C
FN
, triclinic, P1̄ (no. 2), a = 10.8141(6) Å, b = 11.0261(6) Å, c = 11.9967(7) Å, α = 83.398(4)°, β = 65.586(3)°, γ = 81.088(4)°, V = 1284.7 Å
, Z = 2, R
(F) = 0.0490, wR
(F
) = 0.1519, T = 296 K.
We report a general protocol for the convergent synthesis of 1,4-dicarbonyl Z-alkenes form alkynes using α-diazo sulfonium triflate and water. The CO, CC, and C–H bonds are formed under mild ...conditions with a wide range of functional groups tolerated. The reaction exhibits excellent Z-selectivity and complete regioselectivity. The resulting 1,4-dicarbonyl Z-alkenes can smoothly undergo follow-up conversion to a variety of heteroaromatic scaffolds. Moreover, the reaction also provides a facile access to the corresponding deuterated Z-alkenes and deuterated heteroarenes with a high level of deuterium incorporation (90–97% D-inc.) by directly using D2O, thus rendering the method highly valuable. The comprehensive mechanistic studies indicate that a free carbyne radical intermediate is formed via the photocatalytic single electron transfer process, and KH2PO4 plays a crucial role in significant improvements on yield and selectivity based on density-functional theory calculations, providing a new direction for radical coupling reactions of diazo compounds.
Xiao‐Ke‐An is a traditional Chinese medicine formula for reducing the effects of diabetes by inhibiting dipeptidyl peptidase‐4 (DPP‐4) activity. However, its molecular mechanism is unclear owing to ...the complexity of its components. In this study, methods of molecular docking, molecular dynamics and molecular mechanics/Poisson Boltzmann surface area are combined for analysis. The main hypoglycaemic mechanism of Xiao‐Ke‐An involves multiple components. In particular, MOL003714 shows the strongest binding capacity with a binding free energy of −253.08 kJ mol−1 and thus could be a potent inhibitor of DPP‐4. Additionally, MOL007062 and MOL010404 show strong interactions with superoxide dismutase, tumour necrosis factor‐alpha and caspase‐3, indicating their ability to decrease the symptoms of type II diabetes by alleviating insulin resistance and reducing inflammatory reactions and oxidative stress. This study provides a theoretical basis for the discovery and modification of natural DPP‐4 inhibitors and details the role of Xiao‐Ke‐An.
In this study, hypoglycaemic mechanism of Xiao‐Ke‐An based on DPP‐4 has been explored by molecular docking and dynamic simulation. MOL003714 shows the strongest binding capacity with DPP‐4 and thus could be a potent inhibitor of DPP‐4. In addition, MOL010404 and MOL007062 show additional effects in decreasing the symptoms of type II diabetes by alleviating insulin resistance and reducing inflammatory reactions and oxidative stress.
The microstructure and property degradation of turbine blades in aircraft engines during service would finally pose threat to service safety. But report on systematic research work about ...microstructure and property degradation of serviced turbine blades is limited. In this paper, the 2 super(nd) stage turbine blade made of wrought Ni-based superalloy GH4033 was taken from an aircraft engine and investigated by metallographic analysis and physical and chemical phase analysis after service exposure for about 1600 engine operating hours (EOH). Microstructural features including grain microstructure, gamma+gamma' matrix and grain boundary (GB) carbides in different locations of the serviced blade were observed and quantitatively characterized. Vickers hardness and stress rupture tests were also conducted. The microstructure characterization indicates that the degradation in grain size, gamma' precipitates and GB carbides is rarely observed in the airfoil. The service temperature is estimated to be lower tha
Background. Genital human papillomavirus (HPV) infection is believed to be primarily sexually transmitted. Few studies have documented the detection of HPV in the vagina before first vaginal ...intercourse. Methods. We used a longitudinally followed cohort of adolescent females without prior vaginal intercourse to examine the frequency of detection of vaginal HPV and the association between first reported HPV detection and noncoital sexual behaviors. Results. HPV was detected in 45.5% of subjects (10 of 22) before first vaginal sex. Seven of these 10 subjects reported noncoital behaviors that, in part, might have explained genital transmission. Conclusions. HPV can be detected in the vagina before first sexual intercourse, highlighting the need for early vaccination.
Aconitum, widely used to treat rheumatoid arthritis for thousands of years, is a toxic herb that can frequently cause fatal cardiac poisoning. Aconitum toxicity could be decreased by properly ...hydrolyzing diester-diterpene alkaloids into monoester-diterpene alkaloids. Monoester-diterpene alkaloids, including benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), are the primary active and toxic constituents of processed Aconitum. Cytochrome P450 (CYP) enzymes protect the human body by functioning as the defense line that limits the invasion of toxicants. Our purposes were to identify the CYP metabolites of BAC, BMA, and BHA in human liver microsomes and to distinguish which isozymes are responsible for their metabolism through the use of chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzyme. High-resolution mass spectrometry was used to characterize the metabolites. A total of 7, 8, and 9 metabolites were detected for BAC, BMA, and BHA, respectively. The main metabolic pathways were demethylation, dehydrogenation, demethylation-dehydrogenation, hydroxylation and didemethylation, which produced less toxic metabolites by decomposing the group responsible for the toxicity of the parent compound. Taken together, the results of the chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzymes experiments demonstrated that CYP3A4 and CYP3A5 have essential functions in the metabolism of BAC, BMA, and BHA.
Ionic covalent organic frameworks (COFs) consisting of an anionic or cationic skeleton and corresponding counterions have demonstrated great potential in many application fields such as ion ...conduction, molecular separation, and catalysis. However, arranging anionic and cationic groups into the same COF to form zwitterionic materials is still unexplored. Herein we design the synthesis of three zwitterionic COFs as attractive porous hosts for SO2/CO2 separation and anhydrous proton conduction. The separated cationic and anionic groups in zwitterionic COFs’ channels can act as two different polar sites for SO2 adsorption, allowing zwitterionic COFs to achieve a high SO2 adsorption capacity (216 mL/g, 298 K) and impressive SO2/CO2 selectivity (118, 298 K). Furthermore, after loading with triazole/imidazole, the zwitterionic groups in COFs’ channels can induce complete proton carrier deprotonation, producing more freely migrating protons. The free protons migrate along a continuous hydrogen-bonding network in zwitterionic COFs’ channels, leading to outstanding anhydrous proton conductivity up to 4.38 × 10–2 S/cm, which is much higher than other N-heterocyclic-doped porous materials under anhydrous conditions. Proton dissociation energy calculations combined with frequency-dependent dielectric analysis give insight into the role of zwitterionic COFs for proton conductivity. Our work provides the possibility to design well-defined zwitterionic frameworks for gas separation and ion conduction.
Bioassay-guided investigation of the stem bark of Hopea chinensis led to the isolation of two new polyphenols, hopeachinols C(1) and D(2), together with ten known compounds (3-12). Compounds 1 and 2 ...were determined by extensive analysis of spectroscopic data and computational methods. All of these phytochemicals were tested for acetylcholinesterase inhibitory activity, and five resveratrol-derived compounds (1 and 7-10) exhibited significant activity with their IC₅₀ values ranging from 4.81 to 11.71 µM.
Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal a strong ...genetic dependency between a major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both the ubiquitin ligase complex UBR4-KCMF1 and the acetyltransferase NatC recognize proteins bearing an unacetylated N-terminal methionine followed by a hydrophobic residue. NatC KO-induced protein degradation and phenotypes are reversed by UBR knockdown, demonstrating the central cellular role of this interplay. We reveal that loss of Drosophila NatC is associated with male sterility, reduced longevity, and age-dependent loss of motility due to developmental muscle defects. Remarkably, muscle-specific overexpression of UbcE2M, one of the proteins targeted for NatC KO-mediated degradation, suppresses defects of NatC deletion. In conclusion, NatC-mediated N-terminal acetylation acts as a protective mechanism against protein degradation, which is relevant for increased longevity and motility.
Wet grinding is a process that involves many different subprocesses. In order to model this highly complex process, efficient models of the individual subprocesses are required that are robust enough ...to be used in multiphysics analyses. To approach the modelling of the macroscopic hydrodynamic effects of the grinding wheel as one component of the analysis, this paper is dedicated to the thermo-hydrodynamic problem and its modelling by expanding the isogeometric analysis (IGA) from hydrodynamic analysis to the thermal consideration. Extended by a consideration of flow effects in areas with high surface gradients and particular attention paid to the necessary stabilization of the governing equations, thermo-hydrodynamic systems with temperature- and pressure-dependent fluid properties are considered. Selected benchmarks feasible for computational fluid dynamics (CFD) simulations are used to demonstrate the good suitability of this modelling strategy. The presented modelling strategies can also be applied to lubricated technical systems in general, beyond wet grinding systems.
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