Assessment of the effect of 21-day head-down bed rest on the cardiovascular system by blood protein composition.

Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR.

Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers.

Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease.

Single-Stage Microfluidic Synthesis Route for BaGdF5:Tb3+-Based Nanocomposite Materials: Synthesis, Characterization and Biodistribution.

Rare-earth-doped nanoscaled BaGdF5 is known as an efficient contrasting agent for X-ray micro-CT and NMR as well as a promising candidate for X-ray photodynamic therapy, thereby opening an opportunity for theragnostic applications. Conventional synthesis of Ln-doped BaGdF5 consider a long-lasting batch procedure, while a conjugation with photosensitizer usually implies a separate stage requiring active mixing. To the best of our knowledge, in this work, we for the first time obtain BaGdF5:Tb3+ nanophosphors in a microfluidic route at temperatures as low as 100 °C while decreasing the time of thermal treatment down to 6 min. The proposed synthesis route allows for the obtaining of single-phase and monodisperse BaGd1-xF5:Tbx3+ nanoparticles with an averaged particle size of ca. 7-9 nm and hydrodynamic radius around 22 nm, as estimated from TEM and DLS, respectively. In addition, X-ray-excited optical luminescence has been recorded in situ for the series of nanophosphors synthesis with varied flow rates of Tb3+ and Gd3+ stock solutions, thereby anticipating a possible application of microfluidics for screening a wide range of possible co-dopants and reaction conditions and its effect on the optical properties of the synthesized materials. Moreover, we demonstrated that BaGd1-xF5:Tbx3+@RoseBengal conjugates might be obtained in a single-stage route by implementing an additional mixer at the synthesis outcome, namely, by mixing the resulting reaction mixture containing nanoparticles with an equivalent flow of photosensitizer aqueous solution. In vitro cytotoxicity test declares moderate toxicity effect on different cell lines, while the results of flow cytometry indirectly confirm cellular uptake. Finally, we report long-term biodistribution monitoring of the synthesized nanocomposites assessed by X-ray micro-CT in the in vivo experiments on balb/c mice, which depicts an unusual character of agents' accumulation.

Comparison of Anxiety and Depression Rates in Russian Health Care Professionals in 2020 and 2023.

BACKGROUND: The COVID-19 pandemic had a significant impact on the mental health of medical personnel worldwide, leading to increased levels of anxiety and depression. This study aimed to compare anxiety and depression levels among healthcare workers during the initial wave of the pandemic in April-May 2020 and the post-pandemic period in January-May 2023 in Russia. METHODS: Data from two similar surveys conducted during the respective periods were combined, and a case-control matching approach was used to ensure compatibility between the two samples. The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression levels. RESULTS: The mean total score for Anxiety subscale in 2020 was 4.126 (SD = 3.042), and in 2023 it increased to 6.632 (SD = 4.132) (F=20.751, df (1, 172), p<0.001, η2p=0.108). Similarly, the mean total score for Depression subscale increased from 3.253 (SD = 2.616) in 2020 to 4.115 (SD = 2.939) in 2023 (F=4.177, df (1, 172), p=0.043, η2p=0.024). The proportion of healthcare workers with higher-than-normal levels of anxiety increased from 16.09% in 2020 to 39.08% in 2023, whereas the effect size for depression remained negligible. The increase in anxiety severity was contrary to previous longitudinal studies showing a decrease in anxiety and depression levels after an initial increase during the pandemic. CONCLUSION: The increase in anxiety and depression levels in healthcare workers in 2023 may be attributed to other factors like "special military operation" in Ukraine, sanctions, and announcement of partial mobilization in September 2022. These factors could be perceived as more serious adverse factors, leading to increased anxiety levels.

Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota.

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.

Courtship suppression in Drosophila melanogaster: The role of mating failure.

Drosophila melanogaster is a popular model organism in the study of memory due to a wide arsenal of methods used to analyze neuronal activity. The most commonly used tests in research of behavioral plasticity are shock avoidance associated with chemosensory cues and courtship suppression after mating failure. Many authors emphasize the value of courtship suppression as a model of behavior most appropriate to natural conditions. However, researchers often investigate courtship suppression using immobilized and decapitated females as targets of courtship by males, which makes the data obtained from such flies less valuable. In our study, we evaluate courtship suppression towards immature mobile non-receptive females after training with mated or immature females combined with an aversive stimulus (quinine). We have shown that the previously described mechanisms of courtship suppression, as a result of the association of the courtship object with the repellent, as well as due to increased sensitivity to the anti-aphrodisiac cVA after mating failure, are not confirmed when immature mobile females are used. We discuss the reasons for the discrepancies between our results and literature data, define the conditions to be met in the courtship suppression test if the aim is to analyze the natural forms of behavioral plasticity, and present data on the test modifications to approximate conditions to natural ones.

Synthesis, Characterization and Biodistribution of GdF3:Tb3+@RB Nanocomposites.

Herein we report the development of a nanocomposite for X-ray-induced photodynamic therapy (X-PDT) and computed tomography (CT) based on PEG-capped GdF3:Tb3+ scintillating nanoparticles conjugated with Rose Bengal photosensitizer via electrostatic interactions. Scintillating GdF3:Tb3+ nanoparticles were synthesized by a facile and cost-effective wet chemical precipitation method. All synthesized nanoparticles had an elongated "spindle-like" clustered morphology with an orthorhombic structure. The structure, particle size, and morphology were determined by transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) analysis. The presence of a polyethylene glycol (PEG) coating and Rose Bengal conjugates was proved by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and ultraviolet-visible (UV-vis) analysis. Upon X-ray irradiation of the colloidal PEG-capped GdF3:Tb3+-Rose Bengal nanocomposite solution, an efficient fluorescent resonant energy transfer between scintillating nanoparticles and Rose Bengal was detected. The biodistribution of the synthesized nanoparticles in mice after intravenous administration was studied by in vivo CT imaging.

Blood Plasma Proteins Associated With Heart Rate Variability in Cosmonauts Who Have Completed Long-Duration Space Missions.

The study presents the results of evaluating the changes in the concentrations of blood plasma proteins associated with heart rate variability (HRV) in cosmonauts who have completed space missions lasting about 6months. The concentrations of 125 proteins were quantified in biological samples of the cosmonauts' blood plasma. The subgroups of proteins associated with the physiological processes of the HRV autonomic regulation were identified using bioinformatic resources (Immunoglobulin heavy constant mu, Complement C1q subcomponent subunit C, Plasma serine protease inhibitor, Protein-72kDa type IV collagenase, Fibulin-1, Immunoglobulin lambda constant 3). The concentration of these proteins in the blood plasma before the flight, and the dynamics of concentration changes on the 1st and 7th days of the post-flight rehabilitation period differed in the groups of cosmonauts with a predominance of sympathetic or parasympathetic modulating autonomous influences. The dynamics of changes in the concentrations of the identified set of proteins reveal that in cosmonauts with a predominance of sympathetic modulating influences, the mechanisms of autonomic regulation are exposed to significant stress in the recovery period immediately after the completion of the space mission, compared with the cosmonauts with a predominance of parasympathetic modulating influences.

BaGdF5 Nanophosphors Doped with Different Concentrations of Eu3+ for Application in X-ray Photodynamic Therapy.

X-ray photodynamic therapy (XPDT) has been recently considered as an efficient alternative to conventional radiotherapy of malignant tissues. Nanocomposites for XPDT typically consist of two components-a nanophosphor which re-emits X-rays into visible light that in turn is absorbed by the second component, a photosensitizer, for further generation of reactive oxygen species. In this study, BaGdF5 nanophosphors doped with different Eu:Gd ratios in the range from 0.01 to 0.50 were synthesized by the microwave route. According to transmission electron microscopy (TEM), the average size of nanophosphors was ~12 nm. Furthermore, different coatings with amorphous SiO2 and citrates were systematically studied. Micro-CT imaging demonstrated superior X-ray attenuation and sufficient contrast in the liver and the spleen after intravenous injection of citric acid-coated nanoparticles. In case of the SiO2 surface, post-treatment core-shell morphology was verified via TEM and the possibility of tunable shell size was reported. Nitrogen adsorption/desorption analysis revealed mesoporous SiO2 formation characterized by the slit-shaped type of pores that should be accessible for methylene blue photosensitizer molecules. It was shown that SiO2 coating subsequently facilitates methylene blue conjugation and results in the formation of the BaGdF5: 10% Eu3+@SiO2@MB nanocomposite as a promising candidate for application in XPDT.

Visualization of different anatomical parts of the enucleated human eye using X-ray micro-CT imaging.

Micro-CT visualization allows reconstruction of eye structures with the resolution of light microscopy and estimation of tissue densities. Moreover, this method excludes damaging procedures and allows further histological staining due to the similar steps in the beginning. We have shown the feasibility of the lab-based micro-CT machine usage for visualization of clinically important compartments of human eye such as trabecular outflow pathway, retina, iris and ciliary body after pre-treatment with iodine in ethanol. We also identified the challenges of applying this contrasting technique to lens, cornea, and retina and proposed alternative staining methods for these tissues. Thereby this work provides a starting point for other studies for imaging of human eyes in normal and pathological conditions using lab-based micro-CT systems.

The Effect of Five-Day Dry Immersion on the Nervous and Metabolic Mechanisms of the Circulatory System.

The purpose of the study was to investigate the regulatory and metabolic changes in the circulatory system when simulating microgravity conditions in a five-day dry immersion. These changes reflect the adaptation processes characteristic for the initial stages of a space flight or a short-duration space flight. Studies were conducted with 13 healthy male volunteers aged 21 to 29 years. The assessment of regulatory and metabolic processes in the circulatory system was based on the heart rate variability (HRV) and urine proteomic profile analysis. It was found that the restructuring of hemodynamics during 5 days hypogravity begins with the inclusion of the nervous circuit of regulation, and for manifestations at the body fluids protein composition level and activation of the metabolic regulation, these periods are apparently insufficient. Perhaps this is due to the fact that the metabolic regulation, being evolutionarily ancient and genetically determined, is more stable and requires more time for its pronounced activation when stimulated by extreme life conditions.

Bismuth nanowires: electrochemical fabrication, structural features, and transport properties.

Electrochemical aspects of Bi electrocrystallization from a bath containing bismuth nitrate in a mixture of ethylene glycol and water are addressed. Bismuth nanowires with diameters of 50-120 nm and a length of up to a few dozen microns were prepared by electrodeposition into the pores of anodic aluminium oxide templates. Crystal structure and morphology of electrodeposited materials were characterized using electron microscopy, selected area electron diffraction, and X-ray diffraction analysis. Factors affecting the formation of single or polycrystalline nanowires and their crystallographic orientation are discussed. The prospects of electrodeposited Bi nanostructures for microelectronics are illustrated by the quantitative resistivity measurements of highly texturized Bi nanowires with a diameter of ca. 100 nm and a length varying from 160 to 990 nm in a temperature range from 300 to 1.2 K.

Urine proteome changes associated with autonomic regulation of heart rate in cosmonauts.

BACKGROUND: The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions. Urine proteome of each cosmonaut was analyzed before and after space flight, depending on the initial parameters characterizing the regulatory mechanisms of the cardiovascular system. RESULTS: The proteins cadherin-13, mucin-1, alpha-1 of collagen subunit type VI (COL6A1), hemisentin-1, semenogelin-2, SH3 domain-binding protein, transthyretin and serine proteases inhibitors realize a homeostatic role in individuals with different initial type of the cardiovascular system regulation. The role of significantly changed urine proteins in the cardiovascular homeostasis maintenance is associated with complex processes of atherogenesis, neoangiogenesis, activation of calcium channels, changes in cell adhesion and transmembrane properties, changes in extracellular matrix, participation in protection from oxidative stress and leveling the effects of hypoxia. Therefore, the concentrations of these proteins significantly differ between groups with dominant parasympathetic and sympathetic influences. CONCLUSION: The space flight induced urine proteome changes are significantly different in the groups identified by heart rate autonomic regulation peculiarities before space flight. All these proteins regulate the associated biological processes which affect the stiffness of the vascular wall, blood pressure level, the severity of atherosclerotic changes, the rate and degree of age-related involution of elastin and fibulin, age-related increase in collagen stiffness, genetically determined features of elastin fibers. The increased vascular rigidity (including the aorta) and of myocardium may be regarded as a universal response to various extreme factors. Significant differences in the semi-quantitative analysis of signal proteins between groups with different types of autonomic regulation are explained by a common goal: to ensure optimal adaptation regardless of age and of the genetically determined type of responses to the extreme environmental factors effects.

Presenilin-1 Delta E9 Mutant Induces STIM1-Driven Store-Operated Calcium Channel Hyperactivation in Hippocampal Neurons.

Presenilins regulate calcium homeostasis in the endoplasmic reticulum, and dysregulation of intracellular calcium has been implicated in the pathogenesis of Alzheimer disease. Elevated presenilin-1 (PS1) holoprotein levels have been detected in postmortem brains of patients carrying familial Alzheimer disease (FAD) PS1 mutations. This study examines the effect of the FAD presenilin mutant that lacks the ninth exon (PS1 ∆E9) and does not undergo endoproteolysis on store-operated calcium (SOC) entry. Significant enhancement of SOC channel activation was detected by electrophysiological measurements in hippocampal neurons with PS1 ∆E9 mutant expression. Here, we show that (i) the hyperactivation of SOC channels is mediated by the STIM1 sensor and can be attenuated by STIM1 knockdown or 2-aminoethoxydiphenyl borate application, (ii) the STIM2 is not involved in pathological changes of SOC entry, (iii) the pathological SOC entry demonstrates properties of both TRPC and Orai subunit composition, and (iiii) transgenic Drosophila flies with PS1 ∆E9 expression in the cholinergic neuron system show short-term memory loss, which can be abolished by 2-aminoethoxydiphenyl borate feeding.

Long-range atmospheric transport Beryllium-7 to region the Sea of Japan.

Concentrations of cosmogenic beryllium-7((7)Be) and atmospheric aerosols were measured in the atmosphere of the coastal zone of Vladivostok in 2013-2014. The (7)Be concentrations ranged from 0.5 to 4.1 mBq/m(3), with the lowest values in summer and the highest in spring and autumn; the mean value was 2.2 mBq/m(3). Analysis of meteorological data in the synoptic scale showed an inverse correlation with wet deposition rates R = -0.55 (p = 0.0001) and H2O mixing ratio R = -0.49 (p = 0.0001) and a positive with an average maximum height of 120-h backward trajectories of air masses R = 0.65 (p = 0.0001). Angular cluster analysis showed the (7)Be concentration to be dependent on the north-western (R = 0.53, p = 0.001) and eastern winds (R = -0.7, p = 0.0001 for 2013 and R = -0.49, p = 0.002 for 2014). The multiple regression analysis identified five factors in (7)Be concentration: altitudes (b = 0.44), air temperature (b = 0.36), a portion of trajectories in the pacific (North-East direction) cluster (b = -0.32), aerosol concentrations (b = 0.28) and wet precipitation rates (b = -0.24). The model has a good correlation with the data (adjusted R(2) = 0.55). It was found that the direction and height of the air masses trajectories in the lower troposphere strongly influence the concentration of (7)Be.

Radioactive isotopes in atmospheric aerosols over Russia and the Sea of Japan following nuclear accident at Fukushima Nr. 1 Daiichi Nuclear Power Station in March 2011.

Artificial radionuclides, such as iodine-131 ((131)I), cesium-134 ((134)Cs), and cesium-137 ((137)Cs), as well as natural isotopes of beryllium-7 ((7)Be) and potassium-40 ((40)K) have been registered in atmospheric aerosols over Vladivostok selected from 11 March to 17 June 2011. Additionally, (134)Cs and (137)Cs were detected in atmospheric aerosols over Tomsk selected from 16 March to 17 June 2011. Artificial radionuclides were also discovered in atmospheric wet depositions sampled in Vladivostok from 3 to 17 May 2011. Moreover, these radionuclides have been registered in atmospheric aerosols over the sea surface of the Sea of Japan selected from 3 to 31 May 2011 during an expedition of the "Nadezhda" sailing ship. From 18 March to 15 April, an increase in concentrations of atmospheric aerosols over Vladivostok from 108.8 to 321.5 µg/m(3) has been registered. It was accompanied by increased activity concentrations of (134)Cs, (137)Cs, and the (131)I. During the period from 18 March to 15 April, activity concentrations of (137)Cs and (134)Cs in atmospheric aerosols increased 100 times compared with the minimum detectable concentration (MDC) level and peaked in the weekly sample gathered from 8 to 15 April (145.0 and 105.3 µBq/m(3), respectively). Variability of concentrations of natural isotopes of (7)Be and (40)K was not greater than 1 order of magnitude throughout the sampling period. Maximal values of (137)Cs and (134)Cs concentrations (1,281.5 ± 141 and 384.4 ± 42.3 µBq/m(3), respectively) in Tomsk were reached in samples taken from 1 to 2 April. For the atmospheric aerosol samples from the Sea of Japan, the largest concentration of (131)I (392.3 ± 215.7 µBq/m(3)) was detected from 13 to 19 May, while all other samples had much lower concentration values. Synoptic analysis of back trajectories movement of air masses showed that the radioactive cloud came to Vladivostok from the regions of Siberia and northeastern part of China. Synoptic analysis for Tomsk showed that during the period of maximal activity concentrations (1-9 April), air masses were arriving from the European part of Russia and north of Kazakhstan.

Oxidative status shifts in uterine cervical incompetence patients.

Uterine cervical incompetence (UCI) is a pregnancy complication affecting about 10% of the pregnancies in the western world. Studying the etiology of the UCI requires a specific approach adequate for this highly heterogenous syndrome. Oxidative status disorders are associated with various pathologies, including pregnancy complications. As such, general oxidative status profiling is a promising methodology to treat UCI. We aimed at assaying the closely interrelated oxidative status markers in the uterine cervical incompetence patients by means of the systems biology-oriented approach. Chemiluminescent assay, circulating thioredoxin 1 protein, uric acid, and homocysteine level measurements were used to assess the character of the oxidative status regulation in the UCI patients. We found UCI to be associated with the atypical plasma oxidative status deregulation; UCI plasma samples demonstrated lowered proneness to the pro-oxidative processes, and this was not due to the excessive antioxidant activity. There were neither signs of oxidative stress nor destructive pro-oxidant feedforward circuit locking in the UCI group. We also report increased circulating levels of uric acid in the UCI patients.