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Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

Signal Transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang Jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang Yuanyu Huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key Laboratory of Tropical Disease research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key Laboratory of Antiviral Drug research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health *** light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently ***,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 *** aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,*** protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion

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Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering research Center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina Department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific research Center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina Department of Infectious Diseases and Nursing research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 *** I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low ***,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into *** address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa *** Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus *** the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an ***,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent *** confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal *** inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased ***,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

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Advances in DNA methylation and its role in cytoplasmic male sterility in higher plants

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Journal of Integrative Agriculture 2024年第1期23卷 1-19页

作者： Atiqur Rahman Hasan Sofiur Rahman Shakil Uddin Naima Sultana Shirin Akhter Ujjal Kumar Nath Shamsun Nahar Begum Mazadul Islam Afroz Naznin Nurul Amin Sharif Ahmed Akbar Hossain Department of Genetics and Plant Breeding Bangladesh Agricultural UniversityMymensingh 2202Bangladesh Plant Breeding Division Bangladesh Institute of Nuclear AgricultureMymensingh 2202Bangladesh Tuber Crop research Centre Bangladesh Agricultural Research Institute(BARI)Joydebpur 1701Bangladesh Horticulture research Centre Bangladesh Agricultural Research Institute(BARI)Joydebpur 1701Bangladesh Biotechnology Division Bangladesh Agricultural Research Institute(BARI)Joydebpur 1701Bangladesh International Rice research institute Bangladesh OfficeDhaka 1213Bangladesh Division of Soil Science Bangladesh Wheat and Maize Research InstituteDinajpur 5200Bangladesh

The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop *** methylation plays a part in the regulation of both the chromatin structure and gene expression,and the enzyme involved,DNA methyltransferase,executes the methylation process within the plant *** regulating crucial biological pathways,epigenetic changes actively contribute to the creation of the ***,epigenome editing may assist in overcoming some of the drawbacks of genome editing,which can have minor off-target consequences and merely facilitate the loss of a gene’s *** drawbacks include gene knockout,which can have such off-target *** review provides examples of several molecular characteristics of DNA methylation,as well as some plant physiological processes that are impacted by these epigenetic changes in the *** also discuss how DNA alterations might be used to improve crops and meet the demands of sustainable and environmentally-friendly farming.

关键词： DNA methylation epigenetics CMS male sterility chromatin architecture gene expression higher plants

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Supramolecular Manipulation of Intracellular Acidic Vesicles to Improve Cellular Self-Repair and Self-Defense

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CCS Chemistry 2024年第6期6卷 1487-1498页

作者： Ziyi Wang Chen Sun Yu Dong Yuan-Fu Ding Chen Zhao Ian Wa Ho Jiahong Lu Ruibing Wang State Key Laboratory of Quality research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao 999078China

Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and ***,artificially manipulating intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and ***,a supramolecular strategy to efficiently tether and fuse acidic vesicles(i.e.,lysosomes,late endosomes,autolysosomes,and phagosomes)has been developed for the first time to enhance the digestion of cellular wastes and foreign matter,including pathogens.A linear polyethylene glycol(PEG)derivative dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEG-ADA,was designed to target intracellular acidic vesicles via MOR and to decorate their surfaces with ***,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic acid(HA)induced supramolecular tethering and fusion of acidic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of acidic *** a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstrating that supramolecular regulation of the dynamics of intracellular acidic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.

关键词： supramolecular chemistry organelle regulation intracellular acidic vesicles lysosomes selfdefense self-repair

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Traceless photodegradable polymer cocoons for universal protein delivery and light-controlled gene editing

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Science China Chemistry 2024年第2期67卷 664-676页

作者： Huaibin Yu Meron Tsegay Kifle Lili Chen Feihong Xiong Yan Zhang Shangbang Gao Wei Hou Shuliang Chen Weining Zhao Yuzhou Wu Hubei Engineering research Center for Biomaterials and medical Protective Materials Hubei Key Laboratory of Bioinorganic Chemistry&Materia MedicaKey Laboratory of Material Chemistry for Energy Conversion and StorageMinistry of EducationSchool of Chemistry and Chemical EngineeringHuazhong University of Science and Technology(HUST)Wuhan430074China Zhengzhou research institute Harbin Institute of TechnologyZhengzhou450000China College of Life Science and Technology Huazhong University of Science and Technology(HUST)Wuhan430074China institute of medical Virology School of Basic Medical SciencesWuhan UniversityWuhan430071China College of Pharmacy Shenzhen Technology UniversityShenzhen518118China

Polymer conjugation was found highly valuable in clinic to improve the bioavailability of protein ***,it is still a tremendous challenge to achieve a complete release of original proteins from the conjugated hybrid under external stimulus to recover active proteins in the targeted ***,we report a general light-controlled protein delivery methodology by weaving a photodegradable polymer cocoon around proteins,which could reliably protect them from degradation in the dark while efficiently releasing them under illumination without any residual *** surface charge of the polymer shell is easily tunable to facilitate efficient cell *** versatility of this strategy is demonstrated by the delivery of the Cas9/sg RNA complex that realized light-controlled gene editing both in vitro and in vivo,and such repertoire is of particular value in regard to minimizing the off-target toxicity of CRISPR-Cas9-based gene therapy.

关键词： photodegradable polymer-protein conjugate protein delivery light control gene editing

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Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 75-81,I0047-I0052页

作者： Xiaoling Liao Shuo Feng Yicong Wang Yuesong Pan Weiqi Chen Hui Qu Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research Center for Neurological Diseases Beijing TiantanHospitalCapital Medical UniversityBeijingChina Chinese institute for Brain research BeijingChina National Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment ***,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic ***,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains *** To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin *** Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in *** patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to *** primary endpoint is a new stroke or END within 90 *** primary safety endpoint is severe or moderate bleeding within 90 *** The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with *** registration number NCT05310968.

关键词： Aspirin regimen centre

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China institute of Basic medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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EVEscape: Revealing potential escape sites based on the viral variation landscape

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Biophysics Reports 2024年第2期10卷 133-134页

作者： Yaling Li Aiping Wu Hang-Yu Zhou Zhejiang Lab State Key Laboratory of Common Mechanism research for Major Diseases Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences & Peking Union Medical College

The continuous mutation and evolution of viruses to evade the host immune response present a formidable challenge to combating infectious diseases. Accurate prediction of viral immune escape sites is crucial for disease diagnosis, therapy development, vaccine design, and other strategies aimed at combating emerging infectious diseases. During the COVID-19 pandemic,

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HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

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Science Bulletin 2024年第2期69卷 173-178页

作者： Siyuan Jiang Xiaoqi Han Tihui Liu Ying He Zidong Zhao Tongfeng Liu Shuwen Cheng Jihang Zhang Liqiang Duan Yajuan Liu Tianyou Cheng Yong Liu Qinong Ye Shan Gao Zhongda Hospital Medical SchoolAdvanced Institute for Life and HealthSoutheast UniversityNanjing 20096China medical School of Guizhou University Guiyang 550025China Shanxi Academy of Advanced research and Innovation Taiyuan 030032China Zhongda Hospital School of Life Sciences and TechnologyAdvanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Nanjing University medical School Nanjing 210046China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430072China Department of medical Molecular Biology Beijing Institute of BiotechnologyCollaborative Innovation Center for Cancer MedicineBeijing 100850China

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

关键词： endocytosis cargo uptake

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High-entropy alloys in thermoelectric application:A selective review

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Chinese Physics B 2024年第5期33卷 1-11页

作者：任凯霍文燚陈帅程渊王彪张刚 Zhengzhou University Advanced medical research Center Luoyang Central HospitalLuoyang 471099China School of Mechanical and Electronic Engineering Nanjing Forestry UniversityNanjing 210037China Materials Genome institute Shanghai UniversityShanghai 200444China Monash Suzhou research institute Monash UniversitySuzhou 215000China Department of Materials Science and Engineering Monash UniversityClayton VIC 3800Australia research institute of Interdisciplinary Science Dongguan University of TechnologyDongguan 523808China Yangtze Delta Region Academy of Beijing institute of Technology Jiaxing 314019China

Since the superior mechanical,chemical and physical properties of high-entropy alloys(HEAs)were discovered,they have gradually become new emerging candidates for renewable energy *** review presents the novel applications of HEAs in thermoelectric energy ***,the basic concepts and structural properties of HEAs are ***,we discuss a number of promising thermoelectric materials based on ***,the conclusion and outlook are *** article presents an advanced understanding of the thermoelectric properties of HEAs,which provides new opportunities for promoting their applications in renewable energy.

关键词： high-entropy alloys thermoelectric materials thermal conduction

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