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Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles

Acta Pharmaceutica Sinica B 2022年第3期12卷 1523-1533,F0004页

作者： Canhao Wu Qin Xu Huiyuan Wang bin tu Jiaxin Zeng Pengfei Zhao Mingjie Shi Hong Qiu Yongzhuo Huang Artemisinin Research Center First Clinical SchoolGuangzhou University of Chinese MedicineGuangzhou 510450China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Zhongshan Institute for Drug Discovery SIMMCASZhongshan 528437China Center of Clinical Pharmacology The Second Affiliated Hospital of Zhejiang UniversitySchool of MedicineHangzhou 310009China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients Shanghai 201203China Taizhou University School of Advanced StudyInstitute of Natural Medicine and Health ProductTaizhou 318000China

The spread of coronavirus disease 2019(COVID-19)throughout the world has resulted in stressful healthcare burdens and global health *** an effective measure to protect people from infection is an urgent *** blockage of interaction between angiotensin-converting enzyme 2(ACE2)and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)drugs.A full-length ACE2 protein could be a potential drug to block early entry of SARS-Co V-2 into host *** this study,a therapeutic strategy was developed by using extracellular vesicles(EVs)with decoy receptor ACE2 for neutralization of SARS-Co *** EVs embedded with engineered ACE2(EVs-ACE2)were prepared;the EVs-ACE2 were derived from an engineered cell line with stable ACE2 *** potential effect of the EVs-ACE2 on anti-SARS-Co V-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein(S-pseudovirus).EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells,and importantly,the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal ***,the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-Co V-2 *** EVs-based strategy offers a potential route to COVID-19 drug development.

关键词： SARS-CoV-2 COVID-19 Spike protein Pseudovirus Extracellular vesicles ACE2 Intranasal administration Neutralization

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Inhaled heparin polysaccharide nanodecoy against SARS-CoV-2 and variants

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3187-3194页

作者： bin tu Huiyuan Wang Xinran An Jingkun Qu Qianqian Li Yanrong Gao Mingjie Shi Hong Qiu Yongzhuo Huang State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China University of Michigan College of Pharmacy Ann ArborMI 48109USA School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Nanchang University College of Pharmacy Nanchang 330006China Zhongshan Institute for Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan 528437China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients Shanghai 201203China Taizhou University School of Advanced StudyInstitute of Natural Medicine and Health ProductTaizhou 318000China

To the Editor:As of January 27,2022,there were 363,062,293 cases and 5,645,884deaths from the COVID-19 *** prevalent mutated strains have aggravated the global ***-Co V-2 is highly mutable,and the mutations on the spike(S)protein resulted in a high transmission of COVID-19 and vaccine breakthrough *** example,there is a notable decrease in neutralizing ability of BNT162b2 vaccination-elicited antibodies against the Delta and other variants4,5,and attenuation of peak viral burden and vaccine effectiveness are reduced with Delta variant6.

关键词： SARS-CoV-2 Delta variant Heparan sulfate Spike protein Heparin nanoparticle Pulmonary delivery

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Remodeling “cold” tumor immune microenvironment via epigenetic-based therapy using targeted liposomes with in situ formed albumin corona

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Acta Pharmaceutica Sinica B 2022年第4期12卷 2057-2073页

作者： Yang He Yuefei Fang Meng Zhang Yuge Zhao bin tu Mingjie Shi Bahtiyor Muhitdinov Akmal Asrorov Qin Xu Yongzhuo Huang State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Zhongshan Institute for Drug Discovery Chinese Academy of SciencesZhongshan 528437China Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Artemisinin Research Center Guangzhou University of Chinese MedicineGuangzhou 510450China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310006China Institute of Bioorganic Chemistry Uzbekistan Academy of SciencesTashkent 100125Uzbekistan National Medical Products Administration Key Laboratory for Quality Research and Evaluation of Pharmaceutical ExcipientsShanghai 201203China

There is a close connection between epigenetic regulation,cancer metabolism,and *** combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer *** an epigenetic regulator of histone acetylation,panobinostat can induce histone acetylation and inhibit tumor cell proliferation,as well as regulate aerobic glycolysis and reprogram intratumoral immune ***1 is a BRD4 inhibitor that can suppress PD-L1 ***,we proposed a chemo-free,epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer.A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 *** was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin *** lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells(e.g.,tumor-associated macrophages).The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune ***,lactic acid production was reduced and angiogenesis inhibited;TAM switched to an anti-tumor phenotype,and the anti-tumor function of the effector CD8+T cells was *** strategy provides a potential method for remodeling the tumor immune microenvironment(TIME).

关键词： tumor immune microenvironment tumor-associated macrophage Epigenetic therapy Immune checkpoint Angiogenesis Panobinostat JQ1 Liposome

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Novel model combining contrast-enhanced ultrasound with serology predicts hepatocellular carcinoma recurrence after hepatectomy

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World Journal of Clinical Cases 2021年第24期9卷 7009-7021页

作者： Hai-bin tu Li-Hong Chen Yu-Jie Huang Si-Yi Feng Jian-Ling Lin Yong-Yi Zeng Department of Ultrasound Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025Fujian ProvinceChina Department of Hepatobiliary Surgery Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhou 350025Fujian ProvinceChina

BACKGROUND Surgery is the primary curative option in patients with hepatocellular carcinoma(HCC).However,recurrence within 2 years is observed in 30%–50%of patients,being a major cause of *** To construct and verify a non-invasive prediction model combining contrastenhanced ultrasound(CEUS)with serology biomarkers to predict the early recurrence of *** Records of 744 consecutive patients undergoing first-line curative surgery for HCC in one institution from 2016–2018 were reviewed,and 292 local patients were selected for *** characteristics including gender and age,CEUS liver imaging reporting and data system(LIRADS)parameters including wash-in time,wash-in type,wash-out time,and wash-out type,and serology biomarkers including alanine aminotransferase,aspartate aminotransferase,platelets,and alpha-fetoprotein(AFP)were *** analysis and multivariate Cox proportional hazards regression model were used to evaluate the independent prognostic factors for tumor *** a nomogram called CEUS model was *** CEUS model was then used to predict recurrence at 6 mo,12 mo,and 24 mo,the cut-off value was calculate by X-tile,and each C-index was *** Kaplan-Meier curve was compared by logrank *** calibration curves of each time were *** A nomogram predicting early recurrence(ER),named CEUS model,was formulated based on the results of the multivariate Cox regression *** nomogram incorporated tumor diameter,preoperative AFP level,and LIRADS,and the hazard ratio was 1.123(95%confidence interval[CI]:1.041-1.211),1.547(95%CI:1.245-1.922),and 1.428(95%CI:1.059-1.925),*** cut-off value at 6 mo,12 mo,and 24 mo was 100,80,and 50,and the C-index was 0.748(95%CI:0.683-0.813),0.762(95%CI:0.704-0.820),and 0.762(95%CI:0.706-0.819),*** model showed satisfactory results,and the calibration at 6 mo was desirable;however,the calibration at 12 and 24 mo should be improv

关键词： Hepatocellular carcinoma Recurrence Prediction Contrast-enhanced ultrasound Liver imaging reporting and data system Alpha-fetoprotein

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Aza-BODIPY molecular assembly at the liquid-solid interface driven by Br…F-BF interactions

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Chinese Chemical Letters 2021年第11期32卷 3566-3569页

作者： Yuchuan Xiao Fangjian Cai Xuan Peng Xiyuan Kang Peng Lei Xin Li Haijun Xu Xunwen Xiao bin tu Qingdao Zeng CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST)Beijing 100190China Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources College of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China School of Materials and Chemical Engineering Ningbo University of TechnologyNingbo 315211China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China CAS Center for Excellence in Nanoscience Beijing Key Laboratory of Micro-Nano Energy and SensorBeijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 100083China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiang 453002China

In this work,two aza-BODIPY derivatives,3,5-diphenyl-1,7-di(p-dodecyloxyphenyl)-aza-BODIPY(CJF)and 3,5-di(p-bromophenyl)-1,7-di(p-dodecyloxyphenyl)-aza-BODIPY(2Br-CJF)acted as model molecules to form the self-assembly monolayers on the solid-liquid *** the utilizing of scanning tunnelling microscope(STM),we demonstrated that intermolecular Br…F-BF interactions existed in 2Br-CJF self-assembly structure and played an important role in strengthening the stability of 2Br-CJF self-assembly *** result is supported by density functional theory(DFT)calculation.

关键词： Aza-BODIPY STM Br…F interaction Self-assembly Surface assembly

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A Fragment Substitution in Promoter of MS92/PTC1 Causes Male Sterility in Rice

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Rice science 2020年第5期27卷 396-404,I0018-I0023页

作者： Qin Peng Deng Luchang Chen Weilan Huang Juan Fan Shijun tu bin Tan Jun Yuan Hua Wang Yuping Ma bingtian Li Shigui Rice Research Institute/State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Sichuan Agricultural UniversityChengdu 611130China Crop Research Institute Sichuan Academy of Agricultural SciencesChengdu 610066China Characteristic Crop Research Institute Chongqing Academy of Agricultural SciencesChongqing 402160China

Persistent tapetal cell1(PTC1) plays a curial role in pollen development, and is thought to function as a transcriptional activator in rice. However, the molecular mechanism of PTC1 in regulating pollen development and its cis-elements are not well understood. We identified a novel weak male sterility mutant(ms92) which exhibited expanded tapetum and shrink pollen grains. Map-based cloning and allelic analysis suggested that the male sterility of ms92 was caused by a DNA fragment substitution in the promoter of PTC1. The decreased expression of MS92/PTC1 in ms92 and cis-element analysis indicated that the substituted sequence contained several potential binding cis-element of negative feedback. MS92/PTC1 was specifically expressed in tapetum and microspores at the young microspore stage, and its protein was localized in nucleus. We further found that MS92/PTC1 functions as a transcription activator by recognizing H3K4me3. Transcriptomic analysis revealed that a number of genes involved in tapetum degeneration and pollen wall formation were down-regulated in ms92, which are the potential targets of MS92/PTC1. The substitution fragment in MS92/PTC1 promoter was essential for pollen development, and we provided a novel mutant for further identifying the cis-elements in promoter and the molecular network of MS92/PTC1.

关键词： rice MS92/PTC1 plant homeodomain finger cis-element male sterility anther

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Adsorption of helical and saddle-shaped oligothiophenes on solid surface

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Science China Chemistry 2018年第7期61卷 844-849页

作者： Ping Li Yongqing Lai Yong Wang Yuxin Qian Wubiao Duan Chunli Li Zhihua Wang Qiaojun Fang Hua Wang bin tu Yanfang Geng Qingdao Zeng CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory of Biological Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Department of Chemistry School of ScienceBeijing Jiaotong UniversityKaifeng 475004China Department Engineering Research Center for Nanomaterials Institution Henan UniversityBeijing 100044China

The arrangement of oligothiophenes is essential for understanding the relationship between structure and properties particularly in the organic electronic field. The self-assembly behaviors of helical(TMS)2-[7]helicene(T1), naphthalene-cored double(TMS)2-[7]helicene(T2), and saddle-shaped cyclooctatetrathiophene(T3), its derivative α,α,α,α-tetraphenyl-cyclooctatetrathiophene(T4) on solid surface are firstly investigated by using a combination of scanning tunneling microscopy(STM) and density functional theory(DFT) calculation. 1,3,5-Tris(10-carboxydecyloxy)-benzene(TCDB) is selected to build flexible host networks to immobilize these oligothiophenes in order to capture their molecular adsorption images successfully. The observed monodisperse or polydisperse filling and long-range alignment of oligothiophenes are described based on the non-covalent interactions and commensurate structure between olihothiophene and cavity. We speculate that those molecularly defined alignments could lead to significantly understanding the application of such ordered monolayer in organic electronic devices.

关键词： oligothiophene helical saddle-type self-assembly scanning tunneling microscopy

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Application of Unloading Fractured Rock Mass under Uniaxial Tension Based on Endochronic Theory

Application of Unloading Fractured Rock Mass under Uniaxial ...

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作者： Li Yu bin tu Nanchang institute of technology School of civil and architecture EngineeringNanchang Institute of Technology

In this paper,the constitutive relation of fractured rock mass under uniaxial tension is derived,and the corresponding numerical solution is *** is found that the kernel function with the Proney expansion can fit well with theρ(z)= Cz).When the parameters of the kernel function are taken from the experimental data,the constitutive equation can be simplified in the initial loading stage,which is in good agreement with Jin Fen gnian’s experimental data under unloading *** simplified equation of the endochronic theory is well verified by the experimental data.

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支持批量证明的SM2适配器签名及其分布式扩展

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软件学报 2024年第5期35卷 2566-2582页

作者：涂彬彬陈宇山东大学网络空间安全学院山东青岛266237 密码科学技术全国重点实验室北京100878 密码技术与信息安全教育部重点实验室(山东大学) 山东青岛266237 山东区块链研究院山东济南250001 泉城实验室山东济南250014

适配器签名,又称无脚本脚本,是解决区块链应用(如密码货币)中扩展性差、吞吐量低等问题的重要密码技术.适配器签名可看作数字签名关于困难关系的扩展,同时具有签名授权和证据提取两种功能,在区块链应用中具有以下优点:(1)降低链上成本;... 详细信息

适配器签名,又称无脚本脚本,是解决区块链应用(如密码货币)中扩展性差、吞吐量低等问题的重要密码技术.适配器签名可看作数字签名关于困难关系的扩展,同时具有签名授权和证据提取两种功能,在区块链应用中具有以下优点:(1)降低链上成本;(2)提高交易的可替代性;(3)突破区块链脚本语言限制.SM2签名是我国自主设计的国家标准签名算法,在各种重要信息系统中有着广泛应用.基于SM2签名构造出高效的适配器签名方案,并在随机谕言机模型下给出安全性证明.所提方案结合SM2签名结构,可避免在预签名阶段生成额外的零知识证明,与现有ECDSA/SM2适配器签名相比更加高效,其中,预签名生成效率提升4倍,预签名验证效率提升3倍.随后,基于SM2协同签名,构造分布式SM2适配器签名,可避免单点故障问题,提升签名私钥安全.最后,在实际应用方面,基于SM2适配器签名构造适用于一对多场景下安全高效的批量原子交换协议.

关键词： SM2算法适配器签名分布式适配器签名区块链原子交换

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Topologically engineering of π-conjugated macrocycles: tunable emission and photochemical reaction toward multi-cyclic polymers

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Chinese Chemical Letters 2024年第10期35卷 233-240页

作者： Yi Liu Peng Lei Yang Feng Shiwei Fu Xiaoqing Liu Siqi Zhang bin tu Chen Chen Yifan Li Lei Wang Qing-Dao Zeng Shenzhen Key Laboratory of Polymer Science and Technology Guangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060China CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Center for Excellence in NanoscienceNational Center for Nanoscience andTechnology(NCNST)Beijing100190China Institute of Critical Materials for Integrated Circuits Shenzhen Polytechnic UniversityShenzhen 518055China

The topology of conjugated macrocycles had significant impacts on their photo-physical and photochemical ***,a series ofπ-conjugated macrocycles with diverse topology were synthesized via intramolecular McMurry *** chemical structure and macrocyclic topology were unambiguously confirmed via NMR,MALDI-TOF mass spectra,crystal analysis and scanning tunneling microscopy(STM).Depending on the structural topology and structural rigidity,these cyclic compounds display obviously distinctive emission behavior and photochemical reactions in the solution and in the solid *** phenylene vinylene macrocycle(denoted as MST)exhibiting aggregation-induced emission behavior,was more vulnerable to photo-cyclization in solution and triplet sensitizer promoted photodimerization due to lower strain and more flourishing intramolecular *** UV light irradiation,relatively more flexible MST could yield the anti-dimer via triplet excimer on the HOPG surface confirmed by STM *** contrast,highly constrained bicyclic analogue(named as DMTPE)with central tetraphenylethene core,displayed high emission quantum yields of 68%both in solution and in the solid state,and was relatively inert to photochemical reactions and yield syn-dimer on the surface via singlet excimer involved[2+2]*** on the solution-mediated photo-polymerization of MST moiety,multicyclic porous carbon-rich ribbon connected with four-membered ring was successfully constructed and validated via STM imaging.

关键词： Conjugated macrocycle Scanning tunneling microscopy Aggregation-induced emission Photochemistry Multicyclicribbon

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