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| 1 | GL3.3, a Novel QTL Encoding a GSK3/SHAGGY- like Kinase, Epistatically Interacts with GS3 to Produce Extra-long Grains in Rice显示文摘 | Duo Xia Nao Zhou Rongjia Liu Wenhan Dan Pingbo Li Bian Wu Junxiao Chen Lingqiang Wang Guanjun Gao Qinglu Zhang Yuqing He | 2018 | Molecular Plant2018，11，5： | 41 |
| 2 | MiR-98 promotes chondrocyte apoptosis by decreasing Bcl-2 expression in a rat model of osteoarthritis显示文摘 | Jing Wang Lingqiang Chen Song Jin Jun Lin Hongmei Zheng Hong Zhang Hongtao Fan Fang He Sha Ma Qin Li | 2016 | Acta Biochimica et Biophysica Sinica2016，48，10： | 8 |
| 3 | CKIP-1 regulates macrophage proliferation by inhibiting TRAF6-mediated Akt activation显示文摘巨噬细胞在开发,动态平衡,织物修理和免疫起枢轴的作用。巨噬细胞增长被刺激殖民地的因素(M-CSF ) 导致了 Akt 发信号的巨噬细胞支持;然而,这个过程怎么被终止,仍然保持不清楚。这里,我们作为巨噬细胞增长的一个新奇禁止者识别酷蛋白 kinase 2-interacting protein-1 (CKIP-1 ) 。在放松巨噬细胞, CKIP-1 是在由组成地活跃的 GSK3β 的丝氨酸 342 点的 phosphorylated;, Akt 的下游的目标。这 phosphorylation 触发 CKIP-1 的 polyubiquitination 和 proteasomal 降级。在 M-CSF 刺激之上, Akt 被 CSF-1R-PI3K 激活然后使 GSK3β 失去活性;,导致 CKIP-1 和 β 的稳定; -catenin 蛋白质。β -catenin 包括 cyclin D 和 c-Myc 支持增长基因的表示。CKIP-1 与 TRAF6,为连接 K63 的 ubiquitination 要求的 ubiquitin ligase 和 Akt 的血浆膜招募交往,并且终止调停 TRAF6 的 Akt 激活。由这个工具, CKIP-1 在 M-CSF 刺激以后在迟了的阶段明确地禁止巨噬细胞增长。而且, CKIP-1 缺乏在老鼠自发地开发的 vitro 和 CKIP-1 −/− 导致增加的增长和巨噬细胞的减少的 apoptosis 巨噬细胞主导的脾大和 myeloproliferation。一起,这些数据证明 CKIP-1 由禁止调停 TRAF6 的 Akt 激活在巨噬细胞动态平衡的规定起一个关键作用。 | Luo Zhang Yiwu Wang Fengjun Xiao Shaoxia Wang Guichun Xing Yang Li Xiushan Yin Kefeng Lu Rongfei Wei Jiao Fan Yuhan Chen Tao Li Ping Xie Lin Yuan Lei Song Lanzhi Ma Lujing Ding Fuchu He Lingqiang Zhang | 2014 | Cell Research2014，24，6： | 7 |
| 4 | Mycobacterium tuberculosis Mce2E suppresses the macrophage innate immune response and promotes epithelial cell proliferation显示文摘The intracellular pathogen Mycobacterium tuberculosis(Mtb)can survive in the host and cause disease by interfering with a variety of cellular functions.The mammalian cell entry 2(mce2)operon of Mtb has been shown to contribute to tuberculosis pathogenicity.However,little is known about the regulatory roles of Mtb Mce2 family proteins towards host cellular functions.Here we show that the Mce2 family protein Mce2E suppressed the macrophage innate immune response and promoted epithelial cell proliferation.Mce2E inhibited activation of the extracellular signal-regulated kinase(ERK)and Jun N-terminal kinase(JNK)mitogen-activated protein kinase(MAPK)signaling pathways in a non-canonical D motif(a MAPK-docking motif)-dependent manner,leading to reduced expression of TNF and IL-6 in macrophages.Furthermore,Mce2E promoted proliferation of human lung epithelium-derived lung adenoma A549 cells by inhibiting K48-linked polyubiquitination of eEF1A1 in aβstrand region-dependent manner.In summary,Mce2E is a novel multifunctional Mtb virulence factor that regulates host cellular functions in a niche-dependent manner.Our data suggest a potential novel target for TB therapy. | Lihua Qiang Jing Wang Yong Zhang Pupu Ge Qiyao Chai Bingxi Li Yi Shi Lingqiang Zhang George Fu Gao Cui Hua Liu | 2019 | Cellular & Molecular Immunology2019，16，4： | 7 |
| 5 | Exploring the diagnosis markers for gallbladder cancer based on clinical data显示文摘一会儿,没有有效标记是可得到的便于胆囊癌症(GBC ) 诊断。这研究试图为 GBC 诊断探索可得到的标记。144 GBC 和 116 个胆石病病人的临床的数据回顾地被考察。逻辑回归分析被执行评估 GBC 风险因素。操作特征(巨鸟) 曲线的接收装置被用来估计风险因素的诊断价值。由比较 GBC 和胆石病病人的特征,下列因素展出了统计差别:年龄,性,胆石,全部的 bilirubin (TB ) ,碱的磷酸酶(高山) , aspartate aminotransferase (著名计算机生产厂商) ,丙氨酸 aminotransferase (中高音) ,血小板计数(PLT ) , CA125 (carcinoembryonic 抗原 125 ) ,和 CA199 (糖类抗原 199 ) 。逻辑回归分析显示了那年龄[机会比率(或) , 1.032;95%confidence 间隔(95% CI ) , 1.004 ~ 1.061;P = 0.024 ] ,性(或, 0.346;95% CI, 0.167 ~ 0.716;P = 0.004 ) ,胆石(或, 0.027;95% CI, 0.007 ~ 0.095;P < 0.001 ) ,高山(或, 1.003;95% CI, 1.000 ~ 1.006;P = 0.032 ) , TB (或, 1.004;95% CI, 1.000 ~ 1.009;P = 0.042 ) ,并且 CA125 (或, 1.007;95% CI, 1.002 ~ 1.013;P = 0.011 ) 是为 GBC 的独立风险因素。根据巨鸟曲线, CA125 [在曲线(AUC ) 下面的区域, 0.720 ] ,高山(AUC, 0.713 ) , TB (AUC, 0.636 ) ,并且年龄(AUC, 0.573 ) 是珍贵诊断标记。基于独立风险因素,另外, GBC 诊断模型被建立。年龄, TB,高山,和 CA125 能被用作 GBC 的辅助诊断因素。当包括地考虑各种各样的风险因素时,诊断模型为 GBC 诊断提供一个量的工具。 | Lingqiang Zhang Runchen Miao Xiude Zhang Wei Chen Yanyan Zhou Ruitao Wang Ruiyao Zhang Qing Pang Xinsen Xu Chang Liu | 2015 | Frontiers of Medicine2015，9，3： | 4 |
| 6 | The deubiquitinase OTUD1 inhibits colonic inflammation by suppressing RIPK1-mediated NF-κB signaling显示文摘The E3 ubiquitin ligase(E3)-mediated ubiquitination and deubiquitinase(DUB)-mediated deubiquitination processes are closely associated with the occurrence and development of colonic inflammation.Ovarian tumor deubiquitinase 1(OTUD1)is involved in immunoregulatory functions linked to infectious diseases.However,the effect of OTUD1 on intestinal immune responses during colonic inflammatory disorders such as inflammatory bowel disease(IBD)remains unclear.Here,we show that loss of OTUD1 in mice contributes to the pathogenesis of dextran sulfate sodium(DSS)-induced colitis via excessive release of proinflammatory cytokines.In addition,bone marrow transplantation experiments revealed that OTUD1 in hematopoietic cells plays a dominant role in protection against colitis.Mechanistically,OTUD1 physically interacts with receptor-interacting serine/threonine-protein kinase 1(RIPK1)and selectively cleaves K63-linked polyubiquitin chains from RIPK1 to inhibit the recruitment of NF-κB essential modulator(NEMO).Moreover,the expression of OTUD1 in mucosa samples from ulcerative colitis(UC)patients was lower than that in mucosa samples from healthy controls.Furthermore,we demonstrate that the UC-associated OTUD1 G430V mutation abolishes the ability of OTUD1 to inhibit RIPK1-mediated NF-κB activation and intestinal inflammation.Taken together,our study unveils a previously unexplored role of OTUD1 in moderating intestinal inflammation by inhibiting RIPK1-mediated NF-κB activation,suggesting that the OTUD1-RIPK1 axis could be a potential target for the treatment of IBD. | Bo Wu Lihua Qiang Yong Zhang Yesheng Fu Mengyuan Zhao Zehui Lei Zhe Lu Yan-Ge Wei Hongmiao Dai Yingwei Ge Mingqiu Liu Xuemei Zhou Zhiqiang Peng Hongchang Li Chun-Ping Cui Jing Wang Hui Zheng Cui Hua Liu Lingqiang Zhang | 2022 | Cellular & Molecular Immunology2022，19，2： | 3 |
| 7 | TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal显示文摘Dysregulation of gut homeostasis is associated with irritable bowel syndrome(IBS),a chronic functional gastrointestinal disorder affecting approximately 11.2%of the global population.The poorly understood pathogenesis of IBS has impeded its treatment.Here,we report that the E3 ubiquitin ligase tripartite motif-containing 27(TRIM27)is weakly expressed in IBS but highly expressed in inflammatory bowel disease(IBD),a frequent chronic organic gastrointestinal disorder.Accordingly,knockout of Trim27 in mice causes spontaneously occurring IBS-like symptoms,including increased visceral hyperalgesia and abnormal stool features,as observed in IBS patients.Mechanistically,TRIM27 stabilizesβ-catenin and thus activates Wnt/β-catenin signaling to promote intestinal stem cell(ISC)self-renewal.Consistent with these findings,Trim27 deficiency disrupts organoid formation,which is rescued by reintroducing TRIM27 orβ-catenin.Furthermore,Wnt/β-catenin signaling activator treatment ameliorates IBS symptoms by promoting ISC self-renewal.Taken together,these data indicate that TRIM27 is critical for maintaining gut homeostasis,suggesting that targeting the TRIM27/Wnt/β-catenin axis could be a potential treatment strategy for IBS.Our study also indicates that TRIM27 might serve as a potential biomarker for differentiating IBS from IBD. | Jing Wang Dongdong Zhao Zehui Lei Pupu Ge Zhe Lu Qiyao Chai Yong Zhang Lihua Qiang Yang Yu Xinwen Zhang Bingxi Li Shu Zhu Lingqiang Zhang Cui Hua Liu | 2023 | Cellular & Molecular Immunology2023，20，2： | 2 |
| 8 | Differential regulation of Apak by various DNA damage signals显示文摘 | Shan Wang Chunyan Tian Tingtiang Xiao Guichun Xing Fuchu He Lingqiang Zhang Hong Chen | 2010 | Molecular and Cellular Biochemistry (-)2010，，1： | 1 |
| 9 | Increased FoxM1 expression is a target for metformin in the suppressionof EMT in prostate cancer显示文摘 | Yiru Wang Binwei Yao Yu Wang Mingbo Zhang Shuai Fu Hanjing Gao Ruiyun Peng Lingqiang Zhang Jie Tang | 2014 | International Journal of Molecular Medicine2014，，6： | 1 |
| 10 | KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration显示文摘 | Shan Wang Zhiqiang Peng Siying Wang Lihua Yang Yuhan Chen Xue Kong Shanshan Song Pei Pei Chunyan Tian Hui Yan Peipei Ding Weiguo Hu Cui Hua Liu Xin Zhang Fuchu He Lingqiang Zhang | 2018 | Cell Research2018，28，5： | 1 |
| 11 | Modeling the Warming Impact of Urban Land Expansion on Hot Weather Using the Weather Research and Forecasting Model: A Case Study of Beijing, China显示文摘The impacts of three periods of urban land expansion during 1990–2010 on near-surface air temperature in summer in Beijing were simulated in this study, and then the interrelation between heat waves and urban warming was assessed. We ran the sensitivity tests using the mesoscale Weather Research and Forecasting model coupled with a single urban canopy model,as well as high-resolution land cover data. The warming area expanded approximately at the same scale as the urban land expansion. The average regional warming induced by urban expansion increased but the warming speed declined slightly during 2000–2010. The smallest warming occurred at noon and then increased gradually in the afternoon before peaking at around 2000 LST—the time of sunset. In the daytime, urban warming was primarily caused by the decrease in latent heat flux at the urban surface. Urbanization led to more ground heat flux during the day and then more release at night, which resulted in nocturnal warming. Urban warming at night was higher than that in the day, although the nighttime increment in sensible heat flux was smaller. This was because the shallower planetary boundary layer at night reduced the release efficiency of near-surface heat. The simulated results also suggested that heat waves or high temperature weather enhanced urban warming intensity at night. Heat waves caused more heat to be stored in the surface during the day, greater heat released at night, and thus higher nighttime warming. Our results demonstrate a positive feedback effect between urban warming and heat waves in urban areas. | Xiaojuan LIU Guangjin TIAN Jinming FENG Bingran MA Jun WANG Lingqiang KONG | 2018 | Advances in Atmospheric Sciences2018，35，6： | 1 |
| 12 | Using the Cooperative Game for Service Placement of Virtual Network Functions显示文摘To address the issues that middleboxes as a fundamental part of today's networks are facing, Network Function Virtualization(NFV)has been recently proposed, which in essence asserts to migrate hardware-based middleboxes into software-based virtualized function entities.Due to the demands of virtual services placement in NFV network environment, this paper models the service amount placement problem involving with the resources allocation as a cooperative game and proposes the placement policy by Nash Bargaining Solution(NBS). Specifically,we first introduce the system overview and apply the rigorous cooperative game-theoretic guide to build the mathematical model, which can give consideration to both the responding efficiency of service requirements and the allocation fairness.Then a distributed algorithm corresponding to NBS is designed to achieve predictable network performance for virtual instances placement.Finally, with simulations under various scenarios,the results show that our placement approach can achieve high utilization of network through the analysis of evaluation metrics namely the satisfaction degree and fairness index. With the suitable demand amount of services, the average values of two metrics can reach above 90%. And by tuning the base placement, our solution can enable operators to flexibly balance the tradeoff between satisfaction and fairness of resourcessharing in service platforms. | XIONG Gang HU Yuxiang WANG Weiming WANG Lingqiang | 2016 | China Communications2016，13，S1： | 1 |
| 13 | N-methylpurine DNA glycosylase inhibits p53-mediated cell cycle arrest and coordinates with p53 to determine sensitivity to alkylating agents显示文摘Alkylating 代理人导致染色体宽的基础损坏,它主要被 N-methylpurine DNA glycosylase (MPG ) 修理。因为导致 MPG 的 apurinic/apyrimidic (AP ) 地点触发更多的海滨裂缝,在肿瘤房间的某些类型的 MPG 的提高的表情授与更高的敏感到完化代理人。然而,药敏感或 insensitivity 的决定因素仍然保持不清楚。这里,我们报导 p53 地位与 MPG 协调在如此的过程起一个枢轴的作用。MPG 表示在胸,肺和结肠癌是积极的(38.7% , 43.4% 和 25.3% ,分别地) 但是在所有邻近的正常纸巾否定。MPG 直接绑在肿瘤 suppressor p53 并且镇压在不着重的房间的 p53 活动。而 MPG 的弄空增加了,减少的 MPG 的 overexpression,包括 p21 的 p53 下游的支持拘捕的基因的表示层次, 14-3-3 σ并且 Gadd45 然而并非 proapoptotic。MPG 的 N 终端区域明确地为和 p53 的 DNA 有约束力的域的相互作用被要求。在 DNA 完化应力之上,在 p53 野类型的肿瘤房间, p53 从 MPG 分裂了并且导致了房间生长拘捕。然后, AP 地点高效地被修理,它导致了 insensitivity 到 alkylating 代理人。由对比,在变异 p53 的房间, AP 地点与低功效被修理。到我们的知识,当 p53 的一个选择管理者,和这些调查结果在癌症治疗提供新卓见进在 MPG 和 p53 之间的功能的连接,这是第一条直接证据证明 DNA 修理酶功能。 | Shanshan Song Guichun Xing Lin Yuan Jian Wang Shan Wang Yuxin Yin Chunyan Tian Fuchu He Lingqiang Zhang | 2012 | Cell Research2012，22，8： | 1 |
| 14 | Differential regulation of Apak by various DNA damage signals显示文摘 | Shan Wang Chunyan Tian Tingtiang Xiao Guichun Xing Fuchu He Lingqiang Zhang Hong Chen | 2010 | Molecular and Cellular Biochemistry (-)2010，，1： | 1 |
| 15 | Novel thioxanthone host material with thermally activated delayed fluorescence for reduced efficiency roll-off of phosphorescent OLEDs显示文摘2,7-Di(9,9-dimethyl-9 H-fluoren-1-yl)-9 H-thioxanthen-9-one(DMBFTX) with thermally activated delayed fluorescence(TADF) was well designed and synthesized. The phosphorescent organic lightemitting device(PHOLED) based on this novel TADF host material displays a stable red phosphorescence region, a peak external quantum efficiency(EQE) value of 12.9% and a low EQE roll-off of 38.8% at a luminance of 10000 cd/m^2, which is benefited from the reverse intersystem crossing(RISC) of TADF host and less populated triplet exitons. Notably, the red device based on the TADF host DMBFTX exhibits superior electroluminescence performance and reduced efficiency roll-off compared with the one hosted by commercially available host 1,3-bis(9-carbazolyl)benzene(mCP), illustrating the high potential of employing the TADF host material with small energy gap to reduce efficiency roll-off in PHOLED. | Hui Wang Xiaopeng Lv Lingqiang Meng Xiaofang Wei Ying Wang Pengfei Wang | 2018 | Chinese Chemical Letters2018，29，3： | 1 |
| 16 | The deubiquitylase UCHL3 maintains cancer stem-like properties by stabilizing the aryl hydrocarbon receptor显示文摘Cancer stem cells(CSCs)exhibit highly aggressive and metastatic features and resistance to chemotherapy and radiotherapy.Aryl hydrocarbon receptor(AhR)expression varies among non-small cell lung cancers(NSCLCs),and the mechanisms that support abnormal AhR expression in CSCs remain elusive.Here,we identified ubiquitin carboxyl terminal hydrolase L3(UCHL3),a DUB enzyme in the UCH protease family,as a bona fide deubiquitylase of the AhR in NSCLC.UCHL3 was shown to interact with,deubiquitylate,and stabilize AhR in a manner dependent on its deubiquitylation activity.Moreover,we showed that UCHL3 promotes the stem-like characteristics and potent tumorigenic capacity of NSCLC cells.UCHL3 increased AhR stability and the binding of AhR to the promoter regions of the“stemness”genes ATP-binding cassette subfamily G member 2(ABCG2),KLF4,and c-Myc.Depletion of UCHL3 markedly downregulated the“stemness”genes ABCG2,KLF4,and c-Myc,leading to the loss of selfrenewal and tumorigenesis in NSCLCs.Furthermore,the UCHL3 inhibitor TCID induced AhR degradation and exhibited significantly attenuated efficacy in NSCLC cells with stem cell-like properties.Additionally,UCHL3 was shown to indicate poor prognosis in patients with lung adenocarcinoma.In general,our results reveal that the UCHL3 deubiquitylase is pivotal for AhR protein stability and a potential target for NSCLC-targeted therapy. | Lianlian Ouyang Bin Yan Yating Liu Chao Mao Min Wang Na Liu Zuli Wang Shouping Liu Ying Shi Ling Chen Xiang Wang Yan Cheng Ya Cao Desheng Xiao Lingqiang Zhang Shuang Liu Yongguang Tao | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 1 |
| 17 | Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation显示文摘 | Shan Li Kefeng Lu Jian Wang Liguo An Guiwen Yang Hui Chen Yu Cui Xiushan Yin Ping Xie Guichun Xing Fuchu He Lingqiang Zhang | 2010 | Molecular and Cellular Biochemistry (-)2010，，1： | 1 |
| 18 | USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency显示文摘The homeobox transcription factor Nanog has a vital role in maintaining pluripotency and self-renewal of embryonic stem cells(ESCs).Stabilization of Nanog proteins is essential for ESCs.The ubiquitin–proteasome pathway mediated by E3 ubiquitin ligases and deubiquitylases is one of the key ways to regulate protein levels and functions.Although ubiquitylation of Nanog catalyzed by the ligase FBXW8 has been demonstrated,the deubiquitylase that maintains the protein levels of Nanog in ESCs yet to be defined.In this study,we identify the ubiquitin-specific peptidase 21(USP21)as a deubiquitylase for Nanog,but not for Oct4 or Sox2.USP21 interacts with Nanog protein in ESCs in vivo and in vitro.The C-terminal USP domain of USP21 and the C-domain of Nanog are responsible for this interaction.USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog,stabilizing Nanog.USP21-mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs.Depletion of USP21 in mouse ESCs leads to Nanog degradation and ESC differentiation.Overall,our results demonstrate that USP21 maintains the stemness of mouse ESCs through deubiquitylating and stabilizing Nanog. | Xingyu Liu Yuying Yao Huiguo Ding Chuanchun Han Yuhan Chen Yuan Zhang Chanjuan Wang Xin Zhang Yiling Zhang Yun Zhai Ping Wang Wenyi Wei Jing Zhang Lingqiang Zhang | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 1 |
| 19 | Characteristics of the three-dimensional deep electrical structure in the Helan Mountains-Yinchuan Basin and its geodynamic implications显示文摘Located in the north segment of the North-South seismic belt where the Alxa block(AB)and the Ordos block(OB)contact,the Helan Mountains-Yinchuan Basin(HLM-YCB)constitutes a typical normal faulting basin-mountain structure on the Chinese mainland.The 1739 M8.0 Pingluo earthquake occurred in the Yinchuan fault depression basin with such a basinmountain structure.Data on five magnetotelluric profiles encompassing distinct segments of the HLM-YCB were utilized for three-dimensional(3D)joint inversion in order to collect fine 3D electrical structure information at a crustal and upper mantle scale across the entire region.The electrical structure between the main blocks in the HLM-YCB and adjacent areas is characterized by east-west horizontal blocks OB,YCB,and HLM,which are divided by the Yellow River fault(F5)with the HLM eastern piedmont fault(F2)as electrical boundary zones on the east and west sides.The two main block units,AB and OB,exhibit an obvious layered resistivity structure.Besides,the HLM-YCB is characterized by a typical basin-mountain structure with the mountains as a high-resistivity body and the basin as a low-resistivity body,and in the northern YCB a large-scale lowresistivity structure exists,extending to the upper mantle,probably derived from the upwelling of mantle-derived materials.It is speculated from a combination of recent 3D crustal movement field information and other data that the HLM-YCB is an active tectonic zone formed via regional tensile action.The formation of the HLM-YCB lies in the interaction of the Tibetan Plateau(TP),AB,and OB and abnormal mantle activities beneath the YCB.The HLM-YCB reflects the joint action of upwelling and diffluence caused by the underplating of hot materials from the deep mantle with gravity and the redistribution of regional tectonic stress on the earth’s surface,which may be the main dynamic reason for the 1739 M8.0 Pingluo earthquake. | Lingqiang ZHAO Xiangyu SUN Yan ZHAN Jing HAN Haibo YANG Peijie WANG Xuehua LIU | 2023 | Science China Earth Sciences2023，66，3： | 0 |
| 20 | Fully synthetic Tn-based three-component cancer vaccine using covalently linked TLR4 ligand MPLA and iNKT cell agonist KRN-7000 as built-in adjuvant effectively protects mice from tumor development显示文摘We present a new strategy for self-adjuvanting vaccine development that has different types of covalently-linked immunostimulants as the carrier molecule.Using Tn antigen as the model,a three-component vaccine(MPLA-Tn-KRN7000)containing the TLR4 ligand MPLA and the iNKT cell agonist KRN7000 was designed and synthesized.This expands fully synthetic self-adjuvanting vaccine studies that use a single carrier to one with two different types of carriers.The corresponding two-component conjugate vaccines Tn-MPLA,Tn-KRN7000 and Tn-CRM197 were also synthesized,as controls.The immunological evaluation found that MPLA-Tn-KRN7000 elicits robust Tn-specific and T cell-dependent immunity.The antibodies specifically recognized,bound to and exhibited complement-dependent cytotoxicity against Tn-positive cancer cells.In addition,MPLA-Tn-KRN7000 increased the survival rate and survival time of tumor-challenged mice,and surviving mice reject further tumor attacks without any additional treatment.Compared to the glycoprotein vaccine Tn-CRM197,the two-component conjugate vaccines,Tn-MPLA and Tn-KRN7000,and the physical mixture of Tn-MPLA and Tn-KRN7000,MPLA-Tn-KRN7000 showed the most effect at combating tumor cells both in vitro and in vivo.The comparison of immunological studies in wild-type and TLR4 knockout mice,along with the test of binding affinity to CD1d protein suggests that the covalently linked MPLA-KRN7000 immunostimulant induces a synergistic activation of TLR4 and iNKT cell that improves the immunogenicity of Tn.This work demonstrates that MPLA-Tn-KRN7000 has the potential to be a vaccine candidate and provides a new direction for fully synthetic vaccine design. | Deying Yang Xiang Luo Qinghai Lian Lingqiang Gao Chengxin Wang Xiaoxiao Qi Rong Zhang Zhongqiu Liu Guochao Liao | 2022 | Acta Pharmaceutica Sinica B2022，12，12： | 0 |
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