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| 1 | Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: challenges and updates显示文摘The efficacy of immunotherapy for advanced non-small cell lung cancer(NSCLC)remains unsatisfactory,as the majority of patients either do not experience an objective response or acquire secondary resistance.As a result,several methods to enhance the systemic efficacy of immunotherapy have been investigated,including a large area of active research by combining immunotherapy with radiation therapy(RT).Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit,we review the progress in this field thus far and explore further avenues for enhancing this combination.This review commences with a discussion of the only two existing randomized trials(and a pooled analysis)showing that the addition of RT to immunotherapy improves the abscopal response rate,progression-free survival,and overall survival in metastatic NSCLC patients.We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT,such as low programmed cell death protein ligand 1(PD-L1)status,tumor mutational burden(TMB),and patient’s immune function.Next,the implementation of RT to overcome immunotherapy resistance is discussed,including a mechanistic discussion and methods with which these mechanisms could be exploited.Lastly,the emerging role of low-dose RT is discussed,which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration.Taken together,given the current state of this rapidly expanding realm,these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients. | Shijie Shang Jie Liu Vivek Verma Meng Wu James Welsh Jinming Yu Dawei Chen | 2021 | Cancer Communications2021,41,11: | 10 |
| 2 | A structural and data-driven approach to engineering a plant cytochrome P450 enzyme显示文摘Functional manipulation of biosynthetic enzymes such as cytochrome P450 s(or P450 s) has attracted great interest in metabolic engineering of plant natural products.Cucurbitacins and mogrosides are plant triterpenoids that share the same backbone but display contrasting bioactivities.This structural and functional diversity of the two metabolites can be manipulated by engineering P450 s.However,the functional redesign of P450 s through directed evolution(DE) or structure-guided protein engineering is time consuming and challenging,often because of a lack of high-throughput screening methods and crystal structures of P450 s.In this study,we used an integrated approach combining computational protein design,evolutionary information,and experimental data-driven optimization to alter the substrate specificity of a multifunctional P450(CYP87 D20)from cucumber.After three rounds of iterative design and evaluation of 96 protein variants,CYP87 D20,which is involved in the cucurbitacin C biosynthetic pathway,was successfully transformed into a P450 mono-oxygenase that performs a single specific hydroxylation at C11 of cucurbitadienol.This integrated P450-engineering approach can be further applied to create a de novo pathway to produce mogrol,the precursor of the natural sweetener mogroside,or to alter the structural diversity of plant triterpenoids by functionally manipulating other P450 s. | Dawei Li Yongshuo Ma Yuan Zhou Junbo Gou Yang Zhong Lingling Zhao Lida Han Sergey Ovchinnikov Ling Ma Sanwen Huang Per Greisen Yi Shang | 2019 | Science China(Life Sciences)2019,62,7: | 5 |
| 3 | CO_2 absorption with ionic liquids at elevated temperatures显示文摘CO_2 capture with ionic liquids(ILs) has attracted many attentions, and most works focused on absorption ability at ambient temperatures, while seldom research was concerned at elevated temperatures.This not only limits the CO_2 absorption application at elevated temperature, but also the determination of the operation condition of the CO_2 desorption generally occurring at higher temperature. This work mainly reported CO_2 solubilities in ILs at elevated temperatures and related properties were also provided. 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide([CnMIm][Tf_2N]) ILs were selected as physical absorbents for CO_2 capture in this work due to their relative higher CO_2 absorption capacities and good thermal stabilities. The long-term stability tests showed that [CnMIm][Tf_2N] is thermally stable at 393.15 K for long time. CO_2 solubilities in [CnMIm][Tf_2N] were systematically determined at temperatures from 353.15 K to 393.15 K. It demonstrated that CO_2 solubility obviously increases with the increase of pressure while slightly decreases with increase of temperature. As the length of alkyl chain on the cation increases, CO_2 solubility in ILs increases. Additionally, the thermodynamic properties including the Gibbs free energy, enthalpy, and entropy of CO_2 were also calculated. | Lu Bai Dawei Shang Mengdie Li Zhongde Dai Liyuan Deng Xiangping Zhang | 2017 | Journal of Energy Chemistry2017,26,5: | 5 |
| 4 | Immune responses of a designed HIV-1 DNA vaccine on rhesus monkeys显示文摘An effective HIV-1 vaccine will be the ultimate solution for the prevention of HIV/AIDS, though HAART plays important roles in treating the disease. In this study, a large-scale recombinant DNA plasmid containing a designed HIV-1 multi-epitope- p24 chimeric gene was prepared and purified. Rhesus monkeys were then inoculated muscularly with the plasmid for four times in week 0, 4, 8 and 18. Whole blood was collected two weeks after the third and fourth inoculation, followed by serum and pe- ripheral blood mononuclear cell (PBMC) separation. The CTL activity and proliferation of PBMCs stimu- lated by macaque MHC-I-restricted HIV-1 CTL epi- tope peptide were analyzed by MTT and LDH release assay, respectively. Th1 cytokines in supernatant of cultured PBMC stimulated by HIV-1 CTL epitope peptide and anti-HIV-1 antibody in serum were as- sayed by ELISA. The results showed that increased CTL target-killing activity, higher secretion of Th1 cytokines (IFN-γ and IL-2) and promoted proliferative reaction of monkey PBMCs stimulated by HIV-1 CTL epitope peptide were detected in the immunization group inoculated by the recombinant DNA vaccine for three times, which were further enhanced by the fourth inoculation. At the same time, HIV-1 specific antibody in serum of immunized monkeys was higher than that in controls. We concluded that the designedHIV-1 DNA vaccine may induce HIV-1 specific cellular and humoral immunity on monkeys. | ZHANG Lishu JIN Ningyi SONG Yingjin SUN Yansong WANG Hong ZHAN Dawei MA Hewen SHANG Yupu JIN Hongtao HONG Baoqing LI Chang | 2006 | Chinese Science Bulletin2006,51,13: | 3 |
| 5 | Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite显示文摘As China’s first X-ray astronomical satellite, the Hard X-ray Modulation Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15, 2017, is a wide-band(1-250 ke V) slat-collimator-based X-ray astronomy satellite with the capability of all-sky monitoring in 0.2-3 Me V. It was designed to perform pointing, scanning and gamma-ray burst(GRB)observations and, based on the Direct Demodulation Method (DDM), the image of the scanned sky region can be reconstructed.Here we give an overview of the mission and its progresses, including payload, core sciences, ground calibration/facility, ground segment, data archive, software, in-orbit performance, calibration, background model, observations and some preliminary results. | Shuang-Nan Zhang TiPei Li FangJun Lu LiMing Song YuPeng X u CongZhan Liu Yong Chen XueLei Cao QingCui Bu Zhi Chang Gang Chen Li Chen TianXiang Chen YiBao Chen YuPeng Chen Wei Cui WeiWei Cui JingKang Deng YongWei Dong Yuan Yuan Du MinXue Fu GuanHua Gao He Gao Min Gao MingYu Ge YuDong Gu Ju Guan Can Gungor ChengCheng Guo DaWei Han Wei Hu Yue Huang Jia Huo ShuMei Jia LuHua Jiang WeiChun Jiang Jing Jin YongJie Jin Bing Li ChengKui Li Gang Li MaoShun Li Wei Li Xian Li XiaoBo Li XuFang Li YanGuo Li ZiJian Li ZhengWei Li XiaoHua Liang JinYuan Liao GuoQing Liu HongWei Liu ShaoZhen Liu XiaoJing Liu Yuan Liu YiNong Liu Bo Lu XueFeng Lu Tao Luo Xiang Ma Bin Meng Yi Nang JianYin Nie Ge Ou JinLu Qu Na Sai RenCheng Shang GuoHong Shen Liang Sun Ying Tan Lian Tao YouLi Tuo Chen Wang ChunQin Wang GuoFeng Wang HuanYu Wang Juan Wang WenShuai Wang YuSa Wang XiangYang Wen BaiYang Wu BoBing Wu Mei Wu GuangCheng Xiao ShaoLin Xiong LinLi Yan JiaWei Yang Sheng Yang YanJi Yang QiBin Yi Bin Yuan AiMei Zhang ChunLei Zhang ChengMo Zhang Fan Zhang HongMei Zhang Juan Zhang Qiang Zhang ShenYi Zhangs Shu Zhang Tong Zhang WanChang Zhang Wei Zhang WenZhao Zhang Yi Zhang YiFei Zhang YongJie Zhang Yue Zhang Zhao Zhang Zhi Zhang ZiLiang Zhang HaiSheng Zhao XiaoFan Zhao ShiJie Zheng JianFeng Zhou YuXuan Zhu Yue Zhu RenLin Zhuang | 2020 | Science China(Physics,Mechanics & Astronomy)2020,63,4: | 2 |
| 6 | Screening for in vitro metabolites of Abelmoschus manihot extract in intestinal bacteria by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry显示文摘 | Caifu Xue Shu Jiang Jianming Guo Dawei Qian Jin-ao Duan Erxin Shang | 2011 | Journal of Chromatography B2011,,32: | 1 |
| 7 | UPLC–QTOF/MS-based screening and identification of the constituents and their metabolites in rat plasma and urine after oral administration of Glechoma longituba extract显示文摘 | Shumao Ni Dawei Qian Jin-ao Duan Jianming Guo Er-xin Shang Yan Shu Caifu Xue | 2010 | Journal of Chromatography B2010,,28: | 1 |
| 8 | Enhanced chemoselectivity of a plant cytochrome P450 through protein engineering of surface and catalytic residues显示文摘Cytochrome P450s(P450s)are the most versatile catalysts utilized by plants to produce structurally and functionally diverse metabolites.Given the high degree of gene redundancy and challenge to functionally characterize plant P450s,protein engineering is used as a complementarystrategy to study the mechanisms of P450-mediated reactions,or to alter their functions.We previously proposed an approach of engineering plant P450s based on combining high accuracy homology models generated by Rosetta combined with data-driven design using evoluti onary information of these enzymes.With this strategy,we repurposed a multi-functional P450(CYP87D20)into a monooxygenase after red esigning its active site.Since most plant P450s are membrane-anchored proteins that are adapted to the micro-environments of plant cells,expressing them in heterologous hosts usually results in problems of expression or activity.Here,we applied compu-tational design to tackle these issues by simultaneous optimization of the protein surface and active site.After screening 17 variants,effective su bstitutions of surface residues were observed to improve both expression and activity of CYP87D20.In addition,the identified substitutions were additive and by com-bining them a highly eficient C11 hydroxylase of cucurbitadienol was created to participate in the mogrol biosynthesis.This study shows the importance of considering the interplay between surface and active site residues for P450 engineering.Our integrated strategy also opens an avenue to create more tai loring enzymes with desired functions for the metabolic engineering of high-valued compounds like mogrol,the precursor of natural sweetener mogrosides. | Xiaopeng Zhang Wei Luo Yinying Yao Xuming Luo Chao Han Yang Zhong Bo Zhang Dawei Li Lida Han Sanwen Huang Per Greisen Yi Shang | 2021 | aBIOTECH2021,2,3: | 1 |
| 9 | Screening for in vitro metabolites of Abelmoschus manihot extract in intestinal bacteria by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry显示文摘 | Caifu Xue Shu Jiang Jianming Guo Dawei Qian Jin-ao Duan Erxin Shang | 2011 | Journal of Chromatography B2011,,32: | 1 |
| 10 | Effects of Nd^(3+) and Sm^(3+) on the proliferation,differentiation and mineralization function of primary osteoblasts in vitro显示文摘A series of experimental methods including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) test,alkaline phosphatase (ALP) activity measurement,Oil Red O stain and measurement,mineralized function expression and quantitive real time RT-PCR (qRT-PCR) were employed to assess the effect of Nd3+ and Sm3+ on the proliferation,differentiation and mineralization function of primary osteoblasts (OBs) in vitro at cell and molecular levels.The experimental results suggest that concentration,culture time and ion species are pivotal factors for switching the biological effects of rare earth ions from toxicity to activity,from damage to protection,or from down-regulation to up-regulation. | ZHANG JinChao SHANG MiQin ZHANG DaWei LI YaPing SUN Jing CHEN Hang | 2010 | Chinese Science Bulletin2010,55,23: | 1 |
| 11 | The multi-omics basis of potato heterosis显示文摘Heterosis is a fundamental biological phenomenon characterized by the superior performance of hybrids over their parents.Although tremendous progress has been reported in seed crops,the molecular mechanisms underlying heterosis in clonally propagated crops are largely unknown.Potato(Solanum tuberosum L.)is the most important tuber crop and an ongoing revolution is transforming potato from a clonally propagated tetraploid crop into a seed-propagated diploidhybrid potato.In our previous study,we developed the first generation of highly homozygous inbred lines of potato and hybrids with strong heterosis.Here,we integrated transcriptome,metabolome,and DNA methylation data to explore the genetic and molecular basis of potato heterosis at three developmental stages.We found that the initial establishment of heterosis in diploid potato was mainly due to dominant complementation.Flower color,male fertility,and starch and sucrose metabolism showed obvious gene dominant complementation in hybrids,and hybrids devoted more energy to primary metabolism for rapid growth.In addition,we identified~2700 allele-specific expression genes at each stage,which likely function in potato heterosis and might be regulated by CHH allele-specific methylation level.Our multi-omics analysis provides insight into heterosis in potato and facilitates the exploitation of heterosis in potato breeding. | Dawei Li Xiaoyue Lu Yanhui Zhu Jun Pan Shaoqun Zhou Xinyan Zhang Guangtao Zhu Yi Shang Sanwen Huang Chunzhi Zhang | 2022 | Journal of Integrative Plant Biology2022,64,3: | 0 |