The purpose of this original study is to critically analyze the emergence and development of the national models of financial regulation; international standards and codes; regional and national financial regulation and supervision (the case of UK, USA, Sweden, EU and Finland). The research raises both academic and regulatory concerns. It aims at shaping changes (innovations) in the supervisory practices of national and international regulators in response to new developments in FinTech markets, digital products, financial instruments and risks. Secondly, it will stimulate more systematic work on regulatory databases, registration and reporting procedures in various economies in different financial markets. The author identifies five main systems of national financial regulatory markets: the multi-tiered, multi-agency US system; the Twin Peaks model (UK); the mega-regulatory model (Sweden). There is a thorough review of international standards and institutions that work for the stability of financial systems. The analysis of regional and national systems of financial regulation and supervision is based on the examples of the EU and Finnish institutions. National macro and microeconomic regulation and supervision have been examined with a focus on the US Federal Reserve and the US Treasury. National and international regulatory institutions have been evolving along several lines. First, minimum capital and credit risk requirements for banks (80s of the 20th century) are complemented in the 21st century by buffer reserves, liquidity and leverage standards. Second, regulation focuses on ensuring the sustainability of the national economy. The regulatory focus is on ensuring the sustainability of national and global financial systems. Third, there is an increase in the number of supervised institutions. Fourth, there is a division of functions between central banks (macroeconomic regulation) and one or two mega-regulators (microeconomic regulation and supervision). Fifth, there is a division of labour between the international financial institutions (BIS, IMF, WB) and national regulators. Sixth, the focus is on protecting consumers and investors, and countering money laundering and the financing of terrorism. Seventh, there is an understanding for a common approach by central banks to new financial technologies and cybersecurity.

The World economy after global crisis of 2008–2009 entered a restructuring era. It defines relevance of researches of its directions and patterns. The principles of determinism and systemic analysis are methodological basis of article. In research were used the methods of processing Big Date, as of continuous changes and the symmetric analysis of macroeconomic indicators according to databases of the IMF, WB, BIS, the Central banks and treasuries. As a result of the research it is proved that depth and globalism of recessionary processes are caused by a combination of crisis of world financial system and civilization problems. Intrinsic signs of risks in the modern economy caused by the duality of the nature of global crises have been identified. There are analyzes: the deficit of resources of the international financial institutions, a negative role of a fixed rate of Yuan, a big share of derivatives and off-balance obligations of banks, use of SPV in structures of deals, growth of debt obligations, trade wars, slowdown in the growth of the Chinese economy, aggravation of contradictions between global and national finances. The thesis is reasonable that deglobalization and dedollarization deepened this conflict, started the rollback mechanism from achievements of globalization, led to tariff wars. By means of a systematization it is proved the key directions of the restructuring of global economy: legal basis, leadership and reserve currency. On the basis of SWOT-analysis of the USA and China it was concluded that the question of leadership of one country should be excluded, but slow transition to use SDR (with a basket from 15–20 currencies) as a reserve.

Ophiura sarsii is a common brittle star species across Arctic and subarctic regions of Atlantic and Pacific oceans. In the Barents Sea O. sarsii is among the dominant echinoderms. We studied genetic diversity of O. sarsii by sequencing the 548 bp fragment of mitochondrial COI gene. O.sarsii demonstrated high genetic diversity in the Barents Sea. Both major Atlantic mtDNA lineages were present in the Barents Sea and were evenly distributed between the northern waters around Svalbard archipelago and the southern part near Murmansk coast of Kola Peninsula. Both regions, as well as other parts of the O.sarsii range, were characterized by high haplotype diversity with a significant number of private haplotypes, being mostly satellites to the two dominant haplotypes, each belonging to a different mtDNA clade. Demographic analyses indicated that the demographic and spatial expansion of Ophiura sarsii in the Barents Sea most plausibly has started during the Bølling–Allerød interstadial, during the deglaciation of the western margin of the Barents Sea.

This report covers the analysis of Intrusion Detection Systems nowadays. Therefore, it focuses on the IDS classification, which includes not only a well-known explanation of Network/Host-Based IDS type but also cloud-based solutions. The paper explores ways of intrusion detection, providing examples of the best detecting tools (OSSEC, Snort or Bro (ZEEK)). Another aspect covered in this report is the juxtaposition of three systems: IDS, IPS and IRS and their response. Finally, there will be presented Intrusion Detection Systems' evasion techniques and challenges, followed by critical conclusions.

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of cancers of different origin to increase the efficacy of cytotoxic agents. Such strategy can be effective to overcome the resistance to standard chemotherapy or anti-angiogenic therapy. This review presents the results of combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells and on animal xenograft models, with a few examples of clinical trials. The effects of such approach on viability of cancer cells and tumor growth, as well as autophagy-dependent and independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ are summarized. Although the majority of experimental studies in vitro and in vivo have shown that CQ/HCQ can effectively sensitize the cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Although pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, the development of more specific compounds is required.

The pathophysiology of many mood disorders is closely related with abnormal stress response associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol overproduction. The hippocampus, key structure of the limbic system responsible for both cognitive and emotional spheres, is selectively vulnerable to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration. The antiGC therapy of psychiatric diseases, in particular depressive disorders, may be a useful additional treatment. Among other approaches, targeting glucocorticoid receptors, abounded in the hippocampus, is regarded as highly promising. However, though the preclinical data provide firm evidence to the concept of antiGC therapy for stress-related diseases, clinical studies still are at the proof-of-concept stage. Noteworthy, chronic GC excess is associated not only with mood diseases, but also with cognitive decline, metabolic disorders, diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate affective symptoms, cognitive disturbances, GC and insulin resistance and adverse side effects of conventional drugs through beneficial effects on hippocampal dysfunction and neurodegeneration, neuroinflammation, and neurogenesis. Since stress/GC-associated neuroinflammation-mediated pathology of the limbic system and, specifically, the hippocampus, is a general feature typical for many brain diseases, the concept of antiGC therapy may be extended, tested and validated in a wider spectrum of cerebral pathologies.

: In this article, the authors propose an algorithmic approach to building a model of the dynamics of economic and, in particular, innovation processes. The approach under consideration is based on a complex algorithm that includes (1) decomposition of the time series into components using singular spectrum analysis; (2) recognition of the optimal component model based on fuzzy rules, and (3) creation of statistical models of individual components with their combination. It is shown that this approach corresponds to the high uncertainty characteristic of the tasks of the dynamics of innovation processes. The proposed algorithm makes it possible to create effective models that can be used both for analysis and for predicting the future states of the processes under study. The advantage of this algorithm is the possibility to expand the base of rules and components used for modeling. This is an important condition for improving the algorithm and its applicability for solving a wide range of problems.

Lymphedema refers to a group of disorders characterized by the accumulation of protein-rich fluid in the interstitial tissues, resulting from an imbalance between lymph production and it’s drainage via lymphatic vessels. More than 10 types of isolated primary LD is described, and among them CELSR1-associated lymphedema are one of the less studied. A family with two sibs, a 17-year-old boy and an 8-year-old girl, both diagnosed with primary LD, presented to the clinic. Both patients were observed with primary symptoms of LD at 2-3 months of age, presented by the swelling of right foot. Lymphatic pathologies were not diagnosed in parents or close relatives. The rare c.7664A>C variant, resulting in the H2555P missense mutation in the intracellular loop of CELSR1 transmembrane domain, was discovered in a patients. The clinical signs, MRL scanning data, in silico predictors and the absence of known pathogenic mutations or rare variants of unknown significance in other genes, associated with the development of primary lymphedema, allow us to assume that c.7664A>C variant of CELSR1 may be responsible for pathogenesis of the disease in the presented family case.

Currently, the use of medications during pregnancy in Latin America is common; studies with Latin American samples find that nearly 90% of pregnant women use some medication at least once during pregnancy. Furthermore, approximately 21% of the respondents self-medicated. Worldwide, the prevalence of this disease is 32%. The most common medications are nonsteroidal anti-inflammatory drugs and analgesics. Many of these drugs are available over the counter without a prescription. For this reason, a systematic review of the literature on the adverse effects on the woman and the fetus was performed. Objective: To determine the adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) on pregnant women and fetuses during pregnancy. Methods: Systematic literature review. The following search strategy was used for the databases: Science Direct, PubMed, Scopus and Web of Science, through September 3, 2022. The population of pregnant women without previous comorbidities was defined. The intervention of interest was the use of NSAIDs during pregnancy. The outcomes of interest were adverse effects for the mother or fetus (weight of the newborn, congenital malformations present in the fetus, systemic effects in the pregnant woman during her gestation period). The types of studies included clinical trials, cohort studies and case‒control studies. Results: 1 study included 2,985 pregnant women without previous comorbidities. The use of aspirin more frequently during pregnancy stands out. The adverse effects on the fetus were preterm birth <37 weeks, low birth weight < 2500 g and increased admission to the neonatal intensive care unit. No adverse effects were found for the mother. Conclusions: There are not enough data indicating that the use of NSAIDs during pregnancy is safe. Some studies show that the use of NSAIDs during pregnancy could be related to problems in the development and growth of the fetus and health effects for the mother during pregnancy, so it is advisable to use these drugs under medical prescription and for the shortest possible time. in the gestation stage.

Development of agriculture in Russia and Belarus is based on the practical implementation of "smart" systems in agriculture based on the use of modern wireless, intelligent technologies and Internet of Things. This review presents research articles (mainly, in Russian) published in the period of 2013 – 2022 on the use of cloud technologies and Internet of Things for the development of agriculture in Russia and Belarus. An analysis of the use of cloud technologies and Internet of Things in the modern world is given on the basis of research articles and reviews published in English in the period of 2017 – 2022. The main directions of digitalization of modern agriculture are listed. The uses of cloud technologies and Internet of Things in agriculture are described along with promising directions for further research and applications.

As of the end of 2022, despite the disruptions caused by the COVID-19 pandemic, the global HIV epidemic persists, with 39 million individuals living with the virus and 1.3 million new infections reported in that year. Opportunistic infections associated with AIDS claimed the lives of over 630,000 people in 2022, contributing to a cumulative death toll exceeding 40.4 million since the disease's emergence in 1981. Although advances in HIV diagnosis and antiretroviral therapy have transformed the disease into a manageable chronic condition, issues like drug resistance, low compliance, and high treatment costs persist. Until a vaccine becomes available, a comprehensive approach involving prevention and therapy is essential, particularly for high-risk populations. Research shows that prevention strategies are more cost-effective than treatment. The development of antiretroviral drugs has also spurred the creation of antivirals for other infections. The emergence of COVID-19 vaccines has opened new avenues for HIV vaccine development, as lessons from vaccine platform technologies like mRNA, viral vectors, and protein subunits can be applied to HIV. This review explores the most promising prophylactic and therapeutic HIV vaccine trials, emphasizing the need for a multi-pronged approach combining vaccines with non-vaccine strategies. Though significant progress is anticipated, the road to a viable HIV vaccine remains long, especially for high-risk populations, such as medical workers, blood transfusion recipients, and drug users. The combinatorial approach, capitalizing on various aspects of immunity, may hold the key to defeating HIV in the future.

In this article, by focusing on the two main protagonists, Mitya Karamazov and Pavel Smerdyakov, we would like to analyze the murder of Fyodor Karamazov, which is the crucial event in the novel The Brothers Karamazov. We have conducted analysis of these two characters from the perspective of literature studies, psychology and psychiatry. Although we agree with Freud’s opinion (1) that it is not important who killed the father, but who wanted to kill him, we hope that our findings will allow us to formulate conclusions that will be helpful in new interpretations of this masterpiece.

The current paper aims to contribute to the literature on community renewable energy by considering two projects developed in the north-west of Italy, in the Piedmont region. The case-studies are analysed by combining two theoretical perspectives: the multilevel perspective and the sociotechnical imaginary approach. On the one hand, applying the first perspective helps reconstruct the context and circumstances that have permitted Piedmont’s energy community projects to emerge. In particular, attention is given to the windows of opportunity created by the passing of the Milleproroghe decree at the national level and by the ensuing regional law 12/2018, which acknowledged the establishment of energy communities in the Piedmont. On the other hand, the sociotechnical imaginary approach allows identifying collective ideas and meanings that emerge when individuals or groups promote a sociotechnical innovation. In our cases, two main future changes are associated with community renewable energy: an integral ecology approach and a stronger sense of community on the one hand, and local development opportunities for rural areas characterised by depopulation, low employment rate and high energy demand, on the other.

A dark region and a bright part of accretion disk are viewed on the first image of the supermassive black hole in the galaxy M87 obtained by the Event Horizon Telescope. We demonstrate that a viewed dark region is a silhouette of the black hole event horizon, while the outline (contour) of this silhouette is an equator of the event horizon globe. A dark silhouette of the black hole event horizon is placed within the expected position of the black hole shadow, which is not revealed on the first image. We calculate numerically a relation between the viewed position of the black hole silhouette and the brightest point in a thin accretion disk in dependence of the black hole spin. A spin of the supermassive black hole in the galaxy M87, derived from this relation, is $a=0.75\pm0.15$.

We investigated the liquid water path and global solar irradiance at ground (Q) according to the ICON model, CLOUDNET measurements in Lindenberg, Munich, Jülich, and BSRN observations in Lindenberg. The liquid water path is underestimated, while global irradiance is overestimated. The lower liquid water path is due to liquid water content underestimation practically in all atmosphere layers and lower frequency of liquid clouds occurrence compare to observations. The latter is partly associated with a reduced model’ sensitivity to the cloud condensation nuclei (CCN). An increase in CCN from 250 cm-3 (typical background value for the region of interest) to 1700 cm-3 (characteristic of polluted continental clouds) leads to an increase in grid-scale liquid water path by 40% and a decrease in Q under overcast conditions by 12%. However, we also showed that liquid water path is not a key factor of Q overestimation. The main factor is an inaccurate description of the cloud spatial structure, where the correct prediction of the direct to global irradiance ratio as a spatial characteristic of clouds plays the most important role compared to standard cloud fraction.

Rapid progress in gene editing based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) has revolutionized the study of gene and genome function and genetic disease correction. While numerous genetically modified cellular and animal models have been created to understand biological processes, the clinical application of CRISPR/Cas tools has been impeded by off-targeting and delivery problems. It is generally accepted that the delivery of CRISPR in the form of a ribonucleoprotein complex (RNP) substantially reduces the time of DNA exposure to the effector nuclease, minimizing off-target effects and facilitating clinical usage. This review focuses on CRISPR/Cas RNP delivery with retro/lentiviral particles and exosomes, whose parallel production by cells transfected with viral vectors is underestimated. We critically evaluate specific mechanisms of extracellular particle formation and loading with CRISPR/Cas for each system. Additionally, the details of Cas-nanoparticle entry and uncoating, previously unappreciated in the context of gene editing efficiency, are discussed. Based on existing knowledge about the consequences of intervention in retroviral assembly, entry, or exosome formation, we outline the potential problems with CRISPR/Cas delivery using extracellular nanoparticles and ways to address them.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

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.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

Magnetorheological processing was applied to polish the working surfaces of the ZnGeP2 single crystal, in which a non-aqueous liquid with magnetic particles of carbonyl iron with the addition of nanodiamonds was used. Samples of a single crystal ZnGeP2 with an angstrom level of surface roughness were received. the use of MRP has allowed more accurately characterizing possible structural defects that have emerged on the surface of a single crystal and have a size of ~ 0.5-1.5 μm. the LIDT value at the indicated or-ders of magnitude of the surface roughness parameters is determined not by the quality of polishing, but by the number of point depressions caused by physical limitations of the structural configuration of the crystal volume. These results are in good agreement with the assumption made about a significant effect of the concentration of dislocations in a ZnGeP2 crystal on LIDT.

This paper presents a new method to model the nonlinear behaviour of masonry double curvature structures, possibly reinforced by composite materials, by means of conventional elasto-plastic analyses. It is meant to be used in professional design, especially for assessment and retrofitting purposes, therefore based on the exploitation of the simplest nonlinear Finite Elements available in a commercial software, namely trusses with elasto-fragile and elasto-ductile behaviour (Cutoff Bars). The numerical static nonlinear analyses are carried out by considering elastic hexahedral elements for bricks and lumping nonlinearities on joints. These have been assumed in turn elastic-brittle and elastic-plastic by using 1D elements, respectively Point Contacts, under No-Tension Material hypothesis, and Cutoff Bars, assigning small tensile resistance to the material. The reinforcement, realised with FRP hooping strips, has been successfully modelled in a similar fashion, i.e. by applying perfectly bonded elastic-plastic Cutoff Bars at the extrados of the dome, where the debonding is accounted for in a conventional way limiting the tensile strength according to Italian Standards indications. The procedure is validated against benchmark models with the same geometry, using experimental data and more refined structural model results for comparison.

Abstract Background: Analysis of different type of consolidation in dogs and cats relay on parenchymal and vascular criteria. Hypothesis: the vascular criteria of the consolidation it’s possible to perform in dogs and cats and vascularisation is different in shred, tissue, nodule, wedge sign and mass. Animals: 347 cats and 634 dogs with different types of consolidations. Methods: Retrospective study between 2018-2023. Lung ultrasound performed in dogs and cats with different types of consolidations. Characteristic of bronchogram: air dynamic and static bronchogram, fluid bronchogram or absence of bronchogram. Types of vascularisations in consolidation: tree like type, residual, chaotic vascularisation and penetrating from the chest wall to consolidation and “vascular sign”. Conclusion and Clinical Importance: Analysis of bronchogram and type of vascularisation in consolidation is possible to perform in dogs and cat. The analysis of mentioned criteria had an impact on subsequent diagnostic and therapeutic decisions

A potassium bromide KBr material, which has been widely used as the key element in the Fourier spectrometers and as the output window of the IR-lasers, has been studied with good advantage via applying the carbon nanotubes in order to modify the potassium bromide surface. The laser oriented deposition method has been used to place the carbon nanotubes at the matrix material surface in the vertical position at the different electric field varied from 100 to 600 V×cm-1. The main idea of the improvement of the spectral properties of the potassium bromide structure is connected with the fact that the refractive index of the carbon nanotubes is substantially less than the refractive index of the studied material, and the small diameter of the carbon nanotubes allows one to embed these nano-objects in the voids of the lattice of the model matrix systems. Moreover, the mechanical characteristics and wetting features of the potassium bromide structures have been investigated under the condition mentioned above. Analytical and quantum-chemical simulations have supported the experimental results.

Urban mobility and sustainable transportation are fundamental for the European Union's goal of achieving climate neutrality by 2050. The EU encourages national governments to prioritize zero-emission urban transport systems that emphasize safety, accessibility, and inclusiveness. Promoting walking plays a fundamental role in sustainable urban mobility, offering advantages such as emission reduction, better air quality, and enhanced public health. Recent research underscores the importance of creating appealing and safe pedestrian environments to encourage walking. These efforts align with the United Nations' Agenda 2030 sustainability goals, particularly Objective 11, which aims to build inclusive, safe, and sustainable cities and communities. This paper explores the factors influencing pedestrians' willingness to walk and categorizes them into four main groups: Physical Characteristics, Comfort, Safety, and Attractiveness. Significantly, the study reveals that the importance of these factors varies based on demographics, mainly the age of the users. Understanding these factors and their relative significance for pedestrian satisfaction is crucial for shaping effective policies and urban planning strategies aimed at promoting sustainable mobility. By prioritizing pedestrian satisfaction and addressing the specific needs and preferences of diverse groups, cities can create more walkable and environmentally friendly urban environments. These findings offer valuable insights for policymakers and urban planners working toward EU climate-neutral objectives and enhancing the well-being of citizens.

This research investigates the utilization of human driving models in autonomous vehicles, particularly in scenarios with minimal or no interactions with other vehicles. Human driving models provide valuable insights into driver behavior and play a crucial role in shaping the behavior of autonomous vehicles, enhancing their performance and user experience. The primary focus of the study is the creation of a planning model for autonomous vehicles when navigating roundabouts in the absence of traffic. This model seeks to emulate human driving behavior, ensuring predictability, safety, optimization of traffic flow, and adaptation to various roundabout geometries. To achieve this, the research introduces a trajectory model that takes into account geometric attributes and speed variations within roundabouts. The model is calibrated using empirical data and generalizes parameters through statistical regression methodologies. This model is referred to as "MRoundabout" and is evaluated for its consistency in generating plans that closely mimic human driving behavior within roundabouts. While the study presents a promising approach, it acknowledges limitations related to the model's reliance on geometric attributes and its inability to account for external factors like weather conditions. This research underscores the importance of bridging the gap between theoretical research and practical application, with the aim of enhancing safety and the overall user experience in real-world driving scenarios.

During the construction of buildings, dangerous chemicals such as benzene, formaldehyde and others are used, which accumulate during the operation of the building. High concentrations of these substances can harm human health. In this article, we have analyzed the possible impact of modular green wall systems on improving of the air. During the research, four different modular green wall systems and various plant species were considered. The result showed that a modular green wall system can improve the air quality by removing harmful pollutants from the air in the buildings. Urban design used to be turned greener and more sustainable using the modern technologies of modular green wall systems. This study focuses on the air-cleaning benefits provided by modular green wall systems and their assessment. This research contributes to fill existing literature gaps on the green wall systems on the buildings and biophilic architecture.

In the present study, we investigate the post-editese phenomenon, i.e., the unique features that set machine translated post-edited texts apart from human-translated texts. We use two literary texts, namely, the English children's novel by Lewis Carroll Alice’s Adventures in Wonderland (AW) and Paula Hawkins' popular book The Girl on the Train (TGOTT) translated from English into Brazilian-Portuguese to investigate whether the post-editese features can be found on the surface of the post-edited (PE) texts. In addition, we examine how the features found in the PE texts differ from the features encountered in the human-translated (HT) and machine translation (MT) versions of the same source text. Results revealed evidence for post-editese for TGOTT only with PE versions being more similar to the MT output than to the HT texts.

The dependence of the width of annual rings of woody plants on the characteristics of the snow cover is analyzed in various natural zones of the West Siberian Plain and adjacent mountainous areas: the maximum thickness and water reserve for the entire winter period and for individual months, the dates of disappearing, establishment, and duration of the occurrence of a stable snow cover. It has been shown that the role of the thickness and water content of snow cover for the radial growth of trees is differentiated by geographical location. On the plain, it intensifies in the forest-tundra and dry steppe. The response of radial growth to snow cover in the upper and lower parts of the forest belt is often opposite. Dates of establishment of stable snow cover are more important for tree growth compared to dates of disappearance. Dates of disappearance of stable snow cover are more significant in the southern regions than in the northern ones. The value of the duration of the period with stable snow cover for tree growth is higher in the southern regions.

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying elderly individuals at risk of sarcopenia. This cross-sectional study aimed to develop a sarcopenia risk screening tool, named Sarc-Global, with enhanced sensitivity, incorporating factors pertinent to the overall health of the elderly. Utilizing the criteria established by EWGSOP2 for diagnosing sarcopenia, we evaluated 395 communi-ty-dwelling elderly individuals. This evaluation served as a reference for assessing the efficacy of two validated questionnaires, Sarc-F and Sarc-CalF, and our newly developed Sarc-Global. Con-structed through multiple logistic regression, Sarc-Global integrates variables such as sex, age, medication use, body mass index, arm circumference, and handgrip strength – all significantly associated with sarcopenia (p

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Solid tumours are characterized by an altered microenvironment (TME) from the physi-cochemical point of view, displaying a highly hypoxic and acidic interstitial fluid. Hy-poxia results from uncontrolled proliferation, aberrant vascularization and altered can-cer cell metabolism. Tumour cellular apparatus adapt to hypoxia by altering its metab-olism and behaviour, increasing its migratory and metastatic abilities by acquisition of a mesenchymal phenotype and selection of aggressive tumour cell clones. Extracellular acidosis is considered a cancer hallmark, acting as a driver of cancer aggressiveness by promoting tumour metastasis and chemoresistance by selecting for more aggressive cell phenotypes, although the underlying mechanism is still not clear. In this context, Ca2+ channels represent good target candidates due to their ability to integrate signals from the TME. Ca2+ channels are pH and hypoxia sensors and alterations in Ca2+ homeostasis in cancer progression and vascularization have been extensively reported. The present review will focus on Ca2+ permeable ion channels, with a major focus on TRP, SOC and PIEZO channels, that are modulated by tumour hypoxia and acidosis as well as the role of the resulted altered Ca2+ signals on cancer progression hallmarks. A deeper compre-hension of the Ca2+ signaling and acidic pH/hypoxia interplay will break new ground for the discovery of alternative and attractive therapeutics targets.

Cytochrome P450 oxidoreductase (POR) is the redox partner of steroid and drug-metabolizing cytochromes P450 located in the endoplasmic reticulum. Mutations in POR cause a broad range of metabolic disorders. The POR variant rs17853284 (P228L) identified by genome sequencing has been linked to lower testosterone levels and reduced P450 activities. We expressed POR wild type and the P228L variant in bacteria, purified the proteins, and performed protein stability and catalytic functional studies. Variant P228L affected the stability of the protein as evidenced by lower unfolding temperatures and higher sensitivity to urea denaturation. A significant reduction of small molecule metabolism was observed with POR P228L while activities of CYP3A4 were reduced by 25%, and activities of CYP3A5, and CYP2C9 were reduced by more than 40% compared to WT POR. The 17,20 lyase activity of CYP17A1 responsible for production of main androgen precursor dehydroepiandrosterone, was reduced to 27% of WT in presence of P228L variant of POR. Based on in silico and in vitro studies we predict that the change of proline to leucine may change the rigidity of the protein, causing conformational changes in POR, leading to altered electron transfer to redox partners. A single amino acid change can affect protein stability and cause a severe reduction in POR activity. Molecular characterization of individual POR mutations is crucial for a better understanding of the impact on different redox partners of POR.

CD15 (Lewis X/Lex) is a fucosyl (3-fucosly-N-acetyl-lactosamine) moiety found on membrane proteins of various cancer cells. These include renal cancer, prostate and bladder cancers, acute leukemias, hepatocellular carcinoma, breast cancer and melanoma. The antigen plays an espe-cially significant role in renal cell carcinoma. Its high expression serves as a good prognostic marker for patients and high hopes are related to its use in the immunotherapy of the tumor. The biological role of CD15 is the interaction with E-, L- and P-selectins (adhesion molecules) and al-lowing for the adhesion with the endothelial cells. In this way, cancer cells start to interact with the endothelium of blood vessels and consequently move out from the blood flow to the sur-rounding tissues. The blockage of antigen’s function results in reduced metastatic potential. Moreover, the molecule may be a therapeutic target against cancer in monoclonal antibod-ies-based therapies. CD15s is a sialyl derivative of CD15, that possess its own unique characteris-tics. Unlike high expression of CD15, which is a prognostic factor in Hodgkin lymphoma, CD15s relate to poor prognosis for the patients. Due to the high abundance in cancer cells, CD15 is con-sidered as a marker of Cancer Stem Cells. This review presents a comprehensive description of the role of CD15 and CD15s in cancer development and metastasis and overviews the clinical appli-cations of the anti-CD15 therapy.

This study examined the efficiency of a combined diagnostic approach in which bioamplification of Arizona 861 S1 citron was integrated with RT‒PCR to detect Citrus tristeza virus (CTV) and Hop Stunt Viroid (HSVd) in Citrus plants. The capacity of the combined method to diagnose mixed infections of CTV and HSVd, along with early single infections of both pathogens, was assessed by evaluating the incubation periods and differential detection capabilities between the combined and direct methods. The bioamplification method exhibited high sensitivity (100%) and specificity (100%) for CTV, enabling early detection even in patients with low-titer infections compared to direct RT‒PCR. However, for HSVd, the combined method achieved 50% sensitivity in early infections, highlighting the need for additional replicates to enhance diagnostic reliability. The relative concentrations of pathogens in mixed and simple infections were evaluated; the analysis revealed no significant differences, suggesting minimal interference between CTV and HSVd. This approach allows early detection of CTV but requires further refinement for HSVd diagnosis. These findings underscore the complementary roles of the cost-effectiveness of direct RT‒PCR and the sensitivity of the combined method in implementing effective disease control strategies in citrus crops.

Acute high altitude illnesses are of great concern for physicians and people traveling to high altitude. High Altitude Pulmonary Edema (HAPE) can be better understood through the Oxygen Transport Triad which involves the Pneumo-Dynamic Pump (Ventilation), the Hemo-Dynamic Pump (Heart and circulation), and Hemoglobin. The two pumps are the first physiologic response upon initial exposure to hypobaric hypoxia. Hemoglobin is the balancing energy-saving time-evolving equilibrating factor. The increased hemoglobin at high altitude reduces the percentage of dissolved oxygen in the arterial oxygen content with respect to sea level. At high altitude, the acid-base balance must be adequately interpreted using the high altitude Van-Slyke correction factors. Pulse-oximetry measurements during breath-holding at high altitude allow for the evaluation of high altitude diseases. The Tolerance to Hypoxia Formula shows that, paradoxically, the higher the altitude the more tolerance to hypoxia. All organisms adapt physiologically and optimally to a high-altitude environment to survive. Reduction of pulmonary hypertension in HAPE through oxygen administration results in a favorable outcome.

Electrostatic interactions have a determining role in conformational and dynamic behavior of polyelectrolyte molecules [1]. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in water solution with the most commonly used K+ or Na+ counterions were investigated using atomistic molecular dynamics (MD) simulations. Seven common force fields, AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and with the non-bonded fix (NBFIX) and electronic continuum corrections (ECC) to were studied. These corrections have bene introduced to correct for the problem of overbinding of ions to the charged groups of polyelectrolytes. Physical properties, such as molecular sizes, local structure and dynamics, were studied using two types of common counterions, potassium and sodium. The results show that in some cases, the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of ions and charged side chain groups. The local structures and dynamics are more sensitive on dihedral angle parameterization resulting in a preference for defined monomer conformations amd the type of correction used.

Cytochrome P450 oxidoreductase (POR) is an essential redox partner for steroid and drug-metabolizing cytochromes P450 located in the endoplasmic reticulum. Mutations in POR lead to metabolic disorders, including congenital adrenal hyperplasia, and affect the metabolism of steroids, drugs, and xenobiotics. In this study, we examined approximately 450 missense variants of the POR gene listed in the Genome Aggregation Database (gnomAD) using eleven different in silico prediction tools. We found that 64 novel variants were consistently predicted to be disease-causing by most tools. To validate our findings, we conducted population analysis and selected two variations in POR for further investigation. The human POR wild type, along with the R268W and L577P variants, were expressed in bacteria and subjected to enzyme kinetic assays using model substrate. We also examined the activities of several cytochrome P450 proteins in the presence of POR (WT or variants) by combining P450 and reductase proteins in liposomes. We observed a decrease in enzymatic activities (ranging from 35% to 85%) of key drug metabolizing enzymes, supported by POR variants R288W and L577P compared to WT-POR. These results validate our approach of curating a vast amount of data from genome projects and provide an updated and reliable reference for diagnosing POR deficiency.

One method of creating a brass coating is through electrodeposition, which is most often completed in cyanide galvanic baths. Because of the toxicity of cyanides, many are working on the development of cyanide-free baths, which are promising but not satisfactory to replace the classic methods. The purpose of the study was to explore a new generation of non-aqueous cyanide-free baths based on 1-ethyl-3-methylimidazolium acetate ionic liquids. The study involved the formation of copper, zinc, and brass coatings. The influence of the bath composition, cathodic current density, and temperature was determined. The obtained coatings were characterized by their morphology, chemical composition, roughness, and corrosion resistance. It was found that the structure of the obtained coatings is strongly dependent on the process parameters. The three main structures observed were fine-grained, porous, and olive-like. To the best knowledge of the authors, it is the first time the olive-like structure was observed in the case of an electrodeposited coating. The Cu-Zn coatings consisted of 19–96 at.% copper and exhibited relatively strong corrosion resistance. High improvement of corrosion properties was found in the case of copper and brass coatings with an olive-like structure.

Clinical trials, by contributing to the development of diagnostics and to the search for modern, more effective, and safer therapies, have become one of the most important elements of the healthcare system. The aim of this study was to assess Poles' knowledge and beliefs about clinical trials. Methods: The survey was conducted among Poles aged 18 and over with the help of external company, Ariadna, which is an independent research panel. The questionnaire contained 22 questions, of which 13 questions concerned beliefs and attitudes towards clinical trials. Results: One thousand and seventy-nine participants took part in the study (N = 1079). The mean age of respondents was 44.96 years (SD = 16.30). Slightly more women (N = 568, 52.6%) than men (N = 511, 47.4%) took part in the study. Among the respondents, 86.5% (N = 933) were aware of clinical trials. The main sources of information about clinical trials were the media (53.8%) including the Internet (N= 355, 32.9%), TV (N = 175, 16.2%), press (N = 30, 2.8%) and radio (N = 21, 1.9%). 43.2% (N = 466) of respondents reported little knowledge of clinical trials, while more than three quarters (N = 805, 75.2%) said they would like to learn more about clinical trials. Most respondents (N = 879, 81.4%) agreed with the statement that participation in a clinical trial is completely voluntary, and more than half (N = 580, 53.7%) agreed with the statement that hospitals participating in clinical trials provide better healthcare. The statement that the results of clinical trials are made available to the public was disagreed with by 37.2% (N = 402) of participants. Only 30.3% (N = 327) of participants agreed that clinical trials should be conducted with children. Conclusions: Poles rate their knowledge of clinical trials as low and would like to learn more. To reach the largest possible group of Polish patients, parallel educational activities on multiple levels may have the best effect. Poles' knowledge of clinical trials is mainly based on commercial sources. Further studies in different groups, i.e., clinical trial patients and investigators, are needed.

The COVID-19 pandemic has raised questions about indirect impact in pregnant women on the development of their future children. Investigating the characteristics of lipid metabolism in the "mother-placenta-fetus" system can give information about the pathophysiology of COVID-19 infection during pregnancy. 234 women were included in study. Maternal plasma, cord blood, amniotic fluid lipidome were analyzed using HPLC-MS/MS. Differences in lipid profile were searched by Manna-Whitney and Kruskall-Wallis test, diagnostic model based on logistic regres-sion were bilt by AIC. Elevation levels of lysophospholipids, triglycerides, sphingomyelins, and oxidized lipids was registered in patients’ after COVID-19 maternal and cord plasma. An increase in maternal plasma sphingomyelins and oxidized lipids was observed in cases of infection during the second trimester. In amniotic fluid, compared to the control group, nine lipids are reduced, six lipids are elevated. Levels of phosphoglycerides, lysophosphoglycerides, and phosphatidylinosi-tols decreased during infection in the second and third trimesters of pregnancy. Newborn’s health diagnostic model based on maternal plasma were developed for each group and exhibit good di-agnostic value (AUC> 0.85). Maternal and cord plasma’s lipidome changes during delivery, asso-ciated with Covid-19 infection during pregnancy, are synergistic. The most significant disturbances occur with infections in the second trimester of pregnancy.

Plastics have recently become an indispensable part of everyone's daily life due to their versatility, durability, light weight and low production costs. The increasing production and use of plastics poses a great danger due to the very long period of degradation, but also the negative impact on living organisms. Decomposing plastics lead to the formation of microplastics, which accumulate in the environment and living organisms becoming part of the food chain. Polyvinyl chloride (PVC) contamination of soil and water seriously threatens ecosystems around the world. The durability and low weight make microplastic particles easily transported with water or air and end up in the soil. Thus, the problem of microplastic pollution affects the entire ecosystem. Since microplastics are commonly found in both drinking and bottled water, humans are also exposed to the harmful effects of microplastics. Because of the existing risks associated with PVC microplastic contamination of the ecosystem, intensive research is underway to develop methods to clean and eliminate it from the environment. Pollution of the environment with plastic, especially microplastic, results in the reduction of both water and soil resources used for agricultural and utility purposes. This review provides an overview of PVC's environmental impact and disposal options.

The possibility of using Si-based anodes in lithium-ion batteries is actively investigated due to the increased lithium capacity of silicon. The paper reports the preparation of submicron silicon fibers on glassy carbon in the KI–KF–KCl–K2SiF6 melt at 720°C. For this purpose, the parameters of silicon electrodeposition in the form of fibers were determined by cyclic voltammetry, and ex-perimental samples of ordered silicon fibers with an average diameter from 0.1 to 0.3 μm were obtained under galvanostatic electrolysis conditions. Using the obtained silicon fibers, anode half-cells of lithium-ion battery was fabricated, and its electrochemical performance under mul-tiple lithiation and delithiation was studied. By means of voltametric studies, it is observed that charging and discharging of the anode based on the obtained silicon fibers occurs at potentials from 0.2 to 0.05 V and from 0.2 to 0.5 V, respectively. A change in discharge capacity from 520 to 200 mAh g-1 during the first 50 charge/discharge cycles at a charge current of 0.1C and a Coulomb ef-ficiency of 98-100% was shown. The possibility of charging silicon-based anode samples at charging currents up to 2C was also noted; the discharge capacity ranged from 25 to 250 mAh g-1.

Background: ; Biotechnology is developing at an ever-increasing pace, and the progressive computerisation of health care and research is making it increasingly easy to share data. One of the fastest growing areas is biobanking. However, even with the best equipment and the best trained staff, a biobank will be useless without donors. For this reason, we have decided to gauge Polish citizens' awareness and attitudes towards biobanking and their willingness to donate biological samples. Methods: The survey was conducted among a nationwide group of 1,052 Poles aged 18 and over where the totals for gender, age and place of residence were selected according to representation in the population of adult Poles. The survey was conducted using the Computer Assisted Web Interview (CAWI) technique. Results:; N=701 (66.6%) respondents indicated that they had heard of scientific studies in which samples of biological material such as blood, saliva or urine are collected. More than half of respondents (N=613, 58.3%) have a positive opinion regarding scientific research in which samples of biological material are taken. Only N=220 (20.9%) of respondents had previously encountered the term biobanking. N=687 (65.3%) respondents would participate in a scientific study that biobanked biological material and health information. Conclusions: The level of knowledge and awareness of biobanks and their role in scientific research and the health care system among Polish citizens is low and requires education and information activities.

As long as the non-contact digital printing is not a common standard in the corrugated packaging industry, corrugated board crushing is a real issue that affects the load capacity of the boxes. Crushing mainly occurs during the converting of corrugated board (e.g. analog flexographic printing or laminating) and is a process that cannot be avoided. However, as show in this study, it can be controlled. In this work, extended laboratory tests were carried out on the crushing of double-walled corrugated board. The influence of fully controlled crushing (with a precision: ±10 μm) in the range from 10 to 70 % on different laboratory measurements was checked. Most of the typical mechanical tests were performed e.g. edge crush test, four-point bending test, shear stiffness test, torsional stiffness test, etc. on reference and crushed specimens. The residual thickness reduction of the crushed samples was also controlled. All empirical observations and performed measurements were the basis for building an analytical model of crushed corrugated board. The proven and verified model was then used to study the crushing effect of the selected corrugated board on the efficiency of simple packages with various dimensions.

Radiative budget is one of the key factors influencing climate change. The aim of this study is to analyze radiative regime in Moscow using the MSU-RAD(BSRN) instrumentation complex and to estimate radiative effects of the main atmospheric factors during the 2021-2023 period. Due to variations in aerosol content, the loss of global shortwave irradiance (Q) varies from 37 to 186 W/m2 (or about 18-22%) at different solar elevations with a significant decrease in direct irradiance and increase in diffuse irradiance due to multiple scattering. In winter, we observed the increase in Q of about 45 W/m2 (or 9%) at h=30° due to high surface albedo, smaller aerosol and water vapor content. At the same time, net shortwave irradiance (Bsh) demonstrates a significant decrease due to prevailing effects of snow albedo. A nonlinear dependence of Q and Bsh cloud transmittance on relative sunshine duration (Sd) is observed. Mean changes in Q against the 1955-2020 period are characterized by negative anomalies (-22%) in winter and positive anomalies in summer (+3%) due to the changes in cloudiness, reflected in Sd variations. This is in line with global tendencies in long-term changes of shortwave irradiance in moderate climate in Europe during the last years.

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

Paratuberculosis (PTB) is a chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP) that affects a wide variety of domestic and wild animals. It is considered as one of the diseases with the highest economic impact in the ruminant industry. Despite many efforts and intensive research, PTB control is still controversially discussed and diagnostic and immunoprophylactic tools lack great limitations. Thus, models play a crucial role in understanding the pathogenesis of infection and disease, and in testing novel vaccine candidates. Here, we review the potential and limitations of different experimental approaches currently used in PTB research, focusing on laboratory animals and cell based models. The aim of this review is to offer a vision of the models that have been used and what has been achieved or discovered with each one so that the reader can choose the best model to answer their scientific questions and prove their hypotheses. Also, we bring forward new approaches that we consider worth exploring in the near future.

In rye, there is a considerable variety of grain color which is determined by the diversity of compounds localized in different parts of the grain (caryopsis) - pericarp, testa, and aleurone. The localization of anthocyanins and proanthocyanidins was analyzed in 26 rye samples with identified anthocyanin genes, along with the analysis of CIE color coordinates. The Grain Scan program [1] was used to analyze images of individual grains. The localization of anthocyanins and proanthocyanidins was studied on longitudinal and cross sections of grains using light microscopy and MALDI-imaging. The violet-grained samples contain anthocyanins in the pericarp, and the green-grained samples contain anthocyanins in the aleurone layer. The green, violet and yellow-grained rye, with the exception of two anthocyaninless mutants vi3 and vi6, shows the presence of proanthocyanidins in the brown-colored testa. Four main color groups of the rye grains (yellow, green, brown, violet) could be differentiated using the color coordinate h° (hue angle). Interspecies and intraspecies variability for the localization of colored flavonoids in cereal grains is discussed.

Understanding the catalytic performance of different materials is of crucial importance for further technological advancements. This especially relates to the behavior of different classes of catalysts under operating conditions. Here we analyze the effects of local coordination of metal centers (Mn, Fe, Co) in graphene-embedded Single-Atom Catalysts (SACs). We have started from well-known M@N4-graphene catalysts and systematically replaced nitrogen atoms with oxygen or sulfur atom to obtain M@OxNy-graphene and M@SxNy-graphene SACs (x+y=4). We show that local coordination strongly affects the electronic structure and the reactivity towards hydrogen and oxygen species. However, the stability is even more affected. Using the concept of Pourbaix plots, we show that the replacement of nitrogen atoms coordinating metal center with O or S destabilizes SACs towards the dissolution, while the metal centers get easily covered by O and OH acting as additional ligands at high anodic potentials and high pH values. Thus, not only should local coordination be considered in terms of the activity of SACs, but it is also necessary to consider its effects on the speciation of SACs' active centers under different potential and pH conditions.

Mechanical damage of plant tissues leads to the activation of methanol production and its release in the atmosphere. The gaseous methanol or vapors emitted by the damaged plant induce resistance in neighboring intact plants to bacterial pathogens but create favorable conditions for the viral infection spread. Among Nicotiana benthamiana methanol-inducible genes (MIGs) most are associated with plant defense and intercellular transport. Here we characterize NbMIG21 that encodes a 209-aa protein (NbMIG21p) which does not share any homology with annotated proteins. NbMIG21p was demonstrated to contain nucleolus localization signals (NoLS). Co-localization studies with fibrillarin and coilin, nucleolus and Cajal bodies marker proteins, revealed that NbMIG21p is distributed between these subnuclear structures. Our results show that recombinant NbMIG21 possess DNA-binding properties . Similar to gaseous methanol effect an increased NbMIG21 expression leads to the downregulation of the nuclear import of NLS-containing proteins as was demonstrated on the model GFP-NLS protein. Moreover, upregulated NbMIG21 facilitates tobacco mosaic virus (TMV) intercellular transport. We identified NbMIG21 promoter (PrMIG21) and showed that it is methanol-sensitive thus induction of NbMIG21 expression occurs at the level of transcription. Our findings suggest that methanol-activated NbMIG21 might participate in creating favorable conditions for the viral reproduction and spread.

This review covers the last 25 years literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as Vorinostat) acting as HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds reported displayed good to excellent inhibitory activity against HDACs and in many cases showed anti-proliferative activity against human cancer cell lines.

The Wnt/β-catenin signaling deregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of the study was to immunohisto-chemically evaluate and compare the expression of Fzd8, WNT1, GSK-3ß and β-catenin genes in the hearts of rats with spontaneous hypertension (SHR) and DOCA-salt- induced hypertension. The myocardial expression Fzd8, WNT1, GSK-3ß and β-catenin was detected by immunohisto-chemistry and the gene expression was assessed with real-time PCR method. In SHR immunore-activity of Fzd8, WNT1, GSK-3β and β-catenin was attenuated in comparison to normotensive animals. In DOCA-salt immunoreactivity of Fzd8, WNT1, GSK-3β and β-catenin was enhanced. In SHR, decrease in the expression of genes encoding Fzd8, WNT1, GSK-3ß and β-catenin was observed compared to the control group. Increased expression of genes encoding Fzd8, WNT1, GSK-3ß and β-catenin was demonstrated in the hearts of rats DOCA-salt. Wnt signaling may play an essential role in the pathogenesis of arterial hypertension and the accompanying heart damage. Obtained results may constitute the basis for further research aimed at better under-standing the role of the Wnt/β-catenin pathway in the functioning of the heart.

Energy citizenship is increasingly receiving attention and highlights the transformation from passive to active energy consumers who are aware of and responsible for the energy transition. The topic is often associated with energy communities, which are regarded as organizations that allow citizens to directly engage in energy and broader sustainability initiatives. The objective of the article is to examine the extent of public and private engagement in the energy transition among cooperative members as well as the propensity of energy communities to promote empowerment and inclusivity. To this end, we employ a mixed-methods approach, involving a sample of 5402 participants and 20 qualitative interviews in two prominent energy cooperatives in Europe, Ecopower in Flanders and è nostra in Italy. Our results show that although a small group of members demonstrate strong and active engagement, the majority of members prefer to engage informally, while still benefitting from the empowerment provided by their cooperative. Interestingly, one subset of members is more closely aligned with the role of financial investors. Eventually, flexibility in defining and framing expectations of member engagement can play a crucial role in promoting inclusivity within energy communities, especially by bringing closer those relatively less familiar with the issue.

This review summarizes the currently known biochemical neuroadaptive mechanisms of remote ischemic conditioning. In particular, it focuses on the significance of the pro-adaptive effects of remote ischemic conditioning, which allow prevention of neurological and cognitive impairments associated with hippocampal dysregulation after brain damage. The neuro-immuno-humoral pathway of transmitting a conditioning stimulus, as well as the molecular basis of the early and delayed phases of neuroprotection, including anti-apoptotic, antioxidant and anti-inflammatory components, are also outlined. Based on the close interplay between the effects of ischemia, especially mediated by interaction of HIF factors and steroid hormones, the involvement of the hypothalamic-pituitary-adrenocortical system in remote ischemic conditioning is also discussed.

Helminths are commonly found in grazing equids, with the cyathostomin nematodes and the cestode, Anoplocephala perfoliata, being the most prevalent. Most horses harbour low burdens of these parasites and do not develop signs of infection; however, in a small number of animals, high burdens can accumulate and cause disease. Cyathostomins are associated with a syndrome known as larval cyathostominosis. This occurs when large numbers of larvae emerge from the large intestinal wall. This disease has a case fatality rate of up to 50%. A. perfoliata infection has been associated with various types of colic, with burdens of >20 worms associated with pathogenicity. Anthelmintic resistance is a serious problem in cyathostomins and is emerging in A. perfoliata. Control methods that reduce reliance on anthelmintics now need to be applied, especially as no new dewormer compounds are on the horizon. Sustainable control methods must employ diagnostics to identify horses that require treatment. Coprological tests (faecal egg counts, FEC), have been used for several decades to inform treatment decisions to reduce helminth egg shedding. These tests cannot be used to assess host burdens as FEC do not correlate with cyathostomin or A. perfoliata burdens. In the last decade, new tests have become available that measure parasite-specific antibodies, levels of which have been shown to correlate with parasite burden. These tests measure antigen-specific IgG(T) and are available in serum (cyathostomin, A. perfoliata) or saliva (A. perfoliata) formats. Tests for other helminths have been developed as research tools and need to be translated to support equine clinicians in practice. A key element of sustainable control strategies is that diagnostics must be used in combination with management approaches to reduce environmental transmission of helminths; this will help limit the proportion of horses harbouring parasite burdens that need to be targeted by treatment.

We study the robustness of the cμ-rule for the optimal allocation of a resource consisting of one unreliable server to parallel queues with two different classes of customers. The customers in queues can be served with respect to a FCFS retrial discipline, when the customers at the head of queues repeatedly tries to occupy the server in a random time. It is proved that for the scheduling problem in the system without arrivals the cμ-rule minimizes the total average cost. For the system with arrivals it is difficult directly to prove the optimality of the same policy with explicit relations. We derived for an infinite-buffer model a static control policy that also prescribes for the certain values of system parameters the service exclusively for the class-i customers if both of queues are not empty with the aim to minimize the average cost per unit of time. It is also shown that in a finite-buffer case the cμ-rule fails.

In engineering practice, one can often encounter issues related to optimization where the goal is to minimize material consumption, minimize stresses or deflections of the structure. In most cases, these issues are addressed with finite element analysis software and simple optimization algorithms. However, in the case of optimization of certain structures, it is not co straightforward. An example of such constructions are bubble deck ceilings, where in order to reduce the dead weight, air cavities are used, which are regularly arranged over the entire surface of the ceiling. In the case of these slabs, the flexural stiffness is not constant in all its cross-sections, which means that the use of structural finite elements (plate or shell) for static calculations is not possible, and therefore the optimization process becomes more difficult. The paper presents a minimization procedure of the weight of bubble deck slabs using numerical homogenization and sequential quadratic programming with constraints. Homogenization allows to determine the effective stiffnesses of the floor, which in the next step are sequentially corrected by changing the geometrical parameters of the floor and voids in order to achieve the assumed deflection. The presented procedure allows to minimize the use of material in a quick and effective way by automatically determining the optimal parameters describing the geometry of the bubble deck floor cross-section.

Ion-exchange membranes (IEMs) are widely used in desalination, waste water treatment, food, energy production and other applications. There is a strong demand for cost-effective IEMs characterized by high selective transport of ions of a certain sign of charge. In this paper, we simulate the experimental results of V. Sarapulova et al. (IJMS 2021) on the modification of an inexpensive anion-exchange membrane (CJMA-7, Hefei Chemjoy Polymer Materials Co. Ltd., China) with a perfluorosulfonated ionomer (PFSI). The modification was made in several stages including keeping the membrane at a low temperature, applying a PFSI solution on its surface, and subsequent drying it at an elevated temperature. We apply the known microheterogeneous model with some new amendments to simulate each stage of the membrane modification. It has been shown that the PFSI film formed on the membrane-substrate does not affect significantly its properties due to the small thickness of the film (4 m) and similar properties of the film and substrate. The main effect is caused by the fact that PFSI material “clogs” the macropores of the CJMA-7 membrane, thereby blocking the transport of coions through the membrane. In this case, the membrane microporous gel phase, which has a high selectivity to counterions, remains the primary pathway for both counterions and coions. Due to the above modification of the CJMA-7 membrane, the coion (Na+) transport number in the membrane equilibrated with 1 M NaCl solution decreased from 0.11 to 0.03. Thus, the modified membrane becomes comparable in its transport characteristics with more expensive IEMs available on the market.

The non-linear analysis of hollow-core concrete slabs requires the use of advanced numerical techniques, proper constitutive models both for concrete and steel as well as particular computational skills. If prestressing, cracking, crack opening, material softening, etc. are also to be taken into account, then the computational task can far exceed the capabilities of an ordinary engineer. In order for the calculations to be carried out in a traditional design office, simplified calculation methods are needed. Preferably based on the linear finite element (FE) method with a simple approach that takes into account material nonlinearities. In this paper the simplified analysis of hollow-core slabs based on the generalized nonlinear constitutive law is presented. In the proposed method a simple decomposition of the traditional iterative linear finite element analysis and the non-linear algebraic analysis of the plate cross-section is used. Through independent analysis of the plate cross-section in different deformation states, a degraded plate stiffness can be obtained, which allows iterative update of displacements and rotations in the nodes of the FE model. Which in turn allows to update the deformation state and then correct translations and rotations in the nodes again. The results obtained from the full detailed 3D nonlinear FEM model and from the proposed approach are compared for different slab cross-sections. The obtained results from both models are consistent.

In the paper, a modified nonlinear finite element method for analysis of trapezoidal plates geometrically reduced to shallow-shell Reissner-Mindlin formulation is presented. Due to the method proposed the complex plate cross-section and nonlinear materials may be modelled and no implementation of advanced constitutive law via user subroutines is needed. The generalized nonlinear constitutive law is used to update the stiffness of the plate element. The method enables modeling of complicated cross-sections, such as steel trapezoidal sheets, metal facing sandwich panels or reinforced concrete. Additionally, for those geometrically complex sections an advanced nonlinear material may be adopted. To verify the proposed method, a selected trapezoidal sheets were modeled in a commercial software as full 3D shell structures. By comparing displacements and forces, it was shown that both models behave almost identically, however, the simplified model has about 300-400 times less degrees of freedom, thus it is much more efficient.

The human proteome is composed from diverse and heterogeneous gene products/proteoforms. Previously, we have been discussing the main technical aspects in developing for inventory of human proteoforms that would be visually attractive, clear, and easy to search (Naryzhny S. J. Proteomics 2018, S1874-3919(18) 30220-3). Here, we present our first draft of the database of proteoforms that is based on this discussion. The database principles and structure are described. The database is called “2DE-pattern” as it contains multiple isoform-centric patterns of proteoforms separated according to 2DE principles.

Emotional dysfunction, including flat affect and emotional perception deficits, is a specific symptom of schizophrenia disorder. We used a modified multimodal odd-ball paradigm with fearful facial expressions accompanied by congruent and non-congruent sounds to investigate the impairment of emotional perception and reaction to other people's emotions. We analyzed subjective assessments and ERP data for emotionally charging congruent and non-congruent stimuli in patients with schizophrenia and healthy peers. The results showed the deficit of multimodal perception of fearful stimuli in patients with schizophrenia compared to healthy controls. The amplitude of N50 was significantly higher in subjects of the control group for non-congruent stimuli than congruent and did not differ in patients with schizophrenia. The dynamics of P100 and N200 components confirmed the impaired sensory gating in patients with schizophrenia. The lower amplitude of P3a could be associated with deficits in verbal memory and attention, less emotional arousal, or incorrect interpretation of emotional valence as specific features of patients. The difficulties in identifying the incoherence of facial and audial components of emotional expression could be significant in understanding the psychopathology of schizophrenia.

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α-L-glutamic acid and α-L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is the search of the ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side chain length, chemical structure and their interplay is required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side chain rotation enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

In the last decades, cultivation of chia (Salvia hispanica L.) has expanded around the world and the seeds have become well known due to their rich composition in nutrients and bioactive compounds. The aim of this work was to evaluate the physical, chemical and nutritional profile of eight chia seeds grown in different Latin-American countries (Argentina, Bolivia, Chile, Ecuador, Mexico, Paraguay and Peru). The results showed that several nutritional parameters such as the protein content and amino acid profile, dietary fiber content, lipid content, mineral composition and phytate present in the seeds depend on the location they were grown in. Other parameters such as ash content, fatty acid profile or physical parameters were uniform across locations (except for color parameters). The results support the notion that nutritional characteristics of seeds are determined by the seed's origin, further analysis is needed to define the exact mechanisms that control the changes in the seeds nutritional properties.

The study assessed the changes in the quality and physical and chemical parameters of apples of four cultivars (‘Gala’, ‘Idared’, ‘Topaz’, ‘Red Prince’) subjected to mechanical vibrations during transport under model conditions and after storage (shelf-life). Quality changes in apples were evaluated based on skin and flesh colour, total soluble solids, dry matter, firmness, titratable acidity, pH value, total polyphenol content and antioxidant capacity. The applied vibrations at a frequency of 28 Hz caused changes in the above parameters, which were visible also after storage and depended on cultivar, but did not show any clear trend or direction. Skin colour varied whereas flesh colour remained stable. Vibrations resulted in a decrease in firmness. The greatest stability of quality parameters, the highest content of bioactive compounds and the highest antioxidant capacity were observed for ‘Red Prince’ and ‘Topaz’ apples – this refers to the control and treated samples before and after storage. However, total polyphenol content and antioxidant capacity increased in all studied cultivars as a result of vibrations and storage, which suggests that 28 Hz mechanical vibrations and short-term cold storage did not reduce the health promoting potential of the apples.

This paper reviews several techniques, including analytical theories and real frequency techniques, to design ultra-wideband impedance matching networks for low-power applications. The comparison of solutions obtained using the simplified real frequency technique to the published solution using Chebyshev filter theory is demonstrated.

Within the framework of the previously proposed formulation of the quantum theory of gravity in terms of world histories, it was suggested that the universe has its own mass. This quantity is analogous to the mass of a particle in relativistic mechanics. The mass of the universe is a distribution of non-zero values of gravitational constraints, which arises and changes in time as a consequence of the initial conditions for fundamental dynamic variables. A formulation of the Euclidean quantum theory of gravity is also proposed to determine the initial state, which can be the source of the universe’s own mass. Being unrelated to ordinary matter, the distribution of its own mass affects the geometry of space and forms a dedicated frame of reference. The existence of selected reference systems is taken into account by the corresponding modification of the system of quantum gravitational constraints. A variant of such a modification of the Wheeler-De Witt equation is the operator representation of gravitational constraints, which, together with the state of the universe, determines the parameters of the reference system in the form of a distribution of the spinor field on a spatial section.

Purpose: The goal of the present study was to investigate chief executives’ intention and potential to create a family-supportive culture in the Brazilian context, further assessing the role of their aspirations in their employees’ perceptions. Methodology: Two researchers conducted 60 minutes of online semi-structured interviews with CEOs of seven companies of different sizes (measured by the number of employees), economic sectors, and capital structure. To complement the data gathered from CEOs, we also conducted private and individual 30-minute online interviews with three employees from each company. Findings: A total of four categories and 11 sub-categories emerged from the analysis of CEO interviews, and four categories and six sub-categories emerged from the analysis of employee interviews. Originality: The results suggest that family-supportive culture is promoted through behaviors that are consistent with the organization’s core values, as well as through commitment of the agenda and resources of the company’s leadership team.

New energy vehicles (NEVs) have been proposed as a promising technology to reduce greenhouse gas (GHG) emissions. China is one of the leading countries in the development of NEVs, and a wide range of companies, including large and smaller businesses, are involved in the Chinese NEV market. Given that the NEV market involves the creation of nascent technologies, there are significant barriers to the development of NEV companies in the business growth stage. This is particularly significant in the case of small and medium-sized enterprises (SMEs). This study surveyed 100 NEV SMEs in China using a structured questionnaire to determine the most significant barriers to the growth of their businesses. Calculating the relative importance index (RII) from the collected questionnaire responses revealed that the most significant barrier at the growth stage is the lack of skilled scientists in China. The most important category of barriers is legal and institutional barriers, which suggests that government intervention in business activities, taxes, and unclear regulations are viewed by entrepreneurs as a serous hindrance to further development in the NEV industry.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), 21% septal reduction therapy. Sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3) and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63 and FLNC; thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p=0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; family studies on some rare variants enriched the worldwide knowledge in HCM.

The sustainability of Indigenous Socioecological Systems (ISES) faces significant threats from global anthropogenic environmental changes, endangering Indigenous People (IP), who safeguard a substantial portion of the world's natural capital. Indigenous Traditional Food Systems (ITFS) are crucial within ISES, providing not only diverse and nutritious food but also holding cultural, spiritual, and economic significance. Despite embodying sustainable lifestyles, Indigenous voices remain underrepresented in climate and sustainability discussions. Addressing this gap, the research adopts the Political Ecological Theoretical Framework (PETF) to analyze the regulatory impact on the adaptability, resilience, and sustainability of ITFS. Two Indigenous communities, the Karen in Thailand and various groups in the Republic of Sakha (Yakutia) in Russia, serve as case studies. The study aims to establish a theoretical framework integrating Indigenous concerns into policies and regulations, emphasizing self-determination, cultural preservation, and land rights. Findings emphasize the necessity for comprehensive legal frameworks prioritizing Indigenous involvement in climate resilience and sustainability efforts, moving beyond symbolic gestures towards meaningful collaboration and decision-making power. Recognizing Indigenous vulnerability and engaging them as active partners is essential for navigating climate challenges within ISES and ITFS.

Herein, we present a combination of experimental and computational study on the mitochondrial F0F1-ATPase nanotoxicity inhibition induced by single-walled carbon nanotubes (SWCNT-pristine, SWCNT-COOH). To this end, the in vitro inhibition responses in submitochondrial particles (SMP) as F0F1-ATPase enzyme were strongly dependent on the concentration assay (from 3 to 5 µg/ml) for both types of carbon nanotubes. Besides, both SWCNTs show an interaction inhibition pattern like the oligomycin A (the specific mitochondria F0F1-ATPase inhibitor). Furthermore, the best crystallography binding pose obtained for the docking complexes based on the free energy of binding (FEB), fit well with the previous in vitro evidences from the thermodynamics point of view. Following an affinity order as: FEB (oligomycin A/F0-ATPase complex) = -9.8 kcal/mol > FEB (SWCNT-COOH/F0-ATPase complex) = - 6.8 kcal/mol ~ FEB (SWCNT-pristine complex) = -5.9 kcal/mol. With predominance of van der Waals hydrophobic nanointeractions with key F0-ATPase binding site residues (Phe 55 and Phe 64). By the other hand, results on elastic network models, and fractal-surface analysis suggest that SWCNTs induce significant perturbations by triggering abnormal allosteric responses and signals propagation in the inter-residue network which could affect the substrate recognition ligand geometrical specificity of the F0F1-ATPase enzyme in order (SWCNT-pristine > SWCNT-COOH). Besides, the performed Nano-QSTR models for both SWCNTs show that this method may be used for the prediction of the nanotoxicity induced by SWCNT. Overall, the obtained results may open new avenues toward to the better understanding and prediction of new nanotoxicity mechanisms, rational drug-design based nanotechnology, and potential biomedical application in precision nanomedicine.

Within the eastern part of the Black Sea and Sea of Azov, the vegetation of charophytes was studied using the Brown-Blanquet approach. For the first time, five communities are described, including three associations and two subassociations from the alliance Charion canescentis Krausch 1964, the order Charetalia intermediae Sauer 1937, and the class Charetea intermediae F. Fukarek 1961. Diagnoses of the described syntaxa are given. A comparison with the Baltic and Mediterranean communities of charophytes is made. It is shown that all the Azov-Black Sea communities with the dominance of charophytes, in contrast to Western European ones, include Lamprothamnium papulosum with high constancy. At the same time, the communities of the southern seas of Russia are characterized by a lower occurrence and abundance of higher aquatic plants (except for Nanozostera noltei) and a slightly higher occurrence of red and green algae. An indirect ordination analysis showed the ecological isolation of the described phytocenoses and revealed two main factors influencing the floristic composition of communities – the granulometric composition of bottom sediments and water eutrophication.

Modern medical needs call for the efficient remedies against bacterial diseases including severe pulmonary infections reported as a secondary SARS-Cov-2 infection. Here, we propose imprinted drug ciprofloxacin (CF) into the polymer based on methyl-β-cyclodextrin (MCD) via template synthesis. The obtained polycarbamide nanoparticles possess CF's sustained drug release. The interaction of human serum albumin (HSA) with CF and CF-MCD carriers was conducted by FRET, FTIR, fluorescence, and circular dichroism spectroscopy. These studies uncovered that MCD decreases CF's binding efficiency by 2 times, whereas CF’s encapsulation in polymer matrix doubles the Ka value. The changes in HSA’s secondary structure indicate no alterations in the main mechanism of complex formation between CF and HSA in the presence of MCD-based carries. The drug delivery system demonstrates prolonged CF release at pH 7.4 in presence of HSA (model conditions of blood plasma). CF-MCD carriers inhibit E. coli and B. subtilis growth, but for MAX systems we observed a MIC’s increase (~2 times). We believe that our findings are important for further development of new efficient drug forms.

Despite prophylaxis and attempts to select a therapy, the frequency of preeclampsia does not decrease, and it still takes the leading position in the structure of maternal mortality and morbidity worldwide. In this review, we present a new theory of the etiology and pathogenesis of preeclampsia which is based on the interaction of Na/K-ATPase and its endogenous ligands including marinobufagenin. The signaling pathway of marinobufagenin involves an inhibition of transcriptional factor Fli1, a negative regulator of collagen synthesis, followed by deposition of collagen in the vascular tissues and altered vascular functions. Moreover, in vitro and in vivo neutralization of marinobufagenin is associated with restoration of Fli1. The inverse relationship between marinobufagenin and Fli1 opens new possibilities in the treatment of cancer: since Fli1 is a proto-oncogene, a hypothesis on suppression of Fli1 by cardiotonic steroids as potential anti-tumor therapeutic strategy is discussed as well. We propose a novel therapy of preeclampsia which is based on immunoneutralization of the marinobufagenin by monoclonal antibodies, which is capable to impair marinobufagenin-Na/K-ATPase interactions.

In recent years, Atherosclerotic Cardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.

At present, magnetic selection of genetically modified cells is mainly performed with surface markers naturally expressed by cells such as LNGFR, CD4 and H-2Kk. The disadvantage of such markers is the possibility of their undesired and poorly predictable expression by unmodified cells before or after cell manipulation, which makes it essential to develop new surface markers that would not have such a drawback. Earlier, modified CD52 surface protein variants with embedded HA and FLAG epitope tags (CD52/FLAG and CD52/HA) were developed by the group of Dr. Mazurov for selection of CRISPR-modified cells using FACS. In the current study, we tested whether these markers can be used for magnetic selection of transduced cells. For this purpose, appropriate constructs were created in MigR1-based bicistronic retroviral vectors containing EGFP and DsRedExpress2 as fluorescent reporters. Cytometric analysis of the transduced NIH 3T3 cell populations after magnetic selection evaluated the efficiency of isolation and purity of the obtained populations, as well as the change in the median fluorescence intensity (MFI). The results of this study demonstrate that the surface markers CD52/FLAG and CD52/HA can be effectively used for magnetic cell selection, and their efficiencies are comparable to that of the commonly used LNGFR marker. At the same time, the significant advantage of these markers is the absence of HA and FLAG epitope sequences in cellular proteins, which rules out spurious co-isolation of negative cells.

Working memory (WM) is a brain system for short-term storage and manipulation of information and plays an important role in complex cognitive tasks. In the synaptic theory of WM memorized elements are stored in the form of short-term potentiated connections in a sample population of neurons. In this paper, we show that such populations can be formed due to the mechanisms of spike-timing-dependent plasticity (STDP) – the phase dependence associated with the ratio of the pulse times of the interacting neurons. We propose a WM model considering two types of plasticity: short-term plasticity and STDP. We have shown formation of neuronal clusters encoding items in the WM model, that can be formed by external stimulation of a group of neurons due to the mechanisms of STDP and hold and reactivated by short-term plasticity mechanisms. The dynamic formation of neuronal clusters instead of pre-formed clusters gives additional flexibility to the model.

The need for quick and easy deflection calculations of various prefabricated slabs causes that simplified procedures and numerical tools are used more and more often. Modelling of full 3D finite element (FE) geometry of such plates is not only uneconomical but often requires the use of complex software and advanced numerical knowledge. Therefore, numerical homogenization is an excellent tool, which can be easily employed to simplify a model, especially when accurate modelling is not necessary. Homogenization allows for simplifying a computational model and replacing a complicated composite structure with a homogeneous plate. Here, a numerical homogenization method based on strain energy equivalence is derived. Using the method proposed, the structure of the prefabricated concrete slabs reinforced with steel spatial trusses is homogenized to a single plate element with an effective stiffness. There is a complete equivalence between the full 3D FE model built with solid elements combined with truss structural elements and the simplified homogenized plate FE model. The method allows for the correct homogenization of any complex composite structures made of both solid and structural elements, without the need to perform advanced numerical analyses. The only requirement is a correctly formulated stiffness matrix of a representative volume element (RVE) and appropriate formulation of the transformation between kinematic constrains on RVE boundary and generalized strains.

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low-molecular-weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plant cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, including carotenoids, tocopherol (vitamin E), ubiquinone and plastoquinone. Their functioning and their reactivity with respect to individual ROS are described. The review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow to obtain various plant lines with given properties in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of the biosynthesis and the content of these antioxidants are discussed.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs), or antimicrobial peptides (AMPs) together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

We construct hypergraphs to analyze functional brain connectivity, leveraging event-related coherence in magnetoencephalography (MEG) data during the visual perception of a flickering image. Principal network characteristics are computed for delta, theta, alpha, beta, and gamma frequency ranges. Employing a coherence measure, a statistical estimate of correlation between signal pairs across frequencies, we generate edge time series, depicting how an edge evolves over time. This forms the basis for constructing an edge-to-edge functional connectivity network. Emphasizing hyperedges as connected components in an absolute-valued functional connectivity network, we focus on exploring these hyperedges in the context of individual variability. Our coherence-based hypergraph construction specifically addresses functional connectivity among four brain lobes: frontal, parietal, temporal, and occipital. This approach enables a nuanced exploration of individual differences within diverse frequency bands, providing insights into the dynamical nature of brain connectivity during visual perception tasks. The results furnish compelling evidence supporting the hypothesis of cortico-cortical interactions occurring across varying scales. The derived hypergraph illustrates robust activation patterns in specific brain regions, indicative of their engagement across diverse cognitive contexts and different frequency bands. Our findings suggest potential integration or multifunctionality within the examined lobes, contributing valuable perspectives to our understanding of brain dynamics during visual perception.

Three-dimensional matrices are a new strategy used to tackle type I diabetes; a chronic metabolic disease characterized by the destruction of beta pancreatic cells. Type I collagen is an abundant extracellular matrix (ECM), component that has been used to support cell growth. However, pure collagen possesses some difficulties including low stiffness and strength, and high susceptibility to cell-mediated contraction. Therefore, we developed a collagen hydrogel with a poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN), functionalized with vascular endothelial growth factor (VEGF) to mimic the pancreatic environment for the sustenance of beta-pancreatic cells. We analyzed the physicochemical characteristic of the hydrogels and found that they were successfully synthesized. The mechanical behavior of the hydrogels improved with the addition of VEGF, and the swelling degree and the degradation were stable over time. In addition, it was found that 5 ng/mL VEGF-functionalized collagen/PEGDA IPN hydrogels sustained and enhanced viability, proliferation, respiratory capacity and functionality of beta pancreatic cells. Hence, this is a potential candidate for future preclinical evaluation, which may be favorable for diabetes treatment.

Macrophage-derived chemokine belongs to the CC subfamily. It is produced by dendritic cells (DCs) and macrophages with or without external stimulation. We have previously shown a statistically significant depletion of MDC/CCL22 concentrations in a number of studies concerning COVID-19. These shifts in concentrations demonstrated stability unrelated to the SARS-CoV-2 genetic variant and remained noticeable even in convalescent patients. In this work, we analyze MDC/CCL22 dynamics in various diseases, including those that manifest with inflammation in lung tissue. In addition, we provide our hypothesis on such a decrease in MDC/CCL22 concentrations in COVID-19. If its secretion by producer cells is unperturbed, then it is possible for viral products to bind to this chemokine and to block its functional activity. There is, however, another possible explanation directly linked to depletion in DC subpopulations and the inhibition of their function. We also discuss MDC/CCL22's role in the immunology of novel coronavirus infection, based on both our own data and other studies.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

The application of diffusion dialysis using various types of ion-exchange membranes for the separation of sulfuric acid and nickel sulfate has been evaluated. The process of dialysis separation of a real waste solution from an electroplating facility containing 252.3 g/L of sulfuric acid, 20.9 g/L of nickel ions and small amounts of zinc, iron, copper ions, etc. has been studied. Heterogeneous cation-exchange membrane containing sulfo groups and heterogeneous anion-exchange membranes with different thicknesses (from 145 μm to 550 μm) and types of fixed groups (4 samples with quaternary amino groups and 1 sample with secondary and tertiary amino groups) are used. The diffusion fluxes of sulfuric acid, nickel sulfate, and the total and osmotic fluxes of the solvent are determined. The use of a cation-exchange membrane does not allow separation of the components, since the fluxes of both components are low and comparable in magnitude. The use of anion-exchange membranes makes it possible to efficiently separate sulfuric acid and nickel sulfate. At the same time, the thin dialysis membrane turns out to be the most effective, as well as the membranes with quaternary amino groups, and the membrane with secondary and tertiary amino groups proved to be the least effective.

Daptomycin is one of the last therapeutic resources for multidrug-resistant gram- positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different, and in some respects are not completely understood. Mutations in several genes have been associated to daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated to daptomycin non- susceptibility, in 9 daptomycin non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: > 1mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin were studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate 5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in rpo genes, cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutations combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed a very high polymorphism in most isolates. Meanwhile, one isolate, St5, showed only single mutation in mprF (P314T).

Elastic properties of materials and their changes with temperature are important for their applications in engineering. A study on the influence of phase composition of AISI 4130 alloy on Young's modulus (Ed), shear modulus (Gd), and damping (Q-1) was carried out by Impulse Excitation Technique (IET). The material characterization was carried out using confocal microscopy, XRD, MET, HV, and dilatometry. A stable structure, composed of ferrite (BCC) and pearlite (α-Fe+Fe3C), was obtained by annealing. Metastable structure of martensite (BCT) was obtained by quenching. The Ed, Gd, and Q-1 were measured, varying the temperature from RT to 900 °C. The values of Ed and Gd, at RT, were determined as 201.5 and 79.2 GPa (annealed), and 190.13 and 76.5 GPa (quenched), respectively. In the annealed steel, the values Ed and Gd decrease linearly on heating up to 650 °C, with the thermal expansion. In the quenched steel, weak changes in the dilatometric curve, Ed, Gd, and Q-1, in the range of 350-450 °C, indicated decompositions of the martensitic phase. Sharp decrease in the moduli and high peak of Q-1, was observed for both samples around 650-900 °C, revealing low lattice elastic stability of the phases during transformations α(BCC)+Fe3C↔γ(FCC).

The circadian and stress-realizing systems are interconnected, and the balance of their interaction determines the state of human health. The objective of this study was to investigate the modulating effect of activating the circadian system on heart rate variability in female medical students with high anxiety while performing a cognitive task. After 20 minutes of adequate stimulation of circadian photoreceptors with a monochromatic blue light, the cognitive task performance resulted in a decrease in sympathetic impact. During the session of using Blue Sky Pro glasses, a trend of increasing heart rate variability was observed in a state of relative rest (especially in the first 5 minutes). A comparative analysis of the parameters of the letter cancellation test before and after light exposure revealed a statistically significant increase in the indexes reflecting mental productivity, work accuracy, and concentration of attention. The results suggest an essential physiological role of the human circadian system in modulating the autonomic and psycho-emotional conditions, as well as cognitive functions of individuals with high anxiety. Our findings indicate the possibility of quickly correcting the balance in human systemic regulatory mechanisms using the activation of retinal circadian photoreceptors by blue light.

This paper considers a new approach to the modeling of the vacuum infusion process at the manufacturing three-dimensional composite parts of complex shape. The developed approach and numerical methods are focused on the reliable prediction with the needed accuracy and elimination the unrecoverable defect of composite structure such as the dry spots. The paper presents some experimental results, which demonstrate two cases of dry spots formation in large aircraft composite panels, and analyses the reasons of these defects arising. Our numerical technique is based on the vacuum infusion of the liquid resin into porous preform as the two phase flow, which is described by the phase field equation coupled with the Richards equation describing the fluid motion in unsaturated soils with spatially varied pressure dependant porosity and saturation. This problem statement allowed to correctly reconstruct the resin front motion and formation of inner and outer dry spots depending on its movement. For the rapid detection of preform zones that are suspicious for defect formation two indicators calculated during process simulation are proposed and tested at the numerical experiments. The auxiliary program tool has been developed in MATLAB environment to correctly detect the times of formation, localization and dimensions of the arising dry spots by using the results of the finite element model simulation.

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2 that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

Visits to coastal and inland-waterways have strong associations with many health and economic benefits but are also opportunities for exposure to environmental pollution. In England, few balanced survey samples exist which can facilitate accurate identification of correlates with recreation in blue spaces. This information could support risk assessment for likelihood of exposure and message targeting in case of environmental threats. We process data from a recent (2022-2023) and large (n = 177,551) survey of English residents to describe demographic, seasonal and regional correlates with any participation in water-based recreational activities in previous year (logistic regression model), and in the previous 28 days (zero-inflated negative binomial regression). Activities studied were: surfing and paddleboarding; open water swimming; scuba-diving and snorkelling; canoeing and kayaking; angling. Summer was associated with most frequent participation, winter with fewest sessions except for rowing. Anglers were group most likely to be socially vulnerable: less likely to be university educated, more likely to be disabled and especially likely to be male. People resident in rural locations were more likely to participate at least once in prior year, but did not have higher participation rates in the previous 28 days. Regional variations in specific activities may suggest where demand for water recreation is unmet. The results provide a reference description of outdoor water-recreationalists doing specific types of activity in England and may be useful when designing emergency messages and otherwise setting policy with regard to management of microbiological, radiological or chemical hazards in coastal and inland waters.

Many stable water dispersions of various chemical compositions containing bioactive chemical compounds: copper silicate, titanium dioxide and zinc oxide (and other auxiliary substances) were developed and fabricated - they were used for preparation of thin hybrid coatings having very good antimicrobial properties against gram negative bacteria (Escherichia coli), gram positive bacteria (Staphylococcus aureus) and yeast fungus (Candida albicans). Polyester (PES) nonwovens were modified by dip-coating, and PES and cotton fabrics - by dip-coating and coating methods.

The aim of this work is research dedicated to the search for new bactericidal systems for use in cosmetic formulations, dermocosmetics, or the production of wound dressings. Over the last two decades chitosan due to its special biological activity, has become a highly indispensable biopolymer with very wide application possibilities. Literature reports on the antibacterial effects of chitosan are very diverse, but our research has shown that they can be successfully improved through chemical modification. Therefore, in this study, results on the synthesis of new Schiff bases chitosan – dCsSB-SFD and dCsSB-PCA obtained using two aldehydes: sodium 4-formylbenzene-1,3-disulfonate (SFD) and 2-pyridine carboxaldehyde (PCA) respectively. Chitosan derivatives synthesized in this way demonstrate stronger antimicrobial activity. Carrying out the procedure of grafting chitosan with a caproyl chain allowed obtaining compatible blends of chitosan derivatives with κ-carrageenan, which are stable hydrogels with a high swelling coefficient. Furthermore, covalently bounded PCL improved the solubility of obtained polymers in organic solvents. With this respect, the Schiff base-containing polymers obtained in this study, with special hydrogel and antimicrobial properties are very promising materials for the potential use as a controlled-release formulation of both, hydrophilic and hydrophobic drugs in cosmetic products for skin health.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

The advent of AI in medicine has transformed various medical specialties, including orthodontics. AI has shown promising results in enhancing the accuracy of diagnoses, treatment planning, and predicting treatment outcomes. With the growing number of AI applications and commercially available tools, there is an increase in their usage in orthodontic practices worldwide. This review aims to explore the principles of artificial intelligence (AI), its applications in the diagnostic process of modern orthodontic practices, and concerns associated with the implementation of AI algorithms in clinical practice. A comprehensive review of the literature was conducted, focusing on five categories where AI has been applied in orthodontics: dental diagnostics, cephalometric evaluation, skeletal age determination, temporomandibular joint (TMJ) evaluation, and extraction decision making. AI has demonstrated high efficacy in all those fields. However, variations in performance and the necessity of manual supervision indicate that AI should be used cautiously in clinical settings. Nevertheless, the high complexity and potential unpredictability of AI algorithms call for cautious implementation and regular manual validation of results. Continuous AI learning, proper governance, and addressing privacy and ethical concerns are crucial for the successful integration of AI into orthodontic practice.

The aim of this work was to study the, so far, unexplored possibility that non-genetic inheritance of animal behavioral characteristics could depend on the state of the parents at the time of conception, by studying inheritance of high and low motor and exploratory activity in the first generation of rats. In this study, we measured the levels of motor and exploratory activity in rats at the ages of 2 and 5 months. Male and female rats were mated at the age of 5 months. The following groups were used: male and female rats with high motor activity at ages of 2 and 5 months (ACT+); male and female rats with high activity at the age of 2 months, but low activity at the age of 5 months (ACT–); male and female rats with low activity at the ages of 2 and 5 months (PAS–); male and female rats with low activity at the age of 2 months, but high activity at the age of 5 months (PAS+). Significant differences in the severity of exploratory activity were found between the offspring of ACT+ and ACT– rats. Moreover, these differences were observed only in males, and not in females. Differences between the offspring of PAS+ and PAS– rats were observed in both the male and female rats. The motor activity of animals in the period from 20 minutes after the start of registration did not differ between groups. Thus, it can be considered that individual characteristics of general motor activity are due to genetically inherited factors, while differences in the level of exploratory activity, apparently, are formed due to non-genetic influences from parents during mating.

The role that Colombia will play in terms of food supply in the coming years has generated a discussion on the agricultural practices implemented, specifically in the use of pesticides. Therefore, this article aims to provide a comprehensive and complete review of the status of pesticide use in the agricultural sector, highlighting the agri-food industry in Colombia. Currently, the use of pesticides has intensified throughout the world, generating a call for attention by governmental entities in terms of regulation. Colombia for the year 2019 presented a rate of use of 7.8 kg/ha of pesticides, placing it among the twenty countries with the highest rate. On the other hand, the quantities and economic benefits of exports and imports are growing steadily. Several organizations have focused their efforts on determining the health consequences that people exposed to chronic and/or acute intoxication may suffer. This has led to cases of cytogenetic, neurocognitive and physical effects, prompting governmental organizations to regulate the use of pesticides. Finally, the need to design pesticide management and handling systems that respond to the needs of producers and the sector, integrating international food safety guidelines, is identified.

We examined PT parameters, geochemical peculiarities, and fluid sources of the Ulug-Sair ore occurrence attributable to class of intrusion-related gold deposits and according to ore mineral assemblages corresponding to Au-Bi type with wide Bi minerals (AgBiTe, Bi2Te2Se, Cu3,07BiS3, Bi), tellurides (Au and Ag), Se-tellurides (Ag and Bi), and selenides (Au, Ag, and Hg). We identified that ‘pre-gold’ quartz-tourmaline veins were deposited using an aqueous Mg-Na-K-chloride fluid with a salinity of 8–10 wt % NaCl eq. At 325–370 °C; host breasts were formed due to a CO2-water fluid containing CH4 and N2, with a salinity of 0,18–6,1 wt % NaCl eq. at least 200–400 °C. Gold-bearing mineral assemblages were formed at P ~ 0,75–1,0 kbar (~ 2,3–3 km) due to CO2-water chloride (Na-K±Fe, Mg) fluid with CH4, Na2SO4, and Na2B2O5, and salinities 1,7–12,5 wt % NaCl eq. during the decreasing temperatures from 360 up to 115 °C (gold-sulfide-quartz veins – 360–130 °С, and gold-telluride-sulfide-quartz veins – 330–115 °C) and variations fO2, fS2, fSe2, and fTe2. The isotopic composition of δ34SH2S fluid (-0,7…+2,5 ‰) indicates the juvenile or magmatic origin of fluid and ore elements. The δ34OH2O fluid indicates that, at an early substage, the formation of ore occurrence involved a fluid of magmatic or metamorphic origin (+7,3…+11,4 ‰), and, in the later substage, it mixed with meteoric waters (-2,3…+9,1 ‰).

Improvement of agronomic traits in crops through gene editing (GE) relies on efficient trans-formation protocols for delivering the CRISPR/Cas9-coded transgenes. Recently, a few embryo-genesis-related genes have been described, the co-delivery of which significantly increases the transformation efficiency with reduced genotype dependency. Here we characterized the trans-genic and GE events in wheat (cv. Fielder) when transformed with the GROWTH-REGULATING FACTOR 4 (GRF4) and its cofactor GRF-INTERACTING FACTOR 1 (GIF1) chimeric gene. Trans-formation efficiency in our experiments ranged from 22% to 68%, and the editing events were faithfully propagated into the following generation. Both low and high copy number integration events were recovered in the T0 population with the various level of integrity of the left and right T-DNA borders. We also generated a population of wheat plants with ten different gRNAs targeting 30 loci in the genome. Comparison of the epigenetic profiles at the target sites and editing efficiency revealed a significant positive correlation between chromatin accessibility and muta-genesis rate. Overall, preliminary screening of the transgene quality and GE events in the T0 population of plants regenerated through the co-delivery of GRF-GIF can allow for the propagation of the best candidates for further phenotypic analysis.