A series (SPUN) of segmented polyurethanes reinforced with the in situ-generated sodium silica-polyphosphate nano-phase (SSP) was characterized by thermogravimetry, differential calorimetry, ...wide-angle and small-angle X-ray diffraction and stress–strain relationships.
Cross-over from the rubber-like to the solid-like mechanical behavior of the SPUN above the apparent percolation threshold
w
≈
40% was considered as evidence for the onset of the “infinite clusters” of SSP nano-domains spanning the entire volumes of initial (i.e., undeformed) samples. The infinite clusters of SSP nano-domains crossed over from the mass fractal-like to the surface fractal-like behavior at the composition-dependent, characteristic X-ray scattering vectors
q*. A continuous nano-phase of the polyurethane coexisting with a continuous nano-phase (infinite cluster) of the SSP is likely to be expanded due to the “negative pressure” effect.
The article describes the typical problems of the Doppler frequency shift (DFS) and its sign determination in a continuous-wave and pulse radars using radiophotonic technologies in single- and ...multi-target tracking modes. The structure of the hardware-software spectrum analyzer and the variants of its mathematical implementation for solving these problems are proposed. The analyzer is functionally universal, however, its main purpose is to solve the problems of the magnitude and sign determination of the DFS using a radiophotonic device based on tandem single-port amplitude and phase modulators (TAPM) in the radar. For the single-target continuous radar tracking mode, a hardware linear filter method with an oblique frequency response and analysis of pairwise beat frequencies is proposed, and for multi-target tracking, it is supplemented by an FFT with further analysis of all received components by scanning with a software ultra-narrow band filter. The absolute error in the DFS determination by the frequency of information signals depends on the bandwidth of the software ultra-narrow band filter (units of Hz). The relative error in the amplitudes of information signals determination does not exceed ±10 -3 in almost the entire range of amplitudes of the hardware linear filter. The ratio D of the obtained amplitudes for a pair of DFS information frequencies assigned to a specific target allows determining its sign: with D<1, the target is receding, with D>1, the target is approaching. Using a method similar to the method for multi-target tracking of a continuous radar, typical problems of the DFS and its sign determination in the pulse radars can be solved.
Two new minor tribromodibenzo-p-dioxins, spongiadioxin C (1) and its methyl ether (2), were isolated from an Australian marine sponge Dysidea dendyi, together with the known minor metabolites methyl ...ethers of spongiadioxins A (4) and B (6) and polybrominated diphenyl ethers (7−9). The structures of the new compounds were established by 1D and 2D NMR spectroscopy and confirmed by synthesis of 2 from diphenyl ether 9. All isolated compounds inhibited the cell division of fertilized sea urchin eggs.
Previously unknown minor brominated compounds
1a
,
1b
, and
2
were isolated from the EtOH extract of the sponge
Aplysina
sp. (South China Sea). Their structures were established by NMR spectroscopic ...methods and mass spectrometry.
Remdesivir is a drug widely used for the etiotropic treatment of COVID-19. According to a number of studies, the incidence of adverse reactions during remdesivir therapy reaches 66%, with the most ...common is an increase in liver function tests.
The aim
of the work was to study the influence of clinical, demographic and pharmacogenetic factors on the development of drug-induced liver damage during remdesivir therapy in COVID-19 patients.
Materials and methods.
The study comprised 100 hospitalized patients treated with remdesivir. The patients were divided into two groups: group 1 (
n
=32) – remdesivir therapy, developed an increase in the level of liver transaminases; group 2 (control,
n
=68) – did not develop this adverse reaction. The patients in both groups underwent a pharmacogenetic study, and a retrospective analysis of medical records was performed. Based on the data obtained, the association of clinical, laboratory, pharmacological and pharmacogenetic parameters with the development of drug-induced liver damage during remdesivir therapy was studied.
Results.
In the group of patients with the development of drug-induced liver damage, people with a high body mass index were significantly more likely than in the control group (30.7±4.2 kg/m
2
in group 1
vs.
27.3±5.5 kg/m
2
in group 2,
p
=0.003), with a history of diabetes mellitus (odds ratio (OR)=2.647, 95% confidence interval (CI)=1.092–6.414, χ
2
=4.785,
p
=0.029), with higher levels of ferritin in the blood (724.03±432.27 and 553.19±358.48 mg/mol, respectively,
p
=0.040), receiving therapy with angiotensin-converting enzyme inhibitors (OR=5.440, 95% CI=2.160–13.699, χ
2
=14.027,
p
=0.000), statins (OR=3.148, 95% CI=1.307–7.581, χ
2
=6.795,
p
=0.009), and also being heterozygous for the polymorphic marker
rs776746
of the
CYP3A5
gene (OR=3.961, 95% CI=1.343–11.686, χ
2
=6.772,
p
=0.009).
Conclusion.
A high body mass index, a history of diabetes mellitus, high levels of ferritin in the blood, concomitant therapy with angiotensin-converting enzyme inhibitors and statins, as well as a carriage of the AG genotype for the polymorphic marker
rs776746
of the
CYP3A5
gene increase the likelihood of developing drug-induced liver damage during remdesivir therapy. In this regard, it is necessary to consider these factors when prescribing remdesivir therapy, conduct a more careful monitoring of clinical and laboratory indicators of liver damage, and develop personalized approaches to the treatment of COVID-19 patients.
► C
N and C
N bond structures on diamond surface after exposure to RF N
2 plasma. ► Partial oxidation of the N-terminated surface after anodic treatment in electrolytes. ► Higher activity to Fe(CN)
6
...3−/4− reactions compared to fully oxygen-terminated surface.
Epitaxial (100)-oriented diamond layer with boron doping above 10
20
cm
−3 was exposed to an RF N
2 plasma, the resulting surface structure and electrochemical characteristics were investigated. The N
2 plasma treatment was combined with
in vacuo pre-heating to remove adsorbates and with surface shielding to reduce plasma-induced corrosion. X-ray photoemission spectroscopy revealed full nitrogenation of the surface with the presence of C
N and C
N bond structures. Anodic treatment in 0.1
M KOH in the oxygen evolution range generated nitrogen–oxygen bonds and carbon–oxygen functionalities which partially substitute the initial nitrogen-termination. The nitrogenated and electrochemically polarised diamond electrode exhibited higher catalytic activity to Fe(CN)
6
3−/4− but slower to Ru(NH
3)
6
3+/2+ redox reactions, as compared to an identical diamond electrode with fully oxygen-terminated surface.
Sepsis-induced multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in critically ill patients and remains impervious to most therapeutic interventions. We utilized ...a clinically relevant murine model of systemic inflammatory response syndrome (SIRS) during early MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. We focused on processes commonly activated across at-risk organs and constructed an SIRS-associated network based on connectivity among the gene members of these functionally coherent pathways. Our analyses led to the identification of several putative drivers of early MODS whose expression was regulated by epidermal growth factor receptor. Our unbiased, integrative method is a promising approach to unravel mechanisms in system-wide disorders afflicting multiple compartments such as sepsis-induced MODS, and identify putative therapeutic targets.
The incidence of hepatocellular carcinoma (HCC) is rapidly rising largely because of increased obesity leading to nonalcoholic steatohepatitis (NASH), a known HCC risk factor. There are no approved ...treatments to treat NASH. Here, we first used single-nucleus RNA sequencing to characterize a mouse model that mimics human NASH-driven HCC, the
mouse fed a high-fat diet. Activation of endoplasmic reticulum (ER) stress and inflammation was observed in a subset of hepatocytes that was enriched in mice that progress to HCC. We next treated
mice with the ER stress inhibitor BGP-15 and soluble gp130Fc, a drug that blocks inflammation by preventing interleukin-6 trans-signaling. Both drugs have progressed to phase 2/3 human clinical trials for other indications. We show that this combined therapy reversed NASH and reduced NASH-driven HCC. Our data suggest that these drugs could provide a potential therapy for NASH progression to HCC.
Seizures were induced in rats using repetitive injections of picrotoxin, PTX (i.p., every 30 min in a dose of 0.9 mg/kg in the first injection and 0.7 mg/kg in subsequent injections). Picamilon (PM) ...and isopicamilon (IPM) in doses of 20 or 50 mg/kg were i.p. injected into animals 30 min prior to injection of PTX. Epileptiform activity (EFA), recorded from the cerebral structures under conditions of preliminary systemic injections of PM and IPM, could be divided into two types characterized by exclusive development of only spike-wave discharges, SWDs (61.3 %) and regular cortical spike activity with generation of separate short-lasting SWDs (38.7%). In rats with EFA of the first type, the frequency and duration of seizure SWDs decreased significantly after injections of PM and IPM in doses of 50 mg/kg. In rats with EFA of the second type, the intensity of SWDs decreased even after injections of these agents in smaller doses (20 mg/kg). The use of IPM as an agent with a protective anticonvulsive action was more effective.
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