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Small-molecule agents for cancer immunotherapy

Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang {1. Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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A Strategy for the Proliferation of Ulva prolifera,Main Causative Species of Green Tides,with Formation of Sporangia by Fragmentation

A Strategy for the Proliferation of Ulva prolifera,Main Caus...

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庆祝中国藻类学会成立30周年暨第十五次学术讨论会

作者： Shan Gao~a Xiaoyuan Chen~a Qianqian Yi~a Guangce Wang~(b 1. Guanghua Pan~a Apeng {1.~(b c) and Guang peng~b a college of Marine science and Engineering Tianjin University of science and Technology Tianjin 300457 China b Institute of Oceanology Chinese Academy of sciences (IOCAS) Qingdao 266071.China c Graduate School Chinese Academy of sciences beijing 1.0039 China

＜正＞Ulva prolifera,a common green seaweed,is one of the causative species of green tides that occurred frequently along the shores of Qingdao in 2008 and had detrimental effects on the preparation for the 2008 {1. Olympic Games sailing competition,since more than 30%of the area of the Games was *** view of the rapid accumulation of the vast biomass of floating *** in green tides,we investigated the formation of sporangia in disks of different diameters excised from U. prolifera,changes of the photosynthetic properties of cells during sporangia formation, and development of *** results suggested that the disks less than 1.00 mm in diameter were optimal for the formation of sporangia,but there was a small amount of spore release in these *** highest percentage of area of spore release occurred in 2.50 mm diameter *** contrast,sporangia were formed only at the cut edges of larger disks（3.00 mm,3.50 mm and 4.00 mm diameter）.Additionally,the majority of spores liberated from the disks appeared vigorous and developed successfully into new *** results implied that fragments of the appropriate size from the *** thalli broken by a variety of factors via producing spores gave rise to the rapid proliferation of the seaweed under field conditions,which may be one of the most important factors to the rapid accumulation of the vast biomass of *** in green tides occurred in Qingdao,2008.

关键词： Ulva prolifera Rapid proliferation Sporangia Spore development

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高浓度Cl^-对NO_2^-和NO_3^-分离测定的影响

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烟台师范学院学报（自然科学版） 2001年第3期17卷 187-190页

作者：吕海涛牟世芬莱阳农学院基础部山东莱阳265200 中国科学院生态环境研究中心北京100085

在 AS4A阴离子色谱柱上 ,研究了高浓度 Cl- 对 NO- 2 和 NO- 3 测定的影响 .提出了在高浓度基体中 ,同时存在自身洗脱效应和在线流动相变化两种洗脱机理 .当基体与待测离子色谱峰发生重叠时 ,基体在抑制器处所交换的 H+ 使部分弱酸型阴... 详细信息

在 AS4A阴离子色谱柱上 ,研究了高浓度 Cl- 对 NO- 2 和 NO- 3 测定的影响 .提出了在高浓度基体中 ,同时存在自身洗脱效应和在线流动相变化两种洗脱机理 .当基体与待测离子色谱峰发生重叠时 ,基体在抑制器处所交换的 H+ 使部分弱酸型阴离子 NO- 2 分子化 ,定量测定产生偏差 ,而对强酸型阴离子 NO- 3 的定量测定没有影响 .

关键词：阴离子交换色谱自身洗脱效应在线流动相变化亚硝酸根硝酸根氯离子分离测定

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Changes of Potassium Currents in Hippocampal Pyramidal Neurons of Scopolamine-induced Memory Deficits Rats

Changes of Potassium Currents in Hippocampal Pyramidal Neuro...

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2002全国青年药理学英文学术会议

作者： ZHONG Chong-Bo, WANG Xiao-liangDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical {1. & peking Union Medical college, beijing 1.0050, China

AIM: To explore the relationship between the memory deficits induced by cholinergic lesion and potassium channels. METHODS: Memory impairment induced by scopolamine (1.g/kg, sc.) was assessed in the Morris water maze. Whole cell configuration of the patch-clamp techniques was used to characterize outward potassium currents in acutely isolated hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. RESULTS: Scopolamine could induce deficits in spatial memory. Donepezil (2mg/kg, po.)

关键词： Scopolamine Donepezil Hippocampal pyramidal neurons Voltage-gated potassium current Patch clamp techniques

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物理法处理地层技术研究与应用进展

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石油钻探技术 2002年第3期30卷 44-46页

作者：陈玲李根生黄中伟中国石化集团公司科技开发部北京100100 石油大学(华东)石油工程学院山东东营257061

分析了地层堵塞机理 ,对现有的几种物理方法处理地层技术进行了介绍 ,在此基础上 ,重点阐述了水力处理地层这一新技术在油田现场应用的几种形式 ,其中包括高压旋转水射流处理近井地层、水力喷砂射孔 (割缝 )、高压水射流深穿透射孔、自... 详细信息

分析了地层堵塞机理 ,对现有的几种物理方法处理地层技术进行了介绍 ,在此基础上 ,重点阐述了水力处理地层这一新技术在油田现场应用的几种形式 ,其中包括高压旋转水射流处理近井地层、水力喷砂射孔 (割缝 )、高压水射流深穿透射孔、自激波动注水技术等 ,同时展望了物理法处理地层技术的研究和发展趋势。

关键词：物理法处理地层技术研究应用进展采油水力射流增产措施防止地层损害提高采收率射孔解堵

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西藏灌木林种群分布格局

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山地学报 2011年第1期29卷 123-128页

作者：张超黄清麟普布顿珠旦增中国林业科学研究院资源信息研究所国家林业局林业遥感与信息技术重点实验室西南林业大学资源学院西藏自治区林业调查规划研究院

以西藏地区370个灌木林标准地调查数据为基础,计算了包括负二项式K值、方差/均值比率t值、丛生指标、平均拥挤指数、聚块性指标、扩散指标、格林指数和Cassic指标,定量测度了各标准地内种群的分布格局类型及集聚强度,分析了西藏灌木种... 详细信息

以西藏地区370个灌木林标准地调查数据为基础,计算了包括负二项式K值、方差/均值比率t值、丛生指标、平均拥挤指数、聚块性指标、扩散指标、格林指数和Cassic指标,定量测度了各标准地内种群的分布格局类型及集聚强度,分析了西藏灌木种群分布格局随海拔和坡度的变化特征。研究结果表明,1.西藏优势灌木种群分布格局包括集群分布和随机分布两种,其中,随机分布占60%;2.随着海拔及坡度的增加,西藏灌木种群均呈现由集群分布向随机分布变化的趋势,且大部分地区的灌木种群呈随机分布。

关键词：西藏灌木林种群分布格局

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Methylation profile of bovine Oct4 gene coding region in relation to three germ layers

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Journal of Integrative Agriculture 2016年第3期15卷 618-628页

作者： ZHOU Xin-yu LIU liang-liang JIA Wen-chao PAN Chuan-ying college of {1. sciences Northwest A&F University School of Computer science & Engineering Jiangsu University of Science and Technology college of Animal {1. and Technology Northwest A&F UniversityShaanxi Key Laboratory of Molecular Biology for Agriculture

Previous studies have shown that octamer-binding transcription factor 4（Oct4） plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1.and embryonic development, in this work, five different tissues（heart, liver, lung, cerebrum and cerebellum） from three germ layers were chosen from low age（50–60 d） and advanced age（60–70 d） of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1.was significant different（P〈0.01. between any two of three germ layers in low age（〈60 d）, but kept steady of advanced age（P〉0.05）（〉60 d）, suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm（cerebrum and cerebellum）, there was no significant methylation difference of Oct4 gene exon 1.between low age and advanced age（P〉0.05）, but the result of endoderm（liver and lung） and mesoderm（heart） were on the contrary（P〈0.01., which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th Cp G-dinucleotide loci of Oct4 gene exon 1.were significantly different between each two of three germ layers（P〈0.05）, indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1.and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further stud{1. bovine embryonic development and cellular reprogramming.

关键词： bovine DNA methylation octamer-binding transcription factor 4(Oct4) exon germ layer

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Interleukin-1. Decreases Calcium Elevation in Excited Cultured Cortical Neurons

Interleukin-1β Decreases Calcium Elevation in Excited Cultu...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Juan-Juan Zhao,Chen Zhou,Shi-Qiang Wang,Zhen Chai~* State Key Laboratory of Biomembrane and Membrane Biotechnology,college of {1. sciences, peking University,beijing 1.0871

Interleukin-1.the first discovered proinflammatory cytokine,plays a key role in numerous central nervous system *** have previously shown that interleukin-1.downregulated Ca currents by decreasing L-type Ca channel *** present study,we examined the effect of interleukin-1.（1.ng/mL,24h） on the elevation of intracellular Ca concentration in cultured rat cortical neurons depolarized with high K solution（90 mM）.The calcium imaging results indicated interleukin-1.reduces calcium elevation by about 30%.This effect was blocked by PKC inhibitor chelerythrine chloride （1.M,24.5h）.Then we investigated p38- MAPK,a downstream target of PKC,with its specific inhibitor SB203580（1.M,24.5h）, which blocked the effect of interleukin-1.on intracellular *** results show interleukin- 1.decreases intracellular calcium elevation in excited cultured cortical neurons via PKC-p38- MAPK pathway.

关键词： Interleukin-1. Calcium Cortical neuron PKC p38-MAPK

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薄膜包装结合1.MCP对大同鲜黄花采后生理及品质影响

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食品与发酵工业 2024年第9期50卷 227-237页

作者：宋燕南王亚希白宇皓杨志国赵迎丽狄建兵王亮山西农业大学食品科学与工程学院山西太原030000

为确定适宜的鲜黄花贮藏条件,达到降低采后损失、延长货架期的目的,该研究采用不同厚度(30μm、40μm、50μm)聚乙烯(polyethylene,PE)薄膜包装结合1.甲基环丙烯(1.methylcyclopropene,1.MCP)对鲜黄花进行自发气调保鲜处理,在(0±0.5)... 详细信息

为确定适宜的鲜黄花贮藏条件,达到降低采后损失、延长货架期的目的,该研究采用不同厚度(30μm、40μm、50μm)聚乙烯(polyethylene,PE)薄膜包装结合1.甲基环丙烯(1.methylcyclopropene,1.MCP)对鲜黄花进行自发气调保鲜处理,在(0±0.5)℃贮藏条件下对鲜黄花相关品质指标变化以及微观结构特征等进行分析。结果表明,薄膜包装结合1.MCP处理是延长鲜黄花保鲜寿命的有效方式。在(0±0.5)℃贮藏条件下,50μm PE薄膜+1.MCP处理有效抑制了鲜黄花呼吸强度和乙烯释放速率的上升,减缓了硬度以及叶绿素含量的下降,维持了鲜黄花的色泽,降低失重率和腐烂率。贮藏至35 d时,50μm PE薄膜+1.MCP处理的呼吸强度、乙烯释放速率、硬度、叶绿素含量为61.25 mg CO_(2)/(kg·h)、55.29μL/(kg·h)、42.41.N、0.01.9 mg/g,失重率和腐烂率比CK处理分别降低了0.66%和80.33%。还抑制组织相对电导率的上升和丙二醛(malondialdehyde,MDA)含量的增高并有效提高了过氧化物酶(peroxidase,POD)、过氧化氢酶(catalase,CAT)活性,抑制了纤维素酶(cellulase,Cx)、β-葡萄糖苷酶(β-glucosidase,β-Glu)活性的上升。贮藏至35 d时,与CK处理相比,50μm PE薄膜+1.MCP处理的组织相对电导率和MDA含量降低了1..1.%、1..51.g/g,POD、CAT活性高达1..05 U/(min·g)、85.28 U/(min·g),Cx、β-Glu活性低至707.86μg/(h·g)、209.41.g/(h·g),较好的保持了鲜黄花的细胞形态。其中,50μm PE薄膜+1.MCP处理为鲜黄花最佳保鲜方案。

关键词：黄花贮藏气调包装 1.甲基环丙烯生理品质

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Different Expression of Caveolin-1.in Rats Liver Development Stages

Different Expression of Caveolin-1 in Rats Liver Development...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Fu-Dan Liu,Cui-ping Liu,Nan Wang,Wei Zou {1. of life science,Liaoning Normal University,Dalian 1.6029

Objective To investigate the relationship between the expression of the membrane protein Caveolin-1.in different parts of liver of different rats' development stages. Methods Immunohistochemical method and western blotting were used to detect the expressions of Caveolin-1.and different parts of liver in rats' different postnatal development *** Terminal line of lobules of liver and differentiation of bile duct area were unclear in 1.t postnatal *** were more clearer in 5th postnatal *** of liver and bile duct areas were maturation in 1.th *** positive expression of caveolin-1.was widely distributed,and stronger in blood vessel endothelial cell and nucleus of *** its expression was increased with the development of *** The results indicate that the expression of Caveolin-1.at the early development stages of *** the development of liver,the expression of caveolin-1.increased.

关键词： Caveolin-1 Different development stage Rats Liver

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