Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer.

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.

Precisely Printable Silk Fibroin/Carboxymethyl Cellulose/Alginate Bioink for 3D Printing.

Three-dimensional (3D) bioprinting opens up many possibilities for tissue engineering, thanks to its ability to create a three-dimensional environment for cells like an extracellular matrix. However, the use of natural polymers such as silk fibroin in 3D bioprinting faces obstacles such as having a limited printability due to the low viscosity of such solutions. This study addresses these gaps by developing highly viscous, stable, and biocompatible silk fibroin-based inks. The addition of 2% carboxymethyl cellulose sodium and 1% sodium alginate to an aqueous solution containing 2.5 to 5% silk fibroin significantly improves the printability, stability, and mechanical properties of the printed scaffolds. It has been demonstrated that the more silk fibroin there is in bioinks, the higher their printability. To stabilize silk fibroin scaffolds in an aqueous environment, the printed structures must be treated with methanol or ethanol, ensuring the transition from the silk fibroin's amorphous phase to beta sheets. The developed bioinks that are based on silk fibroin, alginate, and carboxymethyl cellulose demonstrate an ease of printing and a high printing quality, and have a sufficiently good biocompatibility with respect to mesenchymal stromal cells. The printed scaffolds have satisfactory mechanical characteristics. The resulting 3D-printing bioink composition can be used to create tissue-like structures.

Specifics of Porous Polymer and Xenogeneic Matrices and of Bone Tissue Regeneration Related to Their Implantation into an Experimental Rabbit Defect.

This paper provides a study of two bone substitutes: a hybrid porous polymer and an osteoplastic matrix based on a bovine-derived xenograft. Both materials are porous, but their pore characteristics are different. The osteoplastic matrix has pores of 300-600 µm and the hybrid polymer has smaller pores, generally of 6-20 µm, but with some pores up to 100 µm across. SEM data confirmed the porometry results and demonstrated the different structures of the materials. Therefore, both materials were characterized by an interconnected porous structure and provided conditions for the adhesion and vital activity of human ASCs in vitro. In an experimental model of rabbit shin bone defect, it was shown that, during the 6-month observation period, neither of the materials caused negative reactions in the experimental animals. By the end of the observation period, restoration of the defects in animals in both groups was completed, and elements of both materials were preserved in the defect areas. Data from morphological examinations and CT data demonstrated that the rate of rabbit bone tissue regeneration with the hybrid polymer was comparable to that with the osteoplastic matrix. Therefore, the hybrid polymer has good potential for use in further research and improvement in biomedical applications.

Enterotype-Dependent Probiotic-Mediated Changes in the Male Rat Intestinal Microbiome In Vivo and In Vitro.

Beneficial properties of lactic acid bacteria have been known long ago, but particular interest in probiotics has arisen in the last two decades due to the understanding of the important role of intestinal microflora in human life. Thus, the ability of probiotics to support healthy homeostasis of gut microbiomes has received particular attention. Here, we evaluated the effect of a probiotic consisting of Bifidobacterium longum and Lacticaseibacillus paracasei on the gut microbiome of male rats, assessed their persistence in the fecal biota, and compared probiotic-mediated changes in vitro and in vivo. As expected, microbiomes of two enterotypes were identified in the feces of 21 animals, and it turned out that even a single dose of the probiotic altered the microbial composition. Upon repeated administration, the E1 biota temporarily acquired properties of the E2 type. Being highly sensitive to the intervention of probiotic bacteria at the phylum and genus levels, the fecal microbiomes retained the identity of their enterotypes when transferred to a medium optimized for gut bacteria. For the E2 biota, even similarities between probiotic-mediated reactions in vitro and in vivo were detected. Therefore, fecal-derived microbial communities are proposed as model consortia to optimize the response of resident bacteria to various agents.

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.

Characteristics of the Gut Microbiota in Regard to Atopic Dermatitis and Food Allergies of Children.

The gut microbiota plays an important role in maintaining human health, as well as in the development of various pathologies, as indicated by a large amount of research. One of the manifestations of an imbalance in the gut microbiome composition is the appearance of various diseases or immune reactions, in particular, atopic dermatitis (AD) and/or food allergies (FA). In this research, using 16S NGS sequencing, it was found that the gut microbiome of children with food allergies and children with atopic dermatitis can be characterized as having higher inflammatory potential. Both groups exhibited an abundance of representatives from the Pasteurellaceae and Erysipelotrichaceae families, as well as a decrease in the relative number of representatives from the Barnesiellaceae family compared to healthy participants. In the group of participants with food allergies, there was a decrease in the relative number of Desulfovibrionaceae representatives and Bifidobacteriaceae family enrichment in relatively healthy participants. In addition, when comparing this group with patients with atopic dermatitis, it was revealed that a number of representatives of such families as Erysipelotrichaceae, Ruminococcaceae and Sutterellaceae prevailed. This information confirms that AD and FA correlate with changes in the composition of the gut microbiota. Further research is needed to determine the cause-effect connections and the effect of compounds derived from the microbiota on the AD and FA development and progression, as well as to create new probiotic drugs to prevent and modulate immune responses, including at an early age.

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.

Features of Changes in the Structure and Properties of a Porous Polymer Material with Antibacterial Activity during Biodegradation in an In Vitro Model.

Hybrid porous polymers based on poly-EGDMA and polylactide containing vancomycin, the concentration of which in the polymer varied by two orders of magnitude, were synthesized. The processes of polymer biodegradation and vancomycin release were studied in the following model media: phosphate-buffered saline (PBS), trypsin-Versene solution, and trypsin-PBS solution. The maximum antibiotic release was recorded during the first 3 h of extraction. The duration of antibiotic escape from the polymer samples in trypsin-containing media varied from 3 to 22 days, depending on the antibiotic content of the polymer. Keeping samples of the hybrid polymer in trypsin-containing model media resulted in acidification of the solutions-after 45 days, up to a pH of 1.84 in the trypsin-Versene solution and up to pH 1.65 in the trypsin-PBS solution. Here, the time dependences of the vancomycin release from the polymer into the medium and the decrease in pH of the medium correlated. These data are also consistent with the results of a study of the dynamics of sample weight loss during extraction in the examined model media. However, while the polymer porosity increased from ~53 to ~60% the pore size changed insignificantly, over only 10 µm. The polymer samples were characterized by their antibacterial activity against Staphylococcus aureus, and this activity persisted for up to 21 days during biodegradation of the material, regardless of the medium type used in model. Surface-dependent human cells (dermal fibroblasts) adhere well, spread out, and maintain high viability on samples of the functionalized hybrid polymer, thus demonstrating its biocompatibility in vitro.

Energy Metabolites and Indicative Significance of α-Ketoglutarate and α-Ketoglutaramate in Assessing the Progression of Chronic Hepatoencephalopathy.

In the example of a rat model with chronic hepatoencephalopathy (HE), changes in the organ morphology of rats affect the balance of metabolites of the tricarboxylic acid (TCA) cycle and metabolites of the glutamine-glutamate (Gln-Glu) cycle, namely α-ketoglutarate (αKG) and α-ketoglutaramate (αKGM), as well as the enzymes associated with them, ω-amidase (ωA) and glutamine transaminase (GTK). This model of rats was obtained as a result of 2-22 weeks of consumption by animals of hepatotoxin thioacetamide (TAA) added to drinking water at a concentration of 0.4 g/L. The control (n = 26) and TAA-induced (n = 55) groups of rats consisted of 11 cohorts each. The control cohorts consisted of 2-4 rats, and the TAA-induced cohorts consisted of 4-7 individuals. Every two weeks, samples of blood plasma, liver, kidney, and brain tissues were taken from the next cohort of rats (a total of 320 samples). By the end of the experiment, irreversible morphological changes were observed in the organs of rats: the weight of the animals was reduced up to ~45%, the weight of the kidneys up to 5%, the brain up to ~20%, and the weight of the liver increased up to ~20%. The analysis revealed: (i) a decrease in the activity of ωA and GTK in the tissues of the brain, kidneys, and liver of rats with chronic HE (by ~3, 40, and 65% and ~10, 60, and 70%, respectively); and (ii) the appearance of a significant imbalance in the content of metabolites of the Gln-Glu cycle, αKG, and αKGM. It is indicative that a ~1.5-12-fold increase in the level of αKG in the blood plasma and tissues of the organs of rats with chronic HE was accompanied by a synchronous, ~1.2-2.5-fold decrease in the level of αKGM. The data obtained indicate an essential involvement of the Gln-Glu cycle in the regulation of energy metabolism in rats under conditions of chronic HE. Attention is focused on the significance of the αKG/αKGM ratio, which can act as a potential marker for diagnosing the degree of HE development.

Genomic Signatures of Positive Selection in Human Populations of the OXT, OXTR, AVP, AVPR1A and AVR1B Gene Variants Related to the Regulation of Psychoemotional Response.

The neurobiological systems of maintenance and control of behavioral responses result from natural selection. We have analyzed the selection signatures for single nucleotide variants (SNV) of the genes of oxytocin (OXT, OXTR) and vasopressin (AVP, AVPR1A, AVPR1B) systems, which are associated with the regulation of social and emotional behavior in distinct populations. The analysis was performed using original WGS (whole genome sequencing) data on Eastern Slavs (SlEast), as well as publicly available data from the 1000 Genomes Project on GBR, FIN, IBR, PUR, BEB, CHB, and ACB populations (the latter were taken as reference). To identify selection signatures, we rated the integrated haplotype scores (iHS), the numbers of segregating sites by length (nSl), and the integrated haplotype homozygosity pooled (iHH12) measures; the fixation index Fst was implemented to assess genetic differentiation between populations. We revealed that the strongest genetic differentiation of populations was found with respect to the AVPR1B gene, with the greatest differentiation observed in GRB (Fst = 0.316) and CHB (Fst = 0.325) in comparison to ACB. Also, high Fst values were found for SNVs of the AVPR1B gene rs28499431, rs33940624, rs28477649, rs3883899, and rs28452187 in most of the populations. Selection signatures have also been identified in the AVP, AVPR1A, OXT, and OXTR genes. Our analysis shows that the OXT, OXTR, AVP, AVPR1A, and AVPR1B genes were subject to positive selection in a population-specific process, which was likely contributing to the diversity of adaptive emotional response types and social function realizations.

Finding Predictors of Leg Defects in Pigs Using CNV-GWAS.

One of the most important areas of modern genome research is the search for meaningful relationships between genetic variants and phenotypes. In the livestock field, there has been research demonstrating the influence of copy number variants (CNVs) on phenotypic variation. Despite the wide range in the number and size of detected CNVs, a significant proportion differ between breeds and their functional effects are underestimated in the pig industry. In this work, we focused on the problem of leg defects in pigs (lumps/growths in the area of the hock joint on the hind legs) and focused on searching for molecular genetic predictors associated with this trait for the selection of breeding stock. The study was conducted on Large White pigs using three CNV calling tools (PennCNV, QuantiSNP and R-GADA) and the CNVRanger association analysis tool (CNV-GWAS). As a result, the analysis identified three candidate CNVRs associated with the formation of limb defects. Subsequent functional analysis suggested that all identified CNVs may act as potential predictors of the hock joint phenotype of pigs. It should be noted that the results obtained indicate that all significant regions are localized in genes (CTH, SRSF11, MAN1A1 and LPIN1) responsible for the metabolism of amino acids, fatty acids, glycerolipids and glycerophospholipids, thereby related to the immune response, liver functions, content intramuscular fat and animal fatness. These results are consistent with previously published studies, according to which a predisposition to the formation of leg defects can be realized through genetic variants associated with the functions of the liver, kidneys and hematological characteristics.

Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods.

Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae, Lactobacillaceae, and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae, Chitinophagaceae, Pirellulaceae, Erysipelatoclostridiaceae, Muribaculaceae, and Comamonadaceae, and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.

Current Approaches to Epigenetic Therapy.

Epigenetic therapy is a promising tool for the treatment of a wide range of diseases. Several fundamental epigenetic approaches have been proposed. Firstly, the use of small molecules as epigenetic effectors, as the most developed pharmacological method, has contributed to the introduction of a number of drugs into clinical practice. Secondly, various innovative epigenetic approaches based on dCas9 and the use of small non-coding RNAs as therapeutic agents are also under extensive research. In this review, we present the current state of research in the field of epigenetic therapy, considering the prospects for its application and possible limitations.

GWAS reveals genetic basis of a predisposition to severe COVID-19 through in silico modeling of the FYCO1 protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is heavily reliant on its natural ability to "hack" the host's genetic and biological pathways. The genetic susceptibility of the host is a key factor underlying the severity of the disease. Polygenic risk scores are essential for risk assessment, risk stratification, and the prevention of adverse outcomes. In this study, we aimed to assess and analyze the genetic predisposition to severe COVID-19 in a large representative sample of the Russian population as well as to build a reliable but simple polygenic risk score model with a lower margin of error. Another important goal was to learn more about the pathogenesis of severe COVID-19. We examined the tertiary structure of the FYCO1 protein, the only gene with mutations in its coding region and discovered changes in the coiled-coil domain. Our findings suggest that FYCO1 may accelerate viral intracellular replication and excessive exocytosis and may contribute to an increased risk of severe COVID-19. We found significant associations between COVID-19 and LZTFL1, FYCO1, XCR1, CCR9, TMLHE-AS1, and SCYL2 at 3p21.31. Our findings further demonstrate the polymorphic nature of the severe COVID-19 phenotype.

Properties of Resorbable Conduits Based on Poly(L-Lactide) Nanofibers and Chitosan Fibers for Peripheral Nerve Regeneration.

New tubular conduits have been developed for the regeneration of peripheral nerves and the repair of defects that are larger than 3 cm. The conduits consist of a combination of poly(L-lactide) nanofibers and chitosan composite fibers with chitin nanofibrils. In vitro studies were conducted to assess the biocompatibility of the conduits using human embryonic bone marrow stromal cells (FetMSCs). The studies revealed good adhesion and differentiation of the cells on the conduits just one day after cultivation. Furthermore, an in vivo study was carried out to evaluate motor-coordination disorders using the sciatic nerve functional index (SFI) assessment. The presence of chitosan monofibers and chitosan composite fibers with chitin nanofibrils in the conduit design increased the regeneration rate of the sciatic nerve, with an SFI value ranging from 76 to 83. The degree of recovery of nerve conduction was measured by the amplitude of M-response, which showed a 46% improvement. The conduit design imitates the oriented architecture of the nerve, facilitates electrical communication between the damaged nerve's ends, and promotes the direction of nerve growth, thereby increasing the regeneration rate.

Structure and Properties of Composite Fibers Based on Chitosan and Single-Walled Carbon Nanotubes for Peripheral Nerve Regeneration.

This study focused on a potential application of electrically conductive, biocompatible, bioresorbable fibers for tubular conduits aimed at the regeneration of peripheral nerves. The conducting, mechanical, and biological properties of composite fibers based on chitosan and single-walled carbon nanotubes were investigated in this paper. It was shown that introducing 0.5 wt.% of SWCNT into the composite fibers facilitated the formation of a denser fiber structure, resulting in improved strength (σ = 260 MPa) and elastic (E = 14 GPa) characteristics. Additionally, the composite fibers were found to be biocompatible and did not cause significant inflammation or deformation during in vivo studies. A thin layer of connective tissue formed around the fiber.

Influence of Molecular Weight on Thermal and Mechanical Properties of Carbon-Fiber-Reinforced Plastics Based on Thermoplastic Partially Crystalline Polyimide.

For the first time, a study of the influence of the molecular weight of the thermoplastic partially crystalline polyimide R-BAPB on the thermophysical and mechanical properties of carbon plastics was presented. The molecular weight of polyimide was determined using the method of light scattering and the study of the intrinsic viscosity of polyamic acid solutions. To obtain CFRPs, the uniform distribution of polyimide powder on continuous carbon fibers via electrostatic spraying and further hot calendering and pressing were applied. The study of the structure of the obtained carbon plastics via scanning electron microscopy has shown that the growth of the molecular weight of polyimide prevents the impregnation of carbon fiber with the introduced polyimide. Moreover, an increase in the molecular weight of polyimide leads to a rise in glass transition and thermal decomposition temperatures up to 590 °C, while the degree of crystallinity of CFRP falls. Nonetheless, raising the molecular weight from 22,000 to 70,000 g/mol of a binder polymer improves the interlayer fracture toughness G1C by more than five times.

Pore Structure Tuning of Poly-EGDMA Biomedical Material by Varying the O-Quinone Photoinitiator.

Porous polymer monoliths with thicknesses of 2 and 4 mm were obtained via polymerization of ethylene glycol dimethacrylate (EGDMA) under the influence visible-light irradiation in the presence of a 70 wt% 1-butanol porogenic agent and o-quinone photoinitiators. The o-quinones used were: 3,5-di-tret-butyl-benzoquinone-1,2 (35Q), 3,6-di-tret-butyl-benzoquinone-1,2 (36Q), camphorquinone (CQ), and 9,10-phenanthrenequinone (PQ). Porous monoliths were also synthesized from the same mixture but using 2,2'-azo-bis(iso-butyronitrile) (AIBN) at 100 °C instead o-quinones. According to the results of scanning electron microscopy, all the resulting samples were conglomerates of spherical, polymeric particles with pores between them. Use of mercury porometry showed that the interconnected pore systems of all the polymers were open. The average pore size, Dmod, in such polymers strongly depended on both the nature of the initiator and the method of initiation of polymerization. For polymers obtained in the presence of AIBN, the Dmod value was as low as 0.8 µm. For polymers obtained via photoinitiation in the presence of 36Q, 35Q, CQ, and PQ, the Dmod values were significantly greater, i.e., 9.9, 6.4, 3.6, and 3.7 µm, respectively. The compressive strength and Young's modulus of the porous monoliths increased symbatically in the series PQ < CQ < 36Q < 35Q < AIBN with decreasing proportions of large pores (over 12 µm) in their polymer structures. The photopolymerization rate of the EGDMA and 1-butanol, 30:70 wt% mixture was maximal for PQ and minimal for 35Q. All polymers tested were non-cytotoxic. Based on the data from MTT testing, it can be noted that the polymers obtained via photoinitiation were characterized by their positive effect on the proliferative activity of human dermal fibroblasts. This makes them promising osteoplastic materials for clinical trials.

Porogen Concentration Effect on the Pore Structure and Properties Evolution of Polymer Monolith Based on Oligocarbonate Dimethacrylate OCM-2.

Porous polymer monolith materials of 2-mm thickness were obtained by visible light-induced radical polymerization of oligocarbonate dimethacrylate (OCM-2) in the presence of 1-butanol (10 to 70 wt %) as a porogenic additive. The pore characteristics and morphology of polymers were studied by mercury intrusion porosimetry and scanning electron microscopy. Monolithic polymers with both open and closed pores up to 100 nm in size are formed when the alcohol content in the initial composition is up to 20 wt %. The pore structure in such materials is a system of holes in the bulk of the polymer (hole-type pores). Open interconnected pores with a specific volume up to 2.22 cm3/g and modal pore size up to 10 microns are formed in the volume of the polymer with 1-butanol content of more than 30 wt %. Such porous monoliths are a structure of covalently bonded polymer globules (interparticle-type pores). The free space between the globules represents a system of open interconnected pores. In the transition region of 1-butanol concentrations (from 20 to 30 wt %), areas with both structures and intermediate frameworks, as well as honeycomb structures of polymer globules connected by bridges, are fixed on the polymer surface. It was found that the transition from one type of pore system to another is accompanied by a sharp change in the strength characteristics of the polymer. Approximation of experimental data using the sigmoid function made it possible to determine the concentration of the porogenic agent in the vicinity of which the percolation threshold is observed.

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.