In a saline semi-isolated Lagoon on the Cape Zeleny (White Sea), the annual dynamics of the vertical hydrological structure, and the seasonal dynamics of phytoplankton were traced, including species composition, and vertical distribution, abundance, nutrition type,and biomass.293 species and supraspecific taxa of algae and cyanobacteria were found. Most of the identified species are marine, and 38 species are freshwater. Taxonomic composition changed in the Lagoon during the year. Dinoflagellates dominated in winter and early June; unidentified cocci and flagellates in July; diatoms, dinoflagellates and unidentified cells in August; dinoflagellates in September; and unidentified cocci and flagellates in October–November. The abundance of algae also changed in the Lagoon during the year. The integrated biomass in the water column varied from 0.01 g C/m2 in January to 0.78 g C/m2 in early September. According to the abiotic parameters, the water column of the Lagoon is subdivided into several zones with different conditions and corresponding phytoplankton communities. Similarity between the communities of different horizons was 32-46% in summer and 7% in winter. The chemocline layer was the most populous. Almost the entire year it contained a maximum of phytoplankton biomass, 1-2 orders of magnitude higher than that in the overlying horizons. Comparison phytoplankton in the lagoon and in the nearby sea area was carried out. Despite the connection between the Lagoon and the sea phytoplankton structure in the surface water layer in the Lagoon and in the sea differs significantly in composition, quantitative parameters, and seasonal dynamics. The similarity of the communities in the sea and the Lagoon never exceeded 50%. In terms of biomass, the Lagoon lags behind the sea until mid-summer, but, starting from August, it outnumbers it, and the phytoplankton development in the Lagoon lasts longer, until late autumn. The phytoplankton structure and dynamics in the Lagoon and the sea by 24.5% was related to the daylight, water salinity, oxygen content and pH, but did not depend on water T, underwater illuminance, and depth. Oxygen content and pH are defined by PhP activity. Salinity serves as a vector of the vertical sequence of ecological niches. The daylight length seems to be the crucial factor of the seasonal PhP dynamics in the semi-isolated coastal stratified lakes and lagoons.

This article explores the question of the rate of digital progress in the context of the labor market. Specific features of the current situation are indicated: temporality of socio-technological transformations, which is becoming less and less compatible with the harmonious development of man and society; the pace at which machines acquire intelligence; total devaluation of mental labor; unresolved issue of the role of man in the world of intelligent machines; the criticality of the problem of the labor market, due to its global nature, social significance and the rate of socio-technological changes. It is emphasized that these circumstances in the short term threaten the sustainable development of the global society, whose reactions to the transformation of technological and socio-economic infrastructure are significantly lagging behind. It is concluded that there is an urgent need to strengthen social responsibility, determined by the new ethics of relations between humans and machines with AI, supplemented by the primacy of the dignity of the social role of humans. The authors point out the urgent need to revise ideas about work as the main purpose of a person and about realization in the profession as the main factor that determines the self-esteem of an individual and his social status.

In interepidemic periods, a sapronoses typically employs a variety of mechanisms for maintaining viability of its causative agent in terrestrial parasitic systems, associated with different adaptive strategies utilized by its populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses use resistant cell forms, which is a viable but nonculturable (VBNC) state, and persistence. Implementation of these strategies is conditioned by effects of various stress factors of the habitat and is characterized by decreased metabolism, alteration of the morphology and physiology of bacterial cell, and cessation of its replication. It is important that the resistant forms of cells retain virulence and, as favorable conditions come, turn back into the active vegetative form again. The discovery of the genetic modules of bacterial toxin–antitoxin systems in recent years has made it possible to identify a number of complicated regulatory molecular mechanisms responsible for maintaining the pathogenic potential of resistant forms of causative agents of natural-focus sapronoses in interepidemic periods.

The intricacies of translational strategies make this stage of the implementation of genetic information one of the most difficult to understand and, at the same time, perhaps the most interesting. It also becomes clear that all this variety of strategies is not just a consequence of a long evolutionary history but is of paramount importance for fine-tuning gene expression and metabolic modulation. This is especially true for those organisms that demonstrate predominantly biochemical and physiological reactions with a lack of behavioural ones. Plants are just such a group of organisms. Overcoming unfavourable environmental conditions occupies a key place in plant physiology. This is especially true with the changing conditions of global warming and the irretrievable loss or depletion of natural ecosystems. Conceptually, the response of plants to abiotic stress is a set of complex and intricate strategies. This is dictated both by a variety of abiotic factors that provoke stressful conditions and by a variety of molecular genetic mechanisms that make it possible to fine-tune the metabolic pathways through which the plant organism overcomes non-standard and non-optimal conditions. In the presented review, we tried to focus on the state-of-the-art in the field of translational regulation in plants under abiotic stress conditions. Various regulatory elements and patterns are considered in relative chronological order. We also considered it necessary to pay attention to key high-performance methods for studying the dynamics of genetic information at the stage of translation.

Stress is one of the important factors affecting the growth and development of plants. In recent years, a large body of data on transcriptional changes in response to stress in plants has been obtained. Despite the fact that the important role of the regulation of translation in response to stress has been proven in plants, knowledge in this area remains extremely scarce. In this review, we focused on mRNA translation in the cytoplasm of higher plants. Most of the current research on the effects of translation has been done in yeast and mammalian systems. Translation factors and mechanisms are mostly conserved among eukaryotes; however, some differences are known to exist among plants. A comprehensive understanding of the complex apparatus of translation and its regulation in plants is required. In this work, we have tried to update modern ideas about the regulation of translation under conditions of abiotic stress.

In the proposed article, the issues of increasing the synchronizing ability of the system of coordinated rotation of asynchronous motors are considered. Based on the T-shaped equivalent circuit, electromechanical relationships were obtained with changes in the value of the total rotor resistance and the supply voltage of individual motors. An algorithm for calculating the torques, stator and rotor currents of the motors of the system has been compiled. Based on the calculations obtained, the mechanical characteristics of the system asynchronous motors are constructed for various values of total resistance, supply voltages and rotor positions. The obtained data and graphs confirm the adequacy of the theory obtained in an analytical way. Functional and structural diagrams in small scales have been compiled, which allow simulating transient operation modes of multi-motor asynchronous electric drives in the Matlab application package. Multi-motor asynchronous electric drives with adjustable supply voltages, as well as with preliminary synchronization and synchronous braking, have been developed. Compilation of a program for the stability of a nonlinear system of a multi-motor asynchronous electric drive (MAEDs) with a thyristor voltage converter (TVC) in Matlab. Also, the modes of soft start, load shedding and surge on the motor shaft are simulated, confirming the stability of the system.

There are experimental evidences that chronic social defeat stress is accompanied by development of anxiety- and depression-like state as well as downregulation of serotonergic genes in the midbrain raphe nuclei of male mice. The study was aimed at investigating the effect of chronic lithium chloride (LiCl) administrations on anxiety behavior and the expression of serotonergic genes in the midbrain raphe nuclei of affected mice. The pronounced anxiety in male mice was caused by chronic social defeat stress in daily agonistic interactions. After 6 days of social stress, defeated mice were treated with saline or LiCl (100 mg/kg, i.p. two weeks) against the background of continuing agonistic interactions. The level of anxiety was assessed using behavioral tests. The effect of chronic treatment with LiCl on the expression of serotonergic genes in the midbrain rapher nuclei was also studied. Mild anxiolytic effects of LiCl were found on communication in the partition test. Anxiogenic-like effects assessed using the elevated plus-maze and social interaction tests were found. Chronic LiCl treatment induced overexpression of the serotonergic genes in the midbrain raphe nuclei. The effects of chronic LiCl treatment depends on the method of treatment, psychoemotional state, and experimental context (tests).

Propagation of electromagnetic (EM) waves inside and on the surface of the human body is the subject of active research in area of biomedical applications. This research area is the basis for wireless monitoring of biological object parameters and characteristics. Much attention has been paid to radio-frequency identification systems, which are intended for biomedical applications. Solutions to the following problems are crucial to achieve the stated goals in the area of wireless monitoring: EM wave propagation inside regular and multilayer biological media, through the interface between different media, and on-body surface wave propagation. The biological object monitoring is based on a consideration of the followingprocesses: a) propagation of the EM wave in a biological medium considered as the dielectric with a high dielectric permittivity and substantial conductivity; b) penetration of the EM wave through the biological medium–air interface (wave reflection and refraction); c) propagation of the EM wave in a multi-layer biological medium; d) propagation of the EM wave along the plane or curved surface of biological objects.

Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocytes-derived and TAMs-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.

Background: Takayasu’s arteritis is a rare type of vasculitis, with severe complications like stroke, ischemic heart disease, pulmonary hypertension, secondary hypertension, aneurysms. Diagnosis is conducted by clinical and angiographic criteria. Treatment is medical and surgical, but unfortunately, the outcome is reserved. Case presentation: A 34- year- old Caucasian women had an ischemic stroke (2009). She was diagnosed with Takayasu’s arteritis and she received treatment with methotrexate, prednisolone, antiplatelet agents, with a mild improvement of clinical state. After 5 years (2014) she associated ascending aorta aneurysm, pulmonary hypertension, mild aortic regurgitation. The surgical treatment solved both ascending aorta aneurysm and left carotid artery stenosis (ultrasound in 2009 and computed tomography angiogram in 2014). Morphopathology revealed typical appearance for Takayasu’s arteritis. Tumor necrosis factor inhibitors (TNF-inhibitors) were associated to methotrexate. At 48 years (2023) she developed coronary heart disease (angina, electrocardiogram); echocardiography revealed severe pulmonary hypertension; angiography described normal coronary arteries, abdominal aorta pseudoaneurysm and arterial-venous fistula, with origin in right coronary artery and drainage on medium pulmonary artery. The patient refused surgical/ interventional treatment; she received again TNF- inhibitors, methotrexate, antiplatelet agents, statins. Conclusions: This case report presents us a severe form of Takayasu’s arteritis. We consider that morphopathology had a great importance in revealing to clinicians the typical appearance and the stadialization of inflammatory arterial process: acute or chronic. The verdict of morphopathologist was chronic phase, with acute relapses, so we decided that immunosuppressive treatment was still necessary.

The G-protein-coupled estrogen receptor (GPER; G protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as potential HGSC ovarian cancer origin (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER antagonist in combination with an agonist on cell viability, providing a better understanding of the effects of these compounds on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

The pinning force density FpJc,B=Jc×B (where Jc is the critical current density and B is the applied magnetic field) is one of the main parameters that characterize the resilience of a superconductor to carry a dissipative-free transport current in an applied magnetic field. Kramer (1973 J. Appl. Phys. 44 1360), and Dew-Hughes (1974 Phil. Mag. 30 293) proposed a widely used scaling law for the pinning force density amplitude: FpB=Fp,max×p+qp+qppqq×BBc2p×1-BBc2q, where Fp,max, Bc2, p, and q are free-fitting parameters. Since the late 1970-s till now, several research groups have reported experimental data on the dependence of Fp,max on the average grain size, d, in Nb3Sn-based conductors. Godeke (2006 Supercond. Sci. Techn. 19 R68) proposed that the dependence obeys the law Fp,maxd=A×ln1d+B. However, this scaling law has several problems, for instance, the logarithm is taken from a non-dimensionless variable, and Fp,maxd<0 for large grain sizes, and Fp,maxd→∞ for d→0. Here, we reanalysed the full inventory of publicly available Fp,maxd data for Nb3Sn conductors and found that the dependence can be described by Fp,maxd=Fp,max0×exp-dδ law, where the characteristic length, δ, varies within a remarkably narrow range, that is, δ=175±13 nm, for samples fabricated by different technologies. The interpretation of the result is based on the idea that the in-field supercurrent flows within a thin surface layer (thickness of δ) near the grain boundary surfaces (similar to London’s law, where the self-field supercurrent flows within a thin surface layer with a thickness of the London penetration depth, λ, and the surface is a superconductor-vacuum surface). An alternative interpretation is that δ represents the characteristic length of the exponential decay flux pinning potential from the dominant defects in Nb3Sn superconductors, which are grain boundaries.

In a generalized topological space Tg = (Ω, Tg), ordinary interior and ordinary closure operators intg, clg : P (Ω) −→ P (Ω), respectively, are defined in terms of ordinary sets. In order to let these operators be as general and unified a manner as possible, and so to prove as many generalized forms of some of the most important theorems in generalized topological spaces as possible, thereby attaining desirable and interesting results, the present au- thors have defined the notions of generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, in terms of a new class of generalized sets which they studied earlier and studied their essen- tial properties and commutativity. The outstanding result to which the study has led to is: g-Intg : P (Ω) −→ P (Ω) is finer (or, larger, stronger) than intg : P (Ω) −→ P (Ω) and g-Clg : P (Ω) −→ P (Ω) is coarser (or, smal ler, weaker) than clg : P (Ω) −→ P (Ω). The elements supporting this fact are reported therein as a source of inspiration for more generalized operations.

Carbonization of a biopolymer (lignin) in self-propagating high-temperature synthesis (SHS) led to the production of 2D graphene structures. With the help of modern analytical methods (Raman spectroscopy, X-ray diffraction) and electron microscopy, the resulting product was confirmed to have a few-layer 2D graphene structure. The predicted photovoltaic properties of the resulting few-layer graphene were implemented for laser ignition of a model pyrotechnic composition based on porous silicon. A phenomenological model of the formation mechanism of 2D graphene structures under the conditions of the SHS process is proposed.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

Two clear-air over-the-horizon propagation mechanisms affecting Automatic Identification System (AIS) detection range are considered. Comparison results are presented between the path loss due to tropospheric ducting and path loss due to tropospheric scattering (troposcatter) for the AIS frequencies. The calculations are based on the well-known parabolic equation approximation to the wave equation, in which a simple troposcatter formula is incorporated. In most studied cases the ducting assures significantly greater reduction of path loss than troposcatter even when the AIS frequencies are not well trapped in the duct. Emphasis is placed on elevated trapping layers and some features that may make ducting propagation less favorable in terms of increasing the AIS detection range are discussed.

In a generalized topological space T_g = (Ω, T_g) (T_g-space), the g-topology T_g : P (Ω) −→ P (Ω) can be characterized in the generalized sense by specifying the generalized open, generalized closed sets (g-T_g-open, g-T_g-closed sets), generalized interior, generalized closure operators g-Intg, g-Cl_g : P (Ω) −→ P (Ω) (g-T_g-interior, g-T_g-closure operators), or generalized derived, generalized coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω) (g-T_g-derived, g-T_g-coderived operators), respectively. For very many T_g-spaces, the δ^th-iterates g-Der_g^(δ), g-Cod_g^(δ) : P (Ω) −→ P (Ω) of g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, defined by transfinite recursion on the class of successor ordinals are also themselves g-T_g-derived, g-T_g-coderived operators for new g-topologies in the generalized sense on Ω. Thus, the use of novel definitions of g-T_g-derived, g-T_g-coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, based on a very clever construction, together with their δ^th-iterates g-T_g-operators g-Der_g^(δ), g-Cod_g^(δ) : P (Ω) −→ P (Ω), defined by transfinite recursion on the class of successor ordinals, will give rise to novel generalized g-topologies on Ω. The present authors have been actively engaged in the study of g-T_g-operators in T_g-spaces. The study of the essential properties and the commutativity of novel definitions of g-T_g-interior and g-T_g-closure operators g-Int_g, g-Cl_g : P (Ω) −→ P (Ω), respectively, in T_g has formed the first part, and the study of the essential properties and sets of consistent, independent axioms of novel definitions of g-T_g-exterior and g-T_g-frontier operators g-Ext_g, g-Fr_g : P (Ω) −→ P (Ω), respectively, has formed the second part. In this work, which forms the last part on the theory of g-T_g-operators in T_g-spaces, the present authors propose to present novel definitions and the study of the essential properties of g-T_g-derived and g-T_g-coderived operators g-Der_g, g-Cod_g : P (Ω) −→ P (Ω), respectively, and their δ^th-iterates, and the notions of g-T_g-open and g-T_g-closed sets of ranks δ in T_g-spaces.

(1) Background: In this work, a series of benzimidazole derivatives containing colchicine-like and cathechol-like moieties with methyl group substitution in the benzimidazole ring were evaluated for their in vitro antiproliferative, pro-apoptotic and antioxidative activity against highly invasive breast cancer cell line MDA-MB-231 and related impairment of tubulin dynamics; (2) Methods: MTT assay was used to evaluate the antiproliferative activity. In vitro tubulin polymerization assay as well as docking analysis was applied to prove the alterations in tubulin polymerization. Immunofluorescent and DAPI staining reveal the pro-apoptotic potential of benzimidazole derivatives and the effect on tubulin’s dynamics in living cells. The antioxidant activity was evaluated by scavenging of H2O2 and hypochlorite ion and ortho-phenanthroline tests; (3) Results: The compounds containing colchicine-like moiety displayed significant growth inhibitory effect against cancer cell line as was highlighted the role of methyl functional group on the tubulin aggregation and blockage of mitosis. All compounds showed an ability to scavenge H2O2, while the compounds with cathecol-like moiety were more effective against hypochlorite ion and chelation of iron; (4) Conclusions: The benzimidazole derivative containing colchicine-like moiety and methyl group substitution in benzimidazole ring is a potential antiproliferative and microtubule destabilizing agent.

Effective therapeutics for Alzheimer's disease (AD) are in great demand worldwide. In our previous work, we responded to this need by synthesizing novel drug candidates consisting of 4-amino-2,3-polymethylenequinolines conjugated with butylated hydroxytoluene via fixed-length alkylimine or alkylamine linkers (spacers) and studying their bioactivities pertaining to AD treatment. Here, we report significant extensions of these studies, including the use of variable-length spacers and more detailed biological characterizations. Conjugates were potent inhibitors of acetylcholinesterase (AChE, minimum IC50 15.1±0.2 nM) and butyrylcholinesterase (BChE, minimum IC50 5.96±0.58 nM), with weak inhibition of off-target carboxylesterase. Conjugates with alkylamine spacers were more effective cholinesterase inhibitors than alkylimine analogs. Optimal inhibition for AChE was exhibited by cyclohexaquinoline and for BChE by cycloheptaquinoline. Increasing spacer length elevated potency against both cholinesterases. Structure-activity relationships agreed with docking results. Mixed-type reversible AChE inhibition, dual docking to catalytic and peripheral anionic sites, and propidium iodide displacement suggested the potential of hybrids to block AChE-induced β-amyloid (Aβ) aggregation. Hybrids also exhibited inhibition of Aβ self-aggregation in the thioflavin test; those with a hexaquinoline ring and C8 spacer were the most active. Conjugates demonstrated high antioxidant activity in ABTS and FRAP assays as well as inhibition of luminol chemiluminescence and lipid peroxidation in mouse brain homogenates. Quantum-chemical calculations explained antioxidant results. Computed ADMET profiles indicated favorable blood-brain barrier permeability suggesting CNS activity potential. Thus, the conjugates could be considered promising multifunctional agents for potential treatment of AD.

In recent years, many libraries and archives have started digitizing their collections thus making maps by Indigenous peoples more easily available for scholars to study. While a number of these maps were discussed by G. Malcolm Lewis in the History of Cartography series (volume 2, book 3, Chapter 4: 1984), more have since been found and disseminated. These maps are critical in understanding the historic and current land tenure of Indigenous groups. Further, Indigenous claims to land can be seen in their connections via toponymy. European concepts of territory and political boundaries did not coincide with First Nation/American Indian views resulting in the mistaken view that Natives did not have formal concepts of their territories. Further, Tribes/First Nations with cross-border territory have special jurisdictional problems. This paper will illustrate how many Native residents were very spatially cognizant of their own lands, as well as neighboring nations’ lands, overlaps between groups, hunting territories, populations, and trade networks. Currently, the Sinixt First Nation provides a perfect example of how an Aboriginal people are inputting and using a GIS representation of their territory with proper toponymy and use areas.

In a generalized topological space Tg = (Ω, Tg), generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, are merely two of a number of generalized primitive operators which may be employed to topologize the underlying set Ω in the generalized sense. Generalized exterior and generalized frontier operators g-Extg, g-Frg : P (Ω) −→ P (Ω), respectively, are other generalized primitive operators by means of which characterizations of generalized operations under g-Intg, g-Clg : P (Ω) −→ P (Ω) can be given without even realizing generalized interior and generalized closure operations first in order to topologize Ω in the generalized sense. In a recent work, the present authors have defined novel types of generalized interior and generalized closure operators g-Intg, g-Clg : P (Ω) −→ P (Ω), respectively, in Tg and studied their essential properties and commutativity. In this work, they propose to present novel definitions of generalized exterior and generalized frontier operators g-Extg, g-Frg : P (Ω) −→ P (Ω), respectively, a set of consistent, independent axioms after studying their essential properties, and established further characterizations of generalized operations under g-Intg, g-Clg : P (Ω) −→ P (Ω) in Tg.

Introduction of Cl- and O- atoms into C4-vinyl carbocations was studied by X-ray diffraction analysis and IR spectroscopy. Chlorine atoms are weak electron acceptors in ordinary molecules, but within vinyl carbocations, manifest themselves as strong electron donors that accept a positive charge. The attachment of a Cl atom directly to a C=C bond leads to an increase in the e-density on it, exceeding that of the common double bond. The positive charge should be concentrated on the Cl atom, and weak δ- may appear on the C=C bond. More distant attachment of the Cl atom—to a C atom adjacent to the C=C bond—has a weaker effect on it. If two Cl atoms are attached to the Сγ atom of the vinyl cation, as in Cl2СγСδHСαHCH3, then the cation switches to the allyl type with two practically equivalent and almost uncharged СγСδСα bonds. When such a strong nucleophile as the O atom is introduced into the carbocation, a protonated ester molecule with a C-O(H+)-C group and a C=C bond forms. Nonetheless, in the future, there is still a possibility of obtaining carbocations with a non-protonated C-O-C group.

Introduction: ophthalmological assessment of the retinal circulation and the level of VEGF-A is currently considered a non-invasive and safe diagnostic tool to assess the peripheral microcircu-lation Objective: to study retinal hemodynamics and VEGF-A levels in patients with type 1 diabetes mellitus after pancreas transplantation Settings and Design: A prospective, single-stage, single-center, non-randomized clinical trial Methods: 79 patients (158 eyes) with type 1 diabetes mellitus and end-stage diabetic nephropathy participated in the study. Patients were divided into 3 groups: group 1, potential recipients of pancreas and kidney transplant from the waiting list; group 2, patients after kidney transplanta-tion; and group 3, patients after simultaneous pancreas and kidney transplantation. Ophthalmo-logical examination included measuring the macular hemoperfusion density. The level of VEGF-A was examined in the patients' tear by enzyme immunoassay. Results: retinal hemoperfusion density and VEGF-A concentration were expected to correlate with the severity of diabetic changes in the fundus of patients. A lower index of retinal hemoperfusion density and a high level of VEGF-A were noted in patients with proliferative ret-inopathy and macular oedema. Group 3 showed the lowest frequency of the active phase of the proliferative retinopathy and retinal macular oedema, characterized by a higher retinal hemoperfusion density in the foveal and the parafoveal zone of the macular region, and low VEGF-A concentration in tear. Conclusion: measurement of retinal hemoperfusion density and determination of tear VEGF-A concentration are informative objective methods for diagnosing the severity of diabetic changes of the fundus.

this review summarizes current knowledge of the hydrogen sulfide role in cardiovascular system, the proposed mechanisms of its action and the prospects for its applicability in the treatment of cardiovascular diseases. Hydrogen sulfide was recently recognized as gasotransmitter – simple signaling molecule which freely penetrates the cell membrane and regulates a number of biological functions. In humans endogenous H2S is generated via enzymatic and non-enzymatic pathways and its content varies in different tissues and is strictly regulated. In cardiovascular system H2S is produced by myocardial, vascular and blood cells and regulates a number of vital functions. Numerous experimental data prove that endogenously generated as well as exogenously administered H2S exerts a wide range of actions in cardiovascular system, including vasodilator/vasoconstrictor effects, regulation of blood pressure, pro-apoptotic and anti-proliferative effects in the vascular smooth muscle cells, influence on angiogenesis and erythropoiesis, myocardial cytoprotection in ischemia-reperfusion injury, oxygen sensing, inhibition of platelet aggregation and blood coagulation, modification of erythrocyte microrheological properties (aggregability and deformability). Understanding of molecular mechanisms of H2S action and molecular crosstalk between H2S, NO, and CO is essential for the development of its diagnostic and therapeutic potential.

In a bid to resolve lingering problems in cosmology, more focus is being tilted towards cosmological models in which physical constants of nature are not necessarily real constants, but varying with cosmic time. In this paper we have study cosmology in nonlinear electrodynamics with the Newton's gravitational constant $G$ not a constant but vary in form of power-law of the scale factor of the universe. The evolution of the scale factor $a (t)$ is studied in this model which depends on nonlinear electrodynamics fine tuning term of $\alpha$. Then we check the stability of the model using the speed of sound.

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia less than 50% of patients remain in a long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder which requires therapy in majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first line as well as relapsed setting. Rituximab is the preferred therapy for steroid refractory wAIHA and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of the rituximab and current literature its role in management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

Extracellular vesicles represent a large heterogeneous class of near and long-distance intercellular communication mediators, released by both prokaryotic and eukaryotic cells. Specifically, the scientific community has shown a growing interest in exosomes, which are nano-sized vesicles with an endosomal origin. Not so long ago, the physiological goal of exosome generation was largely unknown and required more investigation; at first, it was hypothesized that exosomes are able to remove excess, rejects and unnecessary constituents from cells to preserve cellular homeostasis. However, thanks to recent studies, the central role of exosomes in regulating cellular dialogue has emerged. Exosomes act as vectors on cell-cell signaling by their cargo, proteins, lipids, and nucleic acids, and influence physiological and pathological processes. The findings on exosomes are widespread in a large spectrum of biomedical applications from diagnosis and prognosis to thera-pies. In this review, we describe exosome biogenesis and the current methods for their isolation and characterization, emphasizing the role of their cargo in female reproductive processes, from gametogenesis to implantation, and the potential involvement in human female disorders.

: Intracellular tripeptide glutathione is an important agent of cell survival in hypoxia. Glutathione covalently binds to SH-groups of hemoglobin cysteine residues, protecting them from irreversible oxidation and changes its affinity to oxygen. Reduced glutathione (GSH) can also form a non-covalent complex with hemoglobin. Previously, we showed that hemoglobin tetramer has four noncovalent binding sites of glutathione GSH molecules inside, two of which are released during hemoglobin transition to deoxy form. In this study, we characterized the conserved cysteine residues and residues of non-covalent glutathione binding sites in the sequences of a number of hypoxia tolerant and hypoxia-sensitive mammals. The alpha subunit of all species considered was found to have no conserved cysteines, whereas the beta subunit contains Cys94 residue, which is conserved across species and whose glutathionylation changes the affinity of hemoglobin for oxygen 5-6-fold. In addition, the key residues of noncovalent glutathione binding sites in both alpha and beta subunits are absolutely conserved in all species considered, suggesting a common mechanism of hemoglobin redox regulation for both hypoxia-sensitive and hypoxia-tolerant mammals. The solvent accessibility of all HbA and HbB residues in oxy- and deoxy- forms was analyzed. The key residue betaCys94 is solvent accessible only in the deoxy form.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

Extremely low-frequency electromagnetic fields (ELF-EMF) are ubiquitous in industrial-11 ized environments due to the continuous use of electrical devices. Our previous studies demon-12 strated ELF-EMF affects muscle cells by modulating oxidative stress and enhancing myo-genesis. 13 This pilot study investigated these effects on skeletal muscles of sedentary adult mice, assessing 14 physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplemen-15 tation. Male C57BL/6 mice were exposed to ELF-EMF (0.1 or 1.0 mT) 1 hour/day up to 5 weeks, and 16 fed a standard diet without or with N-acetyl-cysteine (NAC). Results showed transient increases in 17 muscle strength (after 2-weeks’ exposure at 1.0 mT), potentially linked to muscle fiber recruitment 18 and activation, revealed by higher PAX7 and MyH expression levels. After ELF-EMF exposure, ox-19 idative status assessment revealed transient increases in expression levels of SOD1 and catalase en-20 zymes, in total antioxidant capacity and in protein carbonyl levels, marker of oxidative damage. 21 These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal 22 muscle physiology and NAC supplementation partially mitigates these effects, highlighting the 23 complex interactions between ELF-EMF and antioxidant pathways in vivo. Further investigations 24 on ELF-EMF as a therapeutic modality for muscle health are necessary.

(1) Background: The study of microbiome is being crucial for his role in major systemic diseases, in particular the oral and gut microbiota. In the last years the study of microorganism correlated for example with neurodegenerative disease is increasing the prospective of a possible link between gut microbiota and brain. Here we report a new case report about a patient evaluated genetically firstly for dementia and late-onset dyskinesia, and then tested with 16S metagenomics sequencing. (2) Methods: Starting from buccal swab, we extracted bacterial DNA and then we performed a NGS metagenomics sequencing based on the amplification of hypervariable regions of the 16S in bacteria. (3) Results: The sequencing revealed the presence of Spirochaetes Phylum, a pathogenic bacterium generally known to be able to migrate to the Central Nervous System and not only. (4) Conclusions: Oral infections as our results shows could be possible contributing factors to various neurodegenerative conditions.

Several specific types of generalized compactness of generalized topological spaces have been defined, investigated and related to compactness in ordinary topological spaces from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized compactness in a generalized topological space is reported herein as a starting point for more generalized classes.

Several specific types of ordinary and generalized connectedness in a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new type of generalized connectedness in a generalized topological space is reported herein as a starting point for more generalized types.

Several specific types of generalized maps of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized maps of a generalized topological space is reported herein as a starting point for more generalized classes.

Several specific types of generalized sets of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized sets of a generalized topological space is reported herein as a starting point for more generalized classes.

High-throughput screening technologies continues to produce large amounts of multiomics data from different populations and cell types for various diseases, such as cancer. However, analysis of such data encounters difficulties due to cancer heterogeneity, further exacerbated by human biological complexity and genomic variability. There is a need to redefine the drug discovery development pipeline, bringing an Artificial Intelligence (AI)-powered informational view that integrates relevant biological information and explores new ways to develop effective anticancer approaches. Here, we show SynPred, an interdisciplinary approach that leverages specifically designed ensembles of AI-algorithms, links omics and biophysical traits to predict synergistic anticancer drug synergy. SynPred exhibits state-of-the-art performance metrics: accuracy – 0.85, precision – 0.77, recall – 0.75, AUROC – 0.82, and F1-score - 0.76 in an independent test set. Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application available online at http://www.moreiralab.com/resources/synpred/ was constructed to predict synergistic anticancer drug combinations requiring only the upload of the two drug SMILES to be tested, allowing easy access by non-expert researchers.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

The present study comprises the second part of our previous work that dealt mainly with the phytochemical and physicochemical characterization of green coffee, clove, cinnamon/clove and nutmeg ethanolic extracts of grape origin. In the present study, we focused on producing a discriminating model concerning green coffee, clove, cinnamon, cinnamon and clove, and nutmeg fine powders based on multivariate analysis of variance and supervised learning on data of volatile compounds analysis, carried out with solid phase dynamic extraction in combination with gas chromatography/mass spectrometry. Results showed that 7 volatile compounds namely ethylene, methanol, 3-methylpentane, ethyl acetate, 9-hexadecen-1-ol, toluene, and methyl acetate could differentiate the investigated samples resulting in a 100% classification rate using the cross-validation method of linear discriminant analysis. Results were further confirmed using partial least squares regression analysis. The study contributes to the typification of green coffee, cinnamon, clove, cinnamon and clove and nutmeg, based on selected volatile compounds, and provides further support to the literature by means of possible adulteration given the statistical models developed.

Hereditary cancer syndromes caused by germline mutations account for 5-10% of all cancers. The finding of a genetic mutation could have far-reaching consequences for pharmaceutical therapy, personalized prevention strategies, and cascade testing. According to the National Comprehensive Cancer Network’s (NCCN) and the Italian Association of Medical Oncology (AIOM) guidelines, unaffected family members should be tested only if the affected one is unavailable. This article explores whether germline genetic testing may be offered to high-risk families for hereditary cancer even if a living affected relative is missing. A retrospective study was carried out on 103 healthy subjects tested from 2017 to 2023. We enrolled all subjects with at least two first or second-degree relatives affected by breast, ovarian, pancreatic, gastric, prostate, or colorectal cancer. All subjects were tested by Next Generation Sequencing (NGS) multi-gene panel of 27 cancer-associated genes. In the study population, 5 (about 5%) pathogenic/likely pathogenic variants (PVs/LPVs) were found while 40 (42%) had a Variant of Uncertain Significance (VUS). This study highlights the importance of genetic testing for individuals with a strong family history of hereditary malignancies. This approach would allow women who tested positive to receive tailored treatment and prevention strategies based on their personal mutation status.

In this paper glass crystallization behavior of 50ZnO:47B2O3:3Nb2O3:0.5Eu2O3 (G-0h) glass has been investigated in detail by DSC, XRD and TEM analysis. The luminescent properties of resulted glass-ceramics were also investigated. By XRD and TEM analysis crystallization of several crystalline phases have been proved (α-Zn3B2O6, β-Zn3B2O6 and ZnNb2O6). By calculating of crystal parameters it was found that europium ions are successfully incorporated in the β-Zn3B2O6. Photo-luminescent spectra show an increased emission in the resulting glass-ceramic samples as compared with the parent glass sample because of the higher asymmetry of Eu3+ ions in the crystalline phases obtained. It was established that the optimum emission intensity is registered for glass-ceramic sample obtained after 25 hours heat treatment of the parent glass.

As the demand of heating and air conditioning is increasing day by day due to getting a comfortable life, for that reason, the market for heat pump and air conditioning systems or both, is seeing a steady increase in low global warming potential. All researchers on heat pump and air conditioning systems are searching for environmentally friendly refrigerants. However, a significant number of contemporary refrigerants (HCFCs) have the potential to cause global warming and ozone depletion, such as those found in heat pump air conditioning systems. Using more environmentally friendly refrigerants, including hydrocarbon and blend refrigerant mixtures, is one way to lower GWP and Ozone depletion potential. This study examines the performance of several alternative refrigerants, including R32, R134A, R410A, R22, and R290. In order to examine the performance of R290, theoretical and simulation results are compared on various refrigerants while taking into account a number of performance parameters, including the refrigerant energy efficiency ratio, mass flow rate, coefficient of performance, cooling capacity, and compressor work for one ton of refrigeration (1TR) air conditioners. One player with a very low GWP is R290. However, the only drawback is that it can catch fire and is hazardous to use in split-type commercial heat pump air conditioning applications. The environmental and thermo physical properties of HC-290 are significantly better than those of other materials, according to theoretical and simulation studies utilizing Cool Pack software, hence it is a viable replacement.

The purpose of our work was the search for safe and effective biologically active substances of cardiotropic action among 1,3- thiazole derivatives. New derivatives of 1-[(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-yl]ethan-1-one and ethyl-(2Z)-2-[R-imin]-4-methyl-3-R¹-2,3-dihydro-1,3-thiazole-5-carboxylate were synthesized by the Hantzsch reaction. The structure of the compounds obtained was confirmed by ¹H NMR spectroscopy and by the elemental analysis. The pharmacological screening showed that the obtained substances possess cardiotropic activity. The cardiotropic properties of the new 1,3-thiazole derivatives were studied on the isolated rings of the thoracic aorta of laboratory rats. A prospective substance 1-[(2Z)-2-[(4-methoxyphenyl)imin]-4-methyl-3-(4-methylpiperazin-1-yl) -2,3-dihydro-1,3-thiazol-5-yl]ethan-1-one hydrochloride, which exhibits cardiotropic activity exceeding the activity of L-carnitine and meldonia has been revealed during pharmacological researches of the substances obtained.

This review paper presents a comprehensive synthesis of current knowledge on the contamination of water systems by polycyclic aromatic hydrocarbons (PAHs). PAHs, organic contaminants characterized by two or more fused aromatic rings, are notably problematic due to their persistence, bioaccumulation, and significant health risks. The review commences with an examination of various sources of PAHs in aquatic environments, encompassing both anthropogenic activities, such as industrial discharges, urban runoff, and oil spills, and natural phenomena including volcanic eruptions and wildfires. Subsequently, the discussion shifts to the distribution patterns of PAHs within different aquatic ecosystems, with an analysis of factors that influence their transport. Considerable focus is placed on the entry mechanisms of PAHs into water systems and their interactions with diverse environmental matrices. Additionally, the ecotoxicological effects of PAHs on aquatic life are scrutinized, with particular emphasis on molecular, individual, and ecosystemic impacts. This includes an exploration of PAH bioaccumulation in aquatic organisms and their potential mutagenic and carcinogenic consequences. The review further addresses the challenges associated with detecting and quantifying PAHs in aquatic settings, reflecting on the advancements in analytical methodologies and the complexities introduced by their varied physicochemical properties. The paper concludes with a summary of existing regulatory frameworks and guidelines governing PAH contamination in water systems, underscoring the imperative for global collaboration in the monitoring and management of PAH pollution.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary & safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

Solid-state batteries (SSBs) have emerged as a promising alternative to conventional lithium-ion batteries, with notable advantages in safety, energy density, and longevity, yet the environmental implications of their lifecycle, from manufacturing to disposal, remain a critical concern. This review paper examines the environmental impacts associated with the production, use, and end-of-life management of SSBs, starting with the extraction and processing of raw materials which highlights significant natural resource consumption, energy use, and emissions. A comparative analysis with traditional battery manufacturing underscores the environmental hazards of novel materials specific to SSBs. The review also assesses the operational environmental impact of SSBs by evaluating their energy efficiency and carbon footprint in comparison to conventional batteries, followed by an exploration of end-of-life challenges including disposal risks, regulatory frameworks, and the shortcomings of existing waste management practices. A significant focus is placed on recycling and reuse strategies, reviewing current methodologies like mechanical, pyrometallurgical, and hydrometallurgical processes, along with emerging technologies that aim to overcome recycling barriers, while also analyzing the economic and technological challenges of these processes. Additionally, real-world case studies are presented, serving as benchmarks for best practices and highlighting lessons learned in the field. In conclusion, the paper identifies research gaps and future directions for reducing the environmental footprint of SSBs, underscoring the need for interdisciplinary collaboration to advance sustainable SSB technologies and contribute to balancing technological advancements with environmental stewardship, thereby supporting the transition to a more sustainable energy future.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Several specific types of ordinary and generalized separation axioms of a generalized topological space have been defined and investigated for various purposes from time to time in the literature of topological spaces. Our recent research in the field of a new class of generalized separation axioms of a generalized topological space is reported herein as a starting point for more generalized classes.

Sudden cardiac arrest (SAC) is a leading cause of mortality. In recent years, though, many lives have been saved through the use of defibrillators by random bystanders. As a result, defibrillators have been popping up in various locations. In this work we propose a state mandate demanding the presence of a defibrillator at every pharmacy store and argue that it could greatly enhance and augment the impact of the defibrillator network. We support our claim via detailed calculations of the immediate (a defibrillator readily available) and partial (a defibrillator available at a reasonable distance) population coverage achievable by the implementation of our proposal, taking the Argolis area in Peloponnese Greece as a case study. Our findings indicate that, in addition to other benefits, the use of pharmacies to establish a defibrillator network could bring an eight-fold increase in the immediate population coverage of defibrillators and would provide immediate / partial access to a defibrillator to 18 / 24 incidents of SCA per year that would otherwise lead to death, potentially leading to the saving of numerous lives. Alternative scenaria are also discussed.

The objective of this study was aimed to study the sensory processes of the “human-computer interaction” model when classifying visual images with an incomplete set of signs based on the analysis of early, middle, late and slow components of event-related potentials (ERPs). 26 healthy subjects (men) aged 20-22 years were investigated. ERPs in 19 monopolar sites according to the 10/20 system were recorded. Discriminant and factor analysis were applied. The component N450 is the most specialized indicator of the perception of unrecognizable (oddball) visual images. The amplitude of the ultra-late components N750 and N900 is also higher under conditions of presentation of the oddball image, regardless of the location of the registration points. The results of the study are discussed in the light of the paradigm of the P300 wave application in brain-computer interface systems, as well as with the peculiarities in brain pathology. Promising directions for the development of studies of the “Brain Computer Interface” (BCI) P300 systems are to increase the throughput of information flows. To extend the application of the P300 ERPs to multiple modalities, the underlying physiological mechanisms and responses of the brain for a particular sensory system and mental function must be carefully examined.

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation uses blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte Antigen 4 and anti-programmed Death-1 antibodies has shown promise by enhancing T cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T cell receptors could further augment the anti-tumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

The article deals with issues related to social and moral education and development of preschool children. The theoretical understanding of the current state of this field is reflected in the modern normative documents "On education in the Russian Federation", the state educational standards. Analysis of theoretical and practice-oriented research in this area shows that the phrase "moral education" today is gradually replaced by "social and moral education", "social and moral development". This trend is found in preschool pedagogy (work L. V. Abramova, R. S. Bure, S. M. Zyryanova, N.A. Karataeva, G. M. Kiseleva, I. F. Sleptsova, etc.). It is the study of social and moral representations of preschool children that many relevant diagnostic methods are aimed at: to explain the actions of children, their relationship with each other and adults, to assess these actions (i.e. to correlate the situation with the moral norm). The presented research was based on the method of research of moral representations of children of senior preschool age, developed by G. A. Uruntaeva and Yu.A. Afon'kina. The analysis of the results showed that children of senior preschool age willingly included in the retelling of the actions described in the situation, but find it difficult to assess what is happening from a moral point of view. It is obvious that psychological and pedagogical work is necessary in this direction, taking into account the age characteristics of children, as well as social and moral guidelines relevant to the current situation of development of society.

This article presents the results of research on the influence of polymetallic dust aerial emissions on the pollution levels in the soil and plants by heavy metals which have been under impact of the “Severonickel” smelter complex on the Kola peninsula (Russia) for many years. Research using soil- and bio-indicators was carried out at fixed measuring points in the years 1980-1999 (high aerotechnogenic emissions) and 2000-2019 (low aerotechnogenic emissions). The organic horizon (forest litter) of the Al-Fe-humus podzol, leaves of Vaccinium myrtillus L., V. vitis-idaea L., V. uliginosum L., Empetrum hermaphroditum Hagerup and one-year old Scots pine needles Pinus sylvestris L. as well as tree rings of Pinus sylvestris L. were used for bioindication research. The content of heavy metals was determined by the AAS method. During these time periods, the volume of atmospheric emissions of sulfur dioxide decreased 5 fold, polymetallic dust by 3.5 times, while the level of forest litter pollution by heavy metals in the buffer zone increased by 2 times, and did not change significantly in the impact zone. The decrease in atmospheric emissions of pollutants led to a 1.5- fold increase in the width of the annual rings of pine trunks in the impact zone, while in the buffer zone the differences were insignificant. At present, the content of Ni and Cu in the leaves of the wild dwarf-shrubs and pine needles in the impact zone has decreased by 5 times compared with 1980-1999 due to a decrease in polymetallic dust on the leaf surface.

We review time expansion wave theory and refine our model showing it to accurately match observed cosmological luminosity data. The theory augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension that we observe as the expansion of the universe. This leads us to explain mass creation, the speed of light limit, gravity, black holes without singularities and other macroscopic effects. Our model leads to an expansion velocity of 6.87 0.36 × 106 ms-1, which results in a Hubble expansion rate constant of 71.3 3.7 km/s/Mpc. Because of the finite window of time in which we exist, an extra a degree of freedom is available leading to interesting interpretations at the subatomic level. At this size range, then a spin is allowed within the time dimension explaining why wave particle duality occurs and explains the electromagnetic force and other quantum mechanical properties. It provides a solution to the double slit conundrum and can explain how quantum entangled partners can behave in a quantum way and pass seemingly time-defying information. The potential quantitative origin of the fine structure constant which governs the size of the electromagnetic force is also strongly indicated by this theory.

The Fuzzy Transportation Problem (FTP) represents a significant extension of the Classical Transportation Problem (TP) by introducing uncertainly and imprecision into the parameters involved. Various algorithms have been proposed to solve the FTP, including fuzzy linear programming, metaheuristic algorithms and fuzzy mathematical programming techniques combined with Artificial Neural Networks. This paper presents the application of Trigonometric Acceleration Coefficients-PSO (TrigAc-PSO), a variation of the Classical Particle Swarm optimization algorithm, which is an innovative algorithm originally developed for solving the TP. TrigAC-PSO, has demonstrated remarkable success in optimizing various problem domains in crisp environments.

The fatty acid elongase ELOngation of Very-Long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, do-cosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in-vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondial-dehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with high voltage-dependent anion channel (VDAC) and adenine nucleotide trans-locase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission elec-tron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

Abstract: A new method for constructing exact solutions of the General Relativity equations for a dusty matter with fractal property is proposed. This method allows to find the solution of the GR-equations in terms of matter velocities : the connection coefficients and the Ricci tensor of space-time are expressed in terms of matter velocities; the metric tensor and the matter density are found as functions of velocity from the GR-equations. The connection coefficients and the Ricci tensor are invariant with respect to the discrete scaling transformation of velocity , where is constant. Therefore, the found solution can be used to simulate the fractal properties of the cosmic web in terms of matter velocities. This solution includes isotropic and anisotropic distributions of matter density. In an isotropic case, there is a class of exact solutions including both the well-known Friedmann’s solution and a solution with a periodic distribution of the matter density in space. This last solution may be used to simulate the quasi-periodic distribution of matter in the cosmic web. It is possible that, the cosmic web and its fractal properties are the space-time primary properties. These properties are described with a deformation tensor of the space-time.

Huge filaments with scales from several hundred megaparsecs to gigaparsecs are detected in the distribution of galaxies and clusters, quasars, gamma-bursters. The hypothesis on the nature of the huge filaments as regions of space-time deformation is proposed. An anisotropic deformation of the local region is described by the strain tensor, it depends on the velocities of matter. Galaxies get an extra velocity in the region, which leads to the formation of filamentary structures. The class of exact solution of the GR equations is constructed by introducing the special definition of the Christoffel symbols as function of the velocity of matter. With a definition of these symbols, the motion matter equation turns into identity. For the sake of simplicity, an ideal fluid is considered.

By combining general relativity and CPT symmetry, the theory of CPT gravity predicts gravitational repulsion between matter and CPT-transformed matter, i.e. antimatter inhabiting an inverted space-time. Such repulsive gravity turned out to be an excellent candidate for explaining the accelerated expansion of the Universe, without the need for dark energy. The recent results of the ALPHA-g experiment, which show gravitational attraction between antihydrogen atoms and the Earth, seem to undermine this success in the cosmological field. Analyzing the above theory, we find two solutions that can be consistent with the experimental results, while preserving the large-scale gravitational repulsion. The first highlights how repulsive gravity can be the result of the interaction with an inverted space-time, but occupied by matter and not antimatter, and therefore the antimatter present in our space-time has no reason to exhibit gravitational repulsion. The second retains the original CPT transformation, resulting in repulsive gravity between matter and antimatter, but with the caveat that antimatter immersed in our space-time cannot exhibit the PT transformation which is the cause of the repulsion. Finally, it is shown that, in a Newtonian approximation of the geodesic equation, time reversal is not a necessary operation for repulsive gravity, therefore opening the possibility of an expanding cosmos with a single time direction.

The spin magnetic moments and spin g factors (g_s = -2) of electron, muon and tau are explained based on the electric charges (EC) and lepton charges (LC) in terms of the three-dimensional quantized space model. The spin g factors of electron, muon and tau are g_s = -2 which is the sum of the EC g factor (g_EC = -1) and the LC g factor (g_LC = -1). The spin g factor (g_s = -2) of the electron is predicted by the Dirac’s equation. The orbit g factors of electron, muon and tau are g_L = g_EC = -1 from the EC g factor (g_EC = -1) without the contribution of the LC g factor (g_LC = -1). The spin g factors of the elementary fermions are calculated from the equation of g_s = g_EC + g_LC + g_CC where g_EC = EC/|EC|, g_LC = LC/|LC| and g_CC = CC/|CC|. For example, the spin g factors of the neutrinos and dark matters are g_s = -1. The spin g factors of the u and d quarks are g_s = 0 and g_s = -2, respectively. The g factor problem of neutrinos with the non-zero LC charges are solved by the LC Coulomb force of F_c(LC) ≈0. It is, for the first time, proposed that the binary motion (fluctuations) of the m_EC and m_LC masses for the electron, muon and tau leptons make the anomalous g factor. This binary motion could be originated from the virtual particle processes including the photons. Also, the weak force (beta) decay is closely related to the binary motion of the m_EC and m_LC for the electron, muon and tau leptons.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

With increasing interest in the use of additive manufacturing techniques in the construction industry, static rheological properties of fresh concrete have necessarily come into focus. In particular, the knowledge and control of static yield stress (SYS) and its development over time are crucial for mastering formwork-free construction, e.g. by means of layered extrusion. Furthermore, solid understanding of the influences of various concrete constituents on the initial SYS of the mixture and the structural build-up rate is required for purposeful material design. This contribution is concentrated on the effect of aggregates on these rheological parameters. The volume fraction of aggregates was varied in the range of 35 to 55 % by volume under condition of constant total surface area of the particles. The total surface area per unit volume of cement paste was equal to 5.00, 7.25 and 10.00 m²/l, conditioned on the constant volume fraction of aggregates. Both variations were enabled by changing the particle size distributions of the aggregates while holding the cement paste composition constant for all concrete mixtures. To characterise the SYS and the structural build-up, constant shear rate tests with a vane-geometry rotational rheometer were performed. It was found that in the ranges under investigation the variation in volume fraction had a more pronounced effect on the static rheological properties of concrete than did the variation in surface area. An accurate mathematical description of the relationship between the initial SYS of concrete and the relative volume fraction of aggregate based on the Chateau-Ovarlez-Trung model was proposed. Challenges in deriving a similar relationship for the structural build-up rate of concrete were highlighted.

HLA-G is an immune checkpoint molecule with immunosuppressive and anti-inflammatory activities, and its expression and level of its soluble form (sHLA-G) may play an important role in tumor prognosis. The HLA-G 14 bp ins/del polymorphism and the plasma level of soluble HLA-G (sHLA-G) were investigated by a polymerase chain reaction and ELISA, respectively, in 59 glioma patients. A significantly higher proportion of glioma patients had the 14 nt insert in both homozygous and heterozygous states compared to the control group. Glioma patients had also higher plasma levels of sHLA-G. Patients with methylated MGMT promoter had lower levels of sHLA-G than those with unmethylated MGMT promoter. Level of sHLA-G negatively correlated with the overall survival of patients. Glioblastoma patients who survived more than one year after diagnosis had lower levels of sHLA-G than those surviving less than one year. Patients with sHLA-G levels below the cut off value 40 U/mL survived significantly longer than patients with sHLA-G above 40 U/mL. The levels of sHLA-G also negatively correlated with the level of IL-6 (P=0.0004) and positively with IL-10/IL-6 (P=0.046). Conclusion: The presence of 14 nt insert in both homozygous and heterozygous states of the HLA-G 14 bp ins/del polymorphism is more frequent in glioma patients and the elevated plasma levels of sHLA-G are negatively associated with their survival.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

Background: The two-stage technique combining the Endoscopic Retrograde CholangioPancreatography (ERCP) with common bile duct (CBD) clearance carried out before the laparoscopic cholecystectomy represents the most common approach for CBD stones. Over time, different techniques have been proposed to manage cholecysto- choledocholithiasis (CCL) advantageously in one stage. Among these, the laparoendoscopic rendez-vous (LERV) addresses the CCL issue with a laparoscopic cholecystectomy with insertion of a guide wire performed at initial stage of the procedure, followed by the clearance of the bile duct carried out by the endoscopists. The goal of this study was to evaluate the efficacy and safeness of LERV procedure recording results and complications, also making a comparison between our results and current literature. Methods: We reviewed our experience of all consecutive patients with cholecysto-choledocholithiasis managed with LERV between January 2018 and December 2023. LERV success rate, operative time, length of hospital stay, stone recurrence, incidence of endoscopic and surgical complications were analysed. Results: A total of 120 patients underwent LERV in our facilities. We reported a 97% LERV success rate, 1.6% conversion-to-open rate, a median intraoperative time of 122 (range 95-220) min. The median hospital stay was 4 (range 2-38) days. An overall morbidity of 15% was reported (18/120): 15 Clavien-Dindo type 1/2, 2 type 3a and one type 3b. In two cases a re-operation during the hospital stay was necessary. At a median follow-up of 14 months (3-59) five patients experienced stone recurrence requiring redo-ERCP in two cases. Conclusion: LERV offers the significant advantage of a single stage procedure and hospitalisation along with a lower risk of post-ERCP pancreatitis, failed CBD cannulation and complications. Our experience confirms safety and effectiveness of the technique for CCL management.

Mobile robots need an environmental perception ability in order to interact with the surrounding environment. In this paper we present the G-SLAM method, where the map is consisted of a cloud of scattered points in the continuous space and each point is accompanied by an obstacle existence probability. On the other hand the robot's pose (and trajectory) is estimated by an particle filters while the cloud of points is estimated by an adaptive recursive algorithm which is presented. Main feature of the presented method is the adaptive repositioning of the scattered points and their convergence around obstacles. In addition to our previous publications, In this paper a mathematical derivation of the method is presented and real case scenarios are discussed, presented and compared with other methods.

The cruise ship industry has become a well-implemented industry in the Baltic Sea area, and each year, the number of cruise ship passengers rises steadily. Efficient waste management in cruising ports around the Baltic Sea is a crucial element in minimizing environmental impacts. This research involves the four selected ports of Copenhagen, Helsinki, Stockholm and Tallinn. The study applies statistics and interview data to the analysis of waste management systems for cruise ship-generated waste. The interview data involves 14 executives and professionals responsible for environmental issues and decision making in their respective ports. The interviews highlighted the need for standardized environmental legislation and related procedures, which would result in coherent measurement systems. These systems would enable transparent environmental monitoring, thus maintaining the ports’ competitiveness. A common environmental legislation would support the emerging waste management system for the whole Baltic Sea area. We suggest that ports should focus on handling specific types of wastes and collaborate as a spatial network. Specialization to allow discharge of certain fractions of waste is essential. The paper concludes by addressing demands for future research, particularly vessel- and customer behavior focused studies.

:. Background and Objectives: Pulmonary embolism, PE, incidence had been increasing in the last ten years. Computed thoracic pulmonary angiography, CTPA, had a major role in confirming PE di-agnosis.The main purpose of the study was to establish the prognostic value of a CTPA parameter: pulmonary artery obstruction index, PAOI, for PE risk assessment . A second objective of the re-search was to investigate the predictive accuracy of biomarkers (D-dimer, and cardiac Troponin T, c-TnT ), and PAOI, in 7-day mortality. The third objective of the study was the relationship between PAOI, and these biomarkers, in different etiologies of PE. Materials and Methods: The study com-prised 109 patients with PE, hospitalized, and treated between February 2021, and August 2022. They had different etiologies: deep vein thrombosis, DVT; persistent atrial fibrillation, AF; chronic obstructive pulmonary disease, COPD, exacerbation; Covid; and cancers. The investigations were the following: clinical examination; D-dimer testing, as a mandatory method for PE suspicion( values ≥ 500 µg/L were highly suggestive for PE); c-TnT , as a marker of myocardial injury(values ≥ 14 ng/L were abnormal); CTPA, with right ventricle dysfunction, RVD, signs, and PAOI. Treat-ments were according to PE risk: systemic thrombolysis (in high risk , and hemodynamic instability); low weight molecular heparins, LWMH, after systemic thrombolysis, or in high risk PE, with he-modynamic stability; direct oral anticoagulants, DOAC (in low, and intermediate risk). Results: The relationship PAOI- D-dimer, and PAOI- c-TnT, had very strong statistical correlation, for the entire sample, and for DVT, AF, COPD, Covid subgroups ( Rho = 0.815-0.982). PAOI had a high predic-tive accuracy for intermediate , and high risk together (area under curve, AUC=0.948), and high risk PE (AUC= 0.993). For 7-day mortality, D-dimer , and c-TnT had high predictive accura-cy(AUC=0.921, and 0.979). PAOI had statistical significance for 7-day mortality in Covid (p=0.045), and cancer (p=0.038) patients. Conclusions: PAOI was an important tool for PE risk as-sessment. D-dimer , and c-TnT were valuable predictors, for 7-day mortality in PE. PAOI, and D-dimer; PAOI, and c-TnT were strongly correlated, for the entire PE sample, and for DVT, AF, COPD, and Covid patients.

For each $t\in(-1,1)$, exact values of the least upper bounds $$ H(t)=\sup_{\E X=t,\,\E X^2=1} \frac{\E\abs{X}^3}{\E \abs{X-t}^3},\quad \sup_{\E X=t,\,\E X^2=1} \frac{L_1(X)}{L_1(X-t)} $$ are obtained, where $L_1(X)=\E|X|^3/(\E X^2)^{3/2}$ is the non-cental Lyapunov ratio. It is demonstrated that these values are attained only at two-point distributions. As a corollary, S.\,Shorgin's conjecture is proved that states that the exact value is $$ \sup\frac{L_1(X)}{L_1(X-\E X)}= \frac{\sqrt{17 + 7\sqrt7}}{4} = 1.4899\ldots, $$ where the supremum is taken over all non-degenerate distributions of the random variable $X$ with the finite third moment. Also, in terms of the central Lyapunov ratio $L_1(X-\E X)$, an analog of the Berry--Esseen inequality is proved for Poisson random sums of independent identically distributed random variables with the constant $$ 0.3031\cdot H\left(\frac{\E X}{\sqrt{\E X^2}}\right) \left(1-\frac{(\E X)^2}{\E X^2}\right)^{3/2} \le 0.3031\cdot \frac{\sqrt{17 + 7\sqrt7}}{4}<0.4517.$$ where $\Law(X)$ is the common distribution of the summands.

This study considers an application of the first-order Grey Markov Model to foresee the values of Italian power generation in relation to the available energy sources. The model is used to fit data from the Italian energy system from 2000 to 2022. The integration of Markovian error introduces a random element to the model, which is able now to capture inherent uncertainties and misalignments between the Grey model predictions and the real data. This application provides valuable insights for strategic planning in the energy sector and future developments. The results show good accuracy of the predictions, which provides powerful information for the effective implementation of energy policies concerning the evolution of energy demand in the country. Despite advancements, Italy’s 2032 energy mix will still significantly rely on fossil fuels, emphasizing the need for sustained efforts beyond 2032 to enhance sustainability.

In this study we have investigated the effect of the addition of Nb2O5 (up to 5 mol%) on the structure and luminescent properties of ZnO-B2O3 glass doped with 0.5 mol % Eu2O3 by using of infrared (IR), Raman and photoluminescence (PL) spectroscopy. Physical properties as molar volume, oxygen packing density and glass transition temperature were determined using the results of differential thermal analyisis (DTA) and Archimedes principle for density. IR and Raman spectra revealed that niobium ions incorporate into the base zinc borate glass as NbO4 trtraherda and NbO6 octahedra. A strong red emission from the 5D0 level of Eu3+ ions was registered under near UV (392 nm) excitation using the sharp 7F0 - 5L6 transition of Eu3+. The integrated fluorescence intensity ratio R (5D0 → 7F2/5D0 → 7F1) was calculated to estimate the degree of asymmetry around the active ion, suggesting a location of Eu3+ in non-centrosymmetric sites. The higher Еu3+ luminescence emission observed in zinc borate glasses containing 1÷5 mol% Nb2O5 compared to the Nb2O5-free zinc borate glass evidences that Nb2O5 is suitable component for modification of host glass structure and improving the emission intensity.

The powdered sorbents were applied in a batch system under "static" conditions and showed a much higher adsorption capacity than the granular one. These type of sorbents are more suitable for small quantities of water with a high concentration of arsenic. The possibilities of using all the tested methods for arsenic removal have been evaluated, and a scheme of the technological process has been proposed.

Natural risks encompass a range of disasters and dangers, requiring comprehensive management through assessments, anticipations, and advanced alert systems. Our specific focus is on landslides in challenging terrains. The evaluation of landslide risks employs sophisticated multicriteria models, such as the weighted sum approach, integrating qualitative parameters. Despite the challenges of the rugged terrain in Northern Algeria, it paradoxically hosts a dense population attracted by valuable hydro-agricultural resources. Our research is dedicated to studying landslide risks in these areas, particularly in the Mila region, with the aim of constructing a statistical model integrating considerations of both danger and vulnerability. This complex process identifies threats and their determining factors, including geomorphology and socio-economic conditions. The result is a valuable tool for effective risk management, strengthening safety and resilience against natural disasters. By understanding the intricate interplay of geological, environmental, and social elements, our research can contribute to the development of targeted interventions, fostering a more resilient community in the face of natural adversities.

Introduction: The trophoblast derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. The aim of this study was to establish relationship between concentrations of soluble Human Leukocyte Antigen-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of the fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices were determined in 41 uncomplicated singleton pregnancies. Results: The sHLA-G levels were unchanged both in amniotic fluid and in serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β=0.63, p<0.01). Significant correlation was found between serum sHLA-G level and abdominal measurement (β=0.41, p<0.05) and estimated fetal weight (β=0.41, p<0.05). The amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p<0.01 and VFI: β = -0.44, p<0.01, respectively) were negatively interrelated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p<0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator for placental function, whereas the sHLA-G level in serum can be a prognostic modality for feto-placental insufficiency.

We describe our investigations of the surface physicochemical and biological properties of polylactic acid modified by silver, argon and carbon ion implantation to doses of 1 × 10¹⁴, 1 × 10¹⁵ and 1 × 10¹⁶ ion/cm² at energies of 20 keV (for C and Ar) and 40 keV (for Ag). X-ray analysis shows enhancement of coherent scattering regions and lattice constant increase after ion implantation. Secondary electron mass-spectrometry indicates that Ag concentration in the subsurface layer is less than 80%, but at a depth of 500 nm does not exceed 1–2%. The silver forms metal particles in the subsurface layer rather than making additional chemical bonds with polymer atoms. Atomic force microscopy reveals that the higher the irradiation dose the larger the surface roughness of the samples. Ag-irradiated samples implanted to a dose of 1 × 10¹⁶ ions/cm² have the highest roughness, 190 nm. Our investigation of the cytotoxicity of two individual donor macrophages shows that Ag-implanted polylactic acid has no negative impact on immune system cells and could be a promising material for biomedical application.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Mercury has a strong environmental impact since both its organic and inorganic forms are toxic and it represents a pollutant of global concern. Liquid Hg is highly volatile and it can be released during natural and anthropogenic processes in the hydrosphere, biosphere and atmosphere. In this study the distribution of Gaseous Elemental Mercury (GEM) and the total and leached mercury concentrations on paints, plasters, roof tiles, concretes, metals, dust and wood structures were determined in the main buildings and structures of the former Hg-mining area of Abbadia San Salvatore (Siena, Central Italy). The mining complex (divided into 7 units) covers a surface of about 65 ha and contains mining structures and managers and workers buildings. In this work, nine surveys of GEM measurements were carried out from July 2011 to August 2015 for the buildings and structures located in the units 2, 3 and 6. Moreover, detailed measurements were performed in February, April, July, September and December 2016 in the edifices and mining structures of Unit 6. GEM concentrations showed a strong variability in terms of space and time mostly depending on the distance from the building hosting driers, furnaces and condensers and ambient temperature, respectively. In the Unit 2 surveys carried out in the hotter period (from June to September) showed GEM concentrations up to 27,500 ng m⁻³, while in the Unit 6 they were on average much higher and occasionally they saturated the GEM measurement device (>50,000 ng m⁻³). Concentrations of total (in mg kg⁻¹) and leached (in μg L⁻¹) mercury measured in different building materials (up to 46,580 mg kg⁻¹ and 4,470 mg L⁻¹ for total and leached mercury, respectively) showed for the same type of material highly variable values in dependence on the edifice or mining structure from which they were collected. The results obtained in this study are of relevant interest for the operational cleanings to be carried out during the reclamation activities.

Little has been written in literature about the clinical comparison of the single use of chlorhexidine (CHX) rather than its combination with cetylpyridinium chloride (CPC). The purpose of this study was to compare the clinical effectiveness of two at-home antiseptic regimens. Healthy subjects scheduled for dental surgery were enrolled. After the surgery, patients were randomly allocated in a first group (Group A) which received a manual ultra soft toothbrush (Mentadent Professional®), an antiseptic toothpaste with 0,12% CHX and Vitamin B3 (Mentadent Professional Azione Intensiva Gengive®) and an antiseptic mouthwash with 0,12% CHX and 0,07% CPC. The second group (Group B) received solely an antiseptic mouthwash with 0,2% in conjunction with Anti Discoloration System (Curasept ADS/DNA®) and were encouraged to use their usual toothbrush and toothpaste. Patients were instructed to use the products twice a day and to rinse for 30 seconds. On day 7, patients were examined for the Early Healing Score, Visual Plaque Index of the sutures, Numerical Rating Scale and mouthwash taste. Group A showed a statistically significant levels of EHS and taste satisfaction. The regimen based on CHX associate with vitamin B3 in the toothpaste and CPC in the mouthwash resulted in superior clinical outcomes and satisfaction compared to solely CHX.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

The present paper reports exact results for the muon self-energy and anomalous g-factor. A unique to the muon cut-off terms that remove the radial singularity in the system and regularize the corresponding electrodynamics are presented. Equations of motion and a transcendental equation satisfied by the muon anomalous g-factor are derived, with solution a_m=0.001165920162(198). The obtained value matches the latest experimental one found in the literature to about 0.43 ppb ruling out a possible tension between theory and experiment.

In this paper, we investigate some kind of Dynkin game under $g$-expectation induced by backward stochastic differential equation (shortly for BSDE). We define the lower and upper value functions $\underline{V}_t=ess\sup\limits_{\tau\in{\mathcal{T}_t}} ess\inf\limits_{\sigma\in{\mathcal{T}_t}}\mathcal{E}^g_t[R(\tau,\sigma)]$ and $\overline{V}_t=ess\inf\limits_{\sigma\in{\mathcal{T}_t}}ess\sup\limits_{\tau\in{\mathcal{T}_t}}\mathcal{E}^g_t[R(\tau,\sigma)]$, respectively. Under some regular assumptions, a pair of saddle point is obtained and the value function of Dynkin game $V(t)=\underline{V}_t=\overline{V}_t$ follows. Furthermore, the constrained case of Dynkin game is also considered.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

Motivated by important applications to the analysis of complex noise-induced phenomena, a problem of the constructive description of randomly forced equilibria for nonlinear systems with multiplicative noise is considered. Using apparatus of the first approximation systems, we construct an approximation of mean square deviations that explicitly takes into account the presence of multiplicative noise. This approximation is compared with the widely used approximation based on the stochastic sensitivity technique. The general mathematical results are illustrated with the example of the van der Pol oscillator with hard excitement.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Peritoneal dialysis (PD) is a home-based efficacious modality for replacement of renal function in end-stage kidney failure patients but is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of long-term morpho-functional peritoneal changes eventually resulting in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile proves quite difficult. New approaches targeting the composition of the PD solution include replacement of glucose with other osmotic agents and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include infusion of mesenchymal cells or the administration of orally active agents. In the present article we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

We report the negative effective mass metamaterials based on the electro-mechanical coupling exploiting plasma oscillations of a free electron gas. The negative mass appears as a result of vibration of a metallic particle with a frequency of ω which is close to the frequency of the plasma oscillations of the electron gas m_2 relatively to the ionic lattice m_1. The plasma oscillations are represented with the elastic spring k_2=ω_p^2 m_2, where ω_p is the plasma frequency. Thus, the metallic particle vibrated with the external frequency ω is described by the effective mass m_eff=m_1+(m_2 ω_p^2)/(ω_p^2-ω^2 ) , which is negative when the frequency ω approaches ω_p from above. The idea is exemplified with two conducting metals, namely Au and Li embedded into various matrices. The one-dimensional lattice built of the identical metallic micro-elements m_eff connected by ideal springs k_1 representing various media such as polydimethylsiloxane and soda-lime glass is treated. The optical and acoustical branches of longitudinal modes propagating through the lattice are elucidated for various ratios ω_1/ω_p . The 1D lattice built of the thin metallic wires giving rise to the low frequency plasmons is treated. The possibility of the anti-resonant propagation, strengthening the effect of the negative mass occurring under  = p = 1 is addressed.

Currently, there is a high interest in smart sensors and integrated composite materials in various industries such as construction, aviation, automobile, medical, information technology, communication, and manufacturing. Here, a new conceptual design for a force and temperature sensor system is developed by integrating fiber optic Bragg grating sensors embedded within composite materials, and a mathematical model is proposed that allows one to estimate strain and temperature based on signals obtained from optical Bragg gratings. This is important for understanding the behaviors of sensors under different conditions and for creating effective monitoring systems. Describing the strain gradient distribution, especially considering different materials with different values of Young's modulus, provides insight into how different materials respond to applied forces and temperature changes. The shape of the strain gradient distribution was obtained, which is a quadratic function with a maximum value of 1500 µ, with a maximum value at the center of the lattice and a symmetrically decreasing strain value with distance from the central part of the fiber Bragg grating. With axial strain at the installation site of the Bragg grating sensor under applied force values ranging from 10 to 11 N, the change in strain was linear. As a result of theoretical research, it was found that the developed system with fiber-optic sensors based on Bragg gratings embedded in composite materials is resistant to external influences and temperature changes.

Design process can be divided into stages of analysis and synthesis. This paper presents the application of the object-oriented technique to the synthesis as well as theoretical considerations concerning to design of gear size ranges. The synthesis consists in composition (aggregation) of single details into units – according to the rule: “from details up to general view”. The basics of the object-oriented synthesis were formulated. Furthermore, the consecutive stages of synthesis were formulated. The interactions between these stages were discussed. Some aspects were described in details e.g.: creation of interfaces for performance of the embodiment phase the designed artefact via CAD system drawing with specification (dimensions are still parametrically set). The final step of the procedure is creation of so called substantial (concrete) form of artifacts i.e. final assignment of dimensions which stored in the special data base. The final stage of the design process is issuing of technical documentation (technical drawings) created automatically via CAD system. The considerations are terminated by the list of advantages connected with the object-oriented approach to design (in comparison to the traditional way).

For this research we are selected three indicators of wheat: yield (t/ha), producer price (USD/t) and share of the harvested area under wheat in relation to the total land area of country (%). The mentioned indicators were analyzed for the period 2006-2021 in thirty-two European countries. The purpose of the research is to determine which of the mentioned indicators achieve average annual growth/decrease rates, what is the correlation between them, how European countries are grouped with their similarities and differences. The research examines the impact of the COVID-19 pandemic on the mentioned indicators in a two time phases: Phase I, before the pandemic (2006-2019); Phase II, during the pandemic (2020-2021). The methodological approach to the research topic involved the application of descriptive statistics, as the method of principal components analysis (abbr. PCA) with graphics. A positive correlation exists only between the yield of wheat and the share of the harvested area under wheat in the total area of the land (0.291). PCA method showed that countries are grouped differently depending on the observed indicator and the analyzed time phase.

Zeolite Y with microporous and hierarchical structure containing Ti–Ni and Ti–Co oxides were obtained as active photocatalysts. Different Ti amounts (5, 10% TiO2) were supported, followed by loading of Ni or Co oxides (5 %). The X-ray diffraction evidenced the presence of TiO2 as anatase. N2 adsorption-desorption results showed type IV isotherms, for hierarchical zeolite Y samples, and a combination of type IV and I isotherms, for zeolite Y samples. UV–Vis diffuse reflectance spectra showed shift of absorption band to visible with increasing of Ti loading and especially after Co and Ni addition. A significant effect of the support was evidenced for Ti and interaction with Co/Ni species. The zeolite Y support stabilizes Ti in the 4+ oxidation state while hierarchical zeolite Y support favored the formation of Ti 3+ species and oxidation of Co and especially of Ni to 3+. Photocatalytic activity, under UV and visible light, was evaluated in degradation of amoxicillin, used as a model test. The photocatalytic mechanism was investigated using ethanol, p-benzoquinone and KI as ·OH, ·O2- radicals and hole (h+) scavengers. The best results were obtained for the immobilized Ni-Ti species on hierarchical zeolite Y support.

Matrix metalloproteinases (MMPs) are often considered biomarkers of skin fibrosis. At the early stages of the pathological process, an elevation of their enzymatic activity causes significant changes in the composition of the extracellular matrix. MMPs secreted by immune cells facilitate their migration to the site of damage. Then, the immune cells eliminate the affected cells and biomolecules. Moreover, bidirectional changes in the activity of proteolytic enzymes, including MMPs, accompany wound healing. This study aimed to assess changes in the expression of Mmp2, Mmp3, and Mmp9 after treating the mice with laser therapy using the experimental model of bleomycin-induced skin fibrosis. Using immunohistochemistry, we characterized the histological features of scarred skin. We also analyzed changes in the expression of MMPs using real-time polymerase chain reaction before and after the irradiation with laser. We showed that treatment of the mice with CO2 laser partially normalized the histological features of scarred skin. We also noticed a decrease in the expression of Mmp2, Mmp3 (both p &lt; 0.05), and Mmp9 (p = 0.065) during scar healing. The obtained results suggest that normalization of skin homeostasis requires a control of MMPs activities via induction of their genes.

Voronoi entropy for the random patterns and patterns demonstrating various elements of symmetry are calculated. The symmetric patterns are characterized by the values of the Voronoi entropy very close to those inherent to random ones. This contradicts the idea that the Voronoi entropy quantifies the ordering of the seed points, constituting the pattern. The extension of the Shannon-like formula embracing symmetric patterns is suggested. Analysis of Voronoi diagrams enables revealing of the elements of symmetry of the pattern.

To meet the dual-carbon objective, China's economy needs to move from a carbon-intensive to a green economy. Green technology innovation and renewable energy development are key to promoting green economic growth. The study uses 2010–2022 provincial panel data from 30 Chinese provinces. The super-efficient SBM model measures the province's green economic growth index. A panel fixed-effects model is used to experimentally evaluate how green technology innovation and renewable energy development affect green economic growth. Green financing moderates and a panel threshold model tests the threshold effect of renewable energy development on green economic growth. The results demonstrate that (1) China's green economic growth is rising and has a "U" shape. (2) all selected variables significantly impact green economic growth. However, population density, government intervention, and industrial structure are inversely associated with GEG. Green economic growth is significantly boosted by the moderate role of green finance in the development of renewable energy and green technological innovation. (3) Renewable energy development has a single threshold non-linear effect on green economic growth, depending on its development level and green technological innovation. Considering China's current condition and research findings, this study examines the green energy transition to promote green economic growth and high-quality economic development. Meanwhile, puts forward some important policy recommendations.

Generally, stochastic functional differential equations (SFDEs) pose a challenge as they often lack explicit exact solutions. Consequently, it becomes necessary to seek certain favorable conditions under which numerical solutions can converge towards the exact solutions. This article aims to delve into the convergence analysis of solutions for stochastic functional differential equations by employing the framework of G-Brownian motion. To establish the goal, we find a set of useful monotone type conditions and work within the space Cr((−∞,0];Rn). The investigation conducted in this article confirms the mean square boundedness of solutions. Furthermore, this study enables us to compute both LG2 and exponential estimates.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.