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Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery

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Research 2024年第1期2023卷 315-337页

作者： Chong Qiu Fei Xia Junzhe Zhang Qiaoli Shi Yuqing Meng Chen Wang Huanhuan Pang Liwei Gu Chengchao Xu qiuyan guo Jigang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Nephrology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong 518020China

Nanocarriers have therapeutic potential to facilitate drug delivery,including biological agents,smallmolecule drugs,and nucleic ***,their efficiency is limited by several factors;among which,endosomal/lysosomal degradation after endocytosis is the most *** review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport *** strategies include promoting endosomal/lysosomal escape,using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/*** the basis of the findings of this review,we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

关键词： somal drugs finding

Targeted combination therapy for glioblastoma by co-delivery of doxorubicin,YAP-siRNA and gold nanorods

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Journal of Materials Science & Technology 2021年第4期63卷 81-90页

作者： Lihuang Li qiuyan guo Yanxiu Liu Mindan Lu Jun Yang Yunlong Ge Qiang Zhang Benqiang Sun Xiumin Wang Li Liang-cheng Lei Ren Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen Department of BiomaterialsCollege of MaterialsXiamen UniversityXiamen 361005China School of Pharmaceutical Sciences Fujian Provincial Key Laboratory of Innovative Drug Target ResearchXiamen UniversityXiamen 361102China Department of Neurosurgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China Stomatological Hospital of Xiamen Medical College Xiamen 361105China State Key Lab of Physical Chemistry of Solid Surfaces Xiamen UniversityXiamen 361005China

The combination of brain targeting drug delivery systems and multi-modal intervention pose a promising therapeutic approach for glioblastoma *** this study,we developed an angiopep-2 peptide modified cationic liposome loaded with doxorubicin,YAP-siRNA and gold nanorods(D/R@Ang2-Lip+Au)simultaneously,which has high encapsulating efficiency for doxorubicin(95.4%)and effective binding of siRNA at N/P ratio of 20:*** fluorescence imaging and flow cytometry analysis revealed high cellular uptake of D/R@Ang2-Lip+***-time quantitative polymerase chain reaction and western blot analysis indicated that D/R@Ang2-Lip+Au could effectively inhibit the expression of YAP *** vitro and in vivo studies showed that D/R@Ang2-Lip+Au had the ability to target glioblastoma cells,and achieved better anti-proliferative effects compared with non-targeted D/R@Lip+***,in vivo experiment demonstrated that D/R@Ang2-Lip+Au was able to cross the blood-brain barrier,and combination therapy could significantly inhibit tumor ***,the multifunctional D/R@Ang2-Lip+Au might provide a novel approach for effectively delivery of DOX,YAP-siRNA and AuNRs into the glioblastoma cells simultaneously and exerting synergistic therapeutic effects.

关键词： doxorubicin glioblastoma simultaneous

Biomolecular network-based synergistic drug combination discovery:a combination of paeoniflorin and liquiritin alleviates neuropathic pain by inhibiting neuroinflammation via suppressing the chemokine signaling pathway

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1804-1806页

作者： qiuyan guo Weijie Li Chao Wang Xia Mao Xiaoyue Wang Wenjia Chen Haiyu Xu Qian Wang Yanqiong Zhang Na Lin Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University100191 BeijingChina

Dear Editor,Neuropathic pain(NP)resulting from injuries or diseases affecting the somatosensory nervous system is highly prevalent in various pathological conditions.1 Since NP is debilitating and impacts health and the quality of life,there is an urgent need for effective non-addictive new *** Chinese medicine(TCM)has been increasingly used for its benefits in relieving pain in ***-Tou Decoction(WTD),which was first described by the famous TCM classic“Jin Gui Yao Lue”,is one of the most effective TCM herbal prescriptions for pain management.A growing body of clinical evidence shows that WTD markedly alleviates different types of NP,such as trigeminal neuralgia,inflammatory pain,and cancer-induced pain,with a total effectiveness of~80%.2 Our previous data demonstrated the analgesic effects of WTD via suppression of glial cell activation and neuroinflammation and further revealed that WTD attenuated NP partially by inhibiting spinal astrocytic IL-1R1/TRAF6/JNK signaling and regulating the glutamatergic system in CA3 in spinal nerve ligation(SNL)-induced NP in vivo.3,4 However,the bioactive compounds(BACs)of WTD that have an effect on NP and the underlying mechanisms remain unclear.

关键词： pain inflammation inhibiting

Single-cell transcriptome analysis reveals the regulatory effects of artesunate on splenic immune cells in polymicrobial sepsis

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Journal of Pharmaceutical Analysis 2023年第7期13卷 817-829页

作者： Jiayun Chen Xueling He Yunmeng Bai Jing Liu Yin Kwan Wong Lulin Xie Qian Zhang Piao Luo Peng Gao Liwei Gu qiuyan guo Guangqing Cheng Chen Wang Jigang Wang 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 SciencesBeijing100700China Department of Nephrology Shenzhen Key Laboratory of Kidney Diseasesand Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdong518020China

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ *** on the therapeutic effect and mechanism of immunomodulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various immune cells remain *** study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental *** scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during *** could restore neutrophils’chemotaxis and immune function in the septic *** inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during *** also promoted the differentiation and activity of splenic B cells in mice with *** results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the ***,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

关键词： Artesunate Sepsis Single-cell RNA sequencing Immunomodulatory activity

Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

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Journal of Pharmaceutical Analysis 2023年第8期13卷 908-925页

作者： qiuyan guo Jiangpeng Wu Qixin Wang Yuwen Huang Lin Chen Jie Gong Maobo Du Guangqing Cheng Tianming Lu Minghong Zhao Yuan Zhao Chong Qiu Fei Xia Junzhe Zhang Jiayun Chen Feng Qiu Jigang Wang 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 SciencesBeijing100700China School of Chinese Materia Medica and State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of Nephrology Shenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and Engineering Institute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenGuangdong518033China

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune ***,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling ***,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.

关键词： Tripterygium glycosides tablet Acute liver injury scRNA-seq

18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

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Journal of Pharmaceutical Analysis 2022年第4期12卷 570-582页

作者： Qian Zhang Piao Luo Liuhai Zheng Jiayun Chen Junzhe Zhang Huan Tang Dandan Liu Xueling He Qiaoli Shi Liwei Gu Jiahao Li qiuyan guo Chuanbin Yang Yin Kwan Wong Fei Xia Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica Chinese Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of SingaporeSingapore117543Singapore Department of Geriatrics Shenzhen People's Hospital(The Second Clinical Medical CollegeJinan University)Shenzhen518020China

Hepatic stellate cells(HSCs)are essential drivers of *** activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in *** the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ *** a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated ***1 knockdown also led to ROS-mediated apoptosis in activated ***,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.

关键词： Glycyrrhetinic acid Hepatic fibrosis Peroxiredoxin Reactive oxygen species Apoptosis

The Factors Influencing the Odor of PVC Leather

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The Factors Influencing the Odor of PVC Leather

A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers

2020中国汽车工程学会年会暨展览会

作者： Zhao Fu guo qiuyan Yue Ping Li Li Geely Automobile Research Institute（Ningbo） Co. Ltd.

With the enrichment of interior styling materials and the improvement of consumers’ awareness of environmental protection,the interior air performance has increasingly become a serious problem in the automotive *** the main sources of odor in the car,we mainly focus on the seats,dashboard,carpet and other interior parts made of non-metallic *** PVC leather,an important component of seats,as the main research object,this paper analyzed the possible sources of influencing PVC leather odor through processing technology and raw materials,and focused on the influence of different plasticizers on PVC leather *** material selection and optimization scheme of plasticizer material are given through many *** we can improve the odor performance of PVC leather,and ultimately reduce the odor complaints of the vehicle.

关键词： Car odor PVC leather plasticizer odor complaints

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Journal of Pharmaceutical Analysis 2022年第6期12卷 879-888页

作者： Yuqing Meng Jiayun Chen Yanqing Liu Yongping Zhu Yin-Kwan Wong Haining Lyu Qiaoli Shi Fei Xia Liwei Gu Xinwei Zhang Peng Gao Huan Tang qiuyan guo Chong Qiu Chengchao Xu Xiao He Junzhe Zhang Jigang Wang Artemisinin Research Center and Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China Department of Biological Sciences National University of Singapore117543Singapore Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy PhysicsChinese Academy of SciencesBeijing100049China

The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and ***,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in ***,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic *** identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct *** were also more biological processes enriched with these *** applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with *** strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

关键词： Protein corona Nanoparticles Mass spectrometry Proteomic analysis Pharmacodynamic biomarkers

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云计算中虚拟资源管理技术研究

现代电子技术 2016年第1期39卷 35-39页

作者：郭秋滟西昌学院汽车与电子工程学院四川西昌615013

为了确保云计算提供的服务质量,解决云计算资源的不确定性因素,围绕资源预测、资源分配、资源迁移三个方面展开研究。提出了基于资源相似度的性能预测方法,基于多维度质量及负载均衡的资源分配技术以及节点效能和失效规律的资源动态迁... 详细信息

为了确保云计算提供的服务质量,解决云计算资源的不确定性因素,围绕资源预测、资源分配、资源迁移三个方面展开研究。提出了基于资源相似度的性能预测方法,基于多维度质量及负载均衡的资源分配技术以及节点效能和失效规律的资源动态迁移技术。为了验证上述技术方案的合理性和有效性,在对上述技术进行深入研究的基础上,借助相关仿真软件并结合模拟参数设计了多组实验。通过对得到的实验数据和结果进行比较和分析,验证了提出的资源预测技术、资源分配技术、资源迁移技术的正确性和有效性。

关键词：云计算资源管理性能预测资源分配资源迁移