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The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination with GTE as stimulants of physical performance in a forced swimming rat experimental model. The determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry of blood plasma; biochemistry of erythrocytes; hematology; immunology; gene expression of slow- and fast-twitch muscles (m. soleus, SOL, and m. extensor digitorum longus, EDL, respectively); and morphometric indicators of slow- and fast-twitch muscles. Regarding the negative control (intact animals), the maximum number of changes in all blocks of indicators was recorded in the GTE + ACR group, whose animals showed the maximum functional result and minimum lactate values on the last day of the experiment. Next, in terms of the number of changes, were the groups ACR, ACL, GTE + ACL, GTE and NaCl (positive control). In general, the number of identified adaptive changes was proportional to the functional state of the animals of the corresponding groups, in terms of the duration of the swimming load in the last four days of the experiment. However, not only the total number but also the qualitative composition of the identified changes is of interest. The results of a comparative analysis suggest that, in the model of forced swimming we developed, GTE promotes restoration of the body and moderate mobilization of the immune system, while small doses of ammonium salts, especially ammonium carbonate, contribute to an increase in physical performance, which is associated with satisfactory restoration of skeletal muscles and the entire body. The combined use of GTE with ammonium salts does not give a clearly positive effect. [ABSTRACT FROM AUTHOR]

Carvone belongs to the chemical family of terpenoids and is the main component of various plant oils. Carvone and its hydrogenated products are used in the flavouring and food industries. A quantitative thermodynamic analysis of the general network of carvone hydrogenation reactions was performed based on the thermochemical properties of the starting carvone and all possible intermediates and end products. The enthalpies of vaporisation, enthalpies of formation, entropies and heat capacities of the reactants were determined by complementary measurements and a combination of empirical, theoretical and quantum chemical methods. The energetics and entropy change in the hydrogenation and isomerisation reactions that take place during the conversion of carvone were derived, and the Gibbs energies of the reactions were estimated. It was shown that negative Gibbs energies are recorded for all reactions that may occur during the hydrogenation of carvone, although these differ significantly in magnitude. This means that all these reactions are thermodynamically feasible in a wide range from ambient temperature to elevated temperatures. Therefore, all these reactions definitely take place under kinetic and not thermodynamic control. Nevertheless, the numerical Gibbs energy values can help to establish the chemoselectivity of catalysts used to convert carvone to either carvacarol or to dihydro- and terahydrocarvone, either in carvotanacetone or carveol. [ABSTRACT FROM AUTHOR]

The identification of the genetic causes of inherited disorders from next-generation sequencing (NGS) data remains a complicated process, in particular due to challenges in interpretation of the vast amount of generated data and hundreds of candidate variants identified. Inconsistencies in variant classification, where genetic centers classify the same variant differently, can hinder accurate diagnoses for rare diseases. Publicly available databases that collect data on human genetic variations and their association with diseases provide ample opportunities to discover conflicts in variant interpretation worldwide. In this study, we explored patterns of variant classification discrepancies using data from ClinVar, a public archive of variant interpretations. We found that 5.7% of variants have conflicting interpretations (COIs) reported, and the vast majority of interpretation conflicts arise for variants of uncertain significance (VUS). As many as 78% of clinically relevant genes harbor variants with COIs, and genes with high COI rates tended to have more exons and longer transcripts, with a greater proportion of genes linked to several distinct conditions. The enrichment analysis of COI-enriched genes revealed that the products of these genes are involved in cardiac disorders, muscle development, and function. To improve diagnoses, we believe that specific variant interpretation rules could be developed for such genes. Additionally, our findings underscore the need for the publication of variant pathogenicity evidence and the importance of considering every variant as VUS unless proven otherwise. [ABSTRACT FROM AUTHOR]

Over the last two decades, numerous genome-wide association studies (GWAS) have been performed to unveil the genetic architecture of human complex traits. Despite multiple efforts aimed at the trans-biobank integration of GWAS results, no systematic analysis of the variant-level properties affecting the replication of known associations (or identifying novel ones) in genome-wide meta-analysis has yet been performed using biobank-scale data. To address this issue, we performed a systematic comparison of GWAS summary statistics for 679 complex traits in the UK Biobank (UKB) and FinnGen (FG) cohorts. We identified 37,148 index variants with genome-wide associations with at least one trait in either cohort or in the meta-analysis, only 3528 (9.5%) of which were shared between UKB and FG. Nearly twice as many variants (6577) were replicated in another dataset at the significance level adjusted for the number of variants selected for replication. However, as many as 9230 loci failed to be replicated. Moreover, as many as 5813 loci were observed as significant associations only in meta-analysis results, highlighting the importance of trans-biobank meta-analysis efforts. We showed that variants that failed to replicate in UKB or FG tend to correspond to rare, less pleiotropic variants with lower effect sizes and lower LD score values. Genome-wide associations specific to meta-analysis were also enriched in low-effect variants; however, such variants tended to be more common and have more consistent frequencies between populations. Taken together, our results show a relatively high rate of non-replication of genome-wide associations in the studied cohorts and highlight both widely appreciated and less acknowledged properties of the associations affecting their identification and replication. [ABSTRACT FROM AUTHOR]

A male factor, commonly associated with poor semen quality, is revealed in about 50% of infertile couples. CFTR gene (Cystic Fibrosis Transmembrane Conduction Regulator) variants are one of the common genetic causes of azoospermia-related male infertility. Notably, the spectrum and frequency of pathogenic CFTR variants vary between populations and geographical regions. In this work, we made an attempt to evaluate the allele frequency (AF) of 12 common CFTR variants in infertile Russian men and healthy individuals from different districts of Russia. Because of the limited number of population-based studies on Russian individuals, we characterized the population AFs based on data from the Registry of Russian cystic fibrosis (CF) patients. In addition to the CF patient registry, we estimated the local frequencies of the same set of variants based on the results of genotyping of CF patients in local biocollections (from St. Petersburg and Yugra regions). AFs of common CFTR variants calculated based on registry and biocollection data showed good concordance with directly measured population AFs. The estimated region-specific frequencies of CFTR variants allowed us to uncover statistically significant regional differences in the frequencies of the F508del (c.1521_1523del; p.Phe508del) and CFTRdele2,3(21kb) (c.54-5940_273+10250del21kb; p.Ser18ArgfsX) variants. The data from population-based studies confirmed previous observations that F508del, CFTRdele2,3(21kb), and L138ins (c.413_415dup; p.Leu138dup)variants are the most abundant among infertile patients, and their frequencies are significantly lower in healthy individuals and should be taken into account during genetic monitoring of the reproductive health of Russian individuals. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy is a neuromuscular disorder caused by mutations in both copies of the survival motor neuron gene 1 (SMN1), which lead to reduction in the production of the SMN protein. Currently, there are several therapies that have been approved for SMA, with many more undergoing active research. While various biomarkers have been proposed for assessing the effectiveness of SMA treatment, a universally accepted one still has not been identified. This study aimed to describe a fast and reliable method using the number of gems in cell nuclei as a potential tool for assessment of splicing correction of oligonucleotide efficacy in SMA cells. To gain insight into whether the number of gems in cell nuclei varies based on their SMN genotype and whether the increase in gem number is associated with therapeutic response, we utilized fibroblast cell cultures obtained from a patient with SMA type II and from a healthy individual. We discovered a remarkable difference in the number of gems found in the nuclei of these cells, specifically when counting gems per 100 nuclei. The SMA fibroblasts treated with antisense oligonucleotide showed beneficial effects in correcting the abnormal splicing of SMN2 exon 7. It was observed that there was a significant increase in the number of gems in the treated cells compared to the intact SMA cells. The results obtained significantly correlate with an increase of full-length SMN transcript sharing. Based on our findings, we propose using the quantity of gems as a reliable biomarker for SMA drug development. [ABSTRACT FROM AUTHOR]

Simple Summary: Genome-wide association studies (GWAS) are a powerful tool for the identification of genes affecting human traits. Still, the interpretation of GWAS results is complicated, and new tools are actively being developed. Due to the scarcity of available datasets, simulation of GWAS data with known genetic effects is important as it enables accurate evaluation of such tools. In this study, we developed a flexible tool, bioGWAS, that provides a set of important functionalities for simulating GWAS results. We demonstrate that bioGWAS can efficiently generate GWAS results with predefined causal genes and biological processes and is capable of recapitulating the results of published GWAS studies. We thus believe that bioGWAS is an excellent method for testing bioinformatics software for GWAS results processing, as well as for the generation of datasets for educational purposes. Genome-wide association studies (GWAS) have proven to be a powerful tool for the identification of genetic susceptibility loci affecting human complex traits. In addition to pinpointing individual genes involved in a particular trait, GWAS results can be used to discover relevant biological processes for these traits. The development of new tools for extracting such information from GWAS results requires large-scale datasets with known biological ground truth. Simulation of GWAS results is a powerful method that may provide such datasets and facilitate the development of new methods. In this work, we developed bioGWAS, a simple and flexible pipeline for the simulation of genotypes, phenotypes, and GWAS summary statistics. Unlike existing methods, bioGWAS can be used to generate GWAS results for simulated quantitative and binary traits with a predefined set of causal genetic variants and/or molecular pathways. We demonstrate that the proposed method can recapitulate complete GWAS datasets using a set of reported genome-wide associations. We also used our method to benchmark several tools for gene set enrichment analysis for GWAS data. Taken together, our results suggest that bioGWAS provides an important set of functionalities that would aid the development of new methods for downstream processing of GWAS results. [ABSTRACT FROM AUTHOR]

Pregnancy loss is the most frequent complication of a pregnancy which is devastating for affected families and poses a significant challenge for the health care system. Genetic factors are known to play an important role in the etiology of pregnancy loss; however, despite advances in diagnostics, the causes remain unexplained in more than 30% of cases. In this review, we aggregated the results of the decade-long studies into the genetic risk factors of pregnancy loss (including miscarriage, termination for fetal abnormality, and recurrent pregnancy loss) in euploid pregnancies, focusing on the spectrum of point mutations associated with these conditions. We reviewed the evolution of molecular genetics methods used for the genetic research into causes of pregnancy loss, and collected information about 270 individual genetic variants in 196 unique genes reported as genetic cause of pregnancy loss. Among these, variants in 18 genes have been reported by multiple studies, and two or more variants were reported as causing pregnancy loss for 57 genes. Further analysis of the properties of all known pregnancy loss genes showed that they correspond to broadly expressed, highly evolutionary conserved genes involved in crucial cell differentiation and developmental processes and related signaling pathways. Given the features of known genes, we made an effort to construct a list of candidate genes, variants in which may be expected to contribute to pregnancy loss. We believe that our results may be useful for prediction of pregnancy loss risk in couples, as well as for further investigation and revealing genetic etiology of pregnancy loss. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2D) is a chronic metabolic disease characterized by insulin resistance and β-cell dysfunction and leading to many micro- and macrovascular complications. In this study we analyzed the circulating miRNA expression profiles in plasma samples from 44 patients with T2D and 22 healthy individuals using next generation sequencing and detected 229 differentially expressed miRNAs. An increased level of miR-5588-5p, miR-125b-2-3p, miR-1284, and a reduced level of miR-496 in T2D patients was verified. We also compared the expression landscapes in the same group of patients depending on body mass index and identified differential expression of miR-144-3p and miR-99a-5p in obese individuals. Identification and functional analysis of putative target genes was performed for miR-5588-5p, miR-125b-2-3p, miR-1284, and miR-496, showing chromatin modifying enzymes and apoptotic genes being among the significantly enriched pathways. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal bacteria by means of 16S rRNA gene sequencing, and some clinically significant viruses detected with a customized primer panel for NGS-based study. The clinical group included patients with Crohn's disease (IBD, n = 9), or GVHD (n = 6) subjected to fecal microbiota transplantation (FMT) from healthy donors. The stool specimens were taken initially, and 5 times post-FMT until day 120. Using NGS approach, we have found a higher abundance of Proteobacterota phylum in GVHD, especially, at later terms post-FMT. Moreover, we found an early increase of Klebsiella and E. coli/Shigella abundance in GVHD, along with decreased relative content of Faecalibacterium. Upon evaluation of intestinal phageome, the relative amount of Caudoviricetes class was higher in GVHD. A significant correlation was found between Proteobacteria and Caudoviricetes, thus suggesting their association during the post-FMT period. Moreover, the relative amounts of five Caudoviricetes phage species showed distinct correlations with Klebsiella and Enterococcus ratios at different terms of FMT. In conclusion, parallel use of 16S rRNA gene sequencing and targeted NGS viral panel is a feasible and useful option for tracing specific viral strains in fecal microbiota. The developed array of viral primers may be extended to detect other phages infecting the clinically relevant bacteria. [ABSTRACT FROM AUTHOR]

Today, whole-exome sequencing (WES) is used to conduct the massive screening of structural and regulatory genes in order to identify the allele frequencies of disease-associated polymorphisms in various populations and thus detect pathogenic genetic changes (mutations or polymorphisms) conducive to malfunctional protein sequences. With its extensive capabilities, exome sequencing today allows both the diagnosis of monogenic diseases (MDs) and the examination of seemingly healthy populations to reveal a wide range of potential risks prior to disease manifestation (in the future, exome sequencing may outpace costly and less informative genome sequencing to become the first-line examination technique). This review establishes the human genetic passport as a new WES-based clinical concept for the identification of new candidate genes, gene variants, and molecular mechanisms in the diagnosis, prediction, and treatment of monogenic, oligogenic, and multifactorial diseases. Various diseases are addressed to demonstrate the extensive potential of WES and consider its advantages as well as disadvantages. Thus, WES can become a general test with a broad spectrum pf applications, including opportunistic screening. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease caused by mutations in the SMN1 gene. Existing therapies demonstrate positive results on SMA patients but still might be ameliorated in efficacy and price. In the presented study we designed antisense oligonucleotides (AONs), targeting intronic splicing silencer sites, some were modified with 2′-O-methyl, others with LNA. The AONs have been extensively tested in different concentrations, both individually and combined, in order to effectively target the ISS-N1 and A+100G splicing silencer regions in intron 7 of the SMN2 gene. By treating SMA-cultured fibroblasts with certain AONs, we discovered a remarkable increase in the levels of full-length SMN transcripts and the number of nuclear gems. This increase was observed to be dose-dependent and reached levels comparable to those found in healthy cells. When added to cells together, most of the tested molecules showed a remarkable synergistic effect in correcting splicing. Through our research, we have discovered that the impact of oligonucleotides is greatly influenced by their length, sequence, and pattern of modification. [ABSTRACT FROM AUTHOR]

Phenotypicheterogeneity is a phenomenon in which distinct phenotypes can develop in individuals bearing pathogenic variants in the same gene. Genetic factors, gene interactions, and environmental factors are usually considered the key mechanisms of this phenomenon. Phenotypic heterogeneity may impact the prognosis of the disease severity and symptoms. In our work, we used publicly available data on the association between genetic variants and Mendelian disease to investigate the genetic factors (such as the intragenic localization and type of a variant) driving the heterogeneity of gene–disease relationships. First, we showed that genes linked to multiple rare diseases (GMDs) are more constrained and tend to encode more transcripts with high levels of expression across tissues. Next, we assessed the role of variant localization and variant types in specifying the exact phenotype for GMD variants. We discovered that none of these factors is sufficient to explain the phenomenon of such heterogeneous gene–disease relationships. In total, we identified only 38 genes with a weak trend towards significant differences in variant localization and 30 genes with nominal significant differences in variant type for the two associated disorders. Remarkably, four of these genes showed significant differences in both tests. At the same time, our analysis suggests that variant localization and type are more important for genes linked to autosomal dominant disease. Taken together, our results emphasize the gene-level factors dissecting distinct Mendelian diseases linked to one common gene based on open-access genetic data and highlight the importance of exploring other factors that contributed to phenotypic heterogeneity. [ABSTRACT FROM AUTHOR]

Upgrading the properties of diesel fractions is considered one of the crucial processes in the petrochemical industry; and for this purpose in laboratory-scale researching it is studied on the base of the hydroisomerization of n-hexadecane as a main model reaction. Recently, zeolite-based bifunctional catalysts have proven their efficiency due to their remarkable acidity, shape-selectivity and relative resistance to deactivation. In this review, different topological-type zeolite-based catalysts, the mechanism of their catalytic effect in n-C16 isomerization, and the principles of shape-selectivity are reviewed. A comparison of their structural-operational characteristics is made. The impact of some feedstock impurities on the catalyst's performance and deactivation due to carbonaceous deposits as well as various modern eco-friendly cost-effective synthesis techniques are also discussed. [ABSTRACT FROM AUTHOR]

Lopes–Maciel–Rodan syndrome (LOMARS) is an extremely rare disorder, with only a few cases reported worldwide. LOMARS is caused by a compound heterozygous mutation in the HTT gene. Little is known about LOMARS pathogenesis and clinical manifestations. Whole exome sequencing (WES) was performed to achieve a definitive molecular diagnosis of the disorder. All NGS-identified variants underwent the Sanger confirmation. In addition, a literature review on genetic variations in the HTT gene was conducted. The paper reports a case of LOMARS in a pediatric patient in Russia. A preterm girl of non-consanguineous parents demonstrated severe psychomotor developmental delays in her first 12 months. By the age of 6 years, she failed to develop speech but was able to understand everyday phrases and perform simple commands. Autism-like behaviors, stereotypies, and bruxism were noted during the examination. WES revealed two undescribed variants of unknown clinical significance in the HTT gene, presumably associated with the patient's phenotype (c.2350C>T and c.8440C>A). Medical re-examination of parents revealed that the patient inherited these variants from her father and mother. Lopes–Maciel–Rodan syndrome was diagnosed based on overlapping clinical findings and the follow-up genetic examination of parents. Our finding expands the number of reported LOMARS cases and provides new insights into the genetic basis of the disease. [ABSTRACT FROM AUTHOR]

The Fischer–Tropsch process is considered one of the most promising eco-friendly routes for obtaining synthetic motor fuels. Fischer–Tropsch synthesis is a heterogeneous catalytic process in which a synthesis gas (CO/H2) transforms into a mixture of aliphatic hydrocarbons, mainly linear alkanes. Recently, an important direction has been to increase the selectivity of the process for the diesel fraction. Diesel fuel synthesized via the Fischer–Tropsch method has a number of advantages over conventional fuel, including the high cetane number, the low content of aromatic, and the practically absent sulfur and nitrogen impurities. One of the possible ways to obtain a high yield of diesel fuel via the Fischer–Tropsch process is the development of selective catalysts. In this review, the latest achievements in the field of production of diesel via Fischer–Tropsch synthesis using catalysts are reviewed for the first time. Catalytic systems based on Al2O3 and mesoporous silicates, such as MCM-41, SBA-15, and micro- and mesoporous zeolites, are observed. Together with catalytic systems, the main factors that influence diesel fuel selectivity such as temperature, pressure, CO:H2 ratio, active metal particle size, and carrier pore size are highlighted. The motivation behind this work is due to the increasing need for alternative processes in diesel fuel production with a low sulfur content and better exploitation characteristics. [ABSTRACT FROM AUTHOR]

Bacterial microbiota in stool may vary over a wide range, depending on age, nutrition, etc. The purpose of our work was to discriminate phyla and genera of intestinal bacteria and their biodiversity within a healthy population (North-Western Russia) compared to the patients with type 1 diabetes mellitus (T1DM). The study group included 183 healthy persons 2 to 53 years old (a mean of 26.5 ± 1.0 years old), and 41 T1DM patients (mean age 18.2 ± 1.8 years old). The disease onset was at 11 ± 1.5 years, with a T1DM experience of 7 ± 1.5 years. Total DNA was isolated from the stool samples, and sequencing libraries were prepared by amplifying the V3–V4 region of the 16S rRNA gene sequenced by Illumina MiSeq. Bioinformatic processing of NGS databases was adapted for microbiota evalutaion. Despite the broad scatter, the biological diversity for bacterial microbiota expressed as the Shannon index was significantly increased from younger to older ages in the comparison group, higher in adult healthy persons, with a trend for decrease in the Actinomycetota phylum which includes Bifidobacterium longum species. Similar but non-significant age trends were noted in the T1DM group. Concordant with the Bacillota prevalence in stool samples of diabetic patients, some anaerobic bacteria (Faecalibacteria, Lachnospira and Ruminococcae, Roseburia) were enriched in the T1DM microbiome against controls. Hence, correction of microbiota for Ruminococcus and Lachnospiraceae requires future search for new probiotics. Lower abundance of Actinomycetota and Bifidobacter in T1DM suggests potential usage of Bifidobacter-based probiotics in this cohort. [ABSTRACT FROM AUTHOR]

The diving reflex is an oxygen-saving mechanism which is accompanied by apnea, reflex bradycardia development, peripheral vasoconstriction, spleen erythrocyte release, and selective redistribution of blood flow to the organs most vulnerable to lack of oxygen, such as the brain, heart, and lungs. However, this is a poorly studied form of hypoxia, with a knowledge gap on physiological and biochemical adaptation mechanisms. The reflective sympathetic constriction of the resistive vessels is realized via ADRA1A. It has been shown that ADRA1A SNP (p.Arg347Cys; rs1048101) is associated with changes in tonus in vessel walls. Moreover, the Cys347 allele has been shown to regulate systolic blood pressure. The aim of this work was to evaluate whether the ADRA1A polymorphism affected the pulmonary vascular reactions in men and women in response to the diving reflex. Men (n = 52) and women (n = 50) untrained in diving aged 18 to 25 were recruited into the study. The vascular reactions and blood flow were examined by integrated rheography and rheography of the pulmonary artery. Peripheral blood circulation was registered by plethysmography. The ADRA1A gene polymorphism (p.Arg347Cys; rs1048101) was determined by PCR-RFLP. In both men and women, reflective pulmonary vasodilation did occur in response to the diving reflex, but in women this vasodilation was more pronounced and was accompanied by a higher filling of the lungs with blood.. Additionally, ADRA1A SNP (p.Arg347Cys; rs1048101) is associated with sex. Interestingly, women with the Arg347 allele demonstrated the highest vasodilation of the lung vessels. Therefore, our data may help to indicate women with the most prominent adaptive reactions to the diving reflex. Our data also indicate that women and men with the Cys allele of the ADRA1A gene polymorphism have the highest risk of developing lung hypertension in response to the diving reflex. The diving reflex is an oxygen-saving mechanism which is accompanied by apnea, reflex bradycardia development, peripheral vasoconstriction, spleen erythrocyte release, and selective redistribution of blood flow to the organs most vulnerable to lack of oxygen, such as the brain, heart, and lungs. However, this is a poorly studied form of hypoxia, with a knowledge gap on physiological and biochemical adaptation mechanisms. [ABSTRACT FROM AUTHOR]

Gliomas, one of the most severe malignant tumors of the central nervous system, have a high mortality rate and an increased risk of recurrence. Therefore, early glioma diagnosis and the control of treatment have great significance. The blood plasma samples of glioma patients, patients with skull craniectomy defects, and healthy donors were studied using terahertz time-domain spectroscopy (THz-TDS). An analysis of experimental THz data was performed by machine learning (ML). The ML pipeline included (i) THz spectra smoothing using the Savitzky–Golay filter, (ii) dimension reduction with principal component analysis and t-distribution stochastic neighborhood embedding methods; (iii) data separability analyzed using Support Vector Machine (SVM), Random Forest (RF), and Extreme Gradient Boosting (XGBoost). The ML models' performance was evaluated by a k-fold cross validation technique using ROC-AUC, sensitivity, and specificity metrics. It was shown that tree-based ensemble methods work more accurately than SVM. RF and XGBoost provided a better differentiation of the group of patients with glioma from healthy donors and patients with skull craniectomy defects. THz-TDS combined with ML was shown to make it possible to separate the blood plasma of patients before and after tumor removal surgery (AUC = 0.92). Thus, the applicability of THz-TDS and ML for the diagnosis of glioma and treatment monitoring has been shown. [ABSTRACT FROM AUTHOR]

The oxidative dehydrogenation of alkanes is a prospective method for olefins production. CO2-assisted propane dehydrogenation over metal oxide catalysts provides an opportunity to increase propylene production with collateral CO2 utilization. We prepared the chromia catalysts on various mesoporous aluminosilicate supports, such as halloysite nanotubes, nanostructured core/shell composites of MCM-41/halloysite (halloysite nanotubes for the core; silica of MCM-41-type for the shell), and MCM-41@halloysite (silica of MCM-41-type for the core; halloysite nanotubes for the shell). The catalysts have been characterized by X-ray fluorescence analysis, low-temperature nitrogen adsorption, X-ray diffraction, temperature-programmed reduction, temperature-programmed desorption of ammonia, transmission electron microscopy with energy-dispersive X-ray spectroscopy, and thermogravimetric analysis. The catalysts' performance in carbon-dioxide-assisted propane dehydrogenation has been estimated in a fixed-bed reactor at atmospheric pressure. The most stable catalyst is Cr/halloysite, having the lowest activity and the largest pore diameter. The catalyst, Cr/MCM-41/HNT, shows the best catalytic performance: having the highest conversion (19–88%), selectivity (83–30%), and space–time yield (4.3–7.1 mol C3H6/kg catalyst/h) at the temperature range of 550–700 °C. The highest space–time yield could be related to the uniform distribution of the chromia particles over the large surface area and narrow pore size distribution of 2–4 nm provided by the MCM-41-type silica and transport channels of 12–15 nm from the halloysite nanotubes. [ABSTRACT FROM AUTHOR]

We report on the case of prenatal detection of trisomy 2 in placental biopsy and further algorithm of genetic counseling and testing. A 29-year-old woman with first-trimester biochemical markers refused chorionic villus sampling and preferred targeted non-invasive prenatal testing (NIPT), which showed low risk for aneuploidies 13, 18, 21, and X. A series of ultrasound examinations revealed increased chorion thickness at 13/14 weeks of gestation and fetal growth retardation, a hyperechoic bowel, challenging visualization of the kidneys, dolichocephaly, ventriculomegaly, increase in placental thickness, and pronounced oligohydramnios at 16/17 weeks of gestation. The patient was referred to our center for an invasive prenatal diagnosis. The patient's blood and placenta were sampled for whole-genome sequencing-based NIPT and array comparative genomic hybridization (aCGH), respectively. Both investigations revealed trisomy 2. Further prenatal genetic testing in order to confirm trisomy 2 in amniocytes and/or fetal blood was highly questionable because oligohydramnios and fetal growth retardation made amniocentesis and cordocentesis technically unfeasible. The patient opted to terminate the pregnancy. Pathological examination of the fetus revealed internal hydrocephalus, atrophy of brain structure, and craniofacial dysmorphism. Conventional cytogenetic analysis and fluorescence in situ hybridization revealed chromosome 2 mosaicism with a prevalence of trisomic clone in the placenta (83.2% vs. 16.8%) and a low frequency of trisomy 2, which did not exceed 0.6% in fetal tissues, advocating for low-level true fetal mosaicism. To conclude, in pregnancies at risk of fetal chromosomal abnormalities that refuse invasive prenatal diagnosis, whole-genome sequencing-based NIPT, but not targeted NIPT, should be considered. In prenatal cases of trisomy 2, true mosaicism should be distinguished from placental-confined mosaicism using cytogenetic analysis of amniotic fluid cells or fetal blood cells. However, if material sampling is impossible due to oligohydramnios and/or fetal growth retardation, further decisions should be based on a series of high-resolution fetal ultrasound examinations. Genetic counseling for the risk of uniparental disomy in a fetus is also required. [ABSTRACT FROM AUTHOR]

Single-cell RNA sequencing (scRNA-seq) is a method that focuses on the analysis of gene expression profile in individual cells. This method has been successfully applied to answer the challenging questions of the pathogenesis of multifactorial diseases and open up new possibilities in the prognosis and prevention of reproductive diseases. In this article, we have reviewed the application of scRNA-seq to the analysis of the various cell types and their gene expression changes in normal pregnancy and pregnancy complications. The main principle, advantages, and limitations of single-cell technologies and data analysis methods are described. We discuss the possibilities of using the scRNA-seq method for solving the fundamental and applied tasks related to various pregnancy-associated disorders. Finally, we provide an overview of the scRNA-seq findings for the common pregnancy-associated conditions, such as hyperglycemia in pregnancy, recurrent pregnancy loss, preterm labor, polycystic ovary syndrome, and pre-eclampsia. [ABSTRACT FROM AUTHOR]

Although high altitude training has been increasingly popular among endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. Seven elite female speed skaters were profiled on the 18th day of high-altitude adaptation. Whole blood RNA-seq before and after an intense 1 h skating bout was used to measure gene expression changes associated with exercise. In order to identify the genes specifically regulated at high altitudes, we have leveraged the data from eight previously published microarray datasets studying blood expression changes after exercise at sea level. Using cell type-specific signatures, we were able to deconvolute changes of cell type abundance from individual gene expression changes. Among these were PHOSPHO1, with a known role in erythropoiesis, and MARC1 with a role in endogenic NO metabolism. We find that platelet and erythrocyte counts uniquely respond to altitude exercise, while changes in neutrophils represent a more generic marker of intense exercise. Publicly available data from both single cell atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for the dynamic evaluation of physiological changes in an athlete's body. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has drawn the attention of many researchers to the interaction between pathogen and host genomes. Over the last two years, numerous studies have been conducted to identify the genetic risk factors that predict COVID-19 severity and outcome. However, such an analysis might be complicated in cohorts of limited size and/or in case of limited breadth of genome coverage. In this work, we tried to circumvent these challenges by searching for candidate genes and genetic variants associated with a variety of quantitative and binary traits in a cohort of 840 COVID-19 patients from Russia. While we found no gene- or pathway-level associations with the disease severity and outcome, we discovered eleven independent candidate loci associated with quantitative traits in COVID-19 patients. Out of these, the most significant associations correspond to rs1651553 in MYH14p = 1.4 × 10−7), rs11243705 in SETX (p = 8.2 × 10−6), and rs16885 in ATXN1 (p = 1.3 × 10−5). One of the identified variants, rs33985936 in SCN11A, was successfully replicated in an independent study, and three of the variants were found to be associated with blood-related quantitative traits according to the UK Biobank data (rs33985936 in SCN11A, rs16885 in ATXN1, and rs4747194 in CDH23). Moreover, we show that a risk score based on these variants can predict the severity and outcome of hospitalization in our cohort of patients. Given these findings, we believe that our work may serve as proof-of-concept study demonstrating the utility of quantitative traits and extensive phenotyping for identification of genetic risk factors of severe COVID-19. [ABSTRACT FROM AUTHOR]

Human herpes virus 6A (HHV-6A) is able to integrate into the telomeric and subtelomeric regions of human chromosomes representing chromosomally integrated HHV-6A (ciHHV-6A). The integration starts from the right direct repeat (DRR) region. It has been shown experimentally that perfect telomeric repeats (pTMR) in the DRR region are required for the integration, while the absence of the imperfect telomeric repeats (impTMR) only slightly reduces the frequency of HHV-6 integration cases. The aim of this study was to determine whether telomeric repeats within DRR may define the chromosome into which the HHV-6A integrates. We analysed 66 HHV-6A genomes obtained from public databases. Insertion and deletion patterns of DRR regions were examined. We also compared TMR within the herpes virus DRR and human chromosome sequences retrieved from the Telomere-to-Telomere consortium. Our results show that telomeric repeats in DRR in circulating and ciHHV-6A have an affinity for all human chromosomes studied and thus do not define a chromosome for integration. [ABSTRACT FROM AUTHOR]

In recent years, great advances have been made in the field of collection, storage, and analysis of biological samples. Large collections of samples, biobanks, have been established in many countries. Biobanks typically collect large amounts of biological samples and associated clinical information; the largest collections include over a million samples. In this review, we summarize the main directions in which biobanks aid medical genetics and genomic research, from providing reference allele frequency information to allowing large-scale cross-ancestry meta-analyses. The largest biobanks greatly vary in the size of the collection, and the amount of available phenotype and genotype data. Nevertheless, all of them are extensively used in genomics, providing a rich resource for genome-wide association analysis, genetic epidemiology, and statistical research into the structure, function, and evolution of the human genome. Recently, multiple research efforts were based on trans-biobank data integration, which increases sample size and allows for the identification of robust genetic associations. We provide prominent examples of such data integration and discuss important caveats which have to be taken into account in trans-biobank research. [ABSTRACT FROM AUTHOR]

Complications endangering mother or fetus affect around one in seven pregnant women. Investigation of the genetic susceptibility to such diseases is of high importance for better understanding of the disease biology as well as for prediction of individual risk. In this study, we collected and analyzed GWAS summary statistics from the FinnGen cohort and UK Biobank for 24 pregnancy complications. In FinnGen, we identified 11 loci associated with pregnancy hypertension, excessive vomiting, and gestational diabetes. When UK Biobank and FinnGen data were combined, we discovered six loci reaching genome-wide significance in the meta-analysis. These include rs35954793 in FGF5 ( p = 6.1 × 10 − 9 ), rs10882398 in PLCE1 ( p = 8.9 × 10 − 9 ), and rs167479 in RGL3 ( p = 5.2 × 10 − 9 ) for pregnancy hypertension, rs10830963 in MTNR1B ( p = 4.5 × 10 − 41 ) and rs36090025 in TCF7L2 ( p = 3.4 × 10 − 15 ) for gestational diabetes, and rs2963457 in the EBF1 locus ( p = 6.5 × 10 − 9 ) for preterm birth. In addition to the identified genome-wide associations, we also replicated 14 out of 40 previously reported GWAS markers for pregnancy complications, including four more preeclampsia-related variants. Finally, annotation of the GWAS results identified a causal relationship between gene expression in the cervix and gestational hypertension, as well as both known and previously uncharacterized genetic correlations between pregnancy complications and other traits. These results suggest new prospects for research into the etiology and pathogenesis of pregnancy complications, as well as early risk prediction for these disorders. [ABSTRACT FROM AUTHOR]

(1) Hypophosphatasia (HPP) is a rare inherited disease caused by mutations (pathogenic variants) in the ALPL gene which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by impaired bone mineral metabolism due to the low enzymatic activity of TNSALP. Knowledge about the structure of the gene and the features and functions of various ALPL gene variants, taking into account population specificity, gives an understanding of the hereditary nature of the disease, and contributes to the diagnosis, prevention, and treatment of the disease. The purpose of the study was to describe the spectrum and analyze the functional features of the ALPL gene variants, considering various HPP subtypes and clinical symptoms in Russian children. (2) From 2014–2021, the study included the blood samples obtained from 1612 patients with reduced alkaline phosphatase activity. The patients underwent an examination with an assessment of their clinical symptoms and biochemical levels of TNSALP. DNA was isolated from dried blood spots (DBSs) or blood from the patients to search for mutations in the exons of the ALPL gene using Sanger sequencing. The PCR products were sequenced using a reagent BigDye Terminator 3.1 kit (Applied Biosystems). Statistical analysis was performed using the GraphPad Prism 8.01 software. (3) The most common clinical symptoms in Russian patients with HPP and two of its variants (n = 22) were bone disorders (75%), hypomyotonia (50%), and respiratory failure (50%). The heterozygous carriage of the causal variants of the ALPL gene was detected in 225 patients. A total of 2 variants were found in 27 patients. In this group (n = 27), we identified 28 unique variants of the ALPL gene, of which 75.0% were missense, 17.9% were frameshift, 3.6% were splicing variants, and 3.6% were duplications. A total of 39.3% (11/28) of the variants were pathogenic, with two variants being probably pathogenic, and 15 variants had unknown clinical significance (VUS). Among the VUS group, 28.6% of the variants (7/28) were discovered by us for the first time. The most common variants were c.571G > A (p.Glu191Lys) and c.1171del (Arg391Valfs*12), with frequencies of 48.2% (13/28) and 11% (3/28), respectively. It was found that the frequency of nonsense variants of the ALPL gene was higher (p < 0.0001) in patients with the perinatal form compared to the infantile and childhood forms of HPP. Additionally, the number of homozygotes in patients with the perinatal form exceeded (p < 0.01) the frequencies of these genotypes in children with infantile and childhood forms of HPP. On the contrary, the frequencies of the compound-heterozygous and heterozygous genotypes were higher (p < 0.01) in patients with infantile childhood HPP than in perinatal HPP. In the perinatal form, residual TNSALP activity was lower (p < 0.0005) in comparison to the infantile and childhood (p < 0.05) forms of HPP. At the same time, patients with the heterozygous and compound-heterozygous genotypes (mainly missense variants) of the ALPL gene had greater residual activity (of the TNSALP protein) regarding those homozygous patients who were carriers of the nonsense variants (deletions and duplications) of the ALPL gene. Residual TNSALP activity was lower (p < 0.0001) in patients with pathogenic variants encoding the amino acids from the active site and the calcium and crown domains in comparison with the nonspecific region of the protein. [ABSTRACT FROM AUTHOR]

In recent years evidence has been accumulated showing that miRNAs can act as potential biomarkers or targets for therapy of preterm birth, one of the most important problems in modern obstetrics. We have performed a prospective study of the miRNA profile in the plasma during the first and second trimesters in pregnant women with high risk of preterm birth (n = 13 cases and n = 11 controls). For the study group plasma blood samples at 9–13 weeks before diagnosis and at 22–24 weeks after start of therapy were selected. Using high-throughput sequencing technology we detected differences in the levels of 15 miRNAs (3 upregulated—hsa-miR-122-5p, hsa-miR-34a-5p, hsa-miR-34c-5p; 12 downregulated—hsa-miR-487b-3p, hsa-miR-493-3p, hsa-miR-432-5p, hsa-miR-323b-3p, hsa-miR-369-3p, hsa-miR-134-5p, hsa-miR-431-5p, hsa-miR-485-5p, hsa-miR-382-5p, hsa-miR-369-5p, hsa-miR-485-3p, hsa-miR-127-3p) (log2(FC) ≥ 1.5; FDR ≤ 0.05) during the first trimester compared with the control (non-high-risk of preterm birth pregnant women). All downregulated miRNAs in the first trimester from the placenta-specific C14MC cluster. During the second trimester no differentially expressed miRNAs were found. Our results suggest that the miRNA profile in plasma during early pregnancy may predict a high risk of preterm birth, which is important in preventing gestational problems as early as possible. [ABSTRACT FROM AUTHOR]

Metformin is an oral hypoglycemic agent widely used in clinical practice for treatment of patients with type 2 diabetes mellitus (T2DM). The wide interindividual variability of response to metformin therapy was shown, and recently the impact of several genetic variants was reported. To assess the independent and combined effect of the genetic polymorphism on glycemic response to metformin, we performed an association analysis of the variants in ATM, SLC22A1, SLC47A1, and SLC2A2 genes with metformin response in 299 patients with T2DM. Likewise, the distribution of allele and genotype frequencies of the studied gene variants was analyzed in an extended group of patients with T2DM (n = 464) and a population group (n = 129). According to our results, one variant, rs12208357 in the SLC22A1 gene, had a significant impact on response to metformin in T2DM patients. Carriers of TT genotype and T allele had a lower response to metformin compared to carriers of CC/CT genotypes and C allele (p-value = 0.0246, p-value = 0.0059, respectively). To identify the parameters that had the greatest importance for the prediction of the therapy response to metformin, we next built a set of machine learning models, based on the various combinations of genetic and phenotypic characteristics. The model based on a set of four parameters, including gender, rs12208357 genotype, familial T2DM background, and waist–hip ratio (WHR) showed the highest prediction accuracy for the response to metformin therapy in patients with T2DM (AUC = 0.62 in cross-validation). Further pharmacogenetic studies may aid in the discovery of the fundamental mechanisms of type 2 diabetes, the identification of new drug targets, and finally, it could advance the development of personalized treatment. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a common chronic disease whose etiology is known to have a strong genetic component. Standard genetic approaches, although allowing for the detection of a number of gene variants associated with the disease as well as differentially expressed genes, cannot fully explain the hereditary factor in T2D. The explosive growth in the genomic sequencing technologies over the last decades provided an exceptional impetus for transcriptomic studies and new approaches to gene expression measurement, such as RNA-sequencing (RNA-seq) and single-cell technologies. The transcriptomic analysis has the potential to find new biomarkers to identify risk groups for developing T2D and its microvascular and macrovascular complications, which will significantly affect the strategies for early diagnosis, treatment, and preventing the development of complications. In this article, we focused on transcriptomic studies conducted using expression arrays, RNA-seq, and single-cell sequencing to highlight recent findings related to T2D and challenges associated with transcriptome experiments. [ABSTRACT FROM AUTHOR]

We performed a comparative cytogenomic analysis of cultured and uncultured uterine leiomyoma (UL) samples. The experimental approach included karyotyping, aCGH, verification of the detected chromosomal abnormalities by metaphase and interphase FISH, MED12 mutation analysis and telomere measurement by Q-FISH. An abnormal karyotype was detected in 12 out of 32 cultured UL samples. In five karyotypically abnormal ULs, MED12 mutations were found. The chromosomal abnormalities in ULs were present mostly by complex rearrangements, including chromothripsis. In both karyotypically normal and abnormal ULs, telomeres were ~40% shorter than in the corresponding myometrium, being possibly prerequisite to chromosomal rearrangements. The uncultured samples of six karyotypically abnormal ULs were checked for the detected chromosomal abnormalities through interphase FISH with individually designed DNA probe sets. All chromosomal abnormalities detected in cultured ULs were found in corresponding uncultured samples. In all tumors, clonal spectra were present by the karyotypically abnormal cell clone/clones which coexisted with karyotypically normal ones, suggesting that chromosomal abnormalities acted as drivers, rather than triggers, of the neoplastic process. In vitro propagation did not cause any changes in the spectrum of the cell clones, but altered their ratio compared to uncultured sample. The alterations were unique for every UL. Compared to its uncultured counterpart, the frequency of chromosomally abnormal cells in the cultured sample was higher in some ULs and lower in others. To summarize, ULs are characterized by both inter- and intratumor genetic heterogeneity. Regardless of its MED12 status, a tumor may be comprised of clones with and without chromosomal abnormalities. In contrast to the clonal spectrum, which is unique and constant for each UL, the clonal frequency demonstrates up or down shifts under in vitro conditions, most probably determined by the unequal ability of cells with different genetic aberrations to exist outside the body. [ABSTRACT FROM AUTHOR]

Although circulating microRNAs (miRNAs) in maternal blood may play an important role in regulation of pregnancy progression and serve as non-invasive biomarkers for different gestation complications, little is known about their profile in blood during normally developing pregnancy. In this study we evaluated the miRNA profiles in paired plasma and serum samples from pregnant women without health or gestational abnormalities at three time points using high-throughput sequencing technology. Sequencing revealed that the percentage of miRNA reads in plasma and serum decreased by a third compared to first and second trimesters. We found two miRNAs in plasma (hsa-miR-7853-5p and hsa-miR-200c-3p) and 10 miRNAs in serum (hsa-miR-203a-5p, hsa-miR-495-3p, hsa-miR-4435, hsa-miR-340-5p, hsa-miR-4417, hsa-miR-1266-5p, hsa-miR-4494, hsa-miR-134-3p, hsa-miR-5008-5p, and hsa-miR-6756-5p), that exhibit level changes during pregnancy (p-value adjusted < 0.05). In addition, we observed differences for 36 miRNAs between plasma and serum (p-value adjusted < 0.05), which should be taken into consideration when comparing the results between studies performed using different biosample types. The results were verified by analysis of three miRNAs using qRT-PCR (p < 0.05). The present study confirms that the circulating miRNA profile in blood changes during gestation. Our results set the basis for further investigation of molecular mechanisms, involved in regulation of pregnancy, and the search for biomarkers of gestation abnormalities. [ABSTRACT FROM AUTHOR]

Hydrogenation of CO2 relative to valuable chemical compounds such as methanol or dimethyl ether (DME) is an attractive route for reducing CO2 emissions in the atmosphere. In the present work, the hydrogenation of CO2 into DME over CuO-In2O3, supported on halloysite nanotubes (HNT) was investigated in the temperature range 200–300 °C at 40 atm. HNT appears to be novel promising support for bifunctional catalysts due to its thermal stability and the presence of acidic sites on its surface. CuO-In2O3/HNT catalysts demonstrate higher CO2 conversion and DME selectivity compared to non-indium CuO/HNT catalysts. The catalysts were investigated by N2 adsorption, X-ray diffraction, hydrogen-temperature programmed reduction and transition electron microscopy. The acid sites were analyzed by temperature programmed desorption of ammonia. It was shown that CuO/HNT was unstable under reaction conditions in contrast to CuO-In2O3/HNT. The best CuO-In2O3/HNT catalyst provided CO2 conversion of 7.6% with 65% DME selectivity under P = 40 atm, T = 250 °C, gas hour space velocity 12,000 h−1 and H2:CO2 = 3:1. [ABSTRACT FROM AUTHOR]

Keywords: petrochemical synthesis; oil refining; zeolites; aluminosilicates; organic and metal-organic frameworks; nanotubes; hydroprocessing; C-1 chemistry EN petrochemical synthesis oil refining zeolites aluminosilicates organic and metal-organic frameworks nanotubes hydroprocessing C-1 chemistry 602 1 05/26/21 20210501 NES 210501 In modern industry, more than 90% of processes are catalytic. Petrochemical synthesis, oil refining, zeolites, aluminosilicates, organic and metal-organic frameworks, nanotubes, hydroprocessing, C-1 chemistry 10.3390/catal10050537 2 Kuchinskaya T., Kniazeva M., Samoilov V., Maximov A. In Situ Generated Nanosized Sulfide Ni-W Catalysts Based on Zeolite for the Hydrocracking of the Pyrolysis Fuel Oil into the BTX Fraction. [Extracted from the article]

Clinical tests based on whole-genome sequencing are generally focused on a single task approach, testing one or several parameters, although whole-genome sequencing (WGS) provides us with large data sets that can be used for many supportive analyses. In spite of low genome coverage, data of WGS-based non-invasive prenatal testing (NIPT) contain fully sequenced mitochondrial DNA (mtDNA). This mtDNA can be used for variant calling, ancestry analysis, population studies and other approaches that extend NIPT functionality. In this study, we analyse mtDNA pool from 645 cell-free DNA (cfDNA) samples of pregnant women from different regions of Russia, explore the effects of transportation and storing conditions on mtDNA content, analyse effects, frequency and location of mitochondrial variants called from samples and perform haplogroup analysis, revealing the most common mitochondrial superclades. We have shown that, despite the relatively low sequencing depth of unamplified mtDNA from cfDNA samples, the mtDNA analysis in these samples is still an informative instrument suitable for research and screening purposes. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2D) is a chronic metabolic disease resulting from insulin resistance and progressively reduced insulin secretion, which leads to impaired glucose utilization, dyslipidemia and hyperinsulinemia and progressive pancreatic beta cell dysfunction. The incidence of type 2 diabetes mellitus is increasing worldwide and nowadays T2D already became a global epidemic. The well-known interindividual variability of T2D drug actions such as biguanides, sulfonylureas/meglitinides, DPP-4 inhibitors/GLP1R agonists and SGLT-2 inhibitors may be caused, among other things, by genetic factors. Pharmacogenetic findings may aid in identifying new drug targets and obtaining in-depth knowledge of the causes of disease and its physiological processes, thereby, providing an opportunity to elaborate an algorithm for tailor or precision treatment. The aim of this article is to summarize recent progress and discoveries for T2D pharmacogenetics and to discuss the factors which limit the furthering accumulation of genetic variability knowledge in patient response to therapy that will allow improvement the personalized treatment of T2D. [ABSTRACT FROM AUTHOR]

Novel bimetallic Pd-Mn/Al2O3 catalysts are designed by the decomposition of cyclopentadienylmanganese tricarbonyl (cymantrene) on reduced Pd/Al2O3 in an H2 atmosphere. The peculiarities of cymantrene decomposition on palladium and, thus, the formation of bimetallic Pd-Mn catalysts are studied. The catalysts are characterized by N2 adsorption, H2 pulse chemisorption, temperature-programmed desorption of hydrogen (TPD-H2), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The modified catalysts show the changed hydrogen chemisorption properties and the absence of weakly bonded hydrogen. Using an organomanganese precursor provides an uniform Mn distribution on the catalyst surface. Tested in hydrogenation of acetylene, the catalysts show both higher activity and selectivity to ethylene (20% higher) compared to the non-modified Pd/Al2O3 catalyst. The influence of the addition of Mn and temperature treatment on catalyst performance is studied. The optimal Mn content and treatment temperature are found. It is established that modification with Mn changes the route of acetylene hydrogenation from a consecutive scheme for Pd/Al2O3 to parallel one for the Pd-Mn samples. The reaction rate shows zero overall order by reagents for all tested catalysts. [ABSTRACT FROM AUTHOR]

Bifunctional catalysts on the base of transition metal sulfides (CoMoS and NiWS) and platinum as noble metal were synthesized via wetness impregnation of freshly synthesized Al2O3-SAPO-11 composites, supported with favorable acidic properties. The physical-chemical properties of the prepared materials were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), low-temperature N2 adsorption and high resolution transmission electron microscopy (HR TEM) methods. Catalytic properties were studied in n-hexadecane isomerization using a fixed-bed flow reactor. The catalytic poisons tolerance of transition metal sulfides (TMS)- and Pt-catalysts has been studied for sulfur and nitrogen, with the amount of 10–100 ppm addition to feedstock. TMS-catalysts show good stability during sulfur-containing feedstock processing, whereas Pt-catalyst loses much of its isomerization activity. Nitrogen-containing compounds in the feedstock has a significant impact on the catalytic activity of both TMS and Pt-based catalysts. [ABSTRACT FROM AUTHOR]

Mesoporous ruthenium catalysts (0.74–3.06 wt%) based on ordered Mobil Composition of Matter No. 41 (MCM-41) silica arrays on aluminosilicate halloysite nanotubes (HNTs), as well as HNT-based counterparts, were synthesized and tested in benzene hydrogenation. The structure of HNT core-shell silica composite-supported Ru catalysts were investigated by transmission electron microscopy (TEM), X-ray fluorescence (XRF) and temperature-programmed reduction (TPR-H2). The textural characteristics were specified by low-temperature nitrogen adsorption/desorption. The catalytic evaluation of Ru nanoparticles supported on both the pristine HNTs and MCM-41/HNT composite in benzene hydrogenation was carried out in a Parr multiple reactor system with batch stirred reactors (autoclaves) at 80 °C, a hydrogen pressure of 3.0 MPa and a hydrogen/benzene molar ratio of 3.3. Due to its hierarchical structure and high specific surface area, the MCM-41/HNT composite provided the uniform distribution and stabilization of Ru nanoparticles (NPs) resulted in the higher specific activity and stability as compared with the HNT-based counterpart. The highest specific activity (5594 h−1) along with deep benzene hydrogenation to cyclohexane was achieved for the Ru/MCM-41/HNT catalyst with a low metal content. [ABSTRACT FROM AUTHOR]

Over the recent years, many advances have been made in the research of the genetic factors of pregnancy complications. In this work, we use publicly available data repositories, such as the National Human Genome Research Institute GWAS Catalog, HuGE Navigator, and the UK Biobank genetic and phenotypic dataset to gain insights into molecular pathways and individual genes behind a set of pregnancy-related traits, including the most studied ones—preeclampsia, gestational diabetes, preterm birth, and placental abruption. Using both HuGE and GWAS Catalog data, we confirm that immune system and, in particular, T-cell related pathways are one of the most important drivers of pregnancy-related traits. Pathway analysis of the data reveals that cell adhesion and matrisome-related genes are also commonly involved in pregnancy pathologies. We also find a large role of metabolic factors that affect not only gestational diabetes, but also the other traits. These shared metabolic genes include IGF2, PPARG, and NOS3. We further discover that the published genetic associations are poorly replicated in the independent UK Biobank cohort. Nevertheless, we find novel genome-wide associations with pregnancy-related traits for the FBLN7, STK32B, and ACTR3B genes, and replicate the effects of the KAZN and TLE1 genes, with the latter being the only gene identified across all data resources. Overall, our analysis highlights central molecular pathways for pregnancy-related traits, and suggests a need to use more accurate and sophisticated association analysis strategies to robustly identify genetic risk factors for pregnancy complications. [ABSTRACT FROM AUTHOR]

Halloysite aluminosilicate nanotubes loaded with ruthenium particles were used as reactors for Fischer–Tropsch synthesis. To load ruthenium inside clay, selective modification of the external surface with ethylenediaminetetraacetic acid, urea, or acetone azine was performed. Reduction of materials in a flow of hydrogen at 400 °C resulted in catalysts loaded with 2 wt.% of 3.5 nm Ru particles, densely packed inside the tubes. Catalysts were characterized by N2-adsorption, temperature-programmed desorption of ammonia, transmission electron microscopy, X-ray fluorescence, and X-ray diffraction analysis. We concluded that the total acidity and specific morphology of reactors were the major factors influencing activity and selectivity toward CH4, C2–4, and C5+ hydrocarbons in the Fischer–Tropsch process. Use of ethylenediaminetetraacetic acid for ruthenium binding gave a methanation catalyst with ca. 50% selectivity to methane and C2–4. Urea-modified halloysite resulted in the Ru-nanoreactors with high selectivity to valuable C5+ hydrocarbons containing few olefins and a high number of heavy fractions (α = 0.87). Modification with acetone azine gave the slightly higher CO conversion rate close to 19% and highest selectivity in C5+ products. Using a halloysite tube with a 10–20-nm lumen decreased the diffusion limitation and helped to produce high-molecular-weight hydrocarbons. The extremely small C2–C4 fraction obtained from the urea- and azine-modified sample was not reachable for non-templated Ru-nanoparticles. Dense packing of Ru nanoparticles increased the contact time of olefins and their reabsorption, producing higher amounts of C5+ hydrocarbons. Loading of Ru inside the nanoclay increased the particle stability and prevented their aggregation under reaction conditions. [ABSTRACT FROM AUTHOR]

Polyoxometalate-based ionic liquid hybrid materials with a pyridinium cation, containing Brönsted acid sites, were synthesized and used as catalysts for the oxidation of model and real diesel fuels. Keggin-type polyoxometalates with the formulae [PMo12O40]3−, [PVMo11O40]4−, [PV2Mo10O40]4−, [PW12O40]3− were used as anions. It was shown that increasing the acid site strength leads to an increase of dibenzothiophene conversion to the corresponding sulfone. The best results were obtained in the presence of a catalyst, containing a nicotinic acid derivative as cation and phosphomolybdate as anion. The main factors affecting the process consisting of catalyst dosage, temperature, reaction time, oxidant dosage were investigated in detail. Under optimal conditions full oxidation of dibenzothiophene and more than a 90% desulfurization degree of real diesel fuel (initial sulfur content of 2050 ppm) were obtained (the oxidation conditions: NK-1 catalyst, molar ratio H2O2:S 10:1, molar ratio S:Mo 8:1, 1 mL MeCN, 70 °C, 1 h). The synthesized catalysts could be used five times with a slight decrease in activity. [ABSTRACT FROM AUTHOR]

Bimetallic MnCo catalyst, supported on the mesoporous hierarchical MCM-41/halloysite nanotube composite, was synthesized for the first time and proved its efficacy in the selective oxidation of p-xylene to terephthalic acid under conditions of the AMOCO process. Quantitative yields of terephthalic acid were achieved within 3 h at 200–250 °C, 20 atm. of O2 and at a substrate to the Mn + Co ratio of 4–4.5 times higher than for traditional homogeneous system. The influence of temperature, oxygen, pressure and KBr addition on the catalyst activity was investigated, and the mechanism for the oxidation of p-toluic acid to terephthalic acid, excluding undesirable 4-carboxybenzaldehyde, was proposed. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a multisystem heterogeneous complication of pregnancy remaining a leading cause of maternal and perinatal morbidity and mortality over the world. PE has a large spectrum of clinical features and symptoms, which make diagnosis challenging. Despite a long period of studying, PE etiology is still unclear and there are no reliable rapid tests for early diagnosis of this disease. During the last decade, it was shown that proteins misfolding and aggregation are associated with PE. Several proteins, including amyloid beta peptide, transthyretin, alpha-1 antitrypsin, albumin, IgG k-free light chains, and ceruloplasmin are dysregulated in PE, resulting in toxic deposition of amyloid-like aggregates in the placenta and body fluids. It is also possible that aggregated proteins induce defective trophoblast invasion, placental ischemia, ER stress, and promote PE manifestation. The fact that protein aggregation is an emerging biomarker of PE provides an opportunity to develop new diagnostic approaches based on amyloids special features, such as Congo red (CR) staining and thioflavin T (ThT) enhanced fluorescence. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10−5), rs112984085 in VAV3 (p = 4.8 × 10−4) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10−4), rs34042554 in PCDHA1 (p = 1 × 10−4), and rs144183813 in PLEKHA5 (p = 1.7 × 10−4) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10−5), and rs685523 in ADAMTS13 (p = 1 × 10−6) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations. [ABSTRACT FROM AUTHOR]

Bimetallic catalysts (BMC) for hydroconversion of aromatic hydrocarbons (ArH) have been designed by modification of Ni/Al2O3 with chromium(0) compounds and phosphoromolybdic heteropolyacid (HPA). Catalysts were tested in hydrogenation of benzene and toluene, in hydrodemethylation of pure toluene and they were shown to possess a high activity, selectivity and sulfur tolerance under conditions of the processes above. The activity of BMC in these processes was much higher as compared with that of two-component (Ni-Cr, Ni-HPA) or conventional Ni/Al2O3 catalysts. Using BMC, hydrogenation of benzene and toluene proceeds with activity increased (up to 34–38 mol/kg·h) and toluene hydrodemethylation may be performed with improved selectivity (90.3%) and benzene yield (81%). The high sulfur tolerance of BMC was demonstrated by performing hydrodemethylation of toluene containing up to 500 ppm S. [ABSTRACT FROM AUTHOR]