Perchlozone Resistance in Clinical Isolates of Mycobacterium tuberculosis.

The emergence of drug-resistant tuberculosis forced the development of new drugs and the screening of more effective or less toxic analogues. Mycolic acid biosynthesis is targeted by several antituberculosis drugs, isoniazid being one of the most important in tuberculosis therapy. Recently, perchlozone, acting on another step in the FAS-II cycle, was officially approved for tuberculosis treatment in the Russian Federation and was included in the Russian national clinical guidelines. Using the serial dilution method on 7H10 agar plates for perchlozone and a Sensititre MYCOTB microdilution plate, we analyzed the phenotypic properties of primary clinical isolates of M. tuberculosis and analyzed the molecular determinants of resistance to isoniazid, ethionamide, and perchlozone. We found a wide variation in the MIC of perchlozone from 2 to 64 mg/L, correlating with the overall resistance profile: the MIC was higher for MDR and pre-XDR isolates. The cross-resistance between ethionamide and perchlozone was driven by mutations in the ethA gene encoding monooxygenase responsible for the activation of both drugs. The presumably susceptible to perchlozone and wild-type strains had MICs ranging from 2 to 4 mg/L, and the breakpoint was estimated to be 4 or 8 mg/L. In conclusion, susceptibility to perchlozone is retained for a part of the MDR strains, as is susceptibility to ethionamide, providing the possibility of therapy for such cases based on phenotypic or molecular analysis.

Biosynthesis and Characterization of Gold Nanoparticles Produced Using Rhodococcus Actinobacteria at Elevated Chloroauric Acid Concentrations.

The growing industrial and medical use of gold nanoparticles (AuNPs) requires environmentally friendly methods for their production using microbial biosynthesis. The ability of actinobacteria of the genus Rhodococcus to synthesize AuNPs in the presence of chloroauric acid (HAuCl4) was studied. The effect of elevated (0.8-3.2 mM) concentrations of HAuCl4 on bacterial viability, morphology, and intracellular accumulation of AuNPs by different Rhodococcus species was shown. An increase in surface roughness, a shift of the zeta potential to the positive region, and the formation of cell aggregates of R. erythropolis IEGM 766 and R. ruber IEGM 1135 during nanoparticle synthesis were revealed as bacterial adaptations to toxic effects of HAuCl4. The possibility to biosynthesize AuNPs at a five times higher concentration of chloroauric acid compared to chemical synthesis, for example, using the citrate method, suggests greater efficiency of the biological process using Rhodococcus species. The main parameters of biosynthesized AuNPs (size, shape, surface roughness, and surface charge) were characterized using atomic force microscopy, dynamic and electrophoretic light scattering, and also scanning electron microscopy in combination with energy-dispersive spectrometry. Synthesized by R. erythropolis spherical AuNPs have smaller (30-120 nm) dimensions and are positively (12 mV) charged, unlike AuNPs isolated from R. ruber cells (40-200 nm and -22 mV, respectively). Such differences in AuNPs size and surface charge are due to different biomolecules, which originated from Rhodococcus cells and served as capping agents for nanoparticles. Biosynthesized AuNPs showed antimicrobial activity against Gram-positive (Micrococcus luteus) and Gram-negative (Escherichia coli) bacteria. Due to the positive charge and high dispersion, the synthesized by R. erythropolis AuNPs are promising for biomedicine, whereas the AuNPs formed by R. ruber IEGM 1135 are prone to aggregation and can be used for biotechnological enrichment of gold-bearing ores.

Exposure to metal nanoparticles changes zeta potentials of Rhodococcus cells.

Nanoparticles (NPs) of transition metals and their oxides are widely used in industries and exhibit diverse biological activities - from antimicrobial to growth promoting and regulating biofilms. In this study, the concentration-dependent effects of negatively charged metal and metal oxide NPs on the viability and net surface charge of Rhodococcus cells were revealed. Our hypothesis that zeta potential values of bacterial cells approach the zeta potential of NPs with an increase in the concentration of nanoparticles was statistically validated, thus suggesting the accumulation of nanoparticles on the cell surface. Thus, based on the dynamics of zeta potential, it would be possible to predict the accumulation of metal NPs on the cell surface of particular Rhodococcus species. It seemed that more toxic nanometals (e.g. CuO) accumulate more intensively on the bacterial cell wall than less toxic nanometals (Bi, Ni and Co). Physical properties of NPs, such as shape, size, dispersity and zeta potential, were characterized at different nanoparticle concentrations, in order to explain their diverse effects on bacterial viability, cellular charge and adhesion to hydrocarbons. Interestingly, an increase in Rhodococcus adhesion to n-hexadecane was observed in the presence of Cu and CuO NPs, while treatment with Fe3O4 NPs resulted in a decrease in the adhesive activity. The obtained data help to clarify the mechanisms of nano-bio interaction and make it possible to select metal and metal oxide nanoparticles to modify the surface of bacterial cells without toxic effects.

Molecular Determinants of Ethionamide Resistance in Clinical Isolates of Mycobacterium tuberculosis.

BACKGROUND: Ethionamide and prothionamide are now included in group C of the WHO recommended drugs for the treatment of tuberculosis resistant to rifampicin and multidrug-resistant tuberculosis. The clinical relevance of ethionamide and prothionamide has increased with the wide spread of resistant tuberculosis. METHODS: We retrospectively analyzed 349 clinical isolates obtained between 2016 and 2020. The susceptibility to ethionamide was tested using both the BactecTM MGITTM 960 system and the SensititreTM MYCOTB plate. RESULTS: The MIC of ethionamide increases with the total resistance of the isolates in a row from susceptible to XDR strains. A significant part of the isolates have a MIC below the breakpoint: 25%, 36%, and 50% for XDR, pre-XDR, and MDR strains. Sensitivity and specificity of detection of mutations were 96% and 86% using MGIT resistance as a reference. CONCLUSIONS: Phenotypic methods for testing ethionamide are imperfectly correlated, and the isolates with MIC of 5 mg/L have the intermediate resistance. A significant proportion of resistant TB cases are susceptible and eligible for ethionamide treatment. Resistance could be explained using only analysis of loci ethA, PfabG1, and inhA for most isolates in the Moscow region. The promoter mutation PfabG1 c(-15)t predicts resistance to ethionamide with high specificity but low sensitivity.

Comparison of biomarker and chromatographic analytical approaches to pharmacokinetic study of sitagliptin.

The pharmacokinetic profiling of active compounds is necessary for drug development and application. Approaches to a pharmacokinetic study based on biological markers are alternatives to traditional approaches based on chromatographic methods. The aim of the study was to compare two analytical approaches to pharmacokinetics investigation for an example of sitagliptin in rabbits after one dose oral administration. The method for sitagliptin quantification in rabbit plasma samples based on a correlation between its concentration and dipeptidyl peptidase IV activity was proposed, validated, and applied. The high-performance liquid chromatography (HPLC)-ultraviolet (UV) method was also validated and applied for the same sample analysis. The plasma pharmacokinetics of sitagliptin after oral administration to the rabbits in one dose was characterized after two analytical assays. The close values of the main pharmacokinetic parameters were obtained after two approaches. The nontraditional approach based on correlation of special marker activity and active substance concentration appears to be more sensitive than HPLC-UV. Thus, the sitagliptin concentrations determined by biomarker assay were higher than the lower limit of quantification (LLOQ) for a longer period (more timepoints) than after the HPLC-UV assay. This feature may influence the values of some calculated concentration-dependent (area under the curve [AUC]0-t , etc.) and time-dependent parameters (mean residence time [MRT], T1/2 , etc.). The values of Tmax obtained by the two approaches were similar and adequate for oral drug administration that confirms the correctness of biomarker selection for pharmacokinetics assessment. The obtained results on the example of sitagliptin confirms that the biomarker approach is adequate and applicable for a pharmacokinetics study. Similar approaches may be effective for individual compounds and complex mixtures when it is difficult or impossible to analyze them traditionally by chromatographic methods.

Genetic Profile of Linezolid-Resistant M. tuberculosis Clinical Strains from Moscow.

BACKGROUND: Linezolid, bedaquiline, and newer fluoroquinolones are currently placed as priority Group A drugs for the treatment of drug-resistant tuberculosis. The number of reported linezolid-resistant clinical strains is still low, and the correlation of molecular determinants with phenotype is not perfect. METHODS: We determined the linezolid MICs for clinical isolates from the Moscow region and identified mutations in rplC and rrl genes. RESULTS: All 16 linezolid-resistant isolates had previously reported mutations in the rplC or rrl loci, and 13 of them bore a RplC C154R substitution. Detection of this substitution in a heteroresistant state was not successful, probably, due to the more stable DNA secondary structure of the mutated fragment, which precludes its amplification in mixes with the wild-type DNA. Strains with an rplC mutation had higher linezolid MIC compared to isolates with rrl mutations. CONCLUSIONS: Linezolid resistance mostly emerged during treatment with the latest regimen. Three primary cases with linezolid resistance question the possible transmission of totally drug-resistant tuberculosis in the Moscow region, which demands further investigation.

In vitro activity of bedaquiline against Mycobacterium avium complex.

Introduction. Nontuberculous mycobacteria (NTM) are widespread in the environment and can cause various diseases in humans, especially immunocompromised patients.Hypothesis. Treatment of diseases caused by NTM is a complicated issue, mainly due to the resistance of the pathogen to most antimicrobial agents. Bedaquiline (Bdq) is now widely used for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB).Aim. The main goal of our study was to evaluate the activity of Bdq against Mycobacterium avium complex (MAC), the most common species among NTM.Methodology. A total of 166 MAC cultures (124 Mycobacterium avium and 42 Mycobacterium intracellulare) were studied. The minimum inhibitory concentrations (MICs) of Bdq for M. avium and M. intracellulare were obtained by twofold serial dilutions in the Middlebrook 7H9 medium. MIC ranges were determined and the MIC50, MIC90 and ECOFF values were obtained.Results. The MICs in respect of M. avium ranged from 0.003 to 1.0 µg ml-1; those for M. intracellulare ranged from 0.003 to 0.5 µg ml-1. The Bdq MIC50 and MIC90 values were found to be 0.015 and 0.12 µg ml-1 , respectively, for M. avium and 0.007 and 0.06 µg ml-1, respectively, for M. intracellulare. The tentative ECOFF values for M. avium and M. intracellulare were 0.12 and 0.06 µg ml-1, respectively.Conclusion. The main bedaquiline susceptibility parameters for MAC strains isolated in the Moscow region were determined.

A 61-Year-Old Woman With Insidious Dyspnea and Diffuse Cystic Lung Disease.

A 61-year-old woman, an ex-smoker with a 10 pack year smoking history, was referred to our clinic for the evaluation of insidious dyspnea and diffuse, bilateral infiltrates on a chest radiograph. She reported that she had been experiencing dyspnea on exertion and dry cough for the past 1.5 years. She denied fevers, chills, hemoptysis, or weight loss. Aside from a smoking history, there were no comorbidities or environmental exposures. She had no family history of lung diseases or other disorders. She worked as a school teacher and had no occupational exposures. There were no pets in the home and no prior occupational exposures.

Therapeutic efficacy of arginine-rich exenatide on diabetic neuropathy in rats.

Diabetes mellitus is characterized by metabolic dysregulation associated with a number of health complications. More than 50% of patients with diabetes mellitus suffer from diabetic polyneuropathy, which involves the presence of peripheral nerve dysfunction symptoms. The aim of this study was to evaluate the potential of a new synthetic arginine-rich exendin-4 (Peptide D) in the treatment of complications caused by diabetes, including peripheral neuropathy, in rats. Diabetes was induced by administering streptozotocin (STZ). Three groups of diabetic rats were treated with Peptide D (0.1, 1, and 10 µg/kg). One group of diabetic rats was treated with Byetta® (1 µg/kg) for 80 days. Neuropathic pain development was assessed by tactile allodynia. STZ-treated rats showed an increased level of tactile allodynia unlike naïve animals. A histological study revealed that the diameter of the sciatic nerve fibers in STZ-treated rats was smaller than that of the naïve animals. An IHC study demonstrated decreased expression of myelin basic protein (MBP) in the sciatic nerve of diabetic rats compared to that in the naïve animals. Peptide D reduced the severity of tactile allodynia. This effect was more pronounced in the Peptide D treated groups than in the group treated with Byetta®. Peptide D and Byetta® treatment resulted in increased MBP expression in the sciatic nerve and increased diameter of myelinated nerve fibers. These findings suggest that poly-arginine peptides are promising agents for the treatment of peripheral polyneuropathies.

Rationale for vaccination with trivalent or quadrivalent live attenuated influenza vaccines: Protective vaccine efficacy in the ferret model.

BACKGROUND AND AIM: The majority of seasonal influenza vaccines are trivalent, containing two A virus strains (H1N1 and H3N2) and one B virus strain. The co-circulation of two distinct lineages of B viruses can lead to mismatch between the influenza B virus strain recommended for the trivalent seasonal vaccine and the circulating B virus. This has led some manufacturers to produce quadrivalent influenza vaccines containing one strain from each B lineage in addition to H1N1 and H3N2 strains. However, it is also important to know whether vaccines containing a single influenza B strain can provide cross-protectivity against viruses of the antigenically distinct lineage. The aim of this study was to assess in naïve ferrets the potential cross-protective activity of trivalent live attenuated influenza vaccine (T-LAIV) against challenge with a heterologous wild-type influenza B virus belonging to the genetically different lineage and to compare this activity with effectiveness of quadrivalent LAIV (Q-LAIV) in the ferret model. METHODS AND RESULTS: Ferrets were vaccinated with either one dose of trivalent LAIV containing B/Victoria or B/Yamagata lineage virus, or quadrivalent LAIV (containing both B lineages), or placebo. They were then challenged with B/Victoria or B/Yamagata lineage wild-type virus 28 days after vaccination. The ferrets were monitored for clinical signs and morbidity. Nasal swabs and lung tissue samples were analyzed for the presence of challenge virus. Antibody response to vaccination was assessed by routine hemagglutination inhibition assay. All LAIVs tested were found to be safe and effective against wild-type influenza B viruses based on clinical signs, and virological and histological data. The absence of interference between vaccine strains in trivalent and quadrivalent vaccine formulations was confirmed. Trivalent LAIVs were shown to have the potential to be cross-protective against infection with genetically different influenza B/Victoria and B/Yamagata lineages. CONCLUSIONS: In this ferret model, quadrivalent vaccine provided higher protection to challenge against both B/Victoria and B/Yamagata lineage viruses. However, T-LAIV provided some cross-protection in the case of a mismatch between circulating and vaccine type B strains. Notably, B/Victoria-based T-LAIV was more protective compared to B/Yamagata-based T-LAIV.

Drug susceptibility testing of slowly growing non-tuberculous mycobacteria using slomyco test-system.

OBJECTIVE: The objective of the research was to assess the susceptibility of the slowly growing nontuberculous mycobacteria strains to the antimicrobial drugs used for mycobaterioses treatment using SLOMYCO test system. MATERIALS AND METHODS: We assessed 363 NTM strains: 177 MAC (161 M. avium, 16 M. intracellulare), 112 M. kansasii and 74 M. xenopi collected from the respiratory material of the patients were under the treatment or under diagnostic procedures at our Center, affiliates and the diagnostic department in 2010-2016. Drug sucseptibility for NTM was tested using the Sensititre SLOWMYCO system (TREK DIAGNOSTIC Systems Ltd., UK). MICs were established by microdilutions in Mueller-Hinton broth on polystyrene 96-well plates. The statistical analysis was done using the StatGraphics Plus 5.0 software. The data were compared pairwise using Pearson χ2 test with Yates correction. 95% confidence interval (CI) were calculated. Statistically significant differences were considered for p <0.05. Log-rank test and Kaplan-Meier curves were used to assess the concentration-dependent surveillance probability. RESULTS: The statistically significant differences were revealed in sensitivity/resistance isolates of M. avium and M. intracellulare: M. avium strains were resistant to higher concentrations of amikacin, clarithromycin, linezolid and streptomycin (p <0.01); M. intracellulare strains were resistant to higher concentrations of ethionamide (p <0.05). The isolates of M. avium were significantly more resistant than M. kansasii to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifabutin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). The isolates of M. avium showed significantly higher resistance than M. xenopi to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). Statistically significant differences in the dynamics of the response to the antibacterial effects of isoniazid, linezolid, moxifloxacin, rifampicin, trimethoprim/sulfamethoxazole, ethambutol, and ethionamide were found for M. intracellulare and M. xenopi (complete inhibition of the visible growth of M. intracellulare required higher drugs concentrations, p <0, 05). Comparison of the Kaplan-Meyer curves revealed statistically significant differences in survialence probability of M. kansasii and M. xenopi for amikacin, doxycycline, rifampicin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (a higher number of isolates of M. xenopi were inhibited by low drugs concentrations, p <0.05). CONCLUSIONS: Our data show that M. avium and M. intracellulare were more resistant to the majority of the studied drugs than M. kansasii and M. xenopi.

A new tridecapeptide with an octaarginine vector has analgesic therapeutic potential and prevents morphine-induced tolerance.

A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr-d-Arg-Phe-Gly-NH2 was modified with the inclusion of a (d-Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (d-Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain. The analgesic effects of TDP were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32-1mg/kg) and TDP (0.32-1.8mg/kg) produced significant dose-related antinociceptive effects in the writhing test. The potency of TDP after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model, TDP (0.1, 1 and 10mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of TDP after morphine treatment (7days) produced a significant analgesic effect in morphine-tolerant rats, indicating the absence of cross-tolerance between these two drugs. The combined administration of TDP and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross-tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for TDP, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions.

Chemical Profiling and Bioactivity of Body Wall Lipids from Strongylocentrotus droebachiensis.

The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of sea urchins are intensively studied. However, little is known about the body wall (BW) lipids. Ethanol extract (55 °C) contained about equal amounts of saturated (SaFA) and monounsaturated fatty acids (MUFA) representing 60% of total fatty acids, with myristic, palmitic and eicosenoic acids as major SaFAs and MUFAs, respectively. Non-methylene-interrupted dienes (13%) were composed of eicosadienoic and docosadienoic acids. Long-chain polyunsaturated fatty acids (LC-PUFA) included two main components, n6 arachidonic and n3 eicosapentaenoic acids, even with equal concentrations (15 µg/mg) and a balanced n6/n3 PUFA ratio (0.86). The UPLC-ELSD analysis showed that a great majority of the lipids (80%) in the ethanolic extract were phosphatidylcholine (60 µg/mg) and phosphatidylethanolamine (40 µg/mg), while the proportion of neutral lipids remained lower than 20%. In addition, alkoxyglycerol derivatives-chimyl, selachyl, and batyl alcohols-were quantified. We have assumed that the mechanism of action of body wall lipids in the present study is via the inhibition of MAPK p38, COX-1, and COX-2. Our findings open the prospective to utilize this lipid fraction as a source for the development of drugs with anti-inflammatory activity.

Examination of bedaquiline- and linezolid-resistant Mycobacterium tuberculosis isolates from the Moscow region.

Objectives: To study the isolates with acquired resistance to bedaquiline and linezolid that were obtained from patients enrolled in a clinical study of a novel therapy regimen for drug-resistant TB in Moscow, Russia. Methods: Linezolid resistance was detected using MGIT 960 with a critical concentration of 1 mg/L. The MIC of bedaquiline was determined using the proportion method. To identify genetic determinants of resistance, sequencing of the mmpR ( Rv0678 ), atpE , atpC , pepQ , Rv1979c , rrl , rplC and rplD loci was performed. Results: A total of 85 isolates from 27 patients with acquired resistance to linezolid and reduced susceptibility to bedaquiline (MIC ≥0.06 mg/L) were tested. Most mutations associated with a high MIC of bedaquiline were found in the mmpR gene. We identified for the first time two patients whose clinical isolates had substitutions D28N and A63V in AtpE, which had previously been found only in in vitro -selected strains. Several patients had isolates with elevated MICs of bedaquiline prior to treatment; four of them also bore mutations in mmpR , indicating the presence of some hidden factors in bedaquiline resistance acquisition. The C154R substitution in ribosomal protein L3 was the most frequent in the linezolid-resistant strains. Mutations in the 23S rRNA gene (g2294a and g2814t) associated with linezolid resistance were also found in two isolates. Heteroresistance was identified in ∼40% of samples, which reflects the complex nature of resistance acquisition. Conclusions: The introduction of novel drugs into treatment must be accompanied by continuous phenotypic susceptibility testing and the analysis of genetic determinants of resistance.

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical Mycobacterium tuberculosis Isolates in Moscow, Russia.

BACKGROUND: The goal of this study was to compare the consistency of three assays for the determination of the drug resistance of Mycobacterium tuberculosis (MTB) strains with various resistance profiles isolated from the Moscow region. METHODS: A total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the rpoB, katG, inhA, ahpC, gyrA, gyrB, rrs, eis, and embB genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol. RESULTS: The average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 µg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms. CONCLUSIONS: The quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.

Self-assembling diacetylene molecules on atomically flat insulators.

Single crystal sapphire and diamond surfaces are used as planar, atomically flat insulating surfaces, for the deposition of the diacetylene compound 10,12-nonacosadiynoic acid. The surface assembly is compared with results on hexagonal boron nitride (h-BN), highly oriented pyrolytic graphite (HOPG) and MoS2 surfaces. A perfectly flat-lying monolayer of 10,12-nonacosadiynoic acid self-assembles on h-BN like on HOPG and MoS2. On sapphire and oxidized diamond surfaces, we observed assemblies of standing-up molecular layers. Surface assembly is driven by surface electrostatic dipoles. Surface polarity is partially controlled using a hydrogenated diamond surface or totally screened by the deposition of a graphene layer on the sapphire surface. This results in a perfectly flat and organized SAM on graphene, which is ready for on-surface polymerization of long and isolated molecular wires under ambient conditions.

Self-assembled diacetylene molecular wire polymerization on an insulating hexagonal boron nitride (0001) surface.

The electrical characterization of single-polymer chains on a surface is an important step towards novel molecular device development. The main challenge is the lack of appropriate atomically flat insulating substrates for fabricating single-polymer chains. Here, using atomic force microscopy, we demonstrate that the (0001) surface of an insulating hexagonal boron nitride (h-BN) substrate leads to a flat-lying self-assembled monolayer of diacetylene compounds. The subsequent heating or ultraviolet irradiation can initiate an on-surface polymerization process leading to the formation of long polydiacetylene chains. The frequency of photo-polymerization occurrence on h-BN(0001) is two orders of magnitude higher than that on graphite(0001). This is explained by the enhanced lifetime of the molecular excited state, because relaxation via the h-BN is suppressed due to a large band gap. We also demonstrate that on-surface polymerization on h-BN(0001) is possible even after the lithography process, which opens up the possibility of further electrical investigations.

Bergenia crassifolia (L.) Fritsch--pharmacology and phytochemistry.

PURPOSE: Bergenia crassifolia (L.) Fritsch, a species in the Bergenia genus belongs to the family Saxifragaceae, is valuated for its medicinal application. The review focuses on the medicinal uses, phytochemistry, and the biological activities of B. crassifolia to explore its benefits and potential uses. METHODS: In this review, we summarized data, published in Russia and in other countries related to B. crassifolia. RESULTS: Rhizomes and leaves of this plant are in use as traditional remedies for the treatment of different disorders in the folk medicine systems of Russia and Asia. The plant is a potential source of tannins, benzanoids, flavonoids, polysaccharides and other active compounds. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb and individual compounds, which include adaptogenic, antiinflammatory, antihypertensive, antimicrobial, antioxidant, antiobesity, antitussive, cerebro-protective, hepatoprotective, immunomodulating, and diuretic. CONCLUSION: The review highlights the potential of B. crassifolia for further development of herbal medicines on its base.

Antiallergic effects of pigments isolated from green sea urchin (Strongylocentrotus droebachiensis) shells.

This study was undertaken to evaluate possible antiallergic effects of an extract of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells. Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes allergic conjunctivitis, and rabbit local skin irritation. The extract significantly reduced, in a dose-dependent manner, the histamine-induced contractions of the isolated guinea pig ileum with ID50 =1.2 µg/mL (in equivalents of spinochrome B), had an inhibitory effect on the model of ocular allergic inflammation surpassing the reference drug olopatadine, and did not show any irritating effect in rabbits. The extract predominantly contained polyhydroxy-1,4-naphthoquinone which would be responsible for the pharmacological activity. The active compounds of the extract were evaluated in silico with molecular docking. Molecular docking into H1R receptor structures obtained from molecular dynamic simulations showed that all spinochrome derivatives bind to the receptor active site, but spinochrome monomers fit better to it. The results of the present study suggest possibilities for the development of new agents for treating allergic diseases on the base of pigments from sea urchins shells.

Ordered monomolecular layers as a template for the regular arrangement of gold nanoparticles.

Ordered arrays of metal nanoparticles are important for nanoelectronic and nanophotonic applications. Here, we report the formation of self-assembled arrays of gold nanoparticles on molecular layers of diacetylene compounds on a MoS2(0001) substrate. The arrangement of gold nanoparticles is observed using scanning tunneling microscopy. When gold is deposited on a self-assembled monolayer of 10,12-nonacosadiynoic acid or 10,12-octadecadiynoic acid on a MoS2(0001) substrate, the ordered array of diacetylene moieties in the molecular layer serves as a template for the formation of ordered arrays of gold nanoparticles. In contrast, when gold is deposited on a pristine MoS2(0001) surface or on a molecular layer of stearic acid, the gold nanoparticles are randomly distributed on the surface. It is found that the arrangement of gold nanoparticles is largely determined by the deposition rate; faster deposition results in more ordered arrays of gold nanoparticles. Our observations confirm the role of unsaturated π systems in molecules acting as a template for the regular arrangement of gold nanoparticles; this work will open up new possibilities for interfacial nanoarchitectonics.