Intratumoral Cell Heterogeneity in Patient-Derived Glioblastoma Cell Lines Revealed by Single-Cell RNA-Sequencing.

Glioblastoma cell lines derived from different patients are widely used in tumor biology research and drug screening. A key feature of glioblastoma is the high level of inter- and intratumor heterogeneity that accounts for treatment resistance. Our aim was to investigate whether intratumor heterogeneity is maintained in cell models. Single-cell RNA sequencing was used to investigate the cellular composition of a tumor sample and six patient-derived glioblastoma cell lines. Three cell lines preserved the mutational profile of the original tumor, whereas three others differed from their precursors. Copy-number variation analysis showed significantly rearranged genomes in all the cell lines and in the tumor sample. The tumor had the most complex cell composition, including cancer cells and microenvironmental cells. Cell lines with a conserved genome had less diverse cellularity, and during cultivation, a relative increase in the stem-cell-derived progenitors was noticed. Cell lines with genomes different from those of the primary tumors mainly contained neural progenitor cells and microenvironmental cells. The establishment of cell lines without the driver mutations that are intrinsic to the original tumors may be related to the selection of clones or cell populations during cultivation. Thus, patient-derived glioblastoma cell lines differ substantially in their cellular profile, which should be taken into account in translational studies.

Matrisome Transcriptome Dynamics during Tissue Aging.

The extracellular matrix (ECM) is a complex three-dimensional network of macromolecules that provides structural support for the cells and plays a significant role in tissue homeostasis and repair. Growing evidence indicates that dysregulation of ECM remodeling contributes to various pathological conditions in the body, including age-associated diseases. In this work, gene expression data of normal human tissues obtained from the Genotype-Tissue Expression project, as well as data from MatrisomeDB 2.0, the ECM-protein knowledge database, are used to estimate the age-dependent matrisome transcriptome dynamics in the blood, heart, brain, liver, kidneys, lungs, and muscle. Differential gene expression (DE) analysis revealed dozens of matrisome genes encoding both structural elements of the ECM and ECM-associated proteins, which had a tissue-specific expression profile with age. Among common DE genes that changed expression with age in at least three tissues, COL18A1, MFAP1, IGFBP7, AEBP1, LTBP2, LTBP4, LG14, EFEMP1, PRELP, BGN, FAM20B, CTSC, CTSS, and CLEC2B were observed. The findings of the study also reveal that there are sex-specific alterations during aging in the matrisome gene expression. Taken together, the results obtained in this work may help in understanding the role of the ECM in tissue aging and might prove valuable for the future development of the field of ECM research in general.

Cognitive Impairment in Nonagenarians: Potential Metabolic Mechanisms Revealed by the Synergy of In Silico Gene Expression Modeling and Pathway Enrichment Analysis.

Previous studies examining the molecular and genetic basis of cognitive impairment, particularly in cohorts of long-living adults, have mainly focused on associations at the genome or transcriptome level. Dozens of significant dementia-associated genes have been identified, including APOE, APOC1, and TOMM40. However, most of these studies did not consider the intergenic interactions and functional gene modules involved in cognitive function, nor did they assess the metabolic changes in individual brain regions. By combining functional analysis with a transcriptome-wide association study, we aimed to address this gap and examine metabolic pathways in different areas of the brain of older adults. The findings from our previous genome-wide association study in 1155 older adults, 179 of whom had cognitive impairment, were used as input for the PrediXcan gene prediction algorithm. Based on the predicted changes in gene expression levels, we conducted a transcriptome-wide association study and functional analysis using the KEGG and HALLMARK databases. For a subsample of long-living adults, we used logistic regression to examine the associations between blood biochemical markers and cognitive impairment. The functional analysis revealed a significant association between cognitive impairment and the expression of NADH oxidoreductase in the cerebral cortex. Significant associations were also detected between cognitive impairment and signaling pathways involved in peroxisome function, apoptosis, and the degradation of lysine and glycan in other brain regions. Our approach combined the strengths of a transcriptome-wide association study with the advantages of functional analysis. It demonstrated that apoptosis and oxidative stress play important roles in cognitive impairment.

Machine Learning-Based Decision-Making in Geriatrics: Aging Phenotype Calculator and Survival Prognosis.

Aging is a natural process with varying effects. As we grow older, our bodies become more susceptible to aging-associated diseases. These diseases, individually or collectively, lead to the formation of distinct aging phenotypes. Identifying these aging phenotypes and understanding the complex interplay between coexistent diseases would facilitate more personalized patient management, a better prognosis, and a prolonged lifespan. Many studies distinguish between successful aging and frailty. However, this simple distinction fails to reflect the diversity of underlying causes. In this study, we sought to establish the underlying causes of frailty and determine the patterns in which these causes converge to form aging phenotypes. We conducted a comprehensive geriatric examination, cognitive assessment, and survival analysis of 2,688 long-living adults (median age = 92 years). The obtained data were clustered and used as input data for the Aging Phenotype Calculator, a multiclass classification model validated on an independent dataset of 96 older adults. The accuracy of the model was assessed using the receiver operating characteristic curve and the area under the curve. Additionally, we analyzed socioeconomic factors that could contribute to specific aging patterns. We identified five aging phenotypes: non-frailty, multimorbid frailty, metabolic frailty, cognitive frailty, and functional frailty. For each phenotype, we determined the underlying diseases and conditions and assessed the survival rate. Additionally, we provided management recommendations for each of the five phenotypes based on their distinct features and associated challenges. The identified aging phenotypes may facilitate better-informed decision-making. The Aging Phenotype Calculator (ROC AUC = 92%) may greatly assist geriatricians in patient management.

Decelerated Epigenetic Aging in Long Livers.

Epigenetic aging is a hot topic in the field of aging research. The present study estimated epigenetic age in long-lived individuals, who are currently actively being studied worldwide as an example of successful aging due to their longevity. We used Bekaert's blood-based age prediction model to estimate the epigenetic age of 50 conditionally "healthy" and 45 frail long-livers over 90 years old. Frailty assessment in long-livers was conducted using the Frailty Index. The control group was composed of 32 healthy individuals aged 20-60 years. The DNA methylation status of 4 CpG sites (ASPA CpG1, PDE4C CpG1, ELOVL2 CpG6, and EDARADD CpG1) included in the epigenetic clock was assessed through pyrosequencing. According to the model calculations, the epigenetic age of long-livers was significantly lower than their chronological age (on average by 21 years) compared with data from the group of people aged 20 to 60 years. This suggests a slowing of epigenetic and potentially biological aging in long livers. At the same time, the obtained results showed no statistically significant differences in delta age (difference between the predicted and chronological age) between "healthy" long livers and long livers with frailty. We also failed to detect sex differences in epigenetic age either in the group of long livers or in the control group. It is possible that the predictive power of epigenetic clocks based on a small number of CpG sites is insufficient to detect such differences. Nevertheless, this study underscores the need for further research on the epigenetic status of centenarians to gain a deeper understanding of the factors contributing to delayed aging in this population.

Determination of the Oxygen Content in the LiF-NaF-KF Melt.

The present paper is dedicated to the quantitative determination of oxygen-containing impurities in the LiF-NaF-KF eutectic using electrochemical (cyclic and square-wave voltammetry) and reduction melting methods. The LiF-NaF-KF melt was analyzed before and after purifying electrolysis. The amount of oxygen-containing impurities removed from the salt during purification was determined. It was found that after electrolysis, the concentration of oxygen-containing impurities decreased by 7 times. The results obtained via electrochemical techniques and reduction melting were well-correlated, which made it possible to evaluate the quality of the LiF-NaF-KF F melt. To verify the analysis conditions, mechanical mixtures of LiF-NaF-KF containing Li2O were analyzed using the reduction melting method. The oxygen concentration in the mixtures varied from 0.672 to 2.554 wt. %. Based on the analysis results, the dependence approximated by the straight line was obtained. These data may be used to draw calibration curves and to further develop the procedure of oxygen analysis of fluoride melts.

Gut Microbiome in Post-COVID-19 Patients Is Linked to Immune and Cardiovascular Health Status but Not COVID-19 Severity.

The composition of the gut microbiome stores the imprints of prior infections and other impacts. COVID-19 can cause changes in inflammatory status that persist for a considerable time after infection ends. As the gut microbiome is closely associated with immunity and inflammation, the infection severity might be linked to its community structure dynamics. Using 16S rRNA sequencing of stool samples, we investigated the microbiome three months after the end of the disease/infection or SARS-CoV-2 contact in 178 post-COVID-19 patients and those who contacted SARS-CoV-2 but were not infected. The cohort included 3 groups: asymptomatic subjects (n = 48), subjects who contacted COVID-19 patients with no further infection (n = 46), and severe patients (n = 86). Using a novel compositional statistical algorithm (nearest balance) and the concept of bacterial co-occurrence clusters (coops), we compared microbiome compositions between the groups as well as with multiple categories of clinical parameters including: immunity, cardiovascular parameters and markers of endothelial dysfunction, and blood metabolites. Although a number of clinical indicators varied drastically across the three groups, no differences in microbiome features were identified between them at this follow-up point. However, there were multiple associations between the microbiome features and clinical data. Among the immunity parameters, the relative lymphocyte number was linked to a balance including 14 genera. Cardiovascular parameters were associated with up to four bacterial cooperatives. Intercellular adhesion molecule 1 was linked to a balance including ten genera and one cooperative. Among the blood biochemistry parameters, calcium was the only parameter associated with the microbiome via a balance of 16 genera. Our results suggest comparable recovery of the gut community structure in the post-COVID-19 period, independently of severity or infection status. The multiple identified associations of clinical analysis data with the microbiome provide hypotheses about the participation of specific taxa in regulating immunity and homeostasis of cardiovascular and other body systems in health, as well as their disruption in SARS-CoV-2 infections and other diseases.

Mortality and survival in nonagenarians during the COVID-19 pandemic: Unstable equilibrium of aging.

Introduction: Aging puts the human body under an immense stress and makes it extremely susceptible to many diseases, often leading to poor outcomes and even death. Long-living individuals represent a unique group of people who withstood the stress of time and offer an abundance of information on the body's ability to endure the pressure of aging. In this study, we sought to identify predictors of overall one-year mortality in 1641 long-living individuals. Additionally, we analyzed risk factors for COVID-19-related morality, since statistics demonstrated an extreme vulnerability of older adults. Methods: We conducted a two-stage evaluation, including a comprehensive geriatric assessment for major aging-associated: frailty, cognitive impairment, frontal lobe dysfunction, chronic pain, anxiety, risk of falls, sensory deficit, depression, sarcopenia, risk of malnutrition, fecal and urinary incontinence, dependence in Activities of Daily Living, dependence in Instrumental Activities of Daily Living, polypragmasia, and orthostatic hypotension; extensive blood testing, a survey, and a one-year follow-up interview. Results: The most reliable predictors of overall mortality were cognitive impairment, malnutrition, frailty, aging-associated diseases and blood markers indicating malnutrition-induced metabolic dysfunctions (decreased levels of protein fractions, iron, 25-hydroxyvitamin D, and HDL), and aging biomarkers, such as IGF-1 and N-terminal pro b-type natriuretic peptide. In post-COVID 19 participants, the most significant mortality predictors among geriatric syndromes were depression, frontal lobe dysfunction and frailty, and similar to overall mortality blood biomarkers - 25-hydroxyvitamin D, IGF-1, HDL as well as high white blood cell, neutrophils counts and proinflammatory markers. Based on the results, we built a predictive model of overall mortality in the long-living individuals with f-score=0.76. Conclusion: The most sensitive and reliable predictors of mortality were modifiable. This is another evidence of the critical importance of proper geriatric care and support for individuals in their "golden years". These results could facilitate geriatric institutions in their pursuit for providing improved care and could aid physicians in detecting early signs of potentially deadly outcomes. Additionally, our findings could be used in developing day-to-day care guidelines, which would greatly improve prevention statistics.

The association of osteoporosis and geriatric syndromes in the elderly: data from the Russian epidemiological study EVKALIPT.

Osteoporosis is associated with almost all geriatric syndromes (GSs), and the occurrence of osteoporosis in patients over 65 years of age increases by 1.2-2.5 times. Early diagnosis of osteoporosis and GSs is very important. Additional programs should be adopted by the state to introduce information about the possibilities of working with elderly patients. PURPOSE: To analyze associations of osteoporosis with geriatric syndromes in patients aged 65 years and older in the Russian Federation. METHODS: A total of 4308 patients (30% men) aged 65-107 years were examined and distributed into 3 age groups (65-74 years, 75-84 years, and 85 years and older). All patients underwent a comprehensive geriatric assessment. In the "Falls and risk of falls" module, the number and circumstances of falls over the previous year were analyzed, as well as the history of fractures. The presence of osteoporosis was determined based on medical records. Physical examination included anthropometric measurements and standard enquiry, short physical performance battery (SPPB), dynamometry, measurement of gait velocity, Mini-Cog test, and orthostatic test. RESULTS: A total of 507 patients (11.8%) had evidence of osteoporosis; indications of low-energy fractures in history were recorded in 739 (17.3%) patients. Patients with osteoporosis were older, shorter, and predominantly women; had a lower body weight and a higher Charlson comorbidity index; and took more drugs. Patients with osteoporosis had lower gait velocity, hand grip strength, Barthel index value, and scores of the Lawton instrumental activities of daily living scale, the MNA (Mini Nutritional Assessment) short-form, and the SPPB. Osteoporosis is associated with almost all geriatric syndromes (GSs), and the occurrence of osteoporosis in patients over 65 years of age increases by 1.2-2.5 times. CONCLUSIONS: Osteoporosis is associated with almost all GSs. The association of osteoporosis with advanced GSs aggravates the condition of these patients. Early diagnosis of osteoporosis and GSs is very important. Additional programs should be adopted by the state to introduce information about the possibilities of working with elderly patients: early detection and correction of osteoporosis.

A summary of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis.

Key statements of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis are summarized. They were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis and approved by the Russian Ministry of Health. PURPOSE: To summarize key statements of the Russian clinical practice guidelines for the diagnosis and treatment of osteoporosis. METHODS: The Russian clinical guidelines on the diagnosis and treatment of osteoporosis were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis: These comprised the Russian Association of Endocrinologists, the Russian Association for Osteoporosis, the Association of Rheumatologists of Russia, the Association of Orthopedic surgeons and Traumatologists of Russia, the Russian Association of Gynecologists-Endocrinologists, and the Russian Association of Gerontologists and Geriatrics. The guidelines are based on a systematic literature review and principles of evidence-based medicine and were compiled in accordance with the requirements for clinical recommendations developed by the Ministry of Health of the Russian Federation. RESULTS: Key statements included in the Russian guidelines of osteoporosis approved by the Russian Ministry of Health in 2021 are summarized. The statements are graded based on levels of evidence and supported by short comments. The guidelines are focused on the current approach to screening, diagnosis, differential diagnosis, and treatment of osteoporosis. CONCLUSION: These guidelines are a practical tool for general practitioners, as well as medical specialists, primarily endocrinologists, rheumatologists, orthopedic surgeons, and other physicians who are involved in the management of patients with osteoporosis.

Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: An observational study.

OBJECTIVE: The aim of the study was to assess inflammatory markers and clinical outcomes in adult patients admitted to hospital with mild-to-moderate COVID-19 and treated with a combination of standard-of-care (SOC) and targeted immunosuppressive therapy including anti-IL-17A (netakimab), anti-IL-6R (tocilizumab), or JAK1/JAK2 inhibitor (baricitinib) or with a standard-of-care therapy alone. METHODS: The observational cohort study included 154 adults hospitalized between February and August, 2020 with RT-PCR-confirmed SARS-CoV-2 with National Early Warning Score2 (NEWS2) < 7 and C-reactive protein (CRP) levels ≤ 140 mg/L on the day of the start of the therapy or observation. Patients were divided into the following groups: I) 4 mg baricitinib, 1 or 2 times a day for an average of 5 days (n = 38); II) 120 mg netakimab, one dose (n = 48); III) 400 mg tocilizumab, one dose (n = 34), IV) SOC only: hydroxychloroquine, antiviral, antibacterial, anticoagulant, and dexamethasone (n = 34). RESULTS: CRP levels significantly decreased after 72 h in the tocilizumab (p = 1 x 10-5) and netakimab (p = 8 x 10-4) groups and remained low after 120 h. The effect was stronger with tocilizumab compared to other groups (p = 0.028). A significant decrease in lactate dehydrogenase (LDH) levels was observed 72 h after netakimab therapy (p = 0.029). NEWS2 scores significantly improved 72 h after tocilizumab (p = 6.8 x 10-5) and netakimab (p = 0.01) therapy, and 120 h after the start of tocilizumab (p = 8.6 x 10-5), netakimab (p = 0.001), or baricitinib (p = 4.6 x 10-4) therapy, but not in the SOC group. Blood neutrophil counts (p = 6.4 x 10-4) and neutrophil-to-lymphocyte ratios (p = 0.006) significantly increased 72 h after netakimab therapy and remained high after 120 h. The percentage of patients discharged 5-7 days after the start of therapy was higher in the tocilizumab (44.1%) and netakimab (41.7%) groups than in the baricitinib (31.6%) and SOC (23.5%) groups. Compared to SOC (3 of the 34; 8.8%), mortality was lower in netakimab (0 of the 48; 0%, RR = 0.1 (95% CI: 0.0054 to 1.91)), tocilizumab (0 of the 34; 0%, RR = 0.14 (95% CI: 0.0077 to 2.67)), and baricitinib (1 of the 38; 2.6%, RR = 0.3 (95% CI: 0.033 to 2.73)) groups. CONCLUSION: In hospitalized patients with mild-to-moderate COVID-19, the combination of SOC with anti-IL-17A or anti-IL-6R therapy were superior or comparable to the combination with JAK1/JAK2 inhibitor, and all three were superior to SOC alone. Whereas previous studies did not demonstrate significant benefit of anti-IL-17A therapy for severe COVID-19, our data suggest that such therapy could be a rational choice for mild-to-moderate disease, considering the generally high safety profile of IL-17A blockers. The significant increase in blood neutrophil count in the netakimab group may reflect efflux of neutrophils from inflamed tissues. We therefore hypothesize that neutrophil count and neutrophil-to-lymphocyte ratio could serve as markers of therapeutic efficiency for IL-17A-blocking antibodies in the context of active inflammation.

Clusters of risk factors in metabolic syndrome and their influence on central blood pressure in a global study.

The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified "risky clusters" of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Dynamic Viscosity of the NaF-KF-NdF3 Molten System.

The dynamic viscosity (η) of the molten system (NaF-KF)eut-NdF3 containing NdF3 in an amount from 0 to 15 mol.% was studied by rotational viscometry using a high-temperature rheometer, FRS 1600. Viscosity measurements were carried out in the temperature range from liquidus to 1153 K. The measurement procedure was tested on the (LiF-NaF-KF)eut melt. The choice of the parameter shear rate was carried out according to the viscosity and flow curves. Viscosity does not depend on shear rate, and therefore the investigated melts behave like Newtonian fluids, in the range of 9-19 s-1. The experimentally obtained viscosity values for (NaF-KF)eut-NdF3 melts in a wide temperature range are described by an exponential equation. In the coordinates ln(η) = f(1/T), they are straight lines; however, their temperature coefficients are noticeably different, which indicates significant impacts of composition and temperature.

Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults.

Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals-people over the age of 90 who managed to retain much of their health and functionality-could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).

Physiological health indexes predict deterioration and mortality in patients with COVID-19: a comparative study.

Old age is a crucial risk factor for severe coronavirus disease 2019 (COVID-19), with serious or fatal outcomes disproportionately affecting older adults compared with the rest of the population. We proposed that the physiological health status and biological age, beyond the chronological age itself, could be the driving trends affecting COVID-19 severity and mortality. A total of 155 participants hospitalized with confirmed COVID-19 aged 26-94 years were recruited for the study. Four different physiological summary indices were calculated: Klemera and Doubal's biological age, PhenoAge, physiological dysregulation (PD; globally and in specific systems), and integrated albunemia. All of these indices significantly predicted the risk of death (p < 0.01) after adjusting for chronological age and sex. In all models, men were 2.4-4.4-times more likely to die than women. The global PD was shown to be a good predictor of deterioration, with the odds of deterioration increasing by 41.7% per 0.5-unit increase in the global PD. As for death, the odds also increased by 68.3% per 0.5-unit increase in the global PD. Our results are partly attributed to common chronic diseases that aggravate COVID-19, but they also suggest that the underlying physiological state could capture vulnerability to severe COVID-19 and serve as a tool for prognosis that would, in turn, help inpatient management.

Skin codelivery of contact sensitizers and neurokinin-1 receptor antagonists integrated in microneedle arrays suppresses allergic contact dermatitis.

BACKGROUND: Allergic contact dermatitis (CD) is a chronic inflammatory skin disease caused by type 1 biased adaptive immunity for which there is an unmet need for antigen (Ag)-specific immunotherapies. Exposure to skin sensitizers stimulates secretion of the proinflammatory neuropeptides substance P and hemokinin 1, which signal via the neurokinin-1 receptor (NK1R) to promote the innate and adaptive immune responses of CD. Accordingly, mice lacking the NK1R develop impaired CD. Nonetheless, the role and therapeutic opportunities of targeting the NK1R in CD remain to be elucidated. OBJECTIVE: We sought to develop an Ag-specific immunosuppressive approach to treat CD by skin codelivery of hapten and NK1R antagonists integrated in dissolvable microneedle arrays (MNA). METHODS: In vivo mouse models of contact hypersensitivity and ex vivo models of human skin were used to delineate the effects and mechanisms of NK1R signaling and the immunosuppressive effects of the contact sensitizer NK1R antagonist MNA in CD. RESULTS: We demonstrated in mice that CD requires NK1R signaling by substance P and hemokinin 1. Specific deletion of the NK1R in keratinocytes and dendritic cells, but not in mast cells, prevented CD. Skin codelivery of hapten or Ag MNA inhibited neuropeptide-mediated skin inflammation in mouse and human skin, promoted deletion of Ag-specific effector T cells, and increased regulatory T cells, which prevented CD onset and relapses locally and systemically in an Ag-specific manner. CONCLUSIONS: Immunoregulation by engineering localized skin neuroimmune networks can be used to treat cutaneous diseases that like CD are caused by type 1 immunity.

The Electrical Conductivity of Molten Oxide-Fluoride Cryolite Mixtures.

A new way to reduce the energy consumption during the operation of powerful aluminum reduction cells is suggested via reducing the resistance of the electrolyte, i.e., increasing its electrical conductivity. The electrical conductivity of molten cryolite mixtures NaF-AlF3-CaF2-Al2O3 with cryolite ratio (CR) of 2.1-3.0 and content of CaF2 and Al2O3, up to 8 wt%, was measured at the temperatures from liquidus to 1300 K. Based on the experimental results, a multifunctional equation for the electrical conductivity of oxide-fluoride cryolite melts was evaluated. The experimental and calculated values of the electrical conductivity agree within 1.5%. The activation energy of the electrical conductivity of the NaF-AlF3-CaF2-Al2O3 melts was estimated. The activation energy of electrical conductivity for molten NaF-AlF3 mixtures with CR 3.0 and 2.1, determined by the most mobile cations Na+, increased from 15.8 kJ/mol up to 18.5 kJ/mol. It was found that CR had a greater impact on the activation energy than the changes in the Al2O3 or CaF2 concentrations. Based on the ratio of the activation energies of the electrical conductivity and the viscous flow, the correlation between the electrical conductivity and viscosity of molten cryolite mixtures NaF-AlF3-CaF2-Al2O3 was illustrated.

Investigation of the Quasi-Binary Phase Diagram FLiNaK-NdF3.

The NdF3 solubility in molten eutectic FLiNaK, which is a conceivable medium for a molten salt reactor (MSR), was determined by the quasi-binary phase diagram FLiNaK-NdF3. The eutectic mixture FLiNaK was prepared by direct melting of components LiF, NaF and KF·HF. The acidic anhydrous salt (KF·HF) was used instead of the hygroscopic KF. The NdF3 was sintered by hydrofluorination of Nd2O3. The oxygen impurity in the prepared eutectic FLiNaK, determined by an oxygen analyzer LECO OH836, was 0.036 wt.%, whereas the NdF3 contained 0.04 wt.% of oxygen. A part of the FLiNaK-NdF3 quasi-binary phase diagram was obtained using two thermal analysis techniques: differential thermal analysis (DTA) and differential scanning calorimetry (DSC). The FLiNaK-NdF3 phase diagram in the region of 0-30 mol.% NdF3 contains one eutectic at 2 mol.% NdF3 and 450 °C and two peritectic points: 8 mol.% NdF3 at 500 °C and 22 mol.% NdF3 at 575 °C. The region of the FLiNaK-NdF3 phase diagram below the liquidus line is rather complicated due to the complex structure of the multicomponent system in its molten state, as in its solid state. The NdF3 solubility in FLiNaK is about 5 mol.% at 490 °C and 29 mol.% at 700 °C; this means that the process of the MA transmutation in the MSR can be carried out in molten FLiNaK with a content of actinides as high as 15-20 mol.% in the temperature range of 550-650 °C.

Subfractional Spectrum of Serum Lipoproteins and Gut Microbiota Composition in Healthy Individuals.

Aim: To reveal the relationship between gut microbiota composition and subfractional spectrum of serum lipoproteins and metabolic markers in healthy individuals from Moscow. Methods: The study included 304 participants (104 were men), who underwent thorough preclinical assessment to exclude any chronic disease as well as cardiovascular pathology. Lipoprotein subfractional distribution was analyzed by Lipoprint LDL System (Quantimetrix, Redodno Beach, CA, USA). Gut microbiota composition was assessed by 16S rRNA sequencing of V3-V4 regions. Results: High gut microbiota diversity was positively associated with HDL-cholesterol (C) level and negatively associated with abdominal obesity, BMI, and dyslipidemia. According to selbal analysis, excessive representation of Prevotella spp. was positively associated with IDL-C and LDL-2-C. VLDL-C correlated with Ruminococcus_u/Faecalibacterium_prausnitzii balance. An unexpected positive relationship between LDL-C level and Bifidobacteriaceae_u/Christensenellaceae_u to Bifidobacterium_u balance was found, which may reflect the importance of the integrative microbiota assessment. Low microbiota diversity was associated with obesity, abdominal obesity and low HDL-C level. Conclusions: Gut microbiota imbalance may be one of the components involved in metabolic disorders. The balance of microorganisms and the microbiota diversity may play a more significant role in human health than individual bacterial genera.