2-Furyl-6-nitro-1,2,4-triazolo [1,5-a]pyrimidin-7-one

A sodium salt of 2-(fur-2-yl)-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7-one as a close structural analogue of ZM-241385 was obtained. This heterocycle can serve as an effector for A2a adenosine receptors and possesses antiseptic activity. The structures of compounds were confirmed based on the data of 1H, 13C NMR spectroscopy, IR spectroscopy, and an elemental analysis. The structure of sodium salt 2-furyl-6-nitro-1,2,4-triazolo[1,5-a]pyrimidin-7-one was confirmed by an X-ray diffraction analysis

Encapsulin Based Self-Assembling Iron-Containing Protein Nanoparticles for Stem Cells MRI Visualization

Over the past decade, cell therapy has found many applications in the treatment of different diseases. Some of the cells already used in clinical practice include stem cells and CAR-T cells. Compared with traditional drugs, living cells are much more complicated systems that must be strictly controlled to avoid undesirable migration, differentiation, or proliferation. One of the approaches used to prevent such side effects involves monitoring cell distribution in the human body by any noninvasive technique, such as magnetic resonance imaging (MRI). Long-term tracking of stem cells with artificial magnetic labels, such as magnetic nanoparticles, is quite problematic because such labels can affect the metabolic process and cell viability. Additionally, the concentration of exogenous labels will decrease during cell division, leading to a corresponding decrease in signal intensity. In the current work, we present a new type of genetically encoded label based on encapsulin from Myxococcus xanthus bacteria, stably expressed in human mesenchymal stem cells (MSCs) and coexpressed with ferroxidase as a cargo protein for nanoparticles’ synthesis inside encapsulin shells. mZip14 protein was expressed for the enhancement of iron transport into the cell. Together, these three proteins led to the synthesis of iron-containing nanoparticles in mesenchymal stem cells—without affecting cell viability—and increased contrast properties of MSCs in MRI

Photoluminescent properties of single crystal diamond microneedles

Single crystal needle-like diamonds shaped as rectangular pyramids were produced by combination of chemical vapor deposition and selective oxidation with dimensions and geometrical characteristics depending on the deposition process parameters. Photoluminescence spectra and their dependencies on wavelength of excitation radiation reveal presence of nitrogen- and silicon-vacancy color centers in the diamond crystallites. Photoluminescence spectra, intensity mapping, and fluorescence lifetime imaging microscopy indicate that silicon-vacancy centers are concentrated at the crystallites apex while nitrogen-vacancy centers are distributed over the whole crystallite. Dependence of the photoluminescence on excitation radiation intensity demonstrates saturation and allows estimation of the color centers density. The combination of structural parameters, geometry and photoluminescent characteristics are prospective for advantageous applications of these diamond crystallites in quantum information processing and optical sensing.Authors are grateful for financial support from Russian Federation President Program for young scientist: Grant# МК-9230.2016.2 (for EAO and FTT) and Grant# MK-5860.2016.2 (for KGK).Peer reviewe

Azolo[1,5-<i>a</i>]pyrimidines and Their Condensed Analogs with Anticoagulant Activity

Hypercytokinemia, or cytokine storm, is one of the severe complications of viral and bacterial infections, involving the release of abnormal amounts of cytokines, resulting in a massive inflammatory response. Cytokine storm is associated with COVID-19 and sepsis high mortality rate by developing epithelial dysfunction and coagulopathy, leading to thromboembolism and multiple organ dysfunction syndrome. Anticoagulant therapy is an important tactic to prevent thrombosis in sepsis and COVID-19, but recent data show the incompatibility of modern direct oral anticoagulants and antiviral agents. It seems relevant to develop dual-action drugs with antiviral and anticoagulant properties. At the same time, it was shown that azolo[1,5-a]pyrimidines are heterocycles with a broad spectrum of antiviral activity. We have synthesized a new family of azolo[1,5-a]pyrimidines and their condensed polycyclic analogs by cyclocondensation reactions and direct CH-functionalization and studied their anticoagulant properties. Five compounds among 1,2,4-triazolo[1,5-a]pyrimidin-7-ones and 5-alkyl-1,3,4-thiadiazolo[3,2-a]purin-8-ones demonstrated higher anticoagulant activity than the reference drug, dabigatran etexilate. Antithrombin activity of most active compounds was confirmed using lipopolysaccharide (LPS)-treated blood to mimic the conditions of cytokine release syndrome. The studied compounds affected only the thrombin time value, reliably increasing it 6.5–15.2 times as compared to LPS-treated blood

Comments to the project of Russian clinical practice guidelines for diagnosis and treatment of differentiated thyroid cancer.

The article is dedicated to the discussion about the project of Russian clinical practice guidelines for diagnosis and treatment of differentiated thyroid cancer

Loss of signal during intraoperative neuromonitoring of laryngeal nerves as a predictor of postoperative larynx paresis: Analysis of 1065 consequetive thyroid and parathyroid operations. Surgeons' algorythm (tactics)

During thyroid and parathyroid operations performed with laryngeal nerves neuromonitoring, a segmental or global loss of signal may occur. The most frequent cause of loss of signal – is tension of thyroid gland tissue and at the same time tension of the laryngeal nerves. There is no consensus if this complication arises regarding surgeon’s actions. Aim. Evaluation of predictive value of loss of signal during IONM regarding larynx paresis in postoperative period, and algorithm suggestion in case of loss of signal develops. Materials and methods. 1065 patients were operated on thyroid and parathyroid glands with neuromonitoring of laryngeal nerves. Neuromonitore C2 (Inomed, Emmendingen, Germany) was used. We evaluated frequency of loss of signal, described types of loss of signal, showed sensitivity and specificity of loss of signal and development of postoperative larynx paresis. Results. Loss of signal developed in 32 (1,9%) patients. More frequently loss of signal was detected at left side (p=0,01, χ2 = 4,2 OR=2,9). Sensitivity (Se)  of loss of signal and postoperative larynx paresis development reached 59,2%, specificity – 99,7% (Sp), positive predicitive value (PPV) – 91,4%, negative predictive value (NPV) – 97,8%. There are no statistically reliable differences in recovery periods of larynx function depending on type of loss of signal (segmental or global) (p=0,5). Conclusions. In most cases loss of electromyographical signal indicates injury of laryngeal nerves during operation on thyroid and parathyroid glands. When there is loss of signal in case of bilateral thyroid gland disease it is reasonable to make a decision to stop operation to prevent development of bilateral larynx paresis

Hyperon signatures in the PANDA experiment at FAIR

We present a detailed simulation study of the signatures from the sequential decays of the triple-strange pbar p -> Ω+Ω- -> K+ΛbarK- Λ -> K+pbarπ+K-pπ- process in the PANDA central tracking system with focus on hit patterns and precise time measurement. We present a systematic approach for studying physics channels at the detector level and develop input criteria for tracking algorithms and trigger lines. Finally, we study the beam momentum dependence on the reconstruction efficiency for the PANDA detector