[Study of urinary markers of different podocytopathies by proteomic analysis].

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy characterized by primary podocyte detection and high proteinuria. The search for biomarkers and factors associated with the progression of this disease is an important task nowdays. AIM: To assess the proteomic profile of urine in patients with FSGS and to isolate urinary biomarkers of podocytopathies. MATERIALS AND METHODS: The study included 41 patients diagnosed with chronic glomerulonephritis, 27 men and 14 women. According to the morphological study, 28 patients were diagnosed with FSGS, 9 with steroid-sensitive nephrotic syndrome and 14 with steroid-resistant nephrotic syndrome. The comparison group included 13 patients with membranous nephropathy. The study of the urinary proteome was carried out by targeted liquid chromatography-mass spectrometry using multiple reaction monitoring with synthetic stable isotope labelled peptide standards. RESULTS: The main differences in the protein profile of urine were found in the subgroups of steroid-sensitive (SS) and steroid-resistant (SR) FSGS. In the FSGS SR group, at the onset of the disease, there was a high concentration of proteins reflecting damage to the glomerular filter (apo-lipoprotein A-IV, orosomucoid, cadherin, hemopexin, vitronectin), as well as proteins associated with tubulo-interstitial inflammation and accumulation of extracellular matrix (retinol- and vitamin D-binding proteins, kininogen-1, lumican and neurophilin-2). Compared with the membranous nephropathy group, FSGS patients had significantly higher urinary concentrations of carnosinase, orosomucoid, cadherin-13, tenascin X, osteopontin, and zinc-alpha-2-glycoprotein. CONCLUSION: Thus, in patients with SR FSGS, the proteomic profile of urine includes more proteins at elevated concentrations, which reflects severe damage to various parts of the nephron compared with patients with SS FSGS and membranous nephropathy.

Operational regimes of lasers based on gain media with a large Raman scattering cross-section.

We report on unusual regimes of operation of a laser with a gain medium with a large Raman scattering cross-section, which is often inherent in new types of gain media such as colloidal and epitaxial quantum dots and perovskite materials. These media are characterized by a strong electron-phonon coupling. Using the Fröhlich Hamiltonian to describe the electron-phonon coupling in such media, we analyze the operation of the system above the lasing threshold. We show that below a critical value of the Fröhlich constant, the laser can only operate in the conventional regime: namely, there are coherent cavity photons but no coherent phonons. Above the critical value, a new pump rate threshold appears. Above this threshold, either joint self-oscillations of coherent phonons in the gain medium and photons in a cavity or a chaotic regime are established. We also find a range of the values of the Fröhlich constant, the pump rate, and the resonator eigenfrequency, in which more than one dynamical regime of the system is stable. In this case the laser dynamics is determined by the initial values of the resonator field, the active medium polarization, the population inversion, and phonon amplitude.

A new type of non-Hermitian phase transition in open systems far from thermal equilibrium.

We demonstrate a new type of non-Hermitian phase transition in open systems far from thermal equilibrium, which can have place in the absence of an exceptional point. This transition takes place in coupled systems interacting with reservoirs at different temperatures. We show that the spectrum of energy flow through the system caused by the temperature gradient is determined by the [Formula: see text]-potential. Meanwhile, the frequency of the maximum in the spectrum plays the role of the order parameter. The phase transition manifests itself in the frequency splitting of the spectrum of energy flow at a critical point, the value of which is determined by the relaxation rates and the coupling strength. Near the critical point, fluctuations of the order parameter diverge according to a power law with the critical exponent that depends only on the ratio of reservoirs temperatures. The phase transition at the critical point has the non-equilibrium nature and leads to the change in the energy flow between the reservoirs. Our results pave the way to manipulate the heat energy transfer in the coupled out-of-equilibrium systems.

The first observation of osmotically neutral sodium accumulation in the myocardial interstitium.

The aim of this study was the detection and quantification of the Na+ depositions in the extracellular matrix of myocardial tissue, which are suggested to be bound by negatively charged glycosaminoglycan (GAG) structures. The presented experimental results are based on high resolution X-ray fluorescence (XRF) spectromicroscopy technique used to perform a comparative analysis of sodium containment in intracellular and interstitial spaces of cardiac tissues taken from animals selected by low and high sodium intake rates. The experimental results obtained show that high sodium daily intake can result in a remarkable increase of sodium content in the myocardial interstitium.

[Whole-Genome Duplications in Evolution, Ontogeny, and Pathology: Complexity and Emergency Reserves].

Whole-genome duplication (WGD), or polyploidy, increases the amount of genetic information in the cell. WGDs of whole organisms are found in all branches of eukaryotes and act as a driving force of speciation, complication, and adaptations. Somatic-cell WGDs are observed in all types of tissues and can result from normal or altered ontogenetic programs, regeneration, pathological conditions, aging, malignancy, and metastasis. Despite the versatility of WGDs, their functional significance, general properties, and causes of their higher adaptive potential are unclear. Comparisons of whole-transcriptome data and information from various fields of molecular biology, genomics, and molecular medicine showed several common features for polyploidy of organisms and somatic and cancer cells, making it possible to understand what WGD properties lead to the emergence of an adaptive phenotype. The adaptation potential of WGDs may be associated with an increase in the complexity of the regulation of networks and signaling systems; a higher resistance to stress; and activation of ancient evolutionary programs of unicellularity and pathways of morphogenesis, survival, and life extension. A balance between the cell and organismal levels in controlling gene regulation may shift in stress towards the priority of cell survival, and the shift can lead to cardiovascular diseases and carcinogenesis. The presented information helps to understand how polyploidy creates new phenotypes and why it acts as a driving force of evolution and an important regulator of biological processes in somatic cells during ontogeny, pathogenesis, regeneration, and transformation.

Dialectic Unity of the Domestic and Foreign Policy of China On the Centenary of the Communist Party of China.

This July marks the 100th anniversary of the founding of the Chinese Communist Party. This event motivated the authors of this article to consider the main problems that modern Chinese society is solving, the place of the PRC in the world economy and politics at the beginning of the third decade of the 21st century, and China's growing influence on the planet. China's undoubted successes, including in the fight against the coronavirus pandemic and in overcoming the recession caused by tough quarantine measures in early 2020, show the considerable viability of the state created by the Chinese communists, which is increasingly at the forefront of the world in the economy, science and technology, and culture. However, the path to the current rise of the great power was by no means an easy one, and the prospects for its development are perhaps one of the most debated issues in international discussions. China never tires of emphasizing the specifics of its history. At the same time, the diversity of the internal conditions of the colossal country together with the skillful application of carefully studied foreign experience yielded the extraordinary wealth of forms of development, which can serve as a guarantee of new achievements and, possibly, useful universals for all humankind.

Quantum theory of Rayleigh scattering.

We suggest a quantum description of Rayleigh light scattering on atoms. We show that an entangled state of the excited atom and the incident photon is formed during the scattering. Due to entanglement, a photon is never completely absorbed by the atom. The formation of the scattering spectrum is considered as a relaxation of incident photons to the reservoir of free space modes that are in thermal equilibrium. Additional excitations of the reservoir modes occurring during scattering are treated as scattered light. We show that even if the frequency of incident photons is incommensurate with an atomic transition frequency, the scattered light spectrum has a maximum at the frequency of incident photons. In addition, the linewidth of the scattered light is much smaller than that of the spontaneous emission of a single atom. Therefore, the process can be considered as elastic.

[The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis].

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression. AIM: To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). MATERIALS AND METHODS: The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). RESULTS: In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. CONCLUSION: An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

[Successful treatment of a rare variant of mesangioproliferative glomerulonephritis with IgM deposits with Cyclosporin A].

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

Superfast ion scattering by solar wind discontinuities.

Large-amplitude fluctuations of the solar wind magnetic field can scatter energetic ions. One of the main contributions to these fluctuations is provided by solar wind discontinuities, i.e., rapid rotations of the magnetic field. This study shows that the internal configuration of such discontinuities plays a crucial role in energetic ion scattering in pitch angles. Kinetic-scale discontinuities accomplish very fast ion pitch-angle scattering. The main mechanism of such pitch-angle scattering is the adiabatic invariant destruction due to separatrix crossings in the phase space. We demonstrate that efficiency of this scattering does not depend on the magnetic field component across the discontinuity surface, i.e., both rotational and almost tangential discontinuities scatter energetic ions with the same efficiency. We also examine how the strong scattering effect depends on the deviations of the discontinuity magnetic field from the force-free one.

[Autoimmunity and autoinflammation in pathogenesis of immunoinflammatory diseases].

Rheumatic diseases relate to the group of the immunoinflammatory diseases (IID), in pathogenesis of which have a value both autoimmune and autoinflammatory processes. AIM: To present the heterogeneous pathogenesis of inflammation in IID. MATERIALS AND METHODS: It is inspected 260 patients (pts) with IID: 242 pts with systemic autoimmune diseases (SAD): 65 systemic lupus erythematosis, 50 systemic sclerosis, 127 systemic vasculitides (SV) and 18 patients with autoinflammatory diseases (AID): 8 Behcets disease, 2 periodic disease, 5 familial cold fever, 2 idiopathic lobular panniculitis and 1 relapsing polychondritis. Is carried out a study of complement, antigen of von Willebrand factor (FW:AG), antinuclear antibodies, antibodies to DNA, anti-endothelial antibodies, antibodies to topoizomeraze I (anti-Scl-70), antineutrophilic cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aCL IgG and aCL IgM), cryoglobulins, VS, CRP. RESULTS: SAD were characterized by the synthesis of wide antibodies spectrum. As the basic serological marker at the screening it follows to consider antinuclear antibodies (75%). Practically in all groups it took place hypcomlemetemia with reduction of C3 and C4 complement. With systemic lupus erythematosis are revealed antibodies to DNA (71%), with ANCA-associated SV-ANCA (94%), aKL (14%); with SSD aScl-70 (17%). At Wegener granulomatosis ANCA are determined in 94% patients in the active stage. It is noted correlation ANCA with the index of the clinical activity of vasculitis. In the remaining SV groups ANCA were separated in the single cases. Cryoglobulins are noted in all patients with cryoglobulinemic vasculitis. aCL IgG and aCL IgM were the markers of antiphospholipid syndrome. Аnti-endothelial antibodies had significant oscillation spectrum. High indices FW:AG are noted with all above nosologic forms indicated, especially with Wegener granulomatosis and vasculitis hemorrhagic. Among the laboratory tests of inflammatory activity should be considered the determination of VS, CRP and FV:AG, which is also considered the marker of vascular wall defeat. Is given clinical characteristic and changes in the laboratory indices at AID: Conclusion.Isolation from the group IID of patients with AID serves as indication for a genetic study of this contingent with the approval of use for their treatment of biological therapy. Isolation from the group SAD patients with AID serves as indication for a genetic study of this contingent with the approval of use for their treatment of biological therapy.

Effect of Sol-Gel Alumina Biocomposite on the Viability and Morphology of Dermal Human Fibroblast Cells.

This paper is the continuation of our previous work on the ability of biocomposites based on sol-gel alumina (boehmite) to promote skin recovery from burns and atrophic scars. The present study describes the increasing of the cytoplasma volume and the number of filopodias of HDF cells, which for the first time indicates their proliferation on the alumina itself and on alumina-based biocomposite. Studies in vivo confirm the efficiency of the composite in the treatment of atrophic scars.

[Acute appendicitis within the strangulated femoral hernia]. / Sluchai ostrogo appenditsita v ushchemlennoi bedrennoi gryzhe.

Femoral hernia strangulation is usually observed in middle-aged women. There are few case reports of appendix strangulation in the femoral hernia. Acute appendicitis in a strangulated femoral hernia is relatively rare (0.4% of cases). Clinical case of acute destructive appendicitis within a strangulated femoral hernia in an elderly woman is reported in the article. If there is doubt about the urgency of surgical intervention, surgeon needs to take a proactive stance and lean toward emergency surgery. Surgeon should be aware of possible strangulation-associated destructive appendicitis due to injury of the appendix.

New Perspective on the Reversibility of ATP Synthesis and Hydrolysis by Fo×F1-ATP Synthase (Hydrolase).

Fo×F1-ATPases of mitochondria, chloroplasts, and microorganisms catalyze transformation of proton motive force (the difference between the electrochemical potentials of hydrogen ion across a coupling membrane) to the free energy of ATP phosphoryl potential. It is often stated that Fo×F1-ATPases operate as reversible chemo-mechano-electrical molecular machines that provide either ATP synthesis or hydrolysis depending on particular physiological demands of an organism; the microreversibility principle of the enzyme catalysis is usually taken as a dogma. Since 1980, the author has upheld the view that the mechanisms of ATP synthesis and hydrolysis by the Fo×F1 complex are different (Vinogradov, A. D. (2000) J. Exp. Biol., 203, 41-49). In this paper, the author proposes a new model considering the existence in coupling membranes of two non-equilibrium isoforms of Fo×F1 unidirectionally catalyzing synthesis and/or hydrolysis of ATP.

[Cerebral perfusion, arterial hypertension and endothelial dysfunction in rheumatoid arthritis]. / Mozgovaia perfuziia, arterial'naia gipertenziia i éndotelial'naia disfunktsiia pri revmatoidnom artrite.

To study the relationship between cerebral perfusion with arterial hypertension (AH) and the state of endothelium in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Seventy-eight patients with RA were divided into two groups: with- and without AH.The functional methods included ultrasonic duplex angioscanning and dopplerografy of the extracranial and intracranial arteries of the head and neck and daily 24 hour monitoring of arterial blood pressure (BP). C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), von Willebrand Factor antigen (vWF AG), interleukin-8 (Il-8), rheumatoid factor (RF) IgG, endothelin-1 (ET-1) were determined by immunoenzyme analysis and velocity of sedimentation (VS). The dysfunction of endothelium was evaluated by calculation of the number of desquamated endotheliocytes cells (DE). RESULTS: AH occurred in 46 (59%) patients. Cerebral hypoperfusion was observed in patients with RA in whom the reduction in the high-speed indices of blood flow were correlated with BP increase. There were negative correlations between the linear speed of blood flow on the common carotid arteries and average day and night systolic BP, average day and night diastolic BP, indices of time systolic BP and diastolic BP and avariability of BP. The same results were established for the intracranial arteries: inverse correlations between the linear speed on the anterior cerebral arteries and average day systolic BP. The signs of endothelial dysfunction represented by significant differences among the indices of activation of endothelium in RA patients in comparison with the control group were shown. Content of ET-1, sVCAM-1, vWF AG, Il-8, CRP was higher in RA. The number of DE was significantly higher as well. These indices showed significant differences depending on RA activity. Correlation analysis revealed that the markers of endothelium activation sVCAM-1, vWF AG were positively correlated with the indices of immune inflammation. CONCLUSION: An increase in the activity of inflammatory process in RA leads to endothelial dysfunction, which contributes to the increase in the peripheral vascular resistance of cerebral arteries, reduction in the high-speed indices of blood flow, growth of BP variability and the increase in load by pressure.

Enhancement of the Raman Effect by Infrared Pumping.

We propose a method for increasing Raman scattering from an ensemble of molecules by up to 4 orders of magnitude. Our method requires an additional coherent source of IR radiation with the half-frequency of the Stokes shift. This radiation excites the molecule electronic subsystem that in turn, via Fröhlich coupling, parametrically excites nuclear oscillations at a resonant frequency. This motion is coherent and leads to a boost of the Raman signal in comparison to the spontaneous signal because its intensity is proportional to the squared number of molecules in the illuminated volume.

Evolutionary framework of the human interactome: Unicellular and multicellular giant clusters.

The main contradiction of multicellularity (MCM) is between the unicellular (UC) and multicellular (MC) levels. In human interactome we revealed two giant clusters with MC and UC medians (and several smaller ones with MC medians). The enrichment of these clusters by phylostrata and by functions support the MC versus UC division. The total interactome and the giant clusters show a core-periphery evolutionary growth. From viewpoint of the MCM, the most important is the placement of genes, appearing at UC evolutionary stage, in the MC clusters. Thus, genes involved in vesicle-mediated transport, cell cycle, cellular responses to stress, post-translational modifications and many diseases appeared at UC evolutionary stage but are placed mostly in MC clusters. Genes downregulated with age are enriched in UC cluster, whereas the upregulated genes are preferentially placed in MC giant cluster. The tumor suppressor and pluripotency regulating pathways are also enriched in MC giant cluster. Therefore, this cluster probably operates as 'internal manager' constraining runaway unicellularity. The clusters have denser interactions within than between them, therefore they can serve as attractors (stable states of dynamic systems) of cellular programs. Importantly, the UC cluster have a higher inside/outside connection ratio compared with MC clusters, which suggests a stronger attractor effect and may explain why cells of MC organisms are prone to oncogenesis. The evolutionary clustering of human interactome elucidates the MC control over functions appearing at UC evolutionary stage and can build a framework for biosystems studies focusing on the interplay between UC and MC levels.

Mechanical Twinning is a Correlated Dynamic Process.

Plastic deformation and fracture of materials is accompanied by generation of elastic wave transients known as acoustic emissions (AE). A novel complex methodology combining the statistical analysis of distributions of time intervals between the successive AE events, and the unsupervised cluster analysis of the time series is proposed to test for possible correlations between emitting sources and to highlight their intrinsic dynamics. Aiming at revealing the essential temporal features of the twinning and dislocation dynamics, the proposed methodology was applied to the AE signals produced during plastic deformation in a magnesium alloy where both primary deformation modes - dislocation slip and twinning - operate concurrently. It has been undoubtedly demonstrated that the mechanical twinning belongs to a class of non-Poisson processes having a memory of the past in the millisecond range. As opposes to the correlated behaviour of twins, it was shown that the dislocation slip falls into the category of Poisson processes caused by independent sources.