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Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals

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Cellular & Molecular Immunology 2022年第5期19卷 588-601页

作者： Zi-Wei Ye Chon Phin Ong Kaiming Tang Yilan Fan cuiting luo Runhong Zhou Peng luo Yun Cheng Victor Sebastien Gray Pui Wang Hin Chu Jasper Fuk-Woo Chan Kelvin Kai-Wang To Honglin Chen Zhiwei Chen Kwok-Yung Yuen Guang Sheng Ling Shuofeng Yuan Dong-Yan Jin Department of Microbiology Li Ka Shing Faculty of MedicineThe University of Hong Kong102 Pokfulam RoadPokfulamHong KongChina State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong102 Pokfulam RoadPokfulamHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong Kong21 Sassoon RoadPokfulamHong KongChina

Live attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA,adenoviral vector and inactivated vaccines fail to ***,we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene,which encodes 2′-O-methyltransferase,is catalytically disrupted by a point *** virus,designated d16,was severely attenuated in hamsters and transgenic mice,causing only asymptomatic and nonpathogenic infection.A single dose of d16 administered intranasally resulted in sterilizing immunity in both the upper and lower respiratory tracts of hamsters,thus preventing viral spread in a contact-based transmission *** also robustly stimulated humoral and cell-mediated immune responses,thus conferring full protection against lethal challenge with SARS-CoV-2 in a transgenic mouse *** neutralizing antibodies elicited by d16 effectively cross-reacted with several SARS-CoV-2 *** immunoglobulin A was detected in the blood and nasal wash of vaccinated *** work provides proof-of-principle evidence for harnessing NSP16-deficient SARS-CoV-2 for the development of live attenuated vaccines and paves the way for further preclinical studies of d16 as a prototypic vaccine strain,to which new features might be introduced to improve safety,transmissibility,immunogenicity and efficacy.

关键词： Live attenuated vaccine NSP16 2'-O-methyltransferase T-cell response Mucosal immunity Sterilizing immunity

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Targeting papain-like protease for broad-spectrum coronavirus inhibition

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Protein & Cell 2022年第12期13卷 940-953页

作者： Shuofeng Yuan Xiaopan Gao Kaiming Tang Jian-Piao Cai Menglong Hu Peng luo Lei Wen Zi-Wei Ye cuiting luo Jessica Oi-Ling Tsang Chris Chun-Yiu Chan Yaoqiang Huang Jianli Cao Ronghui Liang Zhenzhi Qin Bo Qin Feifei Yin Hin Chu Dong-Yan Jin Ren Sun Jasper Fuk-Woo Chan Sheng Cui Kwok-Yung Yuen State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong SARChina Department of Microbiology Li Ka ShingFaculty of MedicineThe University of Hong KongPokfulamHong Kong SARChina NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong SARChina Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCAUSA Key Laboratory of Tropical Translational Medicine of Ministry of Education Hainan Medical UniversityHaikou 571199China Academician Workstation of Hainan Province Hainan Medical UniversityHaikou 571199China Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases The University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou Laboratory Guangzhou 510320China Department of Clinical Microbiology and Infection Control The University of Hong Kong-Shenzhen HospitalShenzhen 518053China

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral *** the multi-functional papain-like protease(PLpro)domain of the viral nsp3 holds ***,none of the known coronavirus PLpro inhibitors has been shown to be in vivo ***,we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity,including against the Sarbecoviruses(SARSCoV-1 and SARS-CoV-2),Merbecovirus(MERS-CoV),as well as the Alphacoronavirus(hCoV-229E and hCoVOC43).Importantly,F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice.F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage,as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase *** the significant difference of substrate recognition,mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue,whereas an allosteric inhibitor of MERSPLpro interacting with its 271E *** proof-ofconcept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anticoronavirus *** orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.

关键词： protease inhibitor coronavirus Nsp3 antiviral

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杜仲叶中一个新天然产物及其活性研究

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中药药理与临床 2020年第6期36卷 104-109页

作者：董芬邓娇罗翠婷范捷江汉大学附属医院武汉430015 贵州师范大学荞麦产业技术研究中心贵阳550001 湛江中医学校湛江524094

目的:对杜仲叶化学成分及其药理活性进行研究。方法:运用多种色谱技术进行分离纯化,并根据理化性质和波谱数据鉴定化合物结构。采用MTS法和微量稀释法分别测定化合物体外抗肿瘤活性和抗菌活性,使用ADMET Predictor 9.5软件和Discovery S... 详细信息

目的:对杜仲叶化学成分及其药理活性进行研究。方法:运用多种色谱技术进行分离纯化,并根据理化性质和波谱数据鉴定化合物结构。采用MTS法和微量稀释法分别测定化合物体外抗肿瘤活性和抗菌活性,使用ADMET Predictor 9.5软件和Discovery Studio 4.5软件分别对化合物的吸收、分布、代谢、排泄、毒性(ADMET)和抗菌作用机制进行初步预测。结果:从杜仲叶中分离得到8个化合物,分别为白桦脂酸(1),反式桂皮酸(2),(Z)-氧代二氢吲哚-3-亚基酮(3),熊果酸(4),绿原酸(5),芦丁(6),槲皮素-3-O-阿拉伯基葡萄糖苷(7),2′-亚麻酸单甘油酯(8)。化合物3对标准金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA)的最小抑菌浓度(MIC)值为2μg/mL^8μg/mL。对白血病细胞株(HL-60)、肺癌细胞株(A-549)的IC_(50)值分别为11.03μmoL/L和15.06μmoL/L。结论:化合物2、3、8为首次从该属植物中分离得到。化合物3为一个新的天然产物,对MRSA菌株具有较强的抑制活性,具有较弱的体外肿瘤生长抑制活性。该化合物理论上具有较好的ADMET性质,分子对接初步推断其可能通过抑制金黄色葡萄球菌的DNA旋转酶来起到较强的抗菌活性。

关键词：杜仲叶生物碱抗肿瘤活性金黄色葡萄球菌抑菌活性 (Z)-氧代二氢吲哚-3-亚基酮

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1,3-二羟基呫吨酮类化合物的简洁合成及清除亚硝酸根作用研究

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有机化学 2014年第3期34卷 515-521页

作者：毛双双郑欢欢罗翠婷陈河如暨南大学药学院中药及天然药物研究所广州510632 中国科学院上海药物研究所新药研究国家重点实验室上海201203 广东省中药药效物质基础及创新药物研究重点实验室广州510632

以间苯三酚为起始原料,在伊顿试剂的催化作用下,与不同取代水杨酸反应合成1,3-二羟基呫吨酮类化合物3a^3l 12个,收率63%~87%,并探讨了反应机理及结构-反应活性关系.利用紫外分光光度法测定了所合成化合物对亚硝酸盐的清除作用,结果表明,... 详细信息

以间苯三酚为起始原料,在伊顿试剂的催化作用下,与不同取代水杨酸反应合成1,3-二羟基呫吨酮类化合物3a^3l 12个,收率63%~87%,并探讨了反应机理及结构-反应活性关系.利用紫外分光光度法测定了所合成化合物对亚硝酸盐的清除作用,结果表明,在37℃、pH 3及反应时间为30 min条件下,1,3-呫吨酮类化合物对亚硝酸根均有较好的清除作用,其中化合物3f和3b的清除作用最强,清除率达34%.同时对1,3-二羟基呫吨酮类化合物清除亚硝酸盐的作用机制及构效关系进行了探讨.

关键词：呫吨酮有机合成亚硝酸盐癌症防治伊顿试剂

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福建省南平市姬松茸中重金属含量及二氧化硫残留量调查与膳食风险评估

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现代疾病预防控制 2023年第10期34卷 796-799页

作者：陈涛罗翠婷张泽泉南平市疾病预防控制中心福建南平353000

目的调查福建省南平市市售姬松茸中铅、镉、总砷、总汞含量和二氧化硫残留量,并对其进行膳食风险评估。方法采集南平市市售干姬松茸样品和生产环节的鲜姬松茸样品以及干制品共计55份,按照国家标准方法测定铅、镉、总砷、总汞及二氧化硫... 详细信息

目的调查福建省南平市市售姬松茸中铅、镉、总砷、总汞含量和二氧化硫残留量,并对其进行膳食风险评估。方法采集南平市市售干姬松茸样品和生产环节的鲜姬松茸样品以及干制品共计55份,按照国家标准方法测定铅、镉、总砷、总汞及二氧化硫残留量,根据相关限量标准对指标进行评价,同时通过目标危害系数法进行膳食风险评估。结果20份鲜样各项结果均符合相关标准;35份干制品中重金属含量超标8份,超标率22.9%,其中铅和镉含量符合标准,总砷超标率20.0%,总汞超标率2.9%,未出现两种元素同时超标情况;16份干制品二氧化硫残留量超标,超标率45.7%。结论闽北地区姬松茸存在总砷、总汞超标,总砷和镉具有一定的膳食摄入风险,干制品二氧化硫残留超标率较高。建议生产者在种植时改善生产技术降低姬松茸重金属含量,加工时规范使用添加剂,并建议职能部门加强监管。

关键词：姬松茸铅镉总砷总汞二氧化硫

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Effect of Nb-V microalloying on the hot deformation behavior of medium Mn steels

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 360-368页

作者： Yumeng Wang Qinyi Guo Bin Hu Haiwen luo School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing 100083China

The influence of Nb-V microalloying on the hot deformation behavior and microstructures of medium Mn steel(MMS)was investigated by uniaxial hot compression *** establishing the constitutive equations for simulating the measured flow curves,we successfully constructed deformation activation energy(Q)maps and processing maps for identifying the region of flow *** concluded the following consequences of Nb-V alloying for MMS.(i)The critical strain increases and the increment diminishes with the increasing deformation temperature,suggesting that NbC precipitates more efficiently retard dynamic recrystallization(DRX)in MMS compared with solute Nb.(ii)The deformation activation energy of MMS is significantly increased and even higher than that of some reported high Mn steels,suggesting that its ability to retard DRX is greater than that of the high Mn content.(iii)The hot workability of MMS is improved by narrowing the hot processing window for the unstable flow stress,in which fine recrystallized and coarse unrecrystallized grains are present.

关键词： medium manganese steel niobium-vanadium microalloying flow behavior dynamic recrystallization hot workability

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Exploring practical methods for detecting k-nonseparability in multipartite quantum states

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 255-256页

作者： Shunlong luo Academy of Mathematics and Systems Science Chinese Academy of Sciences

Quantum entanglement, referred to as “spooky action at a distance” by Einstein, is not only an intriguing and fascinating feature of quantum theory challenging our classical intuitions about locality and correlations, but also has practical and profound implications for quantum technologies. Initially described by Einstein, Podolsky and Rosen, as well as by Schro¨dinger, entanglement now has become a basic and crucial ingredient for both foundational and experimental investigations of the quantum world.

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金钱鱼agrp基因cDNA克隆及饥饿与复投喂对其表达的影响

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水产科学 2023年第5期42卷 821-829页

作者：蔡博生陈华慧罗翠婷翟毅李广丽邓思平广东海洋大学水产学院广东湛江524088 广东省名特优鱼类生殖调控与繁育工程技术研究中心广东湛江524088

为探究刺鼠相关蛋白/神经肽Y (AgRP)神经元在金钱鱼应答饥饿与复投喂过程中所起的调控作用,采用反转录PCR自金钱鱼下丘脑克隆了agrp1和agrp2 2种亚型基因,并采用实时荧光定量PCR分析了2种基因在金钱鱼不同组织中的表达情况和正常投喂组(... 详细信息

为探究刺鼠相关蛋白/神经肽Y (AgRP)神经元在金钱鱼应答饥饿与复投喂过程中所起的调控作用,采用反转录PCR自金钱鱼下丘脑克隆了agrp1和agrp2 2种亚型基因,并采用实时荧光定量PCR分析了2种基因在金钱鱼不同组织中的表达情况和正常投喂组(2、7 d)、饥饿组(2、7 d)、复投喂组(饥饿7 d然后复投喂3 h)金钱鱼(体质量52~60 g)下丘脑、肝脏和肠道中agrp1和agrp2基因的表达情况。序列分析结果显示,agrp1和agrp2基因的开放阅读框长度分别为429 bp和351 bp。组织表达结果显示,agrp1基因主要在下丘脑和肌肉中表达,agrp2基因主要在下丘脑和脑垂体中表达。饥饿及复投喂结果表明:下丘脑中,agrp1基因表达水平在饥饿2 d后差异不显著,饥饿7 d后显著下调,复投喂后其表达水平恢复正常;肝脏中,agrp1基因表达水平在饥饿2 d后下调,但饥饿7 d后显著上调,复投喂后其表达水平下调到正常水平;肠道中,agrp1基因表达水平在饥饿2 d后无显著差异,饥饿7 d后显著上调,复投喂后其表达水平下调到正常水平。饥饿和复投喂期间,下丘脑、肝脏和肠道中agrp2基因表达水平与对照组差异不显著。结果表明,下丘脑、肝脏和肠道中的agrp1基因参与了金钱鱼摄食过程的调节。

关键词：金钱鱼刺鼠相关蛋白饥饿及复投喂摄食

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Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

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Neural Regeneration Research 2025年第10期20卷 2895-2897页

作者： Nicolas Hugues Yu luo Department of Molecular and Cellular Biosciences University of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program University of CincinnatiCincinnatiOHUSA Division of Immunobiology Cincinnati Children’s Hospital Medical CenterUniversity of Cincinnati College of MedicineCincinnatiOHUSA

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the *** the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

关键词： Figure signature critical

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Impact of ocean data assimilation on the seasonal forecast of the 2014/15 marine heatwave in the Northeast Pacific Ocean

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 24-31页

作者： Tiantian Tang Jiaying He Huihang Sun Jingjia luo Institute for Climate and Application Research(ICAR)/Key Laboratory of Meteorological Disaster Nanjing University of Information Science and TechnologyNanjingChina

A remarkable marine heatwave,known as the“Blob”,occurred in the Northeast Pacific Ocean from late 2013 to early 2016,which displayed strong warm anomalies extending from the surface to a depth of 300 *** study employed two assimilation schemes based on the global Climate Forecast System of Nanjing University of Information Science(NUIST-CFS 1.0)to investigate the impact of ocean data assimilation on the seasonal prediction of this extreme marine *** sea surface temperature(SST)nudging scheme assimilates SST only,while the deterministic ensemble Kalman filter(EnKF)scheme assimilates observations from the surface to the deep *** latter notably improves the forecasting skill for subsurface temperature anomalies,especially at the depth of 100-300 m(the lower layer),outperforming the SST nudging *** excels in predicting both horizontal and vertical heat transport in the lower layer,contributing to improved forecasts of the lower-layer warming during the *** improvements stem from the assimilation of subsurface observational data,which are important in predicting the upper-ocean *** results suggest that assimilating ocean data with the EnKF scheme significantly enhances the accuracy in predicting subsurface temperature anomalies during the Blob and offers better understanding of its underlying mechanisms.

关键词： Seasonal forecast Ocean data assimilation Marine heatwave Subsurface temperature

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