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Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3643-3660页

作者： Jie Wang Zilong zhang Yan Zhuo zhuan zhang Rongrong Chen Li Liang Xiaohe Jiang Di Nie Chang Liu Zhiwen Zou Xiang Li Jiaxin Li Bingqi Wang Rui Wang Yong Gan Miaorong Yu School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Jiangxi Medical College Nanchang UniversityNanchang 330006China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum(ER)presents an opportunity to amplify the synergistic effects of chemotherapy and *** this study,we initially validated celastrol(CEL)as an inducer of immunogenic cell death(ICD)by promoting ER stress and autophagy in colorectal cancer(CRC)***,an ER-targeted strategy was posited,involving the codelivery of CEL with PD-L1 small interfering RNAs(siRNA)using KDEL peptide-modified exosomes derived from milk(KME),to enhance chemoimmunotherapy *** findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER *** to their non-targeting counterparts,KME exhibited a significant augmentation of the CEL-induced ICD ***,it facilitated the release of danger signaling molecules(DAMPs),thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the ***,the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression,consequently fostering the proliferation and activity of CD8^(+)T ***,the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in ***,a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

关键词： Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress Immunogenic cell death siRNA Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress Immunogenic cell death siRNA

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一种大缸径气缸套毛坯生产线的设计

内燃机与配件 2024年第5期 40-42页

作者：张转立中原内配集团智能装备有限公司河南焦作454750

本文设计了一种大缸径气缸套毛坯生产线,主体为八工位浇注机,其上设置有四个动力头,浇注机的周围呈正八边形设置有八个工位。工位一设置有浇火装置,工位二、三、四为激水工位,工位五、六、七分别设置有拔毛坯装置、拨飞锤装置和模具清... 详细信息

本文设计了一种大缸径气缸套毛坯生产线,主体为八工位浇注机,其上设置有四个动力头,浇注机的周围呈正八边形设置有八个工位。工位一设置有浇火装置,工位二、三、四为激水工位,工位五、六、七分别设置有拔毛坯装置、拨飞锤装置和模具清刷装置、模具喷涂装置。毛坯拔出后经风冷装置及毛坯清刷装置再由多关节机械手放入毛坯筐。挡板由多关节机械手取出后经过挡板清刷喷涂装置处理后再装入模具。该生产线自动化程度高,占地面积小,生产效率得到大幅提高。

关键词：气缸套浇注机清刷喷涂

基于HPLC指纹图谱结合一测多评法的葛花质量控制研究

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天然产物研究与开发 2024年第2期36卷 233-242页

作者：张立军张新玥李鹏张转平朱远锋刘丽王磊吴春燕安康市食品药品检验检测中心安康市天源植物提取有限公司安康725000 商洛市药品检验所商洛726000 北京中医药大学药学院北京100029

建立葛花药材的指纹图谱,并同时建立其中10个主要黄酮类成分含量的一测多评分析方法(QAMS),用于不同产地葛花药材整体质量评价。采用高效液相色谱法(HPLC)对不同产地葛花中主要化学成分进行分析,确定最佳色谱条件,建立指纹图谱;在此基础... 详细信息

建立葛花药材的指纹图谱,并同时建立其中10个主要黄酮类成分含量的一测多评分析方法(QAMS),用于不同产地葛花药材整体质量评价。采用高效液相色谱法(HPLC)对不同产地葛花中主要化学成分进行分析,确定最佳色谱条件,建立指纹图谱;在此基础上,以葛花苷为参照峰,建立QAMS测定葛花10个黄酮类成分含量;并与外标法(ESM)测定结果比较,验证QAMS的准确性。建立了葛花药材指纹图谱,20批葛花和10批粉葛花药材的相似度均大于0.85,标定共有峰分别为18和27个。以葛花苷为参照峰,各个成分校正因子的重复性、耐用性均良好;应用一测多评法测定10个成分的含量,与外标法测定结果比较,含量无明显差异(P>0.05),相对偏差<3.0%。不同产地来源的葛花药材中10个成分含量均存在较大差异,说明应提高葛花药材的质量控制标准。所建立的指纹图谱结合一测多评分析方法简便、可行,可客观、有效的用于不同产地葛花药材质量评价,可以为葛花质量标准修订、优质葛花种质资源的选育和育种提供参考。

关键词：葛花粉葛花指纹图谱一测多评不同产区质量评价

Adsorbability of Mycobacterium phlei on hematite surface

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Journal of University of Science and Technology Beijing 2007年第2期14卷 103-106页

作者： Huifen Yang Qiang zhang zhuan Jiang Civil and Environmental Engineering School University of Science and Technology Beijing Beijing 100083 China

The adsorption of microorganisms on the mineral surface is the base of microorganisms that are considered as mineral processing reagents. The principles of the use of a highly hydrophobic and negatively charged bacterium, Mycobacterium phlei, as a flocculating-flotating agent for finely divided hematite were investigated. The flocculating-floating recovery is strongly dependent on the pH and the dosage of the bacterium. Generally the pH should be controlled over the range of 5.5-7, and the dosage should be controlled about 16 mg/L. The infrared spectrometry analysis indicates that the six functional groups of M. phlei, substituted aromatic compound groups, -（CH2） n-groups, -CH2（-CH3） groups, carbonyl groups, aromatic hydrocarbon groups, and carboxyl groups, are on the hematite surface, among which the first five ones contribute physical adsorption and only the carboxyl groups provide chemisorption. Microscopic analysis reveals that the dimensions and tight aggregation degree of the flocs of hematite particles formed by M. phlei are also impacted by the pH and the content of M. phlei in flotation.

关键词： microorganisms mycobacterium phlei hematite flocculation flotation infrared spectrometry microscopic analysis physical adsorption chemisorption

术中持续输注胰岛素对心肺转流心脏手术患者心肌血流灌注的影响

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临床麻醉学杂志 2024年第5期40卷 497-502页

作者：张转殷佳佳李宁陈超张凯马蓉蓉贯士玉张建友王强李虎扬州大学附属医院麻醉科 225012 扬州大学附属医院心脏大血管中心 225012

目的探讨术中持续输注胰岛素对心肺转流(CPB)心脏手术患者心肌血流灌注的影响。方法选择择期行CPB心脏手术患者48例,男21例,女27例,年龄55~80岁,BMI 18~28 kg/m^(2),ASAⅡ—Ⅳ级。将患者随机分为两组:胰岛素组(I组,n=25)和对照组(C组,n=... 详细信息

目的探讨术中持续输注胰岛素对心肺转流(CPB)心脏手术患者心肌血流灌注的影响。方法选择择期行CPB心脏手术患者48例,男21例,女27例,年龄55~80岁,BMI 18~28 kg/m^(2),ASAⅡ—Ⅳ级。将患者随机分为两组:胰岛素组(I组,n=25)和对照组(C组,n=23)。两组采用相同麻醉方案。麻醉诱导后I组静脉输注胰岛素30 mU·kg^(-1)·h^(-1)、葡萄糖0.12 g·kg^(-1)·h^(-1)、氯化钾0.06 mmol·kg^(-1)·h^(-1)混合液,C组予以生理盐水10 ml/h输注,均输注至术毕。术中目标血糖值为6.1~11.1 mmol/L。于麻醉诱导后10 min(T_(2))和术毕(T_(6))行经食管超声心动图(TEE)检测,记录冠状静脉窦(CS)血流频谱、直径及肺静脉血流频谱,并计算CS净向前血流流速时间积分(VTI)。记录T_(2)、CPB前2 min(T_(3))、CPB结束时(T_(5))和T_(6)时的股动脉平均动脉压(MAP)、中心静脉压(CVP)、每搏量(SV)、心脏指数(CI)及外周血管阻力指数(SVRI)。记录麻醉诱导前5 min(T_(1))、T_(3)、CPB后30 min(T_(4))、T_(5)、T_(6)、术后6 h(T_(7))、术后12 h(T_(8))及术后24 h(T 9)时血糖及乳酸浓度。记录术前1 d、术后1、2 d时超敏C反应蛋白(hs-CRP)、高敏肌钙蛋白I(hs-TnI)和肌酸激酶同工酶(CK-MB)水平。结果与C组比较,I组T_(6)时CS净前向血流VTI及每分钟CS血流量均明显增加(P<0.05),肺静脉心房收缩期峰值流速(ARp)明显减小(P<0.05),T_(5)、T_(6)时SV和CI明显增大、SVRI明显降低(P<0.05),T_(7)、T_(8)时乳酸浓度明显降低(P<0.05),术后1、2 d时hs-CRP和CK-MB水平明显降低(P<0.05),术后2 d时hs-TnI明显降低(P<0.05)。结论CPB心脏手术中持续输注胰岛素,同时维持血糖6.1~11.1 mmol/L,可改善心肌血流灌注,减轻术后炎症反应及心肌损伤。

关键词：胰岛素心肺转流灌注心肌灌注显像冠状静脉窦

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黄芪及活性成分治疗肺癌的研究进展

中国中药杂志 2024年第2期49卷 294-303页

作者：马定财王哲王毛毛张育贵王彦钧刘婷张转红高飞云李越峰甘肃中医药大学甘肃兰州730000 甘肃省中药质量与标准研究重点实验室甘肃兰州730000

肺癌是癌症死亡原因居于首位的恶性肿瘤,其有效治疗是现代医学难题。肺癌属于中医“肺积”“息贲”“劳嗽”等范畴,中医药在治疗肺癌方面已积累大量理论基础和实践经验。黄芪是补气药代表之一,黄芪治疗肺癌以“气虚邪滞”为主要证型,“... 详细信息

肺癌是癌症死亡原因居于首位的恶性肿瘤,其有效治疗是现代医学难题。肺癌属于中医“肺积”“息贲”“劳嗽”等范畴,中医药在治疗肺癌方面已积累大量理论基础和实践经验。黄芪是补气药代表之一,黄芪治疗肺癌以“气虚邪滞”为主要证型,“扶正祛邪”为其基本治则。黄芪治疗肺癌的作用机制有抑制肿瘤细胞增殖及促进凋亡、抑制肿瘤侵袭和迁移、调控肿瘤微环境、抗肿瘤血管生成、调节自噬、诱导巨噬细胞极化、增强机体免疫和抑制免疫逃逸、逆转顺铂耐药等。黄芪治疗肺癌的活性成分有多糖类、皂苷类、黄酮类等。该研究从黄芪治疗肺癌的作用机制以及药物成分基础治疗肺癌两大方面进行综述,为黄芪资源及其活性成分的开发利用提供依据,并为抗肿瘤新药研发提供参考。

关键词：黄芪活性成分肺癌药理活性调节自噬调控肿瘤微环境逆转顺铂耐药

Atmospheric deposition fluxes and health risk assessment of potentially toxic elements in Caohai Lake(Guizhou Province,China)

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Journal of Mountain Science 2022年第4期19卷 1107-1118页

作者： LIN Shao-xia zhang zhuan-ling XIAO Zhi-qiang LIU Xiao-lan zhang Qing-hai State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550014China The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Science Guiyang 550014China Guizhou Academy of Testing and Analysis Guiyang 550014China Guizhou University Guiyang 550025China Guizhou Medical University Guiyang 550025China

In this study,the sources of potentially toxic elements(PTEs)from atmospheric deposition in the waters of Guizhou’s Caohai Lake were investigated in addition to the potential risks to human *** bags were used to enrich PTEs from atmospheric deposition,and eight monitoring sites that best represented geographic variation were established around Caohai *** bags were collected and examined at every 3 months to identify spatiotemporal patterns of dry and wet atmospheric deposition of *** was the most abundant metal identified from deposition in Caohai(72.07%–95.94%),followed by Pb and Cd,while Hg was the least abundant(0.008%–0.354%).The contributions of wet deposition of PTEs were greater than those of dry deposition,and deposition during the heating season from December to April was greater than that between April to *** was mainly derived from atmospheric dry deposition(65.38%–84.44%).Spatial distribution analysis indicated that atmospheric deposition was associated with the intensity of human activities and heating *** via hand-to-mouth contact accounted for over 99%of the total exposure risk although overall exposure was lower than threshold acceptable levels for carcinogenic and non-carcinogenic metals,indicating an overall lack of risk towards human ***,the health risk from atmospheric deposition of PTEs in Caohai Lake may be reduced by focusing on Zn,Pb,and Cd deposition in rainfall and minimizing the hazards associated with hand-to-mouth exposure to PTEs.

关键词： Caohai Lake Potentially toxic elements(PTEs) Atmospheric deposition Health risk assessment Heavy metals

术中肾动脉阻力指数用于预测心脏手术后急性肾损伤的效果

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临床麻醉学杂志 2024年第9期40卷 944-948页

作者：张转陈超张芯绮袁博殷佳佳张荦张建友富智王强郁言龙扬州大学附属医院麻醉科 225012 扬州大学附属医院心脏大血管中心 225012 新疆医科大学儿科学院

目的探讨心肺转流(CPB)心脏手术中肾动脉阻力指数(RI)用于预测术后急性肾损伤(AKI)的效果。方法选择择期行CPB心脏手术患者44例,男21例,女23例,年龄≥18岁,BMI 18.5~30.0 kg/m^(2),ASAⅠ—Ⅲ级。于麻醉诱导后20 min(T_(1))、CPB结束后30... 详细信息

目的探讨心肺转流(CPB)心脏手术中肾动脉阻力指数(RI)用于预测术后急性肾损伤(AKI)的效果。方法选择择期行CPB心脏手术患者44例,男21例,女23例,年龄≥18岁,BMI 18.5~30.0 kg/m^(2),ASAⅠ—Ⅲ级。于麻醉诱导后20 min(T_(1))、CPB结束后30 min(T_(2))经食管超声心动图(TEE)测量左肾动脉收缩期峰值流速(PSV)及舒张末期流速(EDV),计算出左肾动脉RI=(PSV-EDV)÷PSV。采用改善全球肾脏病预后组织(KDIGO)诊断标准判断AKI发生情况,根据术后是否发生AKI将患者分为两组:AKI组和非AKI组。采用多因素Logistic回归分析心脏手术后AKI的危险因素。结果共有16例(36%)发生AKI。与非AKI组比较,AKI组CPB时间及主动脉阻断时间明显延长(P0.720可作为心脏手术后AKI的预测指标。

关键词：肾动脉阻力指数急性肾损伤心脏手术预测经食管超声心动图

Synthesis of 2,3-Diaminoindoles via a Copper-Iodine Co-catalytic Strategy

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Chinese Journal of Chemistry 2023年第24期41卷 3567-3572页

作者： Wenhua Yu Yingying zhang Xiaoxiang zhang Xiaoting Gu Xirui Qing Wanxing Wei zhuan zhang Guanghua Li Taoyuan Liang School of Chemistry and Chemical Engineering Guangxi UniversityNanningGuangxi530004 China Guangxi Key Laboratory of Electrochemical Energy Materials NanningGuangxi530004 China Guangxi Colleges and Universities Key Laboratory of Applied Chemistry Technology and Resource Development NanningGuangxi530004 China Guangxi Key Laboratory of Petrochemical Resource Processing & Process Intensification Technology NanningGuangxi530004 China

A one-pot synthesis of vicinal diamines using indoles,azoles and phenothiazines in a tandem multi-component reaction is *** utilization of a copper-iodine co-catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good *** attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions,showcasing its potential as an alternative approach for synthesizing vicinal ***,the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry.

关键词： Indoles Tandem dual C—H amination Vicinal diamines Copper-iodine co-catalysis Multi-component reaction