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Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li mengxin xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the ***,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a *** long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD *** upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)*** a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary *** meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including *** findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

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路桥工程建设中路基路面施工技术要点

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中国高新科技 2024年第7期 51-52,85页

作者：徐梦新王鹏德州市公路事业发展中心夏津分中心山东德州253200

路基和路面施工是决定路桥工程建设质量的两个关键环节。在路基施工中,需要从路基土方开挖、路基排水和填方压实等环节加强施工管理;在路面施工中,需要从路面材料的质量控制、路面材料的摊铺管理、路面材料的压实控制3个方面把控施工技... 详细信息

路基和路面施工是决定路桥工程建设质量的两个关键环节。在路基施工中,需要从路基土方开挖、路基排水和填方压实等环节加强施工管理;在路面施工中,需要从路面材料的质量控制、路面材料的摊铺管理、路面材料的压实控制3个方面把控施工技术要点。通过树立精细化的管控理念,才能切实提高路桥工程建设质量,提高行车舒适性。

关键词：路桥工程路基排水振动碾压路面施工

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陶行知实业教育思想:时代逻辑、理论逻辑和实践逻辑

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宁波职业技术学院学报 2024年第2期28卷 51-56页

作者：徐梦鑫马香莲赵雨诺宝鸡文理学院陕西宝鸡721013

陶行知先生的实业教育思想是在长期的教育实践探索过程中,在“中体西用”思想的影响下,在批判传统教育和“实业救国”教育思潮的历史基础上产生的,是在“知行合一”学说、儒墨教育思想和实用主义教育思想的影响下形成的。陶行知实业教... 详细信息

陶行知先生的实业教育思想是在长期的教育实践探索过程中,在“中体西用”思想的影响下,在批判传统教育和“实业救国”教育思潮的历史基础上产生的,是在“知行合一”学说、儒墨教育思想和实用主义教育思想的影响下形成的。陶行知实业教育思想的时代逻辑、理论逻辑和实践逻辑是实业教育思想理论体系的有机统一,在理解实业教育思想的基础上深刻挖掘这三重逻辑的内在联系,能够使我国的实业教育呈现出鲜明的时代特色。

关键词：实业教育思想陶行知生利主义

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认知偏差:“双减”政策下家校合作共育的障碍及突破

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西安文理学院学报（社会科学版） 2024年第1期27卷 53-59页

作者：徐梦鑫马香莲蔺春利宝鸡文理学院教育学院陕西宝鸡721013

“双减”政策下家校合作共育可以很好地解放学生,能够持续深入地推进教育改革。有效开展家校合作共育有助于教育在目标与方向上保持一致,形成教育合力有助于实现学生的全面发展、促进学生健康成长也有利于整合教育资源、构建教育的良好... 详细信息

“双减”政策下家校合作共育可以很好地解放学生,能够持续深入地推进教育改革。有效开展家校合作共育有助于教育在目标与方向上保持一致,形成教育合力有助于实现学生的全面发展、促进学生健康成长也有利于整合教育资源、构建教育的良好生态。然而,目前双减政策执行过程中家校双方在各自责任的理解上存在偏差,导致家校合作的实施效果不太理想。在认知方面,学校对家长在青少年儿童全面发展中的影响认识不够全面、教师对家校合作中自身的责任认识不清、家长没有全面认识到家庭教育对青少年儿童的价值和意义。要突破合作共育的现实困境,需要从学校、教师、家长三方面提出具体的改进措施即转变教育观念,确保学生获得优质教育;树立正确的边界意识,把握好合作的“度”;改变家长的观念,促进青少年全面发展。

关键词：家校合作共育认知偏差 “双减”政策下

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Isolation of ^(212)Pb from natural thorium for targeted alpha-therapy

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Chinese Chemical Letters 2022年第7期33卷 3474-3477页

作者： Junyi Chen mengxin xu Yu Liu Dongban Duan Yuxiang Han Zhibo Liu Beijing National Laboratory for Molecular Sciences Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental ScienceCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100871China

Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor ***,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb is a promising α-emitter with an optimal half-life(10.6 h) and favored decay *** interest,^(212)Pb can be extracted directly from natural thorium,which may be abundant in the mining waste of rare-earth,uranium,***,radioactive thorium waste has been a longstanding environmental challenge that needs immediate *** an on-demand and facile process to isolate ^(212)Pb from natural thorium would be ideal to meet the above challenges,yet is *** theory,the ratio of ^(212)Pb tonatTh is below 10^(-13)in commercially available thorium *** a pilot study,2.2 MBq of ^(212)Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective *** radiochemical purity of ^(212)Pb is over 99.9% according to gamma-ray *** purified^(212)Pb was applied to radiolabel a couple of peptides used in clinics(***,TATE and FAPI-04),and the radiochemical yields are>85%.Of note,^(212)Pb can be repeatedly separated from the thorium solution every 2 *** summary,a practical and scalable method was developed to isolate^(212)Pb for potentially clinical use,which may be of great importance as it does not require either cyclotron or nuclear reactor.

关键词： ^(212)Pb Targeted alpha-therapy Radiolabeling Radionuclide generator Solid-phase extraction

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FAP靶向核药物用于肝纤维化诊断的临床前研究

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同位素 2024年第2期37卷 91-96页

作者：徐梦欣蔡杰陈俊艺宋涵博刘宇刘志博北京大学化学与分子工程学院北京100871 昌平国家实验室北京102206 北京大学-清华大学生命科学联合中心北京100871

肝纤维化如果不能及时准确的诊断和干预,将不可避免地演变成肝硬化。尽管肝组织活检是目前肝纤维化的金标准,但由于其无法全面检查所有病变,无创检查仍面临挑战。成纤维活化蛋白(FAP)在肝纤维化中起促进作用,并与疾病进展相关。因此,利... 详细信息

肝纤维化如果不能及时准确的诊断和干预,将不可避免地演变成肝硬化。尽管肝组织活检是目前肝纤维化的金标准,但由于其无法全面检查所有病变,无创检查仍面临挑战。成纤维活化蛋白(FAP)在肝纤维化中起促进作用,并与疾病进展相关。因此,利用无创的FAP靶向诊断核药物有望实现肝纤维化的准确诊断和分期。本研究通过对小鼠腹腔注射四氯化碳,成功建立了不同严重程度的肝纤维化模型。使用^(68)Ga标记的FAP探针TEFAPI-12进行PET显像,结果显示,TEFAPI-12在肝纤维化部位表现出特异性摄取,随着纤维化程度的加重而增加。肝脏^(68)Ga-TEFAPI-12的摄取与肝纤维化的严重程度相关,提示^(68)Ga-FAPI PET在肝纤维化的诊断与分期中具有重要作用。

关键词：肝纤维化成纤维细胞活化蛋白 PET/CT

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The protective nasal boosting of a triple-RBD subunit vaccine against SARS-CoV-2 following inactivated virus vaccination

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2051-2053页

作者： Jingyi Yang Mei-Qin Liu Lin Liu Xian Li mengxin xu Haofeng Lin Min Li Huimin Yan Yao-Qing Chen Zheng-Li Shi Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghai201508China Wuhan Institute of Virology Chinese Academy of SciencesWuhan430071China School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversitySun Yat-sen UniversityShenzhenGuangdong518107China

Dear Editor,Though COVID-19 vaccines have been developed and clinically deployed rapidly,new variants of concern(VOCs)are still emerging frequently and escalating around the *** breakthrough infections occurred even v... 详细信息

关键词： vaccination protective nasal

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Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

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Journal of Pharmaceutical Analysis 2024年第3期14卷 308-320页

作者： mengxin Wang Stephen Vulcano Changlu xu Renjian Xie Weijie Peng Jie Wang Qiaojun Liu Lee Jia Zhi Li Yumei Li Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province Gannan Medical UniversityGanzhouJiangxi341000China School of Rehabilitation Medicine Gannan Medical UniversityGanzhouJiangxi341000China Autoimmunity and Inflammation Program HSS Research InstituteHospital for Special Surgery New YorkNew YorkNY10021USA Division of Oral and Systemic Health Sciences School of DentistryUniversity of CaliforniaLos AngelesCA90095USA School of Medical Information Engineering Gannan Medical UniversityGanzhouJiangxi341000China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsInstitute for Liver Diseases of Anhui Medical UniversitySchool of PharmacyAnhui Medical UniversityHefei230032China School of Basic Medicine Gannan Medical UniversityGanzhouJiangxi341000China Institute of Oceanography Minjiang UniversityFuzhou350108China

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced *** or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy *** data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to *** ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer *** correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well *** work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across *** plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

关键词： Ribosome biogenesis Ribosomopathy gene Cancer treatment target Pharmaceutical target

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A triple-RBD-based mucosal vaccine provides broad protectionagainst SARS-CoV-2 variants of concern

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Cellular & Molecular Immunology 2022年第11期19卷 1279-1289页

作者： Jingyi Yang Mei-Qin Liu Lin Liu Xian Li mengxin xu Haofeng Lin Shuning Liu Yunqi Hu Bei Li Bowen Liu Min Li Ying Sun Yao-Qing Chen Zheng-Li Shi Huimin Yan Vaccine and Immunology Research Center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan University201508 ShanghaiChina Wuhan Institute of Virology Chinese Academy of Sciences430071 WuhanChina University of Chinese Academy of Sciences 100049 BeijingChina School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107 GuangdongChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhou 215123 JiangsuChina Key Laboratory of Tropical Disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouChina

The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broadspectrum protection against the initial infection and thereby curb the transmission ***,we designed a chimeric tripleRBD immunogen,3Ro-NC,harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold.3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of ***,intranasal immunization with 3RoNC plus the mucosal adjuvant KFD(3Ro-NC+KFDi.n)elicits coordinated mucosal IgA and higher neutralizing antibody specificity(closer antigenic distance)against the Omicron *** Omicron-challenged human ACE2 transgenic mice,3Ro-NC+KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung(85.7-fold)and the nasal turbinate(13.6-fold).Nasal virologic control is highly correlated with RBD-specific secretory IgA *** data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection,pathology and transmission potential.

关键词： SARS-CoV-2 Mucosal vaccine Intranasal immunization Triple-RBD Flagellin adjuvant Variant of concern

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Cationic starch microparticles with integrated antibacterial and hemostatic performance

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Science China Technological Sciences 2024年

作者： SU Yang NIU mengxin xu KaiDong xu Chen YANG PeiLang HU Yang xu Fu-Jian Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology Ministry of Education) Beijing Laboratory of Biomedical Material College of Materials Science and Engineering Beijing University of Chemical Technology Department of Burn Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

It is urgently demanded to develop biomaterials with balanced hemostatic/antibacterial ability and facile preparation methods. In this work, cationic starch microparticles (MSQP), prepared by the facile grafting of microporous starch particles (MS) with tunable quaternized polyethyleneimine, were readily constructed as promising hemostatic materials for integrated antibacterial and hemostatic performance. The cationic grafts not only endowed MSQP with good antibacterial ability, but also benefited from biocompatible MS to achieve favorable biocompatibility. Moreover, in vitro results confirmed the superior hemostatic property of MSQP2 (with the medium content of cationic grafts) among three MSQP and pristine MS. After investigating the bloodmaterial interactions of MSQP/MS, the procoagulant mechanism of MSQP2 was revealed that the optimal amount of cationic grafts achieves highly balanced plasma-protein adhesion, platelet adhesion and blood coagulation system. In vivo artery-injury model further demonstrated the superior hemostatic performance of MSQP2 for potential severe hemorrhage. This work sheds light on the design of cationic polymer-based biomaterials for balanced antibacterial and hemostatic functions.

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