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| 1 | A novel cancer vaccine with the ability to simultaneously produce anti-PD-1 antibody and GM-CSF in cancer cells and enhance Th1-biased antitumor immunity显示文摘Tumor escape from immune-mediated destruction has been associated with immunosuppressive mechanisms that inhibit T-cell activation.A promising strategy for cancer immunotherapy is to disrupt key pathways regulating immune tolerance,such as program death-1(PD-1/PD-L1)pathway in the tumor environment.However,the determinants of response to anti-PD-1 monoclonal antibodies(mAbs)treatment remain incompletely understood.In murine models,PD-1 blockade alone fails to induce effective immune responses to poorly immunogenic tumors,but is successful when combined with additional interventions,such as cancer vaccines.Novel cancer vaccines combined with antibody may offer promising control of cancer development and progression.In this investigation,we generated a novel tumor cell vaccine simultaneously expressing anti-PD-1 mAbs and granulocyte-macrophage colony stimulating factor(GM-CSF)in CT26 colon cancer and B16-F10 melanoma.The antitumor effect of the vaccine was verified by therapeutic and adoptive animal experiments in vivo.The antitumor mechanism was analyzed using Flow cytometry,Elispot and in vivo intervention approaches.The results showed that tumor cell vaccine secreting PD-1 neutralizing antibodies and GM-CSF induced remarkable antitumor immune effects and prolonged the survival of tumor-bearing animals compared with animals treated with either PD-1 mAbs or GM-CSF alone.Antitumor effects and prolonged survival correlated with strong antigen-specific T-cell responses by analyzing CD11c^(+)CD86^(+)DC,CD11b^(+)F4/80^(+)MΦcells,increased ratio of Teff/Treg in the tumor microenvironment,and higher secretion levels of Th1 proinflammatory cytokines in serum.Furthermore,the results of ELISPOT and in vivo blocking strategies further confirmed that the antitumor immune response is acquired by CD4 and CD8 T immune responses,primarily dependent on CD4 Th1 immune response,not NK innate immune response.The combination of PD-1 blockade with GM-CSF secretion potency creates a novel tumor cell vaccine immunotherapy,affording significantly improved antitumor responses by releasing the state of immunosuppressive microenvironment and augmenting the tumor-reactive T-cell responses. | Hongwei Tian Gang Shi Qin Wang Yiming Li Qianmei Yang Chunlei Li Guoyou Yang Min Wu Qian Xie Shuang Zhang Yang Yang Rong Xiang Dechao Yu Yuquan Wei Hongxin Deng | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 3 |
| 2 | The Matrix Stiffness and Physical Confinement of Hydrogel Microchannel Jointly Induce the Mesenchymal-Amoeboid Transition for Cancer Cell Migration显示文摘The migration mode transition of cancer cell enhances its invasive capability and the drug resistance,where physical confinement of cell microenvironment has been revealed to induce the mesenchymal-amoeboid transition(MAT).However,most existing studies are performed in PDMS microchannels,of which the stiffness is much higher than that of most mammalian tissues.Therefore,the amoeboid migration transition observed in these studies is actually induced by the synergistic effect of matrix stiffness and confinement.Since the stiffness of cell microenvironment has been reported to influence the cell migration in 2D substrate,the decoupling of stiffness and confinement effects is thus in need for elucidating the underlying mechanism of MAT.However,it is technically challenging to construct microchannels with physiologically relevant stiffness and channel size,where existing microchannel platforms with physiological relevance stiffness are all with>10μm channel width.Such size is too wide to mimic the physical confinement that migrating cancer cells confront in vivo,and also larger than the width of PDMS channel,in which the MAT of cancer cell was observed.Therefore,an in vitro cell migration platform,which could mimic both stiffness and confinement of the native physical microenvironment during cancer metastasis,could profoundly contribute to researches on cancer cell migration and cellular mechanotransduction.In this paper,we overcome the limitations of engineering soft materials in microscale by combining the collagen-alginate hydrogel with photolithography.This enables us to improve the accuracy of molded microchannel,and thus successfully construct a 3D microchannel platform,which matches the stiffness and width ranges of native environmental confinement that migrating cancer cells confront in vivo.The stiffness(0.3~20 kPa),confinement(channel width:3.5~14μm)and the adhesion ligand density of the microchannel can be tuned independently.Interestingly,using this platform,we observed that the migration speed of cancer cell is influenced by the synergistic effect of channel stiffness and width,and the increasing stiffness reverses the effect of channel width on the migration speed of cancer cells.In addition,MAT has a strong correlation with the channel stiffness.These findings make us reconsider the widely accepted hypothesis:physical confinement can induce MAT.Actually,this transition can only occur in stiff confined microenvironment not in soft one.For soft microchannels,the compliance of the channel walls could cause little cell/nucleus deformation,and the MAT could not be induced.To further investigate the mechanism of MAT,we developed a computational model to simulate the effect of nucleus deformation on MAT.With the model,we found that deforming the cell nuclear by decreasing the nucleus stiffness will reduce the cellmigration speed.This implies that nuclear stiffness plays an important role in the regulation of cancer migration speed and thus MAT in microchannels.The effect of channel stiffness on MAT and migration speed as observed in our experiment could partially explain previous findings reported in the literature,where the increasing matrix stiffness of tumor microenvironment promotes cancer metastasis.Our observations thus highlight the critical role of cell nuclear deformation not only in MAT,but also in regulating cellular mechanotransduction and cell-ECM interactions.This developed platform is capable of mimicking the native physical microenvironment during metastasis,providing a powerful tool for high-throughput screening applications and investigating the interaction between cancer migration and biophysical microenvironment. | Meng Wang Bo Cheng Yaowei Yang Han Liu Guoyou Huang Fei Li Feng Xu | 2019 | 医用生物力学2019，34，A01： | 2 |
| 3 | Boundary Element Analysis of Fluid Dynamics of Complex Shapaed Bearing显示文摘 | Yang Dequan Zhang Guoyou | 1991 | Computational Mechanics1991，2，： | 1 |
| 4 | Common Statistical Methods and Reporting of Results in Medical Research显示文摘Statistical analysis is critical in medical research.The objective of this article is to summarize the appropriate use and reporting of commonly used statistical methods in medical research,on the basis of existing statistical guidelines and the authors’experience in reviewing manuscripts,to provide recommendations for statistical applications and reporting. | Guoshuang Feng Guoyou Qin Tao Zhang Zheng Chen Yang Zhao | 2022 | Cardiovascular Innovations and Applications2022，，1： | 1 |
| 5 | Effect of introducing Bacillus thuringiensis gene on nitrogen metabolism in cotton显示文摘 | CHEN Dehua Ye Guoyou Yang Changqin | 2004 | Field Crops Research2004，87，4： | 1 |
| 6 | Boundary Element Analysis of Fluid Dynamics of Complex Shapaed Bearing显示文摘 | Yang Dequan Zhang Guoyou | 1991 | Computational Mechanics1991，2，： | 1 |
| 7 | Numerical Analysis of Hydrodynamics of Floating-ring Bearing显示文摘 | Yang Dequan Zhang Guoyou Lv Shuhui | 2004 | Beijing: ICCP- 6CCP20032004，，5： | 1 |
| 8 | Spectra of p-^(11)B Three-Body Sequential Decay Reaction | Yuan Jian Liu Xiaodong Xu Guoji Sun Zuxun China Institute of Atomic Energy,Beijing 102413Lin Erhkang Wang Changwan Yu Yuehchung Liu Tongyuan Institute of Physics,Academia Sinica,Taipei 11529Tang Guoyou Shi Zhaomin Chen Jinxiang Gong Linghua Yang Qixiang Institute of Heavy Ion Physics,Peking University,Beijing 100871Zhang Peihua Graduate School,the Chinese Academy of Sciences,P.O.Box 3908,Beiting 100039 | 1997 | Chinese journal of nuclear physics1997，，4： | 0 |
| 9 | Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma显示文摘Previous studies suggest that the reduction of SMAD3(mothers against decapentaplegic homolog 3)has a great impact on tumor development,but its exact pathological function remains unclear.In this study,we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues,in which LAMP2A(lysosome-associated membrane protein type 2A)was significantly up-regulated.LAMP2A is a key ratelimiting protein of chaperone-mediated autophagy(CMA),a lysosome pathway of protein degradation that is activated in glioma.We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ,which has been proposed to be a targeting sequence for CMA.In vitro,we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition,which was regulated by LAMP2A and interacted with HSC70(heat shock cognate 71 kDa protein).Using isolated lysosomes,amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process,which affected the CMA pathway in which SMAD3 was involved.Similarly,down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion.Taken together,these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3.Therefore,targeting the SMAD3-LAMP2Amediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy. | Hanqun Liu Yuxuan Yong Xingjian Li Panghai Ye Kai Tao Guoyou Peng Mingshu Mo Wenyuan Guo Xiang Chen Yangfu Luo Yuwan Lin Jiewen Qiu Ziling Zhang Liuyan Ding Miaomiao Zhou Xinling Yang Lin Lu Qian Yang Pingyi Xu | 2022 | Neuroscience Bulletin2022，38，6： | 0 |
| 10 | Global energy transition revolution and the connotation and pathway of the green and intelligent energy system显示文摘The essence of energy system transition is the'energy revolution':The development of the'resource-dominated'energy system with fossil energy as the mainstay has promoted human progress,but it has also triggered energy crisis and ecological environment crisis,which is not compatible with the new demands of the new round of scientific and technological revolution,industrial transformation,and sustainable human development.It is in urgent need to research and develop a new-type energy system in the context of carbon neutrality.In the framework of'technique-dominated'new green and intelligent energy system with'three new'of new energy,new power and new energy storage as the mainstay,the'super energy basin'concepts with the Ordos Basin,Nw China as a representative will reshape the concept and model of future energy exploration and development.In view of the'six inequalities'in global energy and the resource conditions of'abundant coal,insufficient oil and gas and infinite new energy'in China,it is suggested to deeply boost'China energy revolution',sticking to the six principles of independent energy production,green energy supply,secure energy reserve,efficient energy consumption,intelligent energy management,economical energy cost;enhance'energy scientific and technological innovation'by implementing technique-dominated'four major science and technology innovation projects',namely,clean coal project,oil production stabilization and gas production increasing project,new energy acceleration project,and green-intelligent energy project;implement'energy transition'by accelerating the green-dominated'four-modernization development',namely,fossil energy cleaning,large-scale new energy,coordinated centralized energy distribution,intelligent multi-energy management,so as to promote the exchange of two 80%s'in China's energy structure and construct the new green and intelligent energy system. | ZOU Caineng MA Feng PAN Songqi ZHAO Qun FU Guoyou ZHANG Guosheng YANG Yichao YU Hao LIANG Yingbo LIN Minjie WANG Ying XIONG Bo LIU Hanlin | 2023 | Petroleum Exploration and Development2023，50，3： | 0 |
| 11 | miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma显示文摘Introduction:Hepatoblastoma(HB)is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients.The precise molecular mechanisms responsible for HB metastasis remain incom-pletely understood.However,there is evidence suggesting a connection between the dysregulation of microRNAs(miRNAs)and the progression of tumor metastasis in HB.Methods:The study utilized weighted gene co-expression network analysis(WGCNA)to analyze a miRNA microarray dataset of HB.The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR.The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays.The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo.Furthermore,a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB.Results:We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines.Overexpression of miR-181b enhanced scratch healing,cell migration,and invasion abilities in vitro,as well as enhancing HB lung metastasis potential in vivo.Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2(SOCS2)was a direct target of miR-181b.The overexpression of miR-181b resulted in the suppression of SOCS2 expression,subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways.The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells.Conclusion:Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB. | Yong Lv Xiaolong Xie Guoyou Zou Meng Kong Jiayin Yang Jing Chen Bo Xiang | 2023 | Precision Clinical Medicine2023，6，4： | 0 |
| 12 | Genome-wide selection and introgression of Chinese rice varieties during breeding显示文摘China is the largest rice-producing country,but the genomic landscape of rice diversity has not yet been clarified.In this study,we re-sequence 1070 rice varieties collected from China(400)and other regions in Asia(670).Among the six major rice groups(aus,indica-I,indica-II,aromatic,temperate japonica,and tropical japonica),almost all Chinese varieties belong to the indica-II or temperate japonica group.Most Chinese indica varieties belong to indica-II,which consists of two subgroups developed during different phases of rice breeding.The genomic segments underlying the differences between these subgroups span36.32 Mb.The Chinese japonica rice varieties fall into the temperate japonica group,consisting of two subgroups based on their geographical distribution.The genomic segments underlying the differences between these subgroups span 27.69 Mb.These differentiated segments in the Chinese indica varieties span 45 genes with nonsynonymous mutations that are closely related to variations in plant height and grain width.Fifty-four genes with nonsynonymous mutations are associated with the differences in heading date between the two Chinese japonica subgroups.These findings provide new insights into rice diversity in China that will facilitate the molecular breeding. | Jinyue Ge Junrui Wang Hongbo Pang Fei Li Danjing Lou Weiya Fan Ziran Liu Jiaqi Li Danting Li Baoxuan Nong Zongqiong Zhang Yanyan Wang Jingfen Huang Meng Xing Yamin Nie Xiaorong Xiao Fan Zhang Wensheng Wang Jianlong Xu Sung Ryul Kim Ajay Kohli Guoyou Ye Weihua Qiao Qingwen Yang Xiaoming Zheng | 2022 | Journal of Genetics and Genomics2022，49，5： | 0 |
| 13 | Identification of QTLs for Cadmium Tolerance During Seedling Stage and Validation of qCDSL1 in Rice显示文摘Cadmium(Cd)is a non-essential toxic metal that is harmful to plants.To investigate the genetic mechanism of Cd tolerance in rice,quantitative trait loci(QTLs)associated with Cd tolerance at the seedling stage were analyzed using a recombinant inbred line(RIL)population derived from a cross between PA64s and 93-11.A total of 36 QTLs associated with shoot length,root length,shoot dry weight,root dry weight and total dry weight were detected in Hangzhou and Lingshui of China.Among them,15 QTLs were identified under the control condition and 15 QTLs were identified under the Cd stress condition,and 6 QTLs for Cd tolerant coefficient were detected on chromosomes 1,3,7 and 9.The qCDSL1.1 and qCDSL1.2 were identified in Hangzhou and Lingshui,respectively,and had overlapping intervals on chromosome 1.To further confirm the effects of qCDSL1.1 and qCDSL1.2,we developed a chromosome segment substitution line(CSSL),CSSLqCDSL1,in 93-11 background harboring qCDSL1.1/qCDSL1.2 from PA64s.Compared to 93-11,CSSLqCDSL1 had increased shoot length under the Cd stress condition.These results pave the way for further isolation of those genes controlling Cd tolerance in rice and marker-assistant selection of rice elite varieties with Cd tolerance. | Ding Shilin Liu Chaolei Shang Lianguang Yang Shenglong Zhang Anpeng Jiang Hongzhen Ruan Banpu Fang Guonan Tian Biao Ye Guoyou Guo Longbiao Qian Qian Gao Zhenyu | 2021 | Rice science2021，28，1： | 0 |
| 14 | Author Correction: A novel cancer vaccine with the ability to simultaneously produce anti-PD-1 antibody and GM-CSF in cancer cells and enhance Th1-biased antitumor immunity显示文摘Correction to:Signal Transduction and Targeted Therapy(2016)1:16025 http://gffzzd3cc09b8251d45dfs5pf05qn65nuw6cnf.ffgz.tsg.suse.edu.cn/10.1038/sigtrans.2016.25,published online 18 November 2016 Since the publication of this research Article,we retrospected the paper and noticed two inadvertent mistakes that need to be corrected immediately.We have checked the original data and repeated the experiments;the correct data are provided in this Corrigendum as follows.The key findings of the article are not affected by these corrections. | Hongwei Tian Gang Shi Qin Wang Yiming Li Qianmei Yang Chunlei Li Guoyou Yang Min Wu Qian Xie Shuang Zhang Yang Yang Rong Xiang Dechao Yu Yuquan Wei Hongxin Deng | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 0 |
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