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24篇 您的检索式:作者名="Tianshu Xu"
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1Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study显示文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen 2021Cancer Communications2021,41,11:29
2Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology显示文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.Xuchao Zhang Zhiyong Liang Shengyue Wang Shun Lu Yong Song Ying Cheng Jianming Ying Weiping Liu Yingyong Hou Yangqiu Li Yi Liu Jun Hou Xiufeng Liu Jianyong Shao Yanhong Tai Zheng Wang Li Fu Hui Li Xiaojun Zhou Hua Bai Mengzhao Wang You Lu Jinji Yang Wenzhao Zhong Qing Zhou Xuening Yang Jie Wang Cheng Huang Xiaoqing Liu Xiaoyan Zhou Shirong Zhang Hongxia Tian Yu Chen Ruibao Ren Ning Liao Chunyan Wu Zhongzheng Zhu Hongming Pan Yanhong Gu Liwei Wang Yunpeng Liu Suzhan Zhang Tianshu Liu Gong Chen Zhimin Shao Binghe Xu Qingyuan Zhang Ruihua Xu Lin Shen Yilong Wu 2019Cancer Biology & Medicine2019,16,1:14
3Strong ozone production at a rural site in the North China Plain: Mixed effects of urban plumes and biogenic emissions显示文摘Regional ozone(O_3) pollution has drawn increasing attention in China over the recent decade, but the contributions from urban pollution and biogenic emissions have not been clearly elucidated. To better understand the formation of the regional O_3 problem in the North China Plain(NCP), intensive field measurements of O_3 and related parameters were conducted at a rural site downwind of Ji'nan, the capital city of Shandong province, in the summer of 2013. Markedly severe O_3 pollution was recorded, with the O_3 mixing ratios exceeding the Chinese national ambient air quality standard on 28 days(a frequency of 78%) and with a maximum hourly value of 198 ppbv. Extensive regional transport of wellprocessed urban plumes to the site was identified. An observation-constrained chemical box model was deployed to evaluate in situ photochemical O_3 production on two episodes.The results show that the in situ formation accounted for approximately 46% of the observed O_3 accumulation, while the remainder(~54%) was contributed by regional transport of the O_3-laden urban plumes. The in situ ozone production was in a mixed controlled regime that reducing either NOx or VOCs would lead to a reduction of ozone formation. Biogenic VOCs played an important role in the local ozone formation. This study demonstrates the significant mixed effects of both anthropogenic pollution from urban zones and biogenic emission in rural areas on the regional O_3 pollution in the NCP region,and may have general applicability in facilitating the understanding of the formation of secondary pollution over China.Ruihan Zong Xue Yang Liang Wen Caihong Xu Yanhong Zhu Tianshu Chen Lan Yao Liwei Wang Junmei Zhang Lingxiao Yang Xinfeng Wang Min Shao Tong Zhu Likun Xue Wenxing Wang 2018Journal of Environmental Sciences2018,30,9:8
4Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer:a subpopulation analysis of the JACOB trial显示文摘Background:The JACOB trial(NCT01774786)was a double-blinded,placebo-controlled,randomized,multicenter,international,phase III trial evaluating the efficacy and safety of adding pertuzumab to trastuzumab and chemo-therapy in first-line treatment of human epidermal growth factor receptor 2(HER2)-positive metastatic gastric cancer/gastroesophageal junction cancer(GEJC).The aim of this analysis was to investigate efficacy and safety outcomes in the Chinese subpopulation from the JACOB trial.Methods:This post hoc subpopulation analysis included all patients recruited in China's Mainland(n=163;20.9%)between June 2013 and January 2016.The patients were randomly assigned in a 1:1 ratio to receive pertuzumab plus trastuzumab and chemotherapy(pertuzumab group;n=82)or placebo plus trastuzumab and chemotherapy(con-trol group;n=81).Intravenous pertuzumab(840 mg)and trastuzumab(8 mg/kg loading and 6 mg/kg maintenance doses)were given every 3 weeks until disease progression or unacceptable toxicity.Chemotherapy was given as per standard regimens/doses of capecitabine or 5-fluorouracil plus cisplatin.The primary endpoint was overall survival(OS);secondary efficacy endpoints included progression-free survival(PFS),and overall objective response rate(ORR).Results:The median OS was 18.7 months in the pertuzumab group and 16.1 months in the control group(hazard ratio[HR]0.75;95%confidence interval[CI]0.49 to 1.14).The median PFS was 10.5 and 8.6 months in the pertuzumab and control groups,respectively(HR 0.85;95%CI 0.60 to 1.21),and the median ORRs were 68.9%and 55.7%,respectively.The treatment effect in this Chinese subpopulation showed consistency with that in the global ITT population with numerically lower HR for OS and PFS compared with the control group.The safety profiles of the pertuzumab and control groups in this Chinese subpopulation analysis were generally comparable.The most common grade 3-5adverse events were neutropenia,anemia,and leukopenia.However,due to the nature of being a post hoc subgroup analysis,the results presented here are descriptive only and need to be interpreted with caution.Conclusions:OS and PFS were numerically improved by adding pertuzumab to trastuzumab and chemotherapy as first-line treatment in Chinese HER2-positive gastric cancer/GEJC patients,and this regimen demonstrated an acceptable safety profile.Tianshu Liu Yanru Qin Jin Li Ruihua Xu Jianming Xu Shujun Yang Shukui Qin Yuxian Bai Changping Wu Yixiang Mao Haiyan Wu Yilin Ge Lin Shen 2019Cancer Communications2019,39,1:6
5Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach显示文摘Dear Editor,Hepatoid adenocarcinoma(HAC)is a rare pathological subtype of extrahepatic tumor,featured by hepatoid differentiation andα-fetoprotein(AFP)-production[1,2].Hepatoid adenocarcinoma of the stomach(HAS),accounting for 0.3%to 1.0%of all gastric cancers(GCs),has attracted increasing attention due to its high degree of malignancy[3].Compared with classic GC,HAS showed a higher rate of vascular invasion,lymph node metastasis,and liver metastasis,with only 9.0%survival rate at 5 years[4].Currently,there is no effective treatment for HAS,and little is known about its pathogenesis.Herein,we investigated the molecular features of HAS and identified potential therapeutic targets for HAS.Mengxuan Zhu Erbao Chen Shan Yu Chen Xu Yiyi Yu Xin Cao Wei Li Pengfei Zhang Yan Wang Baofeng Lian Shuirong Zhang Yueting Qu Lujia Huang Weiwei Shi Yuehong Cui Li Qian Tianshu Liu 2022Cancer Communications2022,42,10:3
6Outcome of Patients with Colorectal Liver Metastasis: Analysis of 1,613 Consecutive Cases显示文摘Zhu Dexiang Ren Li Wei Ye Wu Haifu Zhong Yunshi Ye Qinghai Zhai Shenyong Xu Bo Liang Li Pan Xiangou Li Haohao Ye Lechi Liu Tianshu Fan Jia Qin Xinyu Xu Jianmin 2012Annals of Surgical Oncology2012,,9:3
7Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling显示文摘Osteoarthritis(OA),in which M1 macrophage polarization in the synovium exacerbates disease progression,is a major cause of cartilage degeneration and functional disabilities.Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported.Here,we report that SHP099,as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2(SHP2),attenuated osteoarthritis progression by inhibiting M1 macrophage polarization.We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice.Compared to wild-type(WT)mice,myeloid lineage conditional Shp2 knockout(c KO)mice showed decreased M1 macrophage polarization and attenuated severity of synovitis,an elevated expression of cartilage phenotype protein collagen II(COL2),and a decreased expression of cartilage degradation markers collagen X(COL10)and matrix metalloproteinase3(MMP3)in OA cartilage.Further mechanistic analysis showed that SHP099 inhibited lipopolysaccharide(LPS)-induced Toll-like receptor(TLR)signaling mediated by nuclear factor kappa B(NF-κB)and PI3K—AKT signaling.Moreover,intra-articular injection of SHP099 also significantly attenuated OA progression,including joint synovitis and cartilage damage.These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.Ziying Sun Qianqian Liu Zhongyang Lv Jiawei Li Xingquan Xu Heng Sun Maochun Wang Kuoyang Sun Tianshu Shi Zizheng Liu Guihua Tan Wenqiang Yan Rui Wu Yannick Xiaofan Yang Shiro Ikegawa Qing Jiang Yang Sun Dongquan Shi 2022Acta Pharmaceutica Sinica B2022,12,7:2
8Toripalimab in advanced biliary tract cancer显示文摘Gemcitabine combined with platinum/fluorouracil drugs is the standard firstline treatment for advanced biliary tract cancers(BTCs).We explored the safety and efficacy of toripalimab plus gemcitabine and S-1(GS)as the first-line treatment for advanced BTCs.At a one-sided significance level of 0.025,a total of 50 patients could provide 80%power to show the efficacy at targeted progression-free survival(PFS)rate at 6 months of 70%versus 40%for the combined treatment.This single-arm,phase II study enrolled 50 patients with advanced BTCs who previously received no systemic treatment.The regimen was as follows:toripalimab(240 mg,i.v.,d1),gemcitabine(1,000 mg/m2,i.v.,d1 and d8),and S-1(40–60 mg bid p.o.,d1–14,Q21d).The primary endpoint was progression-free survival.The secondary endpoints included overall survival(OS),objective response rate(ORR),duration of response(DOR),and safety.The associations between response with PDL1 expression,tumor mutational burden(TMB),and genetic variations were explored.Patients were enrolled from January 2019 to August 2020,with a median follow-up time of 24.0 months(IQR:4.3–31.0 months).Wei Li Yueqi Wang Yiyi Yu Qian Li Yan Wang Chenlu Zhang Xiaojing Xu Xi Guo Yu Dong Yuehong Cui Qing Hao Lujia Huang Houbao Liu Tianshu Liu 2022The Innovation2022,3,4:1
9Synthesis of 15P-Conjugated PPy-modified Gold Nanoparticles and Their Application to Photothermal Therapy of Ovarian Cancer显示文摘WANG Li WANG Liping XU Tianshu GUO Changrun LIU Chuanzhi ZHANG Hao LI Jing LIANG Zhiqing 2014Chemical Research in Chinese Universities2014,30,6:1
10Experimental investigation on a novel liquid cooling device for a prismatic Li-ion battery module operating at high ambient temperature显示文摘A novel liquid cooling device for a prismatic LiFePO4 battery module was proposed and manufactured in this study in order to improve the thermal management performance of the battery module operating at high ambient temperature.A testing system was set up to experimentally measure temperatures in different locations of the battery module consisting of seven 60 Ah cells.Tests were conducted to investigate both the passive and active cooling performances of the proposed system at different ambient temperatures and discharging rates in regarding with the maximum temperature and difference between the maximum and minimum temperatures.The results clearly show that both the ambient temperature and discharging rate play important role on the maximum temperature of the battery module.Passive cooling cannot meet the cooling requirement of the battery module particularly at high ambient temperature of 40℃.In contrary,liquid cooling can successfully reduce the maximum temperature to the required temperature range of the battery module even in high temperature environment and relatively high discharging rate.The effect of water inlet temperature on the cooling performance was also experimentally studied.With the inlet temperature of 28℃,the active cooling device can reduce the maximum temperature of the battery module to about 34.8℃after discharging at 0.6℃for 1000 s.The temperature difference of only 3.8℃was also achieved which suggests a great uniform distribution of temperature in the battery module.XU JiaWei ZHOU TianShu XU XinHai 2020Science China(Technological Sciences)2020,63,10:1
11First-zone distance re- laying algorithm of parallel transmission lines for cross-country earthed faults显示文摘XU Zhenyu LI Wei BI Tianshu 2012IEEE Trans on Power Delivery2012,27,4:1
12Clinical significance of assessing Her2/neu expression in gastric cancer with dual tumor tissue paraffin blocks显示文摘Xiaowen Ge Haixing Wang Haiying Zeng Xuejuan Jin Akesu Sujie Chen Xu Yalan Liu Jie Huang Yuan Ji Yunshan Tan Tianshu Liu Yingyong Hou Jing Qin Yihong Sun Xinyu Qin 2015Human Pathology2015,,6:1
13Flexible and flame-retarding phosphorylated MXene/polypropylene composites for efficient electromagnetic interference shielding显示文摘Flame-retardant composites with high electromagnetic interference(EMI)shielding performance are desirable for electronic device packaging.Despite great potential of MXene for high EMI,it still remains a great challenge to develop high-performance flame-retardant polymer/MXene composites with excellent EMI shielding effectiveness because of the poor oxidative stability of MXene.Herein,phosphorylated MXene/polypropylene(PP)composites are prepared by coating phosphorylated MXene on PP fabric followed by spraying polyethylenimine(PEI)and hot-pressing.The phosphorylated MXene proves to be more durable against oxidation than pure MXene due to the protection effect of polyphosphates.Upon hot-pressing,melted PP fibers are fused together at their contact points and thus as-prepared composites are bi-continuous with two interpenetrating phases.The composites show significantly improved thermal stability and flame retardancy relative to pure PP,with a low total heat release(THR)of 3.7 kJ/g and a heat release rate(HRR)of 50.0 W/g,which are reduced by 78%and 87%,respectively.In addition,the composites exhibit a high electrical conductivity of~36,700 S/m and an EMI shielding performance of~90 d B over the whole frequency range of 8–12 GHz with a thickness of~400μm.The as-developed PP/MXene composites hold great promise for reliable protection of next-generation electronic devices working in complex environments.Tingting Tang Shanchi Wang Yue Jiang Zhiguang Xu Yu Chen Tianshu Peng Fawad Khan Jiabing Feng Pingan Song Yan Zhao 2022Journal of Materials Science & Technology2022,,16:1
14Migration and accumulation mechanisms and main controlling factors of tight oil enrichment in a continental lake basin显示文摘Based on the typical dissection of various onshore tight oil fields in China,the tight oil migration and accumulation mechanism and enrichment-controlling factors in continental lake basins are analyzed through nuclear magnetic resonance(NMR)displacement physical simulation and Lattice Boltzmann numerical simulation by using the samples of source rock,reservoir rock and crude oil.In continental lake basins,the dynamic forces driving hydrocarbon generation and expulsion of high-quality source rocks are the foundational power that determines the charging efficiency and accumulation effect of tight oil,the oil migration resistance is a key element that influences the charging efficiency and accumulation effect of tight oil,and the coupling of charging force with pore-throat resistance in tight reservoir controls the tight oil accumulation and sweet spot enrichment.The degree of tight oil enrichment in continental lake basins is controlled by four factors:source rock,reservoir pore-throat size,anisotropy of reservoir structure,and fractures.The high-quality source rocks control the near-source distribution of tight oil,reservoir physical properties and pore-throat size are positively correlated with the degree of tight oil enrichment,the anisotropy of reservoir structure reveals that the parallel migration rate is the highest,and intralayer fractures can improve the migration and accumulation efficiency and the oil saturation.HU Suyun TAO Shizhen WANG Min PANG Zhenglian BAI Bin CHEN Yanyan LU Shuangfang CHEN Yue YANG Yiqing JIN Xu JIA Jinhua WANG Jian ZHANG Tianshu LIN Senhu WU Yinye 2023Petroleum Exploration and Development2023,50,3:1
15Neuronal NR4A1 deficiency drives complement-coordinated synaptic stripping by microglia in a mouse model of lupus显示文摘Neuropsychiatric lupus(NPSLE)is a frequent manifestation of systemic lupus erythematosus(SLE)that occurs in 40-90%of SLE patients;however,the underlying mechanisms remain elusive,causing a severe lack of therapeutic targets for this condition.Here,we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice,a lupus-prone murine model.We demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglial reactivation before overt peripheral lupus pathology.Xiaojuan Han Tianshu Xu Congzhu Ding Dandan Wang Genhong Yao Hongwei Chen Qijun Fang Gang Hu Lingyun Sun 2022Signal Transduction and Targeted Therapy2022,7,3:1
16First-zone distance relaying algorithm of parallel transmission lines for cross-country grounded faults显示文摘BI Tianshu LI Wei XU Zhenyu 2012IEEE Transactions on Power Delivery2012,27,4:1
17Stochastic Chaos with Its Control and Synchronization显示文摘The discovery of chaos in the sixties of last century was a breakthrough in concept,revealing the truth that some disorder behavior,called chaos,could happen even in a deterministic nonlinear system under barely deterministic disturbance.After a series of serious studies,people begin to acknowledge that chaos is a specific type of steady state motion other than the conventional periodic and quasi-periodic ones,featuring a sensitive dependence on initial conditions,resulting from the intrinsic randomness of a nonlinear system itself.In fact,chaos is a collective phenomenon consisting of massive individual chaotic responses,corresponding to different initial conditions in phase space.Any two adjacent individual chaotic responses repel each other,thus causing not only the sensitive dependence on initial conditions but also the existence of at least one positive top Lyapunov exponent(TLE) for chaos.Meanwhile,all the sample responses share one common invariant set on the Poincaré map,called chaotic attractor,which every sample response visits from time to time ergodically.So far,the existence of at least one positive TLE is a commonly acknowledged remarkable feature of chaos.We know that there are various forms of uncertainties in the real world.In theoretical studies,people often use stochastic models to describe these uncertainties,such as random variables or random processes.Systems with random variables as their parameters or with random processes as their excitations are often called stochastic systems.No doubt,chaotic phenomena also exist in stochastic systems,which we call stochastic chaos to distinguish it from deterministic chaos in the deterministic system.Stochastic chaos reflects not only the intrinsic randomness of the nonlinear system but also the external random effects of the random parameter or the random excitation.Hence,stochastic chaos is also a collective massive phenomenon,corresponding not only to different initial conditions but also to different samples of the random parameter or the random excitation.Thus,the unique common feature of deterministic chaos and stochastic chaos is that they all have at least one positive top Lyapunov exponent for their chaotic motion.For analysis of random phenomena,one used to look for the PDFs(Probability Density Functions) of the ensemble random responses.However,it is a pity that PDF information is not favorable to studying repellency of the neighboring chaotic responses nor to calculating the related TLE,so we would rather study stochastic chaos through its sample responses.Moreover,since any sample of stochastic chaos is a deterministic one,we need not supplement any additional definition on stochastic chaos,just mentioning that every sample of stochastic chaos should be deterministic chaos.We are mainly concerned with the following two basic kinds of nonlinear stochastic systems,i.e.one with random variables as its parameters and one with ergodical random processes as its excitations.To solve the stochastic chaos problems of these two kinds of systems,we first transform the original stochastic system into their equivalent deterministic ones.Namely,we can transform the former stochastic system into an equivalent deterministic system in the sense of mean square approximation with respect to the random parameter space by the orthogonal polynomial approximation,and transform the latter one simply through replacing its ergodical random excitations by their representative deterministic samples.Having transformed the original stochastic chaos problem into the deterministic chaos problem of equivalent systems,we can use all the available effective methods for further chaos analysis.In this paper,we aim to review the state of art of studying stochastic chaos with its control and synchronization by the above-mentioned strategy.Zhang Ying Xu Wei Zhang Tianshu Yang Xiaoli Wu Cunli Fang Tong 2008西北工业大学学报2008,26,6:1
18Field PMU Test and Calibration Method–Part I:General Framework and Algorithms for PMU Calibrator显示文摘Laboratory testing of phasor measurement units(PMUs)guarantees their performance under laboratory conditions.However,many factors may cause PMU measurement problems in actual power systems,resulting in the malfunction of PMU-based applications.Therefore,field PMUs need to be tested and calibrated to ensure their performance and data quality.In this paper(Part I),a general framework for the field PMU test and calibration in different scenarios is proposed.This framework consists of a PMU calibrator and an analysis center,where the PMU calibrator provides the reference values for PMU error analysis.Two steps are implemented to ensure the calibrator accuracy for complex field signals:①by analyzing the frequency-domain probability distribution of random noise,a Fourier-transform-based signal denoising method is proposed to improve the anti-interference capability of the PMU calibrator;and②a general synchrophasor estimation method based on complex bandpass filters is presented for accurate synchrophasor estimations in multiple scenarios.Simulation and experimental test results demonstrate that the PMU calibrator has a higher accuracy than that of other calibrator algorithms and is suitable for field PMU test.The analysis center for evaluating the performance of field PMUs and the applications of the proposed field PMU test system are provided in detail in Part II of the next-step research.Sudi Xu Hao Liu Tianshu Bi 2022Journal of Modern Power Systems and Clean Energy2022,10,6:0
19N-terminal residues of an HIV-1 gp41 membrane-proximal external region antigen influence broadly neutralizing 2F5-like antibodies显示文摘The Human immunodeficiency virus type 1(HIV-1) gp41 membrane proximal external region(MPER) is targeted by broadly neutralizing antibodies(e.g. 2F5, 4E10, Z13 e and m66.6), which makes this region a promising target for vaccine design. One strategy to elicit neutralizing antibodies against the MPER epitope is to design peptide immunogens mimicking neutralization structures. To probe 2F5-like neutralizing antibodies, two yeast-displayed antibody libraries from peripheral blood mononuclear cells from a HIV-1 patient were screened against the 2F5 epitope peptide SP62. Two 2F5-like antibodies were identified that specifically recognized SP62. However,these antibodies only weakly neutralized HIV-1 primary isolates. The epitopes recognized by these two 2F5-like antibodies include not only the 2F5 epitope(amino acids(aa) 662–667 in the MPER)but also several other residues(aa 652–655) locating at the N-terminus in SP62. Experimental results suggest that residues of SP62 adjacent to the 2F5 epitope influence the response of broadly neutralizing 2F5-like antibodies in vaccination. Our findings may aid the design of vaccine immunogens and development of therapeutics against HIV-1 infection.Dezhi Li Jie Liu Li Zhang Tianshu Xu Junheng Chen Liping Wang Qi Zhao 2015Virologica Sinica2015,30,6:0
20JUNB mediates oxaliplatin resistance via the MAPK signaling pathway in gastric cancer by chromatin accessibility and transcriptomic analysis显示文摘tients,and chemotherapy resistance is one of the main reasons for treatment failure.Thus,it is important to reveal the mechanism of oxaliplatin resistance and to seek effective intervention strategies to improve chemotherapy sensitivity,thereby improving the survival and prognosis of gastric cancer patients.To understand the molecular mechanisms of oxaliplatin resistance,we generate an oxaliplatin-resistant gastric cancer cell line and conduct assay for transposase-accessible chromatin sequencing(ATAC-seq)and RNA sequencing(RNA-seq)for both parental and oxaliplatin-resistant AGS cells.A total of 3232 genomic regions are identified to have higher accessibility in ox-aliplatin-resistant cells,and DNA-binding motif analysis identifies JUNB as the core transcription factor in the regulatory network.JUNB is overexpressed in oxaliplatin-resistant gastric cancer cells,and its upregulation is associated with poor prognosis in gastric cancer patients,which is validated by our tissue microarray data.Moreover,chromatin immunoprecipitation sequencing(ChIP-seq)analysis reveals that JUNB binds to the tran-scriptional start site of key genes involved in the MAPK signaling pathway.Knockdown of JUNB inhibits the MAPK signaling pathway and restores sensitivity to oxaliplatin.Combined treatment with the ERK inhibitor piperlongu-mine or MEK inhibitor trametinib effectively overcomes oxaliplatin resistance.This study provides evidence that JUNB mediates oxaliplatin resistance in gastric cancer by activating the MAPK pathway.The combination of MAPK inhibitors with oxaliplatin overcomes resistance to oxaliplatin,providing a promising treatment opportunity for oxaliplatin-resistant gastric cancer patients.Suyao Li Yichou Wei Xun Sun Mengling Liu Mengxuan Zhu Yitao Yuan Jiayu Zhang Yu Dong Keshu Hu Sining Ma Xiuping Zhang Bei Xu Hesheng Jiang Lu Gan Tianshu Liu 2023Acta Biochimica et Biophysica Sinica2023,55,11:0
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