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| 1 | Key technologies for the construction of the Xiluodu high arch dam on the Jinsha River in the development of hydropower in western China显示文摘Hydropower development in China is concentrated in the country's western regions.Among all the rivers in China,the lower course of the Jinsha River contains the richest hydro-energy resource,and therefore,4 mammoth hydropower plants are under construction on this particular section of the river at Wudongde,Baihetan,Xiluodu,and Xiangjiaba.The water-blocking structures of the hydropower facilities at Wudongde,Baihetan and Xiluodu are all arch dams of around 300 m high.In view of changes in the geological conditions at the foundation of the Xiluodu dam on the riverbed after excavation started,the designs of expanding foundation surface excavation and dovetailing the dam body and foundation rock on both upstream and downstream sides were introduced,allowing the arch dam and foundation to fit each other and improving the stress conditions of the dam body and foundation.By dividing the dam body into various concrete sections,the dynamic properties of concrete were adequately adjusted to the distribution of stress in the dam body.In addition,the use of the most optimal concrete material and mixture ratio allowed thermodynamics of concrete to satisfy the requirements of the strength,durability,temperature control and crack prevention of the concrete.Moreover,rigorous temperature control measures were introduced to prevent harmful cracking,thus enhancing the integrity of the arch dam.Furthermore,sophisticated construction machinery,scientific testing methods,and sound construction techniques were employed to ensure the uniformity and reliability of concrete placement.The 'Digital Dam' for the Xiluodu project,which is based on the theory of total life cycle,has supplied strong support for construction process control and decision-making. | Lu Youmei Fan Qixiang Zhou Shaowu Li Bingfeng Li Wenwei | 2012 | Engineering Sciences2012，10，2： | 3 |
| 2 | A chip-level electrothermal-coupled design model for high-power light- emitting diodes 显示文摘 | Shanjin Huang Hao Wu Bingfeng Fan | 2010 | Journal of Applied Physics2010，107，054509： | 1 |
| 3 | Thermal study of high-power nitride-based flip-chip light-emitting diodes 显示文摘 | Bingfeng Fan Hao Wu Yu Zhao | 2008 | IEEE Transactions on Electron Devices2008，55，12： | 1 |
| 4 | Study of phosphor thermal isolated packaging technolosies for hish-power white Light Emitting Diodes显示文摘 | Bingfeng Fan Heo Wu Yu Zhao | 2007 | IEEE Photonics Technology Letters2007，19，15： | 1 |
| 5 | Enhancement of CAR-T cell activity against cholangiocarcinoma by simultaneous knockdown of six inhibitory membrane proteins显示文摘Background:Existing treatments for cholangiocarcinoma have poor efficacy.However,chimeric antigen receptor-T(CAR-T)cells are emerging as a potential therapeutic strategy.Solid tumors possess multiple adverse factors in an immunosuppressive microenvironment that impair CAR-T cell infiltration and function.This study aimed to improve the function of CAR-T cells through knock down immune checkpoints and immunosuppressive molecular receptors.Methods:We evaluated the expression of epidermal growth factor receptor(EGFR)and B7 homolog 3 protein(B7H3)antigens in cholangiocarcinoma tissues using immunohistochemistry and screened specific immune checkpoints in the cholangiocarcinoma microenvironment via flow cytometry.Subsequently,we engineered CAR-T cells targeting EGFR and B7H3 antigens.We simultaneously knocked down immune checkpoints and immunosuppressive molecular receptors in CAR-T cells by constructing two clusters of small hairpin RNAs and evaluated the engineered CAR-T cells for antitumor activity both in vitro,using tumor cell lines and cholangiocarcinoma organoid models,and in vivo,using humanized mouse models.Results:We observed high expression of EGFR and B7H3 antigens in cholangiocarcinoma tissues.EGFR-CAR-T and B7H3-CAR-T cells demonstrated specific anti-tumor activity.We found an abundance of programmed cell death protein 1(PD-1),T cell immunoglobulin and mucin domain-containing protein 3(Tim-3),and T cell immunoglobulin and ITIM domain(Tigit)on infiltrated CD8^(+)T cells in the cholangiocarcinoma microenvironment.We then decreased the expression of these 3 proteins on the surface of CAR-T cells,named PTG-scFV-CAR-T cells.Furthermore,we knocked-down the expression of transforming growth factor beta receptor(TGFβR),interleukin-10 receptor(IL-10R),and interleukin-6 receptor(IL-6R)of PTG-scFV-CAR-T cells.Those cells,named PTG-T16R-scFVCAR-T cells,potently killed tumor cells in vitro and promoted apoptosis of tumor cells in a cholangiocarcinoma organoidmodel.Finally,the PTG-T16R-scFv-CART cells showed greater inhibitory effect on tumor growth in vivo,and were superior in prolonging the survival of mice.Conclusions:Our results revealed that PTG-T16R-scFV-CAR-T cells with knockdown of sextuplet inhibitory molecules exhibited strong immunity against cholangiocarcinoma and long-term efficacy both in vitro and in vivo.This strategy provides an effective and personalized immune cell therapy against cholangiocarcinoma. | Yidan Qiao Jie Chen Xuemei Wang Shumei Yan Jizhou Tan Baijin Xia Yongjian Chen Keming Lin Fan Zou Bingfeng Liu Xin He Yiwen Zhang Xu Zhang Hui Zhang Xiangyuan Wu Lijuan Lu | 2023 | Cancer Communications2023，43，7： | 0 |
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