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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 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.)

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.

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]

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 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]

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]

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]

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]

A series of 2-(1H-indol-2-yl)-3-acrylonitrile derivatives, 2a–x, 3, 4a–b, 5a–d, 6a–b, and 7, were synthesized as potential antitumor and antimicrobial agents. The structures of the prepared compounds were evaluated based on elemental analysis, IR, 1H- and 13NMR, as well as MS spectra. X-ray crystal analysis of the representative 2-(1H-indol-2-yl)-3-acrylonitrile 2l showed that the acrylonitrile double bond was Z-configured. All compounds were screened at the National Cancer Institute (USA) for their activities against a panel of approximately 60 human tumor cell lines and the relationship between structure and in vitro antitumor activity is discussed. Compounds of interest 2l and 5a–d showed significant growth inhibition potency against various tumor cell lines with the mean midpoint GI50 values of all tests in the range of 0.38–7.91 μM. The prominent compound with remarkable activity (GI50 = 0.0244–5.06 μM) and high potency (TGI = 0.0866–0.938 μM) against some cell lines of leukemia (HL-60(TB)), non-small cell lung cancer (NCI-H522), colon cancer (COLO 205), CNS cancer (SF-539, SNB-75), ovarian cancer ((OVCAR-3), renal cancer (A498, RXF 393), and breast cancer (MDA-MB-468) was 3-[4-(dimethylamino)phenyl]-2-(1-methyl-1H-indol-2-yl)acrylonitrile (5c). Moreover, the selected 2-(1H-indol-2-yl)-3-acrylonitriles 2a–c and 2e–x were evaluated for their antibacterial and antifungal activities against Gram-positive and Gram-negative pathogens as well as Candida albicans. Among them, 2-(1H-indol-2-yl)-3-(1H-pyrrol-2-yl)acrylonitrile (2x) showed the most potent antimicrobial activity and therefore it can be considered as a lead structure for further development of antimicrobial agents. Finally, molecular docking studies as well as drug-likeness and ADME profile prediction were carried out. [ABSTRACT FROM AUTHOR]

Ordinary differential equations describe several phenomena in different fields of engineering and physics. Our aim is to use the reproducing kernel Hilbert space method (RKHSM) to find a solution to some ordinary differential equations (ODEs) that are described by using the global derivative. In this research, we used the RKHSM to construct new numerical solutions for nonlinear ODEs with global derivative. The used method systematically produces analytic and approximate solutions in the series's form. We tested three applications for showing the performance of the RKHSM. [ABSTRACT FROM AUTHOR]

mathematical model is developed to study the characteristics of blood flowing through an arterial segment in the presence of a single and a couple of stenoses. The governing equations accompanied by an appropriate choice of initial and boundary conditions are solved numerically by Taylor Galerkin's time-stepping equation, and the numerical stability is checked. The pressure, velocity, and stream functions have been solved by Cholesky's method. Furthermore, an in-depth study of the flow pattern reveals the separation of Reynolds number for the 30 and 50% blockage of single stenosis and 30% blockage of multi-stenosis. The present results predict the excess pressure drop across the stenosis site than it does for the inlet of the artery with single and multiple stenosis and the increase in the velocity is observed at the center of the artery. [ABSTRACT FROM AUTHOR]

Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or S-alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant M. abscessus strains and compared their antimycobacterial activity using M. bovis BCG and M. tuberculosis H37Ra. Benzenesulfonamide-bearing imidazole-2-thiol compound 13, containing 4-CF3 substituent in benzene ring, showed strong antimicrobial activity against the tested mycobacterial strains and was more active than some antibiotics used as a reference. Furthermore, an imidazole-bearing 4-F substituent and S-methyl group demonstrated good antimicrobial activity against M. abscessus complex strains, as well as M. bovis BCG and M. tuberculosis H37Ra. In summary, these results demonstrated that novel benzenesulfonamide derivatives, bearing substituted imidazoles, could be further explored as potential candidates for the further hit-to-lead optimization of novel antimycobacterial compounds. [ABSTRACT FROM AUTHOR]

The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study of 3-arylidene-2-oxindoles as novel NRH:quinone oxidoreductase inhibitors. It was demonstrated that oxindoles with 6-membered aryls in the arylidene moiety were obtained predominantly as E-isomers while for some 5-membered aryls, the Z-isomers prevailed. The most active compounds inhibited NQO2 with an IC50 of 0.368 µM. The presence of a double bond in the oxindoles was crucial for NQO2 inhibition activity. There was no correlation between NQO2 inhibition activity of the synthesized compounds and their cytotoxic effect on the A549 cell line. [ABSTRACT FROM AUTHOR]

Steel forging tools are subjected to a number of tribological wear mechanisms depending on the geometry and surface of the tool and the flow of the material. Thus, there is no single general tribological wear mechanism, and only the predominant wear mechanisms in this case can be indicated. The problem has been known for years, but due to its complexity research on it is still relevant. In this study, the various wear mechanisms of hot work tools are analyzed on the basis of original research. Moreover, the influence of the micro- and macrostructure of the material and of its mechanical, physical, and technological characteristics on susceptibility to a given type of wear is considered. Adhesive wear, wear caused by plastic deformation, mechanical fatigue, thermal fatigue, the influence of hardness, heat treatment, and impact strength on tool wear and the mechanisms causing this wear are discussed in addition to tribological wear mechanisms such as abrasive wear. The influence of thermomechanical history and the characteristics of the tool material, including structural anisotropy, on the wear of these tools is indicated. The analysis of wear mechanisms performed will enable more precise definition of the principles of tool material selection and tool material condition for the hot forging of steel. [ABSTRACT FROM AUTHOR]

Three new compounds including a meroterpenoid (1) and two isocoumarins (8 and 9), together with thirteen known compounds (2–7, 10–16) were isolated from the metabolites of Talaromyces amestolkiae MST1-15. Their structures were identified by a combination of spectroscopic analysis. The absolute configuration of compound 1 was elucidated on the basis of experimental and electronic circular dichroism calculation, and compounds 8 and 9 were determined by Mo2(OAc)4-induced circular dichroism experiments. Compounds 7–16 showed weak antibacterial activities against Stenotrophomonas maltophilia with MIC values ranging from 128 to 512 μg/mL (MICs of ceftriaxone sodium and levofloxacin were 128 and 0.25 μg/mL, respectively). [ABSTRACT FROM AUTHOR]

The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases is a family of serine/threonine kinases that regulates numerous signaling networks that promote cell growth, proliferation, and survival. PIM kinases are commonly upregulated in both solid tumors and hematological malignancies. Recent studies have demonstrated that PIM facilitates immune evasion in cancer by promoting an immunosuppressive tumor microenvironment that suppresses the innate anti-tumor response. The role of PIM in immune evasion has sparked interest in examining the effect of PIM inhibition in combination with immunotherapy. This review focuses on the role of PIM kinases in regulating immune cell populations, how PIM modulates the immune tumor microenvironment to promote immune evasion, and how PIM inhibitors may be used to enhance the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

The genus Talaromyces belongs to the phylum Ascomycota of the kingdom Fungi. Studies have shown that Talaromyces species yield many kinds of secondary metabolites, including esters, terpenes, steroids, alkaloids, polyketides, and anthraquinones, some of which have biological activities such as anti-inflammatory, bacteriostatic, and antitumor activities. The chemical constituents of fungi belonging to the genus Talaromyces that have been studied by researchers over the past several years, as well as their biological activities, are reviewed here to provide a reference for the development of high-value natural products and innovative uses of these resources. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is β-Lactam antibiotics. However, most bacteria have developed resistance against β-Lactams by producing enzymes β-Lactamase or penicillinase. The discovery of new β-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1–5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8–5.3 μg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to β-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance. [ABSTRACT FROM AUTHOR]

The unidirectional rotary and reciprocating sliding experiments of the 40Cr pin/GCr15 disc tribo-pair were carried out on the MFT-5000 Rtec friction and wear tester under the same test conditions with a sliding speed of 0.2 m/s and a load of 150 N. Compared with reciprocating sliding, the tribo-pair in rotary sliding exhibits a stabler friction coefficient and better wear resistance. By analyzing the wear surface morphologies of the two pins, the main wear mechanism was found to be adhesive wear. For the tribo-layer of pin under reciprocating sliding, the surface microstructure plastically converges and forms a ridge from both sides to the middle, while a vortex structure is generated in the tribo-layer of pin under rotating sliding. The metamorphic structure and mircohardness of tribo-layer caused by the sliding forms are the key factors affecting the tribological properties. [ABSTRACT FROM AUTHOR]

Selenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski's Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase. [ABSTRACT FROM AUTHOR]

Background: In the fight against malaria, the discovery of chemical compounds with a novel mode of action and/or chemistry distinct from currently used drugs is vital to counteract the parasite's known ability to develop drug resistance. Another desirable aspect is efficacy against gametocytes, the sexual developmental stage of the parasite which enables the transmission through Anopheles vectors. Using a chemical rescue approach, we previously identified compounds targeting Plasmodium falciparum coenzyme A (CoA) synthesis or utilization, a promising target that has not yet been exploited in anti-malarial drug development. Results: We report on the outcomes of a series of biological tests that help to define the species- and stage-specificity, as well as the potential targets of these chemically diverse compounds. Compound activity against P. falciparum gametocytes was determined to assess stage-specificity and transmission-reducing potential. Against early stage gametocytes IC50 values ranging between 60 nM and 7.5 μM were obtained. With the exception of two compounds with sub-micromolar potencies across all intra-erythrocytic stages, activity against late stage gametocytes was lower. None of the compounds were specific pantothenate kinase inhibitors. Chemical rescue profiling with CoA pathway intermediates demonstrated that most compounds acted on either of the two final P. falciparum CoA synthesis enzymes, phosphopantetheine adenylyltransferase (PPAT) or dephospho CoA kinase (DPCK). The most active compound targeted either phosphopantothenoylcysteine synthetase (PPCS) or phosphopantothenoylcysteine decarboxylase (PPCDC). Species-specificity was evaluated against Trypanosoma cruzi and Trypanosoma brucei brucei. No specific activity against T. cruzi amastigotes was observed; however three compounds inhibited the viability of trypomastigotes with sub-micromolar potencies and were confirmed to act on T. b. brucei CoA synthesis. Conclusions: Utilizing the compounds we previously identified as effective against asexual P. falciparum, we demonstrate for the first time that gametocytes, like the asexual stages, depend on CoA, with two compounds exhibiting sub-micromolar potencies across asexual forms and all gametocytes stages tested. Furthermore, three compounds inhibited the viability of T. cruzi and T. b. brucei trypomastigotes with sub-micromolar potencies and were confirmed to act on T. b. brucei CoA synthesis, indicating that the CoA synthesis pathway might represent a valuable new drug target in these parasite species. [ABSTRACT FROM AUTHOR]

In this review, we describe the latest advances in synthesis, characterization, and applications of polymer brushes. Synthetic advances towards well-defined polymer brushes, which meet criteria such as: (i) Efficient and fast grafting, (ii) Applicability on a wide range of substrates; and (iii) Precise control of surface initiator concentration and hence, chain density are discussed. On the characterization end advances in methods for the determination of relevant physical parameters such as surface initiator concentration and grafting density are discussed. The impact of these advances specifically in emerging fields of nano- and bio-technology where interfacial properties such as surface energies are controlled to create nanopatterned polymer brushes and their implications in mediating with biological systems is discussed. [ABSTRACT FROM AUTHOR]

The article offers information on the 68th Annual Meeting of the Microscopy Society of America, also known as the Microscopy & Microanalysis 2010, which was held in August in Portland, Oregon.

Endophytic fungi are one of prolific sources of bioactive natural products with potential application in biomedicine and agriculture. In our continuous search for antimicrobial secondary metabolites from Fusarium oxysporum R1 associated with traditional Chinese medicinal plant Rumex madaio Makino using one strain many compounds (OSMAC) strategy, two diastereomeric polyketides neovasifuranones A (3) and B (4) were obtained from its solid rice medium together with N-(2-phenylethyl)acetamide (1), 1-(3-hydroxy-2-methoxyphenyl)-ethanone (2) and 1,2-seco-trypacidin (5). Their planar structures were unambiguously determined using 1D NMR and MS spectroscopy techniques as well as comparison with the literature data. By a combination of the modified Mosher's reactions and chiroptical methods using time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) and optical rotatory dispersion (ORD), the absolute configurations of compounds 3 and 4 are firstly confirmed and, respectively, characterized as (4S,7S,8R), (4S,7S,8S). Bioassay results indicate that these metabolites 1–5 exhibit weak inhibitory effect on Helicobacter pylori 159 with MIC values of ≥16 μg/mL. An in-depth discussion for enhancement of fungal metabolite diversity is also proposed in this work. [ABSTRACT FROM AUTHOR]

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b,d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure–activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity. [ABSTRACT FROM AUTHOR]

Human ATP-binding cassette (ABC) subfamily G member 2 (ABCG2) mediates the transport of a wide variety of conventional cytotoxic anticancer drugs and molecular targeted agents. Consequently, the overexpression of ABCG2 in cancer cells is linked to the development of the multidrug resistance (MDR) phenotype. TP-3654 is an experimental second-generation inhibitor of PIM kinase that is currently under investigation in clinical trials to treat advanced solid tumors and myelofibrosis. In this study, we discovered that by attenuating the drug transport function of ABCG2, TP-3654 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic ABCG2 substrate drugs topotecan, SN-38 and mitoxantrone. Moreover, our results indicate that ABCG2 does not mediate resistance to TP-3654 and may not play a major role in the induction of resistance to TP-3654 in cancer patients. Taken together, our findings reveal that TP-3654 is a selective, potent modulator of ABCG2 drug efflux function that may offer an additional combination therapy option for the treatment of multidrug-resistant cancers. [ABSTRACT FROM AUTHOR]