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BACKGROUND Coffee consumption is associated with a reduced risk of several chronic diseases in a dose-dependent manner. Chronic intake results in the transient appearance of bioactive phenolic metabolites in the circulatory system. However, there is a lack of information on the impact of different patterns of coffee consumption on plasma and urinary profiles of phenolic metabolites. OBJECTIVES Plasma and urinary phenolic metabolites were investigated following regular consumption of different daily dosages of coffee or cocoa-based products containing coffee (CBPCC) under a real-life setting. METHODS A repeated-dose, randomized, crossover human intervention was conducted with 21 healthy volunteers. For 1 mo, participants consumed 1) 1 cup of coffee (1C), 2) 3 cups of coffee (3C), or 3) 1 cup of coffee + 2 CBPCC twice daily (PC). Plasma and urine samples were collected over a 24-h period after each treatment. The nutrikinetics and urinary excretion of native, human phase II, and colonic metabolites were assessed. RESULTS A total of 51 (poly)phenolic metabolites were quantified, with 41 metabolites being strictly related to coffee consumption. Significant differences were observed among treatments for most of the metabolites. The metabolites present in the highest amounts were the hydroxycinnamate, phenylpropanoic acid, benzaldehyde, and benzene classes, along with (-)-epicatechin and phenyl-γ-valerolactone derivatives after PC treatment. Daily average concentrations did not exceed 200 nmol/L and were

The reaction of excited nitrogen atoms N(2D) with CH3CCH (methylacetylene) was investigated under single-collision conditions by the crossed molecular beams (CMB) scattering method with mass spectrometric detection and time-of-flight analysis at the collision energy (Ec) of 31.0 kJ/mol. Synergistic electronic structure calculations of the doublet potential energy surface (PES) were performed to assist the interpretation of the experimental results and characterize the overall reaction micromechanism. Theoretically, the reaction is found to proceed via a barrierless addition of N(2D) to the carbon–carbon triple bond of CH3CCH and an insertion of N(2D) into the CH bond of the methyl group, followed by the formation of cyclic and linear intermediates that can undergo H, CH3, and C2H elimination or isomerize to other intermediates before unimolecularly decaying to a variety of products. Kinetic calculations for addition and insertion mechanisms and statistical (Rice-Ramsperger-Kassel-Marcus) computations of product branching fractions (BFs) on the theoretical PES were performed at different values of total energy, including the one corresponding to the temperature (175 K) of Titan’s stratosphere and that of the CMB experiment. Up to 14 competing product channels were statistically predicted, with the main ones, at Ec = 31.0 kJ/mol, being the formation of CH2NH (methanimine) + C2H (ethylidyne) (BF = 0.41), c-C(N)CH + CH3 (BF = 0.32), CH2CHCN (acrylonitrile) + H (BF = 0.12), and c-CH2C(N)CH + H (BF = 0.04). Of the 14 possible channels, seven correspond to H displacement channels of different exothermicity, for a total H channel BF of ∼0.25 at Ec = 31.0 kJ/mol. Experimentally, dynamical information could only be obtained about the overall H channels. In particular, the experiment corroborates the formation of acrylonitrile + H, which is the most exothermic of all 14 reaction channels and is theoretically calculated to be the dominant H-forming channel (BF = 0.12). The products containing a novel C–N bond could be potential precursors to form other nitriles (C2N2, C3N) or more complex organic species containing N atoms in planetary atmospheres, such as those of Titan and Pluto. Overall, the results are expected to have a potentially significant impact on the understanding of the gas-phase chemistry of Titan’s atmosphere and the modeling of that atmosphere.

In this review, the main technological processes involved in the production of color in glasses, ceramics and pigments are reported. Iron (as oxides or dispersed ion) is the main responsible of the color in archeological and historical ceramics and glasses, but other d-metals can be also found (Cu, Ag, Co, Cr, Ni) as nano-particles or dispersed ions. The final coloration is usually a result of the sapient choice of raw materials and firing conditions (temperature, atmosphere). Some pigments are chosen to represent the different, often sophisticated, chemical processes that have been used during the history to produce them: solid state reaction (Egyptian and Chinese Blue, Naples Yellow, Ultramarine Blue), host-guest complexation (Maya Blue), corrosion/redox processes (Lead White, Verdigris), wet/solution synthesis (Prussian Blue, Cadmium Yellow). In addition, a brief overview on the vast production of modern compounds (inorganic and mostly organic) is given. This review shows how behind the artistic choice and way of expression lies a high level of technological skill and chemical knowledge achieved/reached by (ancient) craftsmen to obtain the desired colors.

In this work, we demonstrate a facile synthesis of UiO-66-NH2 metal-organic framework (MOF)/oxidized single-walled carbon nanotubes (ox-SWCNTs) composite at room temperature. Acetic acid (HAc) was used as a modulator to manipulate the morphology of the MOF in these composites. With a zirconium oxide cluster (Zr) to 2-aminoteraphthalate linker (ATA) 1:1.42 ratio and acetic acid modulator, we achieved predominately heterogeneous MOF growth on the sidewalls of CNTs. Understanding the growth mechanism of these composites was facilitated by conducting DFT calculations to investigate the interactions between ox-SWCNTs and the MOF precursors. The synthesized composites combine both microporosity of the MOF and electrical conductivity of the SWCNTs. Gas sensing tests demonstrated higher response for UiO-66-NH2/ox-SWCNT hybrid toward dry air saturated with dimethyl methylphosphonate (DMMP) vapor compared to oxidized single-walled carbon nanotubes (ox-SWCNTs) alone.

Lotic and lentic ecosystems are traditionally viewed as dominated by either benthic or water column processes. However, mid-sized rivers represent a transition zone where both benthic and water column processes may both contribute substantially to ecosystem dynamics. Ecosystem processes such as gross primary production (GPP), ecosystem respiration (ER), or nutrient uptake, and the relative contribution of the water column to these processes at the reach scale, are poorly understood in non-wadeable, mid-sized rivers. To clarify the role of the water column at the reach-scale, and to quantify controls on water column processes, we measured GPP, ER, and uptake of nitrate (NO3−), ammonium (NH4+), and soluble reactive phosphorus (SRP) in the water columns of 15 mid-sized rivers (discharge: 13.5–83.3 m3 s−1) spanning nutrient and total suspended solids gradients. We compared water column metabolic and nutrient uptake rates to reach-scale rates to estimate the contribution of the water column to the entire river. Water column metabolism was autotrophic on the day when measured, GPP increased with nutrient availability, and the water column contributed more to whole river GPP than to ER. Water column nutrient uptake increased with GPP across solutes, and there was a positive relationship between human land use and water column uptake of NO3−–N and SRP. The water column accounted for a substantial proportion of reach-scale metabolism and nutrient uptake, but this contribution depended on suspended material and nutrient availability. Integrating the water column into theory describing lotic ecosystem function should clarify mechanisms controlling metabolism and nutrient processing and enhance management of non-wadeable rivers.

Methylene blue (MB) is one of the dyes used often by the textile industry. Therefore, MB residual is contained in the textile industry waste. MB can irritate, leading to permanent eye and animal injuries; therefore, the textile industry waste concentration must be degraded before disposed to the environment. MB residual in textile industry waste can be treated with activated carbon adsorption. However, the adsorption method is less effective because the deposition takes a long time. This research aims to make activated carbon composites from banana peels and magnesium ferrite (BPAC/MgFe2O4) using the coprecipitation method to obtain activated carbon with magnetic properties (magnetic adsorbent). The obtained composite was characterized using X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM), Energy Dispersive X-Ray (EDX), and Surface Area Analyzer. The adsorption performance of methylene blue on composites was evaluated with variations in pH, concentration, contact time, determination of adsorption isotherms, and kinetics of adsorption. XRD analysis results showed the composite has a cubic crystal structure with a crystallite size of 7.69 nm. SEM analysis results show the surface morphology has pores with irregular shapes. EDX analysis results showed that the composition of activated carbon composite was 65.56% carbon, 2.28% Mg, 5.50% Fe, and 26.66% O. The results surface area analysis showed a composite surface area of 88.134 m2/g. Composite adsorption performance showed maximum results at pH 7, variations in concentration at 10 ppm, and contact time 180 minutes with adsorption capability of 99.26%. Determination of the adsorption isotherm follows the Freundlich adsorption isotherm model with a pseudo-second-order adsorption kinetics model. The obtained BPAC/MgFe2O4 composite can potentially be a magnetic adsorbent capable of adsorbing methylene blue in an aqueous solution.

Highly porous zirconium-based metal–organic frameworks (MOFs) have been widely studied as materials for sorption and destruction of chemical warfare agents (CWAs). It is important to understand the...

Oil-in-water nanoemulsions are promising colloidal dispersions for the delivery of hydrophobic drugs. The use of polysorbate 80 as stabilizing agent in these formulations can improve the delivery of the drug to the brain, thanks to a tropism for apolipoproteins. The aim of this study was to formulate injectable nanoemulsions stabilized by polysorbate 80, which meet United States Pharmacopoeia particle size requirements for parenteral emulsions. Nanoemulsions were prepared by high pressure homogenization and characterized in terms of mean hydrodynamic diameter, Gaussian distribution width, and volume-weighted percentage of fat droplets greater than 1.79 mu m (PFAT(1.79)) or 5 mu m (PFAT(5)). The effect of autoclaving, filtration and loading with nile red (a lipophilic fluorescent dye) on the nanoemulsions was evaluated. Real-time and accelerated stability tests were also performed. To satisfy Unites States Pharmacopoeia particle size specifications, nanoemulsions required six homogenization cycles. PFAT(5) and PFAT(1.79) were the particle size parameters more sensitive to discriminate the effect of homogenization, autoclaving, filtration and loading as well as globule size evolution during real-time stability tests. Results from accelerated stability studies correlated with the PFAT(5) values measured over time. Overall, the study demonstrates that all nanoemulsions studied (autoclaved, filtered or loaded) satisfies United States Pharmacopoeia particle size requirements up to 90 days, maintaining PFAT(5) to values lower than 0.05% v/v.

Ammonia is a widely used toxic industrial chemical that can cause severe respiratory ailments. Therefore, understanding and developing materials for its efficient capture and controlled release is necessary. One such class of materials is 3D porous metal-organic frameworks (MOFs) with exceptional surface areas and robust structures, ideal for gas storage/transport applications. Herein, interactions between ammonia and UiO-67-X (X: H, NH2 , CH3 ) zirconium MOFs were studied under cryogenic, ultrahigh vacuum (UHV) conditions using temperature-programmed desorption mass spectrometry (TPD-MS) and in-situ temperature-programmed infrared (TP-IR) spectroscopy. Ammonia was observed to interact with μ3 -OH groups present on the secondary building unit of UiO-67-X MOFs via hydrogen bonding. TP-IR studies revealed that under cryogenic UHV conditions, UiO-67-X MOFs are stable towards ammonia sorption. Interestingly, an increase in the intensity of the C-H stretching mode of the MOF linkers was detected upon ammonia exposure, attributed to NH-π interactions with linkers. These same binding interactions were observed in grand canonical Monte Carlo simulations. Based on TPD-MS, binding strength of ammonia to three MOFs was determined to be approximately 60 kJ mol-1 , suggesting physisorption of ammonia to UiO-67-X. In addition, missing linker defect sites, consisting of H2 O coordinated to Zr4+ sites, were detected through the formation of nNH3 ⋅H2 O clusters, characterized through in-situ IR spectroscopy. Structures consistent with these assignments were identified through density functional theory calculations. Tracking these bands through adsorption on thermally activated MOFs gave insight into the dehydroxylation process of UiO-67 MOFs. This highlights an advantage of using NH3 for the structural analysis of MOFs and developing an understanding of interactions between ammonia and UiO-67-X zirconium MOFs, while also providing directions for the development of stable materials for efficient toxic gas sorption.

Metal–organic frameworks constructed from multiple (≥3) components often exhibit dramatically increased structural complexity compared to their 2 component (1 metal, 1 linker) counterparts, such as multiple chemically unique pore environments and a plurality of diverse molecular diffusion pathways. This inherent complexity can be advantageous for gas separation applications. Here, we report two isoreticular multicomponent MOFs, bMOF-200 (4 components; Cu, Zn, adeninate, pyrazolate) and bMOF-201 (3 components; Zn, adeninate, pyrazolate). We describe their structures, which contain 3 unique interconnected pore environments, and we use Kohn–Sham density functional theory (DFT) along with the climbing image nudged elastic band (CI-NEB) method to predict potential H2/CO2 separation ability of bMOF-200. We examine the H2/CO2 separation performance using both column breakthrough and membrane permeation studies. bMOF-200 membranes exhibit a H2/CO2 separation factor of 7.9. The pore space of bMOF-201 is significantly different than bMOF-200, and one molecular diffusion pathway is occluded by coordinating charge-balancing formate and acetate anions. A consequence of this structural difference is reduced permeability to both H2 and CO2 and a significantly improved H2/CO2 separation factor of 22.2 compared to bMOF-200, which makes bMOF-201 membranes competitive with some of the best performing MOF membranes in terms of H2/CO2 separations.

Made available in DSpace on 2020-12-12T01:44:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-11-19 Following the information obtained by a rational design study, a cyclic and helical-stabilized analogue of the peptide Cm-p5 was synthetized. The cyclic monomer showed an increased activity in vitro against Candida albicans and Candida parapsilosis, compared to Cm-p5. Initially, 14 mutants of Cm-p5 were synthesized following a rational design to improve the antifungal activity and pharmacological properties. Antimicrobial testing showed that the activity was lost in each of these 14 analogues, suggesting, as a main conclusion, that a Glu-His salt bridge could stabilize Cm-p5 helical conformation during the interaction with the plasma membrane. A derivative, obtained by substitution of Glu and His for Cys, was synthesized and oxidized with the generation of a cyclic monomer with improved antifungal activity. In addition, two dimers were generated during the oxidation procedure, a parallel and antiparallel one. The dimers showed a helical secondary structure in water, whereas the cyclic monomer only showed this conformation in SDS. Molecular dynamic simulations confirmed the helical stabilizations for all of them, therefore indicating the possible essential role of the Glu-His salt bridge. In addition, the antiparallel dimer showed a moderate activity against Pseudomonas aeruginosa and a significant activity against Listeria monocytogenes. Neither the cyclic monomer nor the dimers were toxic against macrophages or THP-1 human cells. Due to its increased capacity for fungal control compared to fluconazole, its low cytotoxicity, together with a stabilized α-helix and disulfide bridges, that may advance its metabolic stability, and in vivo activity, the new cyclic Cm-p5 monomer represents a potential systemic antifungal therapeutic candidate. General Chemistry Department Faculty of Chemistry University of Havana, Zapata y G Center for Natural Products Research Faculty of Chemistry University of Havana, Zapata y G Center for Protein Studies Faculty of Biology University of Havana 25 and i Synthetic Peptides Group Center for Genetic Engineering and Biotechnology, P.O. Box 6162 Institute of Medical Microbiology and Hygiene University Clinic of Ulm, Robert Koch Str. 8 Department of Inorganic Chemistry Analytical and Physical Chemistry Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires Center of Excellence for Research in Sustainable Chemistry (CERSusChem) Department of Chemistry Federal University of São Carlos-UFSCar Laboratory of Pharmaceutical Biotechnology Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP Core Facility for Functional Peptidomics Ulm Peptide Pharmaceuticals (U-PEP) University Ulm Faculty of Medicine Ulm University Institute of Pharmaceutical Biotechnology Ulm University, James-Frank-Ring N27 Laboratory of Pharmaceutical Biotechnology Department of Drugs and Medicines School of Pharmaceutical Sciences UNESP

Metal–organic frameworks (MOFs) and specifically the UiO family of MOFs have been extensively studied for the adsorption and degradation of chemical warfare agents (CWAs) and their simulants. We present a combined experimental and computational study of the adsorption of dimethyl methylphosphonate (DMMP), a CWA adsorption simulant, in functionalized UiO-67. We have used density functional theory (DFT) to design functionalized MOFs having a range of binding energies for DMMP. We have selected three different functionalized MOFs for experimental synthesis and characterization from a total of eight studied with DFT. These three MOFs were identified as having the weakest, intermediate, and strongest binding energies for DMMP of the set, as predicted by our DFT calculations. We find that the order of predicted binding energies agrees with data from temperature-programmed desorption experiments. Moreover, the values of the binding energies are also in good agreement. This serves as a proof of concept that ab in...

Background: Idiopathic pulmonary fibrosis has a median survival time after diagnosis of 2–5 years. The main goal of treating IPF is to stabilize or reduce the rate of disease progression. Nintedanib and Pirfenidone have been a breakthrough in the management of IPF. Here we evaluated the effectiveness of Pirfenidone and Nintedanib in a population of IPF patients diagnosed in the last 12 months at Florence ILD Referral Centre. Methods: In the last 12 months, 82 IPF patients (66 male, mean age 78.3 ± 23.8 years) were diagnosed and started antifibrotic therapy with Pirfenidone or Nintedanib. Their clinical and functional details were analyzed retrospectively at time 0 and after 6 and 12 months of therapy. Results: The median age of the patients treated with Nintedanib was higher than that of the Pirfenidone group (p 0.05). After 1 year, lung function test parameters of patients treated with Pirfenidone had remained stable from baseline. Discussion: This study emphasizes that both antifibrotic drugs appeared to be a good therapeutic choice in terms of functional stabilization, also in older patients. Keywords: Idiopathic pulmonary fibrosis, Pirfenidone, Nintedanib

Several studies have reported model vertical profiles and/or abundance measurements for the main nitrile species observed in Titan’s atmosphere including: hydrogen cyanide (HCN), cyanoacetylene (HC3N), and vinyl cyanide (H2CCHCN) [1-4]. One of the main mechanisms leading to the formation of these nitriles (molecules bearing the CN group) is the reaction of CN radicals with hydrocarbons (molecules with general formula CxHy) involving H elimination (e.g. CN + C2H4 = H2CCHCN + H) or H abstraction (e.g. CN + CH4 = HCN + CH3) [5-9]. In this regard, it is worthwhile to highlight the recent spectroscopic detection of H2CCHCN, obtained using archival data from the Atacama Large Millimeter/submillimeter Array (ALMA), because this species is the best candidate molecule to form stable cell membranes/vesicle structures of potential astrobiological importance in Titan’s hydrocarbon-rich lakes and seas [10-12]. In the upper atmosphere of Saturn’s moon, photolysis of N2 and HCN leads to a continuous supply of reactive neutral species including N(4S, 2D) atoms and CN radicals [2, 13-16] that can further react with hydrocarbons and nitriles leading to two possible outcomes: 1) these reactions can directly contribute to the growth of molecular complexity, leading to a variety of N-rich organic species which, in turn, can act as (some of the) building blocks of life as we know it; 2) break the molecules into smaller but more stable fragments. A detailed knowledge of the relevant potential energy surface for each reactive systems on the basis of quantum-mechanical calculations and laboratory experiments is of pivotal importance in identifying the nature of the primary products and estimating their branching ratios, and hence providing the modellers with solid ground to describe and predict the rich, complex chemical evolution of Titan’s planetary atmosphere. Within this framework, we will report on two elementary chemical processes: 1) N(2D) + H2CCHCN and 2) CN(X2Σ+) + H2CCHCN with emphasis on the N addition or CN addition (followed by H elimination) reactive channel by means of the crossed molecular beams (CMB) technique coupled with mass spectrometric detection and time-of-flight analysis, and we will report on the primary products from the analysis of our measurements. Additional insight on the micromechanism at play and the interpretation of the scattering results is given by new electronic structure calculations of stationary points and product energetics in the potential energy surface of the investigated systems. RRKM statistical calculations for the CN(X2Σ+) + H2CCHCN system allows us to derive the product branching ratios and rate constants under the conditions of the present experiments and of the atmosphere of Titan. Preliminary results and astrophysical implications will be presented. ACKNOWLEDGMENTS: This research was supported by the Italian Space Agency (ASI, DC-VUM-2017-034, Grant n° 2019-3 U.O Life in Space) and the Marie Skłodowska-Curie project "Astro-Chemical Origins” (ACO), grant agreement No 811312. References: [1] P.P. Lavvasa, A. Coustenis, I.M. Vardavas, Planet. Space Sci. 56, 67 (2008) [2] K. Willacy, M. Allen, and Y. Yung, Astrophys. J., 829:79 (2016) [3] A. E. Thelen, C.A. Nixon, N.J. Chanover, M.A. Cordiner, E.M. Molter, N.A. Teanby, P.G.J. Irwin, J. Serigano, S.B. Charnley, Icarus, 319, 417 (2019) [4] V. Vuitton, R.V. Yelle, S.J. Klippenstein, S.M. Hörst, P. Lavvas, Icarus, 324, 120 (2019) [5] L. C. L. Huang, Y. T. Lee, and R. I. Kaiser, J. Chem. Phys. 110, 7119 (1999) [6] L. C. L. Huang, O. Asvany, A. H. H. Chang, N. Balucani, S. H. Lin, Y. T. Lee, R. I. Kaiser, and Y. Osamura, J. Chem. Phys. 113, 8656 (2000) [7] S. C. S. Ely, S. B.Morales, J.-C. Guillemin, S. J.Klippenstein, and I. R. Sims, J. Phys. Chem. A, 117, 12155 (2013) [8] F. Leonori, R. Petrucci, X. Wang, P. Casavecchia, N. Balucani, Chem. Phys. Lett., 553, 1 (2012) [9] N. Balucani, D. Skouteris, F. Leonori, R. Petrucci, M. Hamberg, W. D. Geppert, and P. Casavecchia, J. Phys. Chem. A, 116, 10467 (2012) [10] M. Y. Palmer, M. A. Cordiner, C. A. Nixon, S. B. Charnley, N. A. Teanby, Z. Kisiel. P. G. J. Irwin, M. J. Mumma, Sci. Adv., 3, e1700022 (2017) [11] J. C.-Y. Lai, M. A. Cordiner, C. A. Nixon, R. K. Achterberg, E. M. Molter, N. A. Teanby, M. Y. Palmer, S. B. Charnley, J. E. Lindberg, Z. Kisiel, Astron. J., 154:206 (2017) [12] J. Stevenson, J. Lunine, P. Clancy, Sci. Adv., 1, e1400067 (2015) [13] L. M. Lara, E. Lellouch and V. Shematovich, Astron. Astrophys., 341, 312 (1999) [14] A. Marten, T. Hidayat, Y. Biraud and R. Moreno, Icarus, 158, 532 (2002) [15] E. H. Wilson and S. K. Atreya, Planet. Space Sci., 51, 1017 (2003). [16] N. Balucani, Chem. Soc. Rev. 41, 5473 (2012)

The reaction of the nitrogen atom (N) in its first electronically excited state (2D) with cyanoacetylene (HC3N) has been investigated under single-collision conditions by using the crossed molecula...

The hydrothermal liquefaction reactions (HTL) in subcritical conditions of a lignin residue has been studied on a lab scale. The starting material was a lignin rich residue co-produced by an industrial plant situated in Northern Italy producing lignocellulosic bioethanol. The reactions were carried out in batch mode using stainless steel autoclaves. The experiments were under the following operating conditions: two different temperatures (300–350 °C), the presence of basis catalysts (NaOH, and NH4OH) in different concentrations and the presence/absence of capping agent 2,6-bis-(1,1-dimethylethyl)-4-methylphenol (BHT). Lignin residue and reaction products were characterized by analytical and spectroscopic techniques such as CHN-S, TGA, GC–MS, EPR, and 1H-NMR with (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (T.E.M.P.O.). The addition of BHT did not significantly affect the yield of char which is formed by radical way. Spectroscopic analysis indicated that the level of radicals during the reaction was negligible. Therefore, the results obtained experimentally suggest that the reaction takes place via an ionic route while radical species would play a minor role.

International audience; The reaction between cyano radicals (which are ubiquitous in interstellar clouds) and methylamine (a molecule detected in various interstellar sources) has been investigated in a synergistic experimental and theoretical study. The reaction has been found to be very fast in the entire range of temperatures investigated (23-297 K) by using a CRESU apparatus coupled to pulsed laser photolysis-laser induced fluorescence. The global experimental rate coefficient is given by In addition, dedicated electronic structure calculations of the underlying potential energy surface have been performed, together with capture theory and RRKM calculations. The experimental data have been interpreted in the light of the theoretical calculations and the product branching ratio has been established. According to the present study, in the range of temperatures investigated the title reaction is an efficient interstellar route of formation of cyanamide, NH2CN, another interstellar species. The second most important channel is the one leading to methyl cyanamide, CH3NHCN (an isomer of aminoacetonitrile), via a CN/H exchange mechanism with a yield of 12% of the global reaction in the entire range of temperatures explored. For a possible inclusion in future astrochemical models we suggest, by referring to the usual expression the following values α = 3.68 × 10-12 cm3 molec-1 s-1, β = -1.80, γ = 7.79 K for the channel leading to NH2CN + CH3; α = 5.05 × 10-13 cm3 molec-1 s-1, β = -1.82, γ = 7.93 K for the channel leading to CH3NHCN + H. © 2018 the Owner Societies.

Background Idiopathic pulmonary fibrosis (IPF) is a complex disease with a highly variable clinical course and generally poor prognosis. Classified as a rare disease, significant increases in incidence have been recorded worldwide in recent years. Left untreated IPF is extremely debilitating with substantial personal, social and economic implications. Objectives To discuss how IPF is diagnosed and managed in real life clinical practice with particular reference to Italy and to determine how new and effective therapies can be incorporated into a patient-centred management approach in order to improve the lives of patients with IPF. Outcomes Barriers to early diagnosis are discussed. Cited reasons for delays in diagnosing IPF in Italy include: inherent difficulties in diagnosis; lack of knowledge/awareness of the condition among point-of-contact healthcare professionals; delays in referral to centres of excellence and underestimation of symptoms by both patients and healthcare workers. Valid therapeutic options with demonstrated efficacy in slowing the decline in lung function are now available for patients with IPF. The ASCEND trial confirmed the effects of pirfenidone, approved for the treatment of IPF on the basis of the four phase III trials. Nintedanib, a tyrosine kinase inhibitor that targets the PDGF receptors α/β, FGF receptors 1 to 3, and VEGF receptors 1–3, is approved in the USA and the EU for the treatment of IPF. The TOMORROW and the INPULSIS placebo controlled trials in patients with IPF confirm the efficacy and safety of nintedanib and recent interim analyses endorse its long-term effects in slowing disease progression. Conclusions The importance of early and accurate diagnosis of IPF cannot be underestimated and it is the duty of all healthcare professionals to be vigilant to the symptoms of IPF and to involve a multidisciplinary team in diagnosing and managing IPF early in the course of disease.

A major challenge in the scientific research for strategies that use low-cost renewable energy is to design and develop heterogeneous /homogeneous catalysis processes that use waste CO2 to produce fuels in a circular economy regime. In this paper a theoretical and experimental study aiming at reusing CO2 and implementing a validated laboratory technology based on a prototype methanation reactor producing carbon neutral methane through the chemical conversion of CO2 waste flue gases using renewable energies, is presented. The first operational line of the work is the theoretical, computational and experimental treatment of elementary reactive and non-reactive molecular processes occurring inside the reactor in order to optimize its operating conditions and to identify possible technological improvements that are more compatible with the environment. Experimental determinations of methane yield by the reactor have been carried out using CO2 either taken from commercial bottles or produced from fermentation of wine and vegetable exhausted materials. To this end we have also undertaken a computational and experimental investigation of a new methanation pathway aimed at avoiding the use of the solid catalyst, by exploring mechanisms involving a plasma generation by electrical discharges or by vacuum ultraviolet (VUV) photons on CO2 + H2 gas mixtures. The measurements performed using a microwave discharge beam source developed in our laboratory gave useful indications on how to proceed to develop alternative solutions to the present Ni catalysed apparatus by resorting to a gas-phase-only process for the reduction of CO2 to CH4. These results demonstrate that the chemical reactivity of plasmas containing CO2 should be strongly increased thanks to the presence of CO+ and O+ ions having a very high kinetic energy. These ionic species are produced via Coulomb explosion of CO22+ molecular dications by the same process responsible for the erosion of the atmosphere of Mars.

The interaction between nitrogen atoms in their first electronically excited state 2D and oxygen atoms in their ground state 3P or in the first electronically excited state 1D with toluene has been characterized by electronic structure calculations. We focused our attention, in particular, on the different sites of attack of nitrogen or oxygen to toluene using different methods. Our results suggest that, while for geometry optimizations DFT methods are adequate and different DFT methods provide comparable results, in order to compute accurate energies higher level of calculations, as CCSD(T), are necessary, in particular when strong correlation effects are present.

In this work we characterize an initial van der Waals adduct in the potential energy surface of reaction between cyanoacetylene HC\(_{3}\)N and the cyano radical. The geometry of the CN-HC\(_{3}\)N adduct has been optimized through calculations employing ab initio methods. Results show that the energy of the adduct lays below the reactants. Additionally, a saddle point that connects the adduct to an important intermediate of the PES has been localized, with energy below the reactants. Calculations of the intermolecular potential have been performed and results show that the energy of the van der Waals adduct is higher than estimated with the ab initio methods.

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real-life Italian dermatological clinical practice. A multicenter, 4-week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.

Altres ajuts: Ministerio de Educación (República de Paraguay), BCAL04-451 - 3824321 Scope: Interventions that boost NAD+ availability are of potential therapeutic interest for obesity treatment. The potential of nicotinamide (NAM), the amide form of vitamin B3 and a physiological precursor of nicotinamide adenine dinucleotide (NAD)+, in preventing weight gain has not previously been studied in vivo. Other NAD+ precursors have been shown to decrease weight gain; however, their impact on adipose tissue is not addressed. Methods and results: Two doses of NAM (high dose: 1% and low dose: 0.25%) are given by drinking water to C57BL/6J male mice, starting at the same time as the high-fat diet feeding. NAM supplementation protects against diet-induced obesity by augmenting global body energy expenditure in C57BL/6J male mice. The manipulation markedly alters adipose morphology and metabolism, particularly in inguinal (i) white adipose tissue (iWAT). An increased number of brown and beige adipocyte clusters, protein abundance of uncoupling protein 1 (UCP1), mitochondrial activity, adipose NAD+, and phosphorylated AMP-activated protein kinase (P-AMPK) levels are observed in the iWAT of treated mice. Notably, a significant improvement in hepatic steatosis, inflammation, and glucose tolerance is also observed in NAM high-dose treated mice. Conclusion: NAM influences whole-body energy expenditure by driving changes in the adipose phenotype. Thus, NAM is an attractive potential treatment for preventing obesity and associated complications.

Cu2ZnSnS4 (CZTS) thin films were developed for safe and inexpensive thin films. The research aims to provide detailed information about the morphology of CZTS grown by immersion and sulfurization techniques on soda-lime glass (SLG) and indium tin oxide (ITO). CZTS thin films were prepared in two stages, i.e., CZTS precursors were prepared by substrate immersion in precursor solution firstly and then sulfurization in a furnace with sulfur pellet addition and heat treatment (540 °C for 30 minutes). The CZTS thin films were characterized by XRD, SEM-EDX, and completed by Smartphone and CCD cameras for larger area observation. The EDX test produces Cu-poor and Zn-rich films. The structure of kesterite crystals and amorphous CZTS thin films on SLG and ITO substrates was identified through XRD characterization results. The sequential thickness of films from SLG A’s film, SLG B’s film, SLG C’s film, ITO A’s film, ITO B’s film, ITO C’s film is 11.64 µm, 9.33 µm, 17 µm, 11.96 µm, 3.64 µm, 62.08 µm. CZTS thin-film morphologies observed by using Smartphone camera, CCD, and SEM were showed that there were cracks and voids yielding inhomogeneous grains and high porosity thin films. The comparison revealed that the thin films grown on ITO showed smaller cracks and higher homogeneity than that on SLG.

Made available in DSpace on 2022-04-29T08:30:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-16 Metal-organic frameworks (MOFs) offer many opportunities for applications across biology and medicine. Their wide range of chemical composition makes toxicologically acceptable formulation possible, and their high level of functionality enables possible applications as delivery systems for therapeutics agents. Surface modifications have been used in drug delivery systems to minimize their interaction with the bulk, improving their specificity as targeted carriers. Herein, we discuss a strategy to achieve a tumor-targeting drug-loaded MOF using clickchemistry to anchor functional folic acid (FA) molecules on the surface of N3-bio-MOF-100. Using curcumin (CCM) as an anticancer drug, we observed drug loading encapsulation efficiencies (DLEs) of 24.02 and 25.64% after soaking N3-bio-MOF-100 in CCM solutions for 1 day and 3 days, respectively. The success of postsynthetic modification of FA was confirmed by 1H NMR spectroscopy, Fourier transform infrared spectroscopy (FTIR), and liquid chromatography-mass spectrometry (LC-MS). The stimuli-responsive drug release studies demonstrated an increase of CCM released under acidic microenvironments. Moreover, the cell viability assay was performed on the 4T1 (breast cancer) cell line in the presence of CCM@N3-bio-MOF-100 and CCM@N3-bio-MOF-100/FA carriers to confirm its biological compatibility. In addition, a cellular uptake study was conducted to evaluate the targeting of tumor cells. Department of Drugs and Medicines School of Pharmaceutical Sciences of São Paulo State University (UNESP), Rodovia Araraquara Jau, Km 01-s/n-Campos Ville São Paulo Department of Chemistry University of Pittsburgh, 219 Parkman Avenue Department of Pharmaceutical Sciences School of Pharmaceutical Science of Ribeirão Preto University of São Paulo (USP), Avenida do Café, s/n-Campus da USP Sao Paulo Department of Genetics and Morphology Institute of Biological Sciences University of Brasilia (UnB) Campus Universitario Darcy Ribeiro-Asa Norte, Federal District Institute of Chemistry São Paulo State University (UNESP), Prof. Francisco Degni 55, PO Box 355 São Paulo Department of Drugs and Medicines School of Pharmaceutical Sciences of São Paulo State University (UNESP), Rodovia Araraquara Jau, Km 01-s/n-Campos Ville São Paulo Institute of Chemistry São Paulo State University (UNESP), Prof. Francisco Degni 55, PO Box 355 São Paulo

The reactivity of the prototypical aromatic six-membered N-heterocyclic pyridine is of relevance in atmospheric/combustion chemistry, as well as astrochemistry and prebiotic chemistry. Yet, experimental/theoretical studies of elementary reactions involving pyridine are scarce, with little information on primary reaction products and their branching fractions (BFs). Here, we report crossed molecular beam studies of the reaction of electronically excited atomic nitrogen, N(2D), with pyridine. This reaction can proceed via ring-contraction (BF≈0.35) or H-displacement (BF≈0.65) mechanisms, while the inclusion of N(2D) into the ring leads to pyrimidine + CH. Implications for prebiotic chemistry and the chemistry of Saturn’s moon Titan are noted.

Hypotheses Additives are commonly used to tune macromolecular conformational transitions. Among additives, trehalose is an excellent bioprotectant and among responsive polymers, PNIPAM is the most studied material. Nevertheless, their interaction mechanism so far has only been hinted without direct investigation, and, crucially, never elucidated in comparison to proteins. Detailed insights would help understand to what extent PNIPAM microgels can effectively be used as synthetic biomimetic materials, to reproduce and study, at the colloidal scale, isolated protein behavior and its sensitivity to interactions with specific cosolvents or cosolutes. Experiments The effect of trehalose on the swelling behavior of PNIPAM microgels was monitored by dynamic light scattering; Raman spectroscopy and molecular dynamics simulations were used to explore changes of solvation and dynamics across the swelling-deswelling transition at the molecular scale. Findings Strongly hydrated trehalose molecules develop water-mediated interactions with PNIPAM microgels, thereby preserving polymer hydration below and above the transition while drastically inhibiting local motions of the polymer and of its hydration shell. Our study, for the first time, demonstrates that slowdown of dynamics and preferential exclusion are the principal mechanisms governing trehalose effect on PNIPAM microgels, at odds with preferential adsorption of alcohols, but in full analogy with the behavior observed in trehalose-protein systems.

A jointed experimental and theoretical investigation pointing out new insights about the microscopic mechanism of the volatile organic compounds (VOCs) photocatalytic elimination by TiO2 was done. Methane, hexane, isooctane, acetone and methanol were photomineralized in a batch reactor. Values of K (adsorption constant on TiO2) and k (mineralization rate constant) of the five VOCs (treating the kinetic data through a Langmuir–Hinshelwood approach) were determined. Recorded K (in the range of 0.74 × 10−2–1.11 × 10−2 ppm−1) and k (in the range of 1.9–9.9 ppm min−1) values and performed theoretical calculations allowed us to suggest the involvement of an electron transfer step between the VOC and the hole, TiO2(h+), as the rate-determining one.

Cyanopolyynes are a family of carbon-chain molecules that have been detected in numerous objects of the interstellar medium (ISM), such as hot cores, star forming regions and cold clouds [1–4]. The simplest cyanopolyyne, HC3N, has been among the first organic molecules to be observed in the ISM [5] and up to date also HC5N, HC7N, HC9N and HC11N have been detected [6, 7]. HC3N and HC5N are also abundant in solar-type protostars (see for instance a recent work on IRAS 16293-2422 by Jaber Al-Edhari et al. [8]). Remarkably, HC3N has also been detected in comet C/1995 O1 (Hale-Bopp) and, together with other organic molecules, could be a part of the legacy of interstellar organic chemistry to the newly formed solar systems [9,10]. Cyanoacetylene has been suggested as an important brick in chain elongation processes, via its reaction with the C2H radical producing HC5N. Its reaction with the CN radical, instead, results in a chain termination reaction with the formation of dicyanoacetylene, NC-CC-CN (C4N2). Dicyanoacetylene and higher dicyanopolyynes have not been observed in the ISM so far because they lack a permanent electric dipole moment and cannot be detected through their rotational spectrum. However, it has been suggested that they are abundant in interstellar and circumstellar clouds [11] and account for a significant fraction of the total carbon budget. The reaction between CN radical and cyanoacetylene is also believed to be the main source of C4N2, an observed species in the upper atmosphere of Titan, the massive moon of Saturn [12]. To characterize the chemistry of cyanoacetylene in various extraterrestrial environments, in our laboratory, we have undertaken a systematic investigation of the reactions involving cyanoacetylene and atomic or diatomic radicals which are relatively abundant in space. The investigated reactions include CN + HC3N, O+HC3N and N+HC3N. We have used a sophisticated experimental technique to investigate these reactive systems under single collision conditions in order to be able to establish the nature of the primary products and their branching ratio without ambiguity (for some details see [13]). In addition, we have performed dedicated electronic structure and kinetic calculations to derive the relevant parameters to be included in astrochemical models. Implications for the chemistry of interstellar objects as well as the chemistry of cometary comae and the upper atmosphere of Titan will be noted. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement No 811312 for the project ”Astro-Chemical Origins”. [1] Wyrowski, F., Schilke, P., Walmsley, C.: Vibrationally excited HC3N toward hot cores. Astronomy and Astrophysics 341 (1999) 882–895 [2] Taniguchi, K., Saito, M., Sridharan, T., Minamidani, T.: Survey observations to study chemical evolution from high-mass starless cores to high-mass protostellar objects I: HC3N and HC5N. The Astrophysical Journal 854(2) (2018) 133 [3] Mendoza, E., Lefloch, B., Ceccarelli, C., Kahane, C., Jaber, A., Podio, L., Benedettini, M., Codella, C., Viti, S., Jimenez-Serra, I., et al.: A search for cyanopolyynes in L1157-B1. Monthly Notices of the Royal Astronomical Society 475(4) (2018) 5501–5512 [4] Takano, S., Masuda, A., Hirahara, Y., Suzuki, H., Ohishi, M., Ishikawa, S.i., Kaifu, N., Kasai, Y., Kawaguchi, K., Wilson, T.: Observations of 13C isotopomers of HC3N and HC5N in TMC-1: evidence for isotopic fractionation. Astronomy and Astrophysics 329 (1998) 1156–1169 [5] Turner, B.E.: Detection of interstellar cyanoacetylene. The Astrophysical Journal 163 (1971) L35–L39 [6] Broten, N.W., Oka, T., Avery, L.W., MacLeod, J.M., Kroto, H.W.: The detection of HC9N in interstellar space. 223 (July 1978) L105–L107 [7] Bell, M., Feldman, P., Travers, M., McCarthy, M., Gottlieb, C., Thaddeus, P.: Detection of HC11N in the cold dust cloud TMC-1. The Astrophysical Journal Letters 483(1) (1997) L61–L64 [8] Jaber Al-Edhari, A., Ceccarelli, C., Kahane, C., Viti, S., Balucani, N., Caux, E., Faure, A., Lefloch, B., Lique, F., Mendoza, E., Quenard, D., Wiesenfeld, L.: History of the solar-type protostar IRAS 16293-2422 as told by the cyanopolyynes. A&A 597 (2017) A40 [9] Mumma, M.J., Charnley, S.B. The Chemical Composition of Comets—Emerging Taxonomies and Natal Heritage. Annu. Rev. Astron. Astrophys. 49 (2011) 471–524 [10] Bockelée-Morvan, D., Lis, D. C., Wink, J. E., Despois, D., Crovisier, J., Bachiller, R., et al. New molecules found in comet C/1995 O1 (Hale-Bopp). Investigating the link between cometary and interstellar material.A&A 353 (2000) 1101 [11] Petrie, S., Millar, T., Markwick, A.: NCCN in TMC-1 and IRC+ 10216. Monthly Notices of the Royal Astronomical Society 341(2) (2003) 609–616 [12] Petrie, S., Osamura, Y.: NCCN and NCCCCN formation in titan’s atmosphere: 2. HNC as a viable precursor. The Journal of Physical Chemistry A 108 (2004) 3623–3631 [13] Casavecchia, P., Leonori, L., Balucani, N. Reaction dynamics of oxygen atoms with unsaturated hydrocarbons from crossed molecular beam studies: primary products, branching ratios and role of intersystem crossing. Int. Rev. Phys. Chem. 34 (2015) 161-204

Owing to their peculiar properties nanoparticles of cerium oxide have gained tremendous attention in recent years. As such, bacteria, fungus and algae are used for the development of CeO 2 NPs through the use of both intracellular and extracellular microbial or enzyme cells, proteins and other biomolecule compounds. In this paper we use Sargassum wightii Greville, a biological extract, to synthesize cerium oxide (CeO 2 ) nanoparticles. Algal-biogenic metal oxide synthesis nanoparticles is a safe and economical procedure due to the formation of compact, small nanoparticles. A number of advanced devices, such as UV-visible spectrophotometers, XRD, FTIR and SEM spectroscopy have been identified for prepared CeO 2 NPs. Cerium oxide particles were studied for the antioxidant properties and their antioxidant potency was examined using an in vitro system. The antioxidant strength tests for insoluble solids were conducted using an modified DPPH process. DPPH spray increases with particle size decrease.

Science advances 6(20), eaay3514 - (2020). doi:10.1126/sciadv.aay3514, The degradation of cadmium sulfide (CdS)–based oil paints is a phenomenon potentially threatening the iconic paint-ing The Scream (ca. 1910) by Edvard Munch (Munch Museum, Oslo) that is still poorly understood. Here, we provide evidence for the presence of cadmium sulfate and sulfites as alteration products of the original CdS-based paint and explore the external circumstances and internal factors causing this transformation. Macroscale in situ noninvasive spectroscopy studies of the painting in combination with synchrotron-radiation x-ray microspectroscopy investiga-tions of a microsample and artificially aged mock-ups show that moisture and mobile chlorine compounds are key factors for promoting the oxidation of CdS, while light (photodegradation) plays a less important role. Furthermore, under exposure to humidity, parallel/secondary reactions involving dissolution, migration through the paint, and re-crystallization of water-soluble phases of the paint are associated with the formation of cadmium sulfates., Published by Assoc., Washington, DC [u.a.]

Chlorination is an efficient and low-cost technique in disinfecting water for public water supply. However, during the process, the formation of undesirable by-products called halogen compounds, such as trihalome-thanes (THMs), occurs. Some of these compounds are proven to be carcinogenic to laboratory animals. The goal of this study was to investigate the occurrence of THMs in household reservoirs and the influence of cleaning time of these reservoirs on the formation of THMs. A total of 103 households were investigated in the city of Maringa, State of Parana, Brazil. The residences were classified according to the cleaning time of the reservoir into: up to one year, one to two years and more than two years. Samples were taken from the reservoirs and total trihalomethanes (THMt) were analyzed by gas chromatography (GC-MS), total organic carbon (TOC) by means of a Hach kit for low concentrations and free residual chlorine (CLres) by means of a kit for in loco determination. According to the results, the highest concentrations of THMt were observed in the reservoirs with cleaning time of more than 2 years. However, no amount has exceeded the maximum limit allowed by law. In general, the longer the time for cleaning the reservoir, the greater the degradation of water quality in THMt.

Current evidence accounts for the role of (poly)phenolic compounds in the prevention of non-communicable diseases. Detailed information on population-level intakes is required to translate these findings into recommendations. This work aimed to estimate (poly)phenol intake in the UK population using data from a nationally representative survey. Data from 9374 participants (4636 children aged 1.5–18 years and 4738 adults aged 19 years and over) from the National Diet and Nutrition Survey Rolling Programme (NDNS RP) 2008–2014 was used. (Poly)phenol content of foods consumed in the NDNS RP was identified using Phenol-Explorer and through literature searches. Data on flavonoids, phenolic acids, and stilbenes were collected. Total (poly)phenol content was also assessed. Mean total (poly)phenol intake ranged from 266.6 ± 166.1 mg/day in children aged 1.5–3 years to 1035.1 ± 544.3 mg/day in adults aged 65 years and over, with flavan-3-ols and hydroxycinnamic acids being the most consumed (poly)phenols across all age groups. (Poly)phenol intake was higher in males in all age groups except for adults aged 19–34 and 50–64 years, where intakes were marginally higher in females. Energy-adjusted intakes accounted for the pattern of increasing (poly)phenol intakes with age and a higher intake was observed in females across all age groups, with the exception of children aged 1.5–3 years. The main food sources were non-alcoholic beverages and fruits, being the main compounds flavan-3-ols and caffeoylquinic acids. This analysis provides estimates of (poly)phenol intake from a representative sample of the UK general population, which can help inform the health implications of (poly)phenol intake.

Homocysteine, an amino acid derived from methionine metabolism, has gained great importance as an important risk factor for cardiovascular diseases as the result of its thrombogenic properties and endothelial injury association. However, its role in the etiology and screening of intracranial aneurysms (IAs) has not been well studied. We aimed to test the hypothesis of a positive association between hyperhomocysteinemia (HHcy) and IAs.A case-control study was performed at a vascular neurosurgery unit in Brazil between 2016 and 2017. In total, 180 patients were included: 142 patients with previous IAs (case group) and 38 patients with a previous diagnosis of arteriovenous malformation and no aneurysms on imaging evaluation (control group). HHcy was defined as homocysteine levels greater than 15 μmol/L. Multivariate models were designed to adjust for potential confounders: age, sex, hypertension, dyslipidemia, and smoker status.The case group was older (56.3 ± 12.6 years vs. 40.9 ± 14.0 years, P0.001) and had a greater prevalence of women (76.1% vs. 55.3%, P = 0.012), as well as hypertension (45.1% vs. 2.6%, P0.001), dyslipidemia (60.6% vs. 10.5%, P = 0.001), and smokers (41.5% vs. 0.0%, P 0.001). Median homocysteine in the cases was similar to the controls (10.5 μmol/L [8.3-14.0] vs. 10.7 μmol/L [8.2-13.3], respectively, P = 0.450). There was a trend toward greater HHcy prevalence in the case group (20.4% vs. 7.9%, P = 0.073). HHcy was associated with greater age, male sex, hypertension, and smoking status. After multivariate adjustment, HHcy had no association with IAs (odds ratio 1.34, 95% confidence interval 0.30-5.97, P = 0.703).No association was found between HHcy and IAs.

Dimethyl ether is one of the most abundant interstellar complex organic molecules. Yet its formation route remains elusive. In this work, we have performed electronic structure and kinetics calculations to derive the rate coefficients for two ion-molecule reactions recently proposed as a gas-phase formation route of dimethyl ether in interstellar objects, namely CH3OH + CH3OH_2^+ → (CH3)2OH+ + H2O followed by (CH3)2OH+ + NH3 → CH3OCH3 + NH_4^+. A comparison with previous experimental rate coefficients for the reaction CH3OH + CH3OH_2^+ sustains the accuracy of the present calculations and allows a more reliable extrapolation at the low temperatures of interest in interstellar objects (10-100 K). The rate coefficient for the reaction (CH3)2OH+ + NH3 is, instead, provided for the first time ever. The rate coefficients derived in this work essentially confirm the prediction by Taquet, Wirström & Charnley concerning dimethyl ether formation in hot cores/corinos. Nevertheless, this formation route cannot be efficient in cold objects (like pre-stellar cores) where dimethyl ether is also detected, because ammonia has a very low abundance in those environments.

Exposure to toxic industrial chemicals such as phosgene may occur through accidental or deliberate release. Inhalation may result in an acute lung injury which manifests as hypoxaemia with insufficient oxygen being delivered to the tissues resulting in hypoxia, respiratory failure and death. No effective pharmacological therapy currently exists and treatment remains supportive, often requiring intensive care facilities. In a mass casualty scenario the logistical burden of managing exposed individuals would rapidly overwhelm healthcare systems. This highlights the need to develop post exposure therapeutic strategies to minimise injury severity and increase survival in individuals exposed to toxic chemicals. Our research objective was to investigate a commercial off the shelf (COTS) therapy; ambient air continuous positive airway pressure (CPAP) support, initiated 1h post exposure to explore the concept that early intervention with positive airway pressure would reduce or ameliorate lung injury following exposure to phosgene. This study has demonstrated that CPAP, initiated before overt signs of exposure become manifest, significantly improved survival as well as improving some clinically relevant physiological measures of phosgene-induced acute lung injury over 24h.

The toxic industrial chemical (TIC1) phosgene remains an important chemical intermediate in many industrial processes. Inhalation of phosgene can cause an acute lung injury (ALI) which, in severe cases may result in death. There are currently no effective pharmacological therapies or evidence-based treatment guidelines for managing exposed individuals. N-acetylcysteine (NAC) is a commercially available drug licensed in the UK and elsewhere for the treatment of paracetamol (acetaminophen) overdose. It has a number of mechanisms of action which may provide therapeutic benefit for the treatment of phosgene-induced ALI. It has previously been shown to provide therapeutic efficacy against the lung damaging effects of sulfur mustard vapour exposure, when given by the inhaled route, in the pig (Jugg et al., 2013). Our research objective was to determine whether inhaled NAC might also be therapeutic for other chemicals, in this case, phosgene. This study has demonstrated that multiple nebulised doses, administered from 30 min after exposure of terminally anaesthetised pigs to phosgene, is not an effective therapy when administered at the times and doses employed in this study. There remains no pharmacological treatment for phosgene-induced lung injury.

Purpose. There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. Methods. Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. Results. (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. Conclusions. The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet. This work was partially funded by MRC core funding (Physiological Modelling of Metabolic Risk, MC_UP_A090_1005, and Nutrition, Surveys and Studies, MC_U105960384) and University of Parma core funding (FIL 2014-2017). P.M. was partially funded by a Grant of the Postdoctoral Fellowship Program from Fundación Séneca (Murcia Region, Spain). I.A.L. was supported by a postdoctoral fellowship funded by the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20689).

The β-glucosidase and esterase activities of 31 O. oeni strains were evaluated by fluorimetric methods. The level and distribution among intact cells and supernatant of both β-glucosidase and esterase activity in MRS broth were strongly strain-dependent. In the wine, hydrolytic activities were detected only in the intact cells and their level was related to the cell growth and malolactic activity. Increasing concentration of ethanol (from 12 to 15 (% v/v)) and molecular SO2 (from 0.2 to 0.6 mg L−1) led to a slowdown of bacterial growth and malolactic fermentation (MLF). An inhibitory effect of the lowest doses of molecular sulphur dioxide on both β-glucosidase and esterase activity was highlighted. A synergistic effect among SO2 and ethanol on hydrolytic activities was observed during MLF. Only one strain was able to complete MLF and to produce both hydrolytic activities also in the harshest conditions.

Unprecedented hydrolysis reactions are observed in the gas phase in clusters containing doubly-charged vanadium oxides and hydroxide anions, SO2 and H2O. The experimental and computational study shows the cooperative effects of the vanadium species, V2O62− and HV3O92−, and sulfur dioxide on the enhancement of the hydrogen bonds of water that allows the acid–base reaction and charge separation in the doubly-charged ion.

Background Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. Methods A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. Discussion Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. Trial registration ClinicalTrials.gov, NCT03166540. Registered on May 21, 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2271-2) contains supplementary material, which is available to authorized users.

The aim of this study is to evaluate the association between changes in routinely prescribed laboratory tests and tracheostomy-free survival in amyotrophic lateral sclerosis (ALS). Two hundred seventy-five ALS patients were retrospectively studied. BMI, forced vital capacity, hemoglobin, hematocrit, lymphocytes, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, proteins, albumin, creatine-phosphokinase, iron, ferritin, transferrin, glucose, urea, uric acid, and creatinine were measured every 6 months from baseline to 24 months, death or study end, together with the probability of death or tracheostomy. Missing data were handled using multiple imputation chained equations. Hemoglobin (OR = 1.71, 95%CI 1.24-2.36 for IQR increase), hematocrit (OR = 1.87, 95%CI 1.34-2.63 for IQR increase), urea (OR = 1.51, 95%CI 1.21-1.89 for IQR increase), and uric acid (OR = 1.98, 95%CI 1.23-3.20 for IQR increase) were directly associated, while triglycerides (OR = 0.69, 0.51 to 0.93 for IQR increase) were inversely associated with the odds of death or tracheostomy. In our cohort, an increase of hemoglobin, hematocrit, urea, and uric acid was directly associated, and an increase of triglycerides was inversely associated with the odds of death or tracheostomy. Should these findings be replicated in an external cohort, they might help to discriminate ALS progression and patients' decisions about procedures and end of life.

Background/Aims: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor afatinib is used for the treatment of several malignancies. Afatinib is at least partially effective by triggering apoptosis of tumor cells. Platelets may similarly undergo apoptosis, which is characterized by caspase 3 activation, cell shrinkage and phosphatidylserine translocation. However, an effect of afatinib on platelets has never been reported. The present study explored whether treatment of platelets with afatinib modifies platelet activation and apoptosis in the absence and presence of platelet activators thrombin or collagen related peptide (CRP). Methods: Platelets isolated from wild-type mice were exposed for 30 minutes to afatinib (18 µg/ml) without or with subsequent treatment with thrombin (0.005 U/ml or 0.01 U/ml) or CRP (2 µg/ml or 5 µg/ml). Flow cytometry was employed to estimate Orai1 abundance at the platelet surface with specific antibodies, cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. Results: In the absence of thrombin and CRP, the administration of afatinib (18 µg/ml) slightly, but significantly, increased [Ca2+]i and annexin-V-binding, but did not significantly modify Orai1 abundance, P-selectin abundance, activated αIIbβ3 integrin, cell volume, caspase activity and aggregation. Exposure of platelets to 0.005 U/ml or 0.01 U/ml thrombin or 2 µg/ml or 5 µg/ ml CRP was followed by a significant increase of Orai1 abundance, increase of [Ca2+]i, P-selectin abundance, αIIbβ3 integrin activity, annexin-V-binding, caspase activity, and aggregation, as well as a significant decrease of forward scatter, all effects significantly blunted (thrombin) or virtually abolished (CRP) by afatinib. Conclusions: Afatinib is a powerful inhibitor of platelet activation, platelet apoptosis and platelet aggregation.

Background/Aims: The anaplastic lymphoma kinase (ALK) inhibitor ASP3026 is in clinical development for the treatment of ALK expressing non-small cell lung carcinoma (NSCLC). ASP3026 is in part effective by inducing apoptosis of tumor cells. Erythrocytes lack mitochondria and nuclei, key organelles in the execution of apoptosis, but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Eryptosis is triggered by cell stress, such as energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored, whether ASP3026 impacts on eryptosis. Methods: Human erythrocytes have been exposed to energy depletion (glucose withdrawal for 48 hours), oxidative stress (addition of 0.3 mM tert-butylhydroperoxide [tBOOH] for 50 min) or Ca2+ loading with Ca2+ ionophore ionomycin (1 µM for 60 min) in absence and presence of ASP3026 (1-4 µg/ml). Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, and cell volume from forward scatter. Results: Treatment with ASP3026 alone did not significantly modify annexin-V-binding or forward scatter. Energy depletion, oxidative stress and ionomycin, all markedly and significantly increased the percentage of annexin-V-binding erythrocytes, and decreased the forward scatter. ASP3026 significantly blunted the effect of energy depletion and oxidative stress, but not of ionomycin on annexin-V-binding. ASP3026 did not significantly influence the effect of any maneuver on forward scatter. Conclusions: ASP3026 is a novel inhibitor of erythrocyte cell membrane scrambling following energy depletion and oxidative stress.

Background and Purpose: The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl)-propyl]-2-(trifluoromethyl)-(10)H-phenothiazine dihydrochloride; TFP) may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and inhibited by nitric oxide (NO). We explored whether TFP treatment of erythrocytes induces phosphatidylserine exposure, cell shrinkage, and calcium influx, whether it impairs S-nitrosylation and whether these effects are inhibited by NO. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and protein nitrosylation from fluorescence switch of the Bodipy-TMR/Sypro Ruby signal. Results: Exposure of human erythrocytes to TFP significantly enhanced the percentage of annexin-V-binding cells, raised [Ca2+]i, and decreased S-nitrosylation. The effect of TFP on annexin-V-binding was not affected by removal of extracellular Ca2+ alone, but was significantly inhibited by pre-treatment with sodium nitroprusside (SNP), an effect significantly augmented by additional removal of extracellular Ca2+. A 3 hours treatment with 0.1 µM Ca2+ ionophore ionomycin triggered annexin-V-binding and cell shrinkage, effects fully reversed by removal of extracellular Ca2+. Conclusions: TFP induces eryptosis and decreases protein S-nitrosylation, effects blunted by nitroprusside. The effect of nitroprusside is attenuated in the presence of extracellular Ca2+.

The gas-phase reactivity of doubly-charged vanadium hydroxides anions with SO2 has been studied by experimental and computational methods. The obtained results highlight the role of sulfur dioxide in promoting unprecedented bond-forming reactions, which produce singly-charged products by breaking the Vx Oy skeleton or a terminal V-O bond.

A stereocomplexed poly(lactic acid)-polyethyleneglycol copolymer was synthesized and successfully used as recyclable support for Pt nanoparticles, generated by the metal vapor synthesis technique. The confinement of the Pt nanoparticles were determined by thermal analysis. Hydrogenation reactions of chlorinated aromatic nitro compounds, containing other reducible functional groups, to the corresponding anilines occurred with the latter supported Pt nanoparticles in MeOH under very mild reaction conditions ( i.e . 30 °C, p(H 2 ) = 5.0 bar). The covalently attached polyethyleneglycol polymer significantly increased the catalytic activity of the supported Pt nanoparticles compared to an analogous catalytic system which did not contain polyethyleneglycol but the same sized Pt nanoparticles.

Background/Aims: The steroidal aromatase inactivator exemestane blocks estrogen biosynthesis and is thus employed for the prevention and treatment of breast cancer. Exemestane is in part effective by stimulation of suicidal cell death or apoptosis. Side effects of exemestane treatment include anemia. At least in theory, exemestane induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the stimulation of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, several kinases and caspases. The present study explored, whether exemestane is able to trigger eryptosis and, if so, to shed some light on the signaling involved. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCF fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to exemestane (≥ 10 µg/ml) significantly increased the percentage of annexin-V-binding cells without significantly modifying forward scatter. Exemestane significantly increased Fluo3-fluorescence (10 and 20, but not 40 µg/ml), DCF fluorescence (40 µg/ml), and ceramide abundance (40 µg/ml). The effect of exemestane (40 µg/ml) on annexin-V-binding was significantly blunted by antioxidant N-acetylcysteine (1mM), but was not significantly modified by removal or increase of extracellular Ca2+, by p38 kinase inhibitor SB203580 (2 µM), casein kinase inhibitor D4476 (10 µM) and caspase inhibitor zVAD (10 µM). Conclusions: Exemestane triggers phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled by enhanced [Ca2+]i, oxidative stress, and increased ceramide abundance.

We describe caspofungin pharmacokinetics (PK) after the first and fourth doses in 20 critically ill septic patients. Monte Carlo simulation was used to analyze the probability of target attainment (PTA) (AUC/MIC865) for