Identification of the Metabolic Enzyme Involved Morusin Metabolism and Characterization of Its Metabolites by Ultraperformance Liquid Chromatogaphy Quadrupole Time-of-Flight Mass Spectrometry (UPLC/Q-TOF-MS/MS)

Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from humans (HLMs), rabbits (RAMs), and dogs (DLMs). Four metabolites (M1, M2, M5, and M7) were found in all species and hydroxylation was the major metabolic transformation. CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, and CYP2C19 contributed differently to the metabolism of morusin. Compared to other CYP450 isoforms, CYP3A4 played the most significant role in the metabolism of morusin in human liver microsomes. These results are significant to better understand the metabolic behaviors of morusin among various species

Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle

A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 μg·mL−1 for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 μg·mL−1. The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle

N-Heterocyclic carbene catalyzed radical coupling of aldehydes with redox-active esters

N-Heterocyclic carbene catalyzed radical reactions are challenging and underdeveloped. In a recent study, Ohmiya, Nagao and co-workers found that aldehyde carbonyl carbon centers can be coupled with alkyl radicals under NHC catalysis. An elegant aspect of this study is the use of a redox-active carboxylic ester that behaves as an single-electron oxidant to convert the Breslow intermediate into a radical adduct and concurrently release an alkyl radical intermediate as a reaction partner.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Accepted versio

A new evaluation method for micro-fracture plugging in high-temperature deep wells and its application: A case study of the Xushen Gas Field, Songliao Basin

Micro-fractures are developed in volcanic layers of Cretaceous Yingcheng Fm in the deep part of Xujiaweizi fault depression, Songliao Basin. In the process of well drilling, various complex problems happen, such as borehole wall slabbing and collapse and serious fluid leakage. Based on conventional drilling fluid plugging evaluation methods, the real situations cannot be presented accurately, especially in fracture feature simulation and plugging effect evaluation. Therefore, a specific micro-fracture plugging evaluation method was put forward especially for high-temperature deep wells in the paper. It is a new type of micro-fracture core model with the fracture apertures in the range of 1–50 μm. It is made of aluminosilicate that is compositionally close to natural rocks. It is good in repeatability with fracture-surface roughness, pore development and fracture-surface morphology close to natural fractures. Obviously, this new model makes up for the deficiencies of the conventional methods. A new micro-fracture plugging evaluation instrument was independently designed with operating temperature of 200 °C and operating pressure of 3.5–5.0 MPa. It can be used to simulate the flow regime of downhole operating fluids, with the advantages of low drilling fluid consumption, convenient operation and low cost. The plugging capacity of the organo-silicone drilling fluid system was evaluated by using this instrument. It is shown that the grain size distribution of the drilling fluid is improved and its anti-collapse capacity is enhanced. Based on the field test in Well XSP-3, the safe drilling problems in volcanic layers with developed micro-fractures are effectively solved by using the drilling fluid formula which is optimized by means of this evaluation method. And the safe drilling is guaranteed in the deep fractured formations in this area

NHC-catalyzed covalent activation of heteroatoms for enantioselective reactions

Covalent activation of heteroatoms enabled by N-heterocyclic carbene (NHC) organic catalysts for enantioselective reactions is evaluated and summarized in this review. To date, sulfur, oxygen, and nitrogen atoms can be activated in this manner to react with another substrate to construct chiral carbon–heteroatom bonds with high optical enantioselectivities. The activation starts with addition of an NHC catalyst to the carbonyl moiety (aldehyde or imine) of substrates that contain heteroatoms. The key in this approach is the formation of intermediates covalently bound to the NHC catalyst, in which the heteroatom of the substrate is activated as a nucleophilic reactive site.Ministry of Education (MOE)National Research Foundation (NRF)Published versionWe acknowledge financial support from the National Natural Science Foundation of China (21772029, 21801051, 21961006, 82360589, and 81360589), The 10 Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Guizhou Province Returned Oversea Student Science and Technology Activity Program [(2014)-2], the Science and Technology Department of Guizhou Province ([2018]2802, [2019]1020), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University, Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], and Guizhou University. We also acknowledge Singapore National Research Foundation under its NRF Investigatorship (NRFNRFI2016-06) and Competitive Research Program (NRFCRP22-2019-0002), the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG108/16, RG5/19, RG1/18), MOE AcRF Tier 2 (MOE2019-T2-2-117), MOE AcRF Tier 3 Award (MOE2018-T3-1-003), the Agency for Science, Technology and Research (A*STAR) under its A*STAR AME IRG Award (A1783c0008, A1783c0010), Nanyang Research Award Grant, and Nanyang Technological University

Functionalization of benzylic C(sp3)H bonds of heteroaryl aldehydes through N-heterocyclic carbene organocatalysis

Aryl aldehyde activation: Oxidative activation of 2-methylindole-3-carboxaldehyde (I) through N-heterocyclic carbene (NHC) organocatalysis generates heterocyclic ortho-quinodimethane (II) as a key intermediate. This intermediate then undergoes formal [4+2] cycloaddition with trifluoromethyl ketones or isatins to form polycyclic lactones containing a quaternary carbon center

Disrupted Interhemispheric Synchrony in Default Mode Network Underlying the Impairment of Cognitive Flexibility in Late-Onset Depression

The intuitive association between cognitive impairment and aberrant functional activity in the brain network has prompted interest in exploring the role of functional connectivity in late-onset depression (LOD). The relationship of altered voxel-mirrored homotopic connectivity (VMHC) and cognitive dysfunction in LOD is not yet well understood. This study was designed to examine the implicit relationship between the disruption of interhemispheric functional coordination and cognitive impairment in LOD. N=31 LOD patients and N=37 matched healthy controls (HC) underwent neuropsychological tests and functional magnetic resonance imaging (fMRI) in this study. The intergroup difference of interhemispheric coordination was determined by calculating VMHC value in the global brain. The neuro-behavioral relevancy approach was applied to explore the association between disrupted VMHC and cognitive measures. Receiver operating characteristic (ROC) curve analysis was used to determine the capability of disrupted regional VMHC to distinguish LOD. Compared to the HC group, significantly attenuated VMHC in the superior frontal gyrus, superior temporal gyrus, posterior cerebellar lobe, and post- and precentral gyri were observed in the bilateral brain of LOD patients. The interhemispheric asynchrony in bilateral posterior cerebellar lobes was positively correlated with the performance of trail making test B in LOD patients (r = 0.367, P = 0.040). ROC analysis revealed that regions with abnormal VMHC could efficiently distinguish LOD from healthy controls (AUC = 0.90, P < 0.001). Altered linkage patterns of intrinsic homotopic connectivity and impaired cognitive flexibility was first investigated in LOD, and it would provide a novel clue for revealing the neural substrates underlying cognitive impairment in LOD

Enantioselective sulfonation of enones with sulfonyl imines by cooperative N-heterocyclic-carbene/thiourea/tertiary-amine multicatalysis

Many hands make light work: In an organocatalytic asymmetric sulfonation of enones, the activation of a sulfonyl imine by an N-heterocyclic carbene (NHC) catalyst led to the release of a sulfinic anion, which underwent nucleophilic addition to the enone. The enantioselectivity of the process was controlled by a chiral thiourea/amine co-catalyst through anion recognition and hydrogen-bonding interactions. Tol=p-tolyl