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A concise method of synthesizing the tetracyclic core of annotinolide C has been developed. The key steps include a tandem epoxidation/semipinacol rearrangement step to construct a quaternary aza [6.5] spiro ring (rings A and B), an intramolecular aldol reaction to assemble a [3.2.1] bridged ring system, and tandem semireduction/lactonization to form a five-membered lactone D-ring.

Yun Hong,1,* Da-Peng Dai,2,* Jian-Ping Cai,2 Shuang-Hu Wang,3 Yi-Ran Wang,1,4 Fang-Ling Zhao,2,4 Shan Zhou,2 Quan Zhou,3 Pei-Wu Geng,3 Yun-Fang Zhou,3 Xue Xu,1 Ji-Hua Shi,1 Qing-Feng Luo1 1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, 100730, People’s Republic of China; 3Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People’s Hospital of Lishui, Lishui, 323020, People’s Republic of China; 4Peking University Fifth School of Clinical Medicine, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-Feng Luo, Department of Gastroenterology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Tel + 86 138 1151 9095, Email luoqf2000@126.comPurpose: To study the potential drug–drug interactions between simvastatin and vonoprazan and to provide the scientific basis for rational use of them in clinical practice.Methods: An incubation system was established with rat liver microsomes, and the main metabolite of vonoprazan M-I was detected by UPLC-MS/MS. The IC50 value of simvastatin was then calculated and its inhibitory mechanism against vonoprazan was also analyzed. Twelve SD rats were randomly divided into 2 groups, then they were given simvastatin or saline for 2 weeks continuously. On the day of the experiment, both groups were intragastrically administered with vonoprazan once, followed by the collection of blood at different time points. Then the plasma concentration of vonoprazan and M-I in rats were detected by UPLC-MS/MS.Results: In vitro experiments revealed that simvastatin could inhibit the metabolism of vonoprazan, and its inhibition type belonged to the mixed non-competitive and competitive inhibition model. In vivo experiments in rats demonstrated that the area under concentration time curve (AUC) of vonoprazan was decreased but the clearance (CLz/F) of it was increased in the simvastatin administrated group, as compared to those of the control group. However, M-I in simvastatin treated group exhibited the higher AUC and lower CLz/F values compared to those in the control group. These data indicated that multiple doses of simvastatin administration could reduce the plasma concentration of vonoprazan and accelerate its metabolic rate in rats.Conclusion: Simvastatin could inhibit the metabolism of vonoprazan in vitro but multiple doses of simvastatin exhibited the opposite effect In vivo. Altogether, our data indicated that an interaction existed between simvastatin and vonoprazan and additional cares might be taken when they were co-administrated in clinic.Keywords: vonoprazan, simvastatin, drug–drug interactions, liquid chromatography-tandem mass spectrometry, rat liver microsomes

A tandem Bischler-Napieralski/semipinacol rearrangement reaction has been developed for the purpose of assembling a bis(spirocyclic) indole framework, a privileged structural unit of aspidofractinine-type monoterpenoid indole alkaloids, and was used in combination with a subsequent Mannich reaction to expeditiously construct the central bridged bicyclo[2.2.1]heptane ring system of these molecules with contiguous quaternary centers. The development of this novel strategy culminated in the collective total synthesis of four aspidofractinine alkaloids.

With the acceleration of China’s urbanization process, in order to meet the needs of new urban users’ source-source interaction and multi-energy complementation, this paper proposes a new urban energy interconnection LAN design and construction ideas, from distributed photovoltaic systems, energy storage systems, phase change heat storage. The system and the AC-DC grid interconnection and intercommunication four specific aspects of the design and construction plan, given the electric vehicle charging and discharging interactive operation and phase change heat storage and ground source heat pump combined heating two typical application scenarios.

A sensitive and rapid ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to determine methadone, EDDP, fluoxetine, norfluoxetine, venlafaxine and O-desmethylvenlafaxine in rat plasma using diazepam as the internal standard (IS). Sample preparation was accomplished through a simple one-step protein precipitation with 200 µL acetonitrile added to 100 µL rat plasma. The analytes were separated on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) and the mobile phase was acetonitrile and 0.1 % formic acid in water in gradient elution at a flow rate of 0.40 mL min−1. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with positive electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions. The linearity of this method was found to be within the concentration range of 0.5–250.0 ng mL−1 for methadone, EDDP, fluoxetine and norfluoxetine and 0.4–200.0 ng mL−1 for venlafaxine and O-desmethylvenlafaxine, respectively. The limit of quantification (LOQ) was 0.5 ng mL−1 for methadone, EDDP, fluoxetine and norfluoxetine and 0.4 ng mL−1 for venlafaxine and O-desmethylvenlafaxine, respectively. A time period of 3 min was needed for an analytical run. The method described above was successfully applied to the subsequent pharmacokinetic study.

A novel organocatalytic asymmetric tandem Nazarov cyclization/semipinacol rearrangement reaction using "unactivated" substrates has been developed, generating a series of chiral spiro[4.4]nonane-1,6-diones in up to 96% yield and 97% enantiomeric excess. Significantly, it is the first direct example for asymmetric synthesis of cyclopentanones with four stereocenters using Nazarov cyclization. DFT calculations have been applied to understand the reaction mechanism, stereochemistry, and substituent effects.

The development of low-carbon energy economy has become common choice of the world to solve energy security and environmental issues in the context of climate change and energy issues. Carrying out construction of intelligent community becomes the key technology for optimizing energy efficiency of smart grid. This paper focuses on low-carbon energy management system of intelligent community, which including: construction mode, functional configuration and mode switching condition on low-carbon energy management system of intelligent community as well as the coordination between the upper and lower subsystem. These can provide reference technology solutions for energy management of intelligent community in China.

It is necessary to monitor and optimize work status of central air-conditioning system (CACS) due to its high energy consumption. According to national standard, this paper designed a practical energy-efficiency evaluation method with double-layers structure. The upper-layer indicator reflects the whole energy efficiency of CACS. The lower-layer indicators reflect the energy efficiency of each subsystem of CACS, such as refrigeration system, chilled water system and terminal system. Using this double-layers evaluation system, the managers of CACS can not only observe the whole energy efficiency level but also find out the weak point of the system.

In order to improve the level of automation and security of the low voltage power supply system, this paper proposed the calculation method of short-circuit current criterion under condition of protection action. Firstly, the impact of circuit breakers on the short-circuit current is analyzed. Then, the current criterion under condition of short-circuit protection are given. Finally, using a special case, the calculation process of aforementioned current criterion is given in detail.

According to external dual power line supply and the grid-connected and islanded operating modes of micro-grid and the changeover among them, a control strategy of micro-grid with different kinds of DG (Distributed Generation) is proposed. It monitors the operating states of both micro-grid and power network and provides the unified coordinating control by the controller of micro-grid. In grid-connected mode, all kinds of DG work in constant power mode (P-Q mode) to generate power output for load. In islanded mode, energy storage system works in constant voltage-frequency mode (V-f mode), which is selected as the master power for supporting the voltage and frequency in micro-grid. And the rest works in P-Q mode. The application at one smart community in Shanghai proved its feasibility. The proposed strategy keeps the stable operation of micro-grid and implements the seamless transition between two operating modes by synchronizing device in grid-connected point.

Total syntheses of the biologically important and structurally unique tetracyclic diterpenes conidiogenone, conidiogenol, and conidiogenone B of the cyclopiane class are reported. The absolute configuration of naturally occurring conidiogenone B was also corrected. The key step of our strategy involved the highly efficient construction of both ring C and the quaternary carbon center shared by rings A and C through a one-step regioselective and diastereoselective cycloenlargement in the form of a semipinacol-type rearrangement. In particular, the desired regioselectivity was made possible by properly adjusting the migratory aptitude of the migrating carbon atom through the introduction of an electron-donating phenylthio group at this position.

Total syntheses of the biologically important and structurally unique tetracyclic diterpenes conidiogenone, conidiogenol, and conidiogenone B of the cyclopiane class are reported. The absolute configuration of naturally occurring conidiogenone B was also corrected. The key step of our strategy involved the highly efficient construction of both ring C and the quaternary carbon center shared by rings A and C through a one-step regioselective and diastereoselective cycloenlargement in the form of a semipinacol-type rearrangement. In particular, the desired regioselectivity was made possible by properly adjusting the migratory aptitude of the migrating carbon atom through the introduction of an electron-donating phenylthio group at this position.

Using double-network, double-machine technology, the hardware framework of the energy management system is designed. The software framework scheme is proposed according to different layers. By designing graph, report, alarm, database management, man-machine interface and privilege subsystems on supporting platform, various services are presented. The proposed energy management system integrated many automation systems, such as Distribution Automation system, Advanced Metering Infrastructure and so on. The senior application functions of the energy management system are introduced. Adopting smart grid technology, the proposed scheme provides a new solution to better manage, use, save and monitor energy especially renewable energy. Because of its obvious advantages in enhancing energy efficiency, the introduced energy management system is expected to be widely used in low-carbon community.

The operation control of the micro-grid system is the foundation to protect micro-grid equipment, to realize associate control and optimize economic operation. Looking on Chenjiazhen micro-grid in Shanghai as model, the paper set three hierarchical controls: protection control, micro-grid coordinated controller control which can achieve millisecond time precision and intelligent community energy management system control. Different level control function has been divided. Control functions in all levels complement each other and collaborate together to achieve the coordination and control of micro-grid running.

The micro-grid structure and operation mode are analyzed in this paper. By listing micro-grid typical operation mode, and explains the energy management system, micro-grid controller, electric primary equipment is how to coordinate between control. Analysis of the usual method for the energy management system optimization control strategy will be passed to the micro-grid controller. A kind of brand-new control command transmission mode is put forward for improving the micro-grid control strategy by the efficiency.

A novel organocatalytic asymmetric tandem Nazarov cyclization/semipinacol rearrangement reaction using "unactivated" substrates has been developed, generating a series of chiral spiro[4.4]nonane-1,6-diones in up to 96% yield and 97% enantiomeric excess. Significantly, it is the first direct example for asymmetric synthesis of cyclopentanones with four stereocenters using Nazarov cyclization. DFT calculations have been applied to understand the reaction mechanism, stereochemistry, and substituent effects.

To perform a pharmacogenetic study of a patient with warfarin hypersensitivity and determine the biological function of a novel CYP2C9 mutation.Genomic DNAs were extracted from the warfarin hypersensitive patient and used for genetic screening of CYP2C9, VKORC1 and CYP4F2 by direct sequencing. Acquired sequences were aligned and blasted with public nucleotide database to clarify whether site mutations were present in these 3 genes. Full-length cDNA fragments of CYP2C9*2, *3, *13 and 1400TC were obtained by polymerase chain reaction (PCR) site-directed mutagenesis and used for the insect expression vector construction. According to the manufacturer's instruction, insect cell microsomes expressing 5 CYP2C9 variants were obtained with Bac-to-Bac Baculovirus Expression System. Then CYP2C9 protein expression level for each variant was quantified by Western blot and tolbutamide used as a probing substrate for assessing the in vitro metabolic characteristics of each CYP2C9 variant. Vmax and Km values were calculated and used for evaluating the biological impact of novel 1400TC mutant.One novel nucleotide mutation 1400TC was detected in DNAs of tested patient. And this site mutation resulted in one amino acid change at position 467 of CYP2C9 protein (L467P). Other two candidate genes VKORC1 and CYP4F2 were found to be the wild-type alleles. When expressed in insect cell microsomes, the relative clearance values of CYP2C9 *2, *3, *13 and L467P variants to tolbutamide were 91.58%, 13.55%, 0.11% and 1.59% to that of wild-type protein respectively.1400TC mutation of CYP2C9 gene greatly reduces the in vitro enzymatic activity of CYP2C9. While taking the drugs metabolized by CYP2C9, the patients carrying this mutated allele should take more cautions because their metabolic rates are slower than those of wild-type carriers. Ensuing drug accumulation in vivo may cause potentially serious adverse reactions.

The effects of a premixed layer on the Richmyer—Meshkov instability (RMI) are studied by setting a density gradient for the first shocked fluid in the RMI problems. The RMI with initial density gradients are simulated by using a high resolution arbitrary Lagrangian—Eulerian method. The effects of density gradient and gradient width are analyzed on the basis of the simulation results for the shock from a light fluid to a heavy fluid and for the shock from a heavy fluid to a light fluid. Overall, the premixed layer can suppress the perturbation growth, and the detailed effects are different depending on the detailed premixed configuration. The width of the premixed layer has a very light influence on the perturbation, while the density gradient has quite a significant effect on two kinds of RMIs.