Search Results (47)

Defects are a direct cause of failure in ferromagnetic components, which can be evaluated via electromagnetic non-destructive testing (ENDT) methods. However, the existing studies exhibit several limitations (e.g., inaccurate quantification, over-reliance on algorithms, and non-intuitive result presentation, among others) in quantitative defect evaluation. To accurately describe the quantitative relationship between ENDT signals and defect dimensional parameters, the electromagnetic model and electromagnetic induction model are introduced in this paper to elucidate the physical mechanism of ENDT, as both models provide a basis for the selection of the constitutive relationship for simulation analysis. Then, a higher precision three-dimensional nonlinear finite element simulation model is established, and the effects of the excitation parameters and detection positions on signal characteristics are investigated. The simulation results indicate that the excitation frequency influences both the detection depth and sensitivity of ENDT, while the voltage amplitude affects the peak strength of the magnetic signal. Consequently, the excitation parameters are determined to be a 10 Hz frequency with a 25 V amplitude. Based on the characterization of signal peaks at positions of 0°, 90°, 180°, and 270°, the characteristic parameter K_A of the peak electrical signal curve is proposed as a quantitative index for evaluating defects. The quantitative experimental results show that K_A is related to the defect dimension. Specifically, the K_A value monotonically decreases from a constant greater than 1 to a constant less than 1 as the defect length increases, K_A is positively correlated with the defect width, and K_A follows a parabolic trend (first increase and then decrease) as the defect depth increases. Notably, K_A values associated with defect width and depth remain below 1. All the above findings provide a basis for evaluating defect dimensions. The results of this paper provide a novel ENDT method for evaluating defects, which is of great significance for improving the accuracy of ENDT and promoting its engineering applications. Full article

GSH biosynthesis is enhanced in cancer cells that express the variant isoform of the surface antigen CD44 (CD44v), which is overexpressed in certain types of cancer. The GSH-responsive prodrug Ns-Dox was prepared by modifying the GSH-responsive group 2-nitrobenzene sulfonyl (Ns) with the model drug doxorubicin (Dox). Its function was evaluated based on its molecular interaction with model DNA in terms of its binding constant (K_a). The association constant of Ns-Dox was lower, and its interaction with model DNA was weaker compared to that of Dox, suggesting that Ns-Dox may act as a less toxic prodrug. HCT116 cells with high CD44v expression and GSH levels and BT474 cells with low CD44v expression and GSH levels were used. The addition of Ns-Dox to HCT116 cells produced cytotoxic effects similar to those of Dox. In contrast, a significant difference in viability was observed between Ns-Dox- and Dox-treated BT474 cells at low concentrations. These findings suggest that Ns-Dox functions as a prodrug with low environmental toxicity and a lower GSH concentration in cancer cells. It is efficiently activated to Dox in cells with high GSH production, demonstrating its cell-killing effects. Full article

This study selected three approved folate sources—folic acid (FA), L-5-methyltetrahydrofolate (MTFA), and calcium 5-methyltetrahydrofolate (CMTFA)—to explore their interaction mechanisms with soy protein isolate (SPI) through spectrofluorometric analysis and molecular docking simulations. We investigated how these interactions influence the structural and physicochemical stability of folates and SPI. Three folates spontaneously bound to SPI, forming complexes, resulting in a decrease of approximately 30 kJ·mol⁻¹ in Gibbs free energy and an association constant (K_a) of 10⁵ L·mol⁻¹. The thermodynamic parameters and molecular docking study revealed the unique binding mechanisms of FA and MTFA with SPI. FA’s planar pteridine ring and conjugated double bonds facilitate hydrophobic interactions, whereas MTFA’s reduced ring structure and additional polar groups strengthen hydrogen bonding. Although the formation of SPI–folate complexes did not result in substantial alterations to the SPI structure, their binding has the potential to enhance both the physical and thermal stability of the protein by stabilizing its conformation. Notably, compared with free FA, the FA-SPI complexes significantly enhanced FA’s stability, exhibiting 71.1 ± 1.2% stability under light conditions after 9 days and 63.2 ± 2.6% stability in the dark after 60 days. In contrast, no similar effect was observed for MTFA. This discrepancy can be ascribed to the distinct degradation pathways of the Fa and MTFA molecules. This study offers both theoretical and experimental insights into the development of folate-loaded delivery systems utilizing SPI as a matrix. Full article

This study evaluates how the polarity of the medium affects the binding efficiency of hydrophobic ligands with human serum albumin (HSA). The polarity of the aqueous medium was changed by adding 1,4-dioxane in concentrations of 0%, 10%, and 20% w/w, resulting in solvent mixtures with decreasing dielectric constants (ε = 80, 72, and 63). The addition of 1,4-dioxane did not affect the integrity of the protein, as confirmed by Far-UV-CD, Rayleigh scattering, and time-resolved fluorescence experiments. The impact of medium polarity on the binding constants was evaluated using 1,6-diphenyl-1,3,5-hexatriene (DPH), octyl gallate (OG), quercetin, and rutin as ligands. The association constants of DPH decreased as the medium hydrophobicity increased: at 0%, Ka = 19.8 × 10⁵ M⁻¹; at 10%, Ka = 5.3 × 10⁵ M⁻¹; and at 20%, Ka = 1.7 × 10⁵ M⁻¹. The decrease was still higher using OG: at 0%, Ka = 5.2 × 10⁶ M⁻¹; and at 20%, Ka = 2.2 × 10⁵ M⁻¹. The results in the same direction were obtained using quercetin and rutin as ligands. Molecular dynamics simulations illustrated the hydrophobic effect at the molecular level. The energy barrier for DPH to detach from the protein’s hydrophobic site and to move into the bulk solution was higher at 0% (9 kcal/mol) than at 20% 1,4-dioxane (7 kcal/mol). The difference was higher for OG, with 14 and 6 kcal/mol, respectively. Based on these findings, it was shown that the difference in hydrophobicity between the protein’s microenvironment and the surrounding solvent is an essential component for the effectiveness of the interaction. These results shed light on albumin–ligand complexation, a molecular interaction that has been extensively studied. Full article

Interindividual variability, influenced by patient-specific factors including age, weight, gender, race, and genetics, among others, contributes to variations in therapeutic response. Population pharmacokinetic (popPK) modeling is an essential tool for pinpointing measurable factors affecting dose-concentration relationships and tailoring dosage regimens to individual patients. Herein, we developed a popPK model for salbutamol, a short-acting β₂-agonist (SABA) used in asthma treatment, to identify key patient characteristics that influence treatment response. To do so, synthetic data from physiologically-based pharmacokinetic (PBPK) models was employed, followed by an external validation using real patient data derived from an equivalent study. Thirty-two virtual patients were included in this study. A two-compartment model, with first-order absorption (no delay), and linear elimination best fitted our data, according to diagnostic plots and selection criteria. External validation demonstrated a strong agreement between individual predicted and observed values. The incorporation of covariates into the basic structural model identified a significant impact of age on clearance (Cl) and intercompartmental clearance (Q); gender on Cl and the constant rate of absorption (ka); race on Cl; and weight on Cl in the volume of distribution of the peripheral compartment (V2). This study addresses critical challenges in popPK modeling, particularly data scarcity, incompleteness, and homogeneity, in traditional clinical trials, by leveraging synthetic data from PBPK modeling. Significant associations between individual characteristics and salbutamol’s PK parameters, here uncovered, highlight the importance of personalized therapeutic regimens for optimal treatment outcomes. Full article

This scientific article presents research on the electrical conductivity of imidazole-derived ionic liquids (1-methylimidazolium chloride, 1-ethyl-3-methylimidazolium chloride, 1-butyl-3-methylimidazolium chloride, 1-hexyl-3-methylimidazolium chloride and 1-methyl-3-octylimidazolium chloride) in the temperature range of 278.15–313.15 K in N,N-Dimethylformamide. The measurement methods employed relied mainly on conductometric measurements, enabling precise monitoring of the conductivity changes as a function of temperature. Experiments were conducted at various temperature values, which provided a comprehensive picture of the conducting properties of the investigated ionic liquids. The focus of the study was the analysis of the conductometric results, which were used to determine the conductivity function as a function of temperature. Based on the obtained data, a detailed analysis of association constants (K_A) and thermodynamic parameters such as enthalpy (∆H⁰), entropy (∆S⁰), Gibbs free energy (∆G⁰), Eyring activation enthalpy for charge transport ($\Delta H_{\lambda }^{‡}$) and diffusion processes (D⁰) was carried out. The conductometric method proved to be an extremely effective tool for accurately determining these parameters, significantly contributing to the understanding of the properties of imidazole-derived ionic liquids in the investigated temperature range. As a result, the obtained results not only provide new insights into the electrical conductivity of the studied ionic liquids but also broaden our knowledge of their thermodynamic behavior under different temperature conditions. These studies may have significant implications for the field of ionic liquid chemistry and may be applied in the design of modern materials with desired conducting properties. Full article

Surface Plasmon Resonance (SPR) technology is known to be a powerful tool for studying biomolecular interactions because it offers real-time and label-free multiparameter analysis with high sensitivity. This article summarizes the results that have been obtained from the use of SPR technology in studying the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations. This paper will begin by introducing the working principle of SPR and the kinetic parameters of the sensorgram, which include the association rate constant (k_a), dissociation rate constant (k_d), equilibrium association constant (K_A), and equilibrium dissociation constant (K_D). At the end of the paper, we will summarize the kinetic data on the interaction between angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 obtained from the results of SPR signal analysis. ACE2 is a material that mediates virus entry. Therefore, understanding the kinetic changes between ACE2 and SARS-CoV-2 caused by the mutation will provide beneficial information for drug discovery, vaccine development, and other therapeutic purposes. Full article

Histidine residues play crucial roles in shaping the function and structure of proteins due to their unique ability to act as both acids and bases. In other words, they can serve as proton donors and acceptors at physiological pH. This exceptional property is attributed to the side-chain imidazole ring of histidine residues. Consequently, determining the acid-base dissociation constant (Ka) of histidine imidazole rings in proteins often yields valuable insights into protein functions. Significant efforts have been dedicated to measuring the pKa values of histidine residues in various proteins, with nuclear magnetic resonance (NMR) spectroscopy being the most commonly used technique. However, NMR-based methods encounter challenges in assigning signals to individual imidazole rings and require a substantial amount of proteins. To address these issues associated with NMR-based approaches, a mass-spectrometry-based method known as histidine hydrogen–deuterium exchange mass spectrometry (His-HDX-MS) has been developed. This technique not only determines the pKa values of histidine imidazole groups but also quantifies their solvent accessibility. His-HDX-MS has proven effective across diverse proteins, showcasing its utility. This review aims to clarify the fundamental principles of His-HDX-MS, detail the experimental workflow, explain data analysis procedures and provide guidance for interpreting the obtained results. Full article

The new 5-substituted SN-38 derivatives, 5(R)-(N-pyrrolidinyl)methyl-7-ethyl-10-hydroxycamptothecin (1) and its diastereomer 5(S) (2), were investigated using a combination of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling methods. The chemical stability, configuration stability, and propensity to aggregate as a function of concentration were determined using ¹H NMR. The calculated self-association constants (K_a) were found to be 6.4 mM⁻¹ and 2.9 mM⁻¹ for 1 and 2, respectively. The NMR experiments were performed to elucidate the interaction of each diastereomer with a nicked decamer duplex, referred to as 3. The calculated binding constants were determined to be 76 mM⁻¹ and 150 mM⁻¹ for the 1–3 and 2–3 complexes, respectively. NMR studies revealed that the interaction between 1 or 2 and the nicked decamer duplex occurred at the site of the DNA strand break. To complement these findings, molecular modeling methods and calculation protocols were employed to establish the interaction mode and binding constants and to generate molecular models of the DNA/ligand complexes. Full article

A new method for the determination of cadherin 12 (CDH12)—an adhesive protein that has a significant impact on the development, growth, and movement of cancer cells—was developed and validated. The method is based on a biosensor using surface plasmon resonance imaging (SPRi) detection. A quartz crystal microbalance was used to analyze the characteristics of the formation of successive layers of the biosensor, from the linker monolayer to the final capture of CDH12 from solution. The association equilibrium constant (K_A = 1.66 × 10¹¹ dm³ mol⁻¹) and the dissociation equilibrium constant (K_D = 7.52 × 10⁻¹² mol dm⁻³) of the anti-CDH12 antibody–CDH12 protein complex were determined. The determined analytical parameters, namely the values determining the accuracy, precision, and repeatability of the method, do not exceed the permissible 20% deviations specified by the aforementioned institutions. The proposed method is also selective with respect to possible potential interferents, occurring in up to 100-fold excess concentration relative to the CDH12 concentration. The determined Limit of Quantification (LOQ = 4.92 pg mL⁻¹) indicates the possibility of performing quantitative analysis in human plasma or peritoneal fluid without the need to concentrate the samples; however, particular attention should be paid to their storage conditions, as the analyte does not exhibit high stability. The Passing–Bablok regression model revealed good agreement between the reference method and the SPRi biosensor, with ρ_Spearman values of 0.961 and 0.925. Full article

The spike (S) protein of SARS-CoV-2 is a molecular target of great interest for developing drug therapies against COVID-19 because S is responsible for the interaction of the virus with the host cell receptor. Currently, there is no outpatient safety treatment for COVID-19 disease. Furthermore, we consider it of worthy importance to evaluate experimentally the possible interaction of drugs (approved by the Food and Drug Administration) and the S, considering some previously in silico and clinical use. Then, the objective of this study was to demonstrate the in vitro interaction of ivermectin with S. The equilibrium dialysis technique with UV–Vis was performed to obtain the affinity and dissociation constants. In addition, the Drug Affinity Responsive Target Stability (DARTS) technique was used to demonstrate the in vitro interaction of S with ivermectin. The results indicate the interaction between ivermectin and the S with an association and dissociation constant of Ka = 1.22 µM⁻¹ and Kd = 0.81 µM, respectively. The interaction was demonstrated in ratios of 1:50 pmol and 1:100 pmol (S: ivermectin) by the DARTS technique. The results obtained with these two different techniques demonstrate an interaction between S and ivermectin previously explored in silico, suggesting its clinical uses to stop the viral spread among susceptible human hosts. Full article

pH regulation is essential to allow normal cell function, and their imbalance is associated with different pathologic situations, including cancer. In this study, we present the synthesis of 2-(((2-aminoethyl)imino)methyl)phenol (HL1) and the iron (III) complex (Fe(L1)₂Br, (C1)), confirmed by X-ray diffraction analysis. The absorption and emission properties of complex C1 were assessed in the presence and absence of different physiologically relevant analytes, finding a fluorescent turn-on when OH⁻ was added. So, we determined the limit of detection (LOD = 3.97 × 10⁻⁹ M), stoichiometry (1:1), and association constant (K_as = 5.86 × 10³ M⁻¹). Using DFT calculations, we proposed a spontaneous decomposition mechanism for C1. After characterization, complex C1 was evaluated as an intracellular pH chemosensor on the human primary gastric adenocarcinoma (AGS) and non-tumoral gastric epithelia (GES-1) cell lines, finding fluorescent signal activation in the latter when compared to AGS cells due to the lower intracellular pH of AGS cells caused by the increased metabolic rate. However, when complex C1 was used on metastatic cancer cell lines (MKN-45 and MKN-74), a fluorescent turn-on was observed in both cell lines because the intracellular lactate amount increased. Our results could provide insights about the application of complex C1 as a metabolic probe to be used in cancer cell imaging. Full article

This work was aimed at the development of a sensitive electrochemical detection method for oxycodone in water. Molecularly imprinted electrodes were formed by electro-polymerization process using o-phenylenediamine as a monomer. The electro-polymerization was performed on glassy carbon electrodes in the presence of oxycodone before the extraction of entrapped oxycodone molecules. Various electrochemical techniques were employed to monitor the polymerization and response of the fabricated electrodes toward oxycodone. These techniques included cyclic voltammetry (CV), square wave voltammetry (SWV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The oxycodone concentration was determined using SWV by measuring the change in the oxidation peak current of [Fe(CN)₆]^3−/4− in a 0.1 mM acetate buffer solution. At the optimal electro-polymerization conditions, a calibration curve of the current versus the concentration of oxycodone indicated a linear response at a region from 0.4 nM to 5.0 nM with a detection limit of 1.8 ± 0.239 nM. The MIP-modified electrode’s binding isotherm was fitted using a Langmuir model and showed an association constant, K_A, of 1.12 × 10⁶, indicating a high affinity of oxycodone molecules to binding sites. This sensor has the potential to act as an alternative method suitable for the on-site analysis of oxycodone. Full article

Organophosphorus insecticides (OPs), acting as serine phosphorylating agents in acetylcholinesterase (AChE), are highly effective neurotoxic insecticides. In our previous research, we found that six herbivorous pests and four ladybirds howed significantly higher AChE LC50 values than seven parasitoids and a predator (Epistrophe balteate), and that there was a significant correlation with the corresponding bimolecular rate constant (Ki) value. The Ki value of pests was much smaller than that of natural enemies and had a higher LC50 value.Then, we speculated that the low sensitivity of the pest AChE to OPs may be associated with its higher recovery and lower aging ability. In this work, the I50 and I90 were calculated, to determine the sensibility of AChE in ten representative species, including Plutella xylostella, Prodenia litura, Musca domestica, and Cavia porcellus, to paraoxon and malaoxon. The enzyme activities were measured at various time points, and kinetic calculations were used to obtain their spontaneous reactivation (Ks) and aging (Ka) constants, which were comprehensively compared. We conclude that the Ka and Ks of the AChE inhibited by OPs showed primarily species-specific correlations, and little correlation with the sensitivity to OPs. The differences in the AChE sensitivity to paraoxon among the ten species were much greater than in the sensitivity to malaoxon. Compared to paraoxon, malaoxon was more selective for Cavia porcellus. Coleoptera insects showed a stronger dephosphorylation ability than other insect groups. The recovery ability of phospho-AChE was stronger in mammals than in insects, which could be related to the low sensitivity of the AChE site of action to OPs. The Ka of the AChE inhibited by malaoxon was larger than that inhibited by paraoxon with the corresponding biomaterials, indicating that the OP type had a substantial relationship with the Ka of the AChE. We further discovered that, when insects were inhibited by OP, the tendency of AChE to undergo aging was greater than that of dephosphorylation. Overall, the study provides valuable information on the action mechanism of various OPs on AChE in several species, which could be used to further research into AChE and the potential dangers that organophosphates pose to animals. Full article

Sensitive systems with controlled release of drugs or diagnostic markers are attractive for solving the problems of biomedicine and antitumor therapy. In this study, new decasubstituted pillar[5]arene derivatives containing L-Tryptophan and L-Phenylalanine residues have been synthesized as pH-responsive drug nanocarriers. Fluorescein dye (Fluo) was loaded into the pillar[5]arene associates and used as a spectroscopic probe to evaluate the release in buffered solutions with pH 4.5, 7.4, and 9.2. The nature of the substituents in the pillar[5]arene structure has a huge influence on the rate of delivering. When the dye was loaded into the associates based on pillar[5]arene derivatives containing L-Tryptophan, the Fluo release occurs in the neutral (pH = 7.4) and alkaline (pH = 9.2) buffered solutions. When the dye was loaded into the associates based on pillar[5]arene with L-Phenylalanine fragments, the absence of release was observed in every pH evaluated. This happens as the result of different packing of the dye in the structure of the associate. This fact was confirmed by different fluorescence mechanisms (aggregation-caused quenching and aggregation-induced emission) and association constants. It was shown that the macrocycle with L-Phenylalanine fragments binds the dye more efficiently (lgK_a = 3.92). The experimental results indicate that the pillar[5]arene derivatives with amino acids fragments have a high potential to be used as a pH-responsive drug delivery devices, especially for promoting the intracellular delivering, due to its nanometric size. Full article