One-Pot Synthesis of -Fused Quinolone-4 Tetracyclic Scaffolds from 2,2-Disubstituted Indolin-3-ones.

A cascade transformation of C2-quaternary indoxyls leading to an efficient assembly of complex (dihydro)indolo[1,2-]quinolin-5-one ring systems is reported. The method involves the gram-scale preparation of 2-(2-aryl-3-oxoindolin-2-yl)-2-phenylacetonitriles which are then converted with methyl ketones to the corresponding 2-(2-oxo-2-aryl(alkyl)ethyl)-2-phenylindolin-3-ones. The latter can either be isolated with good yields (75-96%) or, in the case of -nitroacetophenone, used for further base-assisted intramolecular SAr cyclization resulting in indoxyl-fused quinolone-4 hybrids (up to 95%).

[Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019-2022)].

Background: Arterial hypertension (AH) remains the leading risk factor associated with cardiovascular diseases (CVDs), cerebrovascular disease and chronic kidney disease. About 70% of patients with AH who are on monotherapy cannot achieve blood pressure (BP) targets, and therefore all quidelines for the management of AH have recently recommended prescribing combination therapy (PCT). In real clinical practice (RCP), there remains significant uncertainty in the effectiveness and rationality of therapy, despite the wide availability of antihypertensive drugs (AHD) and the presence of recommendations for a stepwise approach to prescribing combinations of specific groups of AHD in different clinical situations.

G-Quadruplex Forming DNA Sequence Context Is Enriched around Points of Somatic Mutations in a Subset of Multiple Myeloma Patients.

Multiple myeloma (MM) is the second most common hematological malignancy, which remains incurable despite recent advances in treatment strategies. Like other forms of cancer, MM is characterized by genomic instability, caused by defects in DNA repair. Along with mutations in DNA repair genes and genotoxic drugs used to treat MM, non-canonical secondary DNA structures (four-stranded G-quadruplex structures) can affect accumulation of somatic mutations and chromosomal abnormalities in the tumor cells of MM patients.

Practical Approaches for the Yeast Genome Modification.

The yeast is a unique genetic object for which a wide range of relatively simple, inexpensive, and non-time-consuming methods have been developed that allow the performing of a wide variety of genome modifications. Among the latter, one can mention point mutations, disruptions and deletions of particular genes and regions of chromosomes, insertion of cassettes for the expression of heterologous genes, targeted chromosomal rearrangements such as translocations and inversions, directed changes in the karyotype (loss or duplication of particular chromosomes, changes in the level of ploidy), mating-type changes, etc. Classical yeast genome manipulations have been advanced with CRISPR/Cas9 technology in recent years that allow for the generation of multiple simultaneous changes in the yeast genome.

Azospirillum brasilense AerC and Tlp4b Cytoplasmic Chemoreceptors Are Promiscuous and Interact with the Two Membrane-Bound Chemotaxis Signaling Clusters Mediating Chemotaxis Responses.

Chemotaxis in and depends on the presence of hexagonal polar arrays composed of membrane-bound chemoreceptors that interact with rings of baseplate signaling proteins. In the alphaproteobacterium Azospirillum brasilense, chemotaxis is controlled by two chemotaxis signaling systems (Che1 and Che4) that mix at the baseplates of two spatially distinct membrane-bound chemoreceptor arrays. The subcellular localization and organization of transmembrane chemoreceptors in chemotaxis signaling clusters have been well characterized but those of soluble chemoreceptors remain relatively underexplored.

The Increased Amyloidogenicity of Spike RBD and pH-Dependent Binding to ACE2 May Contribute to the Transmissibility and Pathogenic Properties of SARS-CoV-2 Omicron as Suggested by In Silico Study.

SARS-CoV-2 is a rapidly evolving pathogen that has caused a global pandemic characterized by several consecutive waves. Based on epidemiological and NGS data, many different variants of SARS-CoV-2 were described and characterized since the original variant emerged in Wuhan in 2019. Notably, SARS-CoV-2 variants differ in transmissibility and pathogenicity in the human population, although the molecular basis for this difference is still debatable.

[Chronic kidney disease in outpatients with arterial hypertension: clinical characteristics and treatment efficacy (according to the national registry)].

Unlabelled: Аim. To investigate the clinical characteristics and quality of treatment (according to the national guidelines) of patients with arterial hypertension (AH) and chronic kidney disease observed in primary health care.

Materials And Methods: The study was carried out on the basis of the AH registry data (n=43 133; 20052019 years).

[Treatment of patients with arterial hypertension in clinical practice in 2010-2020 (according to the national register of hypertension)].

Aim: To analyze therapy in patients with arterial hypertension (AH) in 20102020.

Materials And Methods: Data of hypertensive patients observed in primary health care, entered into the base of hypertension registry for 20102020 years in the whole group (n=44 653) and in a separate subgroup of hypertensive patients in the absence of: ischemic heart disease, a history of myocardial infarction, chronic heart failure (n=20 569).

Results: About 80% of hypertensive patients are patients of high and very high risks (from 2010 to 2020, the proportion of very high cardiovascular risk (CVR) increased from 18.

[Russian Medical Society for Arterial Hypertension expert consensus. Resistant hypertension: detection and management].

The diagnosis of resistant arterial hypertension allows us to single out a separate group of patients in whom it is necessary to use special diagnostic methods and approaches to treatment. Elimination of reversible factors leading to the development of resistant arterial hypertension, such as non-adherence to therapy, inappropriate therapy, secondary forms of arterial hypertension, leads to an improvement in the patient's prognosis. Most patients with resistant hypertension should be evaluated to rule out primary aldosteronism, renal artery stenosis, chronic kidney disease, and obstructive sleep apnea.

[Fetal mediastinal teratomas. Report of two cases].

Teratomas are one of the most common tumors diagnosed in fetuses and newborns. In this age group, extragonadal teratomas predominate, among which the mediastinum ones accounts for up to 15% of teratomas of the perinatal period. They may be associated with the thymus or thyroid gland; in some cases a clear connection with adjacent organs cannot be identified.

Partners in crime: Tbf1 and Vid22 promote expansions of long human telomeric repeats at an interstitial chromosome position in yeast.

In humans, telomeric repeats (TTAGGG) are known to be present at internal chromosomal sites. These interstitial telomeric sequences (ITSs) are an important source of genomic instability, including repeat length polymorphism, but the molecular mechanisms responsible for this instability remain to be understood. Here, we studied the mechanisms responsible for expansions of human telomeric (Htel) repeats that were artificially inserted inside a yeast chromosome.

Synthetic Studies toward 1,2,3,3a,4,8b-Hexahydropyrrolo[3,2-]indole Core. Unusual Fragmentation with 1,2-Aryl Shift.

Base-assisted transformations of 2-(3-oxoindolin-2-yl)acetonitriles were investigated. Unexpectedly, attempted reactions of substrates possessing nonprotected nitrogen atoms were accompanied by unusual extrusions of 2-arylacetonitriles, followed by a 1,2-aryl shift to afford 3-hydroxyindolin-2-ones. On the other hand, the reactions for -alkyl derivatives of oxoindolines took the expected route by only providing 1,2,3,3a,4,8b-hexahydropyrrolo[3,2-]indoles.

Genome Instability in Multiple Myeloma: Facts and Factors.

Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT).

[Antihypertensive therapy in men and women in real clinical practice according to the National register].

Hypertension is one of the most important risk factors for cardiovascular diseases (CVD) in the world, including Russia. Current Guidelines for the management of arterial hypertension do not include different theatment strategies for men and women. Gender and age analysis of antihypertensive treatmen in men and women could reveal unreasonable and non - optimal treatment in each group.

[Metastatic leiomyoma or synchronous lesion of the uteri corpus and vulva?].

Objective: To reveal the morphological characteristics of simultaneously diagnosed leiomyoma of the corpus uteri and vulva.

Subject And Methods: The paper describes a case of multiple uterine leiomyomas concurrent with vulvar leiomyoma in a 39-year-old patient with progressive tumor nodule growth over 2 years. Vulvar tumor was biopsied simultaneously with extirpation of the uterus; vulvar leiomyoma was removed six months later.

Distinct Chemotaxis Protein Paralogs Assemble into Chemoreceptor Signaling Arrays To Coordinate Signaling Output.

Most chemotactic motile bacteria possess multiple chemotaxis signaling systems, the functions of which are not well characterized. Chemotaxis signaling is initiated by chemoreceptors that assemble as large arrays, together with chemotaxis coupling proteins (CheW) and histidine kinase proteins (CheA), which form a baseplate with the cytoplasmic tips of receptors. These cell pole-localized arrays mediate sensing, signaling, and signal amplification during chemotaxis responses.

Clinical features of arterial hypertension in men and women (according to the National Registry of Arterial Hypertension).

Aim: The purpose of this study is to study the effect of sex on the features of therapy of arterial hypertension and the development of cardiovascular complications.

Materials And Methods: Data from the register of AH from outpatient hospital and cardiology departments of hospitals of 22 regions of the Russian Federation were analyzed. Data of medical documents of 33 564 patients with AH [(36.

At the Beginning of the End and in the Middle of the Beginning: Structure and Maintenance of Telomeric DNA Repeats and Interstitial Telomeric Sequences.

Tandem DNA repeats derived from the ancestral (TTAGGG)n run were first detected at chromosome ends of the majority of living organisms, hence the name telomeric DNA repeats. Subsequently, it has become clear that telomeric motifs are also present within chromosomes, and they were suitably called interstitial telomeric sequences (ITSs). It is well known that telomeric DNA repeats play a key role in chromosome stability, preventing end-to-end fusions and precluding the recurrent DNA loss during replication.

Genetic Control of Genomic Alterations Induced in Yeast by Interstitial Telomeric Sequences.

In many organisms, telomeric sequences can be located internally on the chromosome in addition to their usual positions at the ends of the chromosome. In humans, such interstitial telomeric sequences (ITSs) are nonrandomly associated with translocation breakpoints in tumor cells and with chromosome fragile sites (regions of the chromosome that break in response to perturbed DNA replication). We previously showed that ITSs in yeast generated several different types of instability, including terminal inversions (recombination between the ITS and the "true" chromosome telomere) and point mutations in DNA sequences adjacent to the ITS.

[Age-related changes of peripheral nerve system and muscles of the limbs in healthy persons].

Our aim was to present and analyze age-related changes of peripheral nerves and muscles of limbs on a huge population of healthy persons of different ages. Persons aged from 2 months to 87 years were studied by conduction studies (EMG) during the period 2009-2016 years in Scientific Research Institute of Children's Infection. Data of those 1 121confirmed healthy was included in our study.

[Age-related changes of sensory peripheral nerve system in healthy subjects.].

Our aim was to present and evaluate age-related changes of peripheral nerves of limbs on a huge population of healthy subjects of different ages. In 2009-2016 subjects aged from 1months to 90 years were studied by nerve conduction velocity studies (NCV). Data of those confirmed healthy was included in our study.