High-density lipoprotein remodeling affects the osmotic properties of plasma in goldfish under critical salinity.

To investigate the stress response and physiological adaptations of goldfish (Carassius auratus) to critical salinity (CS) waters, we analyzed high-density lipoprotein (HDL) stoichiometry, stress markers (cortisol, glucose), and plasma osmotic properties (Na+ , osmolality, water content) using ichthyology, biochemistry, and proteomics approaches. After 21 days of exposure to CS, plasma concentrations of cortisol, glucose, and Na+ increased, indicating stress. Total plasma osmolality (Osmtotal ) and osmolality generated by inorganic (Osminorg ) and organic osmolytes (Osmorg ) also increased, the latter by ~2%. We associated the increase of Osmorg with (1) increased metabolite concentration (glucose), (2) dissociation of HDL particles resulting in increased HDL number per unit plasma volume (~1.5-2-fold) and (3) increased HDL osmotic activity. HDL remodeling may be the reason for the redistribution of bound and free water in plasma, which may contribute to water retention in plasma and, at the same time, to hemodynamic disturbances under CS conditions. The study's findings suggest that HDL remodeling is an important mechanism for maintaining osmotic homeostasis in fish, which is consistent with current capillary exchange models in vertebrates.

The size effect of BiFeO3 nanocrystals on the spatial spin modulated structure.

The spatial spin modulated structure (SSMS) of the cycloid type present in bulk BiFeO3 prevents the linear magnetoelectric effect. One way to influence this structure is to reduce the crystal size to the nanoscale. Various opinions are circulating in the literature about the effect of nanocrystal size on SSMS, and to investigate this issue, we used a number of methods, with zero-field NMR (ZF NMR) spectroscopy at the forefront. ZF NMR spectroscopy enables the direct observation of the distribution profile of local fields on iron atoms and defines the SSMS presence and its properties. We also examined the synthesized samples using XRD, TEM, and magnetometry. We conclude that SSMS persists as the nanocrystal size decreases to the cycloid period and less, becoming more harmonic. This is accompanied by the change of the anisotropy type from an "easy axis" to an "easy plane". Magnetic measurements show a significant increase in the saturation magnetization, remanent magnetization, coercivity, and exchange bias of nanocrystals with sizes close to the cycloid period, which is probably associated with incomplete spin compensation in the case of an incomplete cycloid period. Despite the fact that SSMS is retained in the samples with decreased size, the magnetic properties experience a sharp increase up to applicable values.

NANOS3 downregulation in Down syndrome hiPSCs during primordial germ cell-like cell differentiation.

Human infertility is a complex disorder at the genetic, molecular, cellular, organ, and hormonal levels. New developing technology based on the generation of human primordial germ cell-like cells (hPGCLCs) from induced pluripotent stem cells (hiPSCs) might improve understanding of early germ cell development (specification, migration, gametogenesis, and epigenetic reconstitutions), as well as offering a solution for infertility and hereditary disorders. In this study, we differentiated hiPSCs with trisomy 21 into hPGCLCs. In vitro-derived germ cells from hiPSCs with Down syndrome (DS) express hPGCLC core circuitry, EOMES, SOX17, and PRDM14 at relatively low levels. TFAP2C and PRDM1 were expressed and remained elevated, whereas NANOS3 and NANOG were downregulated in BMP4-induced hiPSCs with DS. The low level of NANOG and NANOS3 expression might negatively influence hPGCLC generation in DS hiPSCs. We suggest that DS hPGCLCs could be a suitable model for studying human early germ cell development, the epigenetic and molecular mechanisms of PGC specification and formation, as well as related infertility disorders, such as azoospermia and teratozoospermia.

[Clinical and prognostic effect of repeated ten-day courses of low-intensity laser exposure in patients with coronary heart disease]. / Kliniko-prognosticheskii effekt povtornykh desyatidnevnykh kursov nizkointensivnogo lazernogo vozdeistviya na patsientov s ishemicheskoi bolezn'yu serdtsa.

The deterioration in the prognosis of coronary heart disease (CHD) is due to the influence of numerous pathophysiological factors, which is almost impossible to handle with only medication. Positive results obtained after one course of laser therapy (LT) in patients with angina pectoris substantiate the possibility of prolonging the effect when using repeated courses of low-intensity laser exposure. PURPOSE OF THE STUDY: To assess the clinical and prognostic value of repeated courses of low-intensity LT in patients with CHD for 24 months. MATERIAL AND METHODS: The study involved 40 men (mean age 56.6±8.2 years) with exertional angina pectoris with high (0-I functional class - 40%) and lower (II-III functional class - 60%) exercise tolerance (according to the classification of the Canadian Heart Association). Duration of the study was 24 months. All patients underwent 10-day courses of skin LT in the infrared radiation range every 6 months. Initially and after each course of LT, a bicycle ergometer test was performed with an assessment of the threshold values of blood pressure (BP), double product (DP=systolic BP×heart rate) and the ratio of DP to load power (DP/W). The blood levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were studied after each course of LT. RESULTS: Patients had an improvement in their well-being during LT: a decrease in the number of angina attacks, the need for nitroglycerin, antianginal and antihypertensive drugs. A statistically significant increase in exercise tolerance by 33.2-40.1% was revealed since 1 month after each course of LT, according to the results of stress tests. At the same time, the threshold values of blood pressure remained at the initial level, which was regarded as a manifestation of the hypotensive effect. The decrease in the DP/W index by 18.2-29.6% compared with the initial data indicates the energy economization of cardiac activity. LT was accompanied by a statistically significant decrease in blood cholesterol from 6.15±1.26 to 4.84±1.28-5.25±1.53 mmol/l and LDL-C from 4.70±1.16 to 3, 29±1.26-3.96 mmol/l. CONCLUSION: Long-term clinical and preventive effect, good tolerability, availability, absence of side effects substantiate the possibility of widespread use of repeated courses of laser exposure in coronary heart disease.

[Clinical effect, changes in the lipid structure of the erythrocyte membrane and microcirculation in patients with arterial hypertension in combination with coronary heart disease under the influence of laser therapy]. / Klinicheskii effekt, izmenenie lipidnoi struktury eritrotsitarnoi membrany i mikrotsirkulyatsii u bol'nykh arterial'noi gipertoniei v sochetanii s ishemicheskoi bolezn'yu serdtsa pod vliyaniem lazeroterapii.

The high prevalence of the combination of arterial hypertension (AH) with coronary heart disease (CHD) suggests the improvement of their treatment methods. In this regard, it is of interest to assess the dynamics of the clinical picture of patients against the background of pathogenetically determined subcellular and systemic changes under the influence of laser therapy (LT). OBJECTIVE: To evaluate the clinical effect of LT in patients with hypertension in combination with coronary artery disease and trace its relationship with the dynamics of the structure of the lipid bilayer of the erythrocyte membrane and changes in the microvascular bed. MATERIAL AND METHODS: We examined 65 male patients (mean age 50.9±6.3 years) with II-III degree AH in combination with coronary artery disease with angina pectoris. Among them, 40 patients received a 10-day course of LT, and 25 patients underwent simulated laser irradiation. At the initial stage and after 1 month, all patients underwent a bicycle exercise test, a study of the lipid composition of the erythrocyte membrane, including the main fractions of phospholipids and free cholesterol, as well as the level of intracellular Ca2+ and lipid peroxidation products - malondialdehyde and diene conjugates. Microcirculation was assessed using the method of conjunctival biomicroscopy. RESULTS: One month after the course of LT, patients showed a significant increase in exercise tolerance by 37.8%, a decrease in systolic blood pressure with a standard load by 9.9%. The improvement of the clinical picture occurred against the background of a decrease in the activity of lipid peroxidation and structural changes in the cell membrane: an increase in polyunsaturated fractions of phospholipids and a decrease in the cholesterol content, as well as a decrease in the Ca2+ level in the cell from 0.23 [0.19; 0.32] to 0.20 [0.16; 0.26] mmol/l. The results of the analysis of conjunctival biomicroscopy demonstrated a statistically significant decrease in the ratio of arteriolovenular calibers, a limitation of the severity of sludge syndrome by 59%, and an almost twofold (from 3.9±0.52 to 7.2±1.23 cap/mm2) increase in capillary density. CONCLUSION: The data obtained showed that in patients with hypertension in combination with coronary artery disease, LT causes positive changes in the lipid structure of the cell membrane and microcirculation parameters, which is accompanied by a hypotensive effect and an improvement in the clinical and functional state of patients.

Immortalization of Human Keratinocytes Using the Catalytic Subunit of Telomerase.

A new stable line of human keratinocytes was obtained. The cells have altered morphology, both abnormal chromosomal composition and expression of keratinocyte markers, do not show contact inhibition, could be cultured in various media and have limited stratification ability in vitro. Upon transplantation into nude mice the cells have tumorigenic properties.

[Evaluation of choriocapillaris with high-speed spectral-domain optical coherence tomography angiography and image averaging]. / Otsenka statusa khoriokapillyarisa s pomoshch'yu vysokoskorostnoi spektral'noi opticheskoi kogerentnoi tomografii s funktsiei angiografii i tekhnologii usredneniya izobrazhenii.

PURPOSE: To study the capabilities of high-speed spectral-domain optical coherence tomography angiography (SD-OCTA) with image averaging in the evaluation of choriocapillaries in healthy individuals and patients with central serous chorioretinopathy (CSC). MATERIAL AND METHODS: All participants underwent OCTA examination on the SOLIX tomograph (Optovue, USA) using quadruplicate 3×3 mm scan with image averaging. Image analysis was performed in 9-µm custom slab with Phansalkar auto local threshold algorithm and calculation of flow voids larger than 5000 µm2 and 10 000 µm2. The optimal slab depth was determined in healthy eyes by consecutive analysis of the slabs with a 3-µm shift from zero position to 33 µm below Bruch's membrane. RESULTS: The study included 18 eyes of 18 healthy volunteers (40.4±6.0 years old) and 18 fellow eyes of 18 unilateral CSC patients (37.4±10.7 years old). The slab 12 µm below the Bruch's membrane showed the minimal number of flow voids (23.1±7.0 of >5000 µm2 voids per scan) and was chosen for further analysis. The number of flow voids of >5000 µm2 in healthy paired eyes of CSC patients was statistically significantly higher than in the eyes of healthy individuals (32.7±10.7 and 25.3±8.1 voids/scan, respectively; p=0.022). The number of flow voids of >10000 µm2 was also statistically significantly higher in CSC eyes compared to healthy eyes (5.6±3.3 and 3.5±1.9 voids/scan, respectively; p=0.045). There was no statistically significant difference in total area of the voids between the eyes of healthy individuals and CSC patients (96406.1±3924.5 µm2 and 95395.7 ± 3615.1 µm2, respectively; p=0.42). CONCLUSION: The optimal settings for choriocapillaris imaging on the SOLIX tomograph include 9-µm slab 9 to 18 µm below the Bruch's membrane. Using a 9-µm slab 12 µm below the Bruch's membrane, a substantial difference was found in choriocapillaris perfusion between eyes of healthy individuals and CSC patients.

Coexistence of Superconductivity and Charge Density Waves in Tantalum Disulfide: Experiment and Theory.

The coexistence of charge density wave (CDW) and superconductivity in tantalum disulfide (2H-TaS_{2}) at low temperature is boosted by applying hydrostatic pressures to study both vibrational and magnetic transport properties. Around P_{c}, we observe a superconducting dome with a maximum superconducting transition temperature T_{c}=9.1 K. First-principles calculations of the electronic structure predict that, under ambient conditions, the undistorted structure is characterized by a phonon instability at finite momentum close to the experimental CDW wave vector. Upon compression, this instability is found to disappear, indicating the suppression of CDW order. The calculations reveal an electronic topological transition (ETT), which occurs before the suppression of the phonon instability, suggesting that the ETT alone is not directly causing the structural change in the system. The temperature dependence of the first vortex penetration field has been experimentally obtained by two independent methods. While a d wave and single-gap BCS prediction cannot describe the lower critical field H_{c1} data, the temperature dependence of the H_{c1} can be well described by a single-gap anisotropic s-wave order parameter.

[About the formation of property to age in the course of evolution of systems and about the role of this property.]

Natural selection contributes to the survival of those organisms, those communities of social insects, those human societies and those multi-species systems, in which efficiency to use environmental resources is higher than that of others. Therefore, in the course of evolution, the efficiency of use them by the listed systems increased. This increase was due to the specialization of the elements forming these systems. But their far-reaching specialization led to the fact that the listed systems acquired the property of aging. This property increased the adaptability of higher-ranking systems, part of which they were.

[The value of bone mineral density assessment by dual-energy x-ray absorptiometry for prediction of cardiovascular mortality in patients treated with hemodialysis].

AIM: Determine whether bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry can be used as predictor of increased risk of death in hemodialysis patients. MATERIALS AND METHODS: A prospective study was performed of 516 patients with chronic kidney disease treated with hemodialysis (men 265, women 251, mean age 44.811.4 years) who were observed for 5.73.2 years. Before inclusion in the study, in all patients was analyzed bone mineral density using dual-energy X-ray absorptiometry in three standard departments: lumbar vertebrae, proximal femur and distal forearm. The probability analysis of the outcome was carried out using the KaplanMeier method and Cox. RESULTS: During follow-up period 111 (21.5%) patients died, 50.5% from cardiovascular events. Survival analysis by KaplanMeier method allowed to prove the increased risk of death from cardiovascular pathology in hemodailysis patients with low bone mineral density of all evaluated areas. Step-by-step multivariate Cox regression analysis showed that the T score of the femur, showing the difference of BMD of the patient with normal value of BMD for young adult, had the greatest prognostic significance. CONCLUSION: Reduced bone mineral density in patients receiving hemodialysis is associated with an increased risk of death from cardiovascular disease. Dual energy x-ray absorptiometry can be used for assessment of this risk.

[Evaluation of the clinical efficacy of urethroplasty after failed hypospadias repair].

BACKGROUND: Evaluation of surgical treatment of hypospadias is one of the most controversial problem in urology, considering a lack of continuity in the management of these patients between pediatric andrologists and general urologists. Patients who undergone to multiple hypospadias repairs remain one of the most difficult categories for reconstructive urethral surgery and urology in general. MATERIALS AND METHODS: The treatment results of 112 adult patients who had complications of previously performed hypospadias repairs were evaluated. The results of repeated procedures were compared in patients, in whom modified balloon urethral catheter (group 1; n=50) or standard Foley catheter (group 2; n=62) was used, respectively. RESULTS: Most patients after surgery assessed the appearance of the penis as "good" (92% in group 1, 77.4% in group 2). In group 1, satisfactory results was seen in 8% of cases and there were no unsatisfactory results, while in group 2, where standard Foley catheter was used, these values were 19.4% and 3.2%, respectively. In group 1, complication rate was lower than in group 2 (10% versus 41.9%; p<0.05). In group 1, there was a significantly higher proportion of patients with a Qmax score of more or equal 18 ml/s (90% versus 74.2%; p<0.05). CONCLUSIONS: Repeated procedures in adult men with late complications of surgical treatment of hypospadias are quite effective, although they are accompanied by a rather high complications rate. The use of a new model of the urethral catheter with dilating cuff and an irrigation canal allows to improve treatment results in this category of patients.

Mesenchymal Stem Cell Therapy-Is the Vessel Half Full or Half Empty?

The urgency of the search and introduction into medical practice of the method for the therapy of severe forms of pneumonia COVID-19 is due to the lack of effective treatment methods that can destroy the pathogen. Expectations of a good clinical effect from the application of mesenchymal stem cells (MSCs) are not groundless: there is a scientific justification in using MSCs for the treatment of inflammatory diseases and of the proven mechanisms of their action. Along with this, there are very little reliable data about the mechanism of MSCs' action when they are systemically administrated to a human or on the distribution of cells in the body and the long-term consequences of such administration. Data from model experiments are contradictory both concerning the specific action of MSCs and their safety. If clinical studies show an acceptable risk/benefit ratio for the application of MSCs, countries in which such studies have been conducted can expect their introduction into medical practice. In Russia, it is necessary to initiate experimental verification of the specific action of MSCs and the risks of their use in COVID-19 conditions in a sufficient quantity, and, in parallel, to create a mechanism for accelerated but justified admission of biomedical cell products into practice.

[Nutriome as the direction of the "main blow": determination of physiological needs in macro- and micronutrients, minor biologically active substances].

One of the essential parts of fundamental research in Nutrition Science is the determination of the physiological requirements of humans for energy and food substances. Research that has been carried out in this area over the past 90 years, consistently develops and improves the norms of physiological requirements for energy and nutrients for various groups of the population of the Russian Federation. In the 50 years of the last century in this research field, determining the values of daily intake for macronutrients (proteins, lipids and carbohydrates), was in the first place. Then the Era of micronutrients (vitamins, minerals, trace elements) was started, and, finally, now there is the Era of minor food biologically active substances. More and more facts are accumulating about their leading role in regulating metabolism. They can be recognized as endogenous regulators, the primary vital components involved in the formation of human health. In recent years, the new definition of Nutriome is introduced into Nutrition Science. It is considered as a set of essential nutritional factors to maintain a dynamic equilibrium between human being and the environment, aimed to ensure viability, the preservation and reproduction of the species, keeping the adaptive capacity, the system of antioxidant defence, apoptosis, metabolism, and immune system function. The Nutriome is a formula for optimal nutrition, which is continually being improved and supplemented. Knowledge of this formula is the key to forming an optimal diet for a person, and, therefore, to save their health. It is evident that at the population level, the Nutriome has its characteristics, its structure for each age period of human life. The need to develop a formula for optimal nutrition and, consequently, updating nutrient-based dietary guidelines is induced by socio-economic and demographic changes in population, changes in anthropometric characteristics of children and adults, increasing prevalence of socially significant non-communicable diseases, developing studies of the significance of particular food substances and establishing the relationship between nutrition and health.

Detection of small numbers of iPSCs in different heterogeneous cell mixtures with highly sensitive droplet digital PCR.

Induced pluripotent stem cells (iPS cells) are a prospective resource for regenerative biomedicine. iPS cells can differentiate into any type of stem, progenitor and somatic cells to help replace structures within damaged organs or tissues. However, iPS cells themselves, can produce malignant tumors if they are injected into the body of an immunocompatible or immunodeficient recipient. Thus, it is necessary to detect any residual iPS cells content in biomedical cell products obtained from iPS cells and destined for transplantation. In this article we describe searches for iPS cells in heterogeneous cell mixtures, using two different methods-quantitative RT-PCR and droplet digital PCR (ddPCR). In experiments with various heterogeneous mixtures, including mixtures with neural stem cells, we found that the OCT4, TDGF1 and LIN28 genes are the best markers for such a search, and droplet digital PCR provides the greatest measurement accuracy, which is 0.002%. Thus, we have confirmed the advantage of using droplet digital PCR in the search for pluripotent stem cells in heterogeneous cell mixtures. We hope that this data can be useful for biosafety control in regenerative biomedicine.

Modern Technologies Deriving Human Primordial Germ Cells in vitro.

Primordial germ cells (PGCs) are a unique type of stem cells capable of giving rise to totipotent stem cells and ensuring the fertility of an organism and the transfer of its genome to the next generation. PGC research is an important perspective research field of developmental biology that handles many questions of embryogenesis and holds promise for treatments of infertility in the future. Considering ethical concerns related to human embryos, the main research approach in understanding the biology of human PGCs is in vitro studies. In this review, we consider the historical perspective of human PGC studies in vitro, the main existing models, and further outlooks and applications in medicine and science.

Strong interplay between stripe spin fluctuations, nematicity and superconductivity in FeSe.

In iron-based superconductors the interactions driving the nematic order (that breaks four-fold rotational symmetry in the iron plane) may also mediate the Cooper pairing. The experimental determination of these interactions, which are believed to depend on the orbital or the spin degrees of freedom, is challenging because nematic order occurs at, or slightly above, the ordering temperature of a stripe magnetic phase. Here, we study FeSe (ref. )-which exhibits a nematic (orthorhombic) phase transition at Ts = 90 K without antiferromagnetic ordering-by neutron scattering, finding substantial stripe spin fluctuations coupled with the nematicity that are enhanced abruptly on cooling through Ts. A sharp spin resonance develops in the superconducting state, whose energy (∼4 meV) is consistent with an electron-boson coupling mode revealed by scanning tunnelling spectroscopy. The magnetic spectral weight in FeSe is found to be comparable to that of the iron arsenides. Our results support recent theoretical proposals that both nematicity and superconductivity are driven by spin fluctuations.

[Is it possible to rejuvenate the aging global civilization?]

Society is not only social system but also biological system. Growing complexity of biological systems will inevitably lead to the loss of their potential immortality and to the appeared attribute of aging. The aging of the present-day civilization is evidenced by the problems having accumulated. The answer to the question concerning the possibility to prevent collapse depends on the answer to the more general question - whether supra-organismal system that due to the growth of the structure complexity has acquired the property to age without losing achieved complexity can return to ancestral potential immortality. A positive response is given to this question. Supra-organismal systems having been freed from the necessity to age exist. Those are communities of social insects. Some of them were mortal initially but in the course of evolution have lost attribute of aging. Therefore, complex supra-organismal systems, including present-day civilization, can return to ancestral potential immortality not losing the achieved structural complexity. The main obstacle to rejuvenating civilization is not the nature of things but the human mentality.

[The significance of fibroblasts in experimental modeling of proliferative vitreoretinopathy]. / Rol' fibroblastov v modelirovanii proliferativnoi vitreoretinopatii.

AIM: to investigate the role of heterogeneous fibroblasts in the development of epiretinal membrane in eyes with modeled proliferative vitreoretinopathy. MATERIAL AND METHODS: The material for investigation were 6 eyes of 3 Chinchilla rabbits. Suspended fibroblasts (fibroblasts of the human skin - 200000 cells in 0.1 ml) were injected into the vitreous cavity via the pars plana. The animals were followed up for 1 month and then made out of the experiment. The eyes were enucleated and fixed in 10% neutral buffered formalin for routine histological examination. Microscopy was performed on the Leica system. RESULTS: The main clinical and morphological criteria for a rabbit model of PVR induced by intravitreal injection of heterogenic fibroblasts have been established: epiretinal membrane formation, changes in intraocular structures (the retinal pigment epithelium and retina), and inflammation (due to transplantation immunity). Particularities of the epiretinal membrane development and the role of different intraocular structures have been described. CONCLUSION: The experimental fibroblastic model of PVR reproduces the final, fibrous, stage of PVR, which is significant for efficacy evaluation of antiproliferative drugs.

III-V-on-silicon integrated micro - spectrometer for the 3 µm wavelength range.

A compact (1.2 mm2) fully integrated mid-IR spectrometer operating in the 3 µm wavelength range is presented. To our knowledge this is the longest wavelength integrated spectrometer operating in the important wavelength window for spectroscopy of organic compounds. The spectrometer is based on a silicon-on-insulator arrayed waveguide grating filter. An array of InAs0.91Sb0.09 p-i-n photodiodes is heterogeneously integrated on the spectrometers output grating couplers using adhesive bonding. The spectrometer insertion loss is less than 3 dB and the waveguide-referred responsivity of the integrated photodiodes at room temperature is 0.3 A/W.

Highly Anisotropic and Twofold Symmetric Superconducting Gap in Nematically Ordered FeSe_{0.93}S_{0.07}.

FeSe exhibits a novel ground state in which superconductivity coexists with a nematic order in the absence of any long-range magnetic order. Here, we report on an angle-resolved photoemission study on the superconducting gap structure in the nematic state of FeSe_{0.93}S_{0.07}, without the complications caused by Fermi surface reconstruction induced by magnetic order. We find that the superconducting gap shows a pronounced twofold anisotropy around the elliptical hole pocket near Z (0, 0, π), with gap minima at the end points of its major axis, while no detectable gap is observed around Γ (0, 0, 0) and the zone corner (π, π, k_{z}). The large anisotropy and nodal gap distribution demonstrate the substantial effects of the nematicity on the superconductivity and thus put strong constraints on current theories.