A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

The phenomenon of dissipative self-organization is studied on the example of time-crystal networks. Particular attention was given to transient processes, attractor topologies, phase transitions, and asymptotic stability. New concepts were introduced, including topological phases, spinorial states, and bond flavors. Concepts such as ground states, chemical potentials, elastic forces, temperature, and statistical distributions were endowed with a new meaning associated with asymptotic stability. Phenomena usually attributed exclusively to quantum physics have been shown to occur in this essentially classical environment. They coexist with, and in some cases, such as charge quantization, are related to the phenomenon of time dilation. The approach was applied to model vacuum self-organization. We have shown that under the ac-tion of competing forces, such as gravity and antigravity, a cascade of phase transitions can transform an unorganized vacuum into phases in which interactions, fields and waves resemble electromagnetic, weak, and strong, and their elements can be used as building blocks for prototype particles. In addition, some interrelation field parameters and probabilities of particle transmutations were calculated, which are not predicted by the standard model. The results are consistent with the experiment. The presented material and methodology may be of interest for studying self-organization in different environments.

A number of experiments suggest that the elementary particles are non-local entities. A dissipative self-organization, that treats particles as open systems may provide a better understanding of the underlying phenomena than conservative models. The proposed toy model is such an attempt. We found that self-gravitation (although accompanied by self-diffusion) may not only be compatible with the quantum phenomena but is perhaps the major reason for the existence of quantum fields. According to the proposed model, fields/particles (resemble those of the Standard Model) emerge from a dynamic self-organized medium (which we associate with vacuum dust) from competition between self-gravitation and self-diffusion. These forces produce turbulence in the form of vortices (which we call vacuum cells) that serve as the building blocks for fields and particles. Field/particle features and symmetries are based on their internal (intracellular) dynamics and vortex synchronization (intercellular dynamics). This model allows for rough estimations of relative field coupling strengths, the quantity of charges and flavors, the probabilities of quark transmutations, the dimensionality and the topologies of phase spaces, and other Standard Model parameters that came not from the theory but rather determined by experiment.

A total of 381 hepatitis B virus (HBV) DNA sequences collected from 9 groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strain from Central Asian republics and Mongolia. Different HBV subgenotypes predominated in various native Siberian populations. Subgenotype D1 was dominant in Altaian Kazakhs (100%), Tuvans (100%), and Teleuts (100%) of southern Siberia as well as in Dolgans and Nganasans (69%), who inhabit the polar Taimyr Peninsula. D2 was the most prevalent subgenotype in the combined group of Nenets, Komi, and Khants of the northern Yamalo-Nenets Autonomous Region (71%), and in Yakuts (36%) from northeastern Siberia. D3 was the main subgenotype in South Altaians (76%) and Buryats (40%) of southeastern Siberia, and in Chukchi (51%) of the Russian Far East. Subgenotype C2 was found in Taimyr (19%) and Chukchi (27%), while subgenotype A2 was common in Yakuts (33%). In contrast, D2 was dominant (56%) in urban populations of the former western USSR, and D1 (62%) in Central Asian republics and Mongolia. Statistical analysis demonstrated that the studied groups are epidemiologically isolated from each other and might have contracted HBV from different sources during the settlement of Siberia.

The general coupling between particle transport and ionization-recombination processes in hot plasma is considered on the key concept of equilibrium charge state (CS) transport. A theoretical interpretation of particle and CS transport is gained in terms of a two-dimensional (2D) Markovian stochastic (random) processes, a discrete 2D Fokker-Plank-Kolmogorov equation (in charge and space variables) and generalized 2D coronal equilibrium between atomic processes and particle transport. The basic tool for analysis of CS equilibrium and transport is the equilibrium cell (EC) (two states on charge and two on space), which presents (i) a unit phase volume, (ii) the characteristic scale of local equilibrium, (iii) a comprehensive solution for the simplest nonlinear relations between transport and atomic processes. The approach opens up new perspectives on transport studies: (i) the direct modelling of equilibrium and transport of impurity using the atomic data base, (ii) recovery of the complete recombination rate profile based on knowledge of density profiles and ionization rate profiles, (iii) the local transport analysis, based on the reduction of the equilibrium set to the single EC (in particular, central or edge), (iv) analysis of the reduced transport coefficients (diffusion and convection) on the density profile measurements.

An important moment in the establishment of forestry seed orchards is the formation of their optimal composition, avoiding inbreeding depression in the outgoing seed material which occurs due to crossbreeding between closely related plus trees, the clones of which comprise the orchards. It is possible to minimize the negative effect of inbreeding by considering the hereditary aspect of the heterogeneous seed orchard material. The purpose of our work is to provide a comparative assessment of the formation and lignification of xylem in annual shoots of the plus trees of Scots pine. We investigated the formation and lignification of xylem in the annual shoots of the plus trees of Scots pine (Pinus sylvestris L.), found in natural forests in the Nizhny Novgorod region of the Russian Federation. Their vegetative progeny were cultivated in the clone archive stationed in the same region. Analyzing the one-type of the 1-year shoots, the time that the shoots were cut from the branches corresponded to the presence of plants in the characteristic phenological phases of seasonal development. A histochemical study of xylem was conducted, using the qualitative reactions of phloroglucinol to lignin. The power of xylem development was estimated by counting, in the radial direction, the cell rows from the core to the cambium in the microscope’s field of view. A significant differentiation of plus trees was revealed in a complex of signs characterizing the level of xylem development and the degree of xylem cell lignification in the tissues of annual shoots. Phenotypic differences in the physiological state of plus trees appeared given a leveled ecological background, indicating their genotypic determinism. This was confirmed by an analysis of variance. The share of the influence of differences between the proper plus trees was between 25.16% ± 8.91% and 53.98% ± 5.48% of the total phenotypic variance of the signs of the seasonal state of xylem. Factor analysis was used to reduce the number of considered indicators of xylem physiological state. The results allowed a cluster analysis to be carried out on the basis of the normalized values of the initial xylem features as well as the principal components derived from them. The association of plus trees was done on the basis of the similarity of the multidimensional estimates of xylem seasonal condition. The objects that were the most remote from the others were identified. This information provides a reasonable approach to the formation of an assortment of Scots pine seed orchards.

The factors influencing hepatitis E virus (HEV) circulation remain largely unexplored. We investigated HEV seroprevalence in humans and the prevalence of infection in farm pigs and rabbits in different regions of the Russian Federation, as well as the genetic diversity and population dynamics of HEV. Anti-HEV IgG antibody detection rates in the general population increase significantly with age, from 1.5% in children and adolescents under 20 years old to 4.8% in adults aged between 20 and 59 years old, to 16.7% in people aged 60 years and older. HEV seroprevalence varies between regions, with the highest rate observed in Belgorod Region (16.4% compared with the national average of 4.6%), which also has the country’s highest pig population. When compared with the archival data, both increases and declines in HEV seroprevalence have been observed within the last 10 years, depending on the study region. Virus shedding has been detected in 19 out of the 21 pig farms surveyed. On one farm, circulation of the same viral strain for five years was documented. All human and animal strains belonged to the HEV-3 genotype, with its clade 2 sequences being predominant in pigs. Sequences from patients, pigs, and sewage from pig farms clustered together, suggesting a zoonotic infection in humans and possible environmental contamination. The HEV-3 population size predicted using SkyGrid reconstruction demonstrated exponential growth in the 1970s–1990s, with a subsequent decline followed by a short rise around the year 2010, the pattern being similar to the dynamics of the pig population in the country. The HEV-3 reproduction number (Re) predicted using Birth-Death Skyline analysis has fluctuated around 1 over the past 20 years in Russia, but is 10 times higher in Belgorod Region. In conclusion, HEV-3 circulation varies both geographically and temporally, even within a single country. The possible factors contributing to this variability are largely related to the circulation of the virus among farm pigs.

In our work, using the analysis of DNA barcodes and morphology (wing color, male genitalia, sphragis shape in females), we show that the group of species close to P. mnemosyne is represented by two phylogenetic lineages, the western and eastern ones. The eastern lineage includes P. stubbendorfii, P. glacialis and P. hoenei. The western lineage includes three morphologically similar species, P. mnemosyne (Western Eurasia), P. turatii (southwestern Europe) and P. nubilosus stat. nov. (Turkmenistan and NE Iran), as well as P. ariadne (Altai). The latter species differs from the rest of the group in the presence of red spots on the wings. Parnassius mnemosyne s.s. is represented by four differentiated mitochondrial clusters that show clear association with specific geographic regions. We propose to interpret them as subspecies: P. mnemosyne mnemosyne (Central and Eastern Europe, N Caucasus, N Turkey), P. mnemosyne adolphi (the Middle East), P. mnemosyne orientalis (Tian Shan) and P. mnemosyne gigantea (Gissar-Alai in Central Asia). We demonstrate that in P. ariadne the red spots on the wing evolved as a reversion to the ancestral wing pattern. This reversion is observed in Altai, where the distribution areas of the western lineage, represented by P. ariadne, and the eastern lineage, represented by P. stubbendorfii, overlap. These two species hybridize in Altai, and we hypothesize that the color change in P. ariadne is the result of reinforcement of prezygotic isolation in the contact zone. Lectotype of Parnassius mnemosyne var. nubilosus Christoph, 1873 is designated.

Soil organic carbon (SOC) is an essential condition for soil health and a potential sink for greenhouse gases. SOC dynamics in a long-term field experiment with mineral and organic fertilization on loamy sand Podzol in Vladimir Region, Russia, was traced with the dynamic carbon model RothC since 1968 until the present time. During this period, C stock increased 21% compared with the initial level in the treatment with the application of manure in an average annual rate of 10 t·ha-1. The model was also used to forecast SOC changes until 2090 for two contrasting RCP4.5 and RCP8.5 climatic scenarios. Until 2090, the steady growth of SOC stocks is expected in all compared treatments for both climate scenarios. This rate of growth was the highest until 2040, decreased in 2040-2070 and increased again in 2070-2090 for RCP4.5. The highest annual gain was within 21-27‰ under RCP4.5 and 16-21‰ in 2020-2040 in 0-20 cm soil layer. The expected accumulation of C allows increasing current C stock 1.6-1.7 times for RCP4.5 and 2.0-2.2 times for RCP8.5 scenario. Modelling demonstrated potentially more favourable conditions for SOC stability in arable Podzols than in Retisols in Central Russia in the 21st century.

Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of Flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.

This paper develops the study of the effect of powerful ultrasound on the laser breakdown of liquids and a comparative study of the possibilities of acoustic and optical diagnostics of breakdown. The method of laser-induced breakdown spectroscopy (LIBS) for elemental analysis of liquids, along with high efficiency, continues to be less sensitive compared to traditional chemical methods. The paper develops a method of using additional ultrasound irradiation of the laser breakdown area in order to increase the efficiency of LIBS. Using the developed technique, spectral lines of chemical elements such as potassium, manganese, sodium, calcium, etc. were obtained for the first time depending on the frequency and power of ultrasound. It is shown that a sharp increase in the intensity of spectral lines of elements in water during laser breakdown is observed in the field of high-power ultrasound. It indicates an increase in the sensitivity of the combined method of ultrasonic LIBS. Along with the optical spectrum, the spectral and energy characteristics of acoustic emission were studied. An automated complex for hydrophysical and spectral studies is described, which was tested in the Sea of Japan during the voyage No. 81 of the research vessel RV "Professor Gagarinsky" in August 2022.

The presence of bubbles near the sea surface under certain conditions leads to abnormal sound scattering and a significant change in the acoustic properties of the upper layer of the sea. The article presents some results of sound scattering studies under various sea conditions, up to stormy conditions, when extensive bubble clouds arise. By the method of unsteady acoustic spectroscopy, data on the size distribution of bubbles at various depths have been obtained, which can be described by a power function with exponential decay at small bubble sizes of the order of 10 microns. Estimates of the gas content in bubble clouds and their influence on the acoustic characteristics of the upper layer of the sea have been carried out. It is shown that at sufficiently high concentrations, sharp increases in absorption and dispersion of the sound velocity are observed. Modeling of sound propagation in the presence of a quasi-homogeneous bubble layer shows that it leads both to a change in the laws of the average decay of the sound field along the sound propagation path and to a change in the shallow spatial structure of the field.

Oligonucleotide conjugates with boron clusters have found applications in different fields of molecular biology, biotechnology, and biomedicine as potential agents for boron neutron capture therapy, siRNA components, and antisense agents. Particularly, closo-dodecaborate anion represents a high-boron containing residue with remarkable chemical stability and low toxicity, suitable for the engineering of different constructs for biomedicine and molecular biology. In the present work, we synthesized novel oligonucleotide conjugates of closo-dodecaborate attached to the 5'-, 3'-, or both terminal positions of DNA, RNA, 2'-O-Me RNA, and 2'-F-Py RNA oligomers. For their synthesis, we employed click reaction with the azido derivative of closo-dodecaborate. The key physicochemical characteristics of the conjugates have been investigated using high-performance liquid chromatography, gel electrophoresis, UV thermal melting, and circular dichroism spectroscopy. Incorporation of closo-dodecaborate residues at the 3'-end of all oligomers stabilized their complementary complexes, while analogous 5'-modification decreased duplex stability. Two boron clusters attached to the opposite ends of the oligomer only slightly influence the stability of complementary complexes of RNA oligonucleotide and its 2'-O-methyl and 2'-fluoro analogs. On the contrary, the same modification of DNA oligonucleotides significantly destabilized DNA/DNA duplex but gave a strong stabilization of the duplex with RNA target. According to CD spectroscopy results, two terminal closo-dodecaborate residues cause a prominent structural rearrangement of complementary complexes with a substantial shift from B-form to the A-form of the double helix. The revealed changes of key characteristics of oligonucleotides caused by incorporation of terminal boron clusters, such as the increase of hydrophobicity, change of duplex stability, and prominent structural changes for DNA conjugates, should be taken into account for the development of antisense oligonucleotides, siRNAs, or aptamers bearing boron clusters. These features may also be used for engineering of developing NA constructs with pre-defined properties.

The review concerns the chemical structures of all the triterpene glycosides from the most valuable commercially harvesting North Atlantic sea cucumber Cucumaria frondosa and their biological activities. The isolation and structural elucidation of 17 specific triterpene glycosides are described along with isolation and identification of two known glycosides. Antitumor, immunomodulatory, antithrombotic and anti-Alzheimer disease activities are also described. Frondoside A, the major component of the glycosidic fraction seems to be very perspective leader-compound for creation of useful medicinal preparations.

Legume plants enter symbiosis with soil nitrogen-fixing bacteria (rhizobia), thereby gaining access to the assimilable atmospheric nitrogen. This symbiosis is important for agriculture, thus, biofertilizers with effective strains of rhizobia are created for crop legumes to increase their yield and minimize the amounts of mineral fertilizers used. In this work, we sequenced and characterized the genome of Rhizobium leguminosarum bv. viciae strain RCAM1022, a component of the ‘Rhizotorfin’ biofertilizer produced in Russia and used for pea (Pisum sativum L.).

As the problem of traction injuries to brachial plexus is a common one and of high socio-economic significance, the analysis of the surgical outcomes in patients with this pathology is significant for neurosurgery, neurology, traumatology-orthopedics, and rehabilitation. The aim of the research is to compare the short-term outcomes of using various surgical methods for managing patients with closed traction injuries of brachial plexus. Material and methods. The research involved 61 patients with closed traction injury of brachial plexus divided into two groups homogeneous in sex, age and severity of their neurological deficit: Group I – 33 patients who underwent microsurgical neurolysis, Group II – 28 patients who underwent microsurgical neurolysis combined with one-level electrostimulation. The dynamic assessment of clinical and functional status of upper limbs was performed using scale methods and electrophysiological monitoring. Results. The research revealed a more evident recovery of the upper limb function in Group II patients suggesting the method of microsurgical neurolysis combined with electrostimulation to be preferable in case of closed traction injuries to brachial plexus. Conclusion. The combination of microsurgical neurolysis with one-level electrostimulation improves the short-term outcomes of surgical treatment in patients with closed traction injuries of brachial plexus due to a sooner decrease in pain in postoperative period, and positive dynamics of clinical and electrophysiological parameters.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

The need for multi-gene analysis in evolutionary and taxonomic studies is generally accepted. However, sequencing of multiple genes is not always possible. For various reasons, short mito-chondrial DNA barcodes are the only source of molecular information for some species in many genera, although multilocus data are available for other species of the same genera. In particular, such a situation exists in the species-rich butterfly subgenus Polyommatus (Agrodiaetus). Here, we analysed partitioning of this subgenus into species groups by using three data sets. The first data set was represented by short mitochondrial DNA barcodes for all analysed samples. The second and third data sets were represented by combination of short mitochondrial DNA barcodes for a part of the taxa with longer mitochondrial sequences COI+tRNA-Leu+COII (data set 2) and with longer mitochondrial COI+tRNA-Leu+COII and nuclear 5.8S rDNA+ITS2+28S rDNA sequences (data set 3) for the remaining species. We show that DNA barcoding approach (data set 1) failed to reveal the taxonomic structure resulting in numerous polytomies in the phylogenetic tree ob-tained. Combined analysis of the mitochondrial and nuclear sequences (data sets 2 and 3) re-vealed the species groups and position within these species groups even for the taxa for which only short DNA barcodes were available.

The generalized dual-kinetic-balance approach for axially symmetric systems is employed to solve the two-center Dirac problem. The spectra of one-electron homonuclear quasimolecules are calculated and compared with the previous calculations. The analysis of the monopole approximation with two different choices of the origin is performed. Special attention is paid to the lead and xenon dimers, Pb82+–Pb82+–e− and Xe54+–Xe54+–e−, where the energies of the ground and several excited σ-states are presented in the wide range of internuclear distances. The developed method provides the quasicomplete finite basis set and allows for construction of the perturbation theory, including within the bound-state QED.

The body of scientific literature continues to grow annually. Over 1.5 million abstracts of biomedical publications were added to the PubMed database in 2021. Therefore, developing cognitive systems that provide a specialized search for information in scientific publications based on subject area ontology and modern artificial intelligence methods is urgently needed. We previously developed a web-based information retrieval system, ANDDigest, designed to search and analyze information in the PubMed database using a customized domain ontology. This paper presents an improved ANDDigest version that uses fine-tuned PubMedBERT classifiers to enhance the quality of short name recognition for molecular-genetics entities in PubMed abstracts on eight biological object types: cell components, diseases, side effects, genes, proteins, pathways, drugs, and metabolites. This approach increased average short name recognition accuracy by 13%. The new ANDDigest version (01.2022) has a web interface and is freely available to users at https://anddigest.sysbio.ru/.

Novel segmented tick-borne RNA viruses belonging to the group of Jingmenviruses (JMVs) are widespread across Africa, Asia, Europe, and America. In this work, we obtained whole-genome sequences of two Kindia tick virus (KITV) isolates and performed modeling and functional annotation of the secondary structure of 5’ and 3’ UTRs from JMV and KITV viruses. UTRs of various KITV segments are characterized by: (1) polyadenylated 3’ UTRs; (2) 5’ DAR and 3’ DAR motifs; (3) a highly conserved 5’-CACAG-3’ pentanucleotide; (4) a La protein binding site; (5) multiple UAG sites providing interactions with the MSI1 protein; (6) three homologous sequences in the 5’ UTR and 3’ UTR of segment 2; (7) the segment 2 3’ UTR of a KITV/2017/1 isolate comprises two consecutive 40 nucleotide repeats forming a Y-3 structure; (8) a 35-nucleotide deletion in the second repeat of the segment 2 3’ UTR of KITV/2018/1 and KITV/2018/2 isolates, leading to a modification of the Y-3 structure; (9) two pseudoknots in the segment 2 3’ UTR; (10) the 5’ UTR and 3’ UTR are represented by patterns of conserved motifs; (11) the 5’-CAAGUG-3’ sequence occurs in early UTR hairpins. Thus, we identified regulatory elements in the UTRs of KITV, which are characteristic of orthoflaviviruses. This suggests their functional significance for the replication of JMVs and the evolutionary similarity between orthoflaviviruses and segmented flavi-like viruses.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

Practically important properties of real liquids, including seawater, are their nonlinear properties, which include a nonlinear acoustic parameter, as well as cavitation strength – a rupture of the continuity of a liquid at high intensities in an acoustic wave. The manifestation of nonlinear effects is greatly facilitated by the presence of various nuclei in the liquid – gas bubbles, foreign particles, and other inclusions of various origins. For practical applications, it is important to study the properties of real liquids with inclusions in them. Due to the difficulties of measuring cavitation strength by acoustic methods, other methods are being sought. It is proposed to use an optoacoustic method associated with the use of laser radiation that causes optical breakdown - optical cavitation, that accompanied by a strong sound generation effect. The connection between optical breakdown thresholds and acoustic cavitation thresholds has been established, which can later be used to identify cavitation thresholds at high static pressures (at great depths in the sea), where the use of acoustic emitters is extremely difficult. The paper studies the bubble size distribution function in seawater, combined with studies of the acoustic nonlinearity parameter and cavitation strength at various depths. The interrelation of these characteristics for seawater is shown.

Chiral semiconductor nanostructures and nanoparticles are promising materials for applications in biological sensing, enantioselective separation, photonics, and spin-polarized devices. Here, we have studied the induction of chirality in atomically thin only 2 monolayers thick CdSe nanoplatelets (NPLs) grown by a colloidal method and exchanged with L-alanine and L-phenylalanine as model thiol-free chiral ligands. We have developed a novel two-step approach to completely exchange the native oleic acid ligands for chiral amino acids at the basal planes of NPLs. We performed an analysis of the optical and chiroptical properties of the chiral CdSe nanoplatelets with amino acids, which was supplemented by an analysis of the composition and coordination of ligands. After the exchange, the nanoplatelets retain HH, LH and SO exciton absorbance and bright HH exciton luminescence. Capping with thiol-free enantiomer amino acid ligands induce pronounced chirality of excitons in the nanoplatelets, as proven by circular dichroism spectroscopy, with high dissymmetry g-factor up to 3.4 × 10−3 achieved for HH excitons in the case of L-phenylalanine.

New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N'-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or by a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalon- dianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichlorophenyl)- 7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was con-firmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computa-tional scheme. The results revealed that the rate limiting step is a cyclization process leading to the closure of 1,4-dihydropyridine ring with an activation barrier of 28.8 kcal/mol. Some of dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D . Additional-ly, ADMET parameters were calculated and molecular docking studies were performed to identify potential protein targets.

The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individual susceptibility to viral infection. In turn, SARS-CoV-2 can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via ACE2 принимая во внимание его влияние на, other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of LDL, launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized

Current-quark masses are compared to the rest masses allowed by the Helmholtz equation in a polar model. Within the uncertainty of the current u quark mass determination, the current quark mass coincides with the rest mass allowed by the Helmholtz equation in the polar model in accordance with the second root of the zero Neumann function. Current d quark mass coincides with the rest mass calculated in accordance with the third root of the Bessel zero function. On the basis of a comparison of these results with the results obtained earlier for ordinary real particles u and d quarks stability is discussed.

Species of the genus Drosophila have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are underinvestigated. Here we performed the analysis of hybrid female sterility by crossing Drosophila melanogaster females and Drosophila simulans males. Using transcriptomic data analysis, molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Due to the differential expression of genes encoding piRNA pathway components, rhino and deadlock, the functional RDCmel complex in hybrid ovaries was not assembled. However, the activity of the RDCsim complex was maintained in hybrids, independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial AT-chX piRNA targeting of the vasasim allele and a significant zygotic delay in vasamel expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.

Nanoparticles (NPs) have various applications in medicine, cosmetics, optics, catalysis, environmental purification, and other areas nowadays. With an increasing annual production of NPs, the risks of their harmful influence to the environment and human health is rising. Currently, our knowledge about the mechanisms of interaction between NPs and living organisms is limited. Additionally, poor understanding of how physical and chemical characteristic and different conditions influence the toxicity of NPs restrict our attempts to develop the standards and regulations which might allow us to maintain the safe living conditions. The marine species and their habitat environment are under continuous stress due to anthropogenic activities which result in the appearance of NPs in the aquatic environment. Our study aimed to evaluate and compare biochemical effects caused by the influence of different types of carbon nanotubes, carbon nanofibers, and silica nanotubes on four marine microalgae species. We have evaluated the changes in growth-rate, esterase activity, membrane polarization, and size changes of microalgae cells using flow cytometry method. Our results demonstrated that toxic effects caused by the carbon nanotubes strongly correlated with the content of heavy metal impurities in the NPs. More hydrophobic carbon NPs with less ordered structure had a higher impact on the red microalgae P. purpureum because of higher adherence between the particles and mucous covering of the algae; silica NPs caused significant inhibition of microalgae growth-rate predominantly produced by mechanical influence.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

The mechanical properties, structure, and morphology of milled and 3D printed Ti-6Al-4V alloys produced by selective laser melting were investigated in this study. The mechanical properties were investigated by means of nanoindentation, a tensile test, and a three-point bending test. The Atomic Force Microscope (AFM) was used to study the surface topography and roughness of both titanium alloys. The surface structure and phase analysis were studied by a scanning electron microscope (SEM) and through powder X-ray diffraction (XRD). The results from the nanoindentation experiments showed that the 3D-printed sample has higher indentation hardness and modulus than the milled one. The AFM observation of the surface topography of the samples showed that the milled sample has a higher roughness than the 3D-printed one. The tensile test results showed that the 3D printed sample by means of Selective Laser Melting (SLM) technology has about 26% higher tensile strength and smaller elongation than the milled one. The 3-point bending test revealed that the 3D printed Ti-6Al-4V sample has higher flexural strength than the milled one. It was found that the 3D-printed sample has a smaller crystal size than the milled one, which, according to the Hall-Petch relationship, leads to its higher indentation hardness.

In order to achieve global climate goals, it is necessary to estimate greenhouse gases (GHG) fluxes from ecosystems. To obtain a comprehensive assessment of CO2, СН4, N2O natural fluxes for the Russian Federation we used the "bottom-up" method according to [1]. We updated estimates for forest ecosystems based on State Forest Inventory data and satellite monitoring of forest disturbances. For grassland ecosystems, it was based on the correct distribution of areas between steppe and non-steppe zones. The estimated net uptake of natural ecosystems of Russia was 1.1 ± 1.8 billion tons of CO2-eq./year. The study shows that if only CO2 is taken into account, the net absorption of terrestrial ecosystems in Russia corresponds to more than -2.5 billion tons of CO2 (35% of forests’ contribution). However, given the emissions of non-CO2 GHGs, total net absorption in Russia’s natural ecosystems is reduced to about -1 billion tons of CO2-eq (with the forests’ contribution increasing to 80%). With regard to anthropogenic fluxes, the overall balance of GHGs in Russia corresponds to net-emissions of 1 billion tons of CO2-eq/year into the atmosphere. To improve reporting under the Paris Agreement, countries should aim to include only anthropogenic ("manageable") GHG fluxes on managed land.

Barrett’s esophagus (BE) is a premalignant lesion for esophageal adenocarcinoma (EAC). Development of Barrett’s esophagus is caused by biliary reflux that provokes intensive mutagenesis in stem cells of epithelium in distal esophagus and gastro-esophageal junction. Other possible cell origins of Barrett’s esophagus include stem cells of mucosal esophageal glands and their ducts, of stomach, residual embryonic cells and circulating bone marrow stem cells. Classic conception of healing of caustic lesion was replaced by idea of cytokine storm that forms inflammatory microenvironment for phenotypic shift toward intestinal metaplasia of distal esophagus. The review summarizes contemporary concepts of BE and EAC pathogenesis.

Ultralong carbon nanotubes (UCNTs) are highly demanded for nanocomposites applications because of their magnificent physical and chemical properties. UCNTs are synthesized by catalytic chemical vapor deposition (CCVD) method and, before using as fillers in nanocomposites, should be purified from residual catalyst and non-CNT particles without significant destruction or scissoring of UCNTs. The role of water vapor for purification of UCNTs is investigated, the importance of water assistance in this process is confirmed. It was shown that wet air treatment of products of UCNTs CCVD synthesis under mild conditions can be used to decrease sufficiently residual catalyst content without significant carbon losses in comparison with the results obtained with dry air, while the residual iron content was shown to influence heavily on the subsequent oxidation of different forms of carbons, including UCNTs. The increasing of D/G ratio of Raman spectra after wet air treatment of products of UCNTs CCVD synthesis makes it possible to conclude that iron catalyst particles transform into iron oxides and hydroxides that caused inner structural strains and destruction of carbon shells improving removal of the catalyst particles by subsequent acid treatment. UCNTs purification with water assistance can be used to develop economically and ecologically friendly methods for obtaining fillers for nanocomposites of different applications.

The analysis of methods of cleaning and processing of saponite-bearing technogenic waters of diamond mining enterprises of the Arkhangelsk region is carried out. The perspective of the electrochemical separation method for extracting saponite from man-caused waters, providing a targeted change in its structural-texture, physico-chemical and mechanical properties, is shown. The possible directions of realization of saponite and products of its modification in various branches of industry are considered.

Considering that a fair coin has two sides and a cylindrical edge, the probability that it would fall on its edge is calculated, yielding the probability of heads or tails less than 50%. Theoretical models for a static case and for five dynamic cases, without and with rebounds, show that there is a small probability that the coin does not fall on its head or tail, depending on initial toss conditions, the coin geometry and conditions of the coin and landing surfaces. For the dynamic model with rebounds, it is found that the probability that a 50 Eurocent coin thrown from a normal height with common initial velocity conditions and appropriate surface conditions will end up on its edge is in the order of one against several thousand.

The natural product elaiophylin is a macrodiolide with broad biological activities. However, no direct target of elaiophylin in eukaryotes has been described so far, which hinders a systematic explanation of its astonishing activity range. We recently showed that the related conglobatin A, a protein-protein interface inhibitor of the interaction between the N-terminus of Hsp90 and its cochaperone Cdc37, blocks cancer stem cell properties by selectively inhibiting K-Ras4B but not H-Ras. Here we elaborate that elaiophylin likewise disrupts the Hsp90/ Cdc37 interaction, without affecting the ATP-pocket of Hsp90. Similar to conglobatin A, elaiophylin decreased expression levels of the Hsp90 client HIF1⍺, a transcription factor with various downstream targets, including galectin-3. Galectin-3 is a nanocluster scaffold of K-Ras, which explains the K-Ras selectivity of Hsp90 inhibitors. In agreement with this K-Ras targeting and the potent effect on other Hsp90 clients, we observed with elaiophylin treatment a submicromolar IC50 for MDA-MB-231 3D spheroid formation. Finally, a strong inhibition of the same cells grown in the chorioallantoic membrane (CAM) microtumor model was determined. These results suggest that several other macrodiolides may have the Hsp90/ Cdc37 interface as a target site.

TmMgB5O10 spontaneous crystals were synthesized via flux-growth technique from a K2Mo3O10-based solvent. The crystal structure of the compound was solved and refined within the space group P21/n. The first principles calculations of the electronic structure reveal that TmMg-pentaborate is an insulator with an indirect energy band gap of approximately 6.37 eV. Differential scanning calorimetry measurements and powder X-ray diffraction studies of heat-treated solids show that TmMgB5O10 is an incongruent melting compound. A characteristic band of Tm3+ cation corresponding to the 3H6 → 1D2 transition is observed in the photoluminescence excitation spectra of TmMg-borate. The as-obtained crystals exhibit intense blue emission with the emission peaks centered at 455, 479, 667 and 753 nm. The most intensive band corresponds to the 1D2 3F4 transition.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

Estimation of the reality can easily be flawed, hence, in order to result in accurate and useful estimates the process has to be protected from bias and confounding and should follow other methodological milestones inherent to different types of empirical observations. Candidate-gene association studies are a specific form of observations that have been rather extensively applied in psychiatry yielding valuable information on various aspects – when methodologically adequate and used in appropriate settings. However, certain flaws that may occur in such studies might not be bluntly obvious, at least not at first glance, and may pass unnoticed by researchers and reviewers. This case study uses two recent published candidate-gene association reports suggesting involvement of cannabinoid receptor type 1 and of heat shock protein single nucleotide polymorphisms in development of neurocognitive performance and psychopathology in a cohort of adult first episode psychosis patients to point-out the types of flaws inevitably resulting in inaccurate and useless estimates.

The territory of Serbia is vulnerable to various types of natural and man-made disasters. The risk is not equal across the entire territory, depending on the type of hazard and the expected potential for damage. So far, the level of community disaster resilience has not been determined in Serbia. There are no scientific preconditions for its improvement to reduce the future material and intangible consequences of disasters. Regarding that, the project’s main objective is to develop and validate a predictive model of community disaster resilience based on social identity influences through an investigation impact of social identity indicators on the level of community disaster resilience in Serbia. The project is based on the upcoming research on whether the level of community disaster resilience can be predicted based on social identity indicators, how social identity indicators affect different dimensions of community disaster resilience, and how disasters shape social identity. The project is based on multimethod research in which quantitative (face-to-face interviews in 40 of the 191 municipalities), and qualitative (semi-structured interviews) research methodology will be applied. A developed predictive model with an index of community disaster resilience in Serbia will empower the creation of preconditions for designing public policies, strategies and procedures for improving resilience and reducing the consequences of disasters on people and their property and enhancing citizens’ security. The project will encourage the prediction of community disaster resilience based on social identity indicators, improving disaster foresight and preparing to limit disaster losses. Based on the development of analytical frameworks for understanding community disaster resilience and social identity in disasters, essential preconditions for designing innovative information systems will be created to enable local communities to increase their level of resilience.

Analyses of the three predominant types of sedimentation – clastic, carbonate and black shale – revealed their discontinuity/continuity in different facies environments of the Middle and Late Devonian of the central part of the Volga-Urals petroleum province, namely (1) in depressions, both condensed and non-condensed, (2) on the slopes of depressions and (3) in shallow water environments represented by tectonic arches or localised biohermal uplifts. The regional zonation of conodonts, correlated with the global chronostratigraphic scheme, substantiates the stratigraphic completeness of the general Devonian sequence in this area. In particular, the sedimentation of organic-rich black shales, traditionally considered as source rocks, lasted more than 29 million years, starting from the Late Eifel and ending at the Devonian-Carboniferous boundary. There was only one hiatus in the deposition of both black shales and carbonate sediments, lasting about 2.5 million years at the end of the Frasnian. That interval is dominated by clastic sediments, which are considered to be the most productive reservoirs of the Volga-Ural province. In the time interval from the beginning of the Eifel to the end of the Frasnian (about 17 Ma), (a) clastic sediments show the highest accumulation rates; (b) the most complete sequences occur in depressions; and (c) arches and uplifts show the most significant gaps in the geological record. During Famennian, (a) clastic sedimentation has completely ceased; (b) differences between the slopes of troughs and shallow-water environments have diminished, resulting in stable accumulation of carbonate sediments in both settings; (c) the decrease in sequence thickness (up to 50 m) in depressions suggests reduced accumulation rates of deep-water organic-rich black shales. The results help to understand the complex spatial relationship between different coexisting sedimentation types and focus attention to the incompleteness of the geological record in different environments.

Stable suspensions of metal/metalloid oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the Me-NPs were repeatedly injected intraperitoneally (i.p.) 18 times during 6 weeks before measuring a large number of functional, biochemical, morphological and cytological indices for the organism’s status. In many respects, the Al₂O₃-NP was found to be the most toxic species alone and the most dangerous component of the combinations studied. Mathematical modeling with the help of the Response Surface Methodology showed that, as well as in the case of any other binary toxic combinations previously investigated by us, the organism’s response to a simultaneous exposure to any two of the Me-NP species under study was characterized by a complex interaction between all possible types of combined toxicity (additivity, subadditivity or superadditivity of unidirectional action and different variants of opposite effects) depending on which outcome a given type was estimated for and on effect and dose levels. With any third MeO-NP species acting in the background, the type of combined toxicity displayed by the other two remained virtually the same or changed significantly, becoming either more or less unfavorable. Various harmful effects produced by the [Al₂O₃-NP+TiO₂-NP+SiO₂-NP]-combination, including its genotoxicity, were substantially attenuated by giving the rats per os during the entire exposure period a complex of innocuous bioactive substances expected to increase the organism’s antitoxic resistance.

It is shown that structuring at the microlevel is the intrinsic property of water and aqueous solutions. At room conditions water (including "ultrapure" one) and aqueous solutions are dispersed systems in which microcrystals of NaCl, surrounded by a layer of hydrated water (average diameter - 10-15 microns), are "elementary microparticles", which form the basis of the dispersed phase. Possible ways of formation of these microparticles and their evolution in the process of evaporation of unstructured part of water - dispersion medium - are considered. It is shown, in particular, that they are present in the air as aerosol contaminants. When the ionic strength of the solution increases, the water-salt particles coagulate, forming a new phase - coacervates, remaining on the substrate after evaporation of the liquid part of the water. The aggregates of coacervate structures, formed in a liquid medium, are disordered during heating, which can cause a change in a number of physicochemical properties of water at the temperatures of 50°-60°C range that have not been correctly explained in the framework of atomic-molecular concepts.

We present the results on photothermal (PT) and heat conductive properties of nanogranular silicon (Si) films synthesized by evaporation of colloidal droplets (drop-casting) of 100 ± 50 nm sized crystalline Si nanoparticles (NP) deposited on glass substrates. Finite difference time domain (FDTD) and finite element mesh (FEM) modeling of absorbed light intensity and photo-induced spatial temperature distribution across the Si NP films were well correlated with the local temperatures measured by micro-Raman spectroscopy and used for determination of heat conductivities in the films of various thicknesses. Cubic-to-hexagonal phase transition in these films caused by laser heating was found to be heavily influenced by the film thickness and heat conductive properties of glass substrate, on which the films were deposited. Heat conductivities across the drop-casted Si nanogranular films were found to be in the range of lowest heat conductivities of other types of nanostructurely voided Si films due to enhanced phonon scattering across inherently voided topology, weak NP-NP and NP-substrate interface bonding within nanogranular Si films.

Observed sea surface Ka-band normalized radar backscatter cross section (NRCS) and Doppler velocity (DV) exhibit energy at low frequencies (LF) below the surface wave range. It is shown that non-linearity in NRCS-wave slope Modulation Transfer Function (MTF) and inherent NRCS averaging within the footprint account for the NRCS and DV LF variance with the exception of VV NRCS for which almost half of the LF variance is attributable to wind fluctuations. Although the distribution of radar DV is quasi-Gaussian suggesting virtually little impact of non-linearity, the LF DV variations arise due to footprint averaging of correlated local DV and non-linear NRCS. Numerical simulations demonstrate that MTF non-linearity weakly affects traditional linear MTF estimate (less than 10% for |MTF|< 20). Thus the linear MTF is a good approximation to evaluate the DV averaged over large footprints typical of satellite observations.

Pea (Pisum sativum L.), like most legumes, forms mutualistic symbioses with nodule bacteria and arbuscular mycorrhizal (AM) fungi. The positive effect of inoculation is partially determined by the plant genotype, thus, pea varieties with high and low symbiotic responsivity have been described, but the molecular genetic basis of this trait remains unknown. Here, we compare the symbiotically responsive breeding line ‘Triumph’ of grain pea with its parental cultivars ‘Vendevil’ (a donor of high symbiotic responsivity) and ‘Classic’ (a donor of agriculturally valuable traits) using genome and transcriptome sequencing. We show that ‘Triumph’ inherited one-fourth of its genome from ‘Vendevil’, including the genes related to AM and nodule formation, and reveal that under combined inoculation with nodule bacteria and AM fungi, ‘Triumph’ and ‘Vendevil’, in contrast to ‘Classic’, demonstrate similar up-regulation of the genes related to solute transport, hormonal regulation and flavonoid biosynthesis in their roots. We also identify the gene PsGLP2, whose expression pattern distinguishing ‘Triumph’ and ‘Vendevil’ from ‘Classic’ correlates with difference within the promoter region sequence, making it a promising marker for the symbiotic responsivity trait. The results of the study may be helpful for future molecular breeding programs aimed at creation of symbiotically responsive cultivars of pea.

This paper presents the results of quantitative research regarding the examination of the levels of efficiency of the fire protection system and the training of employees in Electrical power distribution of Serbia for fire protection, ie the analysis of the manner of implementation of fire protection measures, and determining whether these measures are adequately applied. Following the subject set in this way, the aim of the research was set, and that is the scientific analysis of the manner of application of fire protection measures. The results of this research showed that the employees of Electro distribution Belgrade perceive the preparedness of their company highly positively and certain socio-demographic characteristics also affect certain attitudes, especially those related to the experience with fire, the knowledge of employees to react in case of fire, and the choice of the appropriate response, assessment of the readiness of the company and the employees themselves. It was found that knowledge of how to react in case of fire is influenced by gender and level of education; the choice of one of the methods of action in case of fire is influenced by gender; the assessment of the readiness of the employees themselves is influenced by the marital status; the desire of employees to participate in training to increase their preparedness for fires is influenced by gender. The results of the research can be used to improve the preparedness of employees in various organizations to respond to disasters caused by fires.

Osteoconductive granulated biopolymers (OGB) are used to restore the lost volume of the jaw bone. OGB is employed as a loose fraction and exhibits physical traits common to bulk mixtures. By removing air bubbles and industrial dust from the OGB fraction through special processing, more accessible spaces are left over for the adsorption of bone growth factors. The recipient site's biological environment alters the OGB fraction's physical characteristics. This is the cause of the OGB fraction's volume changing uncontrollably during the first three weeks following surgery. Predictive indicators for describing the physical processes of osteoconduction include the compaction coefficient and adsorption capacity. Taking into account the prognostic indicators of the dynamics of changes in the physical properties of the OGB fraction in the postoperative period, 3D planning of the bioengineered structure should be done. The OGB fraction's adsorption and drainage properties are optimized by raising the purity of OGB production and preparing the biopolymer for clinical studies.

Emergence of multi drug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis poses a serious threat to TB control as the available treatment options are less effective in these cases. Therefore, new strategies are required for identification of new drugs and drug targets. The M. tuberculosis dihydrodipicolinate synthase is a putative drug target with no potent inhibitor. Here in this study, we have used a comprehensive computational approach to identify small molecule inhibitors and validated them in vitro. As similar structures tend to have similar functions, therefore 3 approaches, namely, (a) known inhibitor-based approach, (b) substrate analogues, (c) product analogues were used for compound screening from various chemical libraries. The fourth approach we have taken is fragment library screening.In vitro studies revealed that β-hydroxypyruvic acid tartronic acid are inhibitors of Mtb-rDapA with maximum inhibition 48% and 51% at 500µM concentrations respectively. We have also observed that β-hydroxypyruvic acid is a time dependent inhibitor of Mtb-rDapA. Further, thermal shift assays showed that β-hydroxypyruvic acid interacts with Mtb-rDapA and the thermal stability of Mtb-rDapA shifted by 3˚C. Among the product analogues of Mtb-DapA, dipicolinic acid showed to bind to Mtb-rDapB shifting thermal stability of Mtb-rDapB by 0.5˚C in binding. Additionally, we have designed a new approach by combining substrate and product analogues to achieve better inhibitions. In vitro assays validated that this combination approach increased maximum inhibition up to 100%. We envision that these compounds would serve as potent leads for tuberculosis drug discovery.

A series of N-acyl derivatives of anabasine and cytisine were prepared to discover novel natural product-based medicinal agents. All synthesized compounds were tested for antimicrobial, antifungal, antiviral and analgesic activity. The most pronounced antibacterial activity was shown by the compounds with isoxazole fragments, while adamantane derivatives showed the greatest antiviral effect. It was found that the majority of anabasine derivatives showed significant analgesic activity reducing the pain response of animals to the irritating effect of acetic acid. The presence of a high level of antimicrobial and antiviral activity in newly synthesized compounds makes it possible to consider them promising for further study of their pharmacological properties.

A problem of efficacy of crystal growth methods for crystallization from solution or melt has been investigated. Axial vibrational control (AVC) technique was considered as a perspective method to manage both heat-mass transfer and chemical component composition of the melts in the case of crystallization of complex chemical compounds. Numerical modeling and the search for generalized dependencies made it possible to predict the AVC parameters that provide optimal heat and mass transfer modes for creating flat liquid-solid interfaces, as well as the component composition of dissociated melts of various chemical compounds – Ge, NaNO3, CdTe.

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

One of the rapidly developing research areas is the creation of systems. which are commonly referred to as cyberphysical complexes. In such systems, devices and complexes interact with a completely different physical nature. The role of a person in such systems usually consists in the formation of final tasks for “artificial intelligence” and executive mechanisms. The functioning of actuators is controlled by accurate information systems.

Background/Objectives: The purpose of the proposed study is disclosure of correlations between the dynamics of the Breathe Rate (BR) and Heart Rate (HR) when performing the intermittent physical operation at maximum power on a cycle ergometer.Methods: The stage on the study of the General functional athlete readiness (GFAR) performed using the sports standard “Red Engine” and the cycle ergometer in 16 volunteers (10 men, 6 women) whose average age was 21±1.17 years. To determine the sports potential of the volunteers in this study, we used own Coefficient of Anaerobic Capacity (CANAC Q, beats). Continuous recording of the heart rate and respiratory rate of volunteers in the maximum power sports test was carried out by the “RheoCardioMonitor” device with an athlete functional readiness module based on the method of Transthoracic electrical impedance rheography (TEIRG).Results: The degree of correlation of functional indicators (M, HR_M, GFAR) with CANAC Q for the group in full (n=80) occurred at a very high level, which confirmed the effectiveness of using the Coefficient of Anaerobic Capacity (CANAC Q) in assessing the general functional athlete readiness of the volunteers. Conclusions: CANAC Q measured in “beats” of the heart and recorded very accurately using the method of transthoracic electrical impedance rheography (TEIRG). For this reason as promising sports PSM-system, CANAC Q can replace the methods for determining the functional athlete readiness by blood lactate concentration and maximum oxygen consumption.

Weak contact metric structures on a smooth manifold, introduced by V. Rovenski and R. Wolak in 2022, have provided new insight into the theory of classical structures. In this paper, we define new structures of this kind (called weak nearly Sasakian and weak nearly cosymplectic and nearly K\"{a}hlerian structures) and study their geometry. We introduce weak nearly K\"{a}hlerian manifolds (generalizing nearly K\"{a}hlerian manifolds) and characterize weak nearly Sasakian and weak nearly cosymplectic hypersurfaces in such Riemannian manifolds.

In this review, severe plastic deformation (SPD) is considered as a materials processing technology. The deformation mode is the principal characteristic differentiating SPD from common forming operations. For large plastic strains, deformation mode depends on the distribution of strain rates between continuum slip lines and can be varied from pure shear to simple shear. A scalar, invariant and dimensionless coefficient of deformation mode is introduced as a normalized speed of rigid rotation. On this basis, simple shear provides the optimum mode for structure modification and grain refinement whereas pure shear is "ideal" for forming operations. Special experiments and SPD practice confirm this conclusion. Various techniques of SPD are classified and described in accordance with simple shear realization or approximation. It is shown that correct analyses of the processing mechanics and technological parameters are essential for comparison of SPD techniques and the development of effective industrial technologies.

Coordination of activities between nuclei and organelles in plant cells involves information exchange, in which phytohormones may play an essential role. Therefore, dissection of the mechanisms of hormone-related integration between phytohormones and mitochondria is an important and challenging task. Here, we found that inputs from multiple hormones may cause changes in transcript accumulation of mitochondrial-encoded genes and nuclear genes encoding mitochondrial (mt) proteins. In particular, treatments with exogenous hormones induced changes in GUS expression in the reporter line possessing a 5'-deletion fragment of the RPOTmp promoter. These changes corresponded in part to up- or downregulation of RPOTmp in wild-type plants, which affected the transcription of mt-encoded genes, implying that promoter fragments of the RPOTmp gene are functionally involved in responses to IAA (indole-3-acetic acid), ACC (1-aminocyclopropane-1-carboxylic acid), and ABA (abscisic acid). Hormone-dependent modulations in the expression of mt-encoded genes can also be mediated through mitochondrial transcription termination factors 15, 17, and 18 of the mTERF family and genes for tetratricopeptide repeat proteins that are coexpressed with mTERF genes, in addition to SWIB5 encoding a mitochondrial SWI/SNF (nucleosome remodelling) complex B protein. These genes specifically responded to hormone treatment, displaying both negative and positive regulation in a context-dependent manner. According to bioinformatic resources, their promoter regions possess putative cis-acting elements involved in responses to phytohormones. Alternatively, hormone-related transcriptional activity of these genes may be modulated indirectly, which is especially relevant for brassinosteroids (BS). In general, the results of the study indicate that hormones are essential mediators that are able to cause alterations in the transcript accumulation of mt-related nuclear genes, which in turn trigger the expression of mt genes.

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

A new variant of the SARS-CoV-2 Omicron BA.5 virus has displaced all previous variants of the virus around the world. Preliminary assessment of the effectiveness of drugs for the prevention and treatment of COVID-19 requires the availability of infection models in animals. In this study, we characterize the infection model SARS-CoV-2 Omicron BA.5 and its progeny sublineage BE.1 in hACE2-transgenic mice and in Syrian hamsters. Both sublineages turned out to be pathogenic for animals – the challenged animals showed weight loss, a high level of viral load and acute inflammation in the lungs. Part of BA.5-infected mice died after virus challenge, indicating that this virus variant is more pathogenic than the previous BA.1 variant but less pathogenic than Wuhan variant.

Cancer is a complex and devastating disease that has engaged scientists and researchers for decades. Despite tremendous efforts, previous hypotheses about cancer development have not achieved significant breakthroughs. Evolutionary Cancer Cell Biology (ECCB) is a novel and emerging branch of oncological science that provides an evolutionary perspective on the origin of cancer. It reveals that the cancer genome evolved hundreds of millions of years ago, long before multicellular organisms such as metazoans and humans emerged. ECCB aims to unify all evolutionary insights, hypotheses, and theories into a cohesive framework. It investigates the intricate relationship between cancer genomics and ancient pre-metazoan genes that emerge when normal cells transform into cancer cells. It challenges the conventional wisdom of cancer research by suggesting that cancer could arise through intrinsic cellular mechanisms without genetic alterations and mutations. Furthermore, it postulates that somatic mutations are only secondary, downstream events in the process of oncogenesis.

Novel tetragonal matrix Ba0.5Gd0.5-xNaxF2.5-x, where x = 0.05, doped by Yb3+, Ho3+, Er3+, was synthesized by molten salt synthesis (MSS) from nitrate flux. XRD data show that tetragonal phase with a = 4.122(1) Å, c = 17.672(1) Å is stable in argon atmosphere up to 960 °C. Luminescence spectra recorded in 500-900 nm and 1050-1700 nm upon 974 nm pumping demonstrated the characteristic luminescence at 1550 nm (4I13/2 → 4I15/2) for Er3+ and 1150 nm (5I6 → 5I8) for Ho3+. The relative thermal sensitivity (Sr) at 296-316 K were 0.3 %*K-1 and 5.5%*К-1 in shortwave infrared (SWIR) and visible range, respectively. Synthesized luminophores can be used as dual-range optical temperature sensors, which simultaneously operating in visible and SWIR ranges.

Amorphous germanium films on non-refractory glass substrates were annealed by ultrashort near-infrared (1030 nm, 1.4 ps) and mid-infrared (1500 nm, 70 fs) laser pulses. Crystallization of germanium irradiated at a laser energy density (fluence) range from 25 to 400 mJ/cm2 under single-shot and multi-shot conditions was investigated using Raman spectroscopy. The dependence of the fraction of the crystalline phase on the fluence was obtained for picosecond and femtosecond laser annealings. The regimes of almost complete crystallization of germanium films over the entire thickness are obtained (from the analysis of Raman spectra with excitation of 785 nm laser). The possibility of scanning laser processing is shown, which can be used to create films of micro and nanocrystalline germanium on flexible substrates.

The problem of optimal scheduling in a system with parallel queues and a single server has been extensively studied in the queueing theory. However, such systems have mostly been studied by assuming homogeneous attributes of arrival and service processes, or in heterogeneous case a Markov random process was usually assumed. In this paper, we explore the possibility of combining simulation and neural network paradigms for optimal scheduling in a heterogeneous system with an arbitrary inter-arrival and service time distributions. The service of any queue by the server is exhaustive. Further routing of the server after the queue has been emptied is as instructed by the trained neural network. Any change in the queue that currently has a server is accompanied by a switching cost. The simulated annealing optimization algorithm which is used to optimize the parameters of the neural network was adapted for numerically evaluated average cost function. A Markov decision problem was formulated for the corresponding markovian queueing system to verify the results of solving the optimization problem. In addition to comparing the actual values of the average cost, the parameter values of the neural network trained on the optimal control policy of the Markov model are also used to determine the domains of parameters required for the simulated annealing defined on a finite discrete domain. Numerical analysis shows the effectiveness of this approach. Moreover, a comparison of the results for different distributions illustrates the insensitivity of the optimal control policy to the shape of the distributions for the same two first moments. Thus, the optimal control policy for an exponential model can be used as a suboptimal one for the general system.

The processes of the sublimation and thermal decomposition of the 1‐ethyl‐3‐methylimidazolium hexafluorophosphate ionic liquid (EMImPF6) were studied by a complex approach including Knudsen effusion mass spectrometry, IR and NMR spectroscopy, and quantum chemical calculations. It was established that the vapor over liquid phase primarily consists of decomposition products under equilibrium conditions. Otherwise, the neutral ion pairs are the only vapor components under Langmuir conditions. To identify the nature of the decomposition products an experiment on the distillation of the ionic liquid was performed and the collected distillate was analyzed. It was revealed by the IR and NMR spectroscopy that EMImPF6 decomposes to substituted imidazole‐2‐ylidene (C6N2H10PF5) and HF. The measured vapor pressure of C6N2H10PF5 reveals a very low activity of the decomposition products (&lt;10–4) in the liquid phase. The absence of significant accumulation of decomposition products in the condensed phase makes it possible to determine the enthalpy of sublimation of the ionic liquid assuming its unchanged activity. The thermodynamics of the EMImPF6 sublimation was studied by Knudsen effusion mass spectrometry. The formation enthalpy of EMImPF6 in ideal gas state was found from combination of the sublimation enthalpy and formation enthalpy of ionic liquid in the condensed state. The obtained value is in good agreement with those calculated by quantum chemical methods.

Optimal control has emerged as an indispensable tool in the domain of mechanical robotic systems. The dynamic processes under consideration in this paper are characterized by differential equations with an unknown coefficient. The problem addressed is time-optimal and exhibits bilinear characteristics. To investigate this inverse optimal problem, the classical method has been employed alongside Pontryagin’s Maximum Principle (PMP). This article aims to provide an exact piecewise function for controlling trajectories, specifically accounting for viscous friction. The goal is to determine the reachability set and to find the minimal process time. Notably, no simplifying assumptions were made during the analytical transformations.

The authors argue that despite significant numbers of foreign workers present in the Russian labor market Russia remains unattractive for highly skilled foreign workers. The economic crisis the country has faced since 2014 has resulted in a further outflow of foreign nationals from OECD countries. So Russia has to look for employees among newcomers from the former Soviet states, the majority of whom come from Central Asia. Russian politics with regard to immigration is characterized by the collision between “geopolitical” and domestic policy rationales. On one hand, seeking to maximize its influence in the post-Soviet space Russia provides preferential conditions of employment for citizens of partner countries in the framework of the Eurasian Economic Union. On the other hand, the Kremlin is afraid to liberalize its approach to immigration and the integration of immigrants through fear of losing popularity among the electorate. The second substantial feature of Russian immigration politics is an extreme level of securitization of migration issues. The government considers these issues primarily through a policing lens. One cannot claim that the Russian state does not take any steps to liberalize “migratory regulation”; however, the effect of these measures is being vastly reduced by new restrictions. In addition, liberally designed laws do not bring the expected results due to the corrupt practices that pervade the whole of migration regulation.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

There are many problems based on solving non-autonomous differential equations of the form x¨(t)+ω2(t)x(t)=0, where x(t) represents the coordinate of a material point and ω is the angular frequency. The inverse problem involves finding the bounded coefficient ω. Continuity of the function ω(t) is not required. The trajectory x(t) is unknown, but the initial and final values of the phase variables are given. The variation principle of minimum time for the entire dynamic process allows for the determination of the optimal solution {x(t),ω(t)}. Thus, the inverse problem is an optimal control problem. No simplifying assumptions were made.

We considered a vacuum polarization around a massive object in the eikonal approximation and found two types of vacuum polarization. The first type has the equation of state similar to radiation and can produce a halo that increases the rotation velocity of a test particle with a radial distance. The second type of vacuum polarization has a more complicated equation of state. As a static physical effect, it produces renormalization of the gravitational constant. Besides, we demonstrate that a nonstationary polarization of the second type caused by a swift increase of the galactic nuclei mass results in a gravitational potential looking like a dark matter halo.

In this paper, we investigate the effects of mean stress, multiaxial loading, and residual stresses on the fatigue life of springs. We study the fatigue life of a homogeneously stressed material subjected to cyclic loading with nonzero mean stress. Traditional methods for estimating fatigue life are based on Goodman and HAIGH diagrams. The formal analytical descriptions, namely "stress-life" and "strain-life" approaches, are found to be more suitable for the numerical methods. The fatigue analysis method described above, which describes crack growth per cycle, is extended. The extensions allow consideration of the mean stress of a load cycle. Closed-form expressions for crack length versus number of cycles are derived. The complementary effects on the fatigue life of springs, which ultimately have a significant influence on the fatigue life of springs, are summarized. For the proposed unified fatigue life functions, the ranges for the stress loading factor are extended by introducing the effective stress intensity. The solution leads to the factor range for the effective stress intensity, the effective mean value of the stress intensity factor and the effective stress ratio. The developed method assumes the homogeneous stress state in the whole spring element. For the non-homogeneously loaded structural elements, the weak-link concept is applied to account for fatigue.

Reparative osteogenesis in the damaged vertebrae is a complex cascade of morphological and biochemical processes that result in the consolidation of the vertebral body. This research was aimed at studying the features of reparative osteogenesis in damaged thoracic and lumbar vertebral bodies at different time points after injury. We analyzed the morphological findings of the vertebral tissues harvested during surgical interventions in 43 patients with recent, subacute and long-standing injuries to thoracic and lumbar spine, and found that cell differentiation in osteogenesis is closely related to angiogenesis and the metabolic cascade. In areas with sufficient oxygenation, good partial pressure of oxygen, and active growth of microvasculature the normal cycle of development and differentiation of osteoblasts and osteocytes occurs, and hypoxia and acidosis lead to pathological osteogenesis. The reclination maneuver with dorsal tools on Day 10-12 of the injury may be ineffective due to the formation of adhesions between fragments, and reclination of the body of the damaged vertebra two weeks or more after the injury is apparently doomed to failure. Timely ventral fusion performed for objective indications is the key to successful rehabilitation of patients, on the one hand, and reduction of the surgical trauma volume in the future, on the other.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically-based lipid disorder with the underestimated actual prevalence. In the recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. However, there is not enough data on their use in real-world clinical implementation. We studied the applicability of the most accessible biochemical algorithms to diagnose FD in clinical practice. We also investi-gated the prevalence of FD in one of the European regions of Russia based on a population sample. In this study there was detected a high prevalence of FD: 1 in 151. We demonstrated that the diagnostic algorithms of FD including a diagnostic apoB levels require correction, taking into account the characteristics of the distribution of apoB levels in the population. At the same time a triglycerides cutoff ≥1.5 mmol/L may be a useful tool in identifying subjects with FD. We also analyzed the presence and pathogenicity of APOE variants associated with the autosomal dominant FD in a large research sample.

Sums of M consecutive squared integers (a+i)^2 equaling squared integers (for a<=1, 0<= i<= M-1) yield remarkable regular linear features when plotting values of M in function of a. These features correspond to groupings of pairs of a values for successive same values of M around straight lines of equation mu*M = 2a and are characterized in this paper for rational values of mu.

Stabilized melanocortin analog peptide ACTH(6-9)PGP (FRWGPGP) possess a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we studied the pro-proliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6-9 (FRWG) linked with the peptide Prolyl-Glycyl-Proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN. The mechanism of its action was the modu-lation of proliferation-related (NF-kB and Nrf-2) and antioxidant-related (HO-1, Nqo1, Gclc) genes and apoptosis decrease.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

The fact that quantum gravity does not admit a co-variant vacuum state has far-reaching consequences for all physics. It points out that space could not be empty, and we return to the notion of an ether . Such a concept requires a preferred reference frame for, e.g., universe expansion and black holes. Here, we intend to discuss vacuum and quantum gravity from three essential viewpoints: universe expansion, black holes existence, and quantum decoherence.

In post-COVID-19 syndrome, clinical presentation of the nerve fiber dysfunction plays an important role. The possibility of autoantigen cross-mimicry of coronavirus infection and the peripheral nervous system need to be investigated. The bioinformatic analysis was applied to search for possible common protein sequences located in the immunological epitopes. Among the autoantigens of the human nervous system, fibroblast growth factor receptor protein 3, myelin protein P0, myelin protein P2, sodium channel protein type 9, alpha protein subunit, plexin-D1 protein and ubiquitin-carboxyl-terminal hydrolase protein of the L1 isoenzyme were selected. The “Alignmentaj” program was created. The UniProt database, Protein Data Bank and AlphaFold databases were used. The analysis of protein sequence similarities of spike glycoproteins in human coronaviruses revealed common pentapeptides of the MERS-CoV-2 virus with the fibroblast growth factor receptor 3 and myelin protein P2. Among seasonal coronaviruses, common peptide sequences were identified in HCoV-HKU-1 virus with sodium channel protein type 9 subunit alpha and Plexin-D1, HCoV-OС43 with Plexin-D1, as well as HCoV-NL63 with Plexin-D1 and Ubiquitin carboxyl-terminal hydrolase isozyme L1. The data obtained make it possible to identify new potential targets for the development of autoimmune reactions that occur against the background of the activity of highly pathogenic and seasonal coronaviruses.

The article presents a new approach to the analysis of the stability of automatic systems with discrete links.In almost all modern automatic control systems, there are links that break signals in time. These are power controlled switches - transistors or thyristors operating in a pulsed mode and digital links in regulators.Time discretization significantly affects the stability of processes in the automatic control system. The theoretical analysis of such systems is rather complicated and requires a significant change in engineering approaches to analysis. In connection with the improvement of digital controllers and a significant increase in their performance, in recent years this problem has practically not been remembered. However, its mathematical "content" has not changed since the 80s of the 20th century, when discreteness began to play a major role among the problems hindering progress in automatic control systems, in terms of the transition to digital systems.In this paper, a new approach is proposed, which consists in interpreting the sampling operation by a link with the proposed frequency characteristic, which determines the suppression of input high-frequency signals. This link greatly simplifies engineering calculations and demonstrates the new capabilities of sampling systems. These possibilities include the rational distribution of digitalization resources - the number of bits and the sampling interval between the regulator channels, depending on the frequency range of the efficiency of these channels. Theoretical statements have been verified and confirmed by simulation. It is shown how this approach makes it possible to formulate new principles of construction of seemingly well-known controllers - PID controllers and variable structure systems (VSS).

We present a very computationally light and fast approximation algorithm and then verify it with genetic algorithm and simulated annealing. We show that our algorithm is on par with GA and SA in terms of output produced while having a tightly bounded time complexity. Our algorithm works best when there is a strong positive correlation between the reliability of a component and its cost. We present two algorithms with the same essence. One of them is system cost bounded and the other is target reliability bounded. Our proposed algorithm works on a subsystem level redundancy instead of component level redundancy.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of &lt;1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Objective: To describe outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low dose hydroxychloroquine, and azithromycin (the triple therapy) dependent on risk stratification. Design: Retrospective case series study. Setting: General practice. Participants: 141 COVID-19 patients with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the year 2020. Main Outcome Measures: Risk-stratified treatment decision, rate of hospitalization and all-cause death. Results: Of 335 positively PCR-tested COVID-19 patients, 127 were treated with the triple therapy. 104 of 127 met the defined risk stratification criteria and were included in the analysis. In addition, 37 treated and eligible patients who were confirmed by IgG tests were included in the treatment group (total N=141). 208 of the 335 patients did not meet the risk stratification criteria and were not treated. After 4 days (median, IQR 3-6, available for N=66/141) of onset of symptoms, 141 patients (median age 58 years, IQR 40-67; 73% male) got a prescription for the triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients of the same community were used as untreated control. 4 of 141 treated patients (2.8%) were hospitalized, which was significantly less (p<0.001) compared with 58 of 377 untreated patients (15.4%) (odds ratio 0.16, 95% CI 0.06-0.5). Therefore, the odds of hospitalization of treated patients were 84% less than in the untreated group. One patient (0.7%) died in the treatment group versus 13 patients (3.5%) in the untreated group (odds ratio 0.2, 95% CI 0.03-1.5; p=0.16). There were no cardiac side effects. Conclusions: Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset with the used triple therapy, including the combination of zinc with low dose hydroxychloroquine, was associated with significantly less hospitalizations and 5 times less all-cause deaths.

he Grassmann variables are used to formally transform a system with constraints into an unconstraint system. As a result, the Schr\"{o}dinger equation arises instead of the Wheeler-DeWitt one. The Schrodinger equation describes a system's evolution, but a definition of the scalar product is needed to calculate the mean values of the operators. We suggest an explicit formula for the scalar product related to the Klein-Gordon scalar product. The calculation of the mean values is compared with an etalon method, in which a redundant degree of freedom is excluded. Nevertheless, we could note that a complete correspondence with the etalon picture is not found. Apparently, the picture with the Grassmann variables requires a further understanding of the underlying Hilbert space.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015 TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of the production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015, TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The present study aims to measure the technical efficiency and establish core factors effecting rice production in Cambodia. Four-years dataset generated from the central government document “Profile on Economics and Social” of entire 25 provinces between 2012-2015 and the stochastic production frontier model (SFA) was applied. The results indicated that the level of output (quantity) of Cambodian rice production varied according to the different level of capital investment in agricultural machineries, total rice actual harvested area, and technically fertilizers application within provinces. Furthermore, evidence revealed the overall mean efficiency of rice production is 78.4% implies that there is still room to further improve technical efficiency by given the same level of inputs and technology. More importantly, the findings revealed that irrigation, production technique and amount of agricultural supporting staffs are being as the most important influencing factors of rice production’s technical efficiency in Cambodia. In conclusion, present study strongly recommends the development of irrigation systems and good water management practices to be considered and bring into more effective actions by the central government as well as related agencies for improving rice production in Cambodia in addition to capital investment and improving technical skills of supporting staffs and rural farmers.

Molecular mimicry between human and microbial/viral/parasite peptides is common and for a long time is associated with the etiology of autoimmune disorders provoked by exogenous pathogens. Increasing evidence accumulated from the past years suggests a strong correlation between the SARS-CoV-2 infection and autoimmunity. The article analyzes the immunogenic potential of the peptides shared between SARS-CoV-2 spike glycoprotein (S-protein and antigens of human endocrinocytes involved in most common autoimmune endocrinopathies. Totally the study revealed 14 pentapeptides shared by S-protein of SARS-CoV-2 and autoantigens of thyroid, pituitary, adrenal cortex and Langerhans’ islets beta-cells, 12 of them belong to immunoreactive epitopes of SARS-CoV-2. The discussion of the data links the results with clinical correlates of COVID-associated autoimmune endocrinopathies. Most common of them is an autoimmune thyroid disease, so the majority of shared pentapeptides belong to marker autoantigens of this disease. Most important in pathogenesis of severe COVID-19, according authors’ opinion, can be autoimmunity against adrenals, because their adequate response prevents from excessive systemic action of inflammatory mediators which cause cytokine storm and hemodynamic shock. The criticism of antigen mimicry concept is given with a statement that peptide sharing is not a guarantee, but just a prerequisite of autoimmunity excess provocation. The last event occurs in carriers of certain HLA haplotypes and in case when shared peptide is used in antigen processing only [1 figure, 5 tables, bibliography 38 references].

Cotton is the most ubiquitous and profitable fiber with diverse industrial and domestic applications. Grown in over 100 countries, it has a global market value of about $40 billion and employs over 350 million people from fields to textile mills, contributing about 7% of total labor-force recruitment in developing economies. Cotton has an indeterminate growth habit and an extensive tap root system affected by soil physicochemical and environmental conditions. There is a consensus among experts that conventional cotton cultivation still has a long way to attain sustainability, which is essential if cotton will maintain its competitive edge over other natural and synthetic fibers like hemp, polyesters, and rayon. Despite several efforts already committed to growing cotton sustainably, sustainability has eluded cotton cultivation globally because of the intense farm inputs (freshwater, pesticides, and heavy-duty equipment) needs, especially in developing economies. Some of the technological advancements towards achieving the goal of sustainable cotton cultivation include the development of new varieties, improved irrigation and mulching and precision agriculture techniques, application of remote sensing and Unmanned Aerial Systems (UAS) combined with image processing, and the introduction of autonomous and multi-purpose robotic platforms for growing and harvesting cotton. This review attempts to evaluate the successes already achieved by stakeholders in moving cotton towards sustainable production and identify areas where efforts are still needed to reach sustainable production and improved profitability goals for cotton with projections for future research directions.

Applications in high-performance computing (HPC) may not use all available computational resources, leaving some of them underutilized. By co-scheduling, i.e. running more than one application on the same computational node, it is possible to improve resource utilization and overall throughput. Some applications may have conflicting requirements on resources and co-scheduling may cause performance degradation, so it is important to take it into account in scheduling decisions. In this paper, we formalized co-scheduling problem and proposed multiple scheduling strategies to solve it: an optimal strategy, an online strategy and heuristic strategies. These strategies vary in terms of the optimality of the solution they produce and a priori information about the system they require. We showed theoretically that the online strategy provides schedules with a competitive ratio that has a constant upper limit. This allowed us to solve the co-scheduling problem using heuristic strategies that approximate this online strategy. Numerical simulations showed how heuristic strategies compare to the optimal strategy for different input systems. We proposed a method for measuring input parameters of the model in practice and evaluated this method on HPC benchmark applications. We showed high accuracy of measurement method, which allows to apply proposed scheduling strategies in scheduler implementation.

Synchronous homopolar machines (SHM) with excitation winding on the stator have attracted the attention of researchers for many decades due to their high reliability. They are used in a variety of applications such as aircraft and railway generators and traction motors. At the same time, the three-dimensional structure of their magnetic circuit makes the problem of their analysis and optimization challenging. This problem becomes even more complicated when considering an SHM with hybrid excitation, with ferrite magnets in the rotor slots. The article proposes a mathematical procedure for optimizing a synchronous homopolar generator with hybrid excitation based on the single-criterion Nelder-Mead method and two-dimensional finite element analysis (FEA). The use of the Nelder-Mead method compared to multicriteria methods and 2D FEA compared to 3D FEA makes possible to significantly reduce the computational burden. As a result of optimization, the power loss and torque ripples of the generator are significantly reduced. The article also compares the characteristics of synchronous homopolar generators with and without ferrite magnets.

In this paper major machine learning (ML) tools and the most important applications developed elsewhere for numerical weather and climate modeling systems (NWCMS) are reviewed. NWCMSs are briefly introduced. The most important papers published in this field in recent years are reviewed. The advantages and limitations of the ML approach in applications to NWCMS are briefly discussed. Currently, this field is experiencing explosive growth. Several important papers are published every week. Thus, this paper should be considered a simple introduction to the problem.

Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads. Despite their unique parameters, one of the major issues of virtually any nanoformulation is the ability to escape degradation in the compartment of endosomes and lysosomes which determines the overall efficiency of nanotherapeutics. In this study, we fabricated all major types of biological and hybrid NPs and studied their response to acidic environment observed in endolysosomal compartment. In this study, we show that EMNVs display increased protonation and swelling relative to EVs and NGs in an acidic environment. Furthermore, the hybrid NPs exhibit an even greater response compared to EMNVs. Short-term incubation of EMNVs in acidic pH corresponding to late endosomes and lysosomes again induces protonation and swelling, whereas hybrid NPs are ruptured, resulting in the decline of their quantities. Our findings demonstrate that in an acidic environment, there is enhanced rupture and release of vesicular cargo observed in hybrid EMNVs that are fused with liposomes compared to EMNVs alone. This was confirmed through PAGE electrophoresis analysis of mCherry protein loaded into nanoparticles. In vitro analysis of NPs colocalization with lysosomes in HepG2 cells demonstrated that EMNVs mostly avoid endolysosomal compartment whereas hybrid NPs escape it over time. To conclude, (1) hybrid biological NPs fused with liposomes appear more efficient in the endolysosomal escape via the mechanism of proton sponge associated with scavenging of protons by NPs, influx of counterions and water, and rupture of endo/lysosomes, but (2) EMNVs are much more efficient than hybrid NPs in actually avoiding endolysosomal compartment in human cells. These results reveal biochemical differences across four major types of biological and hybrid NPs, and indicate that EMNVs are more efficient in escaping or avoiding endolysosomal compartment.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Magnesium, as one of the most abundant cation in the human body, plays an important role in both physiological and pathological processes. In this study, it was shown that a promising biomedical material Mg-substituted hydroxyapatite (Mg-HA) can be synthesized via fast mechanochemical method. For this method, the nature of magnesium-contained carriers was shown to be important. When using magnesium oxide as a source of magnesium, the partial insertion of magnesium cations into the apatite structure occurs. In contrast, when magnesium hydroxide or monomagnesium phosphate is used, a single-phase Mg-HA is formed. Both experimental and theoretical investigations showed that an increase in the Mg content leads to a decrease in the lattice parameters and unit cell volume of Mg-HA. Density functional theory calculations showed the high sensitivity of the lattice parameters towards the crystallographic position of the calcium site substituted by magnesium. It was shown experimentally that insertion of magnesium cations decreases the thermal stability of the hydroxyapatite. The thermal decomposition of Mg-HA leads to the formation of a mixture of stoichiometric HA, magnesium oxide and Mg-substituted tricalcium phosphate phases.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia means low bone regeneration and a chronic inflammatory response. The purpose of the study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on 5 groups of white female Wistar rats: group 1 - regeneration of a bone defect in healthy animals under a blood clot; group 2 - regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3 - bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4 - filling of a bone defect with a CH-SA-HA construct in healthy animals; Group 5 - filling of a bone defect CH-SA-HA in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

S100 is a family of over 20 structurally homologous, but functionally diverse regulatory (calcium/zinc)-binding proteins of vertebrates. The involvement of S100 proteins in numerous vital (patho)physiological processes is mediated by their interaction with various (intra/extra)cellular protein partners, including cell surface receptors. Furthermore, recent studies revealed the ability of specific S100 proteins to affect cell signaling via direct interaction with cytokines. Previously, we have revealed binding of ca. 71% of the four-helical cytokines by S100P protein due to the presence in its molecule of a cytokine-binding site, which overlaps with the binding site for S100P receptor. Here we show that another S100 protein, S100A6 (pairwise sequence identity with S100P of 35%), specifically binds numerous four-helical cytokines. We have studied affinity of recombinant forms of 35 human four-helical cytokines covering all structural families of this fold to Ca2+-loaded recombinant human S100A6, using surface plasmon resonance spectroscopy. S100A6 recognizes 26 of the cytokines from all families of this fold with the equilibrium dissociation constants ranging from 0.3 nM to 12 µM. Overall, S100A6 interacts with ca. 73% of the four-helical cytokines studied to date with selectivity equivalent to that for S100P protein, with the differences limited to binding of Interleukin-2 and Oncostatin-M. The molecular docking study evidences presence in S100A6 molecule of a cytokine-binding site, analogous to that found in S100P. The findings argue the presence in some of the promiscuous members of S100 family of a site specific to a wide range of the four-helical cytokines. This unique feature of the S100 proteins potentially allows them to serve as universal inhibitors of signaling of the four-helical cytokines, which could be of value for reduction of severity of the disorders accompanied by excessive release of the cytokines.