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Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

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biomedical and Environmental Sciences 2024年第2期37卷 178-186页

作者： SONG Yun HE Ying LU Xue Xin ZHANG Xiao Mei JIANG XIAO Lin SONG Qing HUANG Xue Yong MA Hong Xia YU Peng Cheng ZHU Wu Yang Henan provincial Center for Disease Control and Prevention Infectious Disease Prevention and Control InstituteHenan Provincial Key Laboratory of Infectious Disease PathogensZhengzhou 450000HenanChina National Institute for Viral Disease Control and Prevention China CDCKey Laboratory of BiosafetyNational Health CommissionBeijing 102206China shandong provincial Center for Disease Control and Prevention Jinan 250014ShandongChina Qingdao Chengyang District Center for Disease Control and Prevention Qingdao 266108ShandongChina

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

关键词： Rabies Post-exposure immunization Essen regimen RVNAs

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Modularized viromimetic polymer nanoparticle vaccines(VPNVaxs) to elicit durable and effective humoral immune responses

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National Science Review 2024年第3期11卷 200-214页

作者： Zichao Huang Xinyu Zhuang Liping Liu Jiayu Zhao Sheng Ma Xinghui Si Zhenyi Zhu Fan Wu Ningyi Jin Mingyao Tian Wantong Song Xuesi Chen key laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences School of Applied Chemistry and Engineering University of Science and Technology of China Changchun Veterinary Research Institute Chinese Academy of Agricultural Sciences Jilin biomedical polymers Engineering laboratory State key laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences

Virus-like particle(VLP) vaccines had shown great potential during the COVID-19 pandemic, and was thought to be the next generation of antiviral vaccine technology due to viromimetic structures. However,the time-consuming and complicated processes in establishing a current recombinant-protein–based VLP vaccine has limited its quick launch to the out-bursting pandemic. To simplify and optimize VLP vaccine design, we herein report a kind of viromimetic polymer nanoparticle vaccine(VPNVax), with subunit receptor-binding domain(RBD) proteins conjugated to the surface of polyethylene glycol-b-polylactic acid(PEG-b-PLA) nanoparticles for vaccination against SARS-CoV-2. The preparation of VPNVax based on synthetic polymer particle and chemical post-conjugation makes it possible to rapidly replace the antigens and construct matched vaccines at the emergence of different viruses. Using this modular preparation system, we identified that VPNVax with surface protein coverage of 20%–25% had the best immunostimulatory activity, which could keep high levels of specific antibody titers over 5 months and induce virus neutralizing activity when combined with an aluminum adjuvant. Moreover, the polymer nano-vectors could be armed with more immune-adjuvant functions by loading immunostimulant agents or chemical chirality design. This VPNVax platform provides a novel kind of rapidly producing and efficient vaccine against different variants of SARS-CoV-2 as well as other viral pandemics.

关键词： vaccine polymer nanomaterials SARS-CoV-2

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Recent Progress in All-Solution-Processed Organic Solar Cells

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Chinese Journal of Chemistry 2024年第2期42卷 190-198页

作者： Yixuan Xu Qian Wang Wentao Zou Xu Zhang Yanna Sun Yuanyuan Kan Ping Cai Ke Gao School of Materials Science and Engineering&Guangxi key laboratory of Information Materials Guilin University of Electronic TechnologyGuilinGuangxi 541004China shandong provincial key laboratory for Science of Material Creation and Energy Conversion Science Center for Material Creation and Energy ConversionInstitute of Frontier and Interdisciplinary ScienceShandong UniversityQingdaoShandong 266237China

All-solution-processed organic solar cells(OSCs)(from the bottom electrode to the top electrode)are highly attractive thanks to their low cost,lightweight and high-throughput production.However,achieving highly efficient all-solution-processed OSCs remains a significant challenge.One of the key issues is the lack of high-quality solution-processed electrode systems that can replace indium tin oxide(ITO)and vacuum-deposited metal electrodes.In this paper,we comprehensively review recent advances in all-solution-processed osCs,and classified the devices as the top electrode materials,including silver nanowires(AgNWs),conducting polymers and composite conducting materials.The correlation between electrode materials,properties of electrodes,and device performance in all-solution-processed OSCs is elucidated.In addition,the critical roles of the active layer and interface layer are also discussed.Finally,the prospects and challenges of all-solution-processed OSCs are presented.

关键词： Organic solar cells All-solution-processed organic solar cells Solution-processed electrodes High performance Silver nanowires Conductive polymers Composite conducting materials

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Sirt5 desuccinylates Cdc42 to mediate osteoclastogenesis and bone remodeling in mice

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Genes & Diseases 2024年第3期11卷 75-78页

作者： Yuang Zhanngg Jing Wang Jing Luan Chuanju Liu Yazhou Cui Jinxiang Han Department of Orthopedics The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJi'nanShandong 250014China biomedical Sciences College&shandong Medicinal Biotechnology Centre Shandong First Medical University&Shandong Academy of Medical SciencesJi'nanShandong 250117China NHC key laboratory of Biotechnology Drugs(shandong Academy of Medical Sciences) Ji'nanShandong 250117China key Lab for Rare&Uncommon Diseases of shandong Province Ji'nanShandong250117China Department of Orthopaedic Surgery New York University Grossman School of MedicineNew YorkNY 10003USA Department of Cell Biology New York University Grossman School of MedicineNewYorkNY10016USA

Post-translational modifications(PTMs)play a critical role in bone remodeling,with phosphorylation and acetylation being particularly well characterized.Recently,succinylation,a relatively uncommon PTM on lysine,has received considerable research attention for its influence on several physiological and pathological processes and conditions.1 Several substrates involved in mitochondrial pathways have been validated as substrates for the desuccinylase sirtuin 5(Sirt5),a key regulator of succinylation.2 Bone is one of the most metabolically active organs,but the role of succinylation during bone remodeling is not well characterized.

关键词： remodeling organs media

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Enhancing photodynamic inactivation via tunning spatial constraint on photosensitizer

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Science China Chemistry 2024年第2期67卷 652-663页

作者： Chong Li Minghao Han Ji Gao Shuxian Wang Song-Bo Lu Yaxi Li Zhao Liu Chen Zhang Zhaojin Wang Fangliang Wang Yuang Sun Chun Loong Ho Kai Wang Yun Shen Kai Li Shenzhen key laboratory of Smart Healthcare Engineering Guangdong Provincial Key Laboratory of Advanced BiomaterialsDepartment of Biomedical EngineeringSouthern University of Science and TechnologyShenzhen518055China Department of Chemical and Environmental Engineering University of California RiversideRiverside92521USA Department of Electrical and Electronic Engineering Southern University of Science and TechnologyShenzhen518055China

The critical factor of spatial constraint,provided by the external confinement(e.g.,matrix),is often overlooked during photodynamic inactivation,despite playing a crucial role in determining the molecular photophysical process and subsequent antipathogen performance.Here,as a proof-of-concept model,we employed two types of polymers with varying interaction energies with dopants to investigate the intrinsic relationship between spatial constraint and the essential excited-state behaviors of doped photosensitizer(4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)ethyl)-1-methylquinolin-1-ium iodine,TPP).Through experimental investigation and theoretical calculations,we found that TPP tends to remain in the excited state for a shorter dwell time under weaker spatial constraints due to less restricted molecular motion in polyurethane(PU) nanofibers.Consequently,the singlet oxygen(^(1)O_(2)) generated from doped-TPP shows a 9.23-fold enhancement in PU than in the polyvinylchloride(PVC) matrix.Under light irradiation,the PU@TPP nanofiber can efficiently eliminate the coronavirus MHV-A59(≥99.9997%) at a 220,000-fold higher concentration than the infected space.Its antibacterial efficacy has also been demonstrated,with a killing rate of ≥99%.

关键词： photodynamic antibacterial singlet oxygen triphenylamine nanofiber

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Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

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Biophysics Reports 2024年第1期10卷 15-21页

作者： Qinggang Hao Rui Dong Weiyu Bai Dong Chang Xinyi Yao Yingru Zhang Huangying Xu Huiyan Li Xiang Kui Feng Wang Yan Wang Chengqin Wang Yujie Lei Yan Chen Junling Shen Lei Sang Yan Bai Jianwei Sun Center for Life Sciences Yunnan Key Laboratory of Cell Metabolism and Diseases State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan School of Life Sciences Yunnan University key laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province Yan'an Hospital Affiliated to Kunming Medical University shandong provincial key laboratory of Animal Resistance Biology Collaborative Innovation Center of Cell Biology in Universities of Shandong Center for Cell Structure and Function Institute of Biomedical Science College of Life Sciences Shandong Normal University Department of Pathology The Second Affiliated Hospital of Kunming Medical University State key laboratory of Bioactive Molecules and Druggability Assessment Institute of Genomic Medicine College of Pharmacy Jinan University Department of Pathology School of Basic Medicine Qingdao University Department of Thoracic Surgery Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study, we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improves our understanding of the metastasis mechanisms, but also provides potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

关键词： Melanoma Lung metastasis model Gene screening Tail vein injection

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Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu Center for Reproductive Medicine Shandong University CAS key laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong key laboratory of Reproductive Endocrinology of the Ministry of Education Shandong University Center for Reproductive Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse embryos.The allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early embryos.Collectively, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG Han Lin XUE Yan Feng CUI Bao Qiu LIU Hong SHEN Xin Xin shandong provincial Research Center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State key laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

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抗原改造联合纳米肿瘤疫苗用以克服肿瘤新抗原短缺及在多种肿瘤类型上激起强效抗肿瘤免疫反应

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Science Bulletin 2024年第7期69卷 922-932页

作者：陈宏宇黄子超李佳玄董思徐玉笛马胜赵佳雨刘丽萍孙天盟宋万通陈学思 School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China key laboratory of Polymer Ecomaterials Changchun Institue of Applied ChemistryChinese Academy of SciencesChangchun 130022China key laboratory of Organ Regeneration and Transplantation of Ministry of Education Institute of ImmunologyThe First HospitalJilin UniversityChangchun 130021China Jilin biomedical polymers Engineering laboratory Changchun 130022China

Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.

关键词： Cancer immunotherapy Cancer vaccine Neoantigen Nanocarrier Poly(2-oxazoline)s

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Hydrophobic modification of polysaccharides and the construction and properties of their micelles:a review of applications in the field of biomedicine

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Science China Chemistry 2024年第6期67卷 1881-1903页

作者： Dayang Wang Xiaohua Li Huanchen Yao Xin Liu Yan Gao Hailin Cong Bing Yu Youqing Shen College of Chemistry and Chemical Engineering College of Life SciencesCollege of Materials Science and EngineeringInstitute of Biomedical Materials and EngineeringQingdao UniversityQingdao266071China State key laboratory of Bio-Fibers and Eco-Textiles Qingdao UniversityQingdao266071China School of Materials Science and Engineering Shandong University of TechnologyZibo255000China key laboratory of Biomass Chemical Engineering of Ministry of Education Center for Bionanoengineeringand Department of Chemical and Biological EngineeringZhejiang UniversityHangzhou310027China

Nanomedicine delivery technology plays an important role in modern medicine and has shown good therapeutic effects in scientific research.Polysaccharides have the characteristics of wide sources,excellent biocompatibility,and non-toxicity.In addition,there are multifunctional groups on the main chain of polysaccharides,which can be surface-modified or functionalized to have targeting ability through specific sugar parts.Amphiphilic polysaccharide micelles with good biocompatibility,degradability,high safety,easy structural modification,and special core-shell structure are regarded as ideal carriers for nanomedicines.Therefore,this review is focused on the hydrophobic modification designs of polysaccharides,the preparation methods and characteristics of micelles,and the applications of amphiphilic polysaccharide micelles in the field of biomedicine.It is expected to provide some ideas and inspiration for the design of polysaccharide drug carriers.

关键词： polysaccharide hydrophobic modification micelle drug delivery biomedicine

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