Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

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.

The present study is aimed to determine the predicting role of objective (lifestyle) and subjective factors of middle-aged women’s psycho-emotional health such as their attitude towards parents, attachment and separation types. Women who are overloaded with professional and family roles have high stress level, their indicators of psychological well-being and emotional level decrease when they have to give everyday care to their elderly parents. (2) Methods: Sample consists of 146 women aged 38 to 56 ( =41.1, ó=3.5), married (70.5%) and divorced (29.5%), having children of 14-28 years old; giving everyday care to elderly parents for more than 1.5 yrs. Some live separately (62.3 %), or have to cohabitate with parents (37.7%). All women evaluate their life situation as difficult and manifest signs of high psycho-emotional stress. We used methods adapted for the Russian-speaking sample: getting socio-demographic information, an interview; Attachment style and Interpersonal Guilt Questionnaires (study 1); Psychological Separation Inventory, Purpose-in-Life Test, projective methods of incomplete sentences and metaphors` analysis (study 2), mathematical statistics. (3) Results: A number of factors and indicators of women`s psycho-emotional health decrease in the situation of role overload have been identified. Among the factors there are four main types of women’s attitudes towards parents: strong (anxious), distancing, ambivalent, normative closeness, predicting low indicators of psycho-emotional health: dependence on the others` opinions and feedbacks in making decisions, a lack of meaningfulness of life; reduced sense of control over life are showing the decrease. Anxiety about future and neurotic symptoms (increased demands on oneself, irritability, reduced emotional background) distinguish these respondents. (4) Conclusions: The study confirms that middle-aged Russian women`s psycho-emotional health depends on contextual factors (difficult role-overloaded lifestyle) and factors integrating women`s attitudes towards parents, attachment and separation types. Among the most important risk factors there are a difficult life situation, conflict separation type and gilt.

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.

Mechanisms for somatic chromosomal mosaicism (SCM) and chromosomal instability (CIN) are incompletely understood. During SNP-array molecular karyotyping and bioinformatic analyses of children with neurodevelopmental disorders and congenital malformations (n=612), we observed colocalizaion of regular chromosomal imbalances or copy number variations (CNV) with mosaic ones (n=47 or 7.7%). Analyzing molecular karyotyping data and pathways affected by CNV burdens, we proposed a mechanism for SCM/CIN, which had been designated as “chromohelkosis” (from the Greek chromosome ulceration/open wound). Briefly, structural chromosomal imbalances are likely to cause local instability (“wreckage”) at the breakpoints, which results either to partial/whole chromosome loss (e.g. aneuploidy) or elongation of duplicated regions. Accordingly, a function for classical/alpha satellite DNA (protection from the wreckage towards the centromere) has been hypothesized. Since SCM and CIN are ubiquitously involved in development, homeostasis and disease (e.g. prenatal development, cancer, brain diseases, aging), we have metaphorically (ironically) designate the system explaining chromohelkosis contribution to SCM/CIN as the cytogenomic “theory of everything” like the homonymous theory in physics inasmuch as it might explain numerous phenomena in chromosome biology. Recognizing possible empirical and theoretical weaknesses of this “theory”, we nevertheless believe that studies of chromohelkosis-like processes are required to understand structural variability and flexibility of the genome.

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.

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 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.

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.

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.

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.

First, we propose a scale-invariant modified gravity interacting with a neutral scalar inflaton and a Higgs-like SU(2) × U(1) iso-doublet scalar field based on the formalism of non-Riemannian (metric-independent) spacetime volume-elements. This model describes in the physical Einstein frame a quintessential inflationary scenario driven by the “inflaton” together with gravity-inflaton assisted dynamical spontaneous SU(2) × U(1) symmetry breaking in the post-inflationary universe, whereas SU(2) × U(1) symmetry remains intact in the inflationary epoch. Next, we find the explicit representation of the latter quintessential inflationary model with a dynamical Higgs effect as an Eddington-type purely affine gravity.

We present a brief history of the construction of models of the universe, followed by calculations of quantitative characteristics of basic geometric and kinematic properties of the Standard Cosmological Model ($\Lambda$CDM). Using the Friedmann equations of uniform space, we derive equations characterizing a $\Lambda$CDM model that describes a universe corresponding to current observational data. The equations take into account the effects of radiation and ultra-relativistic neutrinos. It is shown that the universe at very early and late stages can be described to sufficient accuracy by simple formulas. Certain important moments of cosmic evolution are determined: the times when densities of the gravitational components of the universe become equal, when they contribute equally to the gravitational force, when the accelerating expansion of space begins, and several others. The dependences of different distances on redshift and the scale factor of space are derived. The distance to the sphere that expands with the speed of light (the Hubble distance), and its current and future acceleration, are found. Concepts of a horizon, second inflation, and second horizon are discussed. We consider the remote future of the universe and the opportunity, in principle, of connection with extraterrestrial civilizations.

Ti and Ti alloys are materials usually used in contact with hard tissue for applications such as artificial joints and dental implants. Ti6Al4V is a very common alloy used for dental implants, owing to its good mechanical properties and corrosion resistance. Nevertheless, because of uncertainties regarding the toxicity of vanadium and its influence on the human body, other Ti alloys containing no vanadium and retaining suitable properties are used. In this work Ti6Al4V and Ti6Al7Nb were oxidized in a water solution of calcium acetate (Ca(CH3COO)2) and calcium glycerophosphate (Ca(PO4CH(CH2OH)2) by Plasma Electrolytic Oxidation (PEO) for 20 minutes and then were hydrothermally treated (HTT) in water (pH=7) and in potassium hydroxide (KOH) solution (pH=11) for 2 hours at 200°C in a pressurized reactor. The surface morphologies, elemental composition and phase components were characterized by Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS) and X-Ray Diffraction (XRD), respectively. The surface roughness was measured by Atomic Force Microscope (AFM) and thickness measurements were made by SEM and thickness gauge. Also, corrosion tests were made to evaluate the corrosion behavior of the two alloys. The aim of this study is to compare two viable Ti alloys, Ti6Al4V and Ti6Al7Nb, and to attain on their surface hydroxyapatite (HA) coating improving the osseointegration, as it simulates a human bone.

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.

Our primary objective is to construct a plausible unified model of inflation, dark energy and dark matter from a fundamental Lagrangian action first principle, where all fundamental ingredients are systematically dynamically generated starting from a very simple model of modified gravity interacting with a single scalar field employing the formalism of non-Riemannian spacetime volume-elements. The non-Riemannian volume element in the initial scalar field action leads to a hidden nonlinear Noether symmetry which produces energy-momentum tensor identified as a sum of a dynamically generated cosmological constant and a dust-like dark matter. The non-Riemannian volume-element in the initial Einstein-Hilbert action upon passage to the physical Einstein-frame creates dynamically a second scalar field with a non-trivial inflationary potential and with an additional interaction with the dynamically generated dark matter. The resulting Einstein-frame action describes a fully dynamically generated inflationary model coupled to dark matter. Numerical results for observables such as the scalar power spectral index and the tensor-to-scalar ratio conform to the latest 2018 PLANCK data.

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.

Aging induces numerous physiological alterations, with immunosenescence emerging as a pivotal factor. This phenomenon has attracted both researchers and clinicians, prompting pro-found questions about its implications for health and disease. Among the contributing factors, one intriguing actor in this complex interplay is human cytomegalovirus (CMV), a member of the herpesvirus family. Latent CMV infection exerts a profound influence on the aging immune system, potentially contributing to age-related diseases. This review delves into the intricate relationship between immunosenescence and CMV, revealing how chronic viral infection im-pacts the aging immune landscape. We explore the mechanisms through which CMV can im-pact both the composition and functionality of immune cell populations and induce shifts in in-flammatory profiles with aging. Moreover, we examine potential role of CMV in such pathol-ogies as cardiovascular diseases, cancer, neurodegenerative disorders, COVID-19, and Long COVID. This review underlines the importance of understanding the complex interplay be-tween immunosenescence and CMV. It offers insights into the pathophysiology of aging and age-associated diseases, as well as COVID-19 outcomes among the elderly. By unraveling the connections between immunosenescence and CMV, we gain a deeper understanding of aging's remarkable journey and the profound role that viral infections play in transforming the human immune system.

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function granting a fine tuning of immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro – or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

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.

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.

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.

The wealth of data obtained during the past 20 years using Laser-Induced Breakdown Spectroscopy (LIBS) indicates that the technique is very promising to detect small chemical contents of alloying elements. The potential of LIBS was looked more seriously during the past two decades or so as more data were obtained on Aluminum and steel to study the phenomena in the condition of local thermodynamic equilibrium and time-delay between a Q-switch laser and an intensified CCD camera. Since the past decade, some data on compounds were also shown to be useful in determining small concentrations of harmful elements. This manuscript is intended to show that the technique of LIBS performance is very promising in fields such as micro-machining, in alloying element analysis, surface cleaning and environmental applications even with lightweight spectrometers having a relatively low resolution, which can potentially be air-borne.

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.

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).

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.

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.

The COVID-19 pandemic has created unique challenges for people with comorbidities, including hereditary diseases and cancer cancers. Several studies have reported a link between the presence of disease-causing genetic variants and the outcome of the COVID-19 infection. In this study, we used clinical exome sequencing in a cohort of 840 COVID-19 patients to identify pathogenic and likely pathogenic genetic variants present in these individuals. While we did not identify any statistically significant differences in the overall burden of pathogenic variants between different patient groups, we discovered three known pathogenic alleles associated with hereditary cancer syndromes, including a frameshift mutation in MSH6 and two missense mutations in TP53. The patients carrying these mutations presented with different severity of the disease and outcome. Thus, a 58-year old male subject with an MSH6 mutation developed a severe form of COVID-19 that resulted in death, even though the patient had few pre-existing conditions and no evidence of malignant tumors. On the other hand, two female subjects carrying pathogenic TP53 variants successfully recovered from the disease despite suffering from various forms of cancer. Our results highlight the importance of personalized approaches to the diagnosis, management and treatment of COVID-19 in patients with specific genetic mutations. Further studies are needed to elucidate the complex relationship between these mutations and COVID-19.

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.

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.

This study compares lifestyles behaviour in Italian and Latvian university students, to assess if there are differences for sex, age, university or studies specialties. An online questionnaire investigating 8 lifestyle dimensions has been compiled by 156 (43,6 % females) from Italy and 105 from Latvia (82,9% females). Answers were collected between April and December 2020. Presence of smokers are negligible. The questionnaire showed to have a good internal consistency (Cronbach α =.929). On the total group, significant statistically differences were found for all the dimensions regarding age, sex, study specialty and university. Physical activity was associated with healthier lifestyles choices. Geographical-induced differences were found (eating and sleep behaviours, alcohol awareness) as well as socio-economic differences. Female students shown to be more stressed than males. Occupational wellness increased by age. Sport students shown more health awareness. Many of the differences found in the total group disappeared when comparing only sport students of the two university, showing females increasing their scores. This result can be explained by a masculinization effect of sport.

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.

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.

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

This study compares lifestyles behaviour in Italian and Latvian university students, to assess if there are differences for sex, age, university or studies specialties. An online questionnaire investigating 8 lifestyle dimensions has been compiled by 156 (43,6 % females) from Italy and 105 from Latvia (82,9% females). Answers were collected between April and December 2020. Presence of smokers are negligible. The questionnaire showed to have a good internal consistency (Cronbach α =.929). On the total group, significant statistically differences were found for all the dimensions regarding age, sex, study specialty and university. Physical activity was associated with healthier lifestyles choices. Geographical-induced differences were found (eating and sleep behaviours, alcohol awareness) as well as socio-economic differences. Female students shown to be more stressed than males. Occupational wellness increased by age. Sport students shown more health awareness. Many of the differences found in the total group disappeared when comparing only sport students of the two university, showing females increasing their scores. This result can be explained by a masculinization effect of sport.

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.

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.

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 dynamics of the main photosynthetic structures is studied by mathematical modeling methods in this article. Chlorophyll portion variability in phytoplankton and the formation of energy-intensive substances in the process of photosynthesis underlie the models. These cellular components are considered in terms of their participation in the growth of specific biomass. Computational experiments are presented that simulate various degrees of environmental friendliness. The corresponding functions are built in accordance with seasonal fluctuations throughout the year in the Far East region of Russia. The stability of model solutions in long-term dynamics is also investigated. The models were tested for biological adequacy and their effectiveness was compared. For the model selected as a result of the comparison, the optimal control problem has been formulated and solved. It is shown that in this way it is possible to reduce the space of the initial components of the model system.

The production of particles outside the region of nucleon-nucleon kinematics due to interactions involving dense cold clusters of quark-gluon matter in nuclei is calculated. The possibility of observing this process in the region of central rapidities and large transverse momenta in heavy ion collisions at low energies with MPD detector at the NICA collider has been demonstrated.

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.

The paper presents an assessment of the growth dynamics of the modal fir plantations in the Lower Angara region. At present, a vast area of fir forests in the Lower Angara region is characterised by a significant decrease in sustainability due to periodic forest fires, insect pests outbreaks and diseases, which lead to their natural degradation and death. However, the intensity of coniferous stand growth in certain forest site characteristics persists in the long term. Therefore, creating regression models of forest growth and development involving the identification of site conditions is very important both from a practical point of view and for environmental monitoring. The materials of the mass inventory of 3491 stands served as the initial data for studying the processes of fir plantations natural growth. The Hoerl Model function is suitable for the best approximation of stand growth since it is characterised by high levelling factor (from 0.970 to 0.987) and a small standard error (not exceeding 7%). As a result of the research, there have been constructed sketches of the growth rate tables for the modal Siberian fir stands of the third bonitet class of the forb and mossy groups of forest types.

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

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.

Sepsis is a life-threatening complication of an infectious process that results from excessive and uncontrolled activation of the host's pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of the Gram-negative bacteria outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed. This review summarizes data on LPS-binding proteins from marine invertebrates (ILBPs), that inhibit LPS toxic effects, and are of interest as potential drugs for the sepsis treatment. The structure, physicochemical properties, antimicrobial and LPS-binding/neutralizing activity of these proteins and their synthetic analogues are considered in details. Problems that arise during clinical trials of potential anti-endotoxic drugs are discussed.

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.

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.

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.

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.

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.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

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.

The EU has set the ambitious target of raising the share of EU energy consumption produced from renewable resources to 32% by 2030 with a target of climate neutrality by 2050. The aim of this paper is to assess the role of biomass usage in the context of these targets. The paper identifies progress made between 2013–2022 by focusing on a selection of EU countries. The largest bio-energy increments of 130PJ, 77PJ and 60PJ were reported for Poland, Sweden, and the Nether-lands. This study valuates the crucial role in co-generation and heat in EU regions, with biomass usage between 55-80% of the combined heat and power (CHP) energy in Nordic countries. The future perspectives for bioenergy based on EU policies, biomass resources and technical issues were addressed. The EU possess around 9% of the global biomass supply, ensuring a certain level of biomass resource dependence. Thus, the biomass usage demand in energy production, non-energy sectors and transport is expected to rise leading to increments of 13%-76% on biomass imports. It appears that bioenergy development is mostly limited by economic issues and uneven support for bioenergy in different EU countries as well as environmental issues. The study shows a promising and sustainable potential of bioenergy in the EU as a renewable energy source while minimizing negative impacts on the environment and the economy. By 2050, liquid biofuels are likely to be increasingly used in the transport sector. Non-energy sector usage of biomass is still in an early stage of development, except for the pulp and paper industry, and significant use of biomass in non-energy sectors seems unlikely in the near future.

The problem of effective immobilization of liquid radioactive waste (LRW) is key to the successful development of nuclear energy. The possibility of using magnesium potassium phosphate (MKP) compound for LRW immobilization on the example of nitric acid solutions containing actinides and rare earth elements (REE), including high level waste (HLW) surrogate solution is considered in the research work. Under the study of phase composition and structure of the MKP compounds obtained by the XRD and SEM methods, it was established that the compounds are composed of crystalline phases - analogues of natural phosphate minerals (struvite, metaankoleite). The hydrolytic stability of the compounds was determined according to the semi-dynamic test GOST R 52126-2003. Low leaching rates of radionuclides from the compound are established, including a differential leaching rate of ²³⁹Pu and ²⁴¹Am - 3.5 × 10^-7 and 5.3 × 10^-7 g/(cm²∙day). As a result of the research work it was concluded that the MKP compound is promising for LRW immobilization and can become an alternative material combining the advantages of easy implementation of the technology like cementation and the high physical and chemical stability corresponding to a glass-like compound.

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.

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.

Scavenging of atmospheric trace gases has been recognized as one of the lifestyle-defining capabilities of microorganisms in terrestrial polar ecosystems. Several metagenome-assembled genomes of as-yet-uncultivated methanotrophic bacteria, which consume atmospheric CH4 in these ecosystems, have been retrieved in cultivation-independent studies. In this study, we isolated and characterized a representative of these methanotrophs, strain D3K7, from a subarctic soil of Northern Russia. Strain D3K7 grows on methane and methanol in a wide range of temperatures, between 5 and 30°C. Weak growth was also observed on acetate. The presence of acetate in the culture medium stimulated growth at low CH4 concentrations (~100 p.p.m.v.). The finished genome sequence of strain D3K7 is 4.15 Mb in size and contains about 3700 protein-encoding genes. According to the result of phylogenomic analysis, this bacterium forms a common clade with metagenome-assembled genomes obtained from the active layer of a permafrost thaw gradient in Stordalen Mire, Abisco, Sweeden, and the mineral cryosol at Axel Heiberg Island in the Canadian high Arctic. This clade occupies a phylogenetic position in between characterized Methylocapsa methanotrophs and representatives of the as-yet-uncultivated Upland Soil Cluster Alpha (USCα). As shown by the global distribution analysis, D3K7-like methanotrophs colonize mostly northern terrestrial ecosystems, such as polar deserts, subarctic soils, permafrost environments, but also occur in boreal peatlands or high-latitude habitats.

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.

This material presents the results of a comparative analysis of the fungal diversity in the world system of microbial culture collections on one side with a variety of known fungal producers on the other side. The main VKM databases used are Fungal DC and Metabolites of Fungi, the central point of analysis - the fungal ability to synthesize promising metabolites for applied use. It indicates that the option of obtaining new promising strains from the collection funds is still underestimated by the scientific community. In particular it is shown that not more than 3% of the total fungal species fund contained in culture collections are used practically. The database Fungal DC developed in VKM is available on-line in www.vkm.ru and www.mycobank.org. It is possible their use will considerably expand the range of studied strains and lead to the acquisition of new scientifically significant data.

The antimicrobial properties of the new strains of microorganisms isolated from natural sources of various ecological niches in the Moscow Region and the Republic of Tatarstan were studied. An antifungal activity of isolates was established in a test culture of toxin-producing microscopic fungi that cause various plant diseases: Fusarium oxysporum, Aspergillus flavus, Penicillium spp. and Candida albicans. Of the 46 studied microorganisms, 4 isolates (Bacillus subtilis, Propionibacterium freudenreichii, Lactobacillus plantarum and Streptomyces spp.) showed an ability to produce biologically active metabolites with a pronounced antimicrobial potential. This is promising in the growth and protection of the Scots pine, pedunculate oak and small-leaved linden forest crops from diseases caused by fungi Lophodermium pinastri Chev. and Microsphaera alphitoides stimulation. Based on selected isolates, a Bacterial product LRV composition has been developed. A Scots pine, pedunculate oak and small-leaved linden seedlings single and double foliar treatment with Bacterial product LRV at a concentration of 10 ml/l led to an increase in the growth of an above-ground part by 31.8, 51.9 and 25.4 %, respectively, and an underground part – by 25.0, 37.2 and 25.7 %, respectively, compared with the control. The weight of seedling at the end of the study exceeded the control variant by an average of 26.0, 44.0 and 78.0 %, respectively. A use of a plant protection Bacterial product LRV did not have a significant effect on a powdery mildew and Schütte disease damage to forest crops. A Biogeosystem Technique methodology has been developed to improve a long-term forest growing.

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

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).

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).

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.

Current article presents the study of psychological wellbeing of adolescents (n=168, age 15-17) gifted in math, humanities and sports and educated in advanced programs for gifted children. Theoretical framework of this study is eudemonic concept of psychological wellbeing by C. Ryff. Psychological wellbeing is measured with Ryff wellbeing scales in Russian adaptation by L.V. Zhukovskaya and E.G. Troshikhina. The study is aimed at understanding differences in psychological wellbeing of gifted teenagers connected to gender and type of giftedness. The results suggest that general wellbeing score did not differ for adolescents with different types of giftedness or of different genders. Separate components of psychological wellbeing, such as purpose in life and self-acceptance, are influenced by activity connected to the talent. Gender differences are subjected to age-specific trends of personal development in adolescence. Type of giftedness might reinforce these trends.

Background/Objectives: An age-associated increase in serum levels of sex hormone binding globulin (SHBG) is considered to be one of the factors leading to the development of male hy-pogonadism. Aim of the study: to study the relationship between the concentration of sex hor-mone-binding globulin in the blood serum and the age of the man, the level of total and free testosterone. A single-center retrospective cross-sectional study was conducted. The results of laboratory tests of 162 male patients aged from 18 to 56 years (median - 34 years) were analyzed. Methods: The level of total testosterone and sex hormone binding globulin (SHBG) was deter-mined by chemiluminescent immunoassay. The level of free testosterone was determined by the calculation method according to Vermeullen. Statistical analysis was performed using SPSS Sta-tistics v23. Results: Correlation analysis did not reveal a significant relationship between age and SHBG levels, as well as between age and total testosterone levels. Serum SHBG concentration showed a significant (p

Photothrombotic stroke (PTS) stimulates the level of N- and C-terminal fragments of Amyloid precursor protein (APP) growth in the cytoplasm of ischemic penumbra cells not earlier but at 24 hours. Here we have shown that APP fragments are visualized in thin unmyelinated fibers of neurons, in containing mitochondria large fibers and in synapses but absent in the nuclei. At 24 hours after PTS, some elements of the destroyed tissue accumulated a significant amount of APP protein. The level of ADAM10 α-secretase decreased on the first day after PTS in the rat brain cortex and ADAM-10 co-localized with the lipid raft marker caveolin-1. PTS caused no changes in the level of β-secretase BACE1 either on the first day after PTS or in the early recovery period. The expression of proteins of the γ-secretase complex: presenilin-1 and nicastrin increased in astrocytes, but not in penumbra neurons after PTS. The β-secretase inhibitor LY2886721 did not affect the infarct size of the mouse cerebral cortex and the level of apoptosis of cells in the perifocal region after PTS. Whereas the inhibitor of γ-secretase DAPT reduced the expression of glial fibrillary acidic protein (GFAP) in astrocytes, prevented the growth of apoptosis of mouse cerebral cortex cells reducing the infarct volume on the 7th and 14th days after PTS. DAPT may be considered as a drug for stroke therapy.

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.

Aims: Heart failure (HF) is frequently accompanied by atrial fibrillation (AF), a combination that worsens the outcomes of both diseases. Despite advances in the treatment of AF, it remains a serious and unsolved problem for clinicians and researchers. The aim of this study was to examine risk factors for incidents of paroxysmal and persistent AF in patients having heart failure with mid-range ejection fraction (HFmrEF). Methods. Overall, 71 patients with HFmrEF and non-valvular AF, including paroxysmal and persistent types, were enrolled in this study. As a control group, 42 HFmrEF patients without AF were also enrolled. All patients underwent detailed physical examination, including resting electrocardiography, echocardiography, and 24-hour ambulatory Holter monitoring. Levels of the inflammation markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured by ELISA and expressed as odds ratios. Results: We show that paroxysmal AF was associated with higher diastolic blood pressure, whereas both paroxysmal and persistent forms of AF were associated with more frequent occurrence of hypertensive crisis episodes and greater body mass index. Progression from paroxysmal to persistent AF was associated with significant ventricular remodeling. Persistent and paroxysmal AF were associated with higher levels of inflammatory markers when compared to HFmrEF patients having no AF. In addition, TGF-1 was significantly increased in HFmrEF patients having persistent but not paroxysmal AF. Conclusions: Occurrence of AF, first paroxysmal and then persistent, in HFmrEF patients is associated with left ventricular remodeling and the appearance of systemic inflammatory and fibrotic markers. Changes in those parameters may be indicators by which to identify patients at increased risk of atrial fibrillation. Further studies are needed to determine the prognostic validity of these markers.

(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.

Design process can be divided into stages of analysis and synthesis. This paper presents the application of the object-oriented technique to the analysis as well as theoretical considerations concerning to design of gear size ranges. This analysis consists in decomposition of the designed artefact (a gear) according to the rule “from general to details view”. The basics of the object-oriented analysis were formulated. Furthermore, design phases and the objects related to theses phases were discussed. The following models have been considered: hierarchical model, entity-relationship model, data-flow model and object model. Analysis is additionally connected with interactions between particular design phases.

The debate about the meaning of life in the literature has been around for a while and portraits a fundamental human need to find a personal path of existence. The meaning of life phenomenon purpose lies in its impact on the psychological wellbeing. Knowing your purpose in life can make it more structured and in balance, therefore more meaningful and comprehensible. However, in the existing body of the academic literature meaning of life is discussed more from the philosophic perspective rather than a practical area, which is not helping to solve the global issues of increasing mental health problems. When social and emotional wellbeing is being affected, it is urgent to apply a practical approach to effectively overcome these states. Introduction of a new, holistic meaning of life model is an attempt to offer a practical solution for society to maintain their mental health through awareness of their life’s purpose. Previously in the pilot study (Dombrovskis, 2017) in a sample group of 100 citizens of Latvia who self-reported being in a crisis situation at the given moment, using qualitive analysis the first component for the model structure was identified – antecedent. In our research antecedent is defined as something that triggers certain action, so in crisis situation person can regain a structure and stability in life. We found 8 different antecedents that trigger behavior of those affected by crisis: achievements; power; success; development; freedom; uniqueness; interesting life and fleeing. To continue to explore other components for our model in the setting of Latvia, this study aims to investigate the demographic and personality related variables that may serve as antecedents and as such become one of component in our model structure. The study used a sample of residents of Latvia representing the total population of 1,110 respondents (633 women, 57%, and 477 men, 43%) who have completed the self-assessment questionnaire Meaning of life scale (MOLS) (online and frontally) designed by the authors on their satisfaction with different factors regarding the meaning of life. Average age of respondents (M=33.88; SD=8,527) varied from 18 to 67. The exploratory and confirmatory analysis confirms the data regarding existence of totally 16 factors: 8 antecedents identified in the pilot study and 8 new antecedents identified in the present study - family relations; level of income; relations with friends/acquaintances; state of health; organization of free time; career growth (achievements); sexual life quality and quality of education. Findings confirm a model’s structure to be complex phenomenon consisting of various components. However, findings suggest that more research should be done to fill the following gaps: 1) identify actions, which are triggered by 16 antecedents; 2) figure out F1, F2 and F3 factor role in the model structure.

We applied evolutionary game theory to extend a resource constrained security game model for confidentiality attacks in an Advanced Metering Infrastructure (AMI), which is a component of IoT-enabled Smart Grids. The AMI is modelled as a tree structure where each node aggregates the information of its children before encrypting it and passing it on to its parent. As a part of the model, we developed a discretization scheme for solving the replicator equations. The aim of this work is to explore the space of possible behaviours of attackers and to develop a framework where the AMI nodes adaptively select the most profitable strategies. Using this model, we simulated the evolution of a population of attackers and defenders on various cases resembling the real life implementation of AMI. We discuss in depth how to enhance security in AMI using evolutionary game theory either by a priori analysis or as a tool to run dynamic and adaptive infrastructure defence.

SLM Additive Manufacturing has demonstrated great potential for aerospace applications when structural elements of individual design and/or complex shape need to be promptly supplied. 3D-printable AlSi10Mg (RS-300) alloy is widely used for the fabrication of different structures in aerospace industry. The importance of the evaluation of residual stresses that arise as a result of complex 3D-printing process thermal history is widely discussed in literature, but systematic assessment remains lacking for their magnitude, spatial distribution, and comparative analysis of different evaluation techniques. In this study we report the results of a systematic study of residual stresses in a 3D-printed double tower shaped samples using several approaches: the contour method, blind hole drilling laser speckle interferometry, X-ray diffraction, and Xe pFIB-DIC micro-ring-core milling analysis. We show that a high level of tensile and compressive residual stresses is inherited from SLM 3D-printing and retained for longer than 6 months. The stresses vary over a significant proportion of the material yield stress. All residual stress evaluation techniques considered returned comparable values of residual stresses even regardless of dramatically different dimensional scales from millimeters for the Contour Method down, laser speckle interferometry and XRD and down to small fractions of a mm (70 μm) for Xe pFIB-DIC ring-core drilling. The use of residual stress evaluation is discussed in the context of optimizing the printing strategy to enhance the mechanical performance and long-term durability.

This article presents an innovative approach to the design of a safe adaptive backstepping control system. Tailored specifically for underactuated marine robots, the system utilizes simple sensors for enhanced practicality and efficiency. Given their operation in diverse oceanic environments fraught with various sources of uncertainties, ensuring the system's safe and robust behavior holds paramount importance in the control literature. To address this concern, this paper introduces a control strategy designed to ensure robustness at both the kinematic and dynamic levels. By emphasizing the compensation for the system uncertainties, the design integrates a straightforward fuzzy system structure. To further ensure the system's safety, a funnel surface is defined, followed by the design of a suitable nonlinear sliding surface as a function of the funnel and tracking error. Specifically leveraging the Lyapunov function, the study formally establishes the Semi-globally Practically Finite-time Stability of the closed-loop system, validated through simulations conducted on underactuated marine robots.

This joint experimental-theoretical work focuses on molecular and photophysical properties of the spiropyran-containing amphiphilic molecule in organic and aqueous solutions. Being dissolved in tested organic solvents, the system demonstrates positive photochromism, i.e. upon UV stimulus the colorless spiropyran form is transformed into colorful merocyanine isomer. However, aqueous solution of the amphiphile possesses a negative photochromism: the orange-red merocyanine form turns to be thermodynamically more stable in water, and both UV and vis stimuli lead to the partial or complete photobleaching of the solution. The explanation of this phenomenon is given on the basis of density functional theory calculations and classical modeling including thermodynamic integration. The simulations reveal that stabilization of merocyanine in water proceeds with the energy of ca. 70 kJ mol−1, and that the Helmholtz free energy of hydration of merocyanine form is 100 kJ mol−1 lower as compared to the behavior of SP isomer in water. The explanation of such a difference lies in the molecular properties of the merocyanine: after ring-opening reaction this molecule transforms into a zwitterionic form, as evidenced by the electrostatic potential plotted around the opened form. The presence of three charged groups on the periphery of a flat conjugated backbone stimulates the self-assembly of merocyanine molecules in water, ending up with the formation of elongated associates with stack-like building blocks, as shown in molecular dynamics simulations of the aqueous solution with the concentration above critical micelle concentration. Our quantitative evaluation of the hydrophilicity switching in spiropyran/merocyanine containing surfactants may prompt the search for new systems, including colloidal and polymeric ones, aiming at remote tuning of their morphology, which could give new promising shapes and patterns for the needs of modern nanotechnology.

We present a case report of a 26-years-old female suffering from Coffin Siris Syndrome, who underwent orthodontic treatment and surgery to solve her malocclusion and improve her aes-thetics and functional occlusion. Methods: The presurgical phase involved multibracket self-ligating attachments, Damon prescription. The patient underwent maxillofacial surgery to correct the severe skeletal malocclusion and relocate the bone bases in the right relationship. The post-surgical orthodontic treatment was performed to complete the alignment. Results: The pa-tient improved her aesthetics and functional abilities. Conclusions: Syndromic patients can un-dergo orthodontictreatment if comorbidities and collaboration allow it. Support and collaboration of families and psychotherapists must be considered, but clinical cases of syndromic patients can be faced and solved. Obviously, each syndromic patient is considered unique, and the risk-benefit ratio must be correctly assessed for each one.

In this study, 10%PTFE/PEEK blend were modified by potassium titanate whisker (PTW) and chopped glass fiber (GF), respectively. The blends were prepared by three-screw extruder. Through the investigation of thermal stability, tribological properties, mechanical properties and rheological behavior, the effects of reinforcing agents were determined. The results illustrated that the mechanical properties of 10%PTFE/PEEK blend can be dramatically improved by adding reinforcing agent of PTW or GF, and the reinforcing effect of GF was especially obvious. As for tribological properties, 1% addition was the best proportion. The friction coefficient and wear rate of the blend with 1% PTW were 0.283 and 4.97 × 10^-6 mm³/N · m, which decreased by 7.2% and 21% compared with those of the blend without reinforcing agent.

In a 24-week-long experiment, 31 rats were assigned to one of 3 groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. Both groups experienced significantly increased caloric intake but did not gain weight above the Control group level. Adipocytes in subcutaneous and visceral adipose depots of both groups had smaller size compared to control and higher density in tissue. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated that in both experimental groups high tissue respiration is associated with better biochemical profile and closer to control adipose tissue morphology. Increased tissue respiration in adipose depots could be an important mechanism of resilience to excessive caloric intake.

We present a new analytical method to find the asymptotic stable equilibria states based on the Markov chain technique. We reveal this method on the SIR-type epidemiological model that we developed for viral diseases with long-term immunity memory pandemic. This is a large-scale model containing 15 nonlinear ODE equations, and classical methods have failed to analytically obtain its equilibria. The proposed method is used to conduct a comprehensive analysis by a stochastic representation of the dynamics of the model, followed by finding all asymptotic stable equilibrium states of the model for any values of parameters and initial conditions.

The development of multidrug resistance by pathogenic bacteria and yeast is a significant medical problem that needs to be addressed. One possible answer could be the combined use of antibiotics and silver nanoparticles, which have different mechanisms of antimicrobial action. Nanoparticles can be combined with antifungal agents in the same way. Biogenic silver nanoparticles synthesized using environmentally friendly technology using extracts of biologically active plants are an effective nanomaterial that needs to be comprehensively investigated for implementation into medical practice. In this study, the synergistic effects arising from their combined use with antibiotics and fungicides against various bacteria and yeasts, included in the ESKAPE list, were studied. Effective concentrations of substances were established, recommendations for the studied pathogenic species were presented and the effect of destruction of the bacterial membrane was illustrated. The most significant synergistic effect was manifested in pathogenic candida and brewer's yeast.

We have found a region in the northwestern Japan Sea near the Subpolar Front where mesoscale eddies regularly form and circulate. The anticyclonic eddy with a strong dynamic feature, vertically extended to the bottom (~3500 m), multilayer core structure and extreme values of temperature and salinity was sampled there in the cruise in May 2004. The altimetry-based eddy tracking showed that it had a life span of nine months with the size reaching 120 km. CTD observational data were used to explore the eddy’s features and vertical structure. The eddy had a multilayer core with different thermohaline characteristics which could be originated by eddy interaction with the surrounding waters during its life. The evolution of the eddy has been studied and analyzed with the help of altimetry-based Lagrangian indicators of water motion. Performing the particle-tracking numerical experiments, we computed the Lagrangian maps that contain information on the origin of water inside the eddy core and its ‘age’ on every day of the eddy’s life. Inspecting daily-computed Lagrangian maps, we documented the essential events in the evolution of the eddy including its formation, splitting, merger, entrainment and detrainment of water, erosion and eventual decay. All these observations have been verified with the infrared satellite images. The new Lagrangian technique has been applied to calculate day by day the content of water of various origin (coastal, subtropical and subarctic) entrained into the eddy core. It has been found that the surface core has been filled mainly with subtropical water originated in the southern flank of the Subpolar Front. The episodes with cardinal changes of ratio of different water types have been recorded and verified with the infrared satellite images and maps of the origin of water inside the eddy core.

Methylation of cytosines at CpG sites in DNA, carried out by de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed by physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduce Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription.

The present paper reports an exact approach quantifying the electromagnetic contribution to the anomalous magnetic moment occurring in isolated system comprised of non-composite particle carrying elementary electric charge. Essential averaging procedure and regularization of the electromagnetic field potentials necessary when quantifying the electromagnetic self-interactions and when deriving equations of motion without singularities and obeying the conservation laws are thoroughly discussed. The study shows that the dynamics of the considered system is associated to unique classical transcendental equations of motion satisfied by the particle's velocity and the electromagnetic contribution to the anomalous $g$-factor known from the quantum electrodynamics. The equations of motion lead to an exact analytical expression for the anomalous $g$-factor that provides more accurate result than that calculated with the aid of quantum electrodynamics. It matches the experimentally measured value reported in the literature to a one part per trillion. We obtain a_e=0.00115965218000(65) thus reveling the potential of non-perturbative, non-probability methods in predicting the electron's anomalous g-factor.

G-quadruplex, a unique secondary structure in nucleic acids found throughout human genome elicited widespread interest in the field of therapeutic research. Being present in key regulatory regions of oncogenes, G-quadruplex structure regulates transcription, translation, splicing, telomere stability etc. Changes in its structure and stability lead to differential expression of oncogenes causing cancer. Thus, targeting G-Quadruplex structures with small molecules/ other biologics has shown elevated research interest. Covering previous reports, in this review we try to enlighten the facts on the structural diversity in G-quadruplex ligands aiming to provide newer insights to design first-in-class drugs for the next generation cancer treatment.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.