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Boosting synergism of chemo- and immunotherapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

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Acta Pharmaceutica Sinica B 2024年第2期14卷 836-853页

作者： Ge Song Minghui Li Shumin Fan Mengmeng Qin Bin shao wenbing Dai Hua Zhang Xueqing Wang Bing He Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Medical Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijing 100142China

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted *** is critical to inspire new potential to remodel the value of this classical therapeutic ***,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic *** in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle *** synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic *** from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with ***,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

关键词： Bisphosphonate coordinationlipid nanogranules Ferroptosis Mevalonatemetabolism Mitochondrial metabolism Nano-systematic biology

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铝热反应的微型实验研究

中国教育技术装备 2006年第4期 6-8页

作者：邵文兵江苏省奔牛高级中学江苏常州 213131

介绍了环保型铝热反应实验演示仪的结构和使用方法．用定量测定和数理统计的方法分析了直接影响实验效果的铝热剂的配方及用量等因素．以便选择最佳实验条件及合理的配方，最后比较了铝热反应微型实验与常规实验的区别。

关键词：铝热反应微型实验演示仪设计

Seasonal Distribution of Bioaerosols in the Coastal Region of Qingdao

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Journal of Ocean University of China 2014年第1期13卷 57-65页

作者： QI Jianhua shao Qian XU wenbing GAO Dongmei JIN Chuan Laboratory of Marine Environment and Ecology of MOE Ocean University of China

Bioaerosols were collected by using a six-stage bioaerosols sampler from September 2007 to August 2008 in the coastal region of Qingdao, China. The terrestrial and marine microbes(including bacteria and fungi) were analyzed in order to understand the distribution features of bioaerosols. The results show that the average monthly concentrations of terrestrial bacteria, marine bacteria, terrestrial fungi and marine fungi are in the ranges of 80–615 CFU m-3, 91–468 CFU m-3, 76–647 CFU m-3 and 231–1959 CFU m-3, respectively. The concentrations of terrestrial bacteria, marine bacteria, terrestrial fungi, marine fungi and total microbes are the highest in each microbial category during fall, high in spring, and the lowest in the summer and winter. The bacterial particles are coarse in spring, autumn and winter. The sizes of fungal particle present the log-normal distribution in all the seasons.

关键词： bioaerosols bacteria fungi seasonal distribution size distribution

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轴承坯料机械手轴盖3D多工位级进模设计

模具技术 2024年第2期 55-63页

作者：汪志敏肖国华王东钢李亚峰徐生李文斌邵钟余健浙江工商职业技术学院机电工程学院浙江宁波315000 嘉兴南洋职业技术学院机电与交通分院浙江嘉兴314031

针对轴承坯料机械手轴盖制件一套三件的成套冲压成型生产要求,运用3D设计软件UG设计了一副11工位连续级进模用于轴盖成套制件的生产。模具中所设计的11工位包括冲孔、落料、拉深、翻边、侧切、侧冲孔等工艺成型手段,模具达到的效果是材... 详细信息

针对轴承坯料机械手轴盖制件一套三件的成套冲压成型生产要求,运用3D设计软件UG设计了一副11工位连续级进模用于轴盖成套制件的生产。模具中所设计的11工位包括冲孔、落料、拉深、翻边、侧切、侧冲孔等工艺成型手段,模具达到的效果是材料利用率达到64.23%,制件生产效率可达45套/min,模具制造成本降低5%。相比于传统多工序多套单冲模成型工艺,生产效率提高10倍以上。模具中,使用1次拉深成型、3次精修,对多级拉深成型件进行加工能有效降低制件加工难度;使用步进电机送料,氮气弹簧压料和顶料,使模具设计难度大为降低;使用了两种楔紧块驱动型侧滑块机构对制件进行工艺面切除加工和精整形,及燕尾槽压块驱动上模侧冲孔滑块机构使制件的侧面加工得到了可靠保证。使用UG设计软件设计了模具的3D结构,较之于2D排位设计方法,更能有效避免设计缺陷,模具设计效率和可靠性更高。

关键词： UG 冲压成型级进模设计 3D模具结构滑块机构拉深冲孔翻边成型

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Inversion of the Volumetric Strain of Aquifer According to the Tidal Effect of Groundwater in North China

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Earthquake Research in China 2014年第4期28卷 520-531页

作者： Yang Liu Ma Jianying Cao Jingquan shao Yongxin Liu wenbing Earthquake Administration of Tianjin Municipality Institute of Geophysics CEA

The change of the confined aquifer level reflects the pore pressure change,and the pore pressure change of the aquifer is closely related to the aquifer pressure. This paper uses the tidal response of the well water level data in the North China region to calculate the tidal factor of each well and extract the effective water trend information. Then,the volumetric strain of an existing confined aquifer well in the North China region is inverted,and the contour maps are plotted on a half-year scale from 2009 to 2012. Results show that it can reflect the state of stress and strain in deep crust to a certain extent in the North China region.

关键词： North China region Water level Tidal factor Volumetric strain

EjBZR1 represses fruit enlargement by binding to the EjCYP90 promoter in loquat

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Horticulture Research 2021年第1期8卷 2068-2081页

作者： wenbing Su Zikun shao Man Wang Xiaoqing Gan Xianghui Yang Shunquan Lin State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources and Key Laboratory of Innovation and Utilization of Horticultural Crop Resources in South China(Ministry of Agriculture and Rural Affairs) College of HorticultureSouth China Agricultural University510642 GuangzhouChina Fruit Research Institute Fujian Academy of Agricultural Science350013 FuzhouChina Key Laboratory of Loquat Germplasm Innovation and Utilization Putian University351100 PutianChina

Loquat(Eriobotrya japonica)is a subtropical tree that bears fruit that ripens during late *** size is one of the dominant factors inhibiting the large-scale production of this fruit *** date,little is known about fruit size *** this study,we first discovered that cell size is more important to fruit size than cell number in loquat and that the expression of the EjBZR1 gene is negatively correlated with cell and fruit ***-induced gene silencing(VIGS)of EjBZR1 led to larger cells and fruits in loquat,while its overexpression reduced cell and plant size in ***,both the suppression and overexpression of EjBZR1 inhibited the expression of brassinosteroid(BR)biosynthesis genes,especially that of *** experiments indicated that EjCYP90A,a cytochrome P450 gene,is a fruit growth activator,while EjBZR1 binds to the BRRE(CGTGTG)motif of the EjCYP90A promoter to repress its expression and fruit cell ***,our results demonstrate a possible pathway by which EjBZR1 directly targets EjCYP90A and thereby affects BR biosynthesis,which influences cell expansion and,consequently,fruit *** findings help to elucidate the molecular functions of BZR1 in fruit growth and thus highlight a useful genetic improvement that can lead to increased crop yields by repressing gene expression.

关键词： thereby finding expansion

转基因玉米GA21品系LAMP检测引物的筛选及方法的建立

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中国食品学报 2014年第10期14卷 216-222页

作者：邵碧英陈文炳曾莹陈彬郑晶缪婷玉彭娟福建出入境检验检疫局福州350001 福建农林大学食品科学学院福州350002

根据转基因玉米GA21品系的特异序列设计了3套环介导等温扩增(LAMP)引物。通过反应温度优化、特异性测定,筛选到1套特异性好的LAMP引物,包括内引物、外引物和环引物各1对。在LAMP反应体系中加入SYBR Green I荧光染料,在实时荧光定量PCR... 详细信息

根据转基因玉米GA21品系的特异序列设计了3套环介导等温扩增(LAMP)引物。通过反应温度优化、特异性测定,筛选到1套特异性好的LAMP引物,包括内引物、外引物和环引物各1对。在LAMP反应体系中加入SYBR Green I荧光染料,在实时荧光定量PCR仪上进行实时监测,对筛选到的LAMP引物进行反应条件、反应体系的优化,建立了转基因玉米GA21品系LAMP检测方法。对该方法的特异性、灵敏度、稳定性进行评价,结果表明建立的LAMP检测方法能特异、灵敏、稳定地检测转基因玉米GA21品系,检测限达到0.05%。将建立的LAMP检测方法应用于玉米及其制品中GA21品系的检测,检测结果与实时荧光PCR法的结果完全一致。

关键词：环介导等温扩增转基因玉米GA21品系特异性检测

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模拟PEG的聚多肽融合技术研究进展

中国药科大学学报 2016年第6期47卷 648-653页

作者：陈荣尹骏邵美姚文兵高向东中国药科大学生命科学与技术学院南京210009

多肽和蛋白质药物特异性高、生物活性高,但是稳定性差、血浆半衰期短,限制了其在临床上的应用。PEG修饰技术是蛋白质长效化的常用手段,但仍存在一定的缺点,因此近年来研究者开发了模拟PEG的聚多肽融合技术。聚多肽融合技术是通过DNA重... 详细信息

多肽和蛋白质药物特异性高、生物活性高,但是稳定性差、血浆半衰期短,限制了其在临床上的应用。PEG修饰技术是蛋白质长效化的常用手段,但仍存在一定的缺点,因此近年来研究者开发了模拟PEG的聚多肽融合技术。聚多肽融合技术是通过DNA重组技术将蛋白质药物与特殊的氨基酸序列融合,增加药物的流体动力学体积或产生电荷效应,从而延缓肾小球滤过,增加融合蛋白的血浆半衰期。本文对已有的多种聚多肽及其在蛋白质长效化方面的研究进行综述。

关键词：聚多肽融合技术治疗蛋白血浆半衰期流体动力学体积肾小球滤过

细胞程序性死亡配体1表位肽疫苗的设计及抗肿瘤活性

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中国药科大学学报 2023年第2期54卷 245-254页

作者：邵世帅段树康田浤姚文兵高向东中国药科大学生命科学与技术学院江苏省生物药物成药性研究重点实验室南京211198

目前已有多款细胞程序性死亡受体1(PD-1)和其配体(PD-L1)免疫检查点阻断抗体用于临床治疗,但只有部分患者表现出临床反应,因此需要一种替代的肿瘤免疫治疗策略。以PD-L1为靶点的治疗性肿瘤疫苗是一种有意义的尝试。本研究设计了以PD-L1... 详细信息

目前已有多款细胞程序性死亡受体1(PD-1)和其配体(PD-L1)免疫检查点阻断抗体用于临床治疗,但只有部分患者表现出临床反应,因此需要一种替代的肿瘤免疫治疗策略。以PD-L1为靶点的治疗性肿瘤疫苗是一种有意义的尝试。本研究设计了以PD-L1为靶点的表位肽疫苗,然后基于人源化免疫系统(HIS)小鼠模型筛选,具有免疫原性的PD-L1表位肽,进一步研究其抗肿瘤活性。结果显示,设计并筛选得到的PD-L1-B1表位肽疫苗不仅成功诱导了PD-L1特异性的体液免疫和细胞免疫,还表现出抗肿瘤活性。此外,免疫治疗还增加了肿瘤的T淋巴细胞浸润,重塑了肿瘤免疫抑制微环境。综上所述,PD-L1-B1表位肽疫苗表现出强效的抗肿瘤活性,对PD-1/PD-L1阻断不敏感的患者可能是一种有效的替代免疫治疗策略。

关键词：肿瘤免疫免疫检查点 PD-L1 表位肽疫苗

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