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41.
Vlad F. Avram Imen Chamkha Eleonor sander-Frostner Johannes K. Ehinger Romulus Z. Timar Magnus J. Hansson Danina M. Muntean Eskil Elmr 《International journal of molecular sciences》2021,22(1)
Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings. 相似文献
42.
Dr. Jie Zang Dr. Fei Ye Dr. Sara M. Ø. Solbak Dr. Lars J. Høj Prof. Mingjie Zhang Prof. Anders Bach 《ChemMedChem》2021,16(6):949-954
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors. 相似文献
43.
Kyle J. Sommers Brian S. Bentley Dr. Robert G. Carden Savannah J. Post Ryan A. Allen Renee C. Kontos Jacob W. Black Prof. William M. Wuest Prof. Kevin P. C. Minbiole 《ChemMedChem》2021,16(3):467-471
Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs. 相似文献
44.
N. Clament Sagaya Selvam Lijie Du Bao Yu Xia Pil J. Yoo Bo You 《Advanced functional materials》2021,31(12):2008190
Electroreduction of small molecules such as H2O, CO2, and N2 for producing clean fuels or valuable chemicals provides a sustainable approach to meet the increasing global energy demands and to alleviate the concern on climate change resulting from fossil fuel consumption. On the path to implement this purpose, however, several scientific hurdles remain, one of which is the low energy efficiency due to the sluggish kinetics of the paired oxygen evolution reaction (OER). In response, it is highly desirable to synthesize high-performance and cost-effective OER electrocatalysts. Recent advances have witnessed surface reconstruction engineering as a salient tool to significantly improve the catalytic performance of OER electrocatalysts. In this review, recent progress on the reconstructed OER electrocatalysts and future opportunities are discussed. A brief introduction of the fundamentals of OER and the experimental approaches for generating and characterizing the reconstructed active sites in OER nanocatalysts are given first, followed by an expanded discussion of recent advances on the reconstructed OER electrocatalysts with improved activities, with a particular emphasis on understanding the correlation between surface dynamics and activities. Finally, a prospect for clean future energy communities harnessing surface reconstruction-promoted electrochemical water oxidation will be provided. 相似文献
45.
Francesca R. Lamastra Mehdi Chougan Emanuele Marotta Samuele Ciattini Seyed Hamidreza Ghaffar Stefano Caporali Francesco Vivio Giampiero Montesperelli Ugo Ianniruberto Mazen J. Al-Kheetan Alessandra Bianco 《Ceramics International》2021,47(14):20019-20031
The impact of graphite nanoplatelets (GNPs) on the physical and mechanical properties of cementitious nanocomposites was investigated. A market-available premixed mortar was modified with 0.01% by weight of cement of commercial GNPs characterized by two distinctively different aspect ratios.The rheological behavior of the GNP-modified fresh admixtures was thoroughly evaluated. Hardened cementitious nanocomposites were investigated in terms of density, microstructure (Scanning Electron Microscopy, SEM and micro–Computed Tomography, μ-CT), mechanical properties (three-point bending and compression tests), and physical properties (electrochemical impedance spectroscopy, EIS and thermal conductivity measurements). At 28 days, all GNP-modified mortars showed about 12% increased density. Mortars reinforced with high aspect ratio GNPs exhibited the highest compressive and flexural strength: about 14% and 4% improvements compared to control sample, respectively. Conversely, low aspect ratio GNPs led to cementitious nanocomposites characterized by 36% decreased electrical resistivity combined with 60% increased thermal conductivity with respect to the control sample. 相似文献
46.
Aguayo-Canela Francisco José Alaiz-Moretón Héctor García-Ordás María Teresa Benítez-Andrades José Alberto Benavides Carmen García-Rodríguez Isaías 《The Journal of supercomputing》2021,77(11):13046-13068
The Journal of Supercomputing - The increasing number of connected devices and the complexity of Internet of Things (IoT) ecosystems are demanding new architectures for managing and securing these... 相似文献
47.
48.
Camila C. Lopes Wagner A. Pinheiro Daniel Navarro da Rocha José G. Neves Américo Bortolazzo Correr José R.M. Ferreira Rafael M. Barbosa Jefferson R.F. Soares Jheison L. Santos Marcelo H. Prado da Silva 《Ceramics International》2021,47(6):7653-7665
The repair of bone fractures is a clinical challenge for patients with impaired healing, such as osteoporosis. Currently, different strategies have been developed to design new biomaterials, enhancing their interactions with biological systems and conducting the cellular behavior in the desired direction to help fracture healing. In the present work, hydroxyapatite-graphene oxide (HA-GO) nanocomposites were produced and the morphological and physicochemical influences of the addition of 0.5 wt%, 1.0 wt% and 1.5 wt% of GO to HA were observed. FEG-SEM and TEM analyses of HA-GO nanocomposites showed HA nanoparticles adhered to the surface of the GO sheets, suggesting an effective method to form nanostructured graphene-based biomaterials. As confirmation, physicochemical analyses by Raman, FTIR and TGA demonstrated a strong affinity between HA and GO, according to the increase of concentration from 0.5 wt% to 1.5 wt% GO in the HA-GO nanocomposites. Also, in order to evaluate the HA-GO nanocomposites behavior under biological microenvironment, in vitro bioactivity and indirect cytotoxicity tests were performed. FEG-SEM analyses confirmed the positive results for the bioactivity properties of HA-GO nanocomposite and indirect cytotoxicity demonstrated that even with a decrease in the hDPSCs viability and proliferation, when increasing to 1.5 wt% of GO concentration, high level of cell viability was exhibited by HA-GO nanocomposites. These biological results suggested the 0.5 wt% HA-GO nanocomposite as a potential bioactive bone graft and a promising biomaterial for bone tissue regeneration, when compared to the pure HA. 相似文献
49.
Andrew N. Kuhn Haidong Zhao Uzoma O. Nwabara Xiaofei Lu Mingyan Liu Yung-Tin Pan Wenjin Zhu Paul J. A. Kenis Hong Yang 《Advanced functional materials》2021,31(26):2101668
Copper catalysts are widely studied for the electroreduction of carbon dioxide (CO2) to value-added hydrocarbon products. Controlling the surface composition of copper nanomaterials may provide the electronic and structural properties necessary for carbon-carbon coupling, thus increasing the Faradaic efficiency (FE) towards ethylene and other multi-carbon (C2+) products. Synthesis and catalytic study of silver-coated copper nanoparticles (Cu@Ag NPs) for the reduction of CO2 are presented. Bimetallic CuAg NPs are typically difficult to produce due to the bulk immiscibility between these two metals. Slow injection of the silver precursor, concentrations of organic capping agents, and gas environment proved critical to control the size and metal distribution of the Cu@Ag NPs. The optimized Cu@Ag electrocatalyst exhibited a very low onset cell potential of −2.25 V for ethylene formation, reaching a FE towards C2+ products (FEC2+) of 43% at −2.50 V, which is 1.0 V lower than a reference Cu catalyst to reach a similar FEC2+. The high ethylene formation at low potentials is attributed to enhanced C C coupling on the Ag enriched shell of the Cu@Ag electrocatalysts. This study offers a new catalyst design towards increasing the efficiency for the electroreduction of CO2 to value-added chemicals. 相似文献
50.
L.L. Oliveira J.A. Cortés B.S. Caldeira T. Strusch U. Wiedwald A.Z. Simoes 《Ceramics International》2021,47(15):20768-20780
In this work, praseodymium (Pr) doped cerium oxide (CeO2) was prepared using the microwave-assisted hydrothermal method (MAH) and the properties were investigated by X-ray diffraction analysis (XRD), Raman spectroscopy, Field Emission Gun Scanning Electron Microscope (FEG-SEM), BET method, Photoluminescence spectroscopy (PL), Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–visible spectroscopy (UV–Vis), Electron paramagnetic resonance spectroscopy (EPR) and Magnetometry. The results showed that increasing the Pr-doping promotes a structural disorder due to increased oxygen vacancies. XRD confirmed a cubic structure without deleterious phases with modifications in the structure caused by alteration in the cerium oxidation state as well as changes in the crystallite size and strain obtained by Wellinson-Hall method. Raman spectroscopy shows that changing the Pr content results in samples with different defect densities at short range. FEG-SEM showed that the nanocrystals are agglomerated with small particles tend to aggregate spontaneously to decrease the surface energy. BET method showed that the Pr doping results in a gain of specific surface area. PL indicated that Pr3+ leads to distinct emissions; red emission associated to oxygen vacancies located near the conduction band (shallow defects), green emission associated to electron-hole recombination and orange emission associated to shallow defects and electron-hole recombination. FTIR indicated the complete process of nucleation with no other phase. UV–Vis showed the transitions between oxygen 2p, cerium 4f and praseodymium 4f states. The EPR signal shows events occurring around 344 mT. These events can be related due the presence of paramagnetic elements containing unpaired electrons, such as Ce (III), which is indicative of cerium reduction caused by Pr ions, as evidenced by Rietveld data. Regardless of the Pr concentration used in this research, the magnetic measurements show a superparamagnetic system below the blocking temperature of ~20 K and a paramagnetic system above this temperature, which indicates no significant changes in the average size of the nanoparticles. Surface area, crystallite size and the temperature are important parameters, which control the magnetic properties of such N-type semiconductors. 相似文献