Synthesis of a novel family of water-soluble 2H,3H-[1,3]thia- and -selenazolo[3,2-a]pyridin-4-ium heterocycles by annulation reactions

Regioselective synthesis of a novel family of water-soluble 2H,3H-[1,3]chalcogenazolo[3,2-a]pyridin-4-ium derivatives was developed based on 2-pyridinesulfenyl and -selenenyl halides and unsaturated compounds. The annulation reactions with divinyl sulfide, selenide and N-vinylpyrrolidin-2-one led to addition of the chalcogen atom to the terminal carbon of the double bond whereas the reaction with tetravinylsilane proceeded with opposite regiochemistry. Tricyclic condensed heterocycles were obtained from 2,3-dihydrofuran and cycloalkenes. The products represent novel promising scaffolds for organic synthesis and possible drug discovery.     

Detection of Antibodies Against Foot-and-Mouth Disease Virus Serotypes A,O and Asia-1 by ELISA in Strip-Dried Samples from Vaccinated Bovines

Antibodies against foot-and-mouth disease virus serotypes A, O and Asia-1 were detected by ELISA in liquid and strip-dried samples from vaccinated bovines. The results showed high concordance of the results in both types of serum samples (coefficient of correlation varied from 0.89 to 0.96). Stability studies showed that anti-foot-and-mouth disease virus antibodies can be detected in strip-dried serum samples stored at different temperatures on a level of that in native samples. Preliminary study in strip-dried whole blood samples demonstrated good potential of this sample pretreatment procedure for the following anti-foot-and-mouth virus antibodies testing.

     

Effects of electron tunneling in photophysics of quantum-sized luminescent nanosilicon

The paper deals with the processes of photoburning and dark recovery of the photoluminescence (PL) yield of a “core-shell”-type hybrid nanoparticles Si/SiO _x (npSi/SiO _x ) after exposure to laser light with a wavelength of 405 nm and power density of 0.05–1 W/cm². The PL of npSi/SiO _x occurs after excitation of nanocrystalline Si core and subsequent energy transfer to the luminescent oxygen-deficient centers (ODC) in the SiO _x shell of a nanoparticle. These photoburning effects linearly depend on the power density of the exciting laser light, and the dynamics of the photoburning of PL is significantly non-exponential: the burning rate strongly drops during the exposure. The stop of laser exposure of npSi/SiO _x is accompanied by a slow dark recovery of the quantum efficiency of PL up to its initial level. We have demonstrated the possibility of controlling the photosensibility of npSi/SiO _x through changing the electron affinity of the environment. We have also proposed a physical mechanism that explains the observed photoburning and subsequent dark recovery of npSi/SiO _x PL based on the existence of “traps” for electrons residing in the SiO _x shell, where the electrons come as a result of tunneling from the excited ODC. The limiting time for this process is the lifetime of PL of ODC ranging from 10^?5 to 10^?4 s. The drop of the burning rate during exposure is caused by a strong difference in tunneling probabilities for different pairs of “ODC-trap”. The dark back tunneling of an electron from a trap to the original ODC occurs significantly (7–10 orders of magnitude) slower than the direct tunneling due to higher energy barrier.

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Graphical abstract Dark recovery of photoluminescence efficiency of Si nanoparticles following laser burning in three surrounding media differing in electron affinity

     

Bifurcation in reflection spectra of holographic diffraction grating recorded on dicromated pullulan

Volume diffraction gratings were created holographically on a dichromated pullulan (polysaccharide doped with chromium). Specific and very rare multi-peak structure in the reflection spectra is observed. It was found that multiple peaks are consequence of non-ideal structure of volume diffraction grating. Theoretical analysis and numerical simulations confirm that the observed behavior arise from a slight randomness of grating parameters: refractive index, grating period, film thickness. The results of calculation are in agreement with experimental results.     

A Sharp Condition for Scattering of the Radial 3D Cubic Nonlinear Schrödinger Equation

We consider the problem of identifying sharp criteria under which radial H ¹ (finite energy) solutions to the focusing 3d cubic nonlinear Schrödinger equation (NLS) i? _t u + Δu + |u|² u = 0 scatter, i.e., approach the solution to a linear Schrödinger equation as t → ±∞. The criteria is expressed in terms of the scale-invariant quantities ${\|u_0\|_{L^2}\|\nabla u_0\|_{L^2}}We consider the problem of identifying sharp criteria under which radial H ¹ (finite energy) solutions to the focusing 3d cubic nonlinear Schr?dinger equation (NLS) i∂ _t u + Δu + |u|² u = 0 scatter, i.e., approach the solution to a linear Schr?dinger equation as t → ±∞. The criteria is expressed in terms of the scale-invariant quantities and M[u]E[u], where u ₀ denotes the initial data, and M[u] and E[u] denote the (conserved in time) mass and energy of the corresponding solution u(t). The focusing NLS possesses a soliton solution e ^it Q(x), where Q is the ground-state solution to a nonlinear elliptic equation, and we prove that if M[u]E[u] < M[Q]E[Q] and , then the solution u(t) is globally well-posed and scatters. This condition is sharp in the sense that the soliton solution e ^it Q(x), for which equality in these conditions is obtained, is global but does not scatter. We further show that if M[u]E[u] < M[Q]E[Q] and , then the solution blows-up in finite time. The technique employed is parallel to that employed by Kenig-Merle [17] in their study of the energy-critical NLS.     

Structural and Metabolic Pattern Classification for Detection of Glioblastoma Recurrence and Treatment-Related Effects

Artificial neuronal network (ANN) in classification of glioblastoma multiforme (GBM) recurrence from treatment effects using advanced magnetic resonance imaging techniques was evaluated. In 56 patients with treated GBM, normalised minimal and mean apparent-diffusion coefficient (ADC) values, vessels number on susceptibility-weighted images (SWI) and Cho/Cr ratio were analysed statistically and by ANN. Significant correlation exists between normalised minimal and mean ADC values, and no correlation between ADC and Cho/Cr values. Cut-off values for tumour presence were: 1.14 for normalised minimal ADC (54% sensitivity, 71% specificity), 1.13 for normalised mean ADC (51% sensitivity, 71% specificity), 1.8 for Cho/Cr ratio (92% sensitivity, 82% specificity), grade 2 for SWI (87% sensitivity, 82% specificity). An accurate prediction of ANN to classify patients into GBM progression or treatment effects group was 99% during the training and 96.8% during the testing phase. Multi-parametric ANN allows distinction between GBM recurrence and treatment effects, and can be used in clinical practice.     

Very Stable Two Mega Dalton High-Molecular-Mass Multiprotein Complex from Sea Cucumber Eupentacta fraudatrix

In contrast to many human organs, only the human liver can self-regenerate, to some degree. Some marine echinoderms are convenient objects for studying the processes of regenerations of organs and tissues. For example, sea cucumbers Eupentacta fraudatrix can completely restore within several weeks, the internal organs and the whole body after their division into two or three parts. Therefore, these cucumbers are a very convenient model for studying the general mechanisms of regeneration. However, there is no literature data yet on which biomolecules of these cucumbers can stimulate the regeneration of organs and the whole-body processes. Studying the mechanisms of restoration is very important for modern biology and medicine, since it can help researchers to understand which proteins, enzymes, hormones, or possible complexes can play an essential role in regeneration. This work is the first to analyze the possible content of very stable protein complexes in sea cucumbers Eupentacta fraudatrix. It has been shown that their organisms contain a very stable multiprotein complex of about 2000 kDa. This complex contains 15 proteins with molecular masses (MMs) >10 kDa and 21 small proteins and peptides with MMs 2.0–8.6 kDa. It is effectively destroyed only in the presence of 3.0 M MgCl₂ and, to a lesser extent, 3.0 M NaCl, while the best dissociation occurs in the presence of 8.0 M urea + 0.1 M EDTA. Our data indicate that forming a very stable proteins complex occurs due to the combination of bridges formed by metal ions, electrostatic contacts, and hydrogen bonds.     

Proteomic Signature of Extracellular Vesicles for Lung Cancer Recognition

The proteins of extracellular vesicles (EVs) that originate from tumors reflect the producer cells’ proteomes and can be detected in biological fluids. Thus, EVs provide proteomic signatures that are of great interest for screening and predictive cancer diagnostics. By applying targeted mass spectrometry with stable isotope-labeled peptide standards, we assessed the levels of 28 EV-associated proteins, including the conventional exosome markers CD9, CD63, CD81, CD82, and HSPA8, in vesicles derived from the lung cancer cell lines NCI-H23 and A549. Furthermore, we evaluated the detectability of these proteins and their abundance in plasma samples from 34 lung cancer patients and 23 healthy volunteers. The abundance of TLN1, TUBA4A, HSPA8, ITGB3, TSG101, and PACSIN2 in the plasma of lung cancer patients was measured using targeted mass spectrometry and compared to that in plasma from healthy volunteers. The most diagnostically potent markers were TLN1 (AUC, 0.95), TUBA4A (AUC, 0.91), and HSPA8 (AUC, 0.88). The obtained EV proteomic signature allowed us to distinguish between the lung adenocarcinoma and squamous cell carcinoma histological types. The proteomic cargo of the extracellular vesicles represents a promising source of potential biomarkers.     

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.     

Immobilized enzymes and cells in poly(N-vinyl caprolactam)-based hydrogels

A one-step mild method for entrapping animal cells and enzymes in macroporous composite poly (N-vinyl caprolactam)-calcium alginate (PVCL-CaAlg) hydrogels is described. Some properties of immobilized enzymes, such as thermal and storage stabilities and stability in water/organic media were investigated. Composite PVCL-CaAlg gels were successfully applied to immobilize a number of proteases, namely, trypsin, α-chymotrypsin, carboxypeptidase B, and thrombin. Thermal stability of the immobilized preparations obtained by entrapment in hydrogel beads allowed us to use them at 65–80†C, while the native enzymes were completely inactivated at 50–55°C. Various applications of enzymes and cells immobilized in beads weredemonstrated. Immobilized trypsin and carboxypeptidase B were applied to prepare human insulin from recombinant proinsulin. The hydrogel beads with entrapped α-chymotrypsin were used in enantioselective hydrolysis of Shiff's base of D,L-phenylalanine ethyl ester (SBPH) in acetonitrile/water medium. Thrombin immobilized in PVCL-based hydrogel films was shown to be a promising compound for wound treatment. To prepare pure preparations of monoclonal antibodies (MAb) several hybridoma cell lines, including hybridoma cell lines producing MAb to interleukin-2, were successfully cultivated in the hydrogel beads.