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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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Structural basis of negative regulation of CRISPR-Cas7-11 by TPR-CHAT

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2716-2725页

作者： Tian Hong Qinghua Luo Haiyun Ma Xin Wang Xinqiong Li Chongrong Shen Jie Pang Yan Wang Yuejia Chen Changbin Zhang Zhaoming Su Haohao Dong Xiaodi Tang Department of laboratory Medicine State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina Frontiers Medical Center Tianfu Jincheng LaboratoryWest China HospitalSichuan UniversityChengduChina

CRISPR‒Cas7-11 is a Type Ⅲ-E CRISPR-associated nuclease that functions as a potent RNA editing ***-peptide repeat fused with Cas/HEF1-associated signal transducer(TPR-CHAT)acts as a regulatory protein that interacts with CRISPR RNA(crRNA)-bound Cas7-11 to form a CRISPR-guided caspase complex(Craspase).However,the precise modulation of Cas7-11’s nuclease activity by TPR-CHAT to enhance its utility requires further ***,we report cryo-electron microscopy(cryo-EM)structures of Desulfonema ishimotonii(Di)Cas7-11-crRNA,complexed with or without the full length or the N-terminus of *** structures unveil the molecular features of the Craspase *** analysis,combined with in vitro nuclease assay and electrophoretic mobility shift assay,reveals that DiTPR-CHAT negatively regulates the activity of DiCas7-11 by preventing target RNA from binding through the N-terminal 65 amino acids of DiTPR-CHAT(DiTPR-CHAT_(NTD)).Our work demonstrates that DiTPRCHAT_(NTD) can function as a small unit of DiCas7-11 regulator,potentially enabling safe applications to prevent overcutting and offtarget effects of the CRISPR‒Cas7-11 system.

关键词： CRISPR crRNA TPR

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Structural disruption of melanin-like polymers with boosted UV protection

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Science China Chemistry 2024年第5期67卷 1653-1663页

作者： Zhen Yang Xianheng Wang Wanjie Bai Zikun Zou Haoxing Wu Yiwen Li Department of Radiology Huaxi MR Research CenterFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065China

Manipulating the energy structure of materials represents an efficient way to regulate their light absorption behaviors. For example, constructing donor-acceptor(D-A) structures to increase the polarizability and reduce the energy bandgap of local molecules has been widely used in the field of organic photovoltaics with ordered structures. Remarkably, even in disordered and chaotic systems such as melanin-like polydopamine(PDA), visible and near-infrared light absorption can be significantly improved using this strategy. However, there has been a noticeable dearth of research on the ultraviolet(UV) light absorption regulation of bioinspired polymers with disordered and chaotic architectures by tailoring the D-A microstructures. In this study, a series of benzoheterocyclic molecules with strong electron-donating features screened by molecular simulation calculations were involved in disrupting the D-A structures within PDA. The destruction of D-A structures promoted the increase of the energy band gap and finally boosted the UV absorption of PDA. The resulting PDA nanoparticles with enhanced UV absorption were further employed to fabricate UV shielding composite films to protect the growth of plants from harmful UV radiation. This research may open up new avenues for structural disruption of bioinspired polymers for enhanced photoprotection applications.

关键词： melanin-like polymers polydopamine D-A structure UV absorption photoprotection

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Structural analysis of conformational changes in the mpox virus A7 protein

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Virologica Sinica 2024年第2期39卷 331-334页

作者： Xincheng Ni Kai Wang Yinze Han Jian Lei National Clinical Research Center for geriatrics and State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu610041China

Dear Editor,The mpox(formerly known as monkeypox)disease caused by the mpox virus(MPXV)has infected more than 89,700 people and is linked to 157 deaths in 114 countries worldwide as of September 2023(***).Mpox is a zoonotic disease,the first human case of which was reported in 1970(Breman et al.,1980).Common symptoms in mpox-infected individuals include fever,myalgia,fatigue,headache,and a characteristic rash(Isidro et al.,2022).Current treatments for mpox remain limited,and an in-depth investigation of essential viral protein(s)will help to explore novel drug targets.

关键词： infected headache

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Engineering self-catabolic DNAzyme nanospheres for synergistic anticancer therapy

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Science China Chemistry 2024年第7期67卷 2412-2422页

作者： Yu Chen Yu Guo Jiaoli Wang Ruiting Liu Xiaohai Yang Kemin Wang Ying Pu Hui Shi Jin Huang key laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical EngineeringKey Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceHunan UniversityChangsha 410082China National Clinical Research Center for Geriatric Disorders Department of GeriatricsXiangya HospitalCentral South UniversityChangsha 410008China

DNAzyme-based gene therapy faces some challenges including cell penetration,activity limitation,and co-delivery ***-assembled DNA nanomedicine has attracted widespread attention due to its many *** is urgent to develop a universal DNA degradation strategy for precise programmable drug ***,we reported a self-catabolic DNAzyme nanospheres(SCNS),which could simultaneously achieve cell penetration,activity enhancement,and co-delivery *** SCNS were assembled through Y-DNA stepwise hybridization with each other,which were then loaded with aptamer(Apt),doxorubicin(Dox),and zinc oxide nanoparticles(ZnO NPs).The acid-triggered dissociation of ZnO NPs leads to the generation of Zn^(2+)ions cofactors for immediately self-catabolic DNAzyme *** the disassembly of the SCNS,three types of anticancer treatments would be activated,which include Zn^(2+)involved reactive oxygen species(ROS),Dox-induced chemotherapy,and DNAzyme-based gene *** experimental results show that the nanoplatform(Apt-SCNS-Dox-ZnO)has a good tumor-killing effect and minimal side *** a smart self-driven drug delivery nanoplatform,it is anticipated to displace extraordinary potential in biomedicine and bioengineering.

关键词： DNAzyme nanosphere ZnO NPs ROS Dox anticancer therapy

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Decoding aging: examining the non-evolutionary event from an evolutionary perspective

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Science China Life Sciences 2024年第9期67卷 2026-2029页

作者： Yannan Guo Kang Xu Jianping Cai Zhao Wang Protein Science key laboratory of the Ministry of Education School of Pharmaceutical Sciences Tsinghua University Beijing Institute of geriatrics Beijing HospitalNational Center of Gerontology National Health Commission

In an era marked by increased longevity,a deeper understanding of the older population is vital. By introducing an overlooked evolutionary perspective on aging, this article challenges traditional biogerontology, which primarily focuses on biological and clinical aspects. It articulately differentiates between chronological and physiological aging, suggesting that aging is an evolutionary byproduct rather than a direct evolutionary event.

关键词： LIFE

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Colony-stimulating factor-1 receptor inhibition combined with paclitaxel exerts effective antitumor effects in the treatment of ovarian cancer

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Genes & Diseases 2024年第3期11卷 400-416页

作者： Meijia Yu Yiming Wu Qingfang Li Weiqi Hong Yang Yang Xiaoyi Hu Yanfei Yang Tianqi Lu Xia Zhao Xiawei Wei laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China Department of Gynecology and Obstetrics Development and Related Disease of Women and Children Key Laboratory of Sichuan ProvinceKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second HospitalSichuan UniversityChengduSichuan 610041China Department of Obstetrics and Gynecology The First Affiliated HospitalArmy Medical UniversityChongqing 400038China

Ovarian cancer is the tumor with the highest mortality among gynecological *** have confirmed that paclitaxel chemoresistance is associated with increased infiltration of tumor-associated macrophages(TAMs)in the ***-stimu-lating factor 1(CSF-1)receptor(CSF-1R)plays a key role in regulating the number and differ-entiation of macrophages in certain solid *** are few reports on the effects of targeted inhibition of CSF-1R in combination with chemotherapy on ovarian cancer and the tu-mor ***,we explored the antitumor efficacy and possible mechanisms of the CSF-1R inhibitor pexidartinib(PLX3397)when combined with the first-line chemothera-peutic agent paclitaxel in the treatment of ovarian *** found that CSF-1R is highly ex-pressed in ovarian cancer cells and correlates with poor *** by PLX3397 in combination with paclitaxel significantly inhibited the growth of ovarian cancer both in vitro and in *** of CSF-1R altered the macrophage phenotype and reprogrammed the immunosuppressive cell population in the tumor microenvironment.

关键词： CSF-1R Ovariancancer Paclitaxel PLX3397 Targeted therapy Tumor-associated macrophages

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Ergothioneine and its congeners:anti-ageing mechanisms and pharmacophore

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Protein & Cell 2024年第3期15卷 191-206页

作者： Li Chen Liping Zhang Xujun Ye Zixin Deng Changming Zhao Department of geriatrics Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China key laboratory of Combinatory Biosynthesis and Drug Discovery School of Pharmaceutical SciencesMinistry of EducationWuhan UniversityWuhan 430072China tThese authors contributed equally.

Ergothioneine,Ovothiol,and Selenoneine are sulfur/selenium-containing histidine-derived natural products widely distributed across different *** exhibit significant antioxidant properties,making them as potential lead compounds for promoting *** evidence suggests that Ergothioneine is positively correlated with healthy ageing and *** mechanisms underlying Ergothioneine's regulation of the ageing process at cellular and molecular levels are beginning to be *** this review,we provide an in-depth and extensive coverage of the anti-ageing studies on Ergothioneine and discuss its possible intracellular targeting *** addition,we highlight the recent efforts in elucidating the biosynthetic details for Ergothioneine,Ovothiol,and Selenoneine,with a particular focus on the study of their pharmacophore-forming enzymology.

关键词： Ergothioneine antioxidant anti-ageing longevity biosynthesis enzymology

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Single-cell transcriptomics systematically discloses the immune-inflammatory responses of peripheral blood mononuclear cells for diabetic nephropathy

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Genes & Diseases 2024年第4期11卷 82-85页

作者： Jiangpeng wu Nan Hu Baochun Guo Hualin Ma Lulin Xie Yisha Huang Siyu Xia Yuke Jiang Zhije Li Jigang Wang Xinzhou Zhang Zhen Liang Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China Department of geriatrics and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China State key laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China

Diabetic nephropathy(DN)has become the leading cause of end-stage renal disease with high morbidity and mortality among individuals with diabetes *** functional alterations of renal infiltrating immune cells have been reported as part of the pathological mechanism of DN,the understanding of the immune response underlying peripheral blood mononuclear cells(PBMCs)in DN remains ***,single-cell RNA sequencing(scRNA-seq)was used toprofile the transcriptomic signatures of PBMCs from DN patients.

关键词： nephropathy alterations mortality

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Endogenous retrovirus activation: potential for immunology and clinical applications

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National Science Review 2024年第4期11卷 21-23页

作者： Jundan Yu Peishan Qiu Jingwen Ai Bo Liu Guan-Zhu Han Fan Zhu Wenhong Zhang Jie Cui Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response National Medical Center for Infectious Diseases Huashan Hospital Shanghai Medical College Fudan University CAS key laboratory of Molecular Virology &Immunology Shanghai Institute of Immunity and Infection Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai Huashen Institute of Microbes and Infections College of Life Sciences Nanjing Normal University State key laboratory of Virology and Department of Medical Microbiology School of Basic Medical SciencesWuhan University The Institute of Infection and Health Research Fudan University key laboratory of Medical Molecular Virology(MOE/moh) Shanghai Medical CollegeFudan University laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology Center

Endogenous retroviruses (ERVs), the remnants of ancient retrovirus infections, constitute approximately 8% of the human genome and play important roles in human evolution, development,and diseases. Multiple drugs, such as DNA methyltransferase inhibitors and lysine-specific histone demethylase 1inhibitors, reactivate ERVs, induce viral mimicry and trigger innate immune responses to enhance tumor immunogenicity.

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