Liquid Phase Hydrogenation of Pharmaceutical Interest Nitroarenes over Gold-Supported Alumina Nanowires Catalysts

In this work, Au nanoparticles, supported in Al2O3 nanowires (ANW) modified with (3-aminopropyl)trimethoxysilane were synthetized, for their use as catalysts in the hydrogenation reaction of 4-(2-fluoro-4-nitrophenyl)-morpholine and 4-(4-nitrophenyl)morpholin-3-one. ANW was obtained by hydrothermal techniques and the metal was incorporated by the reduction of the precursor with NaBH4 posterior to superficial modification. The catalysts were prepared at different metal loadings and were characterized by different techniques. The characterization revealed structured materials in the form of nanowires and a successful superficial modification. All catalysts show that Au is in a reduced state and the shape of the nanoparticles is spherical, with high metal dispersion and size distributions from 3.7 to 4.6 nm. The different systems supported in modified-ANW were active and selective in the hydrogenation reaction of both substrates, finding for all catalytic systems a selectivity of almost 100% to the aromatic amine. Catalytic data showed pseudo first-order kinetics with respect to the substrate for all experimental conditions used in this work. The solvent plays an important role in the activity and selectivity of the catalyst, where the highest efficiency and operational stability was achieved when ethanol was used as the solventIndexación: Scopu

Nanocatalizadores metálicos soportados en estructuras 0d y 1d con aplicaciones en química fina

El desafío actual en el diseño racional de catalizadores aplicados en la producción de compuestos químicos de alto valor agregado radica en la preparación de sistemas que sean capaces de operar en ciclos catalíticos consecutivos manteniendo una alta actividad y selectividad en la producción del compuesto de interés.Centro de Investigación y Desarrollo en Ciencias Aplicada

Nanocatalizadores metálicos soportados en estructuras 0d y 1d con aplicaciones en química fina

El desafío actual en el diseño racional de catalizadores aplicados en la producción de compuestos químicos de alto valor agregado radica en la preparación de sistemas que sean capaces de operar en ciclos catalíticos consecutivos manteniendo una alta actividad y selectividad en la producción del compuesto de interés.Centro de Investigación y Desarrollo en Ciencias Aplicada

Catalytic pyrolysis of used tires on noble-metal-based catalysts to obtain high-value chemicals: Reaction pathways

A systematic study on the use of noble metals (Pd, Pt, Au) supported on titanate nanotubes (NT-Ti) for selectively producing BTX and p-cymene from waste tire pyrolysis is provided here. All the materials were characterized for chemical, textural and structural properties using a range of analytical techniques. The M/NT-Ti (M: Pd, Pt, or Au) catalysts exhibit low nanoparticle sizes (1.8 Pt ≈ Au > support > non-catalyst. The Py-GC/MS suggest that the catalysts participate in the secondary reactions of dealkylation, dehydrogenation, isomerization, aromatization, and cyclization leading to a higher formation of BTX than the uncatalyzed reaction. Finally, a comprehensive reaction pathway describing the catalytic pyrolysis of WT over Pd/NT-Ti was proposed by studying the catalytic pyrolysis of individual polymers constituting the waste tires, and D,L-Limonene.Puede accederse a los datos primarios de este trabajo haciendo clic en "Documentos relacionados".Centro de Investigación y Desarrollo en Ciencias Aplicada

Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis

Objectives: Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage. Methods: HK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry. RA FLS were transfected with either HK1 or HK2 siRNA, or infected with either adenovirus (ad)-GFP, ad-HK1 or ad-HK2. FLS migration and invasion were assessed. To study the role of HK2 in vivo, 108 particles of ad-HK2 or ad-GFP were injected into the knee of wild-type mice. K/BxN serum transfer arthritis was induced in HK2F/F mice harbouring Col1a1-Cre (HK2Col1), to delete HK2 in non-haematopoietic cells. Results: HK2 is particular of RA histopathology (9/9 RA; 1/8 OA) and colocalises with FLS markers. Silencing HK2 in RA FLS resulted in a less invasive and migratory phenotype. Consistently, overexpression of HK2 resulted in an increased ability to migrate and invade. It also increased extracellular lactate production. Intra-articular injection of ad-HK2 in normal knees dramatically increased synovial lining thickness, FLS activation and proliferation. HK2 was highly expressed in the synovial lining after K/BxN serum transfer arthritis. HK2Col1 mice significantly showed decreased arthritis severity, bone and cartilage damage. Conclusion: HK2 is specifically expressed in RA synovial lining and regulates FLS aggressive functions. HK2 might be an attractive selective metabolic target safer than global glycolysis for RA treatment

Phylogeographic pattern and extensive mitochondrial DNA divergence disclose a species complex within the Chagas disease vector Triatoma dimidiata.

ABSTARCT: Previous studies have shown that "bioequivalent" generic products of vancomycin are less effective in vivo against Staphylococcus aureus than the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assess in vivo the impact of exposure to innovator and generic products of vancomycin on S. aureus susceptibility. A clinical methicillin-resistant S. aureus (MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ∼7.0 log(10) CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than S. aureus ATCC 29213 but without vancomycin-intermediate S. aureus (VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin

The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but tumor necrosis factor receptor-mediated nuclear factor kappa B signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts, but not leukocytes, facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor alpha-toxin. Naturally elicited antibodies against alpha-toxin contribute to incomplete clinical penetrance. Human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease by disrupting cell-intrinsic immunity to alpha-toxin in nonleukocytic cells.Peer reviewe

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality