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| 1 | Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response显示文摘Personalized immunotherapy targeting tumor-specific antigens(TSAs)could generate efficient and safe antitumor immune response without damaging normal tissues.Although neoantigen vaccines have shown therapeutic effect in clinic trials,precise prediction of neoantigens from tumor mutations is still challenging.The host antitumor immune response selects and activates T cells recognizing tumor antigens.Hence,T cells engineered with T-cell receptors(TCRs)from these naturally occurring tumor antigen-specific T(Tas)cells in a patient will target personal TSAs in his/her tumor.To establish such a personalized TCR-T cell therapy,we comprehensively characterized T cells in tumor and its adjacent tissues by single-cell mRNA sequencing(scRNA-seq),TCR sequencing(TCR-seq)and in vitro neoantigen stimulation.Compared to bystander T cells circulating among tissues,Tas cells were characterized by tumor enrichment,tumor-specific clonal expansion and neoantigen specificity.We found that CXCL13 is a unique marker for both CD4^(+)and CD8^(+)Tas cells.Importantly,TCR-T cells expressing TCRs from Tas cells showed significant therapeutic effects on autologous patient-derived xenograft(PDX)tumors.Intratumoral Tas cell levels measured by CXCL13 expression precisely predicted the response to immune checkpoint blockade,indicating a critical role of Tas cells in the antitumor immunity.We further identified CD200 and ENTPD1 as surface markers for CD4^(^(+))and CD8^(^(+))Tas cells respectively,which enabled the isolation of Tas cells from tumor by Fluorescence Activating Cell Sorter(FACS)sorting.Overall,our results suggest that TCR-T cells engineered with Tas TCRs are a promising agent for personalized immunotherapy,and intratumoral Tas cell levels determine the response to immunotherapy. | Jingjing He Xinxin Xiong Han Yang Dandan Li Xuefei Liu Shuo Li Shuangye Liao Siyu Chen Xizhi Wen Kuai Yu Lingyi Fu Xingjun Dong Kaiyu Zhu Xiaojun Xia Tiebang Kang Chaochao Bian Xiang Li Haiping Liu Peirong Ding Xiaoshi Zhang Zhenjiang Liu Wende Li Zhixiang Zuo Penghui Zhou | 2022 | Cell Research2022，32，6： | 10 |
| 2 | Molecular insights into the heterogeneity of telomere reprogramming in induced pluripotent stem cells显示文摘有各种各样的长度的 telomeres 的返老还童在导致的 pluripotent 干细胞(iPSCs ) 被发现了。telomere 长度规定的机制在 iPSCs 的正式就职和增长期间留下逃犯。我们证明 telomere 动力学在 reprogramming 和经过期间在鼠标 iPSCs 是可变的,并且建议这些差别多半源于多重潜在的因素,包括包括外长的 reprogramming 因素的表示的 telomerase 机械, telomerase 独立的机制和同种细胞的影响。用一个基因模型 telomerase 缺乏(为 iPSCs 的推导和段落的 Terc −/− 和 Terc +/−) 房间,我们发现 telomerase 在 iPSCs 的 reprogramming 和自强起一个关键作用。进一步,当由再结合的延伸和维护的其他的小径也被要求时, telomeres 的 telomerase 维护为真 pluripotency 的正式就职是必要的,然而并非足够。一起, telomere 生物学的几个方面可以在 iPSCs 说明可变 telomere 动力学。尤其是,采用在 iPSC reprogramming 期间维持 telomeres 的机制很类似于胚胎的干细胞的那些。这些调查结果可以也联系到这些机制能为在由体的房间的原子 reprogramming 以后的 telomere 异质负责的克隆的地原子转移。 | Fang Wang Yu Yin Xiaoying Ye Kai Liu Haiying Zhu Lingling Wang Maria Chiourea Maja Okuka Guangzhen Ji Jiameng Dan Bingfeng Zuo Minshu Li Qian Zhang Na Liu Lingyi Chen Xinghua Pan Sarantis Gagos David L Keefe Lin Liu | 2012 | Cell Research2012，22，4： | 7 |
| 3 | LIX1-like protein promotes liver cancer progression via miR-21-3p-mediated inhibition of fructose-1,6-bisphosphatase显示文摘Limb and CNS expressed 1 like(LIX1L) is over-expressed in several types of tumors.However,the function of LIX1L in glucose metabolism and hepatocellular carcinoma(HCC) progression remains elusive.Here we report that LIX1L is over-expressed in human HCC tissues,which predicts unfavorable prognosis.LIX1L deficiency in vivo significantly attenuated liver cancer initiation in mice.Functional studies indicated that LIX1L overexpression elevated proliferation,migratory,invasive capacities of HCC cells in vitro,and promoted liver cancer growth and metastasis in vivo.LIX1L knockdown up-regulated fructose-1,6-bisphosphatase(FBP1) expression to reduce glucose consumption as well as lactate production.Mechanistically,LIX1L increased miR-21-3p expression,which targeted and suppressed FBP1,thereby promoting HCC growth and metastasis.MiR-21-3p inhibitor could abrogate LIX1L induced enhancement of cell migration,invasion,and glucose metabolism.Inhibition of miR-21-3p suppressed tumor growth in an orthotopic tumor model.Our results establish LIX1L as a critical driver of hepatocarcinogenesis and HCC progression,with implications for prognosis and treatment. | Jie Zou Xiaoyun Zhu Dejuan Xiang Yanqiu Zhang Jie Li Zhigui Su Lingyi Kong Hao Zhang | 2021 | Acta Pharmaceutica Sinica B2021，11，6： | 4 |
| 4 | Overexpression of N-cadherin is correlated with metastasis and worse survival in colorectal cancer patients显示文摘N-cadherin is related to the progression and metastases of several solid carcinomas.However,it was still unclear whether N-cadherin is overexpressed in colorectal malignant tumors that have stronger malignant tendency.In this study,we used immunohistochemistry to detect the expression patterns of N-cadherin in both the primary tumors and their normal mucosa tissues of 120patients with colorectal cancer.We revealed that N-cadherin was expressed in 78.3%(94/120)of colorectal tumor tissues and in only 9.2%(11/120)of paired distant normal mucosa tissues with a significant difference(P=0.000).The low,moderate,and high expression of N-cadherin protein was 42.5%,30.8%,and 26.7%,respectively.N-cadherin overexpression was associated with advanced TNM stage,lymph nodes metastasis and distant metastasis(P<0.05).Patients with N-cadherin overexpressed showed the obvious lower overall survival rate than those with moderate and low expression,and patients with low expression had a better survival rate than those with moderate and high expression(P<0.05).In conclusion,high N-cadherin expression may lead to tumor aggressiveness and metastatic potential in colorectal cancer,and may prove to be a possible prognostic factor. | ZHUO HongQing JIANG KeWei DONG LingYi ZHU Yi Lü Liang Lü You ZHANG YanBin ZHANG Hui YE YingJiang WANG Shan | 2013 | Chinese Science Bulletin2013，58，28： | 2 |
| 5 | M0S2 dual-gate transistors with electrostatically doped contacts显示文摘Two-dimensional(2D)transition metal dichalcogenides(TMDs)such as molybdenum disulfide(M0S2)have been intensively investigated because of their exclusive physical properties for advaneed electronics and optoelectronics.In the present work,we study the M0S2 transistor based on a novel tri-gate device architecture,with dual-gate(Dual-G)in the channel and the buried side-gate(Side-G)for the source/drain regi ons.All gates can be in depe ndently con trolled without in terfere nee.For a MoS2 sheet with a thick ness of 3.6 nm,the Schottky barrier(SB)and non-overlapped channel region can be effectively tuned by electrostatically doping the source/drain regions with Side-G.Thus,the extri nsic resista nee can be effectively lowered,and a boost of the ON-state cur re nt can be achieved.Mean while,the cha nn el c ontrol remai ns efficient under the Dual-G mode,with an ON-OFF current ratio of 3 x 107 and subthreshold swing of 83 mV/decade.The corresponding band diagram is also discussed to illustrate the device operati on mechanism.This no vel device structure ope ns up a new way toward fabricati on of high-performance devices based on 2D-TMDs. | Fuyou Liao Yaocheng Sheng Zhongxun Guo Hongwei Tang Yin Wang Lingyi Zong Xinyu Chen Antoine Riaud Jiahe Zhu Yufeng Xie Lin Chen Hao Zhu Qingqing Sun Peng Zhou Xiangwei Jiang Jing Wan Wenzhong Bao David Wei Zhang | 2019 | Nano Research2019，12，10： | 2 |
| 6 | Cryo-EM structures of human pannexin 1 channel显示文摘Dear Editor,Pannexin 1(PANX1)channel mediates adenosine-5’-triphosphate(ATP)release for purinergic signaling,1 playing important roles in multiple physiological and pathological processes including apoptotic clearance,2 inflammatory response,3 cancer progression,and metastasis.4 Diverse stimuli have been reported to activate PANX1 channel,such as voltage,membrane stretch,hypotonicity,elevated extracellular K+or intracellular Ca2+concentration,C-terminal cleavage and phosphorylation.1,5 It is perplexing that PANX1 has been demonstrated to exhibit different unitary channel properties depending on the mode of activation.1,5 Particularly,PANX1 undergoes a stepwise,quantized activation progress upon sequentially cleaving the C-terminal of each subunit. | Qiuheng Jin Bo Zhang Xiang Zheng Ningning Li Lingyi Xu Yuan Xie Fangjun Song Eijaz Ahmed Bhat Yuan Chen Ning Gao Jiangtao Guo Xiaokang Zhang Sheng Ye | 2020 | Cell Research2020，30，5： | 2 |
| 7 | Identification of a novel PHGDH covalent inhibitor by chemical proteomics and phenotypic profiling显示文摘The first rate-limiting enzyme of the serine synthesis pathway(SSP), phosphoglycerate dehydrogenase(PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A(WA), a natural small molecule,as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue(Cys295)of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain(SBD)of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species(ROS) were elevated, leading to the inhibition of tumor proliferation.This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH. | Chen Chen Tianyu Zhu Xiaoqin Liu Dongrong Zhu Yi Zhang Sifang Wu Chao Han Hao Zhang Jianguang Luo Lingyi Kong | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 2 |
| 8 | Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation: A new platform for synergistic oncology therapy显示文摘Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors,it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels,tissues,and cell barriers to thereafter demonstrate excellent antitumor effects.To further overcome these inherent obstacles,we designed and prepared mycoplasma membrane(MM)-fused liposomes(LPs)with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles.We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod(LPsR848).Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848.The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors.Facilitated by the formation of neutrophil extracellular traps(NETs),podophyllotoxin(POD)-loaded MM-fused LPs(MM-LPs-POD)were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation.MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model.Overall,such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy. | Xiaobei Cheng Pei Yu Xiang Zhou Jiale Zhu Yubao Han Chao Zhang Lingyi Kong | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 2 |
| 9 | BAP31 is frequently overexpressed in patients with primary colorectal cancer and correlates with better prognosis显示文摘We previously showed that B cell receptor associated protein 31(BAP31) was significantly upregulated in colorectal cancer compared with normal mucosa epithelia. However, its expression pattern and pathological role in colorectal cancer are not clearly understood. In this study, we investigated whether the expression of BAP31 was associated with the clinicopathological parameters of colorectal cancer. The expression pattern of BAP31 was detected by immunohistochemistry on a tissue microarray in both primary tumor and paired distant normal mucosa samples from 120 consecutive colorectal cancer patients. Furthermore, BAP31 protein expression was also determined in twenty colorectal adenomas and eight liver metastasis samples. There was positive expression of BAP31 in 64.17% of primary tumors and 6.67% in distant normal mucosa (P=0.000). Negative expression of BAP31 was correlated with distant metastasis (P=0.036) and lower tumor differentiation grade (P=0.001). Patients with BAP31-negative expression showed significantly lower overall survival rate (P=0.003) compared to patients with BAP31-positive expression. Our results demonstrate that BAP31 may serve as a candidate prognostic marker in colorectal cancer and negative BAP31 expression may lead to more aggressive invasion of colorectal cancer. | DONG LingYi JIANG KeWei ZHANG YanBin ZHANG Hui ZHUO HongQing CUI ZhiRong YE YingJiang WANG Shan | 2011 | Chinese Science Bulletin2011，56，23： | 2 |
| 10 | Cryo-EM structure of the human α5β3 GABAA receptor显示文摘 | Si Liu Lingyi Xu Fenahui Guan Yun-Tao Liu Yanxiang Cui Qing Zhang Xiang Zheng Guo-Qiang Bi Z. Hong Zhou Xiaokang Zhang Sheng Ye | 2018 | Cell Research2018，28，9： | 2 |
| 11 | Mycorrhizal Synthesis Involving Boletus edulis and Pinus massoniana显示文摘Mycorrhizae involving Boletus edulis and Pinus massoniana have been successfully established and their morphological characteristics described.Optimal conditions for mycorrhizal synthesis were determined using orthogonal testing of three parameters:substrate,age of host plant and inoculation procedure.Following integration analysis of plant survival rates,diameter of seedling rootstock,height of seedling shoot,number of mycorrhizae,ratio of shoot/root biomass,number of mycorrhizae,and the ratio of infected/non-infected root tips,we concluded that a double-layered growth substrate that simulated natural soil structure was superior for mycorrhizal synthesis compared with the more commonly used single-layered peat moss and vermiculite substrate,especially when sepiolite powder was also added. | FU Shaochun TAN Qi CHEN Mingjie SHANG Xiaodong CAI Lingyi ZHANG Meiyan | 2009 | 食用菌学报2009，16，1： | 2 |
| 12 | microRNA-320a inhibits tumor invasion by targeting neuropilin 1 andis associated with liver metastasis in colorectal cancer显示文摘 | Yujun Zhang Xiangjun He Yulan Liu Yingjiang Ye Hui Zhang Peiying He Qi Zhang Lingyi Dong Yujing Liu Jianqiang Dong | 2012 | Oncology Reports2012，，3： | 2 |
| 13 | Correlation and interaction between temperature and freeze-thaw in representative regions of Antarctica显示文摘As the most sensitive and direct indicator of global climate change,the freezing and thawing of the Antarctic ice sheet is of great significance for research on surface mass and energy balance.In this study,four representative regions in Antarctica were selected and correlation analysis,Granger causality testing,and cluster analysis were applied to comprehensively analyze the correlation and response of spatiotemporal variation in freeze-thaw and temperature.The conclusions are as follows.(1)In the Antarctic Peninsula,a phenomenon was demonstrated that the summer shifts rearward.Hotter December and colder March temperatures were observed in the Amery Ice Shelf and Queen Maud Land.(2)The Antarctic Peninsula featured the most severe degree of melting among the four regions,with the largest melt area in the past 30 years appearing during the 2015/2016 season.However,the number of melt days in most areas of the Antarctic Peninsula was observed to have decreased.(3)There is a strong correlation between the freeze-thaw state of the Antarctic ice sheet and temperature,as well as spatial differences among regions,but the data were clustered at different time scales. | Dong Liang Huadong Guo Qing Cheng Lu Zhang Lingyi Kong | 2022 | International Journal of Digital Earth2022，15，1： | 1 |
| 14 | Fabricationand evaluation of chiral monolithic column modified byβ-Cyclodextrin derivatives显示文摘 | Li Yingjie Song Chunhui Zhang Lingyi | 2010 | Talanta2010，80，3： | 1 |
| 15 | Chemical constituents from Alpinia tonkinensis显示文摘 | Zhang Jian Kong Lingyi | 2004 | J Asian Nat Prod Res2004，6，3： | 1 |
| 16 | Overexpression of Hdac6 extends reproductive lifespan in mice显示文摘 | Xiaoxi Zhang Jiao Yang Haiying Wang Renpeng Guo Yu Yin Dongdong Zhang Qian Zhang Hua Wang Zhongcheng Zhou Lingyi Chen Jun Zhou Lin Liu | 2017 | Protein & Cell2017，8，5： | 1 |
| 17 | Brassinosteroid and gibberellin coordinate rice seed germination and embryo growth by regulating glutelin mobilization显示文摘Seed germination is the beginning of a new lifecycle,and involves many complex physiological and biochemical reactions including seed reserve mobilization in the endosperm and nutrient transport and reuse in the embryo.Although glutelin is a dominant storage protein in rice,its contribution to seed germination and its regulatory mechanisms are mostly unknown.Gibberellin (GA) and brassinosteroid (BR),two major growth-promoting phytohormones,also play positive roles in controlling seed germination.However,how GA and BR interact and coordinate seed germination and facilitate glutelin mobilization remains unclear.In the present study,biochemical and physiological analyses of seed germination indicated that both GA and BR promote seed germination and post-germination growth.Exogenous application of GA restored germination defects caused by BR deficiency or insensitivity.Proteomic and q RT-PCR results showed that the expression of several glutelin proteins and their encoding genes was induced by BR and GA in the embryo.Expression assays suggested that the increased accumulation of glutelin protein in the embryo was due to the accelerated degradation of glutelin by a cysteine proteinase (REP-1) in the endosperm.The breakdown of glutelin in the endosperm showed a strict positive correspondence with the length of the shoot.The GluA2 mutation led to reduced degradation rate of glutelin and defects in seed germination,and the promotion effect of GA on seed germination was weakened in the glua2mutant.In vitro culture assay of rice embryos showed that glutelin mobilization functioned downstream of the GA and BR pathways to promote shoot elongation.These findings suggest a mechanism that mediates crosstalk between BR and GA in co-regulating rice seed germination and embryo growth. | Min Xiong Lingyi Chu Qianfeng Li Jiawen Yu Yihao Yang Peng Zhou Yong Zhou Changquan Zhang Xiaolei Fan Dongsheng Zhao Changjie Yan Qiaoquan Liu | 2021 | The Crop Journal2021，9，5： | 1 |
| 18 | Sarcaglarols A-D, Lindenane-Monoterpene Heterodimers from Sarcandra glabra Based on Molecular Networks显示文摘Sarcaglarols A-D(1-4),two pairs of lindenane-monoterpene heterodimers fused by a 1,2-dioxane moiety,were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy.Their planar structures,absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS,NMR spectroscopic data,ECD spectrum,and the X-ray diffraction study of isopropylidene derivatives.An intermolecular[2+2+2]cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane-monoterpene heterodimer skeleton,which can be recognized as the biogenetic precursors of our previous reported lindenane-normonoterpene conjugates.In addition,compounds 1,3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells. | Yongyue Wang Zhirong Cui Jun Chi Pengfei Tang Meihui Zhang Jixin Li Yongyi Li Hao Zhang Jun Luo Lingyi Kong | 2021 | Chinese Journal of Chemistry2021，39，1： | 1 |
| 19 | Journal of Chromatography B显示文摘 | ZHANG Lingyi XU Jin ZH ANG Lihua ZHANG Weibing ZHANG Yukui | 2003 | 793 : 1592003，793，： | 1 |
| 20 | Study on difference between epidermis, phloem and xylem of Radix Ginseng with near-infrared and infrared spectroscopy coupled with principal component analysis显示文摘 | Yanhong Wu Yi Zheng Qingqing Li Jibran Iqbal Lingyi Zhang Weibing Zhang Yiping Du | 2010 | Vibrational Spectroscopy2010，，2： | 1 |
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