Crystal structure and Hirshfeld surface analysis of ethyl (4R,4aS)-2-methyl-5,8-ioxo-6-phenyl-4a,5,6,7,7a,8-hexahydro-4H-furo[2,3-f]isoindole-4-carboxylate

In the title compound, C20H19NO5, the central six-membered ring has a slightly distorted half-chair conformation, with puckering parameters of Q(T) = 0.3387 (11) angstrom, theta = 49.11 (19)degrees and phi = 167.3 (2)degrees. The conformation of the fused pyrrolidine ring is that of an envelope. Molecules are connected by intermolecular C-H center dot center dot center dot O hydrogen bonds, C-H center dot center dot center dot pi interactions and pi-pi stacking interactions [centroid-to-centroid distance = 3.9536 (11) angstrom, with a slippage of 2.047 angstrom], forming a three-dimensional network. The most important contributions to the surface contacts are from H center dot center dot center dot H (46.3%), O center dot center dot center dot H/H center dot center dot center dot O (31.5%) and C center dot center dot center dot H/H center dot center dot center dot C (17.3%) interactions, as concluded from a Hirshfeld surface analysis

Influence of Substituents in a Six-Membered Chelate Ring of HG-Type Complexes Containing an N→Ru Bond on Their Stability and Catalytic Activity

An efficient approach to the synthesis of olefin metathesis HG-type catalysts containing an N→Ru bond in a six-membered chelate ring was proposed. For the most part, these ruthenium chelates can be prepared easily and in high yields based on the interaction between 2-vinylbenzylamines and Ind II (the common precursor for Ru-complex synthesis). It was demonstrated that the increase of the steric volume of substituents attached to the nitrogen atom and in the α-position of the benzylidene fragment leads to a dramatic decrease in the stability of the target ruthenium complexes. The bulkiest iPr substituent bonded to the nitrogen atom or to the α-position does not allow the closing of the chelate cycle. N,N-Diethyl-1-(2-vinylphenyl)propan-1-amine is a limiting case; its interaction with Ind II makes it possible to isolate the corresponding ruthenium chelate in a low yield (5%). Catalytic activity of the synthesized complexes was tested in RCM reactions and compared with α-unsubstituted catalysts obtained previously. The structural peculiarities of the final ruthenium complexes were thoroughly investigated using XRD and NMR analysis, which allowed making a reliable correlation between the structure of the complexes and their catalytic properties

Enhancement of the Local CD8⁺ T-Cellular Immune Response to <i>Mycobacterium tuberculosis</i> in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes

Design and Immunological Properties of the Novel Subunit Virus-like Vaccine against SARS-CoV-2

The COVID-19 pandemic is ongoing, and the need for safe and effective vaccines to prevent infection and to control spread of the virus remains urgent. Here, we report the development of a SARS-CoV-2 subunit vaccine candidate (Betuvax-CoV-2) based on RBD and SD1 domains of the spike (S) protein fused to a human IgG1 Fc fragment. The antigen is adsorbed on betulin adjuvant, forming spherical particles with a size of 100–180 nm, mimicking the size of viral particles. Here we confirm the potent immunostimulatory activity of betulin adjuvant, and demonstrate that two immunizations of mice with Betuvax-CoV-2 elicited high titers of RBD-specific antibodies. The candidate vaccine was also effective in stimulating a neutralizing antibody response and T cell immunity. The results indicate that Betuvax-CoV-2 has good potential for further development as an effective vaccine against SARS-CoV-2

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv

Features of radionuclide research after thyroidectomy at the thyroid gland cancer

Aim To clarify the possibility of postoperative radioisotope studies in determining the remnants of thyroid tissue in patients with thyroid carcinoma. Materials and methods The work is based on the study results of surgical treatment and postoperative examination of 120 patients with thyroid cancer, at the Botkin hospital during the period from 2007 to 2013. All patients were performed extrafascial intervention. 118 (98.3%) patients were provided thyroidectomy (including lymph node dissection). For all patients in the postoperative period after 2–4 weeks were performed thyroid and whole-body scan with iodine and technetium, as well as ultrasound and computed tomography of the neck and the chest cavity. Results During the research, 16 (13.3%) patients after scanning with 123I (7 (5.8%) patients), 131I (3 (2.5%) patients), 99mTs-Pertechnetate (6 (5%) patients) and applying them consistently (6 (5%) patients) received the accumulation of the radiopharmaceutical in the operation area, as in the midline in the area of the isthmus, and the locations of the right, left and pyramidal thyroid share. These facts were interpreted as an accumulation of the isotope in the remnants of thyroid tissue after surgery. With additional research methods were revealed swelling and infiltration of tissues in 10 (8.3%) cases in the sterno-hyoid and sterno-thyroid muscles, and in 6 (5%) cases – in the paratracheal and paralaryngeal areas. After fine-needle aspiration biopsy from infiltrative zone was received cytology of nonspecific inflammation. All patients received antiinflammatory and antibiotic therapy with a positive effect. Control ultrasound noted a gradual reduction of the inflammatory infiltrate. After 6 months of thyroid scan was recorded decrease area of uptake, and a year later its complete disappearance. Conclusions Thus, postoperative radionuclide scanning in patients with thyroid gland carcinoma in some cases gives false-positive results, regardless of the type of used radiopharmaceutical

Advantages of Nuclear Fusion with Polarized Fuel

The use of nuclear polarized fuel, i.e. polarized D, T or 3He, for coming fusion reactors promises to increase their energy output and to optimize the complete fusion process in various ways. But before these advantages can be utilized, several questions must be answered and technical issues must be overcome. Among others, the members of the PREFER collaboration started to investigate the different challenges of “polarized fusion”

SARS-CoV-2 escape from cytotoxic T cells during long-term COVID-19

Here, the authors report accelerated intrahost evolution of SARS-CoV-2 in an immunocompromised patient with non-Hodgkin’s lymphoma with 318 days long COVID-19, and show that changes in the viral genome resulted in escape from T cellular immune response