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Background and Purpose: Several pharmaceutical formulations were investigated to improve the solubility of 5-fluorouracil to enhance bioavailability and therapeutic efficacy. This study aimed to examine the potential use of cyclodextrin-based nanosponges for the incorporation of 5-fluorouracil and to investigate the use of different crosslinking agents on the properties of the resulting drug carrier. 5-Fluorouracil complexation with β-cyclodextrin was also studied to explain the unexpected results of weak 5-fluorouracil incorporation in nanosponge., Experimental Approach: Nanosponges were synthesized by crosslinking β-cyclodextrin with two different crosslinkers; diphenyl carbonate and ethylenediaminetetraacetic dianhydride. The incorporation of 5-fluorouracil into β-cyclodextrin and the prepared nanosponges were assessed by NMR, FTIR, PXRD, DSC, and TGA. In addition, an in vitro release study was carried out to evaluate the potential use of β-cyclodextrin- based nanosponges as pharmaceutical formulations for 5-fluorouracil., Findings / Results: Physicochemical characterization of the dried formulations indicated the complexation of 5-fluorouracil with the β-cyclodextrin polymer. Despite that, no clear manifestation of 5-fluorouracil encapsulation in the prepared β-cyclodextrin-based nanosponge was detected. Furthermore, no significant differences were observed in the release profiles of 5-fluorouracil, β-cyclodextrin complex, and β- cyclodextrin-based nanosponge, suggesting weak complexation and instability in aqueous solutions. EDTA- crosslinked β-cyclodextrin-based nanosponge showed a slight improvement in 5-fluorouracil solubility with a faster initial rate of 5-fluorouracil release., Conclusion and Implications: This study suggested weak complexation between 5-fluorouracil and the β- cyclodextrin polymer or nanosponges. Crosslinking of β-cyclodextrin with EDTA dianhydride crosslinker showed an enhancement in 5-fluorouracil saturation solubility combined with a faster initial rate of drug release., Competing Interests: All authors declared no conflict of interest in this study., (Copyright: © 2022 Research in Pharmaceutical Sciences.)

Steroids are compounds widely available in nature and synthesized for therapeutic and medical purposes. Although several analytical techniques are available for the quantification of steroids, their analysis is challenging due to their low levels and complex matrices of the samples. The efficiency and quick separation of the HPLC combined with the sensitivity, selectivity, simplicity, and cost-efficiency of fluorescence, make HPLC coupled to fluorescence detection (HPLC-FLD) an ideal tool for routine measurement and detection of steroids. In this review, we covered HPLC-FLD methods reported in the literature for the steroids quantification in clinical, pharmaceutical, and environmental applications, focusing on the various approaches of fluorescent derivatization. The aspects related to analytical methodology including sample preparation, derivatization reagents, and chromatographic conditions will be discussed.

The oncogenic Pim kinase proteins (Pim-1/2/3) regulate tumorigenesis through phosphorylating essential proteins that control cell cycle and proliferation. Pim kinase is a potential chemotherapeutic target in cancer and its inhibition is currently the focus of intensive drug design and development efforts. The distinctive presence of proline amino acids in the hinge region provides an opportunity to inhibit Pim kinase while conserving the physiological functions of other kinases and reducing the toxicity profiles of the inhibitors. Various Pim kinase inhibitors have been clinically evaluated for the treatment of hematological cancers, yet none has reached the clinic. In this review, we discuss the design and development of selective and potent Pim inhibitors with novel chemotypes focusing on structural features essential for high potency and selectivity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The lysine specific demethylase enzyme LSD1 regulates the function of histone proteins in cells through the demethylation of specific lysine amino acid residues. Being overexpressed in various cancers, LSD1 is considered as a validated target for cancer treatment. In this study, we describe the discovery of novel LSD1 inhibitors using computational fragment-based drug design approach. Structure-based screening of the Maybridge Ro3 2000 Diversity Fragment Library had identified two sets of fragments that bind to two different regions within the LSD1 active site. De Novo and Multiple Copy Simultaneous search (MCSS) docking, ligand efficiency (LE), and binding energy calculations (BE) had assisted the selection of the best scoring fragments that were grown to produce lead-like compounds. The final grown compounds were docked into the active site of the enzyme using flexible docking and their total binding energies were calculated in order to aid the selection of potential LSD1 inhibitors that will be synthesized and biologically evaluated. Six compounds were synthesized and biologically tested, of which two had showed a promising activity against LSD1. Compound 37, with an amino-carboxamide benzothiazole scaffold, showed the best inhibitory activity with an IC 50 value of 18.4 μM. Compound 37 was chosen as an LSD1 hit inhibitor worthy of further optimization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inhibitors of the enzyme NQO2 (NRH: quinone oxidoreductase 2) are of potential use in cancer chemotherapy and malaria. We have previously reported that non-symmetrical furan amidines are potent inhibitors of NQO2 and here novel analogues are evaluated. The furan ring has been changed to other heterocycles (imidazole, N-methylimidazole, oxazole, thiophene) and the amidine group has been replaced with imidate, reversed amidine, N-arylamide and amidoxime to probe NQO2 activity, improve solubility and decrease basicity of the lead furan amidine. All compounds were fully characterised spectroscopically and the structure of the unexpected product N-hydroxy-4-(5-methyl-4-phenylfuran-2-yl)benzamidine was established by X-ray crystallography. The analogues were evaluated for inhibition of NQO2, which showed lower activity than the lead furan amidine. The observed structure-activity relationship for the furan-amidine series with NQO2 was rationalized by preliminary molecular docking and binding mode analysis. In addition, the oxazole-amidine analogue inhibited the growth of Plasmodium falciparum with an IC 50 value of 0.3 μM., (Copyright © 2018. Published by Elsevier Ltd.)

The growing interest in artificial bioorganic interfaces as a platform for applications in emerging areas as personalized medicine, clinical diagnostics, biosensing, biofilms, prevention of biofouling, and other fields of bioengineering is the origin of a need for in detail multitechnique characterizations of such layers and interfaces. The in-depth analysis of biointerfaces is of special interest as the properties of functional bioorganic coatings can be dramatically affected by in-depth variations of composition. In worst cases, the functionality of a device produced using such coatings can be substantially reduced or even fully lost.

NRH:quinone oxidoreductase 2 enzyme (NQO2) is a potential therapeutic target in cancer and neurodegenerative diseases, with roles in either chemoprevention or chemotherapy. Here we report the design, synthesis and evaluation of non-symmetrical furan-amidines and their analogues as novel selective NQO2 inhibitors with reduced adverse off-target effects, such as binding to DNA. A pathway for the synthesis of the non-symmetrical furan-amidines was established from the corresponding 1,4-diketones. The synthesized non-symmetrical furan-amidines and their analogues showed potent NQO2 inhibition activity with nano-molar IC50 values. The most active compounds were non-symmetrical furan-amidines with meta- and para-nitro substitution on the aromatic ring, with IC50 values of 15 nM. In contrast to the symmetric furan-amidines, which showed potent intercalation in the minor grooves of DNA, the synthesized non-symmetrical furan-amidines showed no affinity towards DNA, as demonstrated by DNA melting temperature experiments. In addition, Plasmodium parasites, which possess their own quinone oxidoreductase PfNDH2, were inhibited by the non-symmetrical furan-amidines, the most active possessing a para-fluoro substituent (IC50 9.6 nM). The high NQO2 inhibition activity and nanomolar antimalarial effect of some of these analogues suggest the lead compounds are worthy of further development and optimization as potential drugs for novel anti-cancer and antimalarial strategies., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Pim-1 kinase, a serine/threonine kinase, is often overexpressed in various cancers, contributing to disease progression and poor prognosis. In this study, we explored the potential of flavonoids as inhibitors of Pim-1 kinase using a combination of molecular docking and steered molecular dynamics (SMD) simulations. Our docking studies revealed two main binding orientations for the flavonoid molecules. The SMD simulations showed that the binding mode with higher pulling forces was linked to stronger inhibitory activity, with a strong positive correlation (R2 = 0.92) between pulling forces and IC50 values. Quercetin stood out as the most potent inhibitor, showing a pulling force of about 820 pN and an IC_(5) 0 of less than 6 µM. Further dynamic simulations indicated that quercetin's hydroxyl groups at the C3, C-5 and C-7 positions formed stable hydrogen bonds with key residues GLU-121, Leu-44 and Val-126, respectively enhancing its binding stability and effectiveness. Our results emphasized the critical role of the hydroxyl group at the C-3 position, which plays a pivotal function in effectively anchoring these molecules in the active site of Pim-1 kinase. Principal component analysis (PCA) of Pim-1 kinase's conformational changes revealed that potent inhibitors like quercetin, galangin, and kaempferol significantly restricted the enzyme's flexibility, suggesting potential inhibitory effect. These findings provide insights into the structural interactions between flavonoids and Pim-1 kinase, offering a foundation for future experimental investigations. However, further studies, including in vitro and in vivo validation, are necessary to assess the pharmacological relevance and specificity of flavonoids in cancer therapy. [ABSTRACT FROM AUTHOR]

Mumps is the most common disease for children, which causes hearing loss in all auditory systems. WHO initiated compulsory vaccination for children who are at age of 12 months to 12 years, since 1967. Children must take two doses of vaccination for mumps. The dynamics of the system describing the mumps transmission is studied in this work. The main aim is to elucidate the nonlinear behavior of the system which can provide insights into the long-term effects of Mumps infection on auditory function. As the fractional-order derivative preserves the impact of system memory, we employ the Caputo fractional derivative as the dynamical system describing modeling to simulate hearing loss in children brought on by the mumps virus. The boundedness existence of the solution and stability analysis of the dynamical system are derived in the framework. The result is derived using a well-known numerical method to capture the corresponding consequences and predict the future consequence of the dynamical system associated with parameters. To testify to the importance of the generalizing classical model with a fractional operator, we plot 2D graphs. This study helps to researcher beginners to understand the essential and fundamental tools while investigating real-world problems. [ABSTRACT FROM AUTHOR]

Substituted furan carboxamide and Schiff base derivatives were evaluated for their hypolipidemic activity. Fourteen derivatives were synthesised: substituted-furan-2-carboxamides of acetophenones, anilines, and benzophenones a (1–8), furan-3-carboxamide (c1), and imines derivatives b (1–5). These compounds were synthesised, purified and fully characterised. All the new derivatives were verified in-vivo utilising Triton WR-1339 induced hyperlipidemic rats as animal model. The potential agents were administered via intraperitoneal injection of 20 mg/kg. Fenofibrate (with a dose 100 mg/kg, orally) was used in this research to validate the model. Remarkably, the new derivatives a (1–8), b (1–5) and c1 have shown significant effect against the whole lipid profile; by lowering the plasma triglyceride (TG), plasma total cholesterol (TC), low-density lipoprotein (LDL) level and elevating high-density lipoproteins (HDL) plasma levels comparing to the hyperlipidemic rats. The agents reduce TG with most significant results by (97%, 96%, 87% and 86%) relating to a1, a3, a8 and b5 respectively. Favourably, some of the proposed agents are more significant in reducing TG than fenofibrate. Some agents reduce LDL with most significant results by (76%, 72%, 60%, 60% and 60%) relating to a1, a3, a5, a8 and b5 respectively, and to a lower extent they increase HDL levels with most significant results by (75%, 64%, and 48%) for a1, a3, and a5 respectively. All the new derivatives were computationally docked at the hPPAR-α active site as possible target for these derivatives. The binding affinities were reported and showed good correlation to the in-vivo results as antihyperlipidemic agents. [ABSTRACT FROM AUTHOR]

Background: There are a variety of lethal infectious diseases that are seriously affecting people's lives worldwide, particularly in developing countries. Hepatitis B, a fatal liver disease, is a contagious disease spreading globally. In this paper, a new hybrid approach of feed forward neural networks is considered to investigate aspects of the SEACTR (susceptible, exposed, acutely infected, chronically infected, treated, and recovered) transmission model of hepatitis B virus disease (HBVD). The combination of genetic algorithms and sequential quadratic programming, namely CGASQP, is applied, where genetic algorithm (GA) is used as the main optimization algorithm and sequential quadratic programming (SQP) is used as a fast-searching algorithm to fine-tune the outcomes obtained by GA. Considering the nature of HBVD, the whole population is divided into six compartments. An activation function based on mean square errors (MSEs) is constructed for the best performance of CGASQP using proposed model. Results: The solution's confidence is boosted through comparative analysis with reference to the Adam numerical approach. The results revealed that approximated results of CGASQP overlapped the reference approach up to 3–9 decimal places. The convergence, resilience, and stability characteristics are explored through mean absolute deviation (MAD), Theil's coefficient (TIC), and root mean square error (RMSE), as well as minimum, semi-interquartile range, and median values with respect to time for the nonlinear proposed model. Most of these values lie around 10−10–10−4 for all classes of the model. Conclusion: The results are extremely encouraging and indicate that the CGASQP framework is very effective and highly feasible for implementation. In addition to excellent reliability and level of precision, the developed CGASQP technique also stands out for its simplicity, wider applicability, and flexibility. [ABSTRACT FROM AUTHOR]

This paper focuses on using piecewise derivatives to simulate the dynamic behavior and investigate the crossover effect within the coupled fractional system with delays by dividing the study interval into two subintervals. We establish and prove significant lemmas concerning piecewise derivatives. Furthermore, we extend and develop the necessary conditions for the existence and uniqueness of solutions, while also investigating the Hyers–Ulam stability results of the proposed system. The results are derived using the Banach contraction principle and the Leary–Schauder alternative fixed-point theorem. Additionally, we employ a numerical method based on Newton’s interpolation polynomials to compute approximate solutions for the considered system. Finally, we provide an illustrative example demonstrating our theoretical conclusions’ practical application. [ABSTRACT FROM AUTHOR]

This study compares the price dynamics of a Caputo fractional order delay differential cobweb model with existing cobweb models that have conformable fractional derivatives, Caputo fractional derivatives, and nonsingular kernel fractional derivatives to determine the effect of the time delay parameter on commodity price, besides the positivity of the solution that was investigated. In contrast to previous research, the stability study shows the practical usefulness of our model since the literature's various time intervals showed short‐term equilibrium price convergence but long‐term price divergence. The results showed that the time gap between supply and demand accounts for the noise associated with the fractional‐order time delay differential cobweb regarding convergence (or divergence), which is nonexistent in the literature models. It is observed in the paper that lower fractional order goes with a higher time delay, while we have the reverse for high fractional order. This depicts the realities of price behaviour in connection with the law of demand and supply of commodities that take a finite period for them to be ready for distribution to the market. It is, therefore, recommended that price adjustment models be modeled using fractional delay differential equations. The numerical simulations were done using MATLAB. [ABSTRACT FROM AUTHOR]

This paper introduces a refined approach for obtaining the analytical solution of the nonlinear shock wave model incorporating fractal derivatives. The Fractal Yang Variational Iteration Strategy (FYVIS) is utilized to obtain the approximate solution of a fractal model in the form of a series under Caputo fractional operator. The suggested method is the composition of the fractal Yang transform and the variational iteration approach. By using the two-scale fractal theory, we transform the fractal model into its traditional problem and then apply the yang transform to generate a recurrence relation. The variational iteration approach is now suitable to handle this recurrence relation without imposing any hypotheses or restrictions on variables. The derived results by the proposed scheme are shown in terms of series solution. Numerical calculations verify the accuracy and consistency of the suggested approach, demonstrating its excellent performance. The dynamic behavior of fractal components is explored by evaluating absolute errors and presenting two-dimensional diagrams across the fractal domain. This investigation underscores that the suggested technique offers an efficient and user-friendly solution for solving the nonlinear shock wave model involving fractal derivatives. [ABSTRACT FROM AUTHOR]

The internet has brought about significant transformations in communication and human behaviour. It has revolutionised how people connect, express themselves, and socialise. The emergence of social media platforms has turned the virtual world into a tangible reality, enabling global connectivity without barriers. Initially designed to stay in touch with acquaintances and share thoughts, social media platforms have evolved to offer a diverse range of services. These platforms have become thriving marketplaces, influencing consumer behaviour in various ways. Platforms like YouTube have witnessed notable changes in the number and nature of advertisements accompanying videos. Due to the revenue-sharing model based on advertisements, YouTube had to increase its video view count. Additionally, YouTube has introduced video categorisation, with one such category being "trending videos." This proposal utilises existing machine learning techniques like support vector, logistic regression and decision tree to predict whether a video will be categorised as trending, employing supervised machine learning methods. The results are then compared based on their accuracy and precision, providing insights into the effectiveness of the techniques. [ABSTRACT FROM AUTHOR]

With the development of technology, more and more cities and highways are installing light reducing structures at the tunnel openings to improve traffic safety and reduce the "black hole effect" and low-angle sunlight glare effect. However, the existing scrims have poor road surface uniformity, bright and dark streaks and uneven road surface brightness, which can bring negative impact on driving. In order to balance the safety and comfort of tunnel light sheds, a new technique is proposed to reduce the negative effects of light sheds based on the multi-source effect of light diffusion panels. The results show that by arranging light diffusion panels on the top of the scrim, the daylight is fully diffused and then irradiated to the road surface under the scrim, avoiding the undesirable phenomenon caused by direct sunlight on the road surface. After the indoor test and numerical model analysis, the effectiveness of the technology is proved to be in compliance with the design specification, and the undesirable phenomena such as bright and dark streaks are avoided, thus ensuring the safety and comfort of traffic at the tunnel entrance. In addition, the average brightness of the road surface of the top arrangement of light diffusion panels is better than that of the two sides, and the light intensity distribution curve of No. 2 panel among the four light diffusion panels used in this paper is the best. The technology can also control the brightness level of the road surface under the shed through the area of light diffusion panels, thus reducing the carbon emission of the tunnel lighting system and achieving the unity of safety, comfort and low carbon environment protection. [ABSTRACT FROM AUTHOR]

Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug–CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems. [ABSTRACT FROM AUTHOR]

Objectives: Narrative review evaluating food contamination by endocrine disruptors present in food packaging. Data source: The terms "endocrine disruptors" and "food packaging" were used in combination in the PubMed, MEDLINE and SciELO databases, evaluating studies, in humans, published in Portuguese, English, French and Spanish between 1990 and 2023. Data synthesis: Packaging, especially those made from plastic or recycled material, is an important source of food contamination by endocrine disruptors. Bisphenols and phthalates are the endocrine disruptors most frequently associated with food contamination from packaging. However, many unknown substances and even those legally authorized can cause harm to health when exposure is prolonged or when substances with additive effects are mixed. Furthermore, the discarding of packaging can cause contamination to continue into the environment. Conclusion: Although packaging materials are essential for the transport and storage of food, many of them are associated with chemical contamination. As it is not possible to exclude them from our routine, it is important to develop research aimed at identifying the endocrine disruptors present in them, including the effects of chronic exposure; and that regulatory agencies and industry come together to reduce or prevent this risk. Additionally, consumers must be instructed on how to purchase products, handle them and prepare them to reduce the migration of chemical substances into food. [ABSTRACT FROM AUTHOR]

Developing countries face enormous challenges with substandard and falsified antimalarial drugs. One specific issue is the lack of a simple, cost-effective, and robust HPLC method to simultaneously determine and quantify the active pharmaceutical ingredients (APIs) in fixed-dose artemether-lumefantrine pharmaceutical dosage forms. The current study developed a novel, simple, sensitive, precise, accurate, and cost-effective RP-HPLC method for the simultaneous determination and quantification of artemether and lumefantrine in pharmaceutical dosage forms. The HPLC analysis was carried out on an Agilent 1260 Infinity Series HPLC system equipped with an ODS Intersil-C8 (150 × 4.6 mm) 5.0 µm column, by isocratic elution. The mobile phase composition consisted of acetonitrile and 0.05% orthophosphoric acid buffer of pH 3.5 in the ratio of 70 : 30 v/v. The analysis was performed at a 1 mL/min flow rate and a column temperature of 25°C. The total run time was 6 minutes. The detection was done with a variable wavelength detector (VWD) at an isosbestic point wavelength (λ) of 210 nm. The developed method was validated according to the ICH guidelines concerning system suitability, specificity, linearity, accuracy, precision, and robustness. The system suitability of the developed method revealed satisfactory theoretical plates and symmetry factors. The method proved to be specific, with no interference of mobile phase or excipients. The calibration plot exhibited linearity over the concentration range of 275–1925 μg/mL with R 2 = 0.9992 for artemether and a range of 150–1050 μg/mL with R 2 = 0.9985 for lumefantrine. The accuracy of the method, determined by the recovery study, was 99.79–100.16% for artemether and 99.04–99.50% for lumefantrine. The % RSD values for intraday precision were 0.175 and 0.203, while interday precision values were 0.340 and 0.554 for artemether and lumefantrine, respectively. The method demonstrated robustness when subjected to slight modifications in the flow rate, column temperature, and mobile phase composition. The developed analytical method proved satisfactory as per ICH guidelines and hence can be used for the determination and quantification of artemether and lumefantrine in bulk drug and pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

Heart failure is a cardiovascular disease with significant morbidity and mortality, affecting a growing number of people worldwide [1]. The aim of this paper is to predict the probability of survival of patients by looking at their various characteristics, diseases, and lifestyles in the most successful way by using various machine learning methods. The 299 patients in the data set we use, had left ventricular systolic dysfunction in 2015 and are classified as New York Heart Association (NYHA) class III and IV. The probability of survival of patients is estimated by applying various machine learning methods on the data set. In this study, there are two versions. In the first version of the study, Principal Component Analysis (PCA) is used to reduce the size of the data set. The performance of the machine learning algorithms is then evaluated using a variety of metrics. In the second version, the data set is only subjected to machine learning techniques, and performance is then assessed. Accuracy, Matthews correlation coefficient (MCC), sensitivity, specifity, F1 score, receiver operating characteristic-area under the curve (ROC-AUC), and precision-recall area under the curve (PR-AUC) values are calculated to measure success. Comparing the two versions reveals that all machine learning algorithms in general have performed better in the second version without PCA. In the second version, the CatBoost algorithm gave the most successful result. Patients with heart failure can have their mortality status predicted using machine learning techniques. The goal of this paper is to look at a variety of characteristics in order to assess the patient's mortality status. The condition of the patient can be improved by selecting the proper treatment based on the mortality situation. [ABSTRACT FROM AUTHOR]

A solid-phase microextraction (SPME) injection gas chromatography was validated with the flame ionization detection method (GC-FID) using a capillary column to detect ethanol. The method was used to determine ethanol in fluids with biomedical, clinical, and forensic importance, including water, phosphate-buffered saline (PBS), and artificial sweat. The strategy produced good peak resolution and showed a linear correlation between the concentration and peak areas for ethanol in all matrices. The inter- and intra-day precisions of the method were below 15.5% and 6.5%, respectively, varying according to the matrix. The method achieved detection limits below 1.3 mg/L, varying according to the matrix. Lower limits were obtained for the aqueous solution (0.22 mg/L), followed by the PBS solution (0.96 mg/L), and finally, the sweat solution (1.29 mg/L). This method is easy to perform and suitable for use in routine clinical biochemistry and forensic laboratories, allowing ethanol detection at lower concentrations using lower temperature and time of extraction, when compared with other studies. [ABSTRACT FROM AUTHOR]

Tinnitus is a syndrome that affects the human auditory system and is characterized by a perception of sounds in the absence of acoustic stimuli, or in total silence. Research indicates that muscarinic acetylcholine receptors (mAChRs), especially the M1 type, have a fundamental role in the alterations of auditory perceptions of tinnitus. Here, a series of computer-aided tools were used, from molecular surface analysis software to services available on the web for estimating pharmacokinetics and pharmacodynamics. The results infer that the low lipophilicity ligands, that is, the 1a–d alkyl furans, present the best pharmacokinetic profile, as compounds with an optimal alignment between permeability and clearance. However, only ligands 1a and 1b have properties that are safe for the central nervous system, the site of cholinergic modulation. These ligands showed similarity with compounds deposited in the European Molecular Biology Laboratory chemical (ChEMBL) database acting on the mAChRs M1 type, the target selected for the molecular docking test. The simulations suggest that the 1 g ligand can form the ligand-receptor complex with the best affinity energy order and that, together with the 1b ligand, they are competitive agonists in relation to the antagonist Tiotropium, in addition to acting in synergism with the drug Bromazepam in the treatment of chronic tinnitus. Description The study of the biological activities of Drynaria bonii led to the ADMET model to be used, mainly in relation to intestinal absorption and brain activity. The web-services made it possible, through a similarity test, to select the M1 muscarinic receptor, used in the ligand-receptor interaction tests, estimating the way of treating tinnitus. [ABSTRACT FROM AUTHOR]

Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising therapeutic target for treating various cancers (such as breast cancer, liver cancer, etc.) and other diseases (blood diseases, cardiovascular diseases, etc.), owing to its observed overexpression, thereby presenting significant opportunities in drug development. Since its discovery in 2004, extensive research has been conducted on LSD1 inhibitors, with notable contributions from computational approaches. This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Computational techniques, such as virtual screening, molecular docking and 3D-QSAR models, have played a pivotal role in elucidating the interactions between these inhibitors and LSD1. Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information for advancing further research on LSD1 inhibitors. [ABSTRACT FROM AUTHOR]

The current study discusses a novel approach for numerically solving MTVO-TFDWEs under various conditions, such as IBCs and DBCs. It uses a class of GSJPs that satisfy the given conditions (IBCs or DBCs). One of the important parts of our method is establishing OMs for Ods and VOFDs of GSJPs. The second part is using the SCM by utilizing these OMs. This algorithm enables the extraction of precision and efficacy in numerical solutions. We provide theoretical assurances of the treatment's efficacy by validating its convergent and error investigations. Four examples are offered to clarify the approach's practicability and precision; in each one, the IBCs and DBCs are considered. The findings are compared to those of preceding studies, verifying that our treatment is more effective and precise than that of its competitors. [ABSTRACT FROM AUTHOR]

The flavoenzyme N-ribosyldihydronicotinamide (NRH):quinone oxidoreductase 2 (NQO2) catalyzes two-electron reductions of quinones. NQO2 contributes to the metabolism of biogenic and xenobiotic quinones, including a wide range of antitumor drugs, with both toxifying and detoxifying functions. Moreover, NQO2 activity can be inhibited by several compounds, including drugs and phytochemicals such as flavonoids. NQO2 may play important roles that go beyond quinone metabolism and include the regulation of oxidative stress, inflammation, and autophagy, with implications in carcinogenesis and neurodegeneration. NQO2 is a highly polymorphic gene with several allelic variants, including insertions (I), deletions (D) and single-nucleotide (SNP) polymorphisms located mainly in the promoter, but also in other regulatory regions and exons. This is the first systematic review of the literature reporting on NQO2 gene variants as risk factors in degenerative diseases or drug adverse effects. In particular, hypomorphic 29 bp I alleles have been linked to breast and other solid cancer susceptibility as well as to interindividual variability in response to chemotherapy. On the other hand, hypermorphic polymorphisms were associated with Parkinson's and Alzheimer's disease. The I and D promoter variants and other NQO2 polymorphisms may impact cognitive decline, alcoholism and toxicity of several nervous system drugs. Future studies are required to fill several gaps in NQO2 research. [ABSTRACT FROM AUTHOR]

Background: Loading Methotrexate, a chemotherapeutic agent, in a nanocarrier can improve its efficacy and lower its side effects. Both PLGA and chitosan were used to formulate Methotrexate nanoparticles. Folate acts as a targeting ligand for anticancer medications. Therefore, folate, chitosan, and PLGA were used to deliver methotrexate. Methods: Folic acid and Chitosan (FA-CS) were conjugated and used to coat Methotrexate-PLGA nanoparticles. The conjugate and the nanoparticles were characterized using Zetasizer to test particle size, polydispersity and charge, SEM was used to test particles' morphology. Both %EE and %LC of MTX in the NPs were measured. Finally, MTX release and the system cytotoxicity were tested in vitro. Results: FTIR, NMR, and XRD proved the successful formation of FA-CS, and the formation of the coated nanoparticles. The particles were spherical with a size ~385 nm, a disparity ~0.27, and a charge ~+15 mV. The %EE and the % LC were 79% and 21.2%, respectively. In vitro release studies revealed nearly complete MTX release after 48 h. In vitro cytotoxicity testing demonstrated that the formulation components are safe and that the incorporation of MTX within the nanoparticles enhanced the drug's cytotoxic effect in comparison to the free drug. Conclusion: loading of MTX in the NPs enhances its chemotherapeutic effect, hence, this system can be used to target carcinogenic cells. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel class of analytic functions in the form h (z) = z p + ∑ k = p + 1 ∞ a k z k in the unit disk. These functions establish a connection between the extended Mittag–Leffler function and the quantum operator presented in this paper, which is denoted by ℵ q , p n (L , a , b) and is also an extension of the Raina function that combines with the Jackson derivative. Through the application of differential subordination methods, essential properties like bounds of coefficients and the Fekete–Szegő problem for this class are derived. Additionally, some results of special cases to this study that were previously studied were also highlighted. [ABSTRACT FROM AUTHOR]

Along with industrial development, the demand for robust and portable sensors has been increasing over the past decade. Notably, current research has paid great attention on the design of miniature sensor based on nanoparticles. Graphene and polyaniline (PANI) are the two nanoparticles receiving intense research interest in this study field owing to their unique electrically conductive property. Fundamentally, the detection of pollutant using either graphene or PANI is following two simple steps, namely the exposure of the nano-sensor to the pollutant-containing environment, and monitoring of the change in electrical conductance of the nano-sensor. In this review, current application of graphene, PANI, and their nanocomposites on the detection of different types of pollutants was revisited. The latest developments regarding the nanoparticles, substrate, pollutant type, fabrication method, and performances were summarized and compared. Based on the summarized information, future directions in further advancing the application of these nano-sensors in the industry were proposed. [ABSTRACT FROM AUTHOR]

In this study, we apply q-symmetric calculus operator theory and investigate a generalized symmetric Sălăgean q-differential operator for harmonic functions in an open unit disk. We consider a newly defined operator and establish new subclasses of harmonic functions in complex order. We determine the sharp results, such as the sufficient necessary coefficient bounds, the extreme of closed convex hulls, and the distortion theorems for a new family of harmonic functions. Further, we illustrate how we connect the findings of previous studies and the results of this article. [ABSTRACT FROM AUTHOR]

In this paper, a novel approximation to the Caputo time fractional derivative of variable order (VO) ν (ξ , η) (0 < ν (ξ , η) < 1) is established. Since time fractional derivatives are integral, with a weakly singular kernel the discretization on the uniform mesh may not lead to satisfactory accuracy. So, numerical approximation is constructed on nonuniform meshes based on Newton interpolation polynomial. As a result, the novel approximation can be viewed as the modification of the existing method [Shen, S., Liu, F., Chen, J., Turner, I. and Anh, V. [2012] "Numerical techniques for the variable order time fractional diffusion equation," Appl. Math. Comput. 218(22), 10861–10870]. The truncation errors and some significant properties of coefficients are analyzed. Furthermore, we derived Scheme-I and Scheme-II with second-order accuracy in spatial direction to solve the mobile–immobile advection–dispersion model (MIMADM) based on the VO Caputo derivative. The designed scheme converts the considered problems into a linear system of equations. Moreover, the stability properties of Scheme-I are discussed in detail. Ultimately, the proposed scheme is examined on several text examples demonstrating the high precision and effectiveness of the scheme. Also, comparative study between the outcomes achieved by implementing the suggested scheme with other numerical scheme in the existing literature is provided and also the acquired numerical results of these applications indicate that the suggested technique performs extremely well in terms of reliability and capability. [ABSTRACT FROM AUTHOR]

This paper presents a new way to solve numerically multiterm variable-order fractional differential equations (MTVOFDEs) with initial conditions by using a class of modified shifted Jacobi polynomials (MSJPs). As their defining feature, MSJPs satisfy the given initial conditions. A key aspect of our methodology involves the construction of operational matrices (OMs) for ordinary derivatives (ODs) and variable-order fractional derivatives (VOFDs) of MSJPs and the application of the spectral collocation method (SCM). These constructions enable efficient and accurate numerical computation. We establish the error analysis and the convergence of the proposed algorithm, providing theoretical guarantees for its effectiveness. To demonstrate the applicability and accuracy of our method, we present five numerical examples. Through these examples, we compare the results obtained with other published results, confirming the superiority of our method in terms of accuracy and efficiency. The suggested algorithm yields very accurate agreement between the approximate and exact solutions, which are shown in tables and graphs. [ABSTRACT FROM AUTHOR]

Background: Laser corneal reshaping is a successful treatment of many refraction disorders. However, some physical demonstrations for the laser interaction with cornea are not fully explained. In the current paper, we present a modified model to precisely investigate the ablation threshold, the ablation rate and the physical/chemical mechanisms in that action. Results: The model discusses the possible photochemical reaction between the incident photons and various components of the cornea. Such photochemical reaction may end by photo-ablation or just molecular electronic excitation. The ablation threshold is also produced by other chemical reaction. Finally another chemical reaction creates out-site fragments. Moreover, the effect of applying different laser wavelengths, namely the common excimer-laser (193-nm), and the solid-state lasers (213-nm & 266-nm) has been investigated. Conclusion: Despite the success and ubiquity of the Argon Fluoride "ArF" laser, our results reveal that a carefully designed 213-nm laser gives the same outcomes with the potential of possible lower operational drawbacks related with heat generation and diffusion. [ABSTRACT FROM AUTHOR]