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Roadmap to be able to Restoration: Year Only two in the COVID-19 Crisis.
This work offers a broadly applicable design route for the development of advanced catalysts with an outstanding combination of activity and reusability for wastewater treatments.Cyclic peptides (CPs) have attracted attention as next-generation drugs because they possess both cell-permeable potential as small molecules and specific affinity similar to antibodies. As intracellular molecules are important targets of CPs, quantitation of the intracellular retention and transmembrane permeability of CPs is necessary for drug development. However, permeated CPs within cells cannot be directly assessed by conventional permeability assays using methods such as artificial membranes and cell monolayers. Here, we propose a new approach using single-cell cytoplasm mass spectrometry (SCC-MS). After cells were incubated with CPs, the cytoplasm was directly collected from a single cell using a microneedle followed by nanoelectrospray ionization mass spectrometry detection of the CPs. The height of the CP peak was plotted against time and fitted with a simple function, y = a(1 - e-bx), to calculate the apparent permeability coefficient (Papp) for both the influx and efflux directions. MCF-7 cells were selected as model cancer cells and cultured with cyclosporin A (CsA) and its demethylated analogs (dmCsA-1, -2, and -3) as model CPs. Papp values (10-6 cm/s) obtained from cells incubated with 50 μM CPs ranged from 0.017 to 0.121 for influx and 0.20 to 1.48 for efflux. The higher efflux ratio was possibly caused by efflux transporters such as P-glycoprotein, a well-known receptor of CsA. The equilibrated intracellular concentration of CPs was estimated to be as low as 4.1-6.8 μM, which showed good consistency with the high efflux ratio. SCC-MS is promising as a reliable permeability assay for next-generation CP-based pharmaceuticals.Temperature dynamics reflect the physiological conditions of cells and organisms. Mitochondria regulate the temperature dynamics in living cells as they oxidize the respiratory substrates and synthesize ATP, with heat being released as a byproduct of active metabolism. Here, we report an upconversion nanoparticle-based thermometer that allows the in situ thermal dynamics monitoring of mitochondria in living cells. We demonstrate that the upconversion nanothermometers can efficiently target mitochondria, and the temperature-responsive feature is independent of probe concentration and medium conditions. The relative sensing sensitivity of 3.2% K-1 in HeLa cells allows us to measure the mitochondrial temperature difference through the stimulations of high glucose, lipid, Ca2+ shock, and the inhibitor of oxidative phosphorylation. Moreover, cells display distinct response time and thermodynamic profiles under different stimulations, which highlight the potential applications of this thermometer to study in situ vital processes related to mitochondrial metabolism pathways and interactions between organelles.Nitrogen can be electrochemically reduced to produce ammonia, which supplies an energy-saving and environmental-benign route at room temperature, but high-efficiency catalysts are sought to reduce the reaction barrier. Here, iron-doped α-MoO3 nanosheets are thus designed and proposed as potential catalysts for fixing N2 to NH3. The α-MoO3 band structure is intentionally modulated by the iron doping, which narrows the band gap of α-MoO3 and turns the semiconductor into a metal-like catalyst. Oxygen vacancies, generated by substituting Mo6+ for Fe3+ anions, are beneficial for nitrogen adsorption at the active sites. In 0.1 M Na2SO4, the Fe-doped MoO3 catalyst reached a high faradaic efficiency of 13.3% and an excellent NH3 yield rate of 28.52 μg h-1 mgcat-1 at -0.7 V versus reversible hydrogen electrode, superior to most of the other metal-based catalysts. Theoretical calculations confirmed that the N2 reduction reaction at the Fe-MoO3 surface followed the distal reaction path.Stevia (Stevia rebaudiana Bertoni) possesses substantial value for its unique sweet compounds-steviol glycosides (SGs). In the metabolic glycosylation grid of SGs, SrUGT91D2 has been shown to catalyze formation of 1,2-β-d-glucoside linkages at the C13- and C19-positions and play a crucial role in the synthesis of SGs, including the formation of stevioside (ST), rebaudioside E (RE), and rebaudioside D (RD). However, the key residues of the SrUGT91D2 enzyme and how SrUGT91D2 affects the accumulation of SGs in S. rebaudiana remain unclear. In the present study, cloning and functional analysis of full-length SrUGT91D2 gene sequences were performed in 10 different S. rebaudiana genotypes with divergent SG compositions. After sequence analysis, it was found that most of the sequences of this gene (more than 50%) in each genotype were consistent with the UGT91D2e_No.5 allele, which has been reported to exert catalytic activity on 1,2-β-d-glucoside. Moreover, six variants (UGT91D2e_No.5, SrUGT91D2-11-14, SrUGT91D2-1191D2. After site-mutation and enzyme assays, it was confirmed that T84, T144, R404, A194, and G409 are the key residues in the SrUGT91D2 protein, especially T144 and G409. This work provided valuable information for understanding the structure-activity relationship of the SrUGT91D2 protein and the molecular mechanism of SG accumulation in stevia.Based on the supramolecular interaction between vancomycin (Van), an antibiotic glycopeptide, and D-Ala-D-Ala (DADA) dipeptides, a novel class of artificial metalloenzymes was synthesized and characterized. The presence of an iridium(III) ligand at the N-terminus of DADA allowed the use of the metalloenzyme as a catalyst in the asymmetric transfer hydrogenation of cyclic imines. In particular, the type of link between DADA and the metal-chelating moiety was found to be fundamental for inducing asymmetry in the reaction outcome, as highlighted by both computational studies and catalytic results. Using the [IrCp*(m-I)Cl]Cl ⊂ Van complex in 0.1 M CH3COONa buffer at pH 5, a significant 70% (S) e.e. was obtained in the reduction of quinaldine B.Vibrationally excited deuterium fluoride (DF) formed by fluorine atom reaction with a solvent was found (Science, 2015, 347, 530) to relax rapidly (less than 10 ps) in acetonitrile-d3 (CD3CN) and dichloromethane-d2 (CD2Cl2). However, insights into how CD2Cl2 facilitates this energy relaxation have so far been lacking, given the weak interaction between DF and a single CD2Cl2. In this work, we report the results of reactive simulations with a two-state reactive empirical valence bond (EVB) potential to study the energy deposited into nascent DF after transition-state passage and of nonequilibrium molecular dynamics simulations using multiple different potential energy functions to model the relaxation dynamics. ATG-017 ic50 For these second simulations, we used the standard Merck molecular force field (MMFF) potential, an MMFF-based covalent-ionic empirical valence bond (EVB) potential (EVBCI), a newly developed potential [referred to as MMFF(rDF)] which extends upon the MMFF potential by making the DF/CD2Cl2 interaction depend on the value of the D-F bond stretching coordinate and by taking the anisotropic charge distribution of the solvent molecules into account, the polarizable atomic multipole optimized energetics for biomolecular applications (AMOEBA) potential, and the quantum mechanics/molecular mechanics (QM/MM) potential.
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