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Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies

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Genes & Diseases 2019年第3期6卷 232-246页

作者： Hongxing shen eddy shih-Hsin yang Marty Conry John Fiveash Carlo Contreras James A.Bonner Lewis Zhichang shi Department of Radiation Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA O’Neal Comprehensive Cancer Center The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Medical Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of surgical Oncology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Department of Microbiology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA Program in Immunology The University of Alabama at Birmingham School of MedicineBirminghamAL35233USA

Immune checkpoint blockade therapies(ICBs)are a prominent breakthrough in cancer immunotherapy in recent years(named the 2013“Breakthrough of the Year”by the science magazine).Thus far,FDA-approved ICBs primarily target immune checkpoints CTLA-4,PD-1,and PD-L1.Notwithstanding their impressive long-term therapeutic benefits,their efficacy is limited to a small subset of cancer patients.In addition,ICBs induce inadvertent immune-related adverse events(irAEs)and can be costly for long-term use.To overcome these limitations,two strategies are actively being pursued:identification of predictive biomarkers for clinical response to ICBs and multi-pronged combination therapies.Biomarkers will allow clinicians to practice a precision medicine approach in ICBs(biomarker-based patient selection)such as treating triple-negative breast cancer patients that exhibit PD-L1 staining of tumor-infiltrating immune cells in1%of the tumor area with nanoparticle albumin-bound(nab)epaclitaxel plus anti-PD-L1 and treating patients of MsI-H or MMR deficient unresectable or metastatic solid tumors with pembrolizumab(anti-PD-1).Importantly,the insights gained from these biomarker studies can guide rational combinatorial strategies such as CDK4/6 inhibitor/fractionated radiotherapy/HDACi in conjunction with ICBs to maximize therapeutic benefits.Further,with the rapid technological advents(e.g.,ATCT-seq),we predict more reliable biomarkers will be identified,which in turn will inspire more promising combination therapies.

关键词： IFN-γ Immune checkpoint Microbiota Microsatellite instability Neoantigen PD-L1 Radiotherapy

Recent surface marine sediments of Cocos Island in Costa Rica

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International Journal of sediment Research 2014年第1期29卷 59-72页

作者： Jeffrey A.sIBAJA-CORDERO Jesús s.TRONCOsO eddy GóMEZ-RAMíREZ Escuela de Biología&Centro de Investigación en Ciencias del Mary Limnología (CIMAR) Universidad de Costa Rica Dr.grad.by Departamento de Ecología y Biología Animal Facultad de Ciencias del MarUniversidad de Vigo Departamento de Ecología y Biología Animal Facultad de Ciencias del MarUniversidad de VigoCampus Lagoas Marcosende Centro de Investigación en Ciencias del Mary Limnología(CIMAR) Universidad de Costa RicaSan Pedro 115012 060 San JoséCosta Rica Dr.(Cand).Departamento de Biología Facultad de Ciencias del Mary AmbientalesUniversidad de Cádiz

subtidal sediments of Isla del Coco(Cocos Island),Costa Rica were described in their grain size,sorting,organic matter,and carbonates from 27 dredge samples(3-75 m),collected in April 2010.The organic matter range between 1.37-3.31%and carbonates presented a mean of 74±17%.The sorting was moderately or poorly.The grain size ranged between 0.1-1.1mm.The pattern is that sediment change from inner to mouth of bays.Carbonates and gravel fractions increased offshore and organic matter have high values inner the bays.Input of vegetal debris and mud was from the rivers of this island covered with rain and cloud forest.

关键词： sand bottom sorting Organic matter Carbonates Isla del Coco

Early-age feed restriction affects viability and gene expression of satellite cells isolated from the gastrocnemius muscle of broiler chicks

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Journal of Animal science and Biotechnology 2013年第1期4卷 49-57页

作者： Yue Li Xiaojing yang Yingdong Ni eddy Decuypere Johan Buyse Nadia Everaert Roland Grossmann Ruqian Zhao Key Laboratory of Animal Physiology & Biochemistry Nanjing Agricultural University Laboratory of Livestock Physiology Department of Functional Genomics & Bioregulation Institute of Animal Genetics Mariensee

Background： Muscle growth depends on the fusion of proliferate satellite cells to existing myofibers. We reported previously that 0-14 day intermittent feeding led to persistent retardation in myofiber hypertrophy. However, how satellite cells respond to such nutritional insult has not been adequately elucidated. Results： One-day-old broiler chicks were allocated to control （Con, ad libitum feeding）, intermittent feeding （IF, feed provided on alternate days） and re-feeding （RF, 2 days ad libitum feeding after 12 days of intermittent feeding） groups. Chickens were killed on Day 15 and satellite cells were isolated. When cultured, satellite cells from the IF group demonstrated significant retardation in proliferation and differentiation potential, while RF partly restored the proliferation rate and differentiation potential of the satellite cells. significant up-regulation of insulin like growth factor I receptor （IGF-IR）（P〈O.05） and thyroid hormone receptor o （TRo）（P〈O.05）, and down-regulation of growth hormone receptor （GHR）（P〈O.01） and IGF-I （P〈O.01） mRNA expression was observed in freshly isolated IF satellite cells when compared with Con cells. In RF cells, the mRNA expression of IGF-I was higher （P〈O.05） and of TRa was lower （P〈O.01） than in IF cells, suggesting that RF restored the mRNA expression of TRa and IGF-I, but not of GHR and IGF-IR. The Bax/Bcl-2 ratio tended to increase in the IF group, which was reversed in the RF group （P〈O.05）, indicating that RF reduced the pro-apoptotic influence of iF. Moreover, no significant effect of T3 was detected on cell survival in IF cells compared with Con （P〈O.O01） or RF （P〈O.05） cells. Conclusions： These data suggest that early-age feed restriction inhibits the proliferation and differentiation of satellite cells, induces changes in mRNA expression of the GH/IGF-I and thyroid hormone receptors in satellite cells, as well as blunted sensitivity of satellite cells to T3, and that RF partially reverses these effects. Thus, a moderate nutritional strategy for feed r

关键词： Feed restriction satellite cells Proliferation Gene expression Chicken

Electrochemical reactivity of In-Pb solid solution as a negative electrode for rechargeable Mg-ion batteries

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Journal of Energy Chemistry 2021年第4期30卷 124-128页

作者： Lucie Blondeau suzy surble eddy Foy Hicham Khodja Magali Gauthier UniversitéParis-saclay CEACNRSNIMBELEEL91191Gif-sur-YvetteFrance UniversitéParis-saclay CEACNRSNIMBELAPA-IRAMAT91191Gif-sur-YvetteFrance

A composite In-Pb:carbon was successfully synthetized by a two-step mechanochemical synthesis in order to obtain an adequate particles size and structure to investigate the electrochemical reactivity of the In-Pb solid solution towards Mg.A potential synergetic coupling of electroactive elements In and Pb was examined using electrochemical and ex situ X-ray diffraction analyses.The potential profile of the solid solution indicates the formation of Mg_(2)Pb and Mg In.However,the diffraction study suggests a peculiar electrochemically-driven amorphization of Mg In during the magnesiation,in strong contrast to Mg In crystallization in In-based and In Bi-based electrodes reported in the literature.Combining In and Pb favors the amorphization of Mg In and a high first magnesiation capacity of about 550 m Ah g^(-1),but is thereafter detrimental to the material’s reversibility.These results emphasize the possible influence of electrochemically-driven amorphization and crystallization processes on electrochemical performance of battery materials.

关键词： Magnesium battery Negative electrode Alloy Amorphization

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强氢氟酸介质中结晶的沸石的独特性质

复旦学报（自然科学版） 2022年第6期61卷 757-767页

作者：赵浩暖 DIB eddy 石点点傅广赢丁瑞琴王宋霞杨洋郎巧霖杨晓波方千荣 VALTCHEV Valentin 中国科学院青岛生物能源与过程研究所分子筛材料研究组山东青岛266101 法国国家研究中心催化与光谱实验室法国卡昂14050 吉林大学无机合成与制备化学实验室吉林长春130012

将分子筛水热结晶合成的化学体系由传统的碱性和中性介质拓展至强酸性范围,为所形成的分子筛带来一系列独特的性质,包括显著的完美晶格结构、憎水性表面、增强的热稳定性以及稳定可靠的微孔扩散性能等。本文结合前期发表的数据和新研究... 详细信息

将分子筛水热结晶合成的化学体系由传统的碱性和中性介质拓展至强酸性范围,为所形成的分子筛带来一系列独特的性质,包括显著的完美晶格结构、憎水性表面、增强的热稳定性以及稳定可靠的微孔扩散性能等。本文结合前期发表的数据和新研究获得的结果详细演示,酸性体系结晶是普适性的分子筛合成方法,所获得的分子筛产品可具有前所未有的完美晶格结构。

关键词：酸性介质中合成沸石完美晶格分子筛骨架局域均匀结构分子筛固体核磁共振

DAC阶梯信号频谱的新简化分析及其基波的非滤波测量

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计量学报 2011年第5期32卷 392-399页

作者：陆祖良黄璐杨雁王磊 eddy so 中国计量科学研究院北京100013 National Research Council Ottawa Canada

提出一个新的简化方法分析了DAC生成的阶梯波频谱，包括幅值和相角。以正弦数字信号的离散值为输入，DAC将生成一个阶梯信号，其中的基波分量与输人的正弦信号之间幅值差为-1．6449／n^2，相位差为-π／n，n为一个周期内离散点的个数；... 详细信息

提出一个新的简化方法分析了DAC生成的阶梯波频谱，包括幅值和相角。以正弦数字信号的离散值为输入，DAC将生成一个阶梯信号，其中的基波分量与输人的正弦信号之间幅值差为-1．6449／n^2，相位差为-π／n，n为一个周期内离散点的个数；而阶梯信号中的谐波位于（tn±1）阶次上，其幅值是基波分量的1／（tn±1）。设计了一个不需滤波器而仅对阶梯波中基波分量作测量的实验，实验结果证实了上述关于基波的分析结论。讨论了各种可能的应用。

关键词：计量学数模转换频谱分析误差分析滤波器

平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的一致性关系

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中华肿瘤杂志 2012年第7期34卷 497-500页

作者：杨吉龙 David Cogdell James eddy Jonathan Trent Nathan Price ZHANG Wei 天津医科大学附属肿瘤医院骨与软组织肿瘤科 300060

目的探讨平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的关系。方法采用安捷伦基凶表达芯片的方法检测31例平滑肌肉瘤和42例胃肠间质瘤中PRUNE2mRNA的表达水平，分析其表达与平滑肌肉瘤患者的预后关系；采用实时荧光定量聚合酶链... 详细信息

目的探讨平滑肌肉瘤中PRUNE2mRNA的表达及其与非编码RNAPCA3的关系。方法采用安捷伦基凶表达芯片的方法检测31例平滑肌肉瘤和42例胃肠间质瘤中PRUNE2mRNA的表达水平，分析其表达与平滑肌肉瘤患者的预后关系；采用实时荧光定量聚合酶链反应的方法分析13例平滑肌肉瘤中PCA3mRNA和PRUNE2mRNA的表达水平并分析二者间的关系。7例前列腺癌组织作为PCA3mRNA表达的阳性对照。结果在31例平滑肌肉瘤中，PRUNE2mRNA的平均表达水平为368．43±29．67，高于37例胃肠间质瘤（82．56±7．45）和7例前列腺癌（4．76±0．98，均P〈0．05）。PRUNE2mRNA高表达的平滑肌肉瘤患者的生存期与低表达者比较，差异无统计学意义（X2=0．96，P=0．326）。PRUNE2mRNA高表达的胃肠间质瘤患者的生存期与低表达者比较，差异无统计学意义（X2=3．10，P=0．078）。平滑肌肉瘤中PcA3mRNA平均表达水平为26．38±3．04，低于前列腺癌（3272．00±240．87，P=0．004）。在平滑肌肉瘤中，PCA3mRNA与PRUNE2mRNA的表达呈正相关（r=0．901，P〈0．001）。结论PRUNE2的表达与平滑肌肉瘤患者的生存期有关，PCA3的表达与PRUNE2mRNA的表达呈正相关。

关键词：平滑肌肉瘤 RNA,未翻译 PRUNE2 PCA3 预后

香港周边海域野生鱼体内DDTs和PCBs的含量分布和食用风险评估

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环境科学 2018年第4期39卷 1861-1871页

作者：苏杨鲍恋君曾永平中国科学院广州地球化学研究所有机地球化学国家重点实验室广州510640 中国科学院大学北京100049 暨南大学环境学院广州510632

为研究香港周边海域鱼体内持久性有机污染物的污染水平、分布特征及其对当地居民的健康风险评估,采集了香港周边海域中31种野生鱼,分析鱼体中两类典型持久性有机污染物,如滴滴涕(DDTs)和多氯联苯(PCBs).结果表明,香港周边海域野生鱼类D... 详细信息

为研究香港周边海域鱼体内持久性有机污染物的污染水平、分布特征及其对当地居民的健康风险评估,采集了香港周边海域中31种野生鱼,分析鱼体中两类典型持久性有机污染物,如滴滴涕(DDTs)和多氯联苯(PCBs).结果表明,香港周边海域野生鱼类DDTs和PCBs的含量范围分别为0.44~17 ng·g^(-1)和0.028~6.3 ng·g^(-1),与国内外其他地方相比处于中低水平.在空间分布上,大屿山西部的鱼体内DDTs含量最低,而吐露港鱼体中PCBs含量最低.鱼类的生活环境及食性影响其在鱼体内DDTs与PCBs的富集程度.来源分析显示野生鱼体内DDTs来源主要为历史残留,迁徙的鱼类可能受沿海岸河口DDTs污染影响.此外,健康风险评估结果表明,香港青少年和成年人长期食用香港周边海域的鱼类可能会存在潜在的终生致癌风险.因此,香港当地居民应尽量减少对其周边海岸野生鱼类的摄入.

关键词：香港野生鱼类滴滴涕多氯联苯风险评估

在轻至中度哮喘病人利用超极化气体~3He-MRI预测支气管扩张剂后气流受限的可逆性

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国际医学放射学杂志 2019年第6期 740-741页

作者： R.L.eddy s.svenningsen C.Licskai D.G.McCormack G.Parraga 薛艺 Robarts Research Institute Department of Medical Biophysics and Division of Respirology Department of Medicine Western University

摘要约有10%的哮喘病人会进展为不可逆的气流受限,但是很难识别有这种转变风险的病人。目的探究轻至中度哮喘病人6年超极化气体~3He-MRI通气缺损的变化情况,

关键词：支气管扩张剂气流受限中度哮喘可逆性 MRI