Tuberculosis situation among the pediatric population of Saratov Region (2015-2019)

Subjects and Methods. Incidence and prevalence of tuberculosis among children and adolescents in Saratov Region were retrospectively analyzed for 2015-2019.Results. The incidence of tuberculosis in children reflects general trends in the epidemic situation over the years in Saratov Region. In this region during 10 years of monitoring, tuberculosis incidence among children decreased 4 times by 2019 and it made 2.3 per 100,000 population, and among adolescents, it decreased 1.6 times (16.3 per 100,000 population). The number of children with post-tuberculosis changes detected for the first time increased 3 times in 2019 versus 2015, and the number of adolescents increased 4.5 times not only due to transition to tuberculosis screening in children aged 8-17 years old by skin test with tuberculosis recombinant allergen but also to the examination of children by computed tomography. The incidence in children followed up as Group IVA in 2019 was 15 times higher than this rate in the overall pediatric population. Analysis of the number of children and adolescents who developed tuberculosis and followed up as Groups IV and VI in 2015-2019 showed that the number of children ill with tuberculosis in Group IV was 3 times higher than the number of children in Group VI.

Differential expression of phospholipase A2 group IVA in cancers of the breast.

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the phospholipase A2 group IVA, PLA2G4A, when comparing primary tumors of the breast to the tissue of origin, the normal breast. PLA2G4A mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of PLA2G4A in primary tumors of the breast was correlated with overall survival in patients with luminal B subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. PLA2G4A may be of relevance to initiation, maintenance or progression of cancers of the female breast.

Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy

The functional state of T cells is a key determinant for effective antitumor immunity and immunotherapy. Cellular metabolism, including lipid metabolism, controls T cell differentiation, survival, and effector functions. Here, we report that development of T cell senescence driven by both malignant tumor cells and regulatory T cells is a general feature in cancers. Senescent T cells have active glucose metabolism but exhibit unbalanced lipid metabolism. This unbalanced lipid metabolism results in changes of expression of lipid metabolic enzymes, which, in turn, alters lipid species and accumulation of lipid droplets in T cells. Tumor cells and Treg cells drove elevated expression of group IVA phospholipase A2, which, in turn, was responsible for the altered lipid metabolism and senescence induction observed in T cells. Mitogen-activated protein kinase signaling and signal transducer and activator of transcription signaling coordinately control lipid metabolism and group IVA phospholipase A2 activity in responder T cells during T cell senescence. Inhibition of group IVA phospholipase A2 reprogrammed effector T cell lipid metabolism, prevented T cell senescence in vitro, and enhanced antitumor immunity and immunotherapy efficacy in mouse models of melanoma and breast cancer in vivo. Together, these findings identify mechanistic links between T cell senescence and regulation of lipid metabolism in the tumor microenvironment and provide a new target for tumor immunotherapy.

Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLA2α/COX-1 Pathway

Macrophages are professional antigen presenting cells with intense phagocytic activity, strategically distributed in tissues and cavities. These cells are capable of responding to a wide variety of innate inflammatory stimuli, many of which are signaled by lipid mediators. The distribution of arachidonic acid (AA) among glycerophospholipids and its subsequent release and conversion into eicosanoids in response to inflammatory stimuli such as zymosan, constitutes one of the most studied models. In this work, we used liquid and/or gas chromatography coupled to mass spectrometry to study the changes in the levels of membrane glycerophospholipids of mouse peritoneal macrophages and the implication of group IVA cytosolic phospholipase A2 (cPLA2α) in the process. In the experimental model used, we observed that the acute response of macrophages to zymosan stimulation involves solely the cyclooxygenase-1 (COX-1), which mediates the rapid synthesis of prostaglandins E2 and I2. Using pharmacological inhibition and antisense inhibition approaches, we established that cPLA2α is the enzyme responsible for AA mobilization. Zymosan stimulation strongly induced the hydrolysis of AA-containing choline glycerophospholipids (PC) and a unique phosphatidylinositol (PI) species, while the ethanolamine-containing glycerophospholipids remained constant or slightly increased. Double-labeling experiments with 3H- and 14C-labeled arachidonate unambiguously demonstrated that PC is the major, if not the exclusive source, of AA for prostaglandin E2 production, while both PC and PI appeared to contribute to prostaglandin I2 synthesis. Importantly, in this work we also show that the COX-1-derived prostaglandins produced during the early steps of macrophage activation restrict tumor necrosis factor-α production. Collectively, these findings suggest new approaches and targets to the selective inhibition of lipid mediator production in response to fungal infection.

Two-dimensional materials of group IVA: Latest advances in epitaxial methods of growth

Two-dimensional materials have become one of the central research topics of scientists around the world after the production of graphene - a monatomic layer of carbon. Currently, two-dimensional crystals are among the most promising materials for next-generation nanoelectronics and photonics. The exploration of the feasibility of 2D materials devices causes a deeper insight into the physical properties of these new materials and provides a starting point for the development of a number of important practical areas. Over the past few years, researchers have been attracting increased attention from graphene-like materials of group IVA elements, such as silicene (Si), germanene (Ge), stanene (Sn), and plumbene (Pb). Experimental production and study of the unique properties of two-dimensional monatomic layers of carbon, silicon, germanium, tin and lead on various substrates created the prerequisites for the development of new generation devices based on them. The wide possibilities for controlling their exotic electronic, magnetic and optical properties through the choice of the substrate, the design and geometry of the two-dimensional layer, as well as by controlling the magnitude of elastic stresses, have made them a dominating topic for studying in the field of nanotechnology and materials sciences. This paper reviews the latest advances in growing silicene, germanene, stanene, and plumbene using epitaxial methods. Growth technologies for creation of high-quality two-dimensional structures of large area required for promising instrumentation area are considered in more details.