of 0.44 ± 0.02 μM, whereas, compound 6k emerged as the top inhibitor of MAO-B with an IC 50 value of 0.06 ± 0.01 μM. All the lead inhibitors were analyzed for the identification of their mechanism of action using Michaelis-Menten kinetics experiments. Compound 6k and 6h depicted a competitive mode of action against AChE and MAO-A, whereas, a non-competitive and mixed-type of inhibition was observed against BuChE and MAO-B by compounds 6k. Molecular docking analysis revealed remarkable binding affinities of the potent inhibitors with specific residues inside the active site of receptors. Furthermore, molecular dynamics simulations were performed to explore the ability of potent compounds to form energetically stable complexes with the target protein. Finally, in silico ADME calculations also demonstrated that the potent compounds exhibit promising pharmacokinetic profile, satisfying the essential criteria for drug-likeness. Altogether, the findings reported in the current work clearly suggest that the identified anthranilamide derivatives have the potential to serve as effective drug candidates for future investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An important component of the pathogenicity of potentially pathogenic bacteria in humans is the urease enzyme. In order to avoid the detrimental impact of ureolytic bacterial infections, the inhibition of urease enzyme appears to be an appealing approach. Therefore, in the current study, morpholine-thiophene hybrid thiosemicarbazone derivatives ( 5a-i ) were designed, synthesized and characterized through FTIR, 1 H NMR, 13 C NMR spectroscopy and mass spectrometry. A range of substituents including electron-rich, electron-deficient and inductively electron-withdrawing groups on the thiophene ring was successfully tolerated. The synthesized derivatives were evaluated in vitro for their potential to inhibit urease enzyme using the indophenol method. The majority of compounds were noticeably more potent than the conventional inhibitor, thiourea. The lead inhibitor, 2-(1-(5-chlorothiophen-2-yl)ethylidene)- N -(2-morpholinoethyl)hydrazinecarbothioamide ( 5g ) inhibited the urease in an uncompetitive manner with an IC 50 value of 3.80 ± 1.9 µM. The findings of the docking studies demonstrated that compound 5g has a strong affinity for the urease active site. Significant docking scores and efficient binding free energies were displayed by the lead inhibitor. Finally, the ADME properties of lead inhibitor ( 5g ) suggested the druglikeness behavior with zero violation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Munir, Zaib, Zia-ur-Rehman, Javed, Roohi, Zaheer, Fatima, Bhat and Khan.)

Strokes are a leading global cause of mortality, underscoring the need for early detection and prevention strategies. However, addressing hidden risk factors and achieving accurate prediction become particularly challenging in the presence of imbalanced and missing data. This study encompasses three imputation techniques to deal with missing data. To tackle data imbalance, it employs the synthetic minority oversampling technique (SMOTE). The study initiates with a baseline model and subsequently employs an extensive range of advanced models. This study thoroughly evaluates the performance of these models by employing k-fold cross-validation on various imbalanced and balanced datasets. The findings reveal that age, body mass index (BMI), average glucose level, heart disease, hypertension, and marital status are the most influential features in predicting strokes. Furthermore, a Dense Stacking Ensemble (DSE) model is built upon previous advanced models after fine-tuning, with the best-performing model as a meta-classifier. The DSE model demonstrated over 96% accuracy across diverse datasets, with an AUC score of 83.94% on imbalanced imputed dataset and 98.92% on balanced one. This research underscores the remarkable performance of the DSE model, compared to the previous research on the same dataset. It highlights the model's potential for early stroke detection to improve patient outcomes., (© 2024. The Author(s).)

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α -glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α -glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α -glucosidase than the standard drug, acarbose (IC 50 = 35.1 ± 0.14  µ M), with IC 50 values ranging from 1.13 to 28.27  µ M. However, compound 5a displayed the highest anti-diabetic activity (IC 50 = 1.13 ± 0.06  µ M). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds ( 5a and 5b ), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC 50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ahmed, Zaib, Bhat, Saeed, Altaf, Zahra, Shabir, Rana and Khan.)

Introduction: The purinergic P2X7 receptor (P2X7R) is expressed on the surface of many different types of cells, including immune cells. Targeting P2X7R with antagonists has been studied for its potential therapeutic effects in a variety of inflammatory illnesses., Area Covered: Many chemical substances, including carboxamides, benzamides and nitrogen containing heterocyclic derivatives have demonstrated promising inhibitory potential for P2X7 receptor. The chemistry and clinical applications of P2X7R antagonists patented from 2018- present are discussed in this review., Expert Opinion: Purinergic receptor inhibitor discovery and application has demonstrated the potential for therapeutic intervention, as demonstrated by pharmacological research. Few chemical modalities have been authorized for use in clinical settings, despite the fact that breakthroughs in crystallography and chemical biology have increased the knowledge of purinergic signaling and its consequences in disease. The many research projects and pharmaceutical movements that sustain dynamic P2X receptor programs over decades are evidence of the therapeutic values and academic persistence in purinergic study. P2X7R is an intriguing therapeutic target and possible biomarker for inflammation. Although several companies like Merck and AstraZeneca have published patents on P2X3 antagonists, the search for P2X7R antagonists has not stopped. Numerous pharmaceutical companies have disclosed different scaffolds, and some molecules are presently being studied in clinical studies.

In the present work, 2-imino-1,3-thiazolines featuring highly fluorinated fragments were synthesized through a straightforward cyclization of diversely substituted thioureas with 2-bromo-1-(4-fluorophenyl)ethan-1-one. The target compounds were obtained in good yields, and structures were established by FTIR and 1 H- and 13 C NMR spectroscopic methods. The in vitro biological assay revealed that all the compounds significantly obstruct the α-glucosidase. Compound 6d (3-fluoro- N -(3-(2-fluorophenyl)-4-(4-fluorophenyl)thiazol-2(3 H )-ylidene)benzamide) showed the highest antidiabetic potential with an IC 50 value of 1.47 ± 0.05 μM. In addition, computational analysis revealed the binding energy of -11.1 kcal/mol for 6d which was lower than the positive standard, acarbose (-7.9 kcal/mol). Several intermolecular interactions between the active site residues and 6d highlight the significance of 2-imino-1,3-thiazoline core in attaining the potent efficacy and making these compounds a valuable pharmacophore in drug discovery., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In this study, the optimization of potassium carbonate (K 2 CO 3 ) exposure conditions for CO 2 capture with the use of 2-methypiperazine (2MPz) and monoethanolamine (MEA) as promoters was investigated. The tested operating conditions for the CO 2 capture process included the pH, temperature, K 2 CO 3 dose, gas flow rate, and pressure, and their effect on the CO 2 absorption/desorption rate and CO 2 absorption efficiency was assessed. Response surface methodology (RSM) was also employed to determine the equations for the optimal long-term operating conditions. The results showed that the CO 2 absorption rate and efficiency increased under K 2 CO 3 exposure with an increase in the pressure and loading rate. Moreover, for the temperature the absorption efficiency first increase and then decreases with increase in temperature, however, the with increase in temperature the faster absorption were observed with lower absorption loading rate. Furthermore, pH had a more complex effect due to its variable effects on the speciation of bicarbonate ions (HCO 3 - ) and carbonate ions (CO 3 2- ). Under higher pH conditions, there was an increase in the concentration of HCO 3 - , which has a higher CO 2 loading capacity than CO 3 2- . Contouring maps were also used to visualize the effect of different exposure conditions on the CO 2 absorption rate and efficiency and the role of 2MPz and MEA as promoters in the K 2 CO 3 solution for CO 2 absorption. The results showed that the mean CO 2 absorption rate was 6.76 × 10 -4  M/L/s with an R 2 of 0.9693 for the K 2 CO 3 solution containing 2MPz. The highest absorption rate (6.56-7.20 × 10 -4  M/L/s) was observed at a temperature of 298-313 K, a pressure of >2 bar, a pH of 8-9, and a loading rate of 80-120 L/h for a concentration of 1-3 M K 2 CO 3 and 0.05-1.5 M 2MPz. The CO 2 absorption efficiency exhibited a variation of 56-70% under the same conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl 4 )-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl 4 ), third group, silymarin (20 mg/kg of body weight), fourth group (CCl 4 +chicory) (1.75 mg/kg of b. wt), fifth group (CCl 4 + chicory at the dose of 2.35 mg/kg), sixth group (CCl 4 + chicory of 3.25 mg/kg), seventh group (CCl 4 +AgNPs 1.75 mg/kg of b. wt.), eighth group (CCl 4 + AgNPs 2.35 mg/kg of body weight), and ninth group (CCl 4 + AgNPs 3.25 mg/kg of b. wt.). Blood samples were taken 24 h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase) , ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25 mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl 4 -intoxicated rats. Histology of the liver sections from CCl 4 -treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Siddiqa, Qureshi, Raja, Khan, Ahmad, Rafique, Ali, Ahmad and Kaushik.)

Dwarfism is a medical term used to describe individuals with a height-vertex measurement that falls below two standard deviations (-2SD) or the third percentile for their gender and age. Normal development of growth is a complicated dynamic procedure that depends upon the coordination of different aspects involving diet, genetics, and biological aspects like hormones in equilibrium. Any severe or acute pathologic procedure may disturb the individual's normal rate of growth. In this research, we examined four (A-D) Pakistani consanguineous families that exhibited syndromic dwarfism, which was inherited in an autosomal recessive pattern. The genomic DNA of each family member was extracted by using phenol-chloroform and Kit methods. Whole Exome Sequencing (WES) of affected family members (IV-11, III-5, IV-4 and III-13) from each group was performed at the Department of Medical Genetics, University of Antwerp, Belgium. After filtering the exome data, the mutations in PPM1F, FGFR3, ERCC2, and PCNT genes were determined by Sanger sequencing of each gene by using specific primers. Afterward, FGFR3 was found to be a suitable drug target among all the mutations to treat achondroplasia also known as disproportionate dwarfism. BioSolveIT softwares were used to discover the lead active inhibitory molecule against FGFR3 . This research will not only provide short knowledge to the concerned pediatricians, researchers, and family physicians for the preliminary assessment and management of the disorder but also provide a lead inhibitor for the treatment of disproportionate dwarfism.Communicated by Ramaswamy H. Sarma.

Diabetes mellitus, one of the major health challenges of the 21st century, is associated with numerous biomedical complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases and liver disorders. To control the chronic hyperglycemic condition, the development of potential inhibitors of drug targets such as α-glucosidase and α-amylase remains a promising strategy and focus of continuous efforts. Therefore, in the present work, a concise library of isobenzofuranone derivatives (3a-q) was designed and synthesized using Suzuki-Miyaura cross-coupling approach. The biological potential of these heterocyclic compounds against carbohydrate-hydrolyzing enzymes; α-glucosidase and α-amylase, was examined. In vitro inhibitory results demonstrated that the tested isobenzofuranones were considerably more effective and potent inhibitors than the standard drug, acarbose. Compound 3d having an IC 50 value of 6.82 ± 0.02 μM was emerged as the lead candidate against α-glucosidase with ⁓127-folds strong inhibition than acarbose. Similarly, compound 3g demonstrated ⁓11-folds higher inhibition strength against α-amylase when compared with acarbose. Both compounds were tested in vivo and results demonstrate that the treatment of diabetic rats with α-amylase inhibitor show more pronounced histopathological normalization in kidney and liver than with α-glucosidase inhibitor. The Lineweaver-Burk plot revealed an uncompetitive mode of inhibition for 3d against α-glucosidase whereas compound 3g exhibited mixed inhibition against α-amylase. Furthermore, in silico molecular docking and dynamics simulations validated the in vitro data for these compounds whereas pharmacokinetics profile revealed the druglike properties of potent inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ovarian cancer is the fifth leading cause of mortality and the most lethal gynecologic malignancy among females. It may arise from atypical borderline tumors (Type I) or serous tubal intraepithelial carcinoma (Type II). The diagnosis of cancer at its early stages is difficult because of non-specific symptoms, most patients are diagnosed at the advanced stage. Several drugs and therapeutic strategies are available to treat ovarian cancer such as surgery, chemotherapy, neoadjuvant therapy, and maintenance therapy. However, the cancer cells have developed resistance to a number of available therapies causing treatment failure. This emerging chemoresistance in ovarian cancer cells is becoming an obstacle due to alterations in multiple cellular processes. These processes involve altered drug target response, drug pumps, detoxification systems, lower sensitivity to apoptosis, and altered proliferation, and are responsible for developing resistance to anticancer medicines. Various research reports have evidenced that these altered processes might play a role in the emergence of resistance. This review addresses the recent advances in understanding the underlying mechanisms of ovarian cancer resistance and covers sophisticated alternative pathways to overcome these resistance mechanisms in patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Probiotics are living microorganisms that are present in cultured milk and fermented food. Fermented foods are a rich source for the isolation of probiotics. They are known as good bacteria. They have various beneficial effects on human health including antihypertensive effects, antihypercholesterolemic effects, prevention of bowel disease, and improving the immune system. Microorganisms including bacteria, yeast, and mold are used as probiotics but the major microorganisms that are used as probiotics are bacteria from the genus Lactobacillus, Lactococcus, Streptococcus , and Bifidobacterium . Probiotics are beneficial in the prevention of harmful effects. Recently, the use of probiotics for the treatment of various oral and skin diseases has also gained significant attention. Clinical studies indicate that the usage of probiotics can alter gut microbiota composition and provoke immune modulation in a host. Due to their various health benefits, probiotics are attaining more interest as a substitute for antibiotics or anti-inflammatory drugs leading to the growth of the probiotic market., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 μg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purinergic signaling is a mechanism in which extracellular purines and pyrimidines interact with specialized cell surface receptors known as purinergic receptors. These receptors are divided into two families of P1 and P2 receptors, each responding to different nucleosides and nucleotides. P1 receptors are activated by adenosine, while P2 receptors are activated by pyrimidine and purines. P2X receptors are ligand-gated ion channels, including seven subunits (P2X1-7). However, P2Y receptors are the G-protein coupled receptors comprising eight subtypes (P2Y1/2/4/6/11/12/13/14). The disorder in purinergic signaling leads to various health-related issues and diseases. In various aspects, it influences the activity of non-neuronal cells and neurons. The molecular mechanism of purinergic signaling provides insight into treating various human diseases. On the contrary, stem cells have been investigated for therapeutic applications. Purinergic signaling has shown promising effect in stem cell engraftment. The immune system promotes the autocrine and paracrine mechanisms and releases the significant factors essential for successful stem cell therapy. Each subtype of purinergic receptor exerts a beneficial effect on the damaged tissue. The most common effect caused by purinergic signaling is the proliferation and differentiation that treat different health-related conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The coronavirus, a subfamily of the coronavirinae family, is an RNA virus with over 40 variations that can infect humans, non-human mammals and birds. There are seven types of human coronaviruses, including SARS-CoV-2, is responsible for the recent COVID-19 pandemic. The current study is focused on the identification of drug molecules for the treatment of COVID-19 by targeting human proteases like transmembrane serine protease 2 (TMPRSS2), furin, cathepsin B, and a nuclear receptor named farnesoid X receptor (FXR). TMPRSS2 and furin help in cleaving the spike protein of the SARS-CoV-2 virus, while cathepsin B plays a critical role in the entry and pathogenesis. FXR, on the other hand, regulates the expression of ACE2, and its inhibition can reduce SARS-CoV-2 infection. By inhibiting these four protein targets with non-toxic inhibitors, the entry of the infectious agent into host cells and its pathogenesis can be obstructed. We have used the BioSolveIT suite for pharmacophore-based computational drug designing. A total of 1611 ligands from the ligand library were docked with the target proteins to obtain potent inhibitors on the basis of pharmacophore. Following the ADMET analysis and protein ligand interactions, potent and druggable inhibitors of the target proteins were obtained. Additionally, toxic substructures and the less toxic route of administration of the most potent inhibitors in rodents were also determined computationally. Compounds namely N-(diaminomethylene)-2-((3-((1R,3R)-3-(2-(methoxy(methyl)amino)-2-oxoethyl)cyclopentyl)propyl)amino)-2-oxoethan-1-aminium (26), (1R,3R)-3-(((2-ammonioethyl)ammonio)methyl)-1-((4-propyl-1H-imidazol-2-yl)methyl)piperidin-1-ium (29) and (1R,3R)-3-(((2-ammonioethyl)ammonio)methyl)-1-((1-propyl-1H-pyrazol-4-yl)methyl)piperidin-1-ium (30) were found as the potent inhibitors of TMPRSS2, whereas, 1-(1-(1-(1H-tetrazol-1-yl)cyclopropane-1‑carbonyl)piperidin-4-yl)azepan-2-one (6), (2R)-4-methyl-1-oxo-1-((7R,11S)-4-oxo-6,7,8,9,10,11-hexahydro-4H-7,11-methanopyrido[1,2-a]azocin-9-yl)pentan-2-aminium (12), 4-((1-(3-(3,5-dimethylisoxazol-4-yl)propanoyl)piperidin-4-yl)methyl)morpholin-4-ium (13), 1-(4,6-dimethylpyrimidin-2-yl)-N-(3-oxocyclohex-1-en-1-yl)piperidine-4-carboxamide (14), 1-(4-(1,5-dimethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(3,5-dimethylisoxazol-4-yl)propan-1-one (25) and N,N-dimethyl-4-oxo-4-((1S,5R)-8-oxo-5,6-dihydro-1H-1,5-methanopyrido[1,2-a][1,5]diazocin-3(2H,4H,8H)-yl)butanamide (31) inhibited the FXR preferentially. In case of cathepsin B, N-((5-benzoylthiophen-2-yl)methyl)-2-hydrazineyl-2-oxoacetamide (2) and N-([2,2'-bifuran]-5-ylmethyl)-2-hydrazineyl-2-oxoacetamide (7) were identified as the most druggable inhibitors whereas 1-amino-2,7-diethyl-3,8-dioxo-6-(p-tolyl)-2,3,7,8-tetrahydro-2,7-naphthyridine-4‑carbonitrile (5) and (R)-6-amino-2-(2,3-dihydroxypropyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (20) were active against furin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The hyperactivity of urease enzyme leads to various complications including gastritis and peptic ulcer. A diverse variety of natural and synthetic inhibitors have shown a tremendous potential to inhibit the urease enzyme, thus decreasing the hyperactivity and reducing the risk for the development of urinary calculi and other similar problems. Therefore, we herein report a family of fused heterocycles such as triazolothiadiazoles ( 4a - h , 5a - f ) and triazolothiadiazines ( 6a - h ) as potential antiurease agents with IC 50 values in the range 10.41-41.20 µM. Several compounds were identified as potential lead candidates. Among them, compounds 4e and 4f from triazolothiadiazole series showed the highest inhibitory potential with IC 50 values of 11.62 ± 0.34 and 10.35 ± 0.14 µM), respectively, whereas 6e from triazolothiadiazine series emerged as the most potent inhibitor with an IC 50 value of 10.41 ± 0.13 µM. These compounds exhibited two-fold strong inhibitory efficacy against urease as compared to standard inhibitor, thiourea (IC 50 = 22.48 ± 0.67 µM). The mechanistic insights from kinetics experiments for compounds 4e , 4f , and 6e revealed the competitive mode of inhibition with K i values of 8.65 ± 0.004, 7.04 ± 0.012, and 8.31 ± 0.007 µM, respectively. The in vitro results were further explored through in silico computational docking analysis which reflects that binding of ligands with Ni ions and His492 play a crucial role in urease inhibition. In silico predicted physicochemical properties and ADME profile reflect drug-like nature of these molecules.Communicated by Ramaswamy H. Sarma.

Yellow fever is a flavivirus having plus-sensed RNA which encodes a single polyprotein. Host proteases cut this polyprotein into seven nonstructural proteins including a vital NS3 protein. The present study aims to identify the most effective inhibitor against the helicase (NS3) using different advanced ligand and structure-based computational studies. A set of 300 ligands was selected against helicase by chemical structural similarity model, which are similar to S -adenosyl-l-cysteine using infiniSee. This tool screens billions of compounds through a similarity search from in-built chemical spaces (CHEMriya, Galaxi, KnowledgeSpace and REALSpace). The pharmacophore was designed from ligands in the library that showed same features. According to the sequence of ligands, six compounds ( 29 , 87 , 99 , 116 , 148 , and 208 ) were taken for pharmacophore designing against helicase protein. Subsequently, compounds from the library which showed the best pharmacophore shared-features were docked using FlexX functionality of SeeSAR and their optibrium properties were analyzed. Afterward, their ADME was improved by replacing the unfavorable fragments, which resulted in the generation of new compounds. The selected best compounds ( 301 , 302 , 303 and 304 ) were docked using SeeSAR and their pharmacokinetics and toxicological properties were evaluated using SwissADME. The optimal inhibitor for yellow fever helicase was 2-amino- N -(4-(dimethylamino)thiazol-2-yl)-4-methyloxazole-5-carboxamide ( 302 ), which exhibits promising potential for drug development.Communicated by Ramaswamy H. Sarma.

Introduction: Cancer contributes to a high mortality rate worldwide spanning its diversity from genetics to resistant therapeutic response. To date emerging strategies to combat and manage cancer are particularly focused on the development of targeted therapies as conventional treatments account for the destruction of normal cells as well. In this regard, medicinal plant-based therapies are quite promising in imposing minimal side effects; however, limitations like poor bioavailability and stability of bioactive phytochemicals are associated with them. In parallel, nanotechnology provides nominal solution to deliver particular therapeutic agent without compromising its stability. Methods: In this study, Solanum nigrum , an effective medicinal plant, loaded arabinoxylan cross-linked β-cyclodextrin nanosponges (SN-AXCDNS) were designed to evaluate antitumor activity against breast cancer. Therefore, SN-AXCDNS were prepared by using cross-linker melt method and characterized by physicochemical and pharmacological parameters. Results: Hydrodynamic size, zeta potential and entrapment efficiency (EE%) were estimated as 226 ± 4 nm, -29.15 ± 5.71 mV and 93%, respectively. Surface morphology of nanocomposites showed spherical, smooth, and porous form. Antitumor pharmacological characterization showed that SN loaded nanosponge demonstrated higher cytotoxicity (22.67 ± 6.11 μg/mL), by inducing DNA damage as compared to void SN extract. Flow cytometry analysis reported that encapsulated extract promoted cell cycle arrest at sub-G1 (9.51%). Moreover, in vivo analysis demonstrates the reduction in tumor weight and 85% survival chances in nanosponge treated mice featuring its effectiveness. In addition, in silico analysis revealed that β-cyclodextrin potentially inhibits MELK in breast cancer cell lines (B.E = -10.1 Kcal/mol). Conclusion: Therefore, findings of current study elucidated the therapeutic potential of β-cyclodextrin based nanosponges to be an alternative approach regarding the delivery and solubilization of antitumor drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Shah, Zaib, Khan, Sliem, Alharbi, Al-Ghorbani, Jawad, Shahzadi and Awan.)

The identification of effective and druggable cholinesterase inhibitors to treat progressive neurodegenerative Alzheimer's disorder remains a continuous drug discovery hunt. In this perspective, the present study investigates the design and discovery of pyrimidine-morpholine hybrids (5a-l) as potent cholinesterase inhibitors. Palladium-catalyzed Suzuki-Miyaura cross-coupling reaction was employed to introduce the structural diversity on the pyrimidine heterocyclic core. A range of commercially available boronic acids was successfully coupled showing a high functional group tolerance. In vitro cholinesterase inhibitory potential using Ellman's method revealed significantly strong potency. Compound 5h bearing a meta-tolyl substituent at 2-position of pyrimidine ring emerged as a lead candidate against AChE with an inhibitory potency of 0.43 ± 0.42 µM, ∼38-fold stronger value than neostigmine (IC 50  = 16.3 ± 1.12 µM). Compound 5h also showed the lead inhibition against BuChE with an IC 50 value of 2.5 ± 0.04 µM. The kinetics analysis of 5h revealed the non-competitive mode of inhibition against AChE whereas computational modelling results of potent leads depicted diverse contacts with the binding site amino acid residues. Molecular dynamics simulations revealed the stability of biomolecular system, while, ADME analysis demonstrated druglikeness behaviour of potent compounds. Overall, the investigated pyrimidine-morpholine scaffold presented a remarkable potential to be developed as efficacious anti-Alzheimer's drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hydrogen production via chemical looping steam methane reforming (CL-SMR) is among the most promising current technologies. This work presents the development in gPROMS Model Builder 4.1.0 ® of a 1D model of an adiabatic packed bed reactor used for chemical looping reforming (CLR). The catalyst used for this process was 18 wt. % NiO with the support of Al 2 O 3 . A brief thermodynamic analysis using Chemical Equilibrium Application (CEA) was carried out to identify the optimum operating conditions. The model was simulated for 10 complete CL-SMR cycles. The effects of variations in temperature, pressure, gas mass velocity, nickel oxide concentration, reactor length, and particle diameter were studied to investigate the performance of the CL-SMR process under these variations. A parametric analysis was carried out for different ranges of conditions: temperatures from 600 to 1,000 K, pressure from 1 to 5 bar, gas mass velocity between 0.5 and 0.9 kg·m -2 s -1 , nickel oxide concentration values between 0.1 and 1 mol·m -3 , particle diameters between 0.7 and 1 mm, and fuel reactor (FR) lengths between 0.5 and 1.5 m. At the optimum temperature (950 K), pressure (1 bar), and steam-to-carbon molar ratio (3/1), with an increase in particle diameter from 0.7 to 1 mm, an 18% decrease in methane conversion and a 9.5% increase in hydrogen yield were observed. Similarly, with an increase in FR length from 0.5 m to 1.5 m, a delay in the temperature drop was observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qayyum, Cheema, Abdullah, Amin, Khan, Lee and Lee.)

Industrial wastewater irrigation of agricultural crops can cause a lot of environmental and health problems in developing countries due to heavy metals deposition in agricultural soils as well as edible plant consumption by human beings. Therefore, this study was conducted to find out the heavy metals concentration in industrial wastewater and soil irrigated with that wastewater. In addition, the aim was to determine the impact of industrial wastewater irrigation on Parthenium hysterophorus and Zea mays genes involved in growth improvement and inhibition. For this purpose, plant samples from agriculture fields irrigated with wastewater from Hattar Industrial Estate (HIE) of Haripur, Pakistan, and control plants from non-contaminated soil irrigated with tape water were collected after 15 and 45 days of germination. Heavy metals concentration in the collected plant samples, wastewater, and soil was determined. The results revealed that the soil of the sample collection site was predominantly contaminated with Cr, Pb, Ni, Cu, Co, Zn, and Cd up to the concentrations of 38.98, 21.14, 46.01, 155.73, 12.50, 68.50, and 7.01 mg/kg, respectively. The concentrations of these heavy metals were found to surpass the permissible limit in normal agricultural soil. Expansins, cystatins (plant growth enhancers), and metacaspases (plant growth inhibitor) gene expression were studied through reverse transcription polymerase chain reaction. The results showed that the expression of these genes was higher in samples collected from wastewater-irrigated soils as compared to control. The expression of these genes was observed in 45 days old samples, 15 days old samples, and control. Taken together, this study suggests the use of Parthenium and maize for phytoremediation and that they should not be used for eating purposes if irrigated with industrial wastewater., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Low-pressure membrane (LPM) filtration, including microfiltration (MF) and ultrafiltration (UF), is a promising technology for the treatment of surface water for drinking and other purposes. Various configurations and operational sequences have been developed to ensure the sustainable provision of clean water by overcoming fouling problems. In the literature, various periodic physical and/or chemical approaches to the cleaning of LPMs have been reported, but little data is available on the aging of MF/UF membranes that results from the interaction between the foulants and the cleaning agent. Periodic physical cleaning of the membrane is expected to return the membrane to its original performance capacity, but it only recovers to a certain level because the remaining foulants cause irreversible fouling. Chemical cleaning can then be employed to recover the membrane from this irreversible fouling but, in the process, it can cause irrecoverable damage to the membrane. In this review, the foulants responsible for irrecoverable damage to MF/UF membranes are summarized, and their interaction with cleaning agents and other foulants is described. The impact of these foulants on various membrane parameters, including filtration efficiency, flux decline, permeability, membrane characterization, and membrane integrity are also summarized and discussed in detail. In addition, mitigation options and future prospects are also discussed with regard to increasing the operational life span of a membrane in a cost-effective manner. Ultimately, this review suggests an advanced control system based on membrane-foulant interactions under the impact of various operational parameters to mitigate the integrity loss of membranes., Competing Interests: Declaration of competing interest Role of foulants in the aging and deterioration of low-pressure membranes 2 during the chemical cleaning process in surface water treatment: A review Imtiaz Afzal Khan, Jong Oh Kim* Department of Civil and Environmental Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The goal of this study was to elucidate the interaction of complex feed solutions under modified membrane fouling models for constant flux operation. The polyvinylidene fluoride membrane (PVDF) was tested for three types of solutions containing inorganic foulants (Al, Mn, and Fe), organic foulants, and suspended solids at 0.5 mM Ca 2+ ionic strength. The membrane's performance was evaluated by measuring the increase in transmembrane pressure (TMP) during two different filtration scenarios: continuous filtration lasting 1 h and cyclic filtration lasting 12 min, with 3 min backwashing cycles included. Statistical analysis (linear regression results (R 2 ), p -value) was used to verify the fouling model propagation along with the determination of the contributing constant of each fouling model. An increasing TMP percentage of 164-302%, 155-300%, and 208-378% for S1 (HA + Ca 2+ ), S2 (inorganics + kaolin + Ca 2+ ), and S3 (HA + inorganics + kaolin + Ca 2+ ) was recorded for 1 h filtration, respectively. Furthermore, a five percent increase in irreversible resistance was noted for the S3 solution due to the strong adsorption potential of foulants for the PVDF membrane caused by the electrostatic and hydration forces of foulants. In addition to that, the participation equation elucidated the contribution of the fouling model and confirmed that complete blocking and cake layer contribution were dominant for the S1 and S3 solutions, while standard blocking was dominant for the S2 solution with a high significance ratio. Moreover, R 2 and cyclic filtration analysis also confirmed the propagation of these fouling models. The statistical confirmation and regression results analysis of the modified model gave comparative results and satisfied the filtration mechanism and can be used for the constant flux dead filtration analysis of water treatment.

Heterogeneous growth of photocatalysts on different porous substrates is a solution to avoid secondary pollution caused by composite photocatalysts themselves. However, the heterogeneous growth of composite photocatalysts with nitrogen-doped carbon quantum dots (NCQDs) inclusions-introduced during synthesis-impedes the direct growth on the substrate. To overcome this problem, NCQDs were grown on a Co 9 S 8 (NCQDs-G@Co 9 S 8 ) layer, decorated on cotton fabric. This optimal coupling mode of NCQDs and Co 9 S 8 showed 54% degradation, compared to 33% dye degradation via NCQDs-doped Co 9 S 8 (NCQDs-D@Co 9 S 8 ). The change in the crystal structure and its lower loading on fabric results in significantly lower performance of NCQDs-D@Co 9 S 8 . Even with the combination of both surface growth and doping (NCQDs-DG@Co 9 S 8 ), the performance was still limited to 42%. In addition, the optimum growth concentration of NCQDs on Co 9 S 8 was observed for 7.5 w/w %, resulting in 92% photocatalytic activity (PCA) in 80 min. Comparing different surface states formed in NCQDs using different solvents, water-based surface states (oxygen-rich surface) are most suitable for the dye degradation. NCQDs-G@Co 9 S 8 also offers 67% Cr-VI reduction to Cr-III, showing its suitability for both inorganic and organic compounds. Better electrode performance was related to suitable charge separation of the composite, where -OH groups mainly contribute in the photocatalytic dye degradation.., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Diabetes mellitus has been considered as a serious health problem worldwide due its high prevalence rate and associated complications. In this context, the current research work aims at exploring new structural leads for the treatment of a major metabolic disorder, diabetes mellitus type 2. The outcomes of our prior studies on a diverse set of triazolothiadiazole and triazolothiadiazine derivatives and their therapeutic potential, encouraged us to explore their anti-diabetic competency by targeting the key carbohydrate catabolic enzyme, α-glucosidase. Therefore, all these analogues were examined to reveal their contribution towards this severe metabolic issue. Interestingly, all the tested compounds (2a-2l and 3a-3p) exhibited several times more potent α-glucosidase inhibitory activities (IC 50 in the range of 2.44-219.93 μM) as compared to marketed drug, acarbose (IC 50  = 873.34 ± 1.67 μM). Furthermore, their mechanism of action was investigated through in vitro kinetics studies which revealed compounds 3a, 3d, 3o, and 2k as competitive inhibitors, and 3f as a mixed type inhibitor of α-glucosidase. In addition, in silico molecular docking and molecular dynamics simulations were applied to observe the mode of interaction of the active hits within the binding pocket of α-glucosidase. Both docking and simulation results favored our in vitro mechanistic analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Dengue virus has emerged as infectious mosquito borne disease involved in lowering platelets and white blood cells (WBC) count particularly. The genome structure is based on several structural and non-structural proteins essential for viral replication and progeny. One of the major proteins of replication is non-structural protein 3 (NS3) that transforms polyproteins into functional proteins with a cofactor non-structural protein (NS2B). Heat Shock Protein 70 (HSP70), is a human protein that assists in replication, viral entry and virion synthesis. Therefore, to inhibit the spread of dengue infection, there is a need of antivirals targeting replication proteins and other human proteins that help in dengue virus multiplication. By systemic approach based on molecular docking, ADMET (absorption, distribution, metabolism, excretion and toxicity) properties and molecular dynamic simulation (MD), potent inhibitors can be predicted. Inhibition of NS2B/NS3 dengue and HSP70 proteins involved in multiple steps in dengue virus progression can be prevented by using different phytochemicals. Molecular docking was performed using AutoDock Vina, PatchDock, and SwissDock. Interactions of obtained complex were observed in PyMOL and PLIP. Validation was checked by PROCHEK, simulation was performed using iMODS followed by preclinical testing by admetSAR. Ladanein, a flavonoid of Orthosiphon aristatus , was obtained as the lead compound to inhibit major replication protein of dengue virus with inhibitory potential against HSP70 protein. In summary, various in silico approaches were used to obtain the best phytochemical having anti-dengue potential.Communicated by Ramaswamy H. Sarma.

In this study, the removal efficiency of chemicals of emerging concerns (CECs) was evaluated under exposure to various doses of UV/H 2 O 2 -based oxidation processes in combination with membrane filtration for three cleaning cycles. Polyethersulphone (PES) and polyvinylidene fluoride (PVDF) materials based membranes were used for this study. The chemical cleaning of the membranes was performed by immersion of the membranes into 1 N HCl followed by adding 3000 mg.L -1 NaOCl for 1hr. Degradation and filtration performance was evaluated using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) and total organic carbon (TOC) analysis. Membrane fouling analysis for assessing the comparative performance of PES and PVDF membranes was determined by specific fouling and fouling indices evaluation. Membrane characterization results show that the alkynes and carbonyl group formation are due to dehydrofluorination and oxidation of PVDF and PES membranes under the attack of foulants and cleaning chemicals, which resulted in a reduction of fluoride percentage and an increase in sulfur percentage in the PVDF and PES membranes. A decrease in the hydrophilicity of the membranes in underexposed conditions was observed and is consistent with an increase in dose. Degradation results of CECs follow with the highest removal efficiency of chlortetracycline (CTC) followed by atenolol (ATL), acetaminophen (ACT), and caffeine (CAF) degradation due to attack on the aromatic ring and the carbonyl group of CECs by OH exposure. Membrane exposed at 3 mg.L-1 dose of UV/H 2 O 2 -based CECs shows minimum alteration with higher filtration efficiency and lower fouling, particularly in PES membranes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chickpea ( Cicer arietinum L.) is a major pulse crop worldwide, renowned for its nutritional richness and adaptability. Weeds are the main biotic factor deteriorating chickpea yield and nutritional quality, especially Asphodelus tenuifolius Cav. The present study concerns a two-year (2018-19 and 2019-20) field trial aiming at evaluating the effect of weed management on chickpea grain quality. Several weed management practices have been here implemented under a factorial randomized complete block design, including the application of four herbicides [bromoxynil (C 7 H 3 Br 2 NO) + MCPA (Methyl-chlorophenoxyacetic acid) (C 9 H 9 ClO 3 ), fluroxypyr + MCPA, fenoxaprop- p -ethyl (C 18 H 16 ClNO 5 ), pendimethalin (C 13 H 19 N 3 O 4 )], the extracts from two allelopathic weeds ( Sorghum halepense and Cyperus rotundus ), two mulches (wheat straw and eucalyptus leaves), a combination of A. tenuifolius extract and pendimethalin, and an untreated check (control). Chickpea grain quality was measured in terms of nitrogen, crude protein, crude fat, ash, and oil content. The herbicides pendimethalin (Stomp 330 EC (emulsifiable concentrate) in pre-emergence at a rate of 2.5 L ha -1 ) and fenoxaprop- p -ethyl (Puma Super 7.5 EW (emulsion in water) in post-emergence at a rate of 1.0 L ha -1 ), thanks to A. tenuifolius control, showed outstanding performance, providing the highest dietary quality of chickpea grain. The herbicides Stomp 330 EC, Buctril Super 40 EC, Starane-M 50 EC, and Puma Super 7.5 EW provided the highest levels of nitrogen. Outstanding increases in crude protein content were observed with all management strategies, particularly with Stomp 330 EC and Puma Super 7.5 EW (+18% on average). Ash content was highly elevated by Stomp 330 EC and Puma Super 7.5 EW, along with wheat straw mulching, reaching levels of 2.96% and 2.94%. Crude fat content experienced consistent elevations across all treatments, with the highest improvements achieved by Stomp 330 EC, Puma Super 7.5 EW, and wheat straw mulching applications. While 2018-19 displayed no significant oil content variations, 2019-20 revealed the highest oil content (5.97% and 5.96%) with herbicides Stomp 330 EC and Puma Super 7.5 EW, respectively, followed by eucalyptus leaves mulching (5.82%). The results here obtained are of key importance in the agricultural and food sector for the sustainable enhancement of chickpea grain's nutritional quality without impacting the environment.

Hyperactivity of the urease enzyme induces the pathogenesis of peptic ulcers and gastritis. The identification of new urease inhibitors can reduce the activity of urease. Therefore, in the current study, we have evaluated 28 analogues of triazolothiadiazole and triazolothiadiazine heteroaromatics for their in vitro urease inhibitory efficacy. All the tested compounds displayed a remarkable inhibitory potential ranging from 3.33 to 46.83 μM. Among them, compounds 5k and 5e emerged as lead inhibitors with IC 50 values of 3.33 ± 0.11 and 3.51 ± 0.49 μM, respectively. The potent inhibitory potential of these compounds was ∼6.5-fold higher than that of the marketed drug thiourea (IC 50 = 22.45 ± 0.30 μM). The mechanistic insights from kinetics experiments of the highest potent inhibitors ( 4g , 5e , and 5k ) revealed a competitive type of inhibition with k i values 2.25 ± 0.0028, 3.11 ± 0.0031, and 3.62 ± 0.0034 μM, respectively. In silico modeling was performed to investigate the binding interactions of potent inhibitors with the enzyme active site residues, which strongly supported our experimental results. Furthermore, ADME analysis also showed good druglikeness properties demonstrating the potential of these compounds to be developed as lead antiurease agents., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Despite the existence of various therapeutic options, NSCLC is still a major health concern due to its aggressive nature and high mutation rate. Consequently, HER3 has been selected as a target protein along with EGFR because of its limited tyrosine kinase activity and ability to activate PI3/AKT pathway responsible for therapy failure. We herein used a BioSolveIT suite to identify potent inhibitors of EGFR and HER3. The schematic process involves screening of databases for constructing compound library comprising of 903 synthetic compounds (602 for EGFR and 301 for HER3) followed by pharmacophore modeling. The best docked poses of compounds with the druggable binding site of respective proteins were selected according to pharmacophore designed by SeeSAR version 12.1.0. Subsequently, preclinical analysis was performed via an online server SwissADME and potent inhibitors were selected. Compound 4k and 4m were the most potent inhibitors of EGFR while 7x effectively inhibited the binding site of HER3. The binding energies of 4k, 4m, and 7x were -7.7, -6.3 and -5.7 kcal/mol, respectively. Collectively, 4k , 4m and 7x showed favorable interactions with the most druggable binding sites of their respective proteins. Finally, in silico pre-clinical testing by SwissADME validated the non-toxic nature of compounds 4k , 4m and 7x providing a promising treatment option for chemoresistant NSCLC.

Stillbirth (SB) is a threshold character that has been detected as the most important factor affecting the future reproductive life of an animal. In buffaloes, stillbirth accounts for approximately 42% of all reproductive disorders being considered as the main reproductive disorder in buffalo calves. The present study aimed to estimate the heritability values and to determine the genetic and phenotypic correlation between stillbirth rate and birth weight (BW) using a Bayesian approach via Gibbs sampling method in a river buffalo population. A stochastic simulation was used to create a population in which random mating was used for 15 discrete generations. A bivariate animal model including maternal effects was used. Maternal effects were significant (p < .05) for both BW and SB. The results showed that when the SB rate increased from 1% to 50%, the estimated direct heritability of SB increased. Yet, by increasing the SB rate from 50% to 99%, a decrease of the SB estimated direct heritability was observed. The genetic correlation between BW and SB was decreased by increasing the level of occurrence of SB in the population from 1% to 99%. The root mean square error (RMSE) of heritability was increased from 40% to 70% level of occurrence of SB. Based on findings, it can be concluded that to reduce stillbirth rate in the population, it is possible to use genetic improvement program and birth weight could be one of the main components of a selection goal., (© 2023 Wiley-VCH GmbH.)

Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

Alzheimer's disease (AD) is one of the progressive neurological disorders and the main cause of dementia all over the world. The multifactorial nature of Alzheimer's disease is a reason for the lack of effective drugs as well as a basis for the development of new structural leads. In addition, the appalling side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with the marketed treatment modalities and many failed clinical trials significantly limit the use of drugs and alarm for a detailed understanding of disease heterogeneity and the development of preventive and multifaceted remedial approach desperately. With this motivation, we herein report a diverse series of piperidinyl-quinoline acylhydrazone therapeutics as selective as well as potent inhibitors of cholinesterase enzymes. Ultrasound-assisted conjugation of 6/8-methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes ( 4a , b ) and (un)substituted aromatic acid hydrazides ( 7a-m ) provided facile access to target compounds ( 8a-m and 9a-j ) in 4-6 min in excellent yields. The structures were fully established using spectroscopic techniques such as FTIR, 1 H- and 13 C NMR, and purity was estimated using elemental analysis. The synthesized compounds were investigated for their cholinesterase inhibitory potential. In vitro enzymatic studies revealed potent and selective inhibitors of AChE and BuChE. Compound 8c showed remarkable results and emerged as a lead candidate for the inhibition of AChE with an IC 50 value of 5.3 ± 0.51 µM. The inhibitory strength of the optimal compound was 3-fold higher compared to neostigmine (IC 50 = 16.3 ± 1.12 µM). Compound 8g exhibited the highest potency and inhibited the BuChE selectively with an IC 50 value of 1.31 ± 0.05 µM. Several compounds, such as 8a-c , also displayed dual inhibitory strength, and acquired data were superior to the standard drugs. In vitro results were further supported by molecular docking analysis, where potent compounds revealed various important interactions with the key amino acid residues in the active site of both enzymes. Molecular dynamics simulation data, as well as physicochemical properties of the lead compounds, supported the identified class of hybrid compounds as a promising avenue for the discovery and development of new molecules for multifactorial diseases, such as Alzheimer's disease (AD).

Purpose: International students are highly vulnerable to the risk of mental health worsening before and during the pandemic (COVID-19). This study investigated international students' mental health pre- and post-pandemic (COVID-19)., Methods: It is a longitudinal study, and data were collected online, pre-pandemic (N = 470) and during the pandemic (N = 420). Using a random sampling technique, a self-administered questionnaire was used to measure mental health, including depression and anxiety., Results: Findings show that international students' mental health was good in pre-pandemic. Meanwhile, international students were found to be more depressed and anxious during the pandemic. Findings also investigated that in the pre-pandemic phase, young students' and mainly females' mental health was worsened., Conclusion: This study concluded that students' mental problems are alarming, so the university should provide psychological services for the student's mental health. Post-pandemic is leaving long-lasting psychological effects and will require further investigation., Competing Interests: The authors declare no conflicts of interest in this study., (© 2023 Jamshaid et al.)