Search

Bemis-Murcko scaffolding [1] is a powerful tool for compound clustering and subsequent analysis. Here, using ChEMBL database [2] and RDKit library [3], we have compiled the dataset of known small molecule drugs, their molecular scaffolds and associated medical indications augmented with the interactive interface. We present these data, which can be used by medicinal chemists to find most promising scaffolds for their tasks using an interactive visualization that can help to evaluate both the diversity of known drugs and pharmacological promiscuity of each particular scaffold visually. Our scripts, that are freely available, can help to carry out such scaffold-based analysis and to visualize a compound library in a similar way.

The current study focuses on the synthesis of gold nanoparticles (AuNPs) using the plum peel extract obtained by deep eutectic solvent (DES) (Betaine-Urea and Choline chloride-Urea). Formation mechanism of DESs and molecular interactions between components has been studied using quantum chemical methods. DESs have been used for obtaining extracts from plum peel. It has been established that the reducing ability of extracts obtained using DESs is higher (489–580 mg ASE/g extract) than when using a traditional aqueous-alcohol solution (336 mg ASE/g extract). Gold nanoparticles were characterized by UV–vis spectroscopy, FTIR, and SEM-XRD analysis. The size of AuNPs was found to be 5–10 nm as per the particle size analyzer, and the zeta potential is − 46 to 47 mV. The scavenging ability of the sample solution to ABTS radical was determined by ABTS radical scavenging test. The AuNPs synthesized by extracting Cl-U exhibited significant antioxidant potential against ABTS•+, with an IC50 of 110 mg/mL. For the first time in a cosmetic product, AgNPs synthesized by plum peel extract in a deep eutectic solvent was used. The creams were evaluated for their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Bacillus subtilis. Results show that the cream with 0.5% AuNp increases the value of moisturizer for the skin.

Goal: We introduce an in-vivo validated finite element (FE) simulation approach for predicting individual knee joint kinematics. Our vision is to improve clinicians' understanding of the complex individual anatomy and potential pathologies to improve treatment and restore physiological joint kinematics. Methods: Our 3D FE modeling approach for individual human knee joints is based on segmentation of anatomical structures extracted from routine static magnetic resonance (MR) images. We validate the predictive abilities of our model using static MR images of the knees of eleven healthy volunteers in dedicated knee poses, which are achieved using a customized MR-compatible pneumatic loading device. Results: Our FE simulations reach an average translational accuracy of 2 mm and an average angular accuracy of 1$^\circ$ compared to the reference knee pose. Conclusions: Reaching high accuracy, our individual FE model can be used in the decision-making process to restore knee joint stability and functionality after various knee injuries.

This paper describes a generative design methodology for a micro hydrodynamic single-RBC (red blood cell) trap for applications in microfluidics-based single-cell analysis. One key challenge in single-cell microfluidic traps is to achieve desired through-slit flowrates to trap cells under implicit constraints. In this work, the cell-trapping design with validation from experimental data has been developed by the generative design methodology with an evolutionary algorithm. L-shaped trapping slits have been generated iteratively for the optimal geometries to trap living-cells suspended in flow channels. Without using the generative design, the slits have low flow velocities incapable of trapping single cells. After a search with 30,000 solutions, the optimized geometry was found to increase the through-slit velocities by 49%. Fabricated and experimentally tested prototypes have achieved 4 out of 4 trapping efficiency of RBCs. This evolutionary algorithm and trapping design can be applied to cells of various sizes.

Abstract Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs. Compared to a standard single extruder, sample exchange time was halved and the workload of users was greatly reduced. In-built temperature control of samples facilitated optimal extrusion and supported sample stability. After commissioning the device with lysozyme crystals, we collected time-resolved data using crystals of a membrane-bound, light-driven sodium pump. Static data were also collected from the soluble protein tubulin that was soaked with a series of small molecule drugs. Using these data, we identify low occupancy (as little as 30%) ligands using a minimal amount of data from a serial crystallography experiment, a result that could be exploited for structure-based drug design.

Introduction. Heart failure (HF) is a growing epidemic with high morbidity and mortality rates. In general, mortality in patients with HF is 10.4% after 30 days from admission, 22% after 1 year, and 42.3% after 5 years, despite the introduction of new evidence-based drug therapy and advance in surgical interventions. There is a range of predictors/ factors that need to be addressed to reduce the risk of mortality and to assess prognosis in patients with heart failure and reduced left ventricular ejection fraction. The aim. To determine the laboratory factors predicting 2-year mortality in patients with coronary artery disease and heart failure and reduced left ventricular ejection fraction after percutaneous coronary intervention (PCI) by analysis of basic patient data. Materials and methods. This one-center analysis, conducted at the Ukrainian Children’s Cardiac Center, Clinic for Adults, included 178 patients who had chronic stable coronary artery disease with heart failure and reduced left ventricular ejection fraction, who underwent PCI in the period between January 2020 and January 2022. The endpoint of our study was all-cause mortality. The studied group of patients was divided into two subgroups: S (“survival”) with patients who survived during the observation period after PCI, and D (“death”) including patients who died before the end of this observation period after the PCI. A p-value of less than 0.05 was considered statistically significant. Results. The mean length of hospital stay was 3 (1-5) days. Total bilirubin, total cholesterol, sodium, N-terminal pro B-type natriuretic peptide (NT-proBNP) level, hemoglobin, albumin and lymphocytes were significantly different in the two subgroups. In the multivariate model, the strongest independent predictors of patient mortality were: elevated NT-proBNP (adjusted hazard ratio [HR] for one standard deviation 1.44, 95% confidence interval [CI] 1.32 to 1.57, p

The review focuses on the collective monograph Dreiser’s Path: A View with a Modern Lens (2023). The scholarly work reevaluates Dreiser's significance as a classic of American literature and offers a contemporary perspective on his legacy through the lens of modern methodologies such as critical race theory, postcolonial theory, gender theory, etc. The attention of prominent researchers in American literature and culture from Russia, the USA, Canada, and the UK is drawn to Dreiser's contradictory and hermetic view of society and its artistic projection. The monograph reevaluates Dreiser's creative legacy, considering both major and well-known works as well as minor forms. The researchers featured in the monograph highlight the reasons why certain laws operate in Dreiser's artistic world, align Dreiser's value system with the social norms prevailing during his time, typologize the components of Dreiser's texts, and theorize them using contemporary methodological tools. They also juxtapose Dreiser's texts with other artifacts of American culture and demonstrate the evolution of Dreiser's perception from the times of the USSR to the present day. The monograph was conceived in 2021 as a special tribute to Theodore Dreiser to mark his 150 anniversary.

Sports governance is a broad domain in which many ambitious goals are expected to be considered by top management. Attending to productive organisational energy may be the key to consolidating and amplifying efforts by members of sports organisations at individual, group and organisational levels in order to achieve those wide-ranging goals. The aim of the article is to discover whether Estonian football organisations with higher results for the dimensions of productive organisational energy also show higher performance. Overall, we reached about 14% of the population of players, coaching staff and management from football organisations in Estonia. Productive organisational energy was measured using affective, cognitive and behavioural dimensions (Cole et al., 2012). Rankings in the league tables for 2020, 2021 and 2022 reflected the performance of the football clubs. The results demonstrated that football clubs that had higher levels of productive organisational energy were mostly placed in the top half of the league table. All three dimensions of productive organisational energy were similarly relevant in regard to performance. The connection between productive organisational energy and performance has so far been analysed only in business organisations and in one health service organisation. We brought the topic to the sports context and distinguished three dimensions of productive organisational energy while comparing the performance of organisations, which has not been done before. We also conducted the first empirical study that considers whether dimensions of productive organisational energy are balanced in better performing clubs.

This study presents a critical review of the experimental vapor-liquid equilibrium (VLE) data for the quaternary acetic acid-ethanol-ethyl acetate-water system and its subsystems that are reported in the literature. The thermodynamic consistency of the VLE data were verified using two integral tests: the Redlich–Kister test and the direct integration of the Gibbs–Duhem equation. The VLE data were correlated using the NRTL equation for further integration. Additionally, the reliable value of the integral derived from the direct integration of the Gibbs–Duhem equation for multicomponent systems under isothermal-isobaric conditions was estimated. This integral can be used for testing the thermodynamic consistency of experimental VLE data.

1,3-Dimethyl-2,3-dihydrobenzo[d]imidazoles, 1H, and 1,1',3,3'-tetramethyl-2,2',3,3'-tetrahydro-2,2'-bibenzo[d]imidazoles, 12, are of interest as n-dopants for organic electron-transport materials. Salts of 2-(4-(dimethylamino)phenyl)-4,7-dimethoxy-, 2-cyclohexyl-4,7-dimethoxy-, and 2-(5-(dimethylamino)thiophen-2-yl)benzo[d]imidazolium (1g–i+, respectively) have been synthesized and reduced with NaBH4 to 1gH, 1hH, and 1iH, and with Na:Hg to 1g2 and 1h2. Their electrochemistry and reactivity were compared to those derived from 2-(4-(dimethylamino)phenyl)- (1b+) and 2-cyclohexylbenzo[d]imidazolium (1e+) salts. E(1+/1•) values for 2-aryl species are less reducing than for 2-alkyl analogues, i.e., the radicals are stabilized more by aryl groups than the cations, while 4,7-dimethoxy substitution leads to more reducing E(1+/1•) values, as well as cathodic shifts in E(12•+/12) and E(1H•+/1H) values. Both the use of 3,4-dimethoxy and 2-aryl substituents accelerates the reaction of the 1H species with PC61BM. Because 2-aryl groups stabilize radicals, 1b2 and 1g2 exhibit weaker bonds than 1e2 and 1h2 and thus react with 6,13-bis(triisopropylsilylethynyl)pentacene (VII) via a “cleavage-first” pathway, while 1e2 and 1h2 react only via “electron-transfer-first”. 1h2 exhibits the most cathodic E(12•+/12) value of the dimers considered here and, therefore, reacts more rapidly than any of the other dimers with VII via “electron-transfer-first”. Crystal structures show rather long central C–C bonds for 1b2 (1.5899(11) and 1.6194(8) Å) and 1h2 (1.6299(13) Å).

It is commonly accepted that dietary nucleotides should be considered as essential nutrients originating mainly but not exclusively from meat and fish dishes. Most research in food science related to nutrition nucleotides is focused on raw products, while the effects of thermal processing of ready-to-eat food on nucleotide content are largely overlooked by the scientific community. The aim of this study is to investigate the impact of thermal processing and cold storage on the content of dietary nucleotides in freshly prepared and canned ready-to-eat meat and fish food. The concentrations of ATP, ADP, AMP, IMP, Ino, and Hx were determined using NMR, HPLC, FPMLC, and ATP bioluminescence analytical techniques; freshness indices K and K1 and adenylate energy charge (AEC) values were estimated to assess the freshness status and confirm a newly unveiled phenomenon of the reappearance of adenylate nucleotides. It was found that in freshly prepared at 65 °C ≤ T ≤ +100 °C and canned food, the concentration of free nucleotides was in the range of 0.001–0.01 µmol/mL and remained unchanged for a long time during cold storage; the correct distribution of mole fractions of adenylates corresponding to 0 < AEC < 0.5 was observed compared to 0.2 < AEC < 1.0 in the original raw samples, with either a high or low content of residual adenylates. It could be assumed that heating at nonenzymatic temperatures T > 65 °C can rupture cell membranes and release residual intracell nucleotides in quite a meaningful concentration. These findings may lead to a conceptual change in the views on food preparation processes, taking into account the phenomenon of the free adenylates renaissance and AEC bioenergetics.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. As MNTs are composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module appears advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated a high affinity for target receptors, as revealed by fluorescent-labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNTs. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

In this study, we evaluated the ability of the synthetic amphipathic helical peptide (SAHP), L-37pA, which mediates pathogen recognition and innate immune responses, to treat acute respiratory distress syndrome (ARDS) accompanied by diffuse alveolar damage (DAD) and chronic pulmonary fibrosis (PF). For the modeling of ARDS/DAD, male ICR mice were used. Intrabronchial instillation (IB) of 200 µL of inflammatory agents was performed by an intravenous catheter 20 G into the left lung lobe only, leaving the right lobe unaffected. Intravenous injections (IVs) of L-37pA, dexamethasone (DEX) and physiological saline (saline) were used as therapies for ARDS/DAD. L37pA inhibited the circulating levels of inflammatory cytokines, such as IL-8, TNFα, IL1α, IL4, IL5, IL6, IL9 and IL10, by 75–95%. In all cases, the computed tomography (CT) data indicate that L-37pA reduced lung density faster to −335 ± 23 Hounsfield units (HU) on day 7 than with DEX and saline, to −105 ± 29 HU and −23 ± 11 HU, respectively. The results of functional tests showed that L-37pA treatment 6 h after ARDS/DAD initiation resulted in a more rapid improvement in the physiological respiratory lung by 30–45% functions compared with the comparison drugs. Our data suggest that synthetic amphipathic helical peptide L-37pA blocked a cytokine storm, inhibited acute and chronic pulmonary inflammation, prevented fibrosis development and improved physiological respiratory lung function in the ARDS/DAD mouse model. We concluded that a therapeutic strategy using SAHPs targeting SR-B receptors is a potential novel effective treatment for inflammation-induced ARDS, DAD and lung fibrosis of various etiologies.

Basis sets consisting of functions that form linearly independent products (LIPs) have remarkable applications in quantum chemistry but are scarce because of mathematical limitations. We show how to linearly transform a given set of basis functions to maximize the linear independence of their products by maximizing the determinant of the appropriate Gram matrix. The proposed method enhances the utility of the LIP basis set technology and clarifies why canonical molecular orbitals form LIPs more readily than atomic orbitals. The same approach can also be used to orthogonalize basis functions themselves, which means that various orthogonalization techniques may be viewed as special cases of a certain nonlinear optimization problem. [ABSTRACT FROM AUTHOR]