Ab initio study of stability and quadrupole coupling constants in borophosphates.

The DFT method was used to predict the formation energies and quadrupole coupling constants CQ in a series of borophosphates: Li3BP2O8, Li2NaBP2O8, Na3BP2O8, Li2B3PO8, Na5B2P3O13, LiNa2B5P2O14 and Na3B6PO13 composed of different networks and different amounts of borate and phosphate units. The change in formation energies with increasing number of B atoms in this series is attributed to the multiplicity of boron sites and is explained by density of states calculations. The calculated CQ values of 7Li, 23Na and 11B are correlated with the coordination and distortion of polyhedra to elucidate the influence of local and more distant environments. As for the CQ of 11B, it should be in the ranges of 0.26-0.36, 0.48-0.84 and ∼1 MHz for boron tetrahedral distortion indices of 0.004-0.013, 0.015-0.019 and 0.033, respectively, whereas CQ ∼3.0 MHz corresponds to boron in a triangular site. The obtained numerical relationships make it possible to predict the quadrupole frequencies for these nuclei based only on their local environment, and vice versa, to propose structural models from NMR data. These results provide guidance for studying similar characteristics of other borophosphates, the structure of which varies depending on the initial reaction, composition and temperature.

Experimental Early Stimulation of Bone Tissue Neo-Formation for Critical Size Elimination Defects in the Maxillofacial Region.

A biomaterial is proposed for closing extensive bone defects in the maxillofacial region. The composition of the biomaterial includes high-molecular chitosan, chondroitin sulfate, hyaluronate, heparin, alginate, and inorganic nanostructured hydroxyapatite. The purpose of this study is to demonstrate morphological and histological early signs of reconstruction of a bone cavity of critical size. The studies were carried out on 84 white female rats weighing 200-250 g. The study group consisted of 84 animals in total, 40 in the experimental group and 44 in the control group. In all animals, three-walled bone defects measuring 0.5 × 0.4 × 0.5 cm3 were applied subperiosteally in the region of the angle of the lower jaw and filled in the experimental group using lyophilized gel mass of chitosan-alginate-hydroxyapatite (CH-SA-HA). In control animals, the bone cavities were filled with their own blood clots after bone trepanation and bleeding. The periods for monitoring bone regeneration were 3, 5, and 7 days and 2, 3, 4, 6, 8, and 10 weeks. The control of bone regeneration was carried out using multiple morphological and histological analyses. Results showed that the following process is an obligatory process and is accompanied by the binding and release of angiogenic implantation: the chitosan construct actively replaced early-stage defects with the formation of full-fledged new bone tissue compared to the control group. By the 7th day, morphological analysis showed that the formation of spongy bone tissue could be seen. After 2 weeks, there was a pronounced increase in bone volume (p < 0.01), and at 6 weeks after surgical intervention, the closure of the defect was 70-80%; after 8 weeks, it was 100% without violation of bone morphology with a high degree of mineralization. Thus, the use of modified chitosan after filling eliminates bone defects of critical size in the maxillofacial region, revealing early signs of bone regeneration, and serves as a promising material in reconstructive dentistry.

Morphological Reconstruction of a Critical-Sized Bone Defect in the Maxillofacial Region Using Modified Chitosan in Rats with Sub-Compensated Type I Diabetes Mellitus.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia leads to low bone regeneration and a chronic inflammatory response. The purpose of this study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high-molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on five groups of white female Wistar rats: group 1-regeneration of a bone defect in healthy animals under a blood clot; group 2-regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3-bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4-filling of a bone defect with a CH-SA-HA construct in healthy animals; group 5-filling of a bone defect with a CH-SA-HA construct in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

NaGaPO4F - a KTiOPO4-structured solid sodium-ion conductor.

Advanced ionic conductors are crucial for a large variety of contemporary technologies spanning solid state ion batteries, fuel cells, gas sensors, water desalination, etc. In this work, we report on a new member of KTiOPO4-structured materials, NaGaPO4F, with sodium-ion conductivity. NaGaPO4F has been obtained for the first time via a facile two-step synthesis consisting of a hydrothermal preparation of an ammonia-based precursor, NH4GaPO4F, followed by an ion exchange reaction with NaNO3. Its crystal structure was precisely refined using a combination of synchrotron X-ray powder diffraction and electron diffraction tomography. The material is thermally stable upon 450 °C showing no significant structural transformations or degradation but only a ∼1% cell volume expansion. Na-ion mobility in NaGaPO4F was investigated by a joint experimental and computational approach comprising solid-state nuclear magnetic resonance (NMR) and density functional theory (DFT). DFT and bond-valence site energy (BVSE) calculations reveal 3D diffusion of sodium in the [GaPO4F] framework with migration barriers amounting to 0.22 and 0.44 eV, respectively, while NMR yields 0.3-0.5 eV that, being coupled with a calculated bandgap of ∼4.25 eV, makes NaGaPO4F a promising fast Na-ion conductor.

Long-term outcomes of third-line therapy with tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: A real-life experience.

Introduction: Tyrosine kinase inhibitor (TKI) therapy has greatly improved the prognosis of patients with chronic myeloid leukemia (CML), improving the survival expectancy of patients with chronic phase (CP) CML to that of the general population. However, despite these advances, nearly 50% of patients with CP CML experience failure to respond to frontline therapy, and most fail to respond to the subsequent second-line TKI. Treatment guidelines for patients failing second-line therapy are lacking. This study aimed to determine the efficacy of TKIs as third-line therapy in a "real-world" clinical practice setting and identify factors favorably influencing the long-term outcomes of therapy. Methods: We have retrospectively analyzed the medical records of 100 patients with CP CML. Results: The median age of the patients was 51 (range, 21-88) years, and 36% of the patients were men. The median duration of the third-line TKI therapy was 22 (range, 1- 147) months. Overall, the rate of achieving complete cytogenetic response (CCyR) was 35%. Among the four patient groups with different levels of responses at baseline, the best results were achieved in the groups with any CyR at the baseline of third-line therapy. Thus, СCyR was reached in all 15 and 8/ 16 (50%) patients with partial cytogenetic response (PCyR) or minimal or minor CyR (mmCyR), respectively, whereas CCyR was detected only in 12/69 (17%) patients without any CyR at baseline (p < 0.001). Univariate regression analysis revealed that the factors negatively associated with CCyR achievement in thirdline TKI therapy were the absence of any CyR on first- or second-line TKI therapy (p < 0.001), absence of CHR prior to third-line TKI (p = 0.003), and absence of any CyR prior to third-line TKI (p < 0.001). During the median observation time from treatment initiation to the last visit [56 (4-180) months], 27% of cases progressed into accelerated phase or blast phase CML, and 32% of patients died. Discussion: Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with CCyR on third-line than in the group without CCyR on third-line therapy. At the last visit, third-line TKI therapy was ongoing in 18% of patients, with a median time of treatment exposure of 58 (range, 6-140) months; 83% of these patients had stable and durable CCyR, suggesting that patients without CHR at baseline and without CCyR at least by 12 months on third-line TKI should be candidates for allogeneic stem cell transplantation, third-generation TKIs, or experimental therapies.

SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19.

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties. While escape from humoral immunity certainly contributes to intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin's lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented the binding of known immunogenic SARS-CoV-2 HLA class I antigens. By experimentally assessing the effect of a subset of the escape mutations, we show that they resulted in a loss of as much as ~1% of effector CD8 T cell response. Our results indicate that CD8 T cell escape represents a major underappreciated contributor to SARS-CoV-2 evolution in humans.

Electronic structure, sodium diffusion and redox potentials of low-symmetry NaMFe(MoO4 )3 (M = Mg, Ni).

Sodium polyanionic compounds with transition metals are of considerable research interest for the search of new cathode materials for sodium-ion batteries. In this work, we employed ab initio calculations to evaluate three key battery properties: phase stability, diffusion barriers and redox voltage of low-symmetry molybdates NaMFe(MoO4 )3 (M = Mg, Ni) with α- and ß-NaFe2 (MoO4 )3 structures. First, we showed that the Hubbard Ucorrection within the GGA + Uapproach is necessary to correctly refer these molybdates to semiconductors. The sodium diffusion along various pathways was thoroughly examined, which allowed us to establish the most probable pathways with the lowest migration barriers. These compounds have different directions of sodium diffusion with twice different barriers that was associated to the peculiarities of their crystal structure. The high potentials and structural stability during sodium extraction, along with low-diffusion barriers predicted for NaMFe(MoO4 )3 (M = Mg, Ni) indicate that these molybdates may be promising high-voltage cathode materials for sodium-ion batteries.

Coexistence of three types of sodium motion in double molybdate Na9Sc(MoO4)6: 23Na and 45Sc NMR data and ab initio calculations.

The rechargeable Na-ion batteries attract much attention as an alternative to the widely used but expensive Li-ion batteries. The search for materials with high sodium diffusion is important for the development of solid state electrolytes. We present the results of experimental and ab initio studies of the Na-ion diffusion mechanism in Na9Sc(MoO4)6. The ion conductivity reaches the value of 3.6 × 10-2 S cm-1 at T ∼ 850 K. The 23Na and 45Sc NMR data reveal the coexistence of three different types of Na-ion motion in the temperature range from 300 to 750 K. They are activated at different temperatures and are characterized by substantially different dynamics parameters. These features are confirmed by ab initio calculations of activation barriers for sodium diffusion along various paths.

Nutritional biomarkers: Current view and future perspectives.

There is a poor relationship between nutrient intake and existing nutritional biomarkers due to variety of factors affecting their sensitivity and specificity. To explore the impact of nutrients at molecular level and devising a sensitive biomarker, proteomics is a central technology with sirtuins as one of the most promising nutritional biomarker. Sirtuins (seven mammalian sirtuins reported so far) have been reported to perform protein deacetylases and ADP-ribosyltransferases activity. It is distributed in different cellular compartments thereby controlling several metabolic processes. Sirtuins are oxidized nicotinamide adenine dinucleotide dependent, which implicates a direct effect of the metabolic state of the cell on its activity. Calorie restriction upregulates the mammalian sirtuin protein levels in variety of tissues and organs where it acts upon both histone and nonhistone substrates. Sirtuin senses nutrient availability and impacts gluconeogenesis, glycolysis, and insulin sensitivity. It deacetylates and inhibits the nuclear receptor that activates fat synthesis and adipogenesis in the body, leading to fat loss and bringing favorable cellular and health changes. Sirtuins mediates intracellular response that promotes cell survival, DNA damage repair thereby increasing the cell longitivity. The activation of sirtuins brings a wide spectrum of other health benefits and its activity levels are indicative of nutritional status as well as disease progression in cancer, inflammation, obesity, cardiovascular diseases, and viral infections. There are several foods that activate sirtuin activity and offer significant health benefits by their consumption.

Mucormycosis in haematological patients: case report and results of prospective study in Saint Petersburg, Russia.

We prospectively observed 36 haematological patients with mucormycosis from nine hospitals of St. Petersburg during 2004-2013. The most frequent underlying diseases were acute leukaemia (64%), and main risk factors were prolonged neutropenia (92%) and lymphocytopenia (86%). In 50% of the patients, mucormycosis was diagnosed 1-65 days after invasive aspergillosis. Main clinical form of mucormycosis was pulmonary (64%), while two or more organ involvement was noted in 50% of the cases. The most frequent aetiological agents of mucormycosis were Rhizopus spp. (48%). Twelve-week survival rate was 50%. Combination therapy (echinocandins + amphotericin B forms) and recovery from the underlying disease significantly improved the survival rate.