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The interaction of alkoxysilanes with nanoscaled giant polyoxoclusters is a challenging route for efficiently building blocks for supramolecular smart design.

The unified space platforms (USP) of foreign countries’ spacecraft, the state and directions of their development are considered. Examples of various platforms, their composition, purpose, features of the load bearing structure, characteristics, advantages and disadvantages are given. USP are characterized by flexible adaptation for solving various tasks, both through the use of various additional modules, and due to their own configuration. The use of USP allows creating spacecraft for various research and experimental tasks, as well as communications and Earth remote sensing with the lowest financial costs and the shortest terms of development.

Altres ajuts: Sponsorship for this study and the Rapid Service Fee were funded by JSC BIOCAD, Ul. Italianskaya 17, St Petersburg, Russia, 191186 Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a ≥ 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P < 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming. Clinical Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT03390101).

Objective and design The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. Subjects The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. Treatment 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. Methods The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. Results 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. Conclusion In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. Trail registration The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

BACKGROUND: Diabetes mellitus leads to disruption of the skin repair processes, but the leading mechanisms of this pathology have not yet been identified. In this regard, in our work, we decided to check how hyperglycaemia affects the process of keratinocyte phenotype changes during wound healing. AIMS: To study the effect of hyperglycaemia on wound healing and differentiation of keratinocytes in a rat streptozotocin-induced diabetes model. MATERIALS AND METHODS: Diabetes mellitus was induced in rats by using streptozotocin, 65 mg / kg, intraperitoneally, once. The wound was applied in the supra-scapular region on the 42nd day, after which (after 8, 16, and 24 days) the repair process was evaluated using histological methods. Immunohistochemistry was used to evaluate the expression of cytokeratin-10 and cytokeratin-17. RESULTS: In rats with diabetes mellitus, wound healing slowed down in the later stages, compared with the control group. In general, wound healing was accompanied by an increase in the expression of cytokeratin-10 in its region compared with intact skin, and contractile keratinocytes activation was disrupted in diabetic rat wounds. CONCLUSIONS: Hyperglycaemia slightly slows wound healing in rats and impairs contractile keratinocytes activation.

Netakimab is a humanised camelid-derived monoclonal antibody targeting interleukin-17A. Here, we report the results of post-hoc analysis of the ASTERA phase 3 study (NCT03447704, February 27, 2018) in patients with active radiographic axial spondyloarthritis (r-axSpA) grouped by baseline C-reactive protein (CRP), baseline sacroiliac joint (SIJ) inflammation through magnetic resonance imaging (MRI) or presence of peripheral arthritis (PA).In this double-blinded, multicentre, randomised, placebo-controlled, phase 3 ASTERA study, 228 adult patients with active r-axSpA received 120 mg of subcutaneous netakimab or placebo at weeks 0, 1, 2, and thereafter every other week. For the subanalysis, 16-week data of 114 netakimab-treated patients with the available baseline CRP and SIJ MRI were grouped by normal (5 mg/L) or abnormal (≥5 mg/L) CRP, by the grade of sacroiliitis (SI) based on the SPARCC MRI score2 (MRI-SI-) or ≥2 (MRI-SI+), or by the presence of PA. ASAS-recommended activity, spinal mobility, and function endpoints for r-axSpA were analysed.At week 16, an improvement in all the outcomes was similar for MRI-SI- and MRI-SI+ patients, except for a change in ASspi-MRI-a which was significantly greater in MRI-SI+. Netakimab was effective regardless of baseline CRP and PA. For patients with CRP ≥5 mg/L, a more pronounced decline in r-axSpA activity was observed with a trend towards the most prominent improvement in ASDAS-CRP and BASDAI for patients with CRP20 mg/L.Subcutaneous netakimab is effective in patients with r-axSpA irrespective of baseline CRP and inflammation on SIJ MRI. The benefit in patients with high CRP (20 mg/L) was more pronounced.

BACKGROUND: The development of diabetes mellitus (DM) is accompanied by hyperglycemia, which leads to the development of neuropathy. We assume that the individual characteristics of the organization of the autonomic nervous system (ANS) in humans affect not only the ability to withstand stress, but can determine the course of diseases, including diabetes. AIMS: The study of the dynamics of heart rate variability and temperature sensitivity in rats against the background of hyperglycemia depending on the organization of the initial regulation of the heart under ANS. MATERIALS AND METHODS: 70 male rats were randomized by weight and level of total heart rate variability (HRV) on animals with initially low and high levels of total HRV. Diabetes was modeled by a single i.p. injection of streptozotocin (STZ). The control group received a single i.p. injection of citrate buffer (CB). Before the induction of diabetes, as well as on 21, 42 and 70 days after the injection of STZ, a comprehensive examination of rats condition was carried out: 1) assessment of HRV; 2) analysis of temperature-pain sensitivity; 3) assessment of glucose and ketone bodies in the blood. Similarly, animals in the CB group were examined. RESULTS: The change in HRV and temperature-pain sensitivity in rats depends on the initial level of HRV. In rats with low variability, the reaction time in the pain test increased by 832% from the 28th day of the experiment, from 21 days the bradycardia increased and the decrease in individual HRV indices at rest, but not the response of these parameters to cold stress. CONCLUSION: The development of ANSs lesion depends on the initial level of HRV. Low variability animals are more resistant to hyperglycemia: the normal ranges of CP reactions from the side of HR, the parameters of total HRV and the CVHS contribution to it are longer, but there is a loss of temperature sensitivity. Initially, highly variable rats with the development of diabetes do not lose temperature sensitivity, but demonstrate an imbalance in the regulatory circuits of heart rate and HRV.

Objectives: Diabetic retinopathy remains the major cause of blindness among the working-age population of developed countries. Considering this, experimental models of diabetes involving laboratory animals are important for assessing clinically significant methods to determine early pathologic alterations of the retina. The early detection of diabetic retinopathy in combination with a search for new pathogenetic targets will enable focusing on new strategies to limit the development of critical changes in the retina and to prolong retinal functioning during the development of diabetes mellitus. Aim: This study aimed to define parameters of electroretinography test that identifies changes due to retinal impairment in diabetes. Methods: Experimental diabetes was induced in Wistar rats by intraperitoneally injecting streptozocin (65 mg/kg; group ‘DM’). The control group (‘CB’) received intraperitoneal injections of the vehicle, i.e. citric buffer. On each consecutive day of the experiment, all rats received insulin detemir (2 u/kg). Ophthalmoscopy and electroretinography were conducted before initiating the experiment and after 50, 58 and 66 days of injectin sptreptozocin. Results: Amid 2u\kg insulin injection the glucose level in venous blood in «DM» group amounted to 30-40 mM. The ophthalmoscopy showed that the optic nerve disk paled by the 50th day, with its line erasing. During electroretinography, wave amplitude in oscillatory potential test tended to decrease. β-wave latency of photopic system increased with α-wave latency of photopic system and α- and β-waves latency of scotopic system not altering. In addition, the amplitude of rhythmic stimulation of 8 and 12 Hz decreased. Conclusion: The most apparent parameters of electroretinography for modelling streptozocin-induced diabetes are wave amplitude during the oscillatory potential test, photopic B-wave latency and the amplitude of rhythmic stimulation. These results suggest that in diabetes, ischaemic injury is an important cause of early dysfunction of inner retinal layers.

A new method of azide–alkyne cycloaddition (AAC) in the presence of Zn(OAc)2 as an inexpensive and environmentally friendly catalyst in neat water has been developed. The proposed methodology has been applied for the synthesis of 1,4-disubstituted-1,2,3-triazoles from terminal alkynes and 1,4,5-trisubstituted-1,2,3-triazoles from internal alkynes. It has been found that Zn-catalyzed AAC is extremely sensitive to steric hindrance in acetylenes and a method of regioselective triazole ring formation has been proposed. Particularly important is the isolation and characterization of a relatively stable Zn-containing intermediate, which has been characterized by NMR and HRMS.

A simple green method for the hydrodediazoniation of arenediazoniumtosylates in water solutions in the presence of Fe-core/carbon-shell nanoparticles as a reagent was developed. In this course, nanoparticles were used as a hydrogen source, but not water.

Mark–recapture ringing data from two sites in northwestern Russia were used to estimate apparent survival rates in populations of Garden Warbler Sylvia borin and Whitethroat S. communis. The computer program MARK was used to estimate survival and recapture rates, adjusted for transient birds, with respect to sexes at each site. Survival rate of Garden Warbler was higher than that of Whitethroat. This difference may reflect the habitat preferences of these species. Survival of Garden Warbler was similar between sexes; females of Whitethroat did not return to the study sites.

The solid solutions of lanthanum niobates substituted by yttrium, bismuth and tungsten were synthesized. The structure of the solid solutions is either LaNbO4-based monoclinic or BiNbO4-based triclinic. The series where niobium is substituted by tungsten on B site reveals phase-modulated structure. The values of cell parameters decrease with increasing the dopant concentration for all samples except the tungsten series although the latter show higher total conductivity., {"references":["M. Huse, T. Norby, R. Haugsrud, \"Effects of A and B site acceptor doping on hydration and proton mobility of LaNbO4\" Int. J. Hydr. En., vol. 37. no. 9, pp. 8004–8016, May 2012.","A.D. Brandao, J. Gracio, G.C. Mather, V.V. Kharton, D.P. Fagg, \"B-site substitutions in LaNb1−xMxO4−δ materials in the search for potential proton conductors (M=Ga, Ge, Si, B, Ti, Zr, P, Al)\" J. Sol. State Chem. vol. 184. no 4, pp. 863-870, Apr. 2011.","S. Wachowski, A. Mielewczyk-Gryn, M. Gazda, \"Effect of isovalent substitution on microstructure and phase transition of LaNb1−xMxO4 (M=Sb, V or Ta; x=0.05–0.3)\" J. Sol. State Chem. vol. 219, pp. 201-209, Nov. 2014.","R. Haugsrud, T. Norby, \"Proton conduction in rare-earth ortho-niobates and ortho-tantalates\", Nat. Mater., vol. 5, pp.193-196, Feb. 2006.","G.C. Mather, C.A.J. Fisher, M.S. Islam, \"Defects, dopants, and protons in LaNbO4\", Chem. Mater., vol. 22, pp. 5912-5917, Oct. 2010.","S.J. Skinner, Y. Kang, \"X-ray diffraction studies and phase transformations of CeNbO4+δ using in situ techniques\", Sol. State Sci, vol. 5, pp. 1475–1479, Nov.-Dec. 2003.","C. Solis, J.M. Serra, \"Adjusting the conduction properties of La0.995Ca0.005NbO4−δ by doping for proton conducting fuel cells electrode operation\", Sol. State Ion., vol. 190, pp.38-45, May 2011.","M.A. Laguna-Bercero, R.D. Bayliss, S.J. Skinner \"LaNb0.84W0.16O4.08 as a novel electrolyte for high temperature fuel cell and solid oxide electrolysis applications\" Sol. State Ion., vol. 262, pp. 298-302, Sept. 2014.","Diffrac Plus: Topas Bruker AXS GmbH, Ostliche. Rheinbruckenstraße 50, D-76187, Karlsruhe, Germany. 2006.\n[10]\tC. Li, R.D. Bayliss, S.J. Skinner, \"Crystal structure and potential interstitial oxide ion conductivity of LnNbO4 and LnNb0.92W0.08O4.04 (Ln = La, Pr, Nd)\", Sol. State Ion., vol. 262, pp. 530–535, Sept. 2014.\n[11]\tR.D. Shannon, \"Revised Effective Ionic Radii and Systematic Studies of Interatomic Distances in Halides and Chalcogenides\", Acta Cryst., vol. 32, iss. 5, pp. 751-767, Sept. 1976.\n[12]\tP. Sarin, R.W.Hughes, D R. Lowry, Z.D. Apostolov, W.M. Kriven, \"High-Temperature Properties and Ferroelastic Phase Transitions in Rare-Earth Niobates (LnNbO4)\" J. Am. Ceram. Soc., vol. 97, no 10, pp. 3307–3319, May 2014."]}

Aqueous suspensions of 10 nm, 50 nm, or 1 μm Fe3O4 particles were injected intraperitoneally (ip) to rats at a dose of 500 mg/kg in 4 mL of sterile deionized water 3 times a week for 5 weeks. Following exposure, functional and biochemical indices and histopathological examinations of spleen and liver tissues of exposed rats were evaluated for signs of toxicity. The iron content of the blood was measured photometrically, and that of the liver and the spleen by atomic adsorption spectroscopy (AAS) and electron paramagnetic resonance (EPR) methods. It was found that, given equal mass doses, Fe3O4 nanoparticles possess considerably higher systemic toxicity than microparticles, but within the nanometric range the relationship between particle size and resorptive toxicity is intricate and nonunique. The latter fact may be attributed to differences in different nanoparticles' toxicokinetics, which are controlled by both more or less substantial direct penetration of nanoparticles through biological barriers and their unequal solubility.

Nanocluster polyoxometalates with a structure of buckyball (fullerene) are a promising means of targeted delivery of drugs in the body. In this paper, based on an analysis of histological sections of liver and kidney and peripheral blood, showed a significant reduction of toxicity of buckyballs, containing ions of molybdenum (VI), the substitution of Mo (V) ions to Fe (III), in contrast to buckyballs based on Mo (V). The absence of accumulation of molybdenum in rats with a daily intramuscular injection of aqueous solutions of both drugs within a month was confirmed.

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e21557 Background: Mitochondrial dysfunction is one of the mechanisms for the development of heart disease that requires close study. Diabetic cardiomyopathy is the leading cause of death in such patients due to the development of heart failure. Chronic pain may be associated with higher prevalence of cardiovascular disease, and little is known about its potential biological consequences. The purpose of this study was to analyze parameters of free radical oxidation and mitochondrial respiration in heart cells in experimental animals with malignant tumors growing in presence of diabetes mellitus (DM) and chronic neurogenic pain. Methods: The study included outbred female rats (n = 32) weighing 180-220 g and C57BL/6 female mice (n = 84) weighing 21-22 g. Experimental groups of rats were: intact animals (n = 8), controls (n = 8) with DM, comparison group (n = 8) with subcutaneously inoculated Guerin’s carcinoma, and main group (n = 8) with Guerin’s carcinoma subcutaneously inoculated after 1 week of persistent hypothyroidism. Experimental groups of mice were: intact animals (n = 21), controls (n = 21) with a model of chronic neurogenic pain (CNP) created by bilateral sciatic nerve ligation, comparison group (n = 21) with subcutaneously inoculated melanoma (B16/F10), and main group (n = 21) with melanoma subcutaneously inoculated 3 weeks after the CNP model was created (CNP+B16/F10). Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/g of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/g of protein), and malondialdehyde (MDA) (nM/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program. Results: DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times (p < 0.05) and downregulated cytochrome C by 1.5 times (p < 0.05) in heart cell mitochondria, compared to intact values. DM+Guerin’s carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times (p < 0.05) and decreased cytochrome C by 1.5 times (p < 0.05), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times (p < 0.05) and decreased cytochrome C by 1.6 times (p < 0.05) in heart cell mitochondria. Conclusions: Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells which results in DNA damage and destabilization of the respiratory chain mediated by free radical oxidation processes.