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Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

Acta Pharmaceutica Sinica B 2022年第1期12卷 451-466页

作者： Xianbin Ma Shaochen Yang Tian Zhang Shuo Wang Qichao Yang Yao Xiao Xiaoxiao Shi Peng Xue Yuejun Kang Gang Liu Zhi-Jun Sun Zhigang Xu Key Laboratory of Luminescence Analysis and molecular Sensing(Southwest university) Ministry of EducationSchool of Materials and Energy&Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and DevicesSouthwest UniversityChongqing 400715China The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of EducationSchool and Hospital of StomatologyWuhan UniversityWuhan 430079China State Key Laboratory of molecular Vaccinology and molecular Diagnostics&Center for molecular imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen 361102China

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels(DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful antitumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

关键词： Bioresponsive Prodrug Nanogel Doxorubicin Mannose Immunogenic cell death Chemotherapy Immunotherapy

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hTFtarget:A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets

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Genomics, Proteomics & Bioinformatics 2020年第2期18卷 120-128页

作者： Qiong Zhang Wei Liu Hong-Mei Zhang Gui-Yan Xie Ya-Ru Miao Mengxuan Xia An-Yuan Guo Department of Bioinformatics and Systems Biology Key Laboratory of Molecular Biophysics of the Ministry of EducationHubei Bioinformatics and Molecular Imaging Key LaboratoryCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Clinical Center of Human Genomic Research Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Transcription factors(TFs)as key regulators play crucial roles in biological *** identification of TF-target regulatory relationships is a key step for revealing functions of TFs and their regulations on gene *** accumulated data of chromatin immunoprecipitation sequencing(ChIP-seq)provide great opportunities to discover the TF-target regulations across different *** this study,we constructed a database named hTFtarget,which integrated huge human TF target resources(7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs)and epigenetic modification information to predict accurate TF-target *** offers the following functions for users to explore TF-target regulations:(1)browse or search general targets of a query TF across datasets;(2)browse TF-target regulations for a query TF in a specific dataset or tissue;(3)search potential TFs for a given target gene or noncoding RNA;(4)investigate co-association between TFs in cell lines;(5)explore potential coregulations for given target genes or TFs;(6)predict candidate TF binding sites on given DNA sequences;(7)visualize ChIP-seq peaks for different TFs and conditions in a genome *** provides a comprehensive,reliable and user-friendly resource for exploring human TF-target regulations,which will be very useful for a wide range of users in the TF and gene expression regulatiol *** is available at bttp://***/hTFtarget.

关键词： Transcription factor ChIP-seq Transcriptional regulation Human Database

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Control of de novo root regeneration efficiency by developmental status of Arabidopsis leaf explants

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Journal of Genetics and Genomics 2019年第3期46卷 133-140页

作者： Jing Pan Fei Zhao Guifang Zhang Yu Pan Lijun Sun Ning Bao Peng Qin Lyuqin Chen Jie Yu Yijing Zhang Lin Xu National Key Laboratory of Plant molecular Genetics CAS Center for Excellence in Molecular Plant Sciences Shanghai Institute of Plant Physiology and Ecology Chinese Academy of Sciences university of Chinese Academy of Sciences School of Life Sciences Nantong University School of Public Health Nantong University Department of Instrument Science and Engineering Shanghai Jiao Tong University Departments of Neurosurgery Psychiatry and Behavioral Sci-ences Stanford University School of Medicine

De novo root regeneration(DNRR) has wide applications in agriculture such as those related to cutting technology. Detached Arabidopsis thaliana leaf explants can regenerate adventitious roots without added hormones. The regenerative ability is highly dependent on the developmental status of the leaf. An immature leaf has a higher regenerative ability, while a mature leaf is difficult to regenerate. Using RNASeq analysis, we showed that the expression levels of many genes, including those in the auxin network,changed during leaf maturation. Particularly, the expression levels of many YUCCA(YUC) genes in the auxin biosynthesis pathway are responsive to leaf maturation. Overexpression of YUC1 in the yuc-1 D dominant mutant rescued the rooting defects caused by leaf maturation. In addition, YUC4 expression levels were also affected by circadian rhythms. The regenerative ability was reduced in both immature and mature mutant leaf explants from the new wuschel-related homeobox 11-3(wox11-3) and wox12-3 mutant alleles created by the CRISPR/Cas9 method. Overall, the transcriptome and genetic data, together with the auxin concentration analysis, indicate that the ability to upregulate auxin levels upon detachment may be reduced during leaf maturation. Thus, multiple developmental and environmental signals may converge to control auxin accumulation, which affects the efficiency of the WOX11/12-mediated DNRR from leaf explants.

关键词： De novo root regeneration WOX11 Arabidopsis Developmental status Circadian rhythms YUCCA

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利用纳米粒子进行肿瘤分子成像

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Engineering 2016年第1期 278-295页

作者：程震闫雪峰孙夕林申宝忠 Sanjiv Sam Gambhir molecular imaging program at stanford Department of Radiology Stanford University molecular imaging Research Center of Harbin Medical university TOF-PET/CT/MR Center the Fourth Hospital of Harbin Medical University Departments of Bioengineering & Materials Science and Engineering Bio-X Program Canary Center at Stanford for Cancer Early Detection Stanford University

分子成像不仅可以利用传统成像技术提供结构图像,也可利用许多新的成像技术提供生物功能信息和分子信息。在过去的几十年间,纳米技术在分子成像中的应用显示了许多明显的优势,并且为活体成像提供了新的机遇。多模态纳米粒子可对肿瘤的... 详细信息

分子成像不仅可以利用传统成像技术提供结构图像,也可利用许多新的成像技术提供生物功能信息和分子信息。在过去的几十年间,纳米技术在分子成像中的应用显示了许多明显的优势,并且为活体成像提供了新的机遇。多模态纳米粒子可对肿瘤的生物性和微环境做出精确评估。本文讨论了与工程化纳米粒子相关的话题,并总结了近几年来这些纳米结构在恶性肿瘤光学成像、超声成像、光声成像、磁共振成像和放射性核素显像中的应用;同时,还讨论了将纳米粒子应用到临床医学中面临的主要挑战。

关键词：肿瘤分子成像纳米粒子

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Technologies for investigating single-molecule chemical reactions

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National Science Review 2024年第8期11卷 322-352页

作者： Chunyan Gao Qinghua Gao Cong Zhao Yani Huo Zhizhuo Zhang Jinlong Yang Chuancheng Jia Xuefeng Guo Center of Single-Molecule Sciences Institute of Modern OpticsFrontiers Science Center for New Organic MatterTianjin Key Laboratory of Micro-Scale Optical Information Science and TechnologyCollege of Electronic Information and Optical EngineeringNankai University Hefei National Research Center for Physical Sciences at Microscale University of Science and Technology of China Beijing National Laboratory for molecular Sciences National Biomedical Imaging CenterCollege of Chemistry and Molecular Engineering Peking University

Single molecules,the smallest independently stable units in the material world,serve as the fundamental building blocks of *** different branches of single-molecule sciences,single-molecule chemical reactions,by revealing the behavior and properties of individual molecules at the molecular scale,are particularly attractive because they can advance the understanding of chemical reaction mechanisms and help to address key scientific problems in broad fields such as physics,chemistry,biology and materials *** review provides a timely,comprehensive overview of single-molecule chemical reactions based on various technical platforms such as scanning probe microscopy,single-molecule junction,single-molecule nanostructure,single-molecule fluorescence detection and crossed molecular *** present multidimensional analys es of single-molecule chemical reactions,offering new perspectives for research in different areas,such as photo catalysis/electrocatalysis,organic reactions,surface reactions and biological ***,we discuss the opportunities and challenges in this thriving field of single-molecule chemical reactions.

关键词： chemical reaction scanning probe microscopy single-molecule junction single-molecule fluorescence crossed molecular beam

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Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL

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Genomics, Proteomics & Bioinformatics 2019年第2期17卷 190-200页

作者： Qiong Zhang Hui Hu Si-Yi Chen Chun-Jie Liu Fei-Fei Hu Jianming Yu Yaohui Wu An-Yuan Guo Hubei Bioinformatics and molecular imaging Key Laboratory Department of Bioinformatics and Systems Biology Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Wuhan 430074 China Institute of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor effi-cacy in clinical trials. In this study,we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells,and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations,e.g.,CD8+T cells and natural killer (NK) cells,in the bone marrow. Additionally,CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways,including the NK cell mediated cytotoxicity and NOD-like recep-tor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g.,miR-148a-3p and miR-375),acting as oncogenes or tumor suppressors,could regulate the crosstalk between the genes encoding transcription factors (TFs,e.g.,JUN and FOS) and histones (e.g.,HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore,many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g.,FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for fur-ther understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.

关键词： CAR-T B-ALL Transcriptome profile lncRNA Regulatory network

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Microfluidics-based strategies for molecular diagnostics of infectious diseases

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Military Medical Research 2022年第6期9卷 727-753页

作者： Xin Wang Xian-Zhe Hong Yi-Wei Li Ying Li Jie Wang Peng Chen Bi-Feng Liu The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics&molecular imaging Key Laboratory Systems Biology ThemeDepartment of Biomedical EngineeringCollegeof Life Science and TechnologyHuazhong University of Scienceand TechnologyWuhan 430074China State Key Laboratory of Magnetic Resonance and Atomic molecular Physics Wuhan National Laboratory for OptoelectronicsNational Centre for Magnetic Resonancein WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan 430071China Department of Radiology Canary Center at Stanford for Cancer Early DetectionSchool of MedicineStanford UniversityPalo AltoCA 94304USA

Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing(POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology,are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site *** diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen *** review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes,including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.

关键词： Microfluidics molecular diagnostics Infectious disease Point-of-care testing(POCT) Digital assay

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GPU accelerated simplified harmonic spherical approximation equations for three-dimensional optical imaging

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Chinese Optics Letters 2016年第7期14卷 80-84页

作者：任胜寒陈雪利曹旭朱守平梁继民 Engineering Research Center of molecular and Neuro imaging of Ministry of Education & School of Life Science and Technology Xidian University

Simplified spherical harmonics approximation （SPN） equations are widely used in modeling light propagation in biological tissues. However, with the increase of order N, its computational burden will severely aggravate. We propose a graphics processing unit （GPU） accelerated framework for SPN equations. Compared with the conven- tional central processing unit implementation, an increased performance of the GPU framework is obtained with an increase in mesh size, with the best speed-up ratio of 25 among the studied cases. The influence of thread distribution on the performance of the GPU framework is also investigated.

关键词： Computer graphics Light propagation program processors

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Retro-enantio isomer of angiopep-2 assists nanoprobes across the blood-brain barrier for targeted magnetic resonance/fluorescence imaging of glioblastoma

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Signal Transduction and Targeted Therapy 2021年第9期6卷 2870-2882页

作者： Ruoxi Xie Zijun Wu Fanxin Zeng Huawei Cai Dan Wang Lei Gu Hongyan Zhu Su Lui Gang Guo Bin Song Jinxing Li Min Wu Qiyong Gong Huaxi MR Research Center(HMRRC) Department of RadiologyFunctional and Molecular Imaging Key Laboratory of Sichuan ProvinceWest China HospitalSichuan UniversityChengduChina Research Unit of Psychoradiology Chinese Academy of Medical SciencesChengduChina Department of Clinic Medical Center Dazhou Central HospitalDazhouChina Laboratory of Clinical Nuclear Medicine Department of Nuclear MedicineWest China HospitalSichuan UniversityChengduChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduChina Department of Chemical Engineering Stanford UniversityStanfordCaliforniaUSA

Glioblastoma(GBM),one of the most common primary intracranial malignant tumours,is very difficult to be completely excised by surgery due to its irregular ***,we use an MRI/NIR fluorescence dual-modal imaging nanoprobe that includes superparamagnetic iron oxide nanoparticles(SPIONs)modified with indocyanine(Cy7)molecules and peptides(ANG orDANG)to locate malignant gliomas and guide accurate *** peptides/Cy7-SPIONs probes displayed excellent tumour-homing properties and barrier penetrating abilities in vitro.

关键词： tumour malignant surgery

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Antigen self-presenting nanovaccine for cancer immunotherapy

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Science Bulletin 2022年第16期67卷 1611-1613页

作者： Xiaoliu Liang Hongwei Cheng Chao Liu Gang Liu State Key Laboratory of molecular Vaccinology and molecular Diagnostics&Center for molecular imaging and Translational Medicine School of Public HealthXiamen UniversityXiamen 361102China

Cancer immunotherapy has made breakthroughs in clinical application and has become the fourth most prevalent tumor treatment method after surgical resection,chemotherapy,and *** mainly enhances the anti-tumor immunity of the tumor microenvironment by stimulating or mobilizing the immune system to control and kill tumor cells[1].T lymphocytes are an important component of the body’s immune system,which indirectly or directly affects the occurrence and development of tumors,and emerging advances in T lymphocyte-based tumor immunotherapy also attract much more *** is a common knowledge that the activation,proliferation,and differentiation of antigen-specific lymphocytes are the key to the successful establishment of anti-tumor immunity,and this process largely depends on the interaction between T cells and antigen-presenting cells(APCs)[1].Activation of CD8+cytotoxic T lymphocytes(CTLs)has proved to be an important role in cancer *** antigens are presented to T cells through major histocompatibility complex class I(MHC-I)molecules on the surface of APCs,thereby stimulating the activation and proliferation of CD8+T cells,and finally producing a strong,sustained,and effective CTL response[2].Therefore,fully mobilizing the function of T lymphocytes is essential for tumor immunotherapy.

关键词： immunity lymphocytes sustained

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