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Supported sub-nano clusters hold great promise as economical and highly active catalysts. However, they tend to deactivate rapidly by poisoning and sintering, impeding their widespread use. We find that self-limiting poisoning can stabilize and promote cluster catalysis, i.e., poisoning is not always detrimental, but can sometimes be exploited. Specifically, Pt-Ge alloy clusters supported on alumina undergo slow coking (carbon deposition) under conditions of thermal dehydrogenation, yet preserve strong binding sites. For the case of Pt4Ge/alumina, theory shows a number of thermally populated isomers, one of which catalyzes carbon deposition. Because the clusters are fluxional at high temperatures, this isomer acts as a gateway, slowly converting all the clusters to Pt4GeC2. The surprising result is that Pt4GeC2 is highly catalytically active and selective against further coking, i.e., coking produces functional, stable catalytic clusters. Ge and C2 have synergistic electronic effects, leading to efficient and highly selective catalytic dehydrogenation that stops at alkenes, and improving stability. Thus, under reaction conditions, the clusters develop into a robust catalyst, suggesting an approach to practicable cluster catalysis.

Utilizing electric fields to catalyze chemical reactions is not a new idea, but in enzymology it undergoes a renaissance, inspired by Warhsel's concept of electrostatic preorganization. According to this concept, the source of the immense catalytic efficiency of enzymes is the intramolecular electric field that permanently favors the reaction transition state over the reactants. Within enzyme design, computational efforts have fallen short in designing enzymes with natural-like efficacy. The outcome could improve if long-range electrostatics (often omitted in current protocols) would be optimized. Here, we highlight the major developments in methods for analyzing and designing electric fields generated by the protein scaffolds, in order to both better understand how natural enzymes function, and aid artificial enzyme design.

Quantum and molecular mechanics (QM/MM) and QM-only (cluster model) modeling techniques represent the two workhorses in mechanistic understanding of enzyme catalysis. One of the stringent tests for QM/MM and/or QM approaches is to provide quantitative answers to real-world biochemical questions, such as the effect of single-point mutations on enzyme kinetics. This translates into predicting the relative activation energies to 1-2 kcal·mol-1 accuracy; such predictions can be used for the rational design of novel enzyme variants with desired/improved characteristics. Herein, we employ glutamate carboxypeptidase II (GCPII), a dizinc metallopeptidase, also known as the prostate specific membrane antigen, as a model system. The structure and activity of this major cancer antigen have been thoroughly studied, both experimentally and computationally, which makes it an ideal model system for method development. Its reaction mechanism is quite well understood: the reaction coordinate comprises a "tetrahedral intermediate" and two transition states and experimental activation Gibbs free energy of ∼17.5 kcal·mol-1 can be inferred for the known kcat ≈ 1 s-1. We correlate experimental kinetic data (including the E424H variant, newly characterized in this work) for various GCPII mutants (kcat = 8.6 × 10-5 s-1 to 2.7 s-1) with the energy profiles calculated by QM/MM and QM-only (cluster model) approaches. We show that the near-quantitative agreement between the experimental values and the calculated activation energies (ΔH⧧) can be obtained and recommend the combination of the two protocols: QM/MM optimized structures and cluster model (QM) energetics. The trend in relative activation energies is mostly independent of the QM method (DFT functional) used. Last but not least, a satisfactory correlation between experimental and theoretical data allows us to provide qualitative and fairly simple explanations of the observed kinetic effects which are thus based on a rigorous footing.

Abstract: A two-dimensional material – Mg2B4C2, belonging to the family of the conventional superconductor MgB2, is theoretically predicted to exhibit superconductivity with critical temperature Tc estimated in the 47–48 K range (predicted using the McMillian-Allen-Dynes formula) without any tuning of external parameters such as doping, strain, or substrate-induced effects. The origin of such a high intrinsic Tc is ascribed to the presence of strong electron-phonon coupling and large density of states at the Fermi level. This system is obtained after replacing the chemically active boron-boron surface layers in a MgB2 slab by chemically inactive boron-carbon layers. Hence, the surfaces of this material are inert. Our calculations confirm the stability of 2D Mg2B4C2. We also find that the key features of this material remain essentially unchanged when its thickness is increased by modestly increasing the number of inner MgB2 layers.

A novel form of charge density analysis, that of isosurface curvature redistribution, is formulated and applied to the toy problem of carbonyl oxygen activation in formaldehyde. The isosurface representation of the electron charge density allows us to incorporate the rigorous geometric constraints of closed surfaces toward the analysis and chemical interpretation of the charge density response to perturbations. Visual inspection of 2D isosurface motion resulting from applied external electric fields reveals how the isosurface curvature flows within and between atoms and that a molecule can be uniquely and completely partitioned into chemically significant regions of positive and negative curvatures. These concepts reveal that carbonyl oxygen activation proceeds primarily through curvature and charge redistribution within rather than between Bader atoms. Using gradient bundle analysis─the partitioning of formaldehyde into infinitesimal volume elements bounded by QTAIM zero-flux surfaces─the observations from visual isosurface inspection are verified. The results of the formaldehyde carbonyl analysis are then shown to be transferable to the substrate carbonyl in the ketosteroid isomerase enzyme, laying the groundwork for extending this approach to the problems of enzymatic catalysis.

The undesirable loss of methane (CH4 ) at remote locations welcomes approaches that ambiently functionalize CH4 on-site without intense infrastructure investment. Recently, we found that electrochemical oxidation of vanadium(V)-oxo with bisulfate ligand leads to CH4 activation at ambient conditions. The key question is whether such an observation is a one-off coincidence or a general strategy for electrocatalyst design. Here, a general scheme of electrocatalytic CH4 activation with d0 early transition metals is established. The pre-catalysts' molecular structure, electrocatalytic kinetics, and mechanism were detailed for titanium (IV), vanadium (V), and chromium (VI) species as model systems. After a turnover-limiting one-electron electrochemical oxidation, the yielded ligand-centered cation radicals activate CH4 with low activation energy and high selectivity. The reactivities are universal among early transition metals from Period 4 to 6, and the reactivities trend for different early transition metals correlate with their d orbital energies across periodic table. Our results offer new chemical insights towards developing advanced ambient electrocatalysts of natural gas.

The mechanisms of action of pyrimidine nucleoside derivatives on model lipid membranes of various compositions were studied. A systematic analysis of the tested agents’ effects on the membrane physicochemical properties was performed. Differential scanning microcalorimetry data indicated that the ability of nucleoside derivatives to disorder membrane lipids depended on the types of nucleoside bases and membrane-forming lipids. The 5′-norcarbocyclic uracil derivatives were found to be ineffective, while N4-alkylcytidines demonstrated the most pronounced effects, significantly decreasing the dipalmitoylphosphocholine melting temperature and cooperativity of phase transition. The elongation of hydrophobic acyl radicals potentiated the disordering action of N4-alkylcytidines, while an increase in hydrophilicity due to replacing deoxyribose with ribose inhibited this effect. The ability of compounds to form transmembrane pores was also tested. It was found that 5-alkyluridines produced single, ion-permeable pores in phosphatidylglycerol membranes, and that methoxy-mycolic acid and trehalose monooleate potentiated the pore-forming activity of alkyloxymethyldeoxyuridines. The results obtained open up perspectives for the development of innovative highly selective anti-tuberculosis agents, which may be characterized by a low risk of developing drug resistance due to the direct action on the membranes of the pathogen.

Background/Objectives: This study aims to explore family dynamics and the economic hardships experienced by families during the COVID-19 pandemic and their associations with adolescents’ health risk behaviours (HRBs). Methods: Based on a representative study of adolescents aged 11–16 conducted in Bulgaria during the COVID-19 pandemic and HBSC data from the pre-pandemic period, logistic regression models were applied, assessing cigarette smoking, vaping, alcohol use, drunkenness, and cannabis use. The independent variables included demographics, Family Affluence Scale (FAS III), family structure, ease of communication with parents, and the authors’ developed questions on parents’ income and economic status change, family conflicts, and missing contact with extended family due to the pandemic. Results: Material status of the family showed increasing differentials in adolescents’ HRBs during the pandemic. Parental unemployment, income reduction, and temporary lay-offs were associated with a higher risk of substance use. Family conflicts, missing contact with extended family, and difficulties in communication with the mother were related to a higher risk of substance use. Communication with the father was significantly associated with alcohol use and drunkenness. Boys had lower odds of vaping and higher odds of alcohol use, drunkenness, and cannabis use. Higher age and minority status were associated with an increase in adolescents’ HRBs. Conclusions: This study highlights the need for special family-focused interventions in times of health and economic crises.

In this study we demonstrated for the first time synthetic procedures for composites of salinomycin (SalH) and two-line ferrihydrite. The products were characterized by various methods such as elemental analysis, attenuated total reflectance–Fourier-transform spectroscopy (ATR-FTIR), electron paramagnetic resonance spectroscopy (EPR), powder X-ray diffraction analysis (XRD), electrospray-ionization mass spectrometry (ESI-MS), thermogravimetric analysis with differential thermal analysis (DTA) and mass spectrometry (TG-DTA/MS). The EPR spectra of the isolated compounds consisted of signals associated with both isolated Fe3+ ions and magnetically coupled Fe3+ ions. Powder XRD analyses of the isolated products showed two intense and broad peaks at 9° and 15° 2Θ, corresponding to salinomycinic acid. Broad peaks with very low intensity around 35°, assigned to two-line ferrihydrite, were also registered. Based on the experimental results, we concluded that salinomycin sodium reacted with Fe(III) chloride to form composites consisting of two-line ferrihydrite and salinomycinic acid. One of the composites exerted pronounced antitumor activity in the sub-micromolar concentration range against human cervical cancer (HeLa), non-small-cell lung cancer (A549), colon cancer (SW480), and ovarian teratocarcinoma (CH1/PA1) cells.

Motivated by the widespread occurrence of directional crystallization in nature, laboratory experiments and industrial facilities, we consider how a two-phase (mushy) region filled simultaneously with liquid and solid material influences the process and changes the solute concentration in both the phases. A mushy layer arising as a result of constitutional supercooling in binary liquids drastically changes all process parameters in comparison with the frequently used approximation of a macroscopically planar phase interface. The heat and mass transfer problem with a moving mushy region is replaced by the equivalent model with a discontinuity interface that divides the liquid and solid phases and inherits the properties of a mushy layer. Analytical solutions that describe both crystallization modes with a planar phase interface and discontinuity interface (representing a mushy layer) are constructed for the steady-state and self-similar conditions. The switching time of the crystallization model with a planar phase interface to the model with a two-phase layer is determined. Our calculations, based on analytical solutions, show that the presence of a mushy layer can change the solute concentration in liquid and solid phases to a few tens of percent as compared to the planar interface model. This explains the importance of accounting for the two-phase region when describing the crystallization of supercooled binary liquids.

The article examines the relation between the architecture of a public square and the level of its social activity. The concept of a place’s sociocultural environment and its influence on the popularity and attractiveness of the area in the city are analyzed in detail. It is suggested that vibrant urban life could be restored using a method of sociocultural programming of city squares by changing the physical conditions of the environment for different scenarios of space use. Emphasis is placed on identifying architectural means for the implementation of sociocultural programmes that create opportunities for various forms of social interaction and everyday and festive activities of people in the public square.

Reaction barriers are key to our understanding of chemical reactivity and catalysis. Certain reactions are so seminal in chemistry that countless variants, with or without catalysts, have been studied, and their barriers have been computed or measured experimentally. This wealth of data represents a perfect opportunity to leverage machine learning models, which could quickly predict barriers without explicit calculations or measurement. Here, we show that the topological descriptors of the quantum mechanical charge density in the reactant state constitute a set that is both rigorous and continuous and can be used effectively for the prediction of reaction barrier energies to a high degree of accuracy. We demonstrate this on the Diels-Alder reaction, highly important in biology and medicinal chemistry, and as such, studied extensively. This reaction exhibits a range of barriers as large as 270 kJ/mol. While we trained our single-objective supervised (labeled) regression algorithms on simpler Diels-Alder reactions in solution, they predict reaction barriers also in significantly more complicated contexts, such a Diels-Alder reaction catalyzed by an artificial enzyme and its evolved variants, in agreement with experimental changes in kcat. We expect this tool to apply broadly to a variety of reactions in solution or in the presence of a catalyst, for screening and circumventing heavily involved computations or experiments.

In the last 50 years, the blue copper proteins became central targets of investigation. Extensive experiments focused on the Cu coordination to probe the effect of local perturbations on its properties. We found that local electric fields, generated by charged residues evolutionarily placed throughout the protein edifice, mainly second sphere, but also more remotely, constitute an additional significant factor regulating blue copper proteins. These fields are not random, but exhibit a highly specific directionality, negative with respect to the and vectors in the Cu first shell. The field magnitude contributes to fine-tuning of the geometric and electronic properties of Cu sites in individual blue copper proteins. Specifically, the local electric fields evidently control the Cu-SMet bond distance, Cu(ii)-SCys bond covalency, and the energies of the frontier molecular orbitals, which, in turn, govern the Cu(ii/i) reduction potential and the relative absorption intensities at 450 nm and 600 nm.

Introduction. An analysis of mathematical models of two-dimensional planned flows was carried out. Such flows are characterized by local depth-averaged velocities and local depths at each point of the flow. The mathematical model formation of the water flow is based on its division into several sections. There is a section where the flow parameters (velocity, depth, width) are kept constant at the stage of flow exit from the pipe — the inertial front. The purpose of the article and its relevance are defined.Materials and methods. By introducing dimensionless complexes on the basis of π-theorem, the formula for the length of inertial front of the water flow at its spreading from a rectangular pipe into a wide diverting channel is derived. An analogy from gas dynamics is used, namely, the transition to the plane of the velocity hodograph. Using the velocity hodograph, the distribution of depths and velocities of the flow along its longitudinal axis of symmetry and along the extreme line of current was obtained. The main computation tasks for the flow parameters have been formulated.Results. Numerical calculations of the formulated main tasks for determining flow parameters are described. Comparison with experimental data is given and the adequacy of the refined mathematical model of a two-dimensional planned flow is confirmed.Conclusions. The resulting formula for the length of the inertial front makes it possible to achieve the desired error in calculating the parameters of the water flow. With flow expansions up to 5, the relative error of the ordinates and flow velocities does not exceed 7–10 %. Calculation formulas and implemented programs will allow HTS designers to quickly and accurately determine the boundaries, speed and depth of free flow on the culvert.

Introduction. Secreted metabolites with enzymatic or toxic properties are important for effecting of Candida spp pathogenicity. The most clinically significant species is C. albicans. However, invasive infections associated with C. auris have a great significance. The aim of the investigation is comparison the some of enzymatic properties and biocidal activity of C. auris with those of C. albicans. Materials and methods. C. albicans and C. auris strains were used in the study. Growth of micromycetes was detected on nutrient agar, Sabouraud agar or blood agar (with hemolysis presence). The Candida spp. proteinase activity was determined on Difco agar with 2% casein and by cleavage of IgG molecules. Candida lipase activity was assessed on the agar with Tween-20. The viability of buccal epithelial cells after exposure (1 4 h) with candida metabolites was estimated by trypan blue assay. Statistical analysis was performed using RStudio software. Results. The best growth of C. albicans was observed on Sabouraud agar, and C. auris on blood agar. Only C. auris had hemolytic and lipase activity. Protease activity of some C. auris strains was noted. They were able to cleave casein and damage IgG molecules. The metabolites of some Candida strains decreased the viability of epithelial cells while the reduction was more pronounced in the experiments with C. auris (р 0.05). Conclusion. The most suitable medium for C. auris culturing was blood agar. Proteolytic, antiglobulin, hemolytic and lipase activities were observed only for C. auris. C. auris demonstrated more invasive capacity compared to C. albicans. The observed micromycete biocidal activity against buccal epithelial cells was strain-dependent.

The results of the studies of the features of adaptation of triploid aspen regenerants obtained in vitro using a hydroponic system are discussed in the article. Triploid clones of aspen (Populus tremula L.) are characterized by rapid growth, high wood quality and increased resistance to diseases and pests compared to diploid clones and can be used to create forest plantations. Use of clonal micropropagation is advisable to preserve the valuable gene pool of triploid forms of aspen, while the adaptation of plants to ex vitro conditions is the most difficult process. Growing plants using the hydroponic method has several advantages. Triploid aspen regenerants, in which the length of the green mass prevails over the root mass, have a normal development without signs of infection and a good turgor of the green mass when they are removed from the test tube during the adaptation. Triploid aspen regenerants with decapitation of the apical shoot have the ratio of the lengths of the green mass to the root mass is close to 1:1, while the predominance of roots with values above the average is observed. Aspen plants with a predominance of root mass over green are formed from regenerants with leaving of 2 internodes and have an average of 2 roots of the first order. Triploid aspen plants-regenerants with biometric parameters of roots 5–7 cm and green mass up to 5 cm had the highest survival rates (94.7–100 %). A gradual decrease in the leaf surface area contributes to a better survival of regenerants, while it is necessary to reduce the humidity level from 100 % at the initial stage of adaptation to 60 % within 5 days, then – on 20 % with an interval of 3 days. The period of adaptation of triploid aspen plants in a hydroponic system is 16 days.

Abstract The ongoing COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people worldwide and has significant implications for public health. Host transcriptomics profiling provides comprehensive understanding of how the virus interacts with host cells and how the host responds to the virus. COVID-19 disease alters the host transcriptome, affecting cellular pathways and key molecular functions. To contribute to the global effort to understand the virus’s effect on host cell transcriptome, we have generated a dataset from nasopharyngeal swabs of 35 individuals infected with SARS-CoV-2 from the Campania region in Italy during the three outbreaks, with different clinical conditions. This dataset will help to elucidate the complex interactions among genes and can be useful in the development of effective therapeutic pathways.

The Hydra nervous system is the paradigm of a ‘simple nerve net’. Nerve cells in Hydra, as in many cnidarian polyps, are organized in a nerve net extending throughout the body column. This nerve net is required for control of spontaneous behavior: elimination of nerve cells leads to polyps that do not move and are incapable of capturing and ingesting prey (Campbell, 1976). We have re-examined the structure of the Hydra nerve net by immunostaining fixed polyps with a novel antibody that stains all nerve cells in Hydra. Confocal imaging shows that there are two distinct nerve nets, one in the ectoderm and one in the endoderm, with the unexpected absence of nerve cells in the endoderm of the tentacles. The nerve nets in the ectoderm and endoderm do not contact each other. High-resolution TEM (transmission electron microscopy) and serial block face SEM (scanning electron microscopy) show that the nerve nets consist of bundles of parallel overlapping neurites. Results from transgenic lines show that neurite bundles include different neural circuits and hence that neurites in bundles require circuit-specific recognition. Nerve cell-specific innexins indicate that gap junctions can provide this specificity. The occurrence of bundles of neurites supports a model for continuous growth and differentiation of the nerve net by lateral addition of new nerve cells to the existing net. This model was confirmed by tracking newly differentiated nerve cells.

Different samples of Asahi model SB-1000 polymer optical fibers arranged at different curvatures were aged to predict the loss of light transmission over 10 years. They were used in the FV0 detector of the ALICE experiment at the LHC. The fibers were exposed to 80°C, maintaining a relative humidity of less than 50% RH. The relative transmission loss was measured before and after aging. A maximum loss of 15% was found for 632 hr of aging, equivalent to 5 years for the ALICE experiment conditions considering thermal aging. This estimate is based on the Arrhenius model, using energy activation data from the literature. Complementary tests were done to analyze the fiber materials, such as XRD (WAX), FTIR, and mechanical tensile tests. For FTIR, no changes are found that indicate modifications in the chemical structure but in the physical properties of the materials. A study based on XRD shows that during the first 72 hr, changes in crystal size were observed, and consequently, there was a loss of transparency. Hence, mechanical tests indicate that the fiber decreases its Young’s modulus with longer aging times, making the material more tenacious to rupture.

Pasteurella canis is a Gram-negative facultative anaerobic bacterium that is a typical commensal of the oral cavity and enteric tract of domestic animals. Human infections caused by this species are most often associated with dog bites and rarely with other animal bites. In this report, we present a case of a 34-year-old man who developed P. canis soft tissue infection of the left hand after a cat bite. The patient was successfully treated by a surgical intervention and antibiotics. The species identification of the isolate was performed by a conventional automatic system and nucleic acid-based methods. The nucleic acid-based methods provide a powerful alternative to the conventional microbiological diagnostic of these bacteria.