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Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

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Cancer Communications 2024年第9期44卷 1005-1017页

作者： Shun Lu Xiaorong Dong Hong Jian Jianhua Chen Gongyan Chen Yuping Sun Yinghua Ji ZipingWang Jianhua Shi Junguo Lu Shaoshui Chen Dongqing Lv Guojun Zhang Chunling Liu Juan Li Xinmin Yu Zhong Lin Zhuang Yu ZhehaiWang Jiuwei Cui Xingxiang Xu Jian Fang Jifeng Feng Zhi Xu RuiMa Jie hu Nong Yang Xiangdong Zhou XiaohongWu Chengping hu Zhihong Zhang You Lu Yanping hu Liyan jiang Qiming wang Renhua Guo Jianying Zhou Baolan Li Chunhong hu Wancheng Tong Helong Zhang LinMa Yuan Chen Zhijun Jie Yu Yao Longzhen Zhang JieWeng Weidong Li Jianping Xiong Xianwei Ye Jianchun Duan Haihua Yang Meili Sun HongyingWei JiaweiWei Zheyu Zhang QiongWu department of Medical Oncology Shanghai Chest Hospital Shanghai JiaoTong UniversityShanghaiP.R.China Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhanHubeiP.R.China department of Medical Oncology-Chest Hunan Cancer Hospital&The Affiliated Cancer Hospital of Central South University Xiangya School of MedicineChangshaHunanP.R.China Thoracic OncologyMedicine HarbinMedical University Cancer HospitalHarbinHeilongjiangP.R.China department of Oncology Jinan Central HospitalJinanShandongP.R.China department of Oncology First Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenanP.R.China department of Chest Medicine Beijing Cancer HospitalBeijingP.R.China department of Internal Medicine Linyi Cancer HospitalLinyiShandongP.R.China department of Respiratory Medicine Nantong Tumor HospitalNantongJiangsuP.R.China department of Oncology Binzhou Medical University HospitalBinzhouShandongP.R.China Breath Internal Medicine Taizhou Hospital of Zhejiang ProvinceLinhaiZhejiangP.R.China department of Respiration The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China department of Lung Internal Medicine Affiliated Tumor Hospital of Xinjiang Medical UniversityUrumqiXinjiangP.R.China department of Thoracic Oncology Sichuan Cancer HospitalChengduSichuanP.R.China Thoracic Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiangP.R.China department of Thoracic Oncology The Fifth Subsidiary Sun Yat-sen University HospitalZhuhaiGuangdongP.R.China department of Oncology The Affiliated Hospital of QingdaoUniversityQingdaoShandongP.R.China department of Oncology Shandong Cancer HospitalJinanShandongP.R.China department of Oncology The First BethuneHospital of Jilin UniversityChangchunJilinP.R.China department of Respiration Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhouJiangsuP.R.China department of Internal

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of *** study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS ***:Eligible patients were enrolled and randomly assigned in a 1.1.ratio to orally receive either aumolertinib or gefitinib in a double-blinded *** with asymptomatic,stable CNS metastases were ***-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 1. months,then every *** responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,1.6 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31.95%confidence interval[CI],0.1.-0.56;P1.and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.1.-0.57;P1..The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,*** risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at *** new safety findings were ***:The

关键词： aumolertinib brain metastasis non-small cell lung cancer third-generation EGFR-TKI

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Penpulimab,an anti-PD-1.antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3056-3062页

作者： Xiaozhong Chen Wei Wang Qingfeng Zou Xiaodong Zhu Qin Lin Yi {1. Yan Sun Liangfang Shen Lin Wang Guorong Zou Xiaoyan Lin Shaojun Lin Minying Li Ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng Lin Shuang huang Tingting Xu Wenting Li Mengying Xia Yu Xia Zhongmin Wang Baiyong Li Jingao Li Chaosu hu department of Radiation Oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and Urology department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical Research Center for Gastrointestinal Cancer in hunan Province ChangshaChina department of Medical Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina department of Radiation Oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina department of Radiation Oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina department of Medical Oncology Cancer Hospital of Shantou University Medical CollegeShantouChina department of Radiation Oncology Peking University Cancer Hospital&InstituteBeijingChina department of Oncology Xiangya Hospital Central South UniversityChangshaChina department of Medical Oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina department of Oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina department of Medical Oncology Fujian Medical University Union HospitalFuzhouChina department of Radiation Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina department of Radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy Center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina department of Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1.PD-1.IgG1.antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in{1. enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1.,as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 1.5 were efficacy *** the data cutoff date(September 28,2022),1.patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=1..1.months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

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Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1.promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1

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Protein & Cell 2024年第6期15卷 419-440页

作者： Wei Ma Lu Zhang Weilong Chen Zhaoxia Chang Juchuanli Tu Yuanyuan Qin Yuwen Yao Mengxue Dong Jiajun Ding Siqin Li Fengkai Li Qiaodan Deng Yifei Yang Tingting Feng Fanrong Zhang Xiying Shao Xueyan He Lixing Zhang Guohong hu Quentin Liu Yi-Zhou jiang Shu Zhu Zhi Xiao Dan Su Tong Liu Suling Liu Fudan university Shanghai Cancer Center & Institutes of Biomedical {1.s State Key Laboratory of Genetic EngineeringCancer InstitutesDepartment of OncologyKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Intelligent Pathology Institute and department of Pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230071China department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Institute of Immunology CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China department of Breast Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Shanghai Institute of Nutrition and Health University of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Sun Yat-sen university Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China department of Breast Surgery Xiangya HospitalChangsha 410008China department of Breast Surgery Tumor Hospital of Harbin Medic

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant ***,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in ***,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant ***,albeit at low biomass,secreted the toxic protein BFT-1.to promote breast cancer cell stemness and *** studies showed that BFT-1.directly bound to NOD1.and stabilized NOD1.***1.was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1.HEY1.signaling pathway to increase ***1.inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

关键词： NOD1 breast chemotherapy

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Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits

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Plant Communications 2024年第6期5卷 173-192页

作者： Xue-Mei Lu Xiao-Fen Yu Guo-Qiang Li Ming-Hao Qu huan Wang Chuang Liu Yu-Ping Man Xiao-Han jiang Mu-Zi Li Jian Wang Qi-Qi Chen Rui Lei Cheng-Cheng Zhao Yun-Qiu Zhou Zheng-Wang jiang Zuo-Zhou Li Shang Zheng Chang Dong Bai-Lin Wang Yan-Xiang Sun hui-Qin Zhang Jie-Wei Li Quan-hui Mo Ying Zhang Xin Lou Hai-Xu Peng Ya-Ting Yi He-Xin Wang Xiu-Jun Zhang Yi-Bo Wang Dan Wang Li Li Qiong Zhang Wen-Xia Wang Yongbo Liu Lei Gao Jin-hu Wu Yan-Chang Wang CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical GardenChinese Academy of SciencesWuhanHubeiChina Key Laboratory of Western china’s Environmental Systems(Ministry of Education) College of Earth and Environmental SciencesLanzhou UniversityLanzhouGansuChina College of Life sciences University of Chinese Academy of SciencesBeijingChina Wuhan Frasergen Bioinformatics Co. LtdWuhanHubeiChina Institute of Soil and Fertilizer Anhui Academy of Agricultural SciencesHefeiChina College of Agricultural sciences Xichang UniversityXichangSichuanChina department of Horticulture Heilongjiang Academy of Agricultural SciencesHarbinHeilongjiangChina College of Life sciences Langfang Normal UniversityLangfangHebeiChina Institute of Horticulture Zhejiang Academy of Agricultural SciencesHangzhouZhejiangChina Guangxi Institute of Botany Chinese Academy of SciencesGuilinGuangxiChina Xi’an Botanical Garden of Shaanxi Province Institute of Botany of Shaanxi ProvinceXi’anShaanxiChina Institute of Modern Agricultural Research Dalian UniversityDalianLiaoningChina Bioinformatics Center College of Plant Science and TechnologyBeijing University of AgricultureBeijingChina College of Agriculture Eastern Liaoning UniversityDandongLiaoningChina Dalian Institute of Chemical Physics Chinese Academy of SciencesDalianLiaoningChina State Environmental Protection Key Laboratory of Regional Eco-process and Function Assessment Chinese Research Academy of Environmental SciencesBeijingChina hubei Hongshan Laboratory WuhanHubeiChina The New Zealand Institute for Plant and Food Research Limited AucklandNew Zealand

Actinidia arguta,the most widely distributed Actinidia species and the second cultivated species in the genus,can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit,rapid softening,and excellent cold *** evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still ***,we generated a chromosome-scale genome assembly of an autotetraploid male *** *** genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 1.6 *** and clustering of 1.1.geographically representative accessions showed that they could be divided into two geographic groups,Southern and Northern,which first diverged 1..9 million years *** underwent two prominent expansions and one demographic bottleneck from the midPleistocene climate transition to the late *** genomics studies using paleoclimate data enabled us to discern the evolution of the species’adaptation to different historical *** genes(AaCEL1.AaPME1.and AaDOF1.related to flesh softening were identified by multi-omics analysis,and their ability to accelerate flesh softening was verified through transient expression assays.A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome(Chr3)or autosomal chromosomes showed biased expression during stamen or carpel *** chromosome-level assembly of the autotetraploid *** genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of ***.

关键词： kiwiberry dioecism adaptive evolution paleoclimate GEA rapid softening

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一氧化氮(NO)熏蒸提高哈密瓜果实采后贮藏的耐冷性

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现代食品科技 2018年第4期34卷 114-120,178页

作者：王鲁阳吴斌敬媛媛胡江伟张平新疆农业大学食品科学与药学学院新疆乌鲁木齐830052 新疆农业科学院农产品贮藏加工研究所新疆乌鲁木齐830091

为了探究一氧化氮(nitric oxide,NO)熏蒸对哈密瓜采后耐冷性的影响。以"西州密25号"为试材,用60μL/L NO气体熏蒸3 h,分别在(1.0.5℃)、(3±0.5℃)、(5±0.5℃)贮藏。统计冷害发病率和冷害指数,测定过氧化氢酶(catalase,CAT)、过氧化物... 详细信息

为了探究一氧化氮(nitric oxide,NO)熏蒸对哈密瓜采后耐冷性的影响。以"西州密25号"为试材,用60μL/L NO气体熏蒸3 h,分别在(1.0.5℃)、(3±0.5℃)、(5±0.5℃)贮藏。统计冷害发病率和冷害指数,测定过氧化氢酶(catalase,CAT)、过氧化物酶(peroxidase,POD)、超氧化物歧化酶(superoxide dismutase,SOD)活性、超氧阴离子(superoxide anion,O_2~ˉ·)产生速率、过氧化氢(hydrogen peroxide,H_2O_2)含量的变化。结果表明:NO处理能提高SOD、POD活性,抑制O_2~ˉ·产生速率。1.条件下,果实冷害发病率最高,NO处理能减轻冷害的发生;3℃条件下,对照果实后期出现冷害,但NO处理果实无冷害发生;5℃条件下,果实后期出现冷害和病害症状,NO处理能减轻果实的冷害和病害。说明NO能够提高抗氧化相关酶的活性,抑制活性氧(reactive oxygen species,ROS)的积累,提高果实的耐冷性;3℃条件下,NO熏蒸既能有效维持果实的贮藏品质又能抑制果实冷害的发生。

关键词：哈密瓜一氧化氮活性氧冷害

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A chromosome-level genome assembly of anesthetic drug–producing Anisodus acutangulus provides insights into its evolution and the biosynthesis of tropane alkaloids

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Plant Communications 2024年第1期5卷 231-244页

作者： Wei Zhou Can Wang Xiaolong Hao Fei Chen Qikai huang Tingyao Liu {1. Xu Shuai Guo Baosheng Liao Zhixiang Liu Yue Feng Yao Wang Pan Liao Jiayu Xue Min Shi Itay Maoz Guoyin Kai zhejiang Provincial International S&T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and TransformationSchool of Pharmaceutical SciencesJinhua AcademyZhejiang Chinese Medical UniversityHangzhouZhejiang 310053China Sanya Nanfan Research Institute from Hainan university Hainan Yazhou Bay Seed LaboratorySanya 572025China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China department of Biology Hong Kong Baptist UniversityKowloon TongHong KongChina College of Horticulture Academy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China department of Postharvest {1. Agricultural Research OrganizationVolcani CenterP.O.Box 15159HaMaccabim Road 68Rishon LeZion 7505101Israel

Tropane alkaloids(TAs),which are anticholinergic agents,are an essential class of natural compounds,and there is a growing demand for TAs with anesthetic,analgesic,and spasmolytic *** acutan-gulus(Solanaceae)is a TA-producing plant that was used as an anesthetic in ancient *** this study,we assembled a high-quality,chromosome-scale genome of *** with a contig N50 of 7.4 Mb.A recent whole-genome duplication occurred in *** after its divergence from other Solanaceae species,which resulted in the duplication of ADC1.and UGT genes involved in TA *** catalytic activities of H6H enzymes were determined for three Solanaceae *** the basis of evolution and co-expressed genes,AaWRKY1. was selected for further analyses,which revealed that its encoded tran-scription factor promotes TA biosynthesis by activating AaH6H1.*** provide useful insights into genome evolution related to TA biosynthesis and have potential implications for genetic manipulation of TA-producing plants.

关键词： Anisodus acutangulus tropane alkaloid biosynthesis hyoscyamine 6 b-hydroxylase AaWRKY1.

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Persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis

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Journal of zhejiang {1.-science B(Biomedicine & Biotechnology) 2009年第4期10卷 280-284页

作者： Xun TAN Ye-wen jiang Yi-jun {1.ANG Song-{1.a {1. department of Veterinary Medicine Zhejiang University Hangzhou 310029 China

This study was designed to investigate persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis. Milk samples were collected at a 1.d interval after the last administration from 34 individual cows that had received intramammary infusions of gentamicin. The doses and treatment times evaluated in this study represented those that have been applied by veterinarians in practice. The tetrazolium chloride assay was used to determine whether there were significant residues of the antibiotic in the samples. Persistence of detectable drug residues in milk from 33 cows (28 cows, ≤6 infusions at ≤0.7 g gentamicin; and 5 cows, 2 infusions at 0.8 g gentamicin) did not exceed 5 d; but 1.cow (5 infusions at 0.8 g gentamicin) had detectable residues in its milk for 9 d. Our results suggest that a 5-d milk withdrawal period might be insufficient to secure the clearance of the contamination of gentamicin, because treatment times and dosages contribute to the antibiotic clearance. A larger scale of samples are needed for further investigations.

关键词： Gentamicin Mastitis Intramammary infusion Residue

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Generated SecPen_NY-ESO-1.ubiquitin-pulsed dendritic cell cancer vaccine elicits stronger and specific T cell immune responses

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Acta Pharmaceutica Sinica B 2021年第2期11卷 476-487页

作者： Yunkai Yang Xiaohan Guo Bo hu Peng He Xiaowu {1. Zuohuan Wang huaxing Zhu Lina hu Minghua Yu Meiqing Feng Shanghai Engineering Research Center of ImmunoTherapeutics School of PharmacyFudan UniversityShanghai 201203China Shanghai Novoprotein Biotechnology Co. Ltd.Shanghai 201203China Medical School of Yichun {1. Yichun 336000China Clinical Research Center 2nd Affiliated HospitalMedical College of Zhejiang UniversityHangzhou 310009China department of Oncology Shanghai Pudong HospitalFudan University Pudong Medicine CenterShanghai 201399China

Dendritic cell-based cancer vaccines(DC vaccines)have been proved efficient and safe in immunotherapy of various cancers,including melanoma,ovarian and prostate ***,the clinical responses were not always *** we proposed a novel strategy to prepare DC *** the present study,a fusion protein SNU containing a secretin-penetratin(SecPen)peptide,NY-ESO-1.and ubiquitin was designed and *** establish the DC vaccine(DC-SNU),the mouse bone marrowderived DCs(BMDCs)were isolated,pulsed with SNU and maturated with cytokine *** peripheral blood mononuclear cells(PBMCs)from C57 BL/6 mice inoculated intraperitoneally with DCSNU were separated and cocultured with MC38/MC38NY-ESO-1.tumor cells or DC *** results show that SNU was successfully *** strategy made NY-ESO-1.entering cytoplasm of BMDCs more efficiently and degraded mainly by *** we expected,mature BMDCs expressed higher CD40,CD80 and CD86 than immature ***,the PBMCs released more IFN-γand TNF-αwhen stimulated with DC-SNU in vitro ***’s more,the PBMCs induced stronger and specific cytotoxicity towards MC38NY-ESO-1.tumor *** the above,it demonstrated that DC-SNU loaded with SecPen and ubiquitin-fused NY-ESO-1.could elicit stronger and specific T cell immune *** strategy can be used as a platform for DC vaccine preparation and applied to various cancers treatment.

关键词： Dendritic cells Cancer vaccine NY-ESO-1 SecPen Ubiquitin

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Optical Spectra and Gain Properties of Ho^(3+)/Pr^(3+)Co-doped LiYF_4 Crystal

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Journal of Materials science & {1. 2014年第9期30卷 910-916页

作者： jiangtao Peng Haiping Xia Peiyuan Wang Haoyang {1. Lei Tang Yuepin Zhang Haoc{1.an jiang Baojiu Chen Key Laboratory of Photo-electronic Materials Ningbo University Ningbo Institute of Materials technology & Engineering Chinese Academy of Sciences department of Physics Dalian Maritime University

The LiYF4 single crystals singly doped Ho3＋ and co-doped Ho3＋, Pr3＋ ions were grown by a modified Bridgman method. The Judd-Ofelt strength parameters （Ω2, Ω4, Ω6） of No3＋ were calculated according to the absorption spectra and the Judd-Ofelt theory, by which the radiative transition probabilities （A）, fluorescence branching ratios （β） and radiative lifetime （τ rad） were obtained. The radiative lifetimes of 5/6 and 5/7 levels in Ho3＋（1.mol%）：LiYF4 are 1..89 and 20.1. ms, respectively, while 9.77 and 1..50 ms in Ho3＋/pr3＋ doped crystals. Hence, the τ rad of 5/7 level decreases significantly by introduction of Pr3＋ into Ho3＋：LiYF4 crystal which is beneficial to the emission of 2.9 μm. The maximum emission cross section of Ho3＋：LiYF4 crystal located at 2.05 μm calculated by McCumber theory is 0.51.×1.-20 cm2 which is compared with other crystals. The maximum emission cross section at 2948 nm in Ho3＋/pr3＋ co-doped LiYF4 crystal obtained by Fuchtbauer- Ladenburg theory is 0.68 × 1.-20 cm2, and is larger than the value of 0.53 × 1.-20 cm2 in Ho3＋ singly doped LiYF4 crystal. Based on the absorption and emission cross section spectra, the gain cross section spectra were calculated. In the Ho3- ions singly doped LiYF4 crystal, the gain cross sections for 2.05 μm infrared emission becomes positive once the population inversion level reaches 30%. It means that the pump threshold for obtaining 2.05 μm laser is probably lower which is an advantage for Ho3＋-doped LiYF4 2.05 μm infrared lasers. The calculated gain cross section for 2.9 μm mid-infrared emission does not become positive until the population inversion level reaches 40% in Ho3＋/pr3＋：LiYF4 crystal, but 50% in Ho3＋ singly doped LiYF4 crystal, indicating that a low pumping threshold is achieved for the H03＋：5/6 → 5/7 laser operation with the introduction of Pr3＋ ions. It was also demonstrated that Pr3＋ ion can deplete rapidly the lower laser Ho3＋：5/7 level and has influence on the Ho3＋：5/6 level. The Ho3＋/pr3＋：LiYF4 crys

关键词： LiYF4 crystal 2.9 μm Ho3/pr3+ Optical spectra Gain cross section

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Torin2 overcomes sorafenib resistance via suppressing mTORC2-AKT-BAD pathway in hepatocellular carcinoma cells

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 547-554页

作者： Yi-Ting hu Zhe-Yue Shu Jing-hua jiang Qin-Fen Xie Shu-Sen Zheng department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalZhejiang Shuren UniversityShulan International Medical CollegeHangzhou 310022China Division of Hepatobiliary Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Hepatobiliary and Pancreatic Surgery Jinhua Municipal Central HospitalJinhua 321000China

Background:Sorafenib is an oral multi-kinase inhibitor that was approved by the US Food and Drug Administration for the treatment of patients with advanced hepatocellular carcinoma(HCC).However,resistance to sorafenib is an urgent problem to be resolved to improve the therapeutic efficacy of *** the activation of AKT/mTOR played a pivotal role in sorafenib resistance,we evaluated the effect of a dual mTOR complex 1.2 inhibitor Torin2 on overcoming the sorafenib resistance in HCC ***:The sorafenib-resistant huh7 and Hep3B cell lines were established from their parental cell *** synergistic effect of sorafenib and Torin2 on these cells was measured by cell viability assay and quantified using the Chou-Talalay *** induced by the combination of sorafenib and Torin2 and the alteration in the specific signaling pathways of interest were detected by Western ***:Sorafenib treatment inversely inhibited AKT in parental but activated AKT in sorafenib-resistant huh7 and Hep3B HCC cells,which underscores the significance of AKT ***2 and sorafenib synergistically suppressed the viability of sorafenib-resistant cells via apoptosis ***2 successfully suppressed the sorafenib-activated mTORC2-AKT axis,leading to the dephosphorylation of Ser1.6 in BAD protein,and increased the expression of total BAD,which contributed to the apoptosis in sorafenibresistant HCC ***:In this study,Torin2 and sorafenib showed synergistic cytostatic capacity in sorafenibresistant HCC cells,via the suppression of mTORC2-AKT-BAD *** results suggest a novel strategy of drug combination for overcoming sorafenib resistance in HCC.

关键词： Torin2 Sorafenib resistance Hepatocellular carcinoma mTORC2-AKT-BAD pathway

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