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1.
Kavitej Samra Mathun Kuganesan William Smith Anna Kleyman Robert Tidswell Nishkantha Arulkumaran Mervyn Singer Alex Dyson 《International journal of molecular sciences》2021,22(6)
Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe−/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) showed significant metabolic activity, dose-dependently decreasing ex vivo O2 consumption (rat soleus muscle, liver) and transiently inhibiting mitochondrial cytochrome C oxidase (liver, heart). Pharmacological manipulation of selenoprotein expression in HepG2 human hepatocytes revealed that the oxidation status of selenium impacts on protein expression; reduced selenide (NaHSe) increased, whereas (oxidized) sodium selenite decreased the abundance of two ubiquitous selenoproteins. An inhibitor of endogenous sulfide production (DL-propargylglycine; PAG) also reduced selenoprotein expression; this was reversed by exogenous NaHSe, but not sodium hydrosulfide (NaHS). NaHSe also conferred cytoprotection against an oxidative challenge (H2O2), and this was associated with an increase in mitochondrial membrane potential. Anesthetized Wistar rats receiving intravenous NaHSe exhibited significant bradycardia, metabolic acidosis and hyperlactataemia. In summary, NaHSe modulates metabolism by inhibition of cytochrome C oxidase. Modification of selenoprotein expression revealed the importance of oxidation status of selenium therapies, with implications for current clinical practice. The utility of NaHSe as a research tool and putative therapeutic is discussed. 相似文献
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3.
Dr. Anders Højgaard Hansen Henriette B. Christensen Dr. Sunil K. Pandey Dr. Eugenia Sergeev Alice Valentini Julia Dunlop Domonkos Dedeo Simone Fratta Dr. Brian D. Hudson Prof. Graeme Milligan Prof. Trond Ulven Prof. Elisabeth Rexen Ulven 《ChemMedChem》2021,16(21):3326-3341
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties. 相似文献
4.
Thomas R. Savage Fernando Almeida-Trasvina Ehecatl A. del-Rio Chanona Robin Smith Dondga Zhang 《American Institute of Chemical Engineers》2021,67(11):e17358
With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems. 相似文献
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6.
Xian Yu Wang Cuicui Wang Ge Smith Leemiller Cheng Haitao 《Holz als Roh- und Werkstoff》2022,80(2):355-365
European Journal of Wood and Wood Products - To obtain the optimum balance between performance and cost, white mud (lime mud) was incorporated into the shell layer of core–shell structured... 相似文献
7.
Steven M. Smith II Lun Feng William G. Fahrenholtz Greg E. Hilmas Tieshu Huang 《Journal of the American Ceramic Society》2022,105(9):5543-5547
A dual-phase high-entropy boride (HEB)/carbide (HEC) ceramic with a fine grain size was synthesized by a sequential boro/carbothermal process. In the first step, an Hf–Nb–Ta–Ti–Zr-containing carbide was synthesized by a carbothermal reduction of oxides followed by the reaction of the carbide with B4C and ZrH2 to convert part of the carbide to boride. The resulting composition was ∼29 vol% HEB with an average grain size of ∼1.1 μm. Solid solution formation occurred at the densification temperature of 1900°C resulting in a relative density higher than 99%. The Vickers hardness was 26.5 ± 1.4 GPa. This is the first report of synthesizing dual-phase boride–carbide high-entropy ceramics from carbothermally synthesized, HEC powders. 相似文献
8.
Dr. Chungsik Kim Mintesinot Kassu Dr. Kenneth P. Smith Prof. James E. Kirby Prof. Roman Manetsch 《ChemMedChem》2021,16(18):2775-2780
Pyrazole-thiazole core-containing compound KP-40 and 20 novel derivatives were designed and synthesized through traditional SAR analysis. These molecules displayed adjunctive activity with meropenem against Gram-negative bacteria evidenced by a range of fractional inhibitory concentration (FIC=0.5–0.25) and minimum adjunctive concentration (MAC=128–32 μM) values. Of this series of molecules, four compounds displayed notable adjunctive potential, with FIC and MAC values of 0.25 and 32 μM, respectively. Moreover, the solubility of these compounds was improved to an acceptable range. Further analysis using our “in house” permeation and efflux multi parameter optimization (PEMPO) algorithm revealed key physicochemical properties that may be critical for the development of active Gram-negative antibacterials. Taking PEMPO scores into consideration prior to executing synthesis of analogs may be a simple, yet rapid and effective strategy that can be used in conjunction with traditional SAR approaches to aid in the design of potent Gram-negative antibacterials. 相似文献
9.
David J. Lawrence Brianna L. Smith Cameron D. Collard Keyton A. Elliott Kyle L. Fakhoury Jeffery D. Mangold Anna N. Soyka 《International Journal of Hydrogen Energy》2021,46(2):1642-1655
Monolithically-integrated tandem photoanodes were fabricated on substrates consisting of epitaxial n-GaAs1-xPx (x ? 0.32) grown on n+-GaAs wafers. A p+-n junction photovoltaic (PV) cell was first formed by zinc diffusion into the n-GaAs0.68P0.32 from a deposited ZnO coating. After diffusion the ZnO serves as a transparent electrical contact to the resulting p+-GaAs0.68P0.32 surface layer. Transparent, conducting SnO2:F provides chemical and mechanical protection for the ZnO and the underlying PV cell, and it electrically connects this cell to a top BiVO4 photocatalyst layer. In some photoanodes, a WO3 thin film was interposed between the SnO2:F and BiVO4. All oxide coatings were produced by ultrasonic spray pyrolysis except WO3, which was spin coated. Unassisted (unbiased) solar water splitting was achieved, with a solar-to-hydrogen efficiency approaching 2%, without addition of any co-catalyst to the BiVO4 surface. This work can provide insights to other researchers regarding scalable, low cost approaches for the planar monolithic integration of oxide photoanode materials with PV cells to create new tandem devices. 相似文献
10.
L. Kung R.M. Savage E.B. da Silva S.A. Polukis M.L. Smith A.C.B. Johnson M.A. Miller 《Journal of dairy science》2021,104(4):4206-4222
We determined if a microbial inoculant could improve the fermentation and aerobic stability of corn silage subjected to various challenges during storage that included an air stress challenge and low packing density. In Experiment 1, whole-plant corn was untreated (CTR) or treated (INO, Lactobacillus buchneri 40788 and Pediococcus pentosaceus 12455. Five individually replicated 7.5-L silos, at a density of 240 kg of dry matter (DM)/m3, for each treatment were kept sealed (NAS) for 19 wk, air stressed early (ES, 3 h/wk for wk 1–9), or air stressed late during storage (LS, 3 h/wk for wk 10–19). Inoculation increased the number of agar-culturable lactic acid bacteria regardless of air stress status, but it did not affect the relative abundance of Lactobacillus. Early, but not late air stress, resulted in silages with a higher relative abundance of Acetobacter when compared with NAS. Silages treated with INO had greater concentrations of acetic acid than CTR. Numbers of yeasts were lowest for INO regardless of air stress and CTR-LS had the most yeasts among all treatments. Silages that were not air stressed had a higher relative abundance of Candida tropicalis than air stressed silages. Monascus purpureus was detected in ES and LS but not in NAS, and its relative abundance was numerically higher in CTR-ES than in INO-ES and statistically higher in CTR-LS compared with INO-LS. Early air stress numerically reduced aerobic stability compared with NAS, and there was a statistical tendency for lower stability in LS compared with NAS. Inoculation improved aerobic stability regardless of when the air stress occurred. In Experiment 2, corn silage was prepared with the same primary treatments of CTR and INO but was packed at a low (LD; 180 kg of DM/m3) or a normal (ND; 240 kg of DM/m3) density and sealed (NAS) or air stressed (AS; 24 h on d 28, 42, and 89) for 92 d of storage. The concentration of acetic acid was greater in INO compared with CTR and in AS compared with NAS. Numbers of yeasts were lower in NAS compared with AS regardless of inoculation and they were lower in INO-AS compared with CTR-AS. Treatment with INO improved aerobic stability but the improvement was better in NAS versus AS and better in ND versus LD. Overall, our experiments corroborate past findings showing that INO markedly improves the aerobic stability of corn silage but they are the first to show that improvement can be sustained even when the silage was exposed to regular air stresses and when packed at a low density. 相似文献