Search

Objective To evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). Design Interventional case series. Participants Patients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. Methods Eleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. Results AO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. Conclusion IRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Muller cell reactive gliosis were identified with AO-OCT.

The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development.

PURPOSE Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common. CONCLUSION In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Sulfation of wheat straw soda lignin by the sulfamic acid–urea mixture in different solvents has been investigated for the first time. The effect of a catalyst used in the lignin sulfation process on the yield of the lignin sulfates and sulfur content in them has been explored. It has been found that the optimal medium for the lignin sulfation with sulfamic acid is dioxane and, in the presence of a catalyst, urea. Although the sulfated lignins obtained using the reaction in dimethyl sulfoxide and diglyme have the maximum sulfur contents (11.2% and 9.9%, respectively), these products are difficult to isolate and purify, which complicates the use of these solvents. Sulfated lignin obtained in the dioxane medium has a high (10.1%) sulfur content and is easy to isolate and purify. The incorporation of sulfate groups into the lignin structure has been confirmed by the infrared and nuclear magnetic resonance spectroscopy investigations. In the infrared spectra of sulfated lignin, characteristic absorption bands at 800–860 and 1260–1200 cm−1 appear. The dominant substitution of aliphatic hydroxyl groups has been confirmed by the nuclear magnetic resonance spectroscopy study. It has been found that, during the modification and purification of lignin, the latter is fractionated, which results in the redistribution of molecular weights toward the high molecular-weight region, as well as the removal of some low-molecular-weight components, which is reflected in a decrease in the number of signals in the nuclear magnetic resonance spectra.

For the first time catalytic systems based on HZSM-5 zeolites (Si/Al=12, 25, 40) with nanosized anatase (NA) were obtained in situ by a modified hydrothermal method and a sol-gel method. Initial HZSM-5 and NA/HZSM-5 were characterized (XRPD, XAS, FT-IR, DSC, BET, XPS, SEM, TPD) and analyzed in the reactions of propane (liquefied petroleum gas) conversion (РС; temperature range 200–870 °С) with the formation of the main products propylene (C3H6, PP) and ethylene (C2H4, ETH) and liquid ethanol conversion (EC; temperature range 150–360 °C) with the formation of diethyl ether ((C2H5)2O, DEE) and ETH. In the PC reaction the maximum selectivity (SETH = 75%) and conversion (αP = 65%) were obtained on HZSM-5(40) (650 °С). With an increase in the NA content in NA/HZSM-5 SETH value increases up to 85%. In the EC reaction SDEE/ETH~98–99% was reached on HZSM-5(25) (200 °C) and HZSM-5(40) (300 °C); the αE to ETH is comparable (94%) for all HZSM-5 (300 °C). Modification of HZSM-5 with NA leads to a shift in the EC reaction temperature to lower temperature region (αE to ETH ~98% at 280 °C) with SDEE/ETH~94–100% for NA/HZSM-5(25) and NA/HZSM-5(12) obtained by a modified hydrothermal method. It was established the relationship between HZSM-5 and NA/HZSM-5 catalytic activity and their characteristics: Si/Al, NA content and Ti coordination number (NA/HZSM-5), the content of "zeolite water" with OH groups, specific surface area, meso- and micropores volume and spherical particles size (HZSM-5), surface energy of adsorption centers (HZSM-5 and NA/HZSM-5), and hence the content of acid sites, the strength of which is also determined by the temperature of the catalytic reaction. The reaction mechanisms have been presented. The obtained NA/HZSM-5 catalysts have a higher or comparable catalytic activity to commercial ones, but low cost, ease of preparation, and versatility.

The work addresses to the study of the molecular and crystal structure and properties of a new energy-intensive compound 3,6-bis(2,2,2-trinitroethylnitramino)-1,2,4,5-tetrazine (NBTAT), first obtained by the authors in 2020. NBTAT compound crystallizes in the monoclinic system, space group P2(1)/n, density at room temperature 1.939 g/cm3. The energies of crystal packing and pairwise intermolecular interactions in NBTAT and its unnitrated analogue BTAT were calculated, and their comparative analysis was carried out. The enthalpy of formation of NBTAT molecules was calculated by quantum-chemical methods using Gaussian 09, and the enthalpy of formation of NBTAT in the solid phase (618 kJ/mol) was estimated. The energy capabilities of NBTAT as an oxidizer of solid composite propellants are estimated. It is shown that in metal-free compositions NBTAT is significantly superior to ammonium perchlorate (AP), dinitramide ammonium salt (ADN), HMX, BTAT at all stages of rocket systems, and is comparable to the superdense CL-20 yielding to the latter at the lower stages and slightly winning at the upper stages.

American student-athletes (SAs) are at heightened risk for hazardous alcohol consumption compared with their nonathlete peers. However, little is known about this risk or the influence of psychosocial predictors on drinking behavior among Canadian SAs. This study compared rates of alcohol use across Canadian SAs and nonathletes and investigated whether the use of athlete-specific psychosocial predictors can improve the prediction of alcohol use outcomes in SAs. Participants (179 varsity athletes and 366 nonathletes) completed anonymous self-report questionnaires. Results suggest that Canadian athletes are at a heightened risk for experiencing alcohol-related problems compared with nonathletes, with general psychosocial predictors explaining the majority of variance in SA alcohol use. However, and quite notably, athlete-specific positive reinforcement motives predicted SA binge drinking. This research provides some of the first evidence of drinking-related problems among Canadian SAs and supports the potential use of preventative efforts to help SAs develop safe strategies for alcohol use.

OBJECTIVES The mitochondrial adenosine triphosphate-sensitive potassium channel is central to pharmacologically induced tolerance to spinal cord injury. We hypothesized that both direct and nitric oxide-dependent indirect activation of the adenosine triphosphate-sensitive potassium channel contribute to the induction of ischemic metabolic tolerance. METHODS Spinal cord injury was induced in adult male C57BL/6 mice through 7 minutes of thoracic aortic crossclamping. Pretreatment consisted of intraperitoneal injection 3 consecutive days before injury. Experimental groups were sham (no pretreatment or ischemia, n = 10), spinal cord injury control (pretreatment with normal saline, n = 27), Nicorandil 1.0 mg/kg (direct and indirect adenosine triphosphate-sensitive potassium channel opener, n = 20), Nicorandil 1 mg/kg + carboxy-PTIO 1 mg/kg (nitric oxide scavenger, n = 21), carboxy-PTIO (n = 12), diazoxide 5 mg/kg (selective direct adenosine triphosphate-sensitive potassium channel opener, n = 25), and DZ 5 mg/kg+ carboxy-PTIO 1 mg/kg, carboxy-PTIO (n = 23). Limb motor function was assessed using the Basso Mouse Score (0-9) at 12-hour intervals for 48 hours after ischemia. RESULTS Motor function was significantly preserved at all time points after ischemia in the Nicorandil pretreatment group compared with ischemic control. The addition of carboxy-PTIO partially attenuated Nicorandil's motor-preserving effect. Motor function in the Nicorandil + carboxy-PTIO group was significantly preserved compared with the spinal cord injury control group (P

Zinc doped Cerium oxide nanoparticles are prepared by a facile single step co-precipitation method. The synthesis method involves co-precipitation of the precursor salts using a non-toxic, green reagent oxalic acid, followed by annealing process at reliable low temperature. The effect of Zn doping on cerium nanoparticles are clearly investigated by the different characterization techniques such as X-Ray Diffraction, Scanning electron microscopy for morphological study, Fourier Transform Infra-Red studies to study the functional groups present and UV–Vis spectroscopy for optical study. The micro-structural and optical studies exhibit remarkable variation in the structural, optical, and morphological properties.

In this study we report a facile, cost effective one step preparation method for the synthesis of Mn doped cerium oxide (CeO2) nanoparticles (NPs) through co-precipitation technique. The synthesis was performed at relatively low temperature using a green reagent oxalic acid as reducing agent. The structural and optical attributes of the samples were characterized by X-Ray Diffraction spectroscopy (XRD), Fourier Transform Infrared Spectroscopy (FTIR), UV–Visible spectroscopy and SEM (Scanning electron microscopy). The XRD and FTIR results show the formation of Mn doped ceria NPs having a cubic fluorite structure. The morphology and chemical composition of the prepared sample was realized using SEM and EDX spectrum. The synthesized Mn doped ceria NPs shows greater absorption in the visible region and reduced particle size compared to pure ceria NPs.

The selection of the optimal cutting parameter in turning operation is very important to achieve high cutting performance. This project deals with the optimization of performance characteristics of turning EN-08, EN-36, mild steel using tungsten carbide inserts by taguchi’s approach. The experiment was performed on the basis of an L-09 orthogonal array given by taguchi’s parameter design approach. To recognize the essential factor, the design of experiment (DOE) is employed using MINITAB-19 software. The cutting parameters are varied to observe performance characteristics and find the optimal outcomes.

This paper presents an experimental investigation on the durability properties of metakaolin (MK) and bottom ash (BA) blended geopolymer under different environmental exposure. The blended geopolymer concrete (GPC) was prepared with sodium based alkaline activators under ambient curing temperature. The concentration of sodium hydroxide used was 8 M. The ratio of sodium silicate to sodium hydroxide was kept as 2.0. The performance of blended geopolymer concrete was compared with conventional concrete (CC). The test results reveal that blended geopolymer concrete develops a better performance against sulphate and acid resistance. Also, MK-BA GPC shows enhanced performance over the conventional concrete in terms of sorptivity, rapid chloride and water absorption.

Amperometric nanobiosensors are crucial time and cost effective analytical tools for the detection of a wide range of bioanalytes, viz. glucose present in complex environments at very low concentrations. Although the excellent analytical performance of nanobiosensors is undoubted, their exact molecular structure often remains unclear. Here, by combining advanced nanoanalytical approaches with theoretical modeling, we conducted a comprehensive study towards the investigation of the molecular structure of a hybrid GOx/Nafion/Pd-NPs layer deposited by electroplating from the multicomponent electrolyte solution on the surface of screen printed electrodes modified with graphene oxide. Specifically, we revealed that Pd2+ cations were adsorbed on GOx amino acid residues, forming the GOx·nPd2+ enzymatic complex. The highest adsorption energy of Pd2+ cations on GOx was found during their interaction with the side chains of basic amino acids and methionine. In addition, we showed and fully validated the end-structure of the one-step designed GOx/Nafion/Pd-NPs nanobiosensor as a structural model mainly composed of GOx and water molecules incorporated into the metal-polymer scaffold. Our approach will thus serve as a guideline for the study of molecular interactions occurring in complex systems and will contribute to the design of the next generation of hybrid nanobiosensors. The proposed mechanism, driving the self-assembly of the hybrid layer, will allow us to construct modular enzymatic nanoanalytical devices with tailored sequences in the future.

Introduction Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system involving astrocytes, B lymphocytes, anti-aquaporin 4, and such inflammatory mediators as interleukin-6. Several immunosuppressants are used in their treatment. Tocilizumab, an interleukin-6 receptor antagonist, may be a treatment option. Method We performed an observational, retrospective study analysing parameters of effectiveness (annualised relapse rate, disability, and radiological progression) and safety of tocilizumab in patients with NMOSD in whom previous immunosuppressant treatment had failed. We aimed to evaluate the effectiveness and safety of tocilizumab in clinical practice in patients with NMOSD not responding to other immunosuppressants. Results Five patients with NMOSD were analysed. Sixty percent of patients were women; mean age at diagnosis was 50±5.3 years and mean progression time was 4.5±3.6 years. Previously administered immunosuppressants were rituximab (in all 5), cyclophosphamide (2), and azathioprine (1). Mean time of exposure to tocilizumab was 2.3±1 years. Mean annualised relapse rate was 1.8±1.3 in the year prior to the introduction of tocilizumab and 0.2±0.4 the year after (P Conclusions In our experience, tocilizumab is safe and effective in patients with NMOSD showing no response to other immunosuppressants.

The grain of rye (Secale cereale L.) used for baking contains a large amount of non-starch polysaccharides, making it an excellent component of functional foods. But rye grain intended for alcohol production and forage use should have a reduced content of these polysaccharides. A comprehensive parameter that can predict the best field of application for winter rye grain is the viscosity of its wholemeal water extract. However, our understanding of the genetic background underlying this key trait and associated features of rye grain is poor. By analyzing six Russian winter rye cultivars, we identified the most contrasting forms and characterized the peculiarities of their water-soluble carbohydrates capable of influencing the viscosity of water extracts. Then, using phylogenetic and transcriptomic analyses, we identified in the rye genome many genes encoding putative glycosyltransferases and glycosylhydrolases responsible for the synthesis and degradation of arabinoxylans, mixed-linkage glucans, cellulose, and some other polysaccharides. We determined the dynamics of mRNA abundance for these genes at three stages of kernel development. Comparisons of gene expression levels in two contrasting cultivars revealed specific members of multigene families that may serve as promising targets for manipulating non-starch polysaccharide content in rye grain. High-viscosity cultivars were characterized by up-regulation of many glycosyltransferases involved in the biosynthesis of arabinoxylans and other cell-wall polysaccharides, whereas low-viscosity cultivars showed up-regulation of several genes encoding polysaccharide-degrading enzymes.

Highly accurate high-throughput experimentation (HTE) data for a set of 21 silicon-bridged C2-symmetric ansa-zirconocenes in propene homopolymerization were collected and were used to develop quant...

Background Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by deficient activity of the alpha-galactosidase A enzyme leading to progressive and multisystemic accumulation of globotriaosylceramide. Recent data point toward oxidative stress signalling which could play an important role in both pathophysiology and disease progression. Methods We have examined oxidative stress biomarkers [Advanced Oxidation Protein Products (AOPP), Ferric Reducing Antioxidant Power (FRAP), thiolic groups] in blood samples from 60 patients and 77 healthy controls. Results AOPP levels were higher in patients than in controls (p p Conclusions Oxidative stress occurs in FD in both treated and naïve patients, highlighting the need of further research in oxidative stress-targeted therapies. Furthermore, we found that oxidative stress biomarkers may represent early markers of disease in treatment-naïve patients with a potential role in helping interpretation of FD-related mutations and time to treatment decision.

Providing a good quality in higher education should be the result of the interaction between the academic team, the students and the institutional learning environment. The quality is guaranteed by the learning environment in which the content of the programs and training opportunities is appropriate for the particular purpose. Aim: To study the organization, quality, consistency and satisfaction in practical training. Materials and Methods: This article presents and analyzes the results of a survey by medical graduates about their assessment of the organization and quality of training during the undergraduate internship. Results: The results show that the practical training of medical graduates is generally at a very high level, according to the indicators, examined in our study. Conclusion: More efforts in improving quality of education are welcome.

Background The G-quadruplex-forming sequence within the KRAS proto-oncogene P1 promoter is a promising target for anticancer therapy. Porphyrin derivatives are among the most rewarding G-quadruplex binders. They can also behave as photosensitizers. Methods Three water-soluble, positively charged porphyrin-like compounds were synthesized and tested for their interaction with the KRAS G-quadruplex by circular dichroism, fluorescence, and molecular docking calculations. For a comparison of ligands binding affinity and selectivity, TMPyP4 was taken as a reference. Results One out of the three tested compounds proved biological activity and selectivity for G-quadruplex over duplex DNA. It also showed to discriminate between different G-quadruplex topologies, with a preference for the parallel over antiparallel conformation. Molecular docking studies suggested a preferential binding to the 3′-end of the KRAS G-quadruplex driven through π-π stacking interactions. Biological assays also revealed a good photodynamic-induced cytotoxicity on HeLa cells. Conclusions The reported results show that these porphyrin-like compounds could actually give the basis for the development of G-quadruplex ligands with effective photodynamic-induced cytotoxicity on cancer cells. General significance The possibility of obtaining photosensitizers with improved physico-chemical features and able to selectively target G-quadruplexes is a very interesting perspective to develop new therapeutic agents.

Objective Investigate a profile of cardiovascular disease (CVD) risk factors by sex among individuals with and without OA, and considering single and multisite joint OA. Methods Data source: Cycle-1, Comprehensive-Cohort, Canadian Longitudinal Study on Aging, a national sample of individuals aged 45-85. Systemic inflammatory/metabolic CVD risk factors collected: C-reactive protein (hsCRP), high density lipoprotein, triglycerides, total cholesterol, body mass index (BMI), systolic blood pressure, and hemoglobin A1c. Smoking history was also collected. Respondents indicated doctor-diagnosed OA in the knees, hips and/or hands, and were characterized as yes/no and single/multisite. Individuals with OA were age-sex matched to non-OA controls. Covariates: age, sex, education, income, physical activity, timed-up-and-go, comorbidities. A latent CVD risk variable was derived in females and males; standardized scores were categorized: lowest/mid-low/mid-high/highest risk. Associations with OA were quantified using ordinal logistic regressions. Results 6098 respondents (3049 with OA) had a median age of 63 years, 55.8% female. One-third of OA respondents were in the highest risk category, versus one-fifth of non-OA. Apart from BMI (the largest contributor in both sexes), hsCRP (an inflammation marker) was predominant in females, and metabolic factors and smoking in males. Overall, OA was associated with worse CVD risk quartiles compared to non-OA. OA was increasingly associated with worse CVD risk quartiles with increasing risk thresholds among females with multisite OA but not males. Conclusions Findings suggest unique CVD risks by sex/multisite subgroups, and point to a potentially important role for inflammation in OA over and above traditional CVD risk factors.

Ammonium persulfate (APS), an oxidizing agent used in hair products, manufacturing, and pool/spa water, can cause skin reactions, including allergic contact dermatitis.To characterize positive patch test reactions to APS (2.5% petrolatum).Retrospective analysis of patients tested to the North American Contact Dermatitis Group screening series from 2015 to 2018.Of 10,526 patients, 193 (1.8%) had positive patch test reactions to APS. Compared with APS-negative patients, APS-positive patients were significantly more likely to be male (43.2% vs 28.0%; P .0001); have primary hand dermatitis (30.2% vs 22.0%; P = .0064), scattered generalized dermatitis (25.5% vs 17.9%; P = .0064), or trunk dermatitis (8.9% vs 4.9%; P = .0123); and have dermatitis that is occupationally related (22.2% vs 10.9%; P .0001). More than half of the APS-positive reactions were currently relevant (57.0%); 19 (9.8%) were related to occupation, especially hairdressers (68.4%). Swimming pools/spas (23.3%) and hair care products (19.2%) were the most common sources of APS.Immediate reactions and follow-up testing were not captured.The proportion of patients positive to APS was 1.8%. APS positivity was significantly associated with male sex and hand dermatitis. Swimming pool/spa chemicals were important sources of APS exposure.

Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating renal neoplastic disorder with limited treatment options. It is characterized by the formation of large fluid-filled cysts that develop from kidney tubules through abnormal cell proliferation and cyst-filling fluid secretion driven by cAMP-dependent Cl−secretion. We have examined the effectiveness of the indazole carboxylic acid, H2-gamendazole (H2-GMZ), a derivative of lonidamine, to inhibit these processes and cyst formation usingin vitroandin vivomodels of ADPKD. H2-GMZ was effective in rapidly blocking forskolin-induced, Cl−-mediated short-circuit currents in human ADPKD cells at 1 μM and it significantly inhibited both cAMP- and EGF-induced proliferation of ADPKD cells with an IC50of 5-10 μM. Western blot analysis of H2-GMZ-treated ADPKD cells showed decreased phosphorylated ERK and hyperphosphorylated Rb levels. H2-GMZ treatment also decreased ErbB2, Akt, and Cdk4, consistent with inhibition of the chaperone Hsp90, and reduced the levels of the CFTR Cl−channel. H2-GMZ-treated ADPKD cultures contained a higher proportion of smaller cells with fewer and smaller lamellipodia and decreased cytoplasmic actin staining, and they were unable to accomplish wound closure even at low H2-GMZ concentrations, consistent with an alteration in the actin cytoskeleton and decreased cell motility. Studies using mouse metanephric organ cultures showed that H2-GMZ inhibited cAMP-stimulated cyst growth and enlargement.In vivo, H2-GMZ (20mg/kg) was effective in slowing postnatal cyst formation and kidney enlargement in thePkd1flox/flox:Pkhd1-Cremouse model. Thus, H2-GMZ treatment decreases Cl−secretion, cell proliferation, cell motility, and cyst growth. These properties, along with its reported low toxicity, suggest that H2-GMZ might be an attractive candidate for treatment of ADPKD.

Plants have a long history of use for their medicinal properties. The complexity of botanical extracts presents unique challenges and necessitates the application of innovative approaches to correctly identify and quantify bioactive compounds. For this study, we used untargeted metabolomics to explore the antimicrobial activity of Rumex crispus (yellow dock), a member of the Polygonaceae family used as an herbal remedy for bacterial infections. Ultra-performance liquid chromatography coupled with high resolution mass-spectrometry (UPLC-MS) was used to identify and quantify the known antimicrobial compound emodin. In addition, we used biochemometric approaches to integrate data measuring antimicrobial activity from R. crispus root starting material and fractions against methicillin-resistant Staphylococcus aureus (MRSA) with UPLC-MS data. Our results support the hypothesis that multiple constituents, including the anthraquinone emodin, contribute to the antimicrobial activity of R. crispus against MRSA.

The detailed experimental studies of the autothermal and steam reforming of model mixtures simulating the composition of commercial diesel fuel were carried out over Rh/Ce0.75Zr0.25O2-δ-ƞ-Al2O3/FeCrAl wire mesh honeycomb catalytic modules. The components of the diesel surrogates were n-hexadecane, o-xylene, and naphthalene as model compounds of aliphatics, mono-aromatics and diaromatics, respectively. It was shown that low reaction rate of diaromatics steam reforming facilitated increasing concentration of C1–C5 hydrocarbon by-products (primarily ethylene) in the gas phase, as well as formation of polyaromatic compounds by concurrent condensation reaction. These undesirable processes were responsible for increasing catalyst coking. Monoaromatic constituents hadn't any significant effect on the progress of undesirable side-reactions during autothermal and steam reforming of diesel surrogates.

The chemisorption of the labile dimeric platinum nitratocomplex [Pt2(μ-OH)2(NO3)8]2- onto graphene oxide doped graphitic C3N4 (g–C3N4–GO) was performed for the first time to prepare PtOx/g–C3N4–GO composites with ionic platinum species (Pt(II)) bonded with N-donor groups of the g-C3N4. The thermal treatment of the obtained composites in the hydrogen atmosphere results in a gradual reduction of Pt(II) species with the formation of Pt/g–C3N4–GO photocatalysts. The Pt/g–C3N4–GO catalysts paired with TEOA sacrificing agent in an aqueous solution were tested in a photoinduced hydrogen evolution reaction under visible light (λ = 425 nm). The photocatalytic activity of prepared materials strongly influenced by the temperature of the reduction stage so that the maximal rate of H2 evolution was revealed for the catalyst (0.5 wt% of Pt) reduced at 400 °C with a quantum efficiency of 3.0% and rate of HER of 5.1 mmol h−1 per 1 g of photocatalysts. The photocatalytic activity of this sample was much higher than the activity of 0.5% Pt/g–C3N4–GO photocatalysts prepared by conventional photoreduction of H2PtCl6 or reduction of this precursor with NaBH4. The Pt/g–C3N4–GO photocatalyst with Pt concentration of 0.1 wt% was prepared using the described protocol and shown specific activity of about 1.4 mol h−1 per 1 g of Pt outperforming analogous material reported to date.

Background:: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a β- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach. Methods:: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50 fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was evaluated in human plasma. Results:: The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma. Conclusions:: The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for β- radio-guided surgery.

Antisense gapmer oligonucleotides containing phosphoryl guanidine (PG) groups, e.g., 1,3-dimethylimidazolidin-2-imine, at three to five internucleotidic positions adjacent to the 3′ and 5′ ends were prepared via the Staudinger chemistry, which is compatible with conditions of standard automated solid-phase phosphoramidite synthesis for phosphodiester and, notably, phosphorothioate linkages, and allows one to design a variety of gapmeric structures with alternating linkages, and deoxyribose or 2′-O-methylribose backbone. PG modifications increased nuclease resistance in serum-containing medium for more than 21 days. Replacing two internucleotidic phosphates by PG groups in phosphorothioate-modified oligonucleotides did not decrease their cellular uptake in the absence of lipid carriers. Increasing the number of PG groups from two to seven per oligonucleotide reduced their ability to enter the cells in the carrier-free mode. Cationic liposomes provided similar delivery efficiency of both partially PG-modified and unmodified oligonucleotides. PG-gapmers were designed containing three to four PG groups at both wings and a central “window” of seven deoxynucleotides with either phosphodiester or phosphorothioate linkages targeted to MDR1 mRNA providing multiple drug resistance of tumor cells. Gapmers efficiently silenced MDR1 mRNA and restored the sensitivity of tumor cells to chemotherapeutics. Thus, PG-gapmers can be considered as novel, promising types of antisense oligonucleotides for targeting biologically relevant RNAs., Graphical abstract, Many successful antisense oligonucleotide designs are gapmers, which contain a central section of DNA phosphorothioates flanked by RNA-like nucleotides. We describe a new type of gapmers with phosphoryl guanidine groups in the flanks, which efficiently silenced MDR1 gene expression and restored the sensitivity of drug-resistant tumor cells to conventional chemotherapy.

The use of glassceramics in photocatalysis is an attractive option for the realization of smart optical fibers and self-cleaning windows. Here we present the photocatalytic activity of germanosilicate glasses embedding Ga2O3 nanocrystals prepared by batch melting and glass heat treatment. The powdered material is used for UV-assisted degradation of rhodamine in water. The kinetics show changes after repeated experiments. In the first cycle, the apparent rate is governed by a second-order reaction with a Gaussian-like shape, whereas the second cycle follows a first-order reaction. The modification appears to be correlated with perturbations in the defect population. Photoluminescence has been used to monitor the evolution of such defects. Kinetic data on photoreactions and defect formation have been modelled in a combined frame in which the defect concentration determines the photocatalytic activity. The results prove the photocatalytic ability of the studied glassceramics. Moreover, the general validity of the kinetic model can be of interest for other systems in which the photocatalytic response depends on photoreactive species concentration.

Currently, alpha-emitting radionuclide 225Ac is one of the most promising isotopes in alpha therapy due to its high linear energy transfer during four sequential alpha decays. However, the main obstacle preventing the full introduction of 225Ac into clinical practice is the lack of stable retention of radionuclides, leading to free circulation of toxic isotopes in the body. In this work, the surface of silica nanoparticles (SiO2 NPs) has been modified with metallic shells composed of titanium dioxide (TiO2) and gold (Au) nanostructures to improve the retention of 225Ac and its decay products within the developed nanocarriers. In vitro and in vivo studies in healthy mice show that the metallic surface coating of SiO2 NPs promotes an enhanced sequestering of radionuclides (225Ac and its daughter isotopes) compared to non-modified SiO2 NPs for a prolonged period of time. Histological analysis reveals that for the period of 3-10 d after the injections, the developed nanocarriers have no significant toxic effects in mice. At the same time, almost no accumulation of leaked radionuclides can be detected in non-target organs (e.g., in the kidneys). In contrast, non-modified carriers (SiO2 NPs) demonstrate the release of free radionuclides, which are distributed over the whole animal body with the consequent morphological changes in the lung, liver and kidney tissues. These results highlight the potential of the developed nanocarriers to be utilized as radionuclide delivery systems and offer an insight into design rules for the fabrication of new nanotherapeutic agents.

Study Objective To compare the recurrence rate, post-treatment American Fertility Society (AFS) score, ongoing pregnancy rate, and endometrial thickness of 3 secondary prevention therapies in preventing recurrent intrauterine adhesions (IUAs) and increasing pregnancy rates in infertile women after hysteroscopic adhesiolysis. Design A retrospective study. Setting A private fertility hospital. Patients A total of 200 consecutive infertile women, with the desire to have a baby and were diagnosed as having IUAs detected by hysterosalpingogram, who underwent hysteroscopic adhesiolysis for IUAs from January, 2018 to May, 2020. Interventions Women who underwent hysteroscopic adhesiolysis received hormone therapy, and one of the 3 secondary preventions: hyaluronic acid (HA) gel alone, intrauterine devices (IUDs) alone, or HA gel + IUD. Measurements and Main Results Of the 200 women included in the final analysis, 121 received HA alone, 59 were treated with IUD alone, and 20 received HA gel + IUD combination. The mean post-treatment AFS score for IUAs was significantly lower in the HA gel + IUD group than the HA alone or the IUD alone groups (adjusted p = .01 and p = .02, respectively). Multivariable analysis revealed a significantly lower recurrence rate in the women after treatment with HA gel + IUD than HA alone (adjusted odds ratio, 0.19; 95% credible interval [CreI], 0.03–0.88). Women treated with HA gel + IUD also had reduced post-treatment AFS scores compared with HA alone (β coefficients, −0.83; 95% CreI, −1.64 to −0.01). For ongoing pregnancy rates after in vitro fertilization, the adjusted odds ratio for HA gel + IUD vs HA alone was 2.03 (95% CreI, 0.44–11.00) and for IUD alone vs HA alone was 1.13 (95% CreI, 0.41–3.29), indicating nonsignificant differences. There were no differences observed in endometrial thickness on the day of embryo transfer among the 3 groups. Conclusion The investigation of the primary outcome in reducing the recurrence rate IUA after treatment demonstrated that a combination of HA gel + IUD provides greater prevention of recurrent IUAs and may decrease post-treatment AFS scores for infertile women undergoing hysteroscopic adhesiolysis. However, for the secondary outcome of increasing pregnancy rates, there was no improvement in the ongoing pregnancy rates after in vitro fertilization.

Supplemental Digital Content is available in the text., Background: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. Methods: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases–based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Results: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). Conclusions: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.

The growing demand on energy storage devices and environmental issues has enhanced the curiosity for metal oxide/porous carbon composite owing to its intriguing properties. Nano metal oxides undergo aggregation at high temperature. To overcome the issues, the studies on nano metal oxides incorporated into the porous carbon matrix are carried out. This review article discuss about the various synthetic strategies of metal oxide/porous carbon composite and their applications towards the environmental, energy devices, catalyst, sensors, etc. In particular the porosity of the carbon with respect to the physiochemical properties of metal oxide/porous carbon composite are discussed and reported. The future trends and development on the nano metal oxide/porous carbon composite and its applications in various fields are discussed.

In modern chemical and biochemical studies, special attention is paid to molecular systems capable of generating nitric oxide (NO), which is one of the most important signalling molecules in the body and can trigger a whole cascade of reactions. Despite the importance of this molecule, the mechanisms of its formation in living organisms remain a subject of debate. This review combines the most important methods of releasing NO from endogenous and exogenous sources. The history of endogenous NO donors dates back more than 150 years, since the synthesis of nitroglycerin, which remains the standard vasodilator today, even though it is known that it and many other similar compounds lead to the development of a nitrate tolerance. Particular awareness is devoted to the mechanisms of NO formation without the participation of enzymes, since these methods are most important for creating exogenous sources of NO as drugs. The study of NO formation methods is centred on both the creation of new NO donors and understanding the mechanisms of tolerance to them.

A gamma-pyrone derivative, comenic acid, activates the opioid-like receptor-mediated signaling pathway that modulates the NaV1.8 channels in the primary sensory neuron membrane. These channels are responsible for the generation of the nociceptive signal; therefore, gamma-pyrones have great therapeutic potential as analgesics, and this effect deserves a deeper understanding. The novelty of our approach to the design of a medicinal substance is based on a combination of the data obtained from living neurons using very sensitive physiological methods and the results of quantum chemical calculations. This approach allows the correlation of the molecular structure of gamma-pyrones with their ability to evoke a physiological response of the neuron. Comenic acid can bind to two calcium cations. One of them is chelated by the carbonyl and hydroxyl functional groups, while the other forms a salt bond with the carboxylate anion. Calcium-bound gamma-pyrones have fundamentally different electrostatic properties from free gamma-pyrone molecules. These two calcium ions are key elements involved in ligand-receptor binding. It is very likely that ion-ionic interactions between these cations and anionic functional groups of the opioid-like receptor activate the latter. The calculated intercationic distance of 9.5 Å is a structural criterion for effective ligand-receptor binding of calcium-bound gamma-pyrones.

Previously we have shown that lactoferrin (LTF), a protein of secondary neutrophilic granules, can be efficiently modified by hypohalous acids (HOCl and HOBr), which are produced at high concentrations during inflammation and oxidative/halogenative stress by myeloperoxidase, an enzyme of azurophilic neutrophilic granules. Here we compared the effects of recombinant human lactoferrin (rhLTF) and its halogenated derivatives (rhLTF-Cl and rhLTF-Br) on functional responses of neutrophils. Our results demonstrated that after halogenative modification, rhLTF lost its ability to induce mobilization of intracellular calcium, actin cytoskeleton reorganization, and morphological changes in human neutrophils. Moreover, both forms of the halogenated rhLTF prevented binding of N-acetylglucosamine-specific plant lectin Triticum vulgaris agglutinin (WGA) to neutrophils and, in contrast to native rhLTF, inhibited respiratory burst of neutrophils induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine and by two plant lectins (WGA and PHA-L). However, we observed no differences between the effects of rhLTF, rhLTF-Cl, and rhLTF-Br on respiratory burst of neutrophils induced by phorbol 12-myristate 13-acetate (PMA), digitonin, and number of plant lectins with different glycan-binding specificity. Furthermore, all rhLTF forms interfered with PMA- and ionomycin-induced formation of neutrophil extracellular traps. Thus, halogenative modification of LTF is one of the mechanisms involved in modulating a variety of signaling pathways in neutrophils to control their pro-inflammatory activity.

It is well known that water significantly lowers mantle solidi. But it turns out this paradigm is not always true. Here, we studied the interaction of K-rich carbonate melts with the natural garnet lherzolite from the Udachnaya kimberlite (Russia) in the presence of water at 3.0–6.5 GPa, corresponding to depths of 100–200 km. We found that at ≤ 1100 °C, the metasomatic interaction consumes garnet, orthopyroxene, and melt to produce phlogopite ± K-richterite + magnesite ± dolomite. Besides, primary clinopyroxene is replaced by one with a lower amount of jadeite component. Thus, the addition of water to the K-rich carbonate melt, infiltrating the subcontinental lithospheric mantle, should yield its partial or complete disappearance accompanied by phlogopitization and carbonation. The studied systems have H2O/K2O = 2, like that in phlogopite, and therefore correspond to carbonated phlogopite peridotite under fluid-absent conditions. At 4.0–6.5 GPa, the solidus of carbonated phlogopite peridotite is controlled by the following reaction: phlogopite + clinopyroxene + magnesite = garnet + orthopyroxene + olivine + hydrous K-carbonatite melt, which is bracketed between 1100 and 1200 °C. At 3 GPa, the solidus temperature decreases to about 1050 °C presumably owing to the Ca-Mg exchange reaction, clinopyroxene + magnesite = orthopyroxene + dolomite, which stabilizes dolomite reacting with phlogopite at a lower temperature than magnesite. Our results suggest that the phlogopite- and carbonate-rich metasomatic vein networks, weakening rigid lithosphere and promoting continental rifting, could be formed as a result of infiltration of hydrous K-carbonatite melt at the base of subcontinental lithospheric mantle. Stretching and thinning of the cratonic lithosphere make geotherms warmer and shifts their intersections with the solidus of carbonated phlogopite peridotite to shallower depths. Consequently, the successive erosion of the continental lithosphere and ascent of the lithosphere-asthenosphere boundary during continental rifting should be accompanied by remelting of phlogopite-carbonate metasomes, upward percolation of K-rich melt, and its solidification at the front of the magmatic-metasomatic mantle system.

Hydroxyapatite (HAP) [Ca10(PO4)6(OH)2] is an excellent bio-ceramic material for artificial bone substitution in biomedical field owing to its chemical and crystallographic similarities of natural bone and teeth. In this research work, we have attempted the synthesis of hydroxyapatite powders with controllable size in the presence of three different surfactants sodium dodecyl sulphate (SDS) which is an anionic surfactant, cetyl trimethylammonium bromide (CTAB) as a cationic surfactant and poly vinyl alcohol (PVA) as a non-ionic surfactant. The as-synthesised HAP powders were characterised by analytical techniques such as FTIR, XRD and SEM. The results have shown that the non-ionic surfactant is a better choice for developing this bio-nanomaterial due to its good dispersing power than CTAB and SDS. The results have also indicated that, nano-hydroxyapatite particle has a uniform morphology, well crystallinity and the particle size was controlled with the use of non-ionic surfactant. The crystallite size was calculated using Scherer’s formula. Experiments were performed under controlled environment by maintaining the required pH, concentration and temperature. The biomedical application studies of the as-synthesised material are yet to be studied.

Human serum albumin (HSA) is a very well-characterized protein, which has already been used for many biocompatible coatings. We hypothesized binding between HSA and magnetic iron oxide nanoparticles (MNPs) as well as HSA coating stability to be pH- and ionic strength-dependent. The impact of phosphate buffer on protein coating was studied at varying pH (6.0, 6.6, and 7.5) and ionic strengths (0.15 and 0.30 M NaCl) using different physicochemical methods. In addition, the stability of HSA coatings on MNPs was studied by means of UV/visible spectrophotometry, dynamic light scattering, and electron magnetic resonance. We used differential scanning calorimetry (DSC) to determine the differences in the change of enthalpies and denaturation temperatures of HSA in various buffer conditions and on the surface of the particles. The binding thermodynamics of HSA and MNPs were determined by isothermal titration calorimetry (ITC), and it was also dependent on pH and ionic strength. The stability of adsorbed layer on MNPs decreases with increasing pH [from weakly acidic (pH 6.0-6.6) to slightly alkaline (pH 7.5)], as well as with an increase of ionic strength. This study develops stable HSA coating on MNPs which might be applied to a wide range of biomedical applications.

The fracture response and resistance to chloride penetration of concrete reinforced with discrete steel fibers (SF) and hybrid blend of steel and macro polypropylene fibers (HyFRC) are evaluated. A significant improvement in fracture response is obtained in HyFRC compared to SF. Cohesive stress-crack opening (σ-w) relationships are obtained for the concrete with and without discrete reinforcement from the measured fracture test responses. The hybrid fiber blend has a higher tensile strength and a significantly higher stress resistance to crack opening when compared to an identical volume fraction of steel fibers. HyFRC also exhibit a lower chloride penetration when compared to control and SF concrete mixtures. The hybrid blend of steel and polypropylene fibers provides improved structural performance due to enhanced resistance to crack opening and an improvement in the durability by reducing the chloride penetration in concrete.

The synergetic effect between algae biomass in co-pyrolysis with synthetic plastics (polypropylene (PP), polyethylene (PE), and expanded polystyrene (EPS)) was investigated in this work. Individual feedstock pyrolysis and co-pyrolysis of algae with PP, PE, and EPS were conducted at a constant supply of microwave energy (420 J/s). Pyrolysis char was used as a susceptor in all the experiments. The average heating rate was varied in the range of ∼50–60 °C/min for achieving the final pyrolysis temperature of 600 °C. In catalytic co-pyrolysis, the ZSM-5 catalyst was used for upgrading the physicochemical properties of pyrolysis oil. The use of catalyst promoted the excessive cracking of biomass in co-pyrolysis, leading to higher gas and coke residue comparatively. The viscosity, density, and flash point of oil obtained in catalytic co-pyrolysis were significantly reduced. While the oil obtained from individual pyrolysis of algae is rich in phenolic derivatives, and that of PP, PE has aliphatic hydrocarbons, and EPS has monoaromatic hydrocarbons as major compounds. The synergistic role of plastic and biomass in co-pyrolysis was observed in the formation of products and oil composition. The bio-oil from catalytic co-pyrolysis is composed of aliphatic oxygenates, aliphatic hydrocarbons, cyclic aliphatic hydrocarbons, and phenolics. The chemicals and hydrocarbons present in the oil have a carbon number in the range of C6 to C30. An increase in carbon and hydrogen elemental composition was observed in bio-oil obtained from co-pyrolysis.

Obviously, the moment has come in agriculture and forestry when we must decide to gradually abandon (where possible) non-selectively acting chemical insecticides, taking into consideration the overall decrease in the total biomass of insects, especially pollinators, and the increased number of diseases and human deaths directly or indirectly associated with chemical insecticides. Yet with the world facing the rapid growth of human populations, the annual reduction of cultivated areas, and substantial losses from insect pests, most experts believe that no serious alternative to chemical insecticides exists. However, there is definitely room to create more well-tailored chemical insecticides. And there is hope, in the form of effective DNA insecticides able to provide an adequate level of safety for non-target organisms. In this short communication describing experiments carried out on the larvae of Ceroplastes japonicus Green (feeding on Ilex aquifolium Linnaeus), we show for the first time the enormous potential for the use of DNA insecticides in the control of soft scale insects and how they could replace non-selective organophosphate insecticides.

The objective of this study was to evaluate the properties of garlic as a growth promoter in larvae of angelfish Pterophyllum scalare and its benefits during transport of juveniles of this species. The experiment was conducted in recirculation aquaculture system, consisting of 20 tanks of 40 L equipped with independent water input and output. We used 1,400 larvae distributed among five treatments, with four repetitions, which totaled 20 experimental units. The treatments were 0, 50, 100, 200, and 400 mg of garlic extract per kilo of feed. The results showed that the inclusion of levels of garlic extract in the feed did not significantly effect the fish’s development or their transport. Neither did the inclusion of levels of garlic extract affect the survival of the larvae during the trial period. New research with extracts of higher dosages should be performed to elucidate the effect of garlic extract as a growth promoter.

Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as “pitó”. This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O-β-D-(6”-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential. Resumo O tilirosídeo é um flavonóide glicosídico presente em muitas espécies de plantas, incluindo Helicteres velutina K. Schum (Malvaceae sensu lato), conhecida no Brasil como “pitó”. Esta molécula mostrou ter muitas atividades biológicas, porém nenhum estudo foi realizado para investigar a toxicidade dessa substância. O presente trabalho teve como objetivo avaliar a possível toxicidade celular in silico, in vitro e ex-vivo do kaempferol-3-O-β-D- (6 ”-Ep-coumaroil) glucopiranosídeo (tilirosídeo), por meio de análises de estrutura química, toxicidade avaliação e propriedades bioativas preditivas, utilizando amostras humanas para testes in vitro e ex-vivo. A análise in silico sugere que o tilirosídeo exibe bom índice de absorção para penetrar nas membranas biológicas. Além disso, apresentou considerável potencial de proteção celular contra os radicais livres e com atividades anticarcinogênica, antioxidante, antineoplásica, antiinflamatória, anti-hemorrágica e antitrombótica. A avaliação dos efeitos hemolíticos e genotóxicos do tilirosídeo mostrou baixas taxas de hemólise nas hemácias e ausência de toxicidade em células da mucosa oral. Os dados obtidos indicam que esta molécula pode possuir uma abordagem terapêutica promissora como uma possível nova droga com potencial biotecnológico.

Nanoarchitectural strategy for design of highly active catalysts with CoMoS encased in 50-nm diameter aluminosilicate tubes (halloysite nanoclay) serving as an abundantly available natural support was proposed. This encapsulation conception implies the protection of active metal sulfides from aggregation, coking and leaching. Synthesized nanocatalytic system was investigated by TEM, XPS, N2 adsorption, hydrogen temperature programmed reduction and desorption of ammonia techniques. Using of Mo-heteropolyacid anionic precursor complex (ca. 10 wt%) possess selective loading of molybdenum oxide into 15-nm diameter inner cavity of the nanotubes (covered with positively charged alumina) by an electrostatic attraction. Subsequent sulfidation results in formation of CoMoS particulate core inside the aluminosilicate shell. These tubular nanoreactors were pelletized using alumina binder to produce a mechanically strong mesoporous catalyst efficient for hydrotreatment of diesel petroleum fraction to clean fuels.

A modified technique for the growth of silicon carbide from silicon by the method of self-consistent substitution of atoms is proposed, which makes it possible to increase the achievable thickness of the formed silicon carbide layer by about an order of magnitude. The technique includes an additional step before the growth process: the surface of the silicon substrate is being saturated with vacancies by annealing in vacuum at T = 1350 ℃ for ~ 30 min. This leads to a change in the mechanism of mass transfer from the interstitial to the vacancy one when silicon atoms are being substituted by carbon atoms. As a result, not only the thickness of the silicon carbide layer increases, but also the separation of silicon carbide from the silicon substrate occurs if the thickness of the SiC layer surpasses 400 nm.

A series of 13 novel cinnamamide-chalcone derivatives (2a-2m) were synthesized and evaluated for their antiproliferative activity against MCF-7, K562, U373MG, and HT-29 cell lines by SRB assay. Considering the activities on MCF-7 cell line, eight compounds were tested for the in-vitro CDK2 inhibition and four (2g, 2h, 2k and 2l) were found to possess good activity (IC5050 values. The most active compounds on CDK2 when docked in EGFR had lower docking scores. Only one compound interacts with Lys721 (β-3 region) and Met769 (hinge region). The stability of interactions with CDK2 was assessed for 2k and 2l by molecular dynamics simulation using Desmond software. In conclusion, three compounds possess excellent activity against MCF-7 cell line and good activity against CDK2.

The purpose of this study was to evaluate gender-specific differences in prevalence and risk factors for alcohol, tobacco, and marijuana use among 50- to 65-year-old Jamaicans. We performed secondary analysis of the 2016 Jamaica National Drug Use Prevalence Survey. The dependent variables were self-reported use of tobacco, alcohol, and marijuana in the 30 days before the survey. The independent variables included general, socioeconomic, and community characteristics and concomitant substance use. Gender-stratified multiple Poisson regressions were conducted. The survey included 1,099 individuals aged 50-65 years; 50.3% were men. Reported use was significantly higher in men than in women: alcohol (54.9% vs. 17.8%), marijuana (22.4% vs. 2.2%), and tobacco (19.2% vs. 3.9%). High income was associated with alcohol use in women, whereas low and middle incomes were associated with marijuana use among men. Being employed was associated with tobacco use among women and with alcohol use among men. Rural residence was associated with alcohol use in women and with marijuana use in men. High neighborhood disorder was associated with tobacco use in women and alcohol and marijuana use in men. Concomitant substance use increased the likelihood of alcohol, tobacco, and marijuana use in men and women. We conclude that gender-sensitive strategies to substance use prevention and treatment are needed in Jamaica.