Search

Your search keyword '"Du, Guoqing"' showing total 163 results
Start Over Author "Du, Guoqing" Search Limiters Available in Library Collection
163 results on '"Du, Guoqing"'

1. PET-SQL: A Prompt-Enhanced Two-Round Refinement of Text-to-SQL with Cross-consistency

Author

Li, Zhishuai, Wang, Xiang, Zhao, Jingjing, Yang, Sun, Du, Guoqing, Hu, Xiaoru, Zhang, Bin, Ye, Yuxiao, Li, Ziyue, Zhao, Rui, and Mao, Hangyu

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence
Abstract

Recent advancements in Text-to-SQL (Text2SQL) emphasize stimulating the large language models (LLM) on in-context learning, achieving significant results. Nevertheless, they face challenges when dealing with verbose database information and complex user intentions. This paper presents a two-stage framework to enhance the performance of current LLM-based natural language to SQL systems. We first introduce a novel prompt representation, called reference-enhanced representation, which includes schema information and randomly sampled cell values from tables to instruct LLMs in generating SQL queries. Then, in the first stage, question-SQL pairs are retrieved as few-shot demonstrations, prompting the LLM to generate a preliminary SQL (PreSQL). After that, the mentioned entities in PreSQL are parsed to conduct schema linking, which can significantly compact the useful information. In the second stage, with the linked schema, we simplify the prompt's schema information and instruct the LLM to produce the final SQL. Finally, as the post-refinement module, we propose using cross-consistency across different LLMs rather than self-consistency within a particular LLM. Our methods achieve new SOTA results on the Spider benchmark, with an execution accuracy of 87.6%.

Published
2024

2. Benchmarking the Text-to-SQL Capability of Large Language Models: A Comprehensive Evaluation

Author

Zhang, Bin, Ye, Yuxiao, Du, Guoqing, Hu, Xiaoru, Li, Zhishuai, Yang, Sun, Liu, Chi Harold, Zhao, Rui, Li, Ziyue, and Mao, Hangyu

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence
Abstract

Large Language Models (LLMs) have emerged as a powerful tool in advancing the Text-to-SQL task, significantly outperforming traditional methods. Nevertheless, as a nascent research field, there is still no consensus on the optimal prompt templates and design frameworks. Additionally, existing benchmarks inadequately explore the performance of LLMs across the various sub-tasks of the Text-to-SQL process, which hinders the assessment of LLMs' cognitive capabilities and the optimization of LLM-based solutions. To address the aforementioned issues, we firstly construct a new dataset designed to mitigate the risk of overfitting in LLMs. Then we formulate five evaluation tasks to comprehensively assess the performance of diverse methods across various LLMs throughout the Text-to-SQL process.Our study highlights the performance disparities among LLMs and proposes optimal in-context learning solutions tailored to each task. These findings offer valuable insights for enhancing the development of LLM-based Text-to-SQL systems., Comment: 26pages, 6figures, 14tables

Published
2024

3. VisionTraj: A Noise-Robust Trajectory Recovery Framework based on Large-scale Camera Network

Author

Li, Zhishuai, Li, Ziyue, Hu, Xiaoru, Du, Guoqing, Nie, Yunhao, Zhu, Feng, Bai, Lei, and Zhao, Rui

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence, Computer Science - Information Retrieval, Computer Science - Machine Learning
Abstract

Trajectory recovery based on the snapshots from the city-wide multi-camera network facilitates urban mobility sensing and driveway optimization. The state-of-the-art solutions devoted to such a vision-based scheme typically incorporate predefined rules or unsupervised iterative feedback, struggling with multi-fold challenges such as lack of open-source datasets for training the whole pipeline, and the vulnerability to the noises from visual inputs. In response to the dilemma, this paper proposes VisionTraj, the first learning-based model that reconstructs vehicle trajectories from snapshots recorded by road network cameras. Coupled with it, we elaborate on two rational vision-trajectory datasets, which produce extensive trajectory data along with corresponding visual snapshots, enabling supervised vision-trajectory interplay extraction. Following the data creation, based on the results from the off-the-shelf multi-modal vehicle clustering, we first re-formulate the trajectory recovery problem as a generative task and introduce the canonical Transformer as the autoregressive backbone. Then, to identify clustering noises (e.g., false positives) with the bound on the snapshots' spatiotemporal dependencies, a GCN-based soft-denoising module is conducted based on the fine- and coarse-grained Re-ID clusters. Additionally, we harness strong semantic information extracted from the tracklet to provide detailed insights into the vehicle's entry and exit actions during trajectory recovery. The denoising and tracklet components can also act as plug-and-play modules to boost baselines. Experimental results on the two hand-crafted datasets show that the proposed VisionTraj achieves a maximum +11.5% improvement against the sub-best model.

Published
2023

4. TPTU-v2: Boosting Task Planning and Tool Usage of Large Language Model-based Agents in Real-world Systems

Author

Kong, Yilun, Ruan, Jingqing, Chen, Yihong, Zhang, Bin, Bao, Tianpeng, Shi, Shiwei, Du, Guoqing, Hu, Xiaoru, Mao, Hangyu, Li, Ziyue, Zeng, Xingyu, and Zhao, Rui

Subjects
Computer Science - Artificial Intelligence
Abstract

Large Language Models (LLMs) have demonstrated proficiency in addressing tasks that necessitate a combination of task planning and the usage of external tools that require a blend of task planning and the utilization of external tools, such as APIs. However, real-world complex systems present three prevalent challenges concerning task planning and tool usage: (1) The real system usually has a vast array of APIs, so it is impossible to feed the descriptions of all APIs to the prompt of LLMs as the token length is limited; (2) the real system is designed for handling complex tasks, and the base LLMs can hardly plan a correct sub-task order and API-calling order for such tasks; (3) Similar semantics and functionalities among APIs in real systems create challenges for both LLMs and even humans in distinguishing between them. In response, this paper introduces a comprehensive framework aimed at enhancing the Task Planning and Tool Usage (TPTU) abilities of LLM-based agents operating within real-world systems. Our framework comprises three key components designed to address these challenges: (1) the API Retriever selects the most pertinent APIs for the user task among the extensive array available; (2) LLM Finetuner tunes a base LLM so that the finetuned LLM can be more capable for task planning and API calling; (3) the Demo Selector adaptively retrieves different demonstrations related to hard-to-distinguish APIs, which is further used for in-context learning to boost the final performance. We validate our methods using a real-world commercial system as well as an open-sourced academic dataset, and the outcomes clearly showcase the efficacy of each individual component as well as the integrated framework.

Published
2023

5. TPTU: Large Language Model-based AI Agents for Task Planning and Tool Usage

Author

Ruan, Jingqing, Chen, Yihong, Zhang, Bin, Xu, Zhiwei, Bao, Tianpeng, Du, Guoqing, Shi, Shiwei, Mao, Hangyu, Li, Ziyue, Zeng, Xingyu, and Zhao, Rui

Subjects
Computer Science - Artificial Intelligence
Abstract

With recent advancements in natural language processing, Large Language Models (LLMs) have emerged as powerful tools for various real-world applications. Despite their prowess, the intrinsic generative abilities of LLMs may prove insufficient for handling complex tasks which necessitate a combination of task planning and the usage of external tools. In this paper, we first propose a structured framework tailored for LLM-based AI Agents and discuss the crucial capabilities necessary for tackling intricate problems. Within this framework, we design two distinct types of agents (i.e., one-step agent and sequential agent) to execute the inference process. Subsequently, we instantiate the framework using various LLMs and evaluate their Task Planning and Tool Usage (TPTU) abilities on typical tasks. By highlighting key findings and challenges, our goal is to provide a helpful resource for researchers and practitioners to leverage the power of LLMs in their AI applications. Our study emphasizes the substantial potential of these models, while also identifying areas that need more investigation and improvement., Comment: Accepted in NeurIPS-2023 Workshop on Foundation Models for Decision Making

Published
2023

9. Morphology and transverse alignment of the patella have no effect on knee gait characteristics in healthy Chinese adults over the age of 40 years

Author

Wang, Zhengming, primary, Lu, Jiehang, additional, Ge, Haiya, additional, Li, Zhengyan, additional, Zhang, Min, additional, Pan, Fuwei, additional, Wang, Rui, additional, Jin, Hengkai, additional, Yang, Guangyue, additional, Shen, Zhibi, additional, Du, Guoqing, additional, and Zhan, Hongsheng, additional

Published
2024
Full Text
View/download PDF

11. Experimental Study on the Horizontal Bearing Characteristic of a Strip-Walled Underground Diaphragm Wall.

Author

Du, Guoqing, Xi, Shuang, Ling, Chen, Shi, Weian, Li, Xiaojuan, Zhu, Mingxing, and Li, Shouguo

Subjects
DIAPHRAGM walls, BENDING moment, STRUCTURAL stability, SAFETY standards, LIVE loads, UNDERGROUND construction
Abstract

Researching and developing a new type of diaphragm wall foundation can solve the probl em that the traditional diaphragm wall structure may not meet the high standards of safety and stability of underground structures in some specific engineering environments. This paper focuses on the horizontal bearing characteristic of a new form of foundation, a strip-walled underground diaphragm wall, through a series of model tests. In the tests, nine plexiglass models with different section sizes, wall spacings and wall heights, as well as loading strategies (horizontal loads along and against the wall in the model), were conducted. The influence of the above factors on the horizontal bearing performance of the foundation and the soil resistance distribution around the wall was studied. The results show that when the horizontal load applied along the wall is greater than 50 N, the growth rate of total displacement at the top of the wall gradually decreases; when a horizontal load is applied against the wall, with a uniform change in wall height, the optimal wall spacing is 11 cm. When the same displacement occurs, the bearing performance of the model under the former loading strategy is generally 10% higher than that under the later loading strategy. In addition, the depth where the maximum bending moment along the wall occurred gradually moves downward with the increase in horizontal load, and the increase in wall spacing and wall height has a positive effect on the horizontal bearing characteristic. With the application of load, the maximum bending moment of the wall will gradually decrease along the depth. The increase in wall spacing and wall height can improve the overall flexural stiffness and horizontal bearing performance of the foundation. Lastly, the group wall effect coefficient, β, is put forward, and a simplified formula for calculating the horizontal bearing capacity of a strip wall foundation is proposed. In the formula, β is negatively correlated with the buried depth of the wall and positively correlated with the distance between the walls, and its coefficient is greater than 1. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. A phosphotyrosine switch regulates organic cation transporters.

Author

Sprowl, Jason A, Ong, Su Sien, Gibson, Alice A, Hu, Shuiying, Du, Guoqing, Lin, Wenwei, Li, Lie, Bharill, Shashank, Ness, Rachel A, Stecula, Adrian, Offer, Steven M, Diasio, Robert B, Nies, Anne T, Schwab, Matthias, Cavaletti, Guido, Schlatter, Eberhard, Ciarimboli, Giuliano, Schellens, Jan HM, Isacoff, Ehud Y, Sali, Andrej, Chen, Taosheng, Baker, Sharyn D, Sparreboom, Alex, and Pabla, Navjotsingh

Subjects
Ganglia, Spinal, Hela Cells, Animals, Humans, Mice, Organoplatinum Compounds, Phosphotyrosine, Organic Anion Transporters, Organic Cation Transport Proteins, Organic Cation Transporter 1, Antineoplastic Agents, Protein Kinase Inhibitors, Models, Molecular, Proto-Oncogene Proteins c-yes, Protein-Tyrosine Kinases, HEK293 Cells, Organic Cation Transporter 2, Oxaliplatin, Liver-Specific Organic Anion Transporter 1, HeLa Cells
Abstract

Membrane transporters are key determinants of therapeutic outcomes. They regulate systemic and cellular drug levels influencing efficacy as well as toxicities. Here we report a unique phosphorylation-dependent interaction between drug transporters and tyrosine kinase inhibitors (TKIs), which has uncovered widespread phosphotyrosine-mediated regulation of drug transporters. We initially found that organic cation transporters (OCTs), uptake carriers of metformin and oxaliplatin, were inhibited by several clinically used TKIs. Mechanistic studies showed that these TKIs inhibit the Src family kinase Yes1, which was found to be essential for OCT2 tyrosine phosphorylation and function. Yes1 inhibition in vivo diminished OCT2 activity, significantly mitigating oxaliplatin-induced acute sensory neuropathy. Along with OCT2, other SLC-family drug transporters are potentially part of an extensive 'transporter-phosphoproteome' with unique susceptibility to TKIs. On the basis of these findings we propose that TKIs, an important and rapidly expanding class of therapeutics, can functionally modulate pharmacologically important proteins by inhibiting protein kinases essential for their post-translational regulation.

Published
2016

16. Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens

Author

Wright, Shaela, primary, Hu, Jianzhong, additional, Wang, Hong, additional, Hyle, Judith, additional, Zhang, Yang, additional, Du, Guoqing, additional, Konopleva, Marina Y., additional, Kornblau, Steven M., additional, Djekidel, Mohamed Nadhir, additional, Rosikiewicz, Wojciech, additional, Xu, Beisi, additional, Lu, Rui, additional, Yang, Jun J., additional, and Li, Chunliang, additional

Published
2023
Full Text
View/download PDF

17. Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells

Author

Rowland, Lauren, Smart, Brandon, Brown, Anthony, Dettorre, Gino M, Gocho, Yoshihiro, Hunt, Jeremy, Yang, Wenjian, Yoshimura, Satoshi, Reyes, Noemi, Du, Guoqing, John, August, Maxwell, Dylan, Stock, Wendy, Kornblau, Steven, Relling, Mary V, Inaba, Hiroto, Pui, Ching-Hon, Bourquin, Jean-Pierre; https://orcid.org/0000-0001-6571-6227, Karol, Seth E, Mullighan, Charles G, Evans, William E, Yang, Jun J, Crews, Kristine R, Rowland, Lauren, Smart, Brandon, Brown, Anthony, Dettorre, Gino M, Gocho, Yoshihiro, Hunt, Jeremy, Yang, Wenjian, Yoshimura, Satoshi, Reyes, Noemi, Du, Guoqing, John, August, Maxwell, Dylan, Stock, Wendy, Kornblau, Steven, Relling, Mary V, Inaba, Hiroto, Pui, Ching-Hon, Bourquin, Jean-Pierre; https://orcid.org/0000-0001-6571-6227, Karol, Seth E, Mullighan, Charles G, Evans, William E, Yang, Jun J, and Crews, Kristine R

Abstract

Resistance of acute lymphoblastic leukemia (ALL) cells to chemotherapy, whether present at diagnosis or acquired during treatment, is a major cause of treatment failure. Primary ALL cells are accessible for drug sensitivity testing at the time of new diagnosis or at relapse, but there are major limitations with current methods for determining drug sensitivity ex vivo. Here, we describe a functional precision medicine method using a fluorescence imaging platform to test drug sensitivity profiles of primary ALL cells. Leukemia cells are co-cultured with mesenchymal stromal cells and tested with a panel of 40 anti-leukemia drugs to determine individual patterns of drug resistance and sensitivity ("pharmacotype"). This imaging-based pharmacotyping assay addresses the limitations of prior ex vivo drug sensitivity methods by automating data analysis to produce high-throughput data while requiring fewer cells and significantly decreasing the labor-intensive time required to conduct the assay. The integration of drug sensitivity data with genomic profiling provides a basis for rational genomics-guided precision medicine. Key features Analysis of primary acute lymphoblastic leukemia (ALL) blasts obtained at diagnosis from bone marrow aspirate or peripheral blood. Experiments are performed ex vivo with mesenchymal stromal cell co-culture and require four days to complete. This fluorescence imaging-based protocol enhances previous ex vivo drug sensitivity assays and improves efficiency by requiring fewer primary cells while increasing the number of drugs tested to 40. It takes approximately 2-3 h for sample preparation and processing and a 1.5-hour imaging time. Graphical overview.

Published
2023

19. Ex vivo Drug Sensitivity Imaging-based Platform for Primary Acute Lymphoblastic Leukemia Cells

Author

Rowland, Lauren, primary, Smart, Brandon, additional, Brown, Anthony, additional, Dettorre, Gino, additional, Gocho, Yoshihiro, additional, Hunt, Jeremy, additional, Yang, Wenjian, additional, Yoshimura, Satoshi, additional, Reyes, Noemi, additional, Du, Guoqing, additional, John, August, additional, Maxwell, Dylan, additional, Stock, Wendy, additional, Kornblau, Steven, additional, Relling, Mary, additional, Inaba, Hiroto, additional, Pui, Ching-Hon, additional, Bourquin, Jean-Pierre, additional, Karol, Seth, additional, Mullighan, Charles, additional, Evans, William, additional, Yang, Jun, additional, and Crews, Kristine, additional

Published
2023
Full Text
View/download PDF

23. Nicotine exacerbates endothelial dysfunction and drives atherosclerosis via extracellular vesicle-miRNA

Author

Wang, Chao, primary, Liu, Cong, additional, Shi, Jiaxin, additional, Li, Hairu, additional, Jiang, Shuangquan, additional, Zhao, Peng, additional, Zhang, Maomao, additional, Du, Guoqing, additional, Fu, Shuai, additional, Li, Shouqiang, additional, Wang, Zhuo, additional, Wang, Xiaokun, additional, Gao, Fei, additional, Sun, Ping, additional, and Tian, Jiawei, additional

Published
2022
Full Text
View/download PDF

24. Abstract 423: Induced proximity and proteolytic targeting of LCK as a novel therapeutic approach in T-cell leukemia

Author

Hu, Jianzhong, primary, Jarusiewicz, Jamie, additional, Min, Jaeki, additional, Yang, Lei, additional, Chepyala, Divyabharathi, additional, Actis, Marisa, additional, Du, Guoqing, additional, Smart, Brandon, additional, Maxwell, Dylan, additional, Xie, Boer, additional, Yoshimura, Satoshi, additional, Peng, Junming, additional, Teachey, David T., additional, Rankovic, Zoran, additional, and Yang, Jun J., additional

Published
2022
Full Text
View/download PDF

26. Circuit Breaker Fault Diagnosis Method Based on Improved One-Dimensional Convolutional Neural Network

Author

Shi, Jie, Du, Guoqing, Shen, Haifeng, Ding, Fei, Kong, Weixiang, Shi, Jie, Du, Guoqing, Shen, Haifeng, Ding, Fei, and Kong, Weixiang

Abstract

Aiming at the problems of manual feature extraction and poor generalization ability of model in traditional circuit breaker fault diagnosis technology, a circuit breaker fault diagnosis method based on improved one-dimensional convolutional neural network is proposed. Firstly, the input feature sequence is adaptively weighted by self-attention mechanism to highlight the weight of important information; Secondly, 1  1 convolution layer and global average pooling layer are used to replace the full connection layer, which reduces the model training parameters, improves the training efficiency and prevents the phenomenon of over-fitting. Aiming at the problem of small number of data samples, the data is enhanced by Generative Adversarial Network. After adding the generated data to the original data, the accuracy of fault identification is further improved. The experimental results show that this method can effectively and accurately identify different fault types of circuit breaker, and verify the feasibility of its engineering application.

Published
2022

27. Nicotine exacerbates endothelial dysfunction and drives atherosclerosis via extracellular vesicle-miRNA.

Author

Wang, Chao, Liu, Cong, Shi, Jiaxin, Li, Hairu, Jiang, Shuangquan, Zhao, Peng, Zhang, Maomao, Du, Guoqing, Fu, Shuai, Li, Shouqiang, Wang, Zhuo, Wang, Xiaokun, Gao, Fei, Sun, Ping, and Tian, Jiawei

Subjects
ENDOTHELIUM diseases, NICOTINE, ATHEROSCLEROSIS, ATHEROSCLEROTIC plaque, CELL communication
Abstract

Aims Nicotine, a major component of tobacco, is an important factor contributing to atherosclerosis. However, the molecular mechanisms underlying the link between nicotine and atherosclerosis are unclear. As extracellular vesicles (EVs) are involved in intercellular communication in atherosclerosis, we investigated whether their influence on arterial pathophysiology under nicotine stimulation. Methods and results EVs from the serum of smokers (smoker-EVs) were significantly increased and exacerbated endothelial inflammation, as well as apoptosis according to functional studies. Meanwhile, inhibition of EVs blunted the nicotine-induced atherosclerosis progression, and injection of nicotine-induced EVs promoted atherosclerosis progression in ApoE–/– mice. Furthermore, quantitative reverse transcription-polymerase chain reaction analysis revealed a remarkable increase in miR-155 levels in smoker-EVs, which was correlated with carotid plaque formation in patients measured by ultrasound imaging. Moreover, CD14 levels were significantly increased in EVs from smokers (representing EVs derived from monocytes), indicating that monocytes are an important source of smoker-EVs. DNA methylation and the transcription factor HIF1α may contribute to increased miR-155 levels in monocytes, as assessed with bisulfite conversion sequencing and chromatin immunoprecipitation. Mechanistically, EVs encapsulated miR-155 induced endothelial cell dysfunction by directedly targeting BCL2, MCL1, TIMP3, BCL6, and activating NF-κB pathway, as verified in a series of molecular and biological experiments. Injecting EVs from nicotine-stimulated monocytes promoted plaque formation and triggered vascular endothelial injury in ApoE–/– mice, whereas inhibition of miR-155 weakened this effect. Conclusion Our findings revealed an EV-dependent mechanism of nicotine-aggravated atherosclerosis. Accordingly, we propose an EV-based intervention strategy for atherosclerosis management. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

31. Development of Proteolytic Targeting Chimeras to Target Lck in T-Cell Acute Lymphoblastic Leukemia

Author

Hu, Jianzhong, primary, Jarusiewicz, Jamie, additional, Min, Jaeki, additional, Yang, Lei, additional, Chepyala, Divyabharathi, additional, Actis, Marisa, additional, Rowland, Lauren, additional, Du, Guoqing, additional, Smart, Brandon, additional, Maxwell, Dylan, additional, Xie, Boer, additional, Yoshimura, Satoshi, additional, Peng, Junmin, additional, Teachey, David, additional, Rankovic, Zoran, additional, and Yang, Jun J., additional

Published
2021
Full Text
View/download PDF

36. A measurement method of knee joint space width by ultrasound: a large multicenter study

Author

Zhu, Jiaan, primary, Li, Bing, additional, Qiu, Li, additional, Liu, Hongmei, additional, Zhang, Mi, additional, Wang, Yuexiang, additional, Wang, Ping, additional, Jiao, Dan, additional, Chen, Tao, additional, Liu, Xueling, additional, Cui, Ligang, additional, Shan, Yong, additional, Luo, Baoming, additional, Lin, Ning, additional, Hua, Xing, additional, Hu, Zhenlong, additional, Hu, Yue, additional, Tu, Bin, additional, Zheng, Yuanyi, additional, Chen, Shuqiang, additional, Xu, Shiliang, additional, Mao, Jianying, additional, Liu, Weiyong, additional, Xiang, Minghui, additional, Li, Jia, additional, Chen, Jian, additional, Tang, Yuanjiao, additional, Chen, Siming, additional, He, Yanni, additional, Dai, Ting, additional, Zhang, Shumin, additional, Zhang, Yuanyuan, additional, Fang, Mingdi, additional, Hao, Shaoyun, additional, Lin, Xiaoyan, additional, He, Xiuzhen, additional, Bao, Bo, additional, Xi, Zhanguo, additional, Peng, Xiaojing, additional, Zhang, Qunxia, additional, and Du, GuoQing, additional

Published
2020
Full Text
View/download PDF

41. Whole-genome noncoding sequence analysis in T-cell acute lymphoblastic leukemia identifies oncogene enhancer mutations

Author

Hu, Shaoyan, Qian, Maoxiang, Zhang, Hui, Guo, Yu, Yang, Jin, Zhao, Xujie, He, Hailong, Lu, Jun, Pan, Jian, Chang, Meimei, Du, Guoqing, Lin, Ting-Nien, Kham, Shirley Kow-Yin, Quah, Thuan Chong, Ariffin, Hany, Tan, Ah-Moy, Cheng, Yong, Li, Chunliang, Yeoh, Allen Eng-Juh, Pui, Ching-Hon, Skanderup, Anders Jacobsen, and Yang, Jun J.

Published
2017
Full Text
View/download PDF

43. Circulating Exosomes Control CD4+T Cell Immunometabolic Functions via the Transfer of miR-142 as a Novel Mediator in Myocarditis

Author

Sun, Ping, Wang, Naixin, Zhao, Peng, Wang, Chao, Li, Hairu, Chen, Qi, Mang, Ge, Wang, Weiwei, Fang, Shaohong, Du, Guoqing, Zhang, Maomao, and Tian, Jiawei

Abstract

CD4+T cells undergo immunometabolic activation to mount an immunogenic response during experimental autoimmune myocarditis (EAM). Exosomes are considered key messengers mediating multiple T cell functions in autoimmune responses. However, the role of circulating exosomes in EAM immunopathogenesis and CD4+T cell dysfunction remains elusive. Our objective was to elucidate the mechanism of action for circulating exosomes in EAM pathogenesis. We found that serum exosomes harvested from EAM mice induced CD4+T cell immunometabolic dysfunction. Treatment with the exosome inhibitor GW4869 protected mice from developing EAM, underlying that exosomes are indispensable for the pathogenesis of EAM. Furthermore, by transfer of EAM exosomes, we confirmed that circulating exosomes initiate the T cell pathological immune response, driving the EAM pathological process. Mechanistically, EAM-circulating exosomes selectively loaded abundant microRNA (miR)-142. We confirmed methyl-CpG binding domain protein 2 (MBD2) and suppressor of cytokine signaling 1 (SOCS1) as functional target genes of miR-142. The miR-142/MBD2/MYC and miR-142/SOCS1 communication axes are critical to exosome-mediated immunometabolic turbulence. Moreover, the in vivoinjection of the miR-142 inhibitor alleviated cardiac injury in EAM mice. This effect was abrogated by pretreatment with EAM exosomes. Collectively, our results indicate a newly endogenous mechanism whereby circulating exosomes regulate CD4+T cell immunometabolic dysfunction and EAM pathogenesis via cargo miR-142.

Published
2020
Full Text
View/download PDF

44. OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues

Author

Drenberg, Christina D., primary, Gibson, Alice A., additional, Pounds, Stanley B., additional, Shi, Lei, additional, Rhinehart, Dena P., additional, Li, Lie, additional, Hu, Shuiying, additional, Du, Guoqing, additional, Nies, Anne T., additional, Schwab, Matthias, additional, Pabla, Navjotsingh, additional, Blum, William, additional, Gruber, Tanja A., additional, Baker, Sharyn D., additional, and Sparreboom, Alex, additional

Published
2017
Full Text
View/download PDF

48. Multikinase Inhibitors Induce Cutaneous Toxicity through OAT6-Mediated Uptake and MAP3K7-Driven Cell Death

Author

Zimmerman, Eric I., primary, Gibson, Alice A., additional, Hu, Shuiying, additional, Vasilyeva, Aksana, additional, Orwick, Shelley J., additional, Du, Guoqing, additional, Mascara, Gerard P., additional, Ong, Su Sien, additional, Chen, Taosheng, additional, Vogel, Peter, additional, Inaba, Hiroto, additional, Maitland, Michael L., additional, Sparreboom, Alex, additional, and Baker, Sharyn D., additional

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results