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Cephalotane-Type Norditerpenoids from Cephalotaxus fortunei ***

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Chinese Journal of Chemistry 2022年第10期40卷 1177-1184页

作者： zhan-peng ge Bin Zhou Flavia M.Zimbres Maria B.Cassera Jin-Xin Zhao Jian-Min Yue State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of Sciences555 Zuchongzhi RoadShanghai 201203China Department of Biochemistry and Molecular Biology Center for Tropical and Emerging Global Diseases(CTEGD)University of GeorgiaAthensGeorgia30602UnitedStates

A chemical investigation of the 95%EtoH extract of the seeds of Cephalotaxus fortunei *** led to the isolation of nine new cephalotane-type norditerpenoids,ceforalides A-I(1-9),and two known analogues(10 and 11).Compounds 1-8 belong to a rare class of A-ring-contracted cephalotane-type norditerpenoids,of which compound 8 incorporates a unique tetrasubstituted 2,5-cyclohexadienone *** 9 is a rare 13,14-seco-17-nor-cephalotane-type *** structures were determined based on NMR,HRESIMS,ECD,and X-ray diffraction *** tests revealed compounds 10 and 11 displayed moderate antimalarial activity.

关键词： Cephalotaxus fortunei var.alpine Natural products Structural elucidation Cephalotane norditerpenoids I Antimalarial activity

Twice-yearly lenacapavir demonstrated exceptional efficacy for HIV prevention

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The Innovation 2024年第5期5卷 9-10页

作者： Shujing Xu peng zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China

Acquired immunodeficiency syndrome(AIDS),a contagious illness arising from the human immunodeficiency virus(HIV),presents significant threats to human health and societal *** on genotypic differences,HIV can be divided into two main subtypes,HIV-1 and HIV-2,of which HIV-1 is the dominant global variant characterized by its heightened transmissibility and *** from 2022 indicate that approximately 39 million people are living with HIV globally,with 1.3 million new cases reported that *** combination antiretroviral therapy(cART)has demonstrated significant effectiveness in combating HIV infection,hurdles such as the emergence of multidrug-resistant HIV strains,potential long-term side effects,limited accessibility in economically underprivileged areas,and obstacles to treatment adherence hinder its widespread implementation.1 This necessitates the development of innovative medications with diverse resistance profiles and new therapeutic *** multifunctional HIV-1 capsid protein(CA)has emerged as a highly promising target in HIV-1 medication *** CA has a fullerene-shaped structure,consisting of 250 hexamers and 12 pentamers,which is crucial for viral ***,CA plays essential roles in multiple events during viral replication,including reverse transcription,nuclear entry,integration site distribution,assembly,and maturation.2 Therefore,CA-targeting small molecules can provide antiviral efficacy in both the early and late stages of the viral life cycle.

关键词： prevention exceptional globally

Jun12682,a potent SARS-CoV-2 papain-like protease inhibitor with exceptional antiviral efficacy in mice

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4189-4192页

作者： Mianling Yang Meehyein Kim peng zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJi’nan 250012China Infectious Diseases Therapeutic Research Center Korea Research Institute of Chemical Technology(KRICT)Daejeon 34114Republic of Korea

Recently,a collaborative research study published in Science,led by Jun Wang,Xufang Deng,Eddy Arnold,and Francesc Xavier Ruiz1,identified a series of potent small molecule inhibitors that specifically target SARS-CoV-2 papain-like protease(PLpro).The study demonstrated nanomolar PLpro inhibitory potency with Ki values ranging from 13.2 to 88.2 nmol/*** employing a structure-based drug design strategy,the researchers discovered an exceptionally promising compound,named Jun12682,that effectively targets both the newly discovered ubiquitin Val70(Val70Ub)-binding site and the known blocking loop(BL2)groove near the S4 subsite of ***,studies on the mechanism of action revealed that Jun12682 inhibits the deubiquitinating and deISGylating activities of PLpro,which are crucial for antagonizing the host’s innate immune response upon viral *** biology studies confirmed the“two-pronged”binding mode of Jun12682,aligning perfectly with their drug design ***,Jun12682 exhibited potent antiviral activity against SARS-CoV-2 and its variants,including nirmatrelvir-resistant mutants,in Caco-2 cells(EC50:0.44e2.02 mmol/L).It is noteworthy that its oral administration significantly improved survival rates and alleviated both lung virus loads and histopathological lesions in a lethal SARS-CoV-2 mouse *** conclusion。

关键词： SARS-CoV-2 Papain-like protease Broad-spectrum Anti-drug resistance Drug candidate

Effects of the Resident Basic Medical Insurance Reform on Household Consumption in China

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China & World Economy 2024年第1期32卷 96-129页

作者： Shuheng Yu Xinxin Ma peng zhan School of Public Affairs Institute for Common Prosperity and DevelopmentZhejiang UniversityChina Faculty of Economics Hosei UniversityJapan

This paper investigates the causal relationship between the Urban and Rural Resident Basic Medical Insurance(URRBMI)reform and household consumption in urban China using data from the Chinese Household Income Project survey and employing combination of the propensity score matching and difference-in-differences *** results yield three ***,the reform affected both the amount and share of household ***,the reform led to an increase in total household consumption,encompassing both medical and nonmedical *** these,the proportion of medical consumption increased,while the proportion of nonmedical consumption ***,the impact of the URRBMI reform varied across consumption categories within nonmedical ***,consumption for education and entertainment industries are positively impacted by the URRBMI reform in terms of both quantity and ***,low-income households benefit more from the URRBMI reform compared to middle-and high-income *** main channels through which the URRBMI reform affects household consumption were the price effect and the crowding out effect on precautionary savings.

关键词： household consumption nonmedical consumption out-of-pocket expenses reimbursement ratio

Vector magnetometry in zero bias magnetic field using nitrogen-vacancy ensembles

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Chinese Physics B 2024年第10期33卷 21-29页

作者： Chunxing Li Fa-zhan Shi Jingwei Zhou peng-Fei Wang CAS Key Laboratory of Microscale Magnetic Resonance and School of Physical Sciences University of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Quantum Information and Quantum Physics University of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230088China

The application of the vector magnetometry based on nitrogen-vacancy(NV)ensembles has been widely investigatedin multiple *** has the superiority of high sensitivity and high stability in ambient conditions with microscale ***,a bias magnetic field is necessary to fully separate the resonance lines of optically detected magneticresonance(ODMR)spectrum of NV *** brings disturbances in samples being detected and limits the rangeof ***,we demonstrate a method of vector magnetometry in zero bias magnetic field using NV *** utilizing the anisotropy property of fluorescence excited from NV centers,we analyzed the ODMR spectrum of NVensembles under various polarized angles of excitation laser in zero bias magnetic field with a quantitative numerical modeland reconstructed the magnetic field *** minimum magnetic field modulus that can be resolved accurately is downto~0.64 G theoretically depending on the ODMR spectral line width(1.8 MHz),and~2 G experimentally due to noisesin fluorescence signals and errors in *** using 13C purified and low nitrogen concentration diamond combinedwith improving calibration of unknown parameters,the ODMR spectral line width can be further decreased below 0.5 MHz,corresponding to~0.18 G minimum resolvable magnetic field modulus.

关键词： vector magnetometry NV ensembles optically detected magnetic resonance(ODMR) zero bias magnetic field

Discovery of GluN2A subtype-selective N-methyl-d-aspartate(NMDA)receptor ligands

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1987-2005页

作者： Liyang Jiang Na Liu Fabao Zhao Boshi Huang Dongwei Kang peng zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

The N-methyl-d-aspartate(NMDA)receptors,which belong to the ionotropic Glutamate receptors,constitute a family of ligand-gated ion *** the various subtypes of NMDA receptors,the GluN1/2A subtype plays a significant role in central nervous system(CNS)*** present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors,encompassing negative allosteric modulators(NAMs),positive allosteric modulators(PAMs)and competitive ***,the ligands’structure–activity relationships(SARs)and the binding models of representative ligands are also discussed,providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

关键词： NMDA receptors GluN2A subtype Subtype-selective ligands SARs Protein ligand interactions

Effect of Al content on modification behavior of non-metallic inclusions in high-strength steel treated with rare earth

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Journal of Iron and Steel Research International 2024年第8期31卷 1886-1899页

作者： zhan-peng Tie Xue-yuan Jiang Hai-yan Tang ·gen Li Yu-hang Wang Jia-quan zhang School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing 100083China Continuous Casting Business Section CISDI Engineering Co.Ltd.Chongqing 401122China Special Steel Institute Central Iron and Steel Research Institute Co.Ltd.Beijing 100081China

The influence of Al content(0.0053,0.0171,and 0.0578 wt.%)on the modification behavior of non-metallic inclusions in 20CrMoVTiB steel treated with rare earth elements was studied through high-temperature experiments and thermodynamic *** results showed that the modification products varied with the Al content in steel under 0.01 wt.%of Ce *** formation sequence of typical rare earth inclusions in steel with the increase in Al content was Ce_(2)O_(3)→CeAlO_(3)→CeAl_(11)O_(18),and the final stable products were highly Al content *** the Al content was 0.0053 wt.%,the stable phase in steel was Ce2O3;while the[Al]reached 0.0171 wt.%,the stable phase became CeA1O_(3).As the A1 content reached 0.0578 wt.%,CeAl_(11)O_(18) became the stable *** a result,increasing the Al content could inhibit the precipitation of Ce_(2)O_(3) inclusions in steel while promote the formation of CeAIO3 and CeAl_(11)O_(18) *** addition,both Ca treatment and Ce treatment could effectively refine the size of inclusions in steel by changing their ***,the feeding amount of Ca wire into molten steel should be appropriately reduced under the condition of adding Ce simultaneously,which is expected to be beneficial for an improved Ce treatment effect.

关键词： Rare earth Al content Steel Inclusion Thermodynamics Ca treatment

Rapid Phase Ambiguity Elimination Methods for DOA Estimator via Hybrid Massive MIMO Receive Array

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Chinese Journal of Electronics 2024年第1期33卷 175-184页

作者： Xichao zhan Zhongwen SUN Feng SHU Yiwen CHEN Xin CHENG Yuanyuan WU Qi zhanG Yifan LI peng zhanG School of Information and Communication Engineering Hainan University School of Electronic and Optical Engineering Nanjing University of Science and Technology

For a sub-connected hybrid multiple-input multiple-output(MIMO) receiver with K subarrays and N antennas, there exists a challenging problem of how to rapidly remove phase ambiguity in only single time-slot. A direction of arrival(DOA) estimator of maximizing received power(Max-RP) is proposed to find the maximum value of K-subarray output powers, where each subarray is in charge of one sector, and the center angle of the sector corresponding to the maximum output is the estimated true DOA. To make an enhancement on precision, Max-RP plus quadratic interpolation(Max-RP-QI) method is designed. In the proposed Max-RP-QI, a quadratic interpolation scheme is adopted to interpolate the three DOA values corresponding to the largest three receive powers of *** achieve the Cramer Rao lower bound, a Root-MUSIC plus Max-RP-QI scheme is developed. Simulation results show that the proposed three methods eliminate the phase ambiguity during one time-slot and also show low computational complexities. The proposed Root-MUSIC plus Max-RP-QI scheme can reach the Cramer Rao lower bound,and the proposed Max-RP and Max-RP-QI are still some performance losses 2–4 d B compared to the Cramer Rao lower bound.

关键词： Phased arrays Interpolation Wireless sensor networks Direction-of-arrival estimation Simulation Receiving antennas Massive MIMO

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu zhan Wang Yuan-Sheng Zang Department of Medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive