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Green and sustainable access to chiral and achiral gold-IBiox complexes is reported. The gold complexes were synthesized using a simple, air-tolerant, weak base protocol carried out in a green solvent. Their catalytic activity was examined in the hydroamination of alkynes. The steric protection afforded the gold center by these ligands was quantified using the %; V; bur; model and compared with the most commonly encountered NHCs.

A simple synthetic pathway to new families of Au–NHC amido complexes under mild reaction conditions is described. Their in vitro anticancer activity was investigated on three human cell lines, showing comparable or even better results than cisplatin.

We present the use of gold sensitizers [Au(SIPr)(Cbz)] (PhotAu 1) and [Au(IPr)(Cbz)] (PhotAu 2) as attractive alternatives to state-of-the-art iridium-based systems. These novel photocatalysts are deployed in [2 + 2] cycloadditions of diallyl ethers and N-tosylamides. The reactions proceed in short reaction times and in environmentally friendly solvents. [Au(SIPr)Cbz] and [Au(IPr)(Cbz)] have higher triplet energy (E-T) values (66.6 and 66.3 kcal mol(-1), respectively) compared to commonly used iridium photosensitizers. These E-T values permit the use of these gold complexes as sensitizers enabling energy transfer catalysis involving unprotected indole derivatives, a substrate class previously inaccessible with state-of-the-art Ir photocatalysts. The photosynthesis of unprotected tetracyclic spiroindolines via intramolecular [2 + 2] cycloaddition using our simple mononuclear gold sensitizer is readily achieved. Mechanistic studies support the involvement of triplet-triplet energy transfer (TTEnT) for both [2 + 2] photocycloadditions.

Along with bright fluorescence in the near-IR range, heptamethine carbocyanine dyes possess affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery as covalent conjugates with cytotoxic compounds. To test the properties, structure-activity relationship, and scope of such conjugates, we synthesized drug-dye dyads of tricarbocyanine dyes with anthracycline drug daunorubicin. We used hydrophilic zwitterionic and hydrophobic positively charged benzoindoline-benzothiazole-based heptamethine dyes as terminal alkyne derivatives and N-acylated or oxime-linked daunorubicin as azido-derivatives. These two alkynes and two azides were coupled to each other by Cu-catalyzed Huisgen-Meldal-Sharpless cycloaddition (click reaction) to afford four conjugates. Molecules based on hydrophobic dyes possess submicromolar cytotoxicity to HCT116 cells. Cytotoxicity, cell penetration, intracellular distribution, apoptosis induction and the effect of antioxidants on toxicity were evaluated. The results show that the structure of the cyanine-anthracycline conjugate (hydrophilicity/hydrophobicity, charge, linker, attachment site) is important for its biological activity, thus, expansion of the chemical space of such conjugates could provide new molecular research tools for diagnostics and therapy.

Multiple sclerosis (MS) is a chronic debilitating disease of unknown etiology. The disease has a seasonal exacerbation of clinical symptoms, which are frequently described in spring and summer. However, the mechanisms of such seasonal exacerbations remain unknown. In this study, we used targeted metabolomics analysis of serum samples using LC-MC/MC to determine seasonal changes in metabolites. We have found changes in multiple metabolites which differed depending on season. The ceramides, belonging to the sphingolipid pathway, were found activated in spring-summer (SS) and fall-winter (FW) MS, suggesting their central role in disease pathogenesis. Our identification of ceramide activation suggests a mechanism of neuron damage in MS which could be further investigated as therapeutic targets.

Рассеянный склероз (РС) – это нейродегенеративное заболевание центральной нервной системы, причины которого в настоящее время остаются неизвестными. Выявление взаимосвязи между наличием антител IgG к нейротропным герпесвирусам и РС может служить диагностическим маркером развития заболевания. В результате определения уровня антител у больных РС установлено, что во время ремиссии у пациентов наблюдается статистически значимо большее количество IgG к цитомегаловирусу по сравнению с пациентами во время обострения заболевания. Полученные результаты позволяют выдвинуть предположение о влиянии цитомегаловируса на развитие РС.

Геморрагическая лихорадка с почечным синдромом (ГЛПС) является природно-очаговым инфекционным заболеванием, которое представляет собой угрозу общественному здравоохранению. Большинство случаев ГЛПС в России регистрируются в Поволжье, где в качестве инфекционного агента в основном идентифицируется вирус Пуумала (PUUV). Лечение ГЛПС носит симптоматический характер, при этом отсутствие специфических мер профилактики, равно как и одобренных вакцин, являются существенным недостатком. С недавнего времени микровезикулы (МВ) рассматриваются в качестве перспективных носителей для доставки вакцинных антигенов, поскольку было показано, что они индуцируют врожденные и адаптивные иммунные реакции. Целью настоящего исследования являлась оценка эффективности (МВ) в качестве средств для доставки структурных белков PUUV и индукция иммунного ответа. Нами было показано, что МВ, несущие белки нуклеокапсида (N) и гликопротеины (Gn / Gc) PUUV способны индуцировать специфический гуморальный иммунный ответ in vivo, что является одним из ключевых факторов в разработке методов вакцинопрофилактики.

Рассеянный склероз (РС) – хроническое инвалидизирующее заболевание неизвестной этиологии. Заболевание характеризуется сезонными обострениями клинических симптомов, которые чаще проявляются весной и летом. Однако механизмы таких сезонных обострений остаются неизвестными. В данной работе мы использовали целевой метаболомный анализ образцов сыворотки с использованием LC-MC/MC для определения сезонных изменений метаболитов. Были выявлены изменения в нескольких метаболитах, которые различались в зависимости от сезона. Было обнаружено также, что церамиды, принадлежащие к сфинголипидному пути, активируются при весенне-летнем и осенне-зимнем РС, что позволяет предположить их центральную роль в патогенезе заболевания. Выявленная активация церамидов наводит на мысль о механизме повреждения нейронов при РС, который можно было бы далее исследовать в качестве терапевтической мишени., Multiple sclerosis (MS) is a chronic debilitating disease of unknown etiology. The disease has a seasonal exacerbation of clinical symptoms, which are frequently described in spring and summer. However, the mechanisms of such seasonal exacerbations remain unknown. In this study, we used targeted metabolomics analysis of serum samples using LC-MC/MC to determine seasonal changes in metabolites. We have found changes in multiple metabolites which differed depending on season. The ceramides, belonging to the sphingolipid pathway, were found activated in spring-summer (SS) and fall-winter (FW) MS, suggesting their central role in disease pathogenesis. Our identification of ceramide activation suggests a mechanism of neuron damage in MS which could be further investigated as therapeutic targets.

Выявление иммуногенных мишеней коронавируса SARS-CoV-2 имеет решающее значение для совершенствования стратегий диагностики и борьбы с заболеванием. Авторы статьи проанализировали гуморальный (ИФА) иммунный ответй на спайковый (S) и нуклеокапсидный (N) белки SARS-CoV-2 в сыворотке крови выздоравливающих пациентов с COVID-19 из Татарстана, Россия. В сыворотке крови выздоравливающих от COVID-19 были идентифицированы множественные пептиды SARS-CoV-2. Кроме того, были выявлены возрастные и гендерные различия в реактивности к S- и N-белковым пептидам. Таким образом, в исследовании была продемонстрирована изменяющаяся картина реактивности иммуногенных пептидов в сыворотке COVID-19 в зависимости от возраста и пола. Полученные данные показывают, как гуморальные иммунные реакции на некоторые из коронавирусных пептидов могут способствовать патогенезу COVID-19., Identifying immunogenic targets of SARS-CoV-2 is essential to develop novel treatments. The authors of the article studied humoral immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins in serum from convalescent COVID-19 patients from Tatarstan, Russia. Multiple SARS-CoV-2 peptides were identified as reacting with convalescent COVID-19 serum. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age and gender was demonstrated. These data highlight how humoral immune responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

N-Heterocyclic carbenes (NHCs) are nowadays ubiquitous in organometallic chemistry and catalysis. Recently, a synthetic method which makes use of weak bases and desirable solvents has emerged as a simple, widely applicable and cost-effective pathway to well defined M-NHC complexes. Herein, recent studies devoted to the weak base approach are examined in detail, in order to showcase the simplicity, scope and variations of the method with regards to the azolium salts, bases and the metal sources, as well as the reaction conditions used. Mechanistic investigations are presented, illustrating the formation of intermediates which are air and moisture stable, prior to the metallation step. Finally, the importance, limitations and future prospects of the weak base route are discussed.

The article is devoted to the analysis of the history of origin and etymology of some mathematical terms that have identical to the usual things names in natural languages. The research was conducted through analysis of literature, related scientific papers. The terms for study were taken from the field of abstract algebra, some of the terms are technical and used in the whole math. The explanation of the etymology of the terms allows getting deeper into the related area of mathematics, to increase level of the subject understanding and mathematical intuition. The research may be useful to students majoring in mathematics and linguistics.

Heptamethine carbocyanine dyes possess bright fluorescence in the near IR range and affinity to cancer cells. Thus, these dyes could be utilized as fluorescent labels and vectors for drug delivery in their covalent conjugates with cytotoxic compounds. In this work we synthesized four drug-dye conjugates of tricarbocyanine dyes with anthracycline drug daunorubicin using a CuAAC reaction. Conjugates with hydrophobic dyes possess submicromolar cytotoxicity. Fluorescent imaging revealed significant accumulation of the conjugates in mitochondria, suggesting an enhancement of an additional mechanism of anthracycline cytotoxicity – generation of ROS. The hypothesis was supported by significant reduction of activity of the conjugates in presence of an antioxidant compound.

In the European part of Russia, the highest number of hemorrhagic fever with renal syndrome (HFRS) cases are registered in the Volga Federal District (VFD), which includes the Republic of Tatarstan (RT). Puumala orthohantavirus (PUUV) is the main causative agent of HFRS identified in the RT. The goal of the current study is to analyze the genetic variations of the PUUV strains and possible presence of chimeric and reassortant variants among the PUUV strains circulating in bank vole populations in the Trans-Kama area of the RT. Complete S segment CDS as well as partial M and L segment coding nucleotide sequences were obtained from 40 PUUV-positive bank voles and used for the analysis. We found that all PUUV strains belonged to RUS genetic lineage and clustered in two subclades corresponding to the Western and Eastern Trans-Kama geographic areas. PUUV strains from Western Trans-Kama were related to the previously identified strain from Teteevo in the Pre-Kama area. It can be suggested that the PUUV strains were introduced to the Teteevo area as a result of the bank voles’ migration from Western Trans-Kama. It also appears that physical obstacles, including rivers, could be overcome by migrating rodents under favorable circumstances. Based on results of the comparative and phylogenetic analyses, we propose that bank vole distribution in the Trans-Kama area occurred upstream along the river valleys, and that watersheds could act as barriers for migrations. As a result, the diverged PUUV strains could be formed in closely located populations. In times of extensive bank vole population growth, happening every 3–4 years, some regions of watersheds may become open for contact between individual rodents from neighboring populations, leading to an exchange of the genetic material between divergent PUUV strains.

In the European part of Russia, the highest number of hemorrhagic fever with renal syndrome (HFRS) cases are registered in the Volga Federal District (VFD), which includes the Republic of Tatarstan (RT). Puumala orthohantavirus (PUUV) is the main causative agent of HFRS identified in the RT. The goal of the current study is to analyze the genetic variations of the PUUV strains and possible presence of chimeric and reassortant variants among the PUUV strains circulating in bank vole populations in the Trans-Kama area of the RT. Complete S segment CDS as well as partial M and L segment coding nucleotide sequences were obtained from 40 PUUV-positive bank voles and used for the analysis. We found that all PUUV strains belonged to RUS genetic lineage and clustered in two subclades corresponding to the Western and Eastern Trans-Kama geographic areas. PUUV strains from Western Trans-Kama were related to the previously identified strain from Teteevo in the Pre-Kama area. It can be suggested that the PUUV strains were introduced to the Teteevo area as a result of the bank voles’ migration from Western Trans-Kama. It also appears that physical obstacles, including rivers, could be overcome by migrating rodents under favorable circumstances. Based on results of the comparative and phylogenetic analyses, we propose that bank vole distribution in the Trans-Kama area occurred upstream along the river valleys, and that watersheds could act as barriers for migrations. As a result, the diverged PUUV strains could be formed in closely located populations. In times of extensive bank vole population growth, happening every 3–4 years, some regions of watersheds may become open for contact between individual rodents from neighboring populations, leading to an exchange of the genetic material between divergent PUUV strains.

Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the “Russia” (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.

The development of novel and operationally simple synthetic routes to carbene‐metal‐amido (CMA) complexes of copper, silver and gold relevant for photonic applications are reported. A mild base and sustainable solvents allow all reactions to be conducted in air and at room temperature, leading to high yields of the targeted compounds even on multigram scales. The effect of various mild bases on the N−H metallation was studied in silico and experimentally, while a mechanochemical, solvent‐free synthetic approach was also developed. Our photophysical studies on [M(NHC)(Cbz)] (Cbz=carbazolyl) indicate that the occurrence of fluorescent or phosphorescent states is determined primarily by the metal, providing control over the excited state properties. Consequently, we demonstrate the potential of the new CMAs beyond luminescence applications by employing a selected CMA as a photocatalyst. The exemplified synthetic ease is expected to accelerate the applications of CMAs in photocatalysis and materials chemistry., N−H metallation routes: Interest in carbene‐metal‐amido (CMA) complexes of the coinage metals has inspired comprehensive efforts towards simplifying their synthesis. We now showcase simple and sustainable routes to various CMAs, using mild conditions for the N−H metallation of carbazole and other amines. The action of a mild base is studied computationally and the photophysical properties of some new CMA complexes are examined.

The synthesis and characterization of novel palladium complexes bearing N-heterocyclic carbenes (NHCs) and 1,4,7-triaza-9-phosphatricyclo[5.3.2.1]tridecane (CAP) are reported. These organometallic complexes can be easily obtained using two different synthetic strategies that involve either the substitution of the pyridine ligand from trans-[Pd(NHC)(Py)Cl2] or by simple addition of the CAP ligand to dimeric species [Pd(NHC)Cl2]2. The mixed NHC/CAP complexes were tested as pre-catalysts in the Buchwald–Hartwig aryl amination coupling, showing good catalytic activity, especially in the case of cis-[Pd(IPr)(CAP)Cl2].

The article presents findings of distribution patterns of Russian grammatical categories computed with the help of MyStem.3 tagger and a proprietary Russian language processor, ETAP-3. The corpus of over 1.1 mln tokens compiled for the study comprises two types of academic textbooks used in Russian schools: Science and Humanities. We computed descriptive metrics of each textbooks with the help of the text analyzer RusAC (http://tykau.pythonanywhere.com/) and pursued the contrastive analysis of Science and Humanities textbook features. Significant differences of two types of the texts were found in distribution patterns of noun cases and verbs tenses, while morphological categories of nouns, adjectives, verbs, and adverbs demonstrate similarities. The specifics of grammatical patterns defined for classroom textbooks can be used in further studies on distribution of morphological patterns and text complexity of Russian academic texts.

Background. Multiple sclerosis (MS) is a chronic debilitating disorder characterized by persisting damage to the brain caused by autoreactive leukocytes. Leukocyte activation is regulated by cytokines, which are readily detected in MS serum and cerebrospinal fluid (CSF). Objective. Serum and CSF levels of forty-five cytokines were analyzed to identify MS diagnostic markers. Methods. Cytokines were analyzed using multiplex immunoassay. ANOVA-based feature and Pearson correlation coefficient scores were calculated to select the features which were used as input by machine learning models, to predict and classify MS. Results. Twenty-two and twenty cytokines were altered in CSF and serum, respectively. The MS diagnosis accuracy was ≥92% when any randomly selected five of these biomarkers were used. Interestingly, the highest accuracy (99%) of MS diagnosis was demonstrated when CCL27, IFN-γ, and IL-4 were part of the five selected cytokines, suggesting their important role in MS pathogenesis. Also, these binary classifier models had the accuracy in the range of 70-78% (serum) and 60-69% (CSF) to discriminate between the progressive (primary and secondary progressive) and relapsing-remitting forms of MS. Conclusion. We identified the set of cytokines from the serum and CSF that could be used for the MS diagnosis and classification.

Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease’s severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates.

Puumala orthohantavirus (PUUV) causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) commonly diagnosed in Europe. The majority of HFRS cases in the European part of Russia are diagnosed in the Volga Federal District, which includes the Republic of Tatarstan (RT). The current study aims to analyze the genetic variability of PUUV in Pre-Kama region of the RT bounded by the Volga, Kama, and Vyatka rivers. In 2017, bank voles were caught in seven isolated forest traps in the Pre-Kama region and for the 26 PUUV-positive samples, the partial small (S), medium (M), and large (L) genome segment sequences were obtained and analyzed. It was determined that all identified PUUV strains belong to the Russian (RUS) genetic lineage, however, the genetic distance between strains is not directly correlated with the geographical distance between bank vole populations. One of the identified strains has S and L segments produced from one parental strain, while the M segment was supplied by another, suggesting that this strain could be the reassortant. We suggest that the revealed pattern of the PUUV strains distribution could be the result of a series of successive multidirectional migratory flows of the bank voles to the Pre-Kama region in the postglacial period.

Multiple sclerosis (MS) is an immune inflammatory disease, where the underlying etiological cause remains elusive. Multiple triggering factors have been suggested, including environmental, genetic and gender components. However, underlying infectious triggers to the disease are also suspected. There is an increasing abundance of evidence supporting a viral etiology to MS, including the efficacy of interferon therapy and over-detection of viral antibodies and nucleic acids when compared with healthy patients. Several viruses have been proposed as potential triggering agents, including Epstein–Barr virus, human herpesvirus 6, varicella–zoster virus, cytomegalovirus, John Cunningham virus and human endogenous retroviruses. These viruses are all near ubiquitous and have a high prevalence in adult populations (or in the case of the retroviruses are actually part of the genome). They can establish lifelong infections with periods of reactivation, which may be linked to the relapsing nature of MS. In this review, the evidence for a role for viral infection in MS will be discussed with an emphasis on immune system activation related to MS disease pathogenesis.

Text complexity as a research problem is equally relevant in linguistics and education since its solution provides an algorithm to match readers of certain categories to texts. Numerous studies have been conducted to identify quantitative and qualitative parameters that affect text complexity in ESOL. However, text complexity range within one proficiency level remains a research niche. The current study is aimed at identifying the range of text complexity fluctuations within one proficiency level and their appropriateness for readers. We conduct a multi-factor analysis and contrast 66 English texts for Basic State Examination (OGE) in readability, average sentence length, word length, number of verbs and nouns, cohesion and lexical diversity. The text features computed with the two online services, Text Inspector and Coh-Metrix, provide slightly different quantitative results though consistent in qualifying the range of text complexity fluctuations as high. The research findings refute the hypothesis of a linear nature of text complexity growth in the textbooks designed to increase students’ proficiency and confirm the lack of correlation between the revealed and claimed complexity of texts. The algorithm suggested by the authors can be useful for textbook writers and test developers selecting reading material for any proficiency level.

The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem/stromal cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. Objectives: The objectives of this study were to analyze the morphology, size distribution, molecular composition, and angiogenic properties of CIMVs-MSCs. Methods: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis, and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using an in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix. Results: Human CIMVs-MSCs retain parental MSCs content, such as growth factors, cytokines, and chemokines: EGF, FGF-2, Eotaxin, TGF-&alpha, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFN&alpha, 2, IFN-&gamma, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-&alpha, TNF-&beta, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cells in vitro. Finally, CIMVs-MSCs can induce angiogenesis in vivo after subcutaneous injection into adult rats. Conclusions: Human CIMVs-MSCs have similar content, immunophenotype, and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.

В статье приведена характеристика персонала поколений «Y» и «Z» и подробно рассмотрены мотивирующие факторы для представителей данных поколений персонала. Представлена подробная сравнительная характеристика системы подбора персонала поколений «Y» и «Z» в организации.