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Disitamab vedotin,a HER2-directed antibody-drug conjugate,in patients with HER2-overexpression and HER2-low advanced breast cancer:a phase I/Ib study

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Cancer Communications 2024年第7期44卷 833-851页

作者： Jiayu Wang Yunjiang Liu Qingyuan Zhang Wei Li Jifeng Feng XiaojiaWang jianmin fang Yiqun Han Binghe Xu Department of Medical Oncology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Breast Center The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebeiP.R.China Department of Breast Medicine Harbin Medical University Cancer HospitalHarbinHeilongjiangP.R.China Department of Medical Oncology The First Hospital of Jilin UniversityChangchunJilinP.R.China Department of Medical Oncology Jiangsu Cancer HospitalNanjingJiangsuP.R.China Department of Breast Medicine Zhejiang Cancer HospitalHangzhouZhejiangP.R.China School of Life Science and Technology Tongji UniversityShanghaiP.R.China

Background:Disitamab vedotin(DV;RC48-ADC)is an antibody-drug conjugate comprising a human epidermal growth factor receptor 2(HER2)-directed antibody,linker and monomethyl auristatin *** studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast,gastric,and ovarian cancers with different levels of HER2 *** this pooled analysis,we report the safety and efficacy of DV in patients with HER2-overexpression and HER2-low advanced breast cancer(ABC).Methods:In the phase I dose-escalation study(C001 CANCER),HER2-overexpression ABC patients received DV at doses of 0.5-2.5 mg/kg once every two weeks(Q2W)until unacceptable toxicity or progressive *** dose range,safety,and pharmacokinetics(PK)were *** phase Ib dose-range and expansion study(C003 CANCER)enrolled two cohorts:HER2-overexpression ABC patients receiving DV at doses of 1.5-2.5 mg/kg Q2W,with the recommended phase 2 dose(RP2D)determined,andHER2-lowABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2-low ***:Twenty-four patients with HER2-overexpression ABC in C001 CANCER,46 patients with HER2-overexpressionABCand 66 patients with HER2-low ABC in C003 CANCER were *** 2.0 mg/kg RP2D Q2W,the confirmed objective response rates were 42.9%(9/21;95%confidence interval[CI]:21.8%-66.0%)and 33.3%(22/66;95%CI:22.2%-46.0%),with median progression-free survival(PFS)of 5.7 months(95%CI:5.3-8.4 months)and 5.1 months(95%CI:4.1-6.6 months)for HER2-overexpression and HER2-low ABC,***(≥5%)grade 3 or higher treatment-emergent adverse events included neutrophil count decreased(17.6%),gamma-glutamyl transferase increased(13.2%),asthenia(11.0%),white blood cell count decreased(9.6%),peripheral neuropathy such as hypoesthesia(5.9%)and neurotoxicity(0.7%),and pain(5.9%).Conclusion:DV demonstrated promising efficacy in HER2-overexpression and HER2-low ABC,with a favorable safety profile at

关键词： antibody-drug conjugate breast cancer clinical trials disitamab vedotin HER2-low HER2-overexpression

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Chitosan Oligosaccharide Induces Plant Resistance Gene Expression in Pinus massoniana

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Journal of Agricultural Science and Technology(A) 2024年第2期14卷 107-117页

作者： Huayang Yin Wanlin Guo Qingtong Wang jianmin fang Hongjian Liu Guangping Dong Xiaojuan Li Institute of Forest Protection Anhui Provincial Academy of ForestryHefei 230031AnhuiChina Key Laboratory of National Forestry and Grassland Administration on Prevention and Control Technology of Pine Wilt Disease Hefei 230031AnhuiChina

Chitosan oligosaccharides(COSs)are the main degradation products from chitosan or chitin and have been reported to induce resistance to diseases in herbaceous plants like cucumber and ***,pine wilt disease(PWD)is a devastating disease of conifer tree ***,we hypothesized that COSs induce plant resistance gene(PRG)expression in the woody plant Masson pine,Pinus *** were inoculated into *** seedlings and the BGISEQ-500 platform was used to generate transcriptomes from COSs-treated *** and control seedlings.A total of 501 differentially expressed genes(DEGs)were identified by comparing the treatment and control groups.A total of 251(50.1%)DEGs were up-regulated in the treatment relative to the control seedlings and 250(49.9%)were *** of COSs induced the expression of 31 PRGs in *** seedlings and the relative expression levels of six of the PRGs were verified by *** is the first study to demonstrate that COS induces the expression of PRGs in a tree *** results provide important insights into the function of COSs and further the prospects of developing a COS-based immune inducer for controlling PWD.

关键词： COS PRG Pinus massoniana pine wilt disease

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Value of Ecosystem Services in Conventional and Organic Rice Paddies:A Case Study in Wannian,Jiangxi,China

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Chinese Journal of Population,Resources and Environment 2010年第2期8卷 47-54页

作者： Zhang Dan Min Qingwen He Lu Cheng Shengkui fang jianmin Institute of Geographic Sciences and Natural Resources Research CAS Beijing 100101 China Graduate School of Chinese Academy of Sciences Beijing 100049 China Agricultural Boureau of Wannian County Wannian Jiangxi 335512 China

In the current study,the ecosystem services(ES) of conventional and organic rice paddies in Wannian,Jiangxi Province,China are ***,the ES at the field level under organic and conventional paddies were *** economic value of ES in organic rice paddies was 30093.08 yuan RMB/ha per year and that of conventional rice paddies was 22 793.31 yuan RMB/ha per *** total indirect value of ES was 14 813.7 yuan RMB/ha per year in organic rice paddies and 12 424.56 yuan RMB/ha per year in conventional *** were significant differences between organic and conventional rice paddies for the economic ***,this economic information was used to extrapolate and to calculate the total and indirect value of ES from rice paddies in *** total and indirect economic values of ES from conventional rice paddies in Wannian were 6791 million and 3702 million yuan RMB per year respectively,and the total and indirect economic values of ES from organic rice paddies in Wannian were 1311 million and 646 million yuan RMB per *** half the area had being converted to organic farming in Wannian,the total and indirect economic values of ES from conventional rice paddies were 3397 million and 1851 million yuan RMB per year,and the total and indirect economic values of ES from organic rice paddies were 5794 million and 2852 million yuan RMB per ***,the total economic value of ES in rice paddies in Wannian was demonstrated through geographic information system techniques.

关键词： conventional rice paddy organic rice paddy economic value ecosystem services GIS

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安徽省薄壳山核桃产地有机磷和拟除虫菊酯农药残留及风险评估

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经济林研究 2024年第3期42卷 69-76页

作者：孙维敏季琳琳陈素传方建民潘婷钱孔屏陈自华安徽省林业科学研究院安徽合肥230088 定远县林业局安徽滁州233200

【目的】调查安徽省薄壳山核桃主产区土壤和果实中有机磷农药和拟除虫菊酯农药残留情况,评估土壤和果实中农药残留风险。【方法】采集安徽省薄壳山核桃主产区土壤和果实样品各13份,分析6种有机磷农药和4种拟除虫菊酯农药的残留,采用风... 详细信息

【目的】调查安徽省薄壳山核桃主产区土壤和果实中有机磷农药和拟除虫菊酯农药残留情况,评估土壤和果实中农药残留风险。【方法】采集安徽省薄壳山核桃主产区土壤和果实样品各13份,分析6种有机磷农药和4种拟除虫菊酯农药的残留,采用风险熵值评估土壤中农药残留的生态风险,采用健康风险评估模型计算果实中农药残留的人体摄入健康风险。【结果】所有土壤样品中均有农药检出,检出浓度范围为n.d.~195.1μg·kg^(-1)(n.d.表示未检出),氯氰菊酯(n.d.~195.1μg·kg^(-1))和甲氰菊酯(n.d.~90.61μg·kg^(-1))检出浓度最高,对硫磷在土壤中检出率为100%,单个土壤样品中最多检出6种农药;果实中仅有一个样品中未检出农药,其他样品中农药检出范围为n.d.~156.3μg·kg^(-1),甲氰菊酯(n.d.~156.3μg·kg^(-1))和氯氰菊酯(n.d.~29.42μg·kg^(-1))检出浓度最高,甲氰菊酯的检出率最高(69.23%),单个果实样品中最多检出4种农药,果实中农药残留浓度均未超过国家标准规定的限量值。土壤中所有农药残留的生态风险介于中等风险和高风险之间,RQ:0.16~2.48(RQ表示生态风险总和)。10种农药的人体健康风险值均小于1,成人摄入果实的健康风险高于儿童。【结论】安徽省薄壳山核桃主产区土壤和果实中存在一定程度的农药残留,土壤中的农药残留存在一定的生态风险,果实中的农药残留不会对人体产生健康风险,研究结果可为安徽省薄壳山核桃的食品安全监管提供参考。

关键词：薄壳山核桃土壤有机磷农药拟除虫菊酯农药风险评估

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Targeting TM4SF1 exhibits therapeutic potential via inhibition of cancer stem cells

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4018-4021页

作者： Guang Chen Xiaofei She Yanxin Yin Junxian Ma Yaqun Gao Hua Gao Huanlong Qin jianmin fang Cancer Center and Research Institute of Intestinal Diseases Shanghai Tenth People’s HospitalSchool of Life Sciences and Technology and School of MedicineTongji UniversityShanghaiPR China Shanghai Key Laboratory of Signaling and Disease Research School of Life Sciences and TechnologyTongji UniversityShanghaiPR China Biomedical Research Center Tongji University Suzhou Institute and Department of NeurologyTongji HospitalTongji UniversityShanghaiPR China

Dear Editor,Cancer stem cells(CSCs)are thought to be responsible for cancer initiation,growth,recurrence,metastasis,and drug resistance.1 Therefore,targeting CSCs is an effective therapeutic approach for cancer.2 However,there are few CSC-specific targets with functional extracellular domains for the development of antibody drugs.3 Our published paper demonstrated that transmembrane 4 L six family member 1(TM4SF1)coupled discoidin domain receptor tyrosine kinase 1(DDR1)under collagen I stimulation activated JAK2-STAT3 *** noncanonical DDR1 signaling sustained the manifestation of CSC traits by inducing SOX2 and NANOG expression and drove multiorgan metastases.

关键词： drugs STAT3 metastasis

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Neo-intline: integrated pipeline enables neoantigen design through the in-silico presentation of T-cell epitope

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5417-5428页

作者： Bingyu Li Ping Jing Genhui Zheng Chenyu Pi Lu Zhang Zuojing Yin Lijun Xu Jingxuan Qiu Hua Gu Tianyi Qiu jianmin fang Laboratory of Molecular Medicine Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji HospitalTongji University Suzhou InstituteTongji UniversityShanghaiChina School of Basic Medical Sciences Henan University of Science and TechnologyLuoyangHenanChina Institute of Clinical Science Zhongshan HospitalFudan UniversityShanghaiChina Oden Institute for Computational Engineering and Sciences(ICES) University of Texas at AustinAustinTXUSA School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Shanghai Institute of Infectious Disease and Biosecurity Fudan UniversityShanghai200032China

Neoantigen vaccines are one of the most effective immunotherapies for personalized tumour *** current immunogen design of neoantigen vaccines is usually based on whole-genome sequencing(WGS)and bioinformatics prediction that focuses on the prediction of binding affinity between peptide and MHC molecules,ignoring other peptide-presenting related *** may result in a gap between high prediction accuracy and relatively low clinical *** this study,we designed an integrated in-silico pipeline,Neo-intline,which started from the SNPs and indels of the tumour samples to simulate the presentation process of peptides in-vivo through an integrated calculation *** on the benchmark dataset of TESLA and clinically validated neoantigens illustrated that neo-intline could outperform current state-of-the-art tools on both sample level and melanoma ***,by taking the mouse melanoma model as an example,we verified the effectiveness of 20 neoantigens,including 10 MHC-I and 10 MHC-II *** in-vitro and in-vivo experiments showed that both peptides predicted by Neo-intline could recruit corresponding CD4^(+)T cells and CD8^(+)T cells to induce a T-cell-mediated cellular immune ***,although the therapeutic effect of neoantigen vaccines alone is not sufficient,combinations with other specific therapies,such as broad-spectrum immune-enhanced adjuvants of granulocyte-macrophage colony-stimulating factor(GM-CSF)and polyinosinic-polycytidylic acid(poly(I:C)),or immune checkpoint inhibitors,such as PD-1/PD-L1 antibodies,can illustrate significant anticancer effects on ***-intline can be used as a benchmark process for the design and screening of immunogenic targets for neoantigen vaccines.

关键词： melanoma prediction enable

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利用诱饵树防治薄壳山核桃星天牛效果探究

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安徽农学通报 2024年第20期30卷 71-75页

作者：汪青桐董广平方建民尹华阳郭婉琳刘洪剑安徽省林业科学研究院安徽合肥230031

星天牛是薄壳山核桃上危害较严重的蛀干类害虫,防治难度较大。为探索薄壳山核桃星天牛绿色高效防治手段,本研究以存活率、平均生长量、受害株率、受害株率减退率、日均单株诱虫量和雌雄比为调查指标开展了以苦楝和复叶槭为诱饵树的引诱... 详细信息

星天牛是薄壳山核桃上危害较严重的蛀干类害虫,防治难度较大。为探索薄壳山核桃星天牛绿色高效防治手段,本研究以存活率、平均生长量、受害株率、受害株率减退率、日均单株诱虫量和雌雄比为调查指标开展了以苦楝和复叶槭为诱饵树的引诱效果试验。结果显示,苦楝和复叶槭的存活率均较高,且苦楝的生长速度明显快于复叶槭;种植诱饵树后,薄壳山核桃的受害率逐年降低,控制在10%以内;与薄壳山核桃相比,两类诱饵树均对星天牛有明显的引诱效果(P0.05);不同诱饵树和不同年份引诱到的星天牛雌虫的平均腹卵量差异无统计学意义(P>0.05)。结合必要的营林和抚育措施,种植苦楝和复叶槭作为诱饵树并配合人工捕杀方式是一种高效绿色防治星天牛的方法。

关键词：薄壳山核桃星天牛苦楝复叶槭绿色防治

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香椿常见病虫害及综合防治措施

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安徽林业科技 2024年第4期50卷 40-43,51页

作者：尹华阳郭婉琳汪青桐董广平方建民李晓娟安徽省林业科学研究院安徽合肥230088 松材线虫病预防与控制技术国家林业和草原局重点实验室安徽合肥230088

香椿用途广泛,是一种重要的经济树种。本文介绍了香椿常见的病虫害,并提出了包括耕作防治、物理防治、化学防治、生物防治在内的综合防治措施,旨在为其病虫害的防治提供参考,促进香椿产业的可持续发展。

关键词：香椿病虫害综合防治

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Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating HSP70 in SHSY-5Y cells

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Translational Neurodegeneration 2017年第1期6卷 119-128页

作者： Hui Sun Ming Jiang Xing Fu Qiong Cai Jingxing Zhang Yanxin Yin Jia Guo Lihua Yu Yun Jiang Yigang Liu Liang Feng Zhiyu Nie jianmin fang Lingjing Jin Department of Neurology Shanghai Tongji HospitalTongji University School of Medicine389 Xincun RoadShanghai 200065People’s Republic of China School of Life Science and Technology Tongji University1239 Siping RoadShanghai 200092People’s Republic of China Biomedical Research Center Tongji University Suzhou InstituteBuilding 2198 Jinfeng RoadWuzhong DistrictSuzhouJiangsu 215101China

Background:Mesencephalic astrocyte-derived neurotrophic factor(MANF)is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress(ER stress).HSP70 family,a chaperon like heat shock protein family,was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y ***,the ER stress relative transcriptome,in MANF signaling cascades is still *** involvement of HSP70,a 70kd member of HSP70 family,need further to be ***:The cell apoptosis was assayed by MTT,TUNEL staining and western blot of cleaved *** differentially expressed genes in SHSY-5Y cells under different conditions(control,6-OHDA,6-OHDA+MANF)were investigated by *** of HSP70 was further confirmed by real-time *** knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling ***:MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y *** ER stress relative genes(HSP70,GRP78,xbp-1,ATF-4,ATF-6,MAPK)were found enriched in 6-OHDA+MANF treatment ***70 was the most significantly up-regulated gene under 6-OHDA+MANF treatment in SHSY-5Y *** knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y ***:MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes,including HSP70 family *** HSP70 expression level plays a key role in MANFmediated survival pathway.

关键词： HSP70 MANF Parkinson’s disease SHSY-5Y cell

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试论广东远洋渔业的发展

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南方经济 2001年第2期30卷 42-44页

作者：方健民广东远洋渔业总公司总经理广东广州510222

本文分析了广东远洋渔业的发展状况和存在的主要问题 ,阐述了发展广东远洋渔业的重要性 ,并就管理决策、经营机制、队伍建设、产业结构调整、政府支持等五方面提出了发展思路。

关键词：广东远洋渔业发展体制改革

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