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We demonstrate the NO2 sensing properties of transparent two-dimensional organic films based on a low-symmetry zinc phthalocyanine (Pc) complexes. The amphiphilic nature of the Pc results in oriented monolayers on substrates, which provide an excellent conformation for Zn-NO2 interactions without strong Pc intermolecular aggregation. Using the Langmuir-Blodgett technique, we form single monolayer films on glass and show their potential for NO2 gas detection. We succeed in detecting 100 ppm NO2, 20 s after gas exposure. We also demonstrate total recovery of the sensing effect by simply heating up to 60 °C. By exhibiting high transparency (~ 97%) and thermal stability, together with low costs and simplicity in scaling the technology for large-area structures, the low-symmetry zinc Pc complexes appear to be highly promising materials for gas sensing applications.

The efficiency of fluorescence DNA labeling was estimated for four fluorescent 2′-deoxyuridine 5′-triphosphate derivatives differing in the orientation of the main dye axis, which passes through the polymethine chain, relative to the linker connecting the dye to the nucleotide. To estimate the polymerase chain reaction (PCR) rate, real-time PCR was run with two commercial hot-start DNA polymerases possessing 5′→3′ exonuclease activity in the presence of an intercalating dye. The efficiency of the test compound incorporation in the PCR product was estimated via a quantitative analysis of the amplification product by agarose gel electrophoresis. The fluorescently labeled product was then hybridized on a biological microchip and the ratio of signals from perfect match and mismatch duplexes was determined. The incorporation efficiency and discrimination between perfect match and mismatch duplexes were found to depend on the relative orientation of the dye and the linker between the dye and pyrimidine base, as well as on the presence of hydrophilic groups in the dye. Compounds that are efficiently incorporated in a growing DNA strand and show a high specificity in hybridization analysis were identified using biochips.

Novel hexadecachloro-substituted Eu, Er and Lu monophthalocyaninates were prepared via two alternative ways: lanthanide ion templated tetramerization of tetrachlorophthalonitrile and metallation of the corresponding phthalocyanine ligand. Target complexes were identified by mass spectrometry and fourier transform infrared spectroscopy. Aggregation behavior of these compounds was investigated using UV–Vis and fluorescence spectroscopy. Hybrid nanoparticle conjugates composed of the gold cores (20 and 30 nm in diameter) covered by the layers of target phthalocyanines were obtained. The formation of phthalocyanine shell on the surface of nanoparticles and its elemental composition were examined using transmission electron microscopy experiments. Reverse saturable absorption effect was found in solution of the erbium complex utilizing z-scan technique. Furthermore, significant increase in the effect was observed in hybrid nanoparticles due to their plasmonic properties.

This study investigated the synthesis and substrate properties of Cy5-labeled dUTP derivatives with different substituents, linkers between the dye unit and pyrimidine heterocycle and fluorophore charges. Fluorescently labeled nucleoside triphosphates were studied as substrates using multiplex PCR with Taq and Vent (exo-) DNA polymerases, the typical representatives of the A and B polymerase families. The efficiency of nucleotide incorporation during PCR was assessed with a multi-parameter hybridization analysis using a diagnostic DNA microarray. The hybridization analysis indirectly estimates the incorporation efficiency of dye-labeled nucleotides in multiplex PCR. Our results demonstrated higher efficiencies of substrates with electrically neutral dyes than electropositive and electronegative Cy5 residues.

A number of fluorescently labeled nucleoside triphosphates containing electroneutral indodicarbocyanine dye (Cy) have been synthesized. The dye has been attached to the C5 position of pyrimidine through the transalkene linkers of different structure. The synthesized labeled nucleoside triphosphates have been tested as substrates for Taq polymerase in PCR using the “TB-biochip” test system.

Here, we describe the synthesis and purification of six deoxyuridine triphosphate derivatives that contain protein-like functional groups and alkene linkers of various lengths. Using KOD XL and Deep Vent polymerases, these derivatives have been incorporated into single-stranded DNA, achieving a high degree of DNA modification. These polymerases are able to utilize highly modified DNA strands as templates for synthesizing unmodified DNA. The synthesized deoxyuridine triphosphate derivatives are promising as substrates for producing modified aptamers to various target proteins using, e.g., the systematic evolution of ligands by exponential enrichment (SELEX) methodology.

The kinetics of DNA labeling during PCR using six fluorescent derivatives of 2′-deoxyuridine 5′-triphosphate has been studied. These compounds differ in their chemical structure, total electric charge and the length of the linker between a dye and the C5 position of a pyrimidine base. The efficiency of the incorporation of the fluorescent derivatives into a growing DNA chain by four commercially available Taq DNA polymerases with 5′→3′ exonuclease and hot start activity has been determined using real-time PCR with a TaqMan probe and the subsequent electrophoretic analysis of the reaction products. Modified deoxyuridines with a total positive or negative charge of the chromophore were practically not incorporated by Taq polymerases during PCR. The modified deoxyuridines with a neutral charge of the chromophore were effectively incorporated into DNA. The extended length of the linker between the pyrimidine base and the chromophore led to a lower PCR inhibition and a more effective inclusion of modified nucleotides in the growing DNA chain. This fact can be explained by the reduced steric effects that were caused by the dye. As a result, the most promising combinations of fluorescently labeled nucleotide and Taq polymerase have been chosen for further use in fluorescent DNA labeling.

// Marina Emelyanova 1 , Lilit Ghukasyan 1 , Ivan Abramov 1, 2 , Oxana Ryabaya 2 , Evgenia Stepanova 2 , Anna Kudryavtseva 1, 3 , Asiya Sadritdinova 1, 3 , Cholpon Dzhumakova 2 , Tatiana Belysheva 2 , Sergey Surzhikov 1 , Lyudmila Lyubchenko 2 , Alexander Zasedatelev 1, 2 and Tatiana Nasedkina 1, 2 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation 2 Blokhin Cancer Research Center, Ministry of Health of the Russian Federation, Moscow, Russian Federation 3 P. Hertsen Moscow Oncology Research Institute, Moscow, Russian Federation Correspondence to: Marina Emelyanova, email: emel_marina@mail.ru Keywords: biochip, somatic mutations, melanoma, diagnostic tool, targeted therapy Received: December 30, 2016 Accepted: March 30, 2017 Published: April 10, 2017 ABSTRACT Target inhibitors are used for melanoma treatment, and their effectiveness depends on the tumor genotype. We developed a diagnostic biochip for the detection of 39 clinically relevant somatic mutations in the BRAF , NRAS , KIT , GNAQ , GNA11 , MAP2K1 and MAP2K2 genes. We used multiplex locked nucleic acid (LNA) PCR clamp for the preferable amplification of mutated over wild type DNA. The amplified fragments were labeled via the incorporation of fluorescently labeled dUTP during PCR and were hybridized with specific oligonucleotides immobilized on a biochip. This approach could detect 0.5% of mutated DNA in the sample analyzed. The method was validated on 253 clinical samples and six melanoma cell lines. Among 253 melanomas, 129 (51.0%) BRAF , 45 (17.8%) NRAS , 6 (2.4%) KIT , 4 (1.6%) GNAQ , 2 (0.8%) GNA11 , 2 (0.8%) MAP2K1 and no MAP2K2 gene mutations were detected by the biochip assay. The results were compared with Sanger sequencing, next generation sequencing and ARMS/Scorpion real-time PCR. The specimens with discordant results were subjected to LNA PCR clamp followed by sequencing. The results of this analysis were predominantly identical to the results obtained by the biochip assay. Infrequently, we identified rare somatic mutations. In the present study we demonstrate that the biochip-based assay can effectively detect somatic mutations in approximately 70% of melanoma patients, who may require specific targeted therapy.

Patients with metastatic melanoma are difficult to treat and have a very poor prognosis because of high resistance to therapy. Recent evidence indicates that tumors could overcome death through autophagy, a survival mechanism, which cancer cells use under lack of energy and nutrient deprivation. Melanoma cells have different sensitivity to temozolomide (TMZ) treatment. In this study, we showed that the combination of autophagy inhibitors chloroquine or LY294002 and TMZ induced enhanced cytotoxicity of alkylating agents on human melanoma cell lines. All assays were performed on patient-derived melanoma cell lines. The effectiveness of the combined treatment of TMZ and autophagy inhibitors was determined using an MTT assay. Next, we analyzed the expression mRNA level of Beclin 1, LC3B, and p62/STSQM1 and the relative expression of LC3B protein under combined treatment. Autophagic flux was determined by analysis of colocalization of Lysotracker Red and LC3B puncta. Apoptosis was measured by Annexin V/PI staining. Cell cycle analyses were carried out by flow cytometry. We showed that autophagy inhibition could enhance melanoma cell death combined with TMZ therapy. Chloroquine synergistically enhanced the TMZ-induced growth arrest and increased the G0/G1 population in Mel Z and Mel IL cell lines, but not Mel MTP. The expression analysis showed that autophagy involvement in TMZ enhanced cytotoxicity. Furthermore, LY294002, an early-stage autophagy, and PI3K inhibitor were found to exert similar effects. Both chloroquine and LY294002 improved the cytotoxic effect of TMZ treatment, making this combination applicable as a potent antitumor treatment for metastatic melanoma.

Recently, we have experimentally observed signatures of sharp exciton peaks in the photoluminescence spectra of bundles of monoatomic carbon chains stabilized by gold nanoparticles and deposited on a glass substrate. Here, we estimate the characteristic energies of excitonic transitions in this complex quasi-one-dimensional nano-system with use of the variational method. We show that the characteristic energy scale for the experimentally observed excitonic fine structure is governed by the interplay between the hopping energy in a Van der Waals quasicrystal formed by parallel carbon chains, the neutral-charged exciton splitting and the positive-negative trion splitting. These three characteristic energies are an order of magnitude lower than the direct exciton binding energy., Comment: 6 pages, 3 figures

Organic semiconductors are a promising platform for ambient polaritonics. Several applications, such as polariton routers, and many-body condensed matter phenomena are currently hindered due to the ultra-short polariton lifetimes in organics. Here, we employ a single-shot dispersion imaging technique, using 4 nanosecond long non-resonant excitation pulses, to study polariton lasing in a $\lambda/2$ planar organic microcavity filled with BODIPY-Br dye molecules. At a power threshold density of $1.5 MW/cm^{2}$, we observe the transition to a quasi-steady state, 1.2 ns long-lived, single-mode polariton lasing and the concomitant superlinear increase of photoluminescence, spectral line-narrowing, and energy blueshift

Using random (combinatorial) DNA-libraries with various degrees of diversity, it was shown that their amplification by polymerase chain reaction in real time resulted in appearance of a maximum on amplification curves. The relative decrease of fluorescence after passing the maximum was directly proportional to the logarithm of the number of oligonucleotide sequence variants in the random DNA-library provided that this number was within in the interval from 1 to 104 and remained practically unaltered when the number of variants was in the interval from 105 to 108. The obtained dependence was used in the course of SELEX to evaluate changes in the diversity of random DNA-libraries from round to round in selection of DNA-aptamers to the recombinant SMAD4 protein. As a result, oligonucleotides containing sequences able to form a site of SMAD4-DNA interactions known as SBE (SMAD-binding element) have been selected thus indicating that the SMAD4-SBE interaction dominates the aptamer selection.Ispol'zuia sluchaĭnye (kombinatornye) DNK-biblioteki s razlichnoĭ stepen'iu raznoobraziia, pokazano, chto ikh amplifikatsiia s pomoshch'iu polimeraznoĭ tsepnoĭ reaktsii v real'nom vremeni kharakterizuetsia nalichiem maksimuma na amplifikatsionnykh krivykh. Ustanovleno, chto otnositel'noe padenie fluorestsentsii posle prokhozhdeniia maksimuma priamo proportsional'na logarifmu chisla variantov oligonukleotidnykh posledovatel'nosteĭ v sluchaĭnoĭ DNK-biblioteke, esli ono lezhit v intervale ot 1 do 104 variantov, i prakticheski ne meniaetsia, esli chislo variantov lezhit v intervale ot 105 do 108. Poluchennaia zavisimost' byla ispol'zovana v khode protsedury SELEX dlia otsenki izmeneniia raznoobraziia sluchaĭnykh DNK-bibliotek ot raunda k raundu pri selektsii DNK-aptamerov k rekombinatnomu belku SMAD4. Rezul'tatom selektsii byl otbor oligonukleotidov, soderzhashchikh posledovatel'nosti, formiruiushchie uchastok vzaimodeĭstviia DNK s SMAD4, izvestnyĭ kak SBE (SMAD-binding element), chto ukazyvaet na SMAD4-SBE vzaimodeĭstvie kak dominiruiushchee v protsesse selektsii DNK-aptamerov k SMAD4.

We report on the origin of energy-shifts in organic polariton condensates. The localised nature of Frenkel excitons in molecular semiconductors precludes interparticle Coulomb exchange interactions -the latter being the dominant mechanism for blueshifts in inorganic semiconductor microcavities that bear Wannier-Mott excitons. We examine the contribution of optically induced change of the intracavity non-linear refractive index, gain induced frequency-pulling and quenching of the Rabi splitting, as well as the role of polariton-exciton and polariton-polariton scattering in the energy-shift of the polariton mode at condensation threshold in strongly coupled molecular dye microcavities. We conclude that blueshifts in organic polariton condensates arise from the interplay of the saturation of molecular optical transitions and intermolecular energy migration. Our model predicts the commonly observed step-wise increase of both the emission energy and degree of linear polarisation at polariton condensation threshold.

Biological microarrays (biochips) are analytical tools that can be used to implement complex integrative genomic and proteomic approaches to the solution of problems of personalized medicine (e.g., patient examination in order to reveal the disease long before the manifestation of clinical symptoms, assess the severity of pathological or infectious processes, and choose a rational treatment). The efficiency of biochips is predicated on their ability to perform multiple parallel specific reactions and to allow one to study the interactions of biopolymer molecules, such as DNA, proteins, glycans, etc. One of the pioneers of microarray technology was the Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences (EIMB), with its suggestion to immobilize molecular probes in the three-dimensional structure of a hydrophilic gel. Since the first experiments on sequencing by hybridization on oligonucleotide microarrays conducted some 30 years ago, the hydrogel microarrays designed at the EIMB have come a long and successful way from basic research to clinical laboratory diagnostics. This review discusses the key aspects of hydrogel microarray technology and a number of state-ofthe-art approaches for a multiplex analysis of DNA and the protein biomarkers of socially significant diseases, including the molecular genetic, immunological, and epidemiological aspects of pathogenesis.

Plasmonic enhancement of absorption in charge‐transfer (CT) complexes formed under NO2 gas adsorption onto 2D hybrid structure, based on the metal–organic monolayer and gold nanoparticles (AuNPs), is demonstrated. By using Langmuir–Blodgett deposition of low‐symmetry zinc phthalocyanine (ZnPc) molecules, the metal–organic monolayer is fabricated with greatly suppressed intermolecular aggregation. Oxidation of the monolayer through coordination of NO2 molecules with axial zinc ions of ZnPc molecules gives rise to the specific absorption band inherited to cation radical ZnPc+. The hybrid AuNPs–ZnPc structure is engineered to maximize exciton–plasmon interaction of CT complexes at the radical form of the metal–organic monolayer. Excellent spectral and spatial overlaps with plasmon resonance boost absorption of CT internal optical transition, so‐called “fingerprint” band, by a factor of six from 0.45% to 2.8% in total. The approach paves the way for efficient plasmonic control over photochemical reactions promoted by charge‐transfer complexes in metal–organic films. In particular, the plasmonic effect is harnessed to improve NO2 gas sensing properties; the experimental study shows a 15‐fold increase of the detection efficiency in the specific band of CT complexes under the gas exposure.

Linear carbon-based materials such as polyyne and cumulene oligomers provide a versatile platform for nano-physics and engineering. Direct gap quasi-1D polyyne structures are promising for the observation of strong and unusual excitonic effects arising due to the two-dimensional quantum confinement. Recently, we reported on the observation of sharp exciton peaks in low temperature photoluminescence spectra of polyyne chains (Kutrovskaya S et al 2020 Nano Lett. 20 6502–9). Here, we analyze the time-resolved optical response of this system. We extend the non-local dielectric response theory to predict the exciton radiative lifetime dependence on the band-gap value and on the length of the chain. A good agreement between the experiment and the theory is achieved.

Here, we describe the synthesis and purification of six deoxyuridine triphosphate derivatives that contain protein-like functional groups and alkene linkers of various lengths. Using KOD XL and Deep Vent polymerases, these derivatives have been incorporated into single-stranded DNA, achieving a high degree of DNA modification. These polymerases are able to utilize highly modified DNA strands as templates for synthesizing unmodified DNA. The synthesized deoxyuridine triphosphate derivatives are promising as substrates for producing modified aptamers to various target proteins using, e.g., the systematic evolution of ligands by exponential enrichment (SELEX) methodology.

One of the most important branch of modern molecular genetics and biomedicine is the search for predictive markers that help choose the most effective way of treatment, drug and also determine its individual dosage. Among the markers, those that can provide the possibility of using a non­invasive, so­called “liquid biopsy” are considered particularly promising. This method allows the condition of the tumor to be assessed by analyzing the body’s natural fluids, such as blood, urine or saliva. Such studies are most convenient in those cases when it is necessary to monitor the effectiveness of therapy in order to record the time of the onset of resistance of tumor cells, the onset of relapse and to move on to the next line of therapy. In the treatment of aggressive and rapidly became metastatic malignant tumors, such as melanoma, the presence of reliable markers that allow quick and accurate determination of treatment tactics is especially important. Nowadays, there is an increasing number of studies devoted to the search for predictive markers of the effectiveness of immunotherapy. Melanoma is one of the most immunogenic tumors and, as a result, has become a model object for research into and introduction of new approaches to immunotherapy. In this study, we compared two groups of patients with metastatic skin melanoma, with different responses to immunotherapy with blockers of immune control points, to identify new predictive expression biomarkers among microRNAs and mRNAs, and to identify the genes responsible for the occurrence of an objective response to therapy. As a result, the study detected several microRNAs with a significant change in expression level within the tumor tissue of patients responding differently to immunotherapy. Differences in the level of expression of their target genes have also been found, that will allow a more detailed analysis of the molecular mechanisms that determine the sensitivity or resistance of malignant melanoma cells to the immunotherapy. Based on the obtained data, we have proposed expression markers (mRNAs and microRNAs) that can be used as predictors of malignant melanoma tumors to immunotherapy.

MLL is involved in fusion genes with more than 100 partner genes, approximately 80 of which have been characterized at the molecular level. MLL fusion genes are often found in infants (60-80% of acute lymphoblastic leukemia (ALL) cases and 40-50% of acute myeloblastic leukemia (AML) cases) and are appreciably rarer (8-10%) in children older than 1 year of age. MLL rearrangements are important markers in diagnosis and treatment choice. To identify the partner gene is of primary importance for prognosis and minimal residual disease monitoring. The structure of the fusion gene, including localization of the MLL breakpoints, is also informative. A method was developed to examine the fusion transcripts in order to identify the partner gene among the six most common ones and to establish the exon structure of the rearranged MLL. The method includes a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify and to fluorescently label a fusion transcript fragment and subsequent hybridization of the product on a biological microchip with immobilized oligonucleotides complementary to exons of MLL and its partner genes AFF1, MLLT1, MLLT3, MLLT4, MLLT10, and ELL. Hybridization results were verified by sequencing the RT-PCR products and, in some cases, performing long-distance inverse PCR (LDI-PCR). The study involved 38 bone marrow samples from ALL patients (including 33 children younger than 1 year of age) and 15 samples from AML patients (including 10 from children younger than 1 year of age). The main partner genes were AFF1 (49%), MLLT1 (27%), MLLT3 (12%), and MLLT10 (12%) in ALL and MLLT3 (80%), MLLT10 (10%), and MLLT4 (10%) in AML. Fusion gene transcripts most commonly included MLL exon 11 (58% of ALL cases and 50% of AML cases), suggesting a breakpoint in MLL intron 11.

Novel phenyl- and phenoxy-substituted subphthalocyanines bearing a halogen ion in the axial position were synthesised. The compounds obtained were characterised by 1H, 13C and 1H–1H nuclear Overhauser effect spectroscopy and high resolution mass spectrometry. The correlation between the position of the Q-band and the nature of axial or peripheral substituents was shown. Redox transitions of the compounds were characterised using cyclic voltammetry in o-dichlorobenzene. The redox potentials determined suggest a higher electron-donating ability of phenyl substituents compared to phenoxy groups. Absorption cross sections, quantum yields of fluorescence and intersystem crossing, lifetimes of excited states and non-linear optical properties were studied using UV–Vis spectroscopy, stationary and time-resolved fluorimetry, and a non-linear Z-scan technique.

Colorectal cancer (CRC) is the third most common malignancy in industrialized countries. Despite the advances in diagnostics and development of new drugs, the 5-year survival remains only 60-65%. Our approach to early diagnostics of CRC is based on the determination of serological signatures with an array of hemispherical hydrogel cells containing immobilized proteins and oligosaccharides (glycochip). The compounds immobilized on the glycochip include tumor-associated glycans (SiaTn, Tn, TF, Le(C) , Le(Y) , SiaLe(A) , and Manβ1-4GlcNAcβ) and antibodies against human immunoglobulins IgG, IgA, and IgM. The glycochip detects antibodies against tumor-associated glycans in patients' sera. The simultaneous measurement of the levels of immunoglobulins enhances the diagnostic impact of the signatures. In this work, we found previously unreported increase in antibodies against oligosaccharide Manβ1-4GlcNAcβ in patients with CRC. In parallel with these experiments, we determined the levels of oncomarkers carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9, CA 125, CA 15-3, human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) using another gel-based biochip with immobilized antibodies (oncochip) developed earlier in our laboratory. In total, 69 samples from healthy donors, 33 from patients with colorectal carcinoma, and 27 from patients with inflammatory bowel diseases were studied. The use of combined signatures of antiglycan antibodies and oncomarkers provides much better predictive value than the conventional measurement of oncomarkers CEA and CA 19-9. Positive predictive value of CRC diagnoses using together glycochip and oncochip reached 95% with the sensitivity and specificity 88% and 98%, respectively. Thus, the combination of antibody profiling with detection of conventional oncomarkers proved to be a promising tool in diagnostics of CRC.

The novel C5-modified nucleotides containing indodicarbocyanine dye bearing a carboxyl group at the 3-position of indolenine have been synthesized and incorporated into DNA by commercially available thermostable Taq DNA polymerase. The efficiency of incorporation of labeled nucleotides during polymerase chain reaction was studied in a TB-biochip and THROMBO-Biochip test systems.

We studied monoatomic linear carbon chains stabilised by gold nanoparticles attached to their ends and deposited on a solid substrate. We observe spectral features of straight chains containing from 8 to 24 atoms. Low temperature PL spectra reveal characteristic triplet fine-structures that repeat themselves for carbon chains of different lengths. The triplet is invariably composed of a sharp intense peak accompanied by two broader satellites situated 15 and 40 meV below the main peak. We interpret these resonances as an edge-state neutral exciton, positively and negatively charged trions, respectively. The time-resolved PL shows that the radiative lifetime of the observed quasiparticles is about 1 ns, and it increases with the increase of the length of the chain. At high temperatures a non-radiative exciton decay channel appears due to the thermal hopping of carriers between parallel carbon chains. Excitons in carbon chains possess large oscillator strengths and extremely low inhomogeneous broadenings., Comment: 23 pages, 5 figures

Using a ladder-type polymer in an optical microcavity in strong coupling, we demonstrate an all-optical transistor with record net gain of ~10 dB/μm, sub-ps switching time, cascaded amplification and all-optical logic operation at ambient conditions.

Active optical elements with ever smaller footprint and lower energy consumption are central to modern photonics. The drive for miniaturization, speed and efficiency, with the concomitant volume reduction of the optically active area, has led to the development of devices that harness strong light–matter interactions. By managing the strength of light–matter coupling to exceed losses, quasiparticles, called exciton-polaritons, are formed that combine the properties of the optical fields with the electronic excitations of the active material. By making use of polaritons in inorganic semiconductor microcavities, all-optical transistor functionality was observed, albeit at cryogenic temperatures1. Here, we replace inorganic semiconductors with a ladder-type polymer in an optical microcavity and realize room-temperature operation of a polariton transistor through vibron-mediated stimulated polariton relaxation. We demonstrate net gain of ~10 dB μm−1, sub-picosecond switching time, cascaded amplification and all-optical logic operation at ambient conditions. Net gain of ~10 dB µm–1 and sub-picosecond switching time are shown at room temperature for optical transistors using polymers in a microcavity.

Inorganic cesium lead halide perovskite nanowires, generating laser emission in the broad spectral range at room temperature and low threshold, have become powerful tools for the cutting-edge applications in the optoelectronics and nanophotonics. However, to achieve high-quality nanowires with the outstanding optical properties, it was necessary to employ long-lasting and costly methods of their synthesis, as well as postsynthetic separation and transfer procedures that are not convenient for large-scale production. Here we report a novel approach to fabricate high-quality CsPbBr

Acral melanoma is one of the most aggressive and fast-growing forms of cutaneous melanoma and is characterized by a predominant location on the palms and feet. Primary tumors, metastases, and normal tissue samples from five acral melanoma patients were examined by massive parallel sequencing, focusing on the coding regions of 4100 genes involved in the origin and progression of hereditary and oncology diseases. Somatic mutations were found in genes related to cell division, proliferation, and apoptosis (BRAF, NRAS, VAV1, GATA1, and GCM2); cell adhesion (CTNND2 and ITGB4); angiogenesis (VEGFA); and the regulation of energy metabolism (BCS1L). Comparisons of target DNA sequences between morphologically normal and primary tumor tissues and between normal and metastatic tissues identified the candidate genes responsible for rapid metastasis in acral melanoma.

The immunological profiles of human specific IgE (sIgE) and specific IgG4 (sIgG4) vary by genetic predisposition, living conditions in different geographical locations and patient’s age. The aim of our study was to analyze sIgE and sIgG4 patterns and their age-dependent changes in patients from the Moscow region. For identifying sIgE and sIgG4 profiles the blood samples from 513 patients aged 6 months to 17 years who were showing symptoms of allergic diseases were analyzed using microarrays containing 31 allergens. The highest sIgE prevalence was observed for birch pollen (32%) among pollen allergens, cat dander (24%) among indoor allergens, and egg whites (21%) among food allergens. The most common sIgG4 response was developed toward egg whites (80% of patients). Age-related elevation was identified for patients with increased sIgE to pollen allergens and indoor allergens (cat or dog dander and house dust mites). For each allergen, the proportion of cases with significant levels of sIgG4 appeared to increase with patients’ age. The data on allergen-specific sIgE and sIgG4 prevalence show both general trends and some local special aspects that are indicative for the Moscow region. This information should be useful in terms of epidemiology of allergic diseases.

Plasmon enhancement of optical absorption in phthalocyanines and related compounds is a highly effective route for substantial improvement of their photophysical properties. Herein, we report the results on the comprehensive study of optical absorption in aluminum phthalocyanine complex in spherical exciton–plasmon nanostructures based on gold nanoparticles. We synthesized hybrid nanoparticles (HNPs) composed of gold cores with an average size of 19 nm coated by phthalocyanines which formed a close-packed molecular shell having a thickness of 2–4 nm. Owing to H-type aggregation of phthalocyanines at the particle surface, the self-assembled molecular shell demonstrates optical properties typical for most of the metal-phthalocyanine thin films. On the basis of the generalized Mie theory and experimental results, we simulated effective absorption spectra of phthalocyanines in HNPs and established a great enhancement of molar absorption coefficient caused by intense plasmonic near field acting on the shell (u...

Antipsychotics are the primary drugs for treating schizophrenia, a severe psychical disease that affects approximately 1% of the population. The mechanism of antipsychotic action has not yet been completely clarified. A number of studies in the field of pharmacogenetics have confirmed the huge influence of several neurotransmitter systems on the efficiency and development of side effects. In the present work, we studied whether there are associations between nine polymorphic variants of five genes of dopaminergic and serotonergic systems (DRD4, HTR2A, TPH1, SLC18A1, and COMT) in schizophrenia patients (Russians and Tatars) and the efficiency of therapy by haloperidol (a typical antipsychotic) according to the positive and negative syndrome scale (PANSS). Interethnic differences in the specificity of genetic factors of sensitivity to haloperidol therapy have been registered. Pharmacogenetic markers of increased and decreased efficiency of the therapy by this drug were established in patients of Russian ethnicity. No genetic markers of the efficiency of haloperidol therapy in the studied genes have been detected in patients of Tatar ethnicity. These results confirm the significance of changes in nucleotide sequences of all studied dopaminergic and serotonergic system genes in the development of individual sensitivity to haloperidol. We consider our data to be preliminary (before their confirmation on larger patient samples).

A comparative study of various approaches to speckle reduction showed that the use of a liquid crystal-based speckle reducer did not allow complete elimination of speckles. The use of mechanical devices for blurring of the speckle pattern in the field of view turned out to be more efficient in the case of quantitative luminescent microscopy. Virtually complete reduction of speckles was observed when a device that combines a ring-shaped fiber-optic light source and a vibration unit that shifts the butt-ends of optical fibers relative to the laser diode during measurement was used. This speckle-reduction approach was successfully used in microarray analysis.

In order to expand the informational capabilities of molecular genetic research, new indotricarbocyanine dyes that fluoresce in the near infrared (IR) spectral region have been synthesized. The developed IR dyes were studied using a biochip-based test system for detection of mutations in the BRCA1/BRCA2 and CHECK2 genes associated with breast cancer. The fluorescent label was introduced to the analyzed DNA during PCR using primers labeled with the synthesized IR dyes. An analyzer that allows recording and processing of images of fluorescent microarrays in the IR spectral region was designed and manufactured. It has been shown that the use of the synthesized dyes enables to conduct analysis in the IR region and improve the reliability of medical diagnostic tests due to low fluorescence intensity of sample components as well as of a biochip substrate and the reagents used for analysis.

Targeted inhibitors of the epidermal growth factor receptor (EGFR) are used for the treatment of non-small cell lung cancer (NSCLC). Somatic mutations in the EGFR gene and key effectors of the EGFR-signaling pathway (KRAS, BRAF, PIK3CA) are associated with sensitivity to these drugs. We developed a highly sensitive LUNG CANCER (LC)-biochip approach for the detection of the most common EGFR, KRAS, PIK3CA, and BRAF gene mutations. The locked nucleic acid clamp PCR technique was used to increase the sensitivity of the assay, then allele-specific hybridization of a fluorescently labeled target on a biochip was performed. To prove the feasibility of the approach, clinical samples from 112 patients with NSCLC were analyzed. A total of 14 EGFR (12.5%) mutations, 21 (18.8%) KRAS mutations, 12 (10.7%) PIK3CA mutations, and 1 BRAF mutation (0.9%) were found. We compared the results with those from direct sequencing. We detected 50 different mutations by the LC-biochip assay and only 33 of them were found by direct sequencing. To demonstrate that the LC-biochip assay did not give false-positive results, the 17 specimens with discordant results were subjected to locked nucleic acid clamp PCR followed by sequencing. The results of this analysis were identical to the results obtained by the LC-biochip assay indicating that the biochip-based assay was both accurate and reliable. This approach was able to detect approximately 0.5% of mutated alleles in wild-type DNA background. The biochip-based assay is a reliable and inexpensive method for the identification of NSCLC patients, who may respond to a specific targeted therapy.

Antipsychotics are the main drugs for the treatment of severe mental illness--schizophrenia affects about 1% of the population. The mechanism of action of neuroleptics is still up to the end. Several studies in the field of pharmacogenetics confirm enourmous influence of several neurotransmitter systems in the brain on the efficiency and the development of side effects. In this paper, we analyzed the association of nine polymorphic variants of five genes of dopaminergic and serotonergic systems DRD4, HTR2A, TPH1, SLC18A1, COMT in Russian and Tatars patients living in the Republic of Bashkortostan (RB) with the efficiency of a typical antipsychotic haloperidol on the scale of positive and negative systems of PANSS. The study established pharmacogenetic markers of increased and decreased effectiveness of therapy with haloperidol in the treatment groups. The results of this study confirm the importance of changes in the nucleotide sequences of the studied genes of the serotoninergic and dopaminergic systems (HTR2A, TPH1, SLC18A1 COMT, DRD4) in the formation of individual sensitivity to haloperidol. The results of our work considered as preliminary contact, requires an increase in the number of samples studied.

To expand the informational capabilities of molecular genetic research, on the biological microchips, new indotricarbocyanine dyes that fluoresce in the near infrared (IR) spectral region have been synthesized. The developed IR dyes were studied using a biochip-based test system for detection of mutations in the BRCA1/BRCA2 and CHECK2 genes associated with breast cancer. The fluorescent label was introduced to the analyzed DNA during PCR using primers labeled with the synthesized IR dyes. An analyzer that allows recording and processing of images of fluorescent microarrays in the IR spectral region was designed and manufactured. It has been shown that the use of the synthesized dyes enables to conduct analysis in the IR region and improve the reliability of medical diagnostic tests due to low fluorescence intensity of sample components as well as of a biochip substrate and the reagents used for analysis.

The incidence of malignant melanoma is increasing. The discovery of agents specifically targeting the mutated cascades has provided a good response for patients with oncogenic B-Raf proto-оncogene, serine/threonine kinase (BRAF). However, numerous studies continue to focus on novel methods of treatment to overcome acquired resistance to novel drugs. Recently, it has been revealed that inhibition of endoplasmic reticulum (ER) stress chaperon 78 kDa glucose-regulated protein 78 (GRP78) leads to down-regulation of autophagy and increased sensitivity to temozolomide (TMZ) treatment. Melanoma cells have a different sensitivity to TMZ treatment, which corresponds to the basal autophagy level. In the present study, we demonstrated that downregulation of GRP78 mitigated chemoresistance to TMZ in three melanoma cell lines. We found that downregulation of GRP78 led to inhibition of autophagy, cell cycle arrest in the G0/G1 phase, and activation of caspase-7-induced apoptosis, and this was affected by the initial autophagy level. Moreover, inhibition of GRP78 mitigated the combined TMZ and chloroquine effect. Our data revealed that autophagy inhibition through downregulation of ER stress response could overcome resistance to TMZ treatment in melanoma cells with a high basal level of autophagy treatment, which makes this combination a potential potent antitumor treatment for metastatic melanoma.

Открытие функционального значения тысяч генов и молекулярных механизмов действия множества ферментов стало революционным событием в биологии, оказавшим и продолжающим оказывать огромное влияние на развитие медицины XXI в. Перед учеными и медиками открылись уникальные возможности для выяснения причин многих инфекционных и наследственных заболеваний, а также разработки эффективных методов их лечения. В свою очередь, развитие новых диагностических методов потребовало и создания новых технологий многопараметрического анализа биологических образцов, с помощью которых можно одновременно исследовать множество белковых и ДНК-маркеров различных заболеваний, функционально-значимых биологических макромолекул и их комплексов. Так появилась технология биологических микрочипов, способных, подобно микрочипам электронным, извлекать и обрабатывать огромные массивы информации из одного небольшого образца биологического материала, полученного от конкретного пациента, {"references":["Khrapko, K. et al. (1989). An oligonucleotide hybridization approach to DNA sequencing. FEBS Letters. 256(1-2):118-22.","Arenkov, P. et al. (2002). Protein microchips: use for immunoassay and enzymatic reactions. Analytical Biochemistry. 278(2):123-31","Колчинский, А. et al. (2004). Микрочипы на основе трехмерных ячеек геля: история и перспективы. Молекулярная биология. 38(1):5-16.","Грядунов, Д. et al. (2009). Технология гидрогелевых биочипов и ее применение в медицинской лабораторной диагностике. Медицинский алфавит. 3:10-14","Zimenkov, D. et al. (2016). Simultaneous drug resistance detection and genotyping of Mycobacterium tuberculosis using a low-density hydrogel microarray. Journal of antimicrobial chemotherapy. 71(6):1520-31.","Gryadunov, D. et al. (2011). Gel-based microarrays in clinical diagnostics in Russia. Expert review of molecular diagnostics. 11:839-53.","Emelyanova, M. et al. (2017). Detection of BRAF, NRAS, KIT, GNAQ, GNA11 and MAP2K1/2 mutations in Russian melanoma patients using LNA PCR clamp and biochip analysis. Oncotarget. 8(32):52304-52320","Feyzkhanova, G. et al. (2017). Development of a microarray-based method for allergen-specific IgE and IgG4 detection. Clinical proteomics. 14:1."]}