95 results on '"Chunyu Deng"'
Search Results
2. Curcumin improves atrial fibrillation susceptibility by regulating tsRNA expression in aging mouse atrium
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Xueshan Luo, Panyue Liu, Xingdong Ye, Jintao He, Yingyu Lai, Yidong Lv, Xiongbin Wu, Yang Liu, Qianhuan Zhang, Hui Yang, Wei Wei, Chunyu Deng, Sujuan Kuang, Shulin Wu, Yumei Xue, and Fang Rao
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Aging ,Oxidative stress ,Inflammation ,tsRNA ,Atrial atrium ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Age is an independent risk factor for atrial fibrillation (AF), and curcumin can delay aging related disease through reducing oxidative stress and inflammation. However, its target in aging-related AF remains unclear. Transfer RNA-derived small RNA (tsRNA) is a novel short non-coding RNA (sncRNA), and exerts a potential regulatory function in aging. This study was to explore the therapeutic targets of curcumin in atrium of aged mice by PANDORA-seq. Aged mice (18 month) were treated with curcumin (100 mg/kg). Rapid transjugular atrial pacing was performed to observe AF inducibility. SA-β-gal staining, reactive oxygen species (ROS) detection and qRT-PCR were used to assess the degree of aging and oxidative stress/inflammation levels. PANDORA-seq was performed to reveal the differentially expressed sncRNAs in the atrium of mice. The results showed that curcumin reduced the susceptibility AF of aged mice by improving aging-related atrial fibrosis. Compared to young mice (5 month) group, aged mice yielded 473 significantly altered tsRNA sequences, while 947 tsRNA sequences were significantly altered after treated with curcumin. Enrichment analysis revealed that the target genes were mainly related to DNA damage and protein modification. Compared with the 5 month group, the expression levels of mature-mt_tRNA-Val-TAC_CCA_end, mature-mt_tRNA-Glu-TTC_CCA_end, and mature-tRNA-Asp-GTC_CCA_end were up-regulated in the 18 month group, while the expression of mature-mt_tRNA-Thr-TGT_5_end was down-regulated. This trend was reversed in the 18 month + curcumin group. Increased cellular ROS levels, inflammation expression and senescence in aged mice atrium were improved by the down-regulation of mature-mt_tRNA-Val-TAC_CCA_end. In conclusion, our findings identified mature-mt_tRNA-Val-TAC_CCA_end participated in the mechanism of aging-related atrial fibrosis, providing new intervention target of aging-related AF.
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- 2024
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3. Unraveling temporal and spatial biomarkers of epithelial-mesenchymal transition in colorectal cancer: insights into the crucial role of immunosuppressive cells
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Muhong Wang, Chunyu Deng, Cheng Yang, Mingze Yan, Haibo Lu, Yan Zhang, Honghao Liu, Zhekuan Tong, Jiaao Ma, Jiaming Wang, Jiahao Wang, Yuhong Xuan, Haiyue Cheng, Kai Zhao, Jiaqi Zhang, Cuicui Chai, Mingzhe Li, and Zhiwei Yu
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Colorectal cancer ,Single-cell RNA-seq ,Spatial transcriptomics ,Tumor immune microenvironment ,Epithelial-mesenchymal transition (EMT) ,Medicine - Abstract
Abstract The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples. Graphical Abstract
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- 2023
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4. Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis
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Yingyu Lai, Jintao He, Xiaoyan Gao, Dewei Peng, Huishan Zhou, Yuwen Xu, Xueshan Luo, Hui Yang, Mengzhen Zhang, Chunyu Deng, Shulin Wu, Yumei Xue, Feng Zhou, and Fang Rao
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Plasminogen activator inhibitor-1 ,p300 ,p53 ,Bioinformatics analysis ,Age-related atrial fibrosis ,Atrial fibrillation ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, is also intimately involved in the fibrosis. Although PAI-1 may be involved in the occurrence of atrial fibrillation (AF) and thrombosis in the elderly, but whether it participated in aging-related atrial fibrosis and the detailed mechanism is still unclear. We compared the transcriptomics data of young (passage 4) versus senescent (passage 14) human atrial fibroblasts and found that PAI-1 was closely related to aging-related fibrosis. Aged mice and senescent human and mouse atrial fibroblasts underwent electrophysiological and biochemical studies. We found that p300, p53, and PAI-1 protein expressions were increased in the atrial tissue of aged mice and senescent human and mouse atrial fibroblasts. Curcumin or C646 (p300 inhibitor), or p300 knockdown inhibited the expression of PAI-1 contributing to reduced atrial fibroblasts senescence, atrial fibrosis, and the AF inducibility. Furthermore, p53 knockdown decreased the protein expression of PAI-1 and p21 in senescent human and mouse atrial fibroblasts. Our results suggest that p300/p53/PAI-1 signaling pathway participates in the mechanism of atrial fibrosis induced by aging, which provides new sights into the treatment of elderly AF.
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- 2023
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5. Residential Appliance Detection Using Attention-based Deep Convolutional Neural Network
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Chunyu Deng, Kehe Wu, and Binbin Wang
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Technology ,Physics ,QC1-999 - Published
- 2022
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6. Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19
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Yunlong Ma, Fei Qiu, Chunyu Deng, Jingjing Li, Yukuan Huang, Zeyi Wu, Yijun Zhou, Yaru Zhang, Yichun Xiong, Yinghao Yao, Yigang Zhong, Jia Qu, and Jianzhong Su
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Single-cell sequencing ,GWAS ,Immune cells ,Inflammatory storm ,COVID-19 ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Understanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown. Methods We constructed a computational framework to characterize the host genetics that influence immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets containing healthy controls and patients with mild, moderate, and severe symptom (N = 606,534 cells). We collected 10 predefined gene sets including inflammatory and cytokine genes to calculate cell state score for evaluating the immunological features of individual immune cells. Results We found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly expressed genes increased with the severity of COVID-19. Three cell subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were highly expressed in these three cell types, respectively. CCR1 +CD16+monocytes and ABO + megakaryocytes with significantly up-regulated genes, including S100A12, S100A8, S100A9, and IFITM1, confer higher risk to the dysregulated immune response among severe patients. CXCR6 + memory CD8+ T cells exhibit a notable polyfunctionality including elevation of proliferation, migration, and chemotaxis. Moreover, we observed an increase in cell-cell interactions of both CCR1 + CD16+monocytes and CXCR6 + memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues. The enhanced interactions of CXCR6 + memory CD8+T cells with epithelial cells facilitate the recruitment of this specific population of T cells to airways, promoting CD8+T cell-mediated immunity against COVID-19 infection. Conclusions We uncover a major genetics-modulated immunological shift between mild and severe infection, including an elevated expression of genetics-risk genes, increase in inflammatory cytokines, and of functional immune cell subsets aggravating disease severity, which provides novel insights into parsing the host genetic determinants that influence peripheral immune cells in severe COVID-19.
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- 2022
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7. Broadband TM-Mode-Pass Polarization Rotator and Power Divider With Tunable Beam-Splitting Ratio
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Chunyu Deng, Mengjia Lu, Yu Sun, Lei Huang, Dongyu Wang, Jingyu Zhang, Guohua Hu, Binfeng Yun, and Yiping Cui
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Polarization rotator ,power divider ,mode conver- sion ,integrated optics ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
A TM-mode-pass polarization rotator and power divider with an arbitrary beam-splitting ratio constructed by an adiabatic taper, a spatial mode order convertor and a multi-mode interferometer (MMI) is proposed on the silicon-on insulator (SOI) platform. Both arbitrary power splitting and polarization selection-rotation can be realized in this single device. The measurements show that a continuously adjustable beam-splitting ratio from 1:99 to 99:1 within a 33.2 mW power consumption from 1520–1580 nm has been realized for the proposed device.
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- 2022
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8. Single cell sequencing analysis identifies genetics-modulated ORMDL3 + cholangiocytes having higher metabolic effects on primary biliary cholangitis
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Bingyu Xiang, Chunyu Deng, Fei Qiu, Jingjing Li, Shanshan Li, Huifang Zhang, Xiuli Lin, Yukuan Huang, Yijun Zhou, Jianzhong Su, Mingqin Lu, and Yunlong Ma
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Single cell sequencing analysis ,GWAS ,Risk genes ,PBC ,ORMDL3 ,Liver cells ,Biotechnology ,TP248.13-248.65 ,Medical technology ,R855-855.5 - Abstract
Abstract Background Primary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear. Results We constructed a powerful computational framework to integrate GWAS summary statistics with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. Based on our multi-omics integrative analysis, 29 risk genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. By combining GWAS summary statistics with scRNA-seq data, we found that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals (Permuted P
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- 2021
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9. Large Group Delay in Silicon-on-Insulator Chirped Spiral Bragg Grating Waveguide
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Yu Sun, Dongyu Wang, Chunyu Deng, Mengjia Lu, Lei Huang, Guohua Hu, Binfeng Yun, Ruohu Zhang, Ming Li, Jianji Dong, Anle Wang, and Yiping Cui
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Spiral Bragg grating waveguide ,linear dispersion ,group delay ,integrated optics ,Applied optics. Photonics ,TA1501-1820 ,Optics. Light ,QC350-467 - Abstract
Limited by large transmission loss, the development of transverse electric (TE) mode silicon-on-insulator (SOI) based on-chip long length chirped grating waveguide faces many difficulties now. To overcome this problem, multi-mode waveguide with a measured transmission loss of 0.7 dB/cm is applied in this paper, and a chirped spiral Bragg grating waveguide (SBGW) is proposed and experimentally demonstrated. The length of the chirped SBGW reaches 2.7 cm, which is the longest SOI based grating reported so far. The total group delay is measured to be 628 ps, with a structure size of only 0.3 mm2 due to the application of spiral configuration. The slope of the linear dispersion is -27.7 ps/nm. This integrated chirped SBGW shows great compatibility with frequently used TE mode SOI devices and has great potential for applications in microwave photonics requiring dispersion control.
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- 2021
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10. Identifying Cancer Driver lncRNAs Bridged by Functional Effectors through Integrating Multi-omics Data in Human Cancers
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Yong Zhang, Gaoming Liao, Jing Bai, Xinxin Zhang, Liwen Xu, Chunyu Deng, Min Yan, Aimin Xie, Tao Luo, Zhilin Long, Yun Xiao, and Xia Li
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Therapeutics. Pharmacology ,RM1-950 - Abstract
The accumulation of somatic driver mutations in the human genome enables cells to gradually acquire a growth advantage and contributes to tumor development. Great efforts on protein-coding cancer drivers have yielded fruitful discoveries and clinical applications. However, investigations on cancer drivers in non-coding regions, especially long non-coding RNAs (lncRNAs), are extremely scarce due to the limitation of functional understanding. Thus, to identify driver lncRNAs integrating multi-omics data in human cancers, we proposed a computational framework, DriverLncNet, which dissected the functional impact of somatic copy number alteration (CNA) of lncRNAs on regulatory networks and captured key functional effectors in dys-regulatory networks. Applying it to 5 cancer types from The Cancer Genome Atlas (TCGA), we portrayed the landscape of 117 driver lncRNAs and revealed their associated cancer hallmarks through their functional effectors. Moreover, lncRNA RP11-571M6.8 was detected to be highly associated with immunotherapeutic targets (PD-1, PD-L1, and CTLA-4) and regulatory T cell infiltration level and their markers (IL2RA and FCGR2B) in glioblastoma multiforme, highlighting its immunosuppressive function. Meanwhile, a high expression of RP11-1020A11.1 in bladder carcinoma was predictive of poor survival independent of clinical characteristics, and CTD-2256P15.2 in lung adenocarcinoma responded to the sensitivity of methyl ethyl ketone (MEK) inhibitors. In summary, this study provided a framework to decipher the mechanisms of tumorigenesis from driver lncRNA level, established a new landscape of driver lncRNAs in human cancers, and offered potential clinical implications for precision oncology. Keywords: cancer drivers, long non-coding RNAs, copy number alterations, cancer hallmarks, immunosuppression
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- 2019
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11. A pan‐cancer atlas of cancer hallmark‐associated candidate driver lncRNAs
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Yulan Deng, Shangyi Luo, Xinxin Zhang, Chaoxia Zou, Huating Yuan, Gaoming Liao, Liwen Xu, Chunyu Deng, Yujia Lan, Tingting Zhao, Xu Gao, Yun Xiao, and Xia Li
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cancer hallmark ,copy number alteration ,driver lncRNA ,mutual exclusivity ,pan‐cancer atlas ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Substantial cancer genome sequencing efforts have discovered many important driver genes contributing to tumorigenesis. However, very little is known about the genetic alterations of long non‐coding RNAs (lncRNAs) in cancer. Thus, there is a need for systematic surveys of driver lncRNAs. Through integrative analysis of 5918 tumors across 11 cancer types, we revealed that lncRNAs have undergone dramatic genomic alterations, many of which are mutually exclusive with well‐known cancer genes. Using the hypothesis of functional redundancy of mutual exclusivity, we developed a computational framework to identify driver lncRNAs associated with different cancer hallmarks. Applying it to pan‐cancer data, we identified 378 candidate driver lncRNAs whose genomic features highly resemble the known cancer driver genes (e.g. high conservation and early replication). We further validated the candidate driver lncRNAs involved in ‘Tissue Invasion and Metastasis’ in lung adenocarcinoma and breast cancer, and also highlighted their potential roles in improving clinical outcomes. In summary, we have generated a comprehensive landscape of cancer candidate driver lncRNAs that could act as a starting point for future functional explorations, as well as the identification of biomarkers and lncRNA‐based target therapy.
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- 2018
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12. Prioritizing Gene Cascading Paths to Model Colorectal Cancer Through Engineered Organoids
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Yanyan Ping, Chaohan Xu, Liwen Xu, Gaoming Liao, Yao Zhou, Chunyu Deng, Yujia Lan, Fulong Yu, Jian Shi, Li Wang, Yun Xiao, and Xia Li
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gene cascading paths ,prioritizing ,colorectal cancer ,engineered organoids ,random walk with restart ,Biotechnology ,TP248.13-248.65 - Abstract
Engineered organoids by sequential introduction of key mutations could help modeling the dynamic cancer progression. However, it remains difficult to determine gene paths which were sufficient to capture cancer behaviors and to broadly explain cancer mechanisms. Here, as a case study of colorectal cancer (CRC), functional and dynamic characterizations of five types of engineered organoids with different mutation combinations of five driver genes (APC, SMAD4, KRAS, TP53, and PIK3CA) showed that sequential introductions of all five driver mutations could induce enhanced activation of more hallmark signatures, tending to cancer. Comparative analysis of engineered organoids and corresponding CRC tissues revealed sequential introduction of key mutations could continually shorten the biological distance from engineered organoids to CRC tissues. Nevertheless, there still existed substantial biological gaps between the engineered organoid even with five key mutations and CRC samples. Thus, we proposed an integrative strategy to prioritize gene cascading paths for shrinking biological gaps between engineered organoids and CRC tissues. Our results not only recapitulated the well-known adenoma–carcinoma sequence model (e.g., AKST-organoid with driver mutations in APC, KRAS, SMAD4, and TP53), but also provided potential paths for delineating alternative pathogenesis underlying CRC populations (e.g., A-organoid with APC mutation). Our strategy also can be applied to both organoids with more mutations and other cancers, which can improve and innovate mechanism across cancer patients for drug design and cancer therapy.
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- 2020
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13. Review on the research and practice of deep learning and reinforcement learning in smart grids
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Dongxia Zhang, Xiaoqing Han, and Chunyu Deng
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Technology ,Physics ,QC1-999 - Abstract
Smart grids are the developmental trend of power systems and they have attracted much attention all over the world. Due to their complexities, and the uncertainty of the smart grid and high volume of information being collected, artificial intelligence techniques represent some of the enabling technologies for its future development and success. Owing to the decreasing cost of computing power, the profusion of data, and better algorithms, AI has entered into its new developmental stage and AI 2.0 is developing rapidly. Deep learning (DL), reinforcement learning (RL) and their combination-deep reinforcement learning (DRL) are representative methods and relatively mature methods in the family of AI 2.0. This article introduces the concept and status quo of the above three methods, summarizes their potential for application in smart grids, and provides an overview of the research work on their application in smart grids.
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- 2018
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14. Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation experimentsResearch in context
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Jinyuan Xu, Aiai Shi, Zhilin Long, Liwen Xu, Gaoming Liao, Chunyu Deng, Min Yan, Aiming Xie, Tao Luo, Jian Huang, Yun Xiao, and Xia Li
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Medicine ,Medicine (General) ,R5-920 - Abstract
Characterizing functions of long noncoding RNAs (lncRNAs) remains a major challenge, mostly due to the lack of lncRNA-involved regulatory relationships. A wide array of genome-wide expression profiles generated by gene perturbation have been widely used to capture causal links between perturbed genes and response genes. Through annotating >600 gene perturbation profiles, over 354,000 causal relationships between perturbed genes and lncRNAs were identified. This large-scale resource of causal relations inspired us to develop a novel computational approach LnCAR for inferring lncRNAs' functions, which showed a higher accuracy than the co-expression based approach. By application of LnCAR to the cancer hallmark processes, we identified 38 lncRNAs involved in distinct carcinogenic processes. The “activating invasion & metastasis” related lncRNAs were strongly associated with metastatic progression in various cancer types and could act as a predictor of cancer metastasis. Meanwhile, the “evading immune destruction” related lncRNAs showed significant associations with immune infiltration of various immune cells and, importantly, can predict response to anti-PD-1 immunotherapy, suggesting their potential roles as biomarkers for immune therapy. Taken together, our approach provides a novel way to systematically reveal functions of lncRNAs, which will be helpful for further experimental exploration and clinical translational research of lncRNAs. Keywords: lncRNA, Function, Gene perturbation, Cancer, Immunotherapy
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- 2018
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15. Case report of familial sudden cardiac death caused by a DSG2 p.F531C mutation as genetic background when carrying with heterozygous KCNE5 p.D92E/E93X mutation
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Yubi Lin, Jiana Huang, Siqi He, Ruiling Feng, ZhiAn Zhong, Yang Liu, Weitao Ye, Xin Li, Hongtao Liao, Hongwen Fei, Fang Rao, Zhixin Shan, Chunyu Deng, Xianzhang Zhan, Yumei Xue, Hui Liu, Bin Zhang, Kejian Wang, Qianhuan Zhang, Shulin Wu, and Xiufang Lin
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Sudden cardiac death ,Arrhythmogenic right ventricular cardiomyopathy/dysplasia ,Ventricular tachycardia ,Electrical storm ,Genetics ,Internal medicine ,RC31-1245 ,QH426-470 - Abstract
Abstract Background Sudden cardiac death (SCD) induced by malignant ventricular tachycardia (MVT) among young adults with right ventricular cardiomyopathy/dysplasia (ARVC/D) is a devastating event. Parts of ARVC/D patients have a mutation in genes encoding components of cardiac desmosomes, such as desmoglein-2 (DSG2), plakophilin-2 and desmoplakin. Case presentation Here we report a potentially pathogenic mutation in the DSG2 gene, which was identified in a family with ARVC/D using Whole Exome Sequencing (WES) and Sanger Sequencing. In all, Patient III:1 with ARVC/D carried the compound heterozygous mutations of DSG2 p.F531C and KCNE5 p.D92E/E93X, which were both inherited from her mother (II:2), who died of SCD. Carriers of DSG2p.F531C showed various phenotypes, such as ARVC/D, SCD, MVT and dilated cardiomyopathy. For III:1, there were significant low-voltage regions in the inferior-apical, inferior-lateral wall of the right ventricular epicardium and outflow tracts of the right ventricle. Under the guidance of a three-dimensional mapping system, MVT was successfully ablated with an epicardial–endocardial approach targeting for late, double or fragmental potentials after implantable cardioverter-defibrillator (ICD) electrical storms. No VT recurrence was observed during the one year of follow-up. Conclusions When coexisting with heterozygous KCNE5 p.D92E/E93X, heterozygous DSG2 p.F531C as a genetic background was found to predispose to ARVC/D, SCD and MVT, which were successfully ablated using an epicardial–endocardial approach.
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- 2018
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16. Research on the Operation and Inspection System of UHV and Cross-Regional Distribution Network Based on Big Data Technology
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Zhixiang Ji and Chunyu Deng
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Engineering (General). Civil engineering (General) ,TA1-2040 - Abstract
With the development of UHV and cross-regional distribution network, the operation and inspection of electric transmission and transformation equipment need to use big data and other new technologies to build a smart grid operation and inspection system, in order to better support the operation and inspection business. This paper analyzes the new development situation of UHV and trans-area power grid and the demand of smart grid operation and inspection service under the new situation. Combining big data analysis technology with production command and management practice, based on data and business requirements, this paper puts forward the data architecture of intelligent operation and inspection system according to big data technology, gives the technical framework and technology selection of intelligent operation and inspection system, then analyzes the application framework of intelligent operation and inspection service. The whole architecture of intelligent operation and inspection system is proposed, which provides better support for the development and application of intelligent operation and inspection system through the key architecture design. It has far-reaching application value and broad application prospect.
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- 2018
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17. Receptor activator of NF-kappaB and podocytes: towards a function of a novel receptor-ligand pair in the survival response of podocyte injury.
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Shuangxin Liu, Wei Shi, Houqin Xiao, Xinling Liang, Chunyu Deng, Zhiming Ye, Ping Mei, Suxia Wang, Xiaoying Liu, Zhixin Shan, Yongzheng Liang, Bin Zhang, Wenjian Wang, Yanhui Liu, Lixia Xu, Yunfeng Xia, Jianchao Ma, and Zhilian Li
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Medicine ,Science - Abstract
BACKGROUND: Glomerulosclerosis correlates with reduction in podocyte number that occurs through mechanisms which include apoptosis. Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of glomerulosclerosis. However, the mechanism by which podocytes respond to injury is poorly understood. TNF and TNF receptor superfamilies are important in the pathogenesis of podocyte injury and apoptosis. The ligand of receptor activator of NF-kappaB (RANKL) and receptor activator of NF-kappaB (RANK) are members of the TNF and receptor superfamilies. We investigated whether RANK-RANKL is a receptor-ligand complex for podocytes responding to injury. METHODOLOGY/PRINCIPAL FINDINGS: In this study, RANKL and RANK were examined in human podocyte diseases and a rat model of puromycin aminonucleoside nephrosis (PAN). Compared with controls, RANK and RANKL were increased in both human podocyte diseases and the rat PAN model; double immunofluorescence staining revealed that RANK protein expression was mainly attributed to podocytes. Immunoelectron microscopy showed that RANK was localized predominantly at the top of the foot process membrane and the cytoplasm of rat podocyte. In addition, RANK was upregulated in mouse podocytes in vitro after injury induced by puromycin aminonucleoside (PA). Knockdown of RANK expression by small interference RNA (siRNA) exacerbated podocyte apoptosis induced by PA. However, RANKL inhibited significantly the apoptosis of podocytes induced by PA. CONCLUSIONS/SIGNIFICANCE: These findings suggest the increase in RANK-RANKL expression is a response to podocyte injury, and RANK-RANKL may be a novel receptor-ligand complex for the survival response during podocyte injury.
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- 2012
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18. Integration of human organoids single-cell transcriptomic profiles and human genetics repurposes critical cell type-specific drug targets for severe COVID-19.
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Yunlong Ma, Yijun Zhou, Dingping Jiang, Wei Dai, Jingjing Li, Chunyu Deng, Cheng Chen, Gongwei Zheng, Yaru Zhang, Fei Qiu, Haojun Sun, Shilai Xing, Haijun Han, Jia Qu, Nan Wu, Yinghao Yao, and Jianzhong Su
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HUMAN genetics ,DRUG target ,LOCUS (Genetics) ,COVID-19 ,GENOME-wide association studies - Abstract
Human organoids recapitulate the cell type diversity and function of their primary organs holding tremendous potentials for basic and translational research. Advances in single-cell RNA sequencing (scRNA-seq) technology and genome-wide association study (GWAS) have accelerated the biological and therapeutic interpretation of traitrelevant cell types or states. Here, we constructed a computational framework to integrate atlas-level organoid scRNA-seq data, GWAS summary statistics, expression quantitative trait loci, and gene-drug interaction data for distinguishing critical cell populations and drug targets relevant to coronavirus disease 2019 (COVID-19) severity. We found that 39 cell types across eight kinds of organoids were significantly associated with COVID-19 outcomes. Notably, subset of lung mesenchymal stem cells increased proximity with fibroblasts predisposed to repair COVID-19-damaged lung tissue. Brain endothelial cell subset exhibited significant associations with severe COVID-19, and this cell subset showed a notable increase in cell-to-cell interactions with other brain cell types, including microglia. We repurposed 33 druggable genes, including IFNAR2, TYK2, and VIPR2, and their interacting drugs for COVID-19 in a cell-type-specific manner. Overall, our results showcase that host genetic determinants have cellular-specific contribution to COVID-19 severity, and identification of cell type-specific drug targets may facilitate to develop effective therapeutics for treating severe COVID-19 and its complications. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Electrical tunable topological valley photonic crystals for on-chip optical communications in the telecom band
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Zhipeng Qi, Guohua Hu, Chunyu Deng, Hao Sun, Yaohui Sun, Ying Li, Bo Liu, Yu Bai, Shuaidong Chen, Yiping Cui, and School of Physical and Mathematical Sciences
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Physics [Science] ,Light Modulation ,Electrical and Electronic Engineering ,Atomic and Molecular Physics, and Optics ,Optical Communications ,Electronic, Optical and Magnetic Materials ,Biotechnology - Abstract
On-chip optical communications are in increasingly demand for low-loss, small-footprint and power-efficient waveguiding solutions in the telecom band. However, most integrated optical circuits suffer from high propagation loss and low integration degree. Through manipulating the valley-dependent topological phase of light, we have experimentally demonstrated both robust optical transport and electrical modulation of lightwaves at telecom wavelengths in the valley photonic crystals. With the adoption of valley kink states, the 25 Gbit/s optical signal at 1550 nm is successfully transmitted through a highly twisted interface. Furthermore, an extreme high data rate of 100 Gbit/s is demonstrated with such topological waveguide by wavelength division multiplexing. The electrical tunability of the topological modulators based on thermo-optic effect is also verified, opening a novel route towards active valley kink photonic devices. Our study shows a great possibility of making use of the topological protection in building up high-speed datalinks on a chip. Published version This work was supported by the Innovation and Entrepreneurship Program of Jiangsu Province (JSSCBS20210467), the Natural Science Foundation of the Jiangsu Higher Institution of China (21KJB140012), the Natural Science Foundation of Jiangsu Province (SBK2021041180), the National Natural Science Foundation of China (62105158, 62075038).
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- 2022
20. Electrical manipulation of lightwaves in the uniaxially strained photonic honeycomb lattices under the pseudomagnetic field
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Zhipeng Qi, Hao Sun, Guohua Hu, Chunyu Deng, Wanghua Zhu, Bo Liu, Ying Li, Shaopeng Liu, Xuechao Yu, and Yiping Cui
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Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Published
- 2023
21. Data from TIP: A Web Server for Resolving Tumor Immunophenotype Profiling
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Xia Li, Yun Xiao, Tingting Zhao, Min Yan, Zhilin Long, Feng Li, Peng Cheng, Huating Yuan, Gaoming Liao, Wei Liu, Xinxin Zhang, Bo Pang, Chunyu Deng, and Liwen Xu
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Systematically tracking the tumor immunophenotype is required to understand the mechanisms of cancer immunity and improve clinical benefit of cancer immunotherapy. However, progress in current research is hindered by the lack of comprehensive immune activity resources and easy-to-use tools for biologists, clinicians, and researchers to conveniently evaluate immune activity during the “cancer-immunity cycle.” We developed a user-friendly one-stop shop web tool called TIP to comprehensively resolve tumor immunophenotype. TIP has the capability to rapidly analyze and intuitively visualize the activity of anticancer immunity and the extent of tumor-infiltrating immune cells across the seven-step cancer-immunity cycle. Also, we precalculated the pan-cancer immunophenotype for 11,373 samples from 33 The Cancer Genome Atlas human cancers that allow users to obtain and compare immunophenotype of pan-cancer samples. We expect TIP to be useful in a large number of emerging cancer immunity studies and development of effective immunotherapy biomarkers. TIP is freely available for use at http://biocc.hrbmu.edu.cn/TIP/.Significance:TIP is a one-stop shop platform that can help biologists, clinicians, and researchers conveniently evaluate anticancer immune activity with their own gene expression data.See related commentary by Hirano, p. 6536
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- 2023
22. Table S1 from TIP: A Web Server for Resolving Tumor Immunophenotype Profiling
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Xia Li, Yun Xiao, Tingting Zhao, Min Yan, Zhilin Long, Feng Li, Peng Cheng, Huating Yuan, Gaoming Liao, Wei Liu, Xinxin Zhang, Bo Pang, Chunyu Deng, and Liwen Xu
- Abstract
Leukocyte signature matrix (LM14), including gene expression matrix and source data.
- Published
- 2023
23. Supplementary Information from TIP: A Web Server for Resolving Tumor Immunophenotype Profiling
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Xia Li, Yun Xiao, Tingting Zhao, Min Yan, Zhilin Long, Feng Li, Peng Cheng, Huating Yuan, Gaoming Liao, Wei Liu, Xinxin Zhang, Bo Pang, Chunyu Deng, and Liwen Xu
- Abstract
Supplementary figures and tables
- Published
- 2023
24. Large Group Delay in Silicon-on-Insulator Chirped Spiral Bragg Grating Waveguide
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Yiping Cui, Lei Huang, Ruohu Zhang, Dongyu Wang, Ming Li, Guohua Hu, Anle Wang, Yu Sun, Mengjia Lu, Jianji Dong, Binfeng Yun, and Chunyu Deng
- Subjects
Materials science ,Spiral Bragg grating waveguide ,business.industry ,Silicon on insulator ,QC350-467 ,Optics. Light ,Grating ,Waveguide (optics) ,Atomic and Molecular Physics, and Optics ,TA1501-1820 ,Transverse mode ,group delay ,linear dispersion ,Fiber Bragg grating ,integrated optics ,Dispersion (optics) ,Chirp ,Optoelectronics ,Applied optics. Photonics ,Electrical and Electronic Engineering ,business ,Group delay and phase delay - Abstract
Limited by large transmission loss, the development of transverse electric (TE) mode silicon-on-insulator (SOI) based on-chip long length chirped grating waveguide faces many difficulties now. To overcome this problem, multi-mode waveguide with a measured transmission loss of 0.7 dB/cm is applied in this paper, and a chirped spiral Bragg grating waveguide (SBGW) is proposed and experimentally demonstrated. The length of the chirped SBGW reaches 2.7 cm, which is the longest SOI based grating reported so far. The total group delay is measured to be 628 ps, with a structure size of only 0.3 mm2 due to the application of spiral configuration. The slope of the linear dispersion is -27.7 ps/nm. This integrated chirped SBGW shows great compatibility with frequently used TE mode SOI devices and has great potential for applications in microwave photonics requiring dispersion control.
- Published
- 2021
25. Compact and broadband silicon mode-order converter using bricked subwavelength gratings
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Mengjia Lu, Chunyu Deng, Yu Sun, Dongyu Wang, Lei Huang, Pengcheng Liu, Dongdong Lin, Wei Cheng, Guohua Hu, Tong Lin, Binfeng Yun, and Yiping Cui
- Subjects
Atomic and Molecular Physics, and Optics - Abstract
A compact and broadband silicon mode-order converter (MOC) scheme by employing reciprocal mode evolution between asymmetric input/output taper and bricked subwavelength gratings (BSWG) is proposed. In the proposed MOC, a quasi-TE0 mode is generated in the BSWG region, which can be regarded as an effective bridge between the two TE modes to be converted. Flexible mode conversion can be realized by only choosing appropriate structure parameters for specific mode transitions between input/output modes and the quasi-TE0 mode. By combing 3D finite difference time domain (FDTD) and particle swarm optimization (PSO) method, TE0-TE1 and TE0-TE2 MOCs are optimal designed, which can efficiently convert TE0 mode to TE1 and TE2 modes with lengths of 9.39 µm and 11.27 µm, respectively. Results show that the insertion losses of 0-TE1 and TE0-TE2 MOCs, the corresponding working bandwidth are 128 nm (1511∼1639 nm) and 126 nm (1527∼1653 nm), respectively. Additionally, the MOCs can be fabricated with only single etch step with minimum feature size of 145 nm.
- Published
- 2022
26. COMMD5 is involved in the mechanisms of hypotension after parathyroidectomy in patients receiving hemodialysis
- Author
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Bohou Li, Xueqin Chen, Juan Hu, Guibao Ke, Nan Jiang, Fengxia Zhang, Zhiwen Lian, Sichun Wen, Qiong Wu, Yubin Xia, Hong Zhang, Sujuan Kuang, Lixia Xu, Chunyu Deng, and Shuangxin Liu
- Subjects
Pharmacology - Published
- 2023
27. Single cell sequencing analysis uncovers genetics-influenced CD16+monocytes and memory CD8+T cells involved in severe COVID-19
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Yunlong Ma, Fei Qiu, Chunyu Deng, Jingjing Li, Yukuan Huang, Zeyi Wu, Yijun Zhou, Yaru Zhang, Yichun Xiong, Yinghao Yao, Yigang Zhong, Jia Qu, and Jianzhong Su
- Abstract
BackgroundUnderstanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown.MethodsWe constructed a powerful computational framework to characterize the host genetics-influenced immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets (N = 606,534 cells).ResultsWe found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly-expressed genetics-risk genes increased with the severity of COVID-19. Three cell-subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were specifically expressed in these three cell types, respectively. CCR1+CD16+monocytes and ABO+ megakaryocytes with significant up-regulated genes including S100A12, S100A8, S100A9, and IFITM1 confer higher risk to the cytokine storms among severe patients. CXCR6+ memory CD8+ T cells exhibit a notable polyfunctionality of multiple immunologic features, including elevation of proliferation, migration, and chemotaxis. Moreover, we observed a prominent increase in cell-cell interactions of both CCR1+ CD16+monocytes and CXCR6+ memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues, and elevated interactions with epithelial cells could contribute to enhance the resident to lung airway for against COVID-19 infection.ConclusionsWe uncover a major genetics-modulated immunological shift between mild and severe infection, including an increase in up-regulated genetic-risk genes, excessive secreted inflammatory cytokines, and functional immune cell subsets contributing high risk to severity, which provides novel insights in parsing the host genetics-influenced immune cells for severe COVID-19.
- Published
- 2022
28. Machine-Learning-Guided Morphology Engineering of Nanoscale Metal-Organic Frameworks
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Yi Liu, Yang Zhou, Cheng Wang, Peican Chen, Chunyu Deng, Zhongming Zeng, Xuefu Hu, Da Zhou, Zeyu Tang, Liangping Xiao, Hong-Gang Liao, Rongkun Lin, Yilong Bi, Ruiyun Huang, Xudong Qian, Jingzheng Zhang, and Wenbin Lin
- Subjects
Materials science ,Cuboctahedron ,Nanostructure ,business.industry ,Machine learning ,computer.software_genre ,Nanomaterials ,Octahedron ,Nanocrystal ,General Materials Science ,Metal-organic framework ,Artificial intelligence ,business ,Science, technology and society ,Nanoscopic scale ,computer - Abstract
Summary Controlling morphology of nanocrystals is one of the central tasks of nanoscience. In this work, we studied nanoscale metal-organic frameworks (nMOFs) from Hf-oxo clusters and linear dicarboxylate ligands with the aid of machine-learning methods for data analysis. Ligand solubility and modulator concentration were found to quantitatively predict the growth of nMOFs with a specific morphology, such as ultrathin two-dimensional film, hexagonal nanoplate, octahedron, cuboctahedron, concave octahedron, or hollow octahedron morphology. With these insights, we use epitaxy growth sequences to design nMOFs of desirable nanostructures with enhanced substrate transport and, hence, increased activities for catalytic olefin hydrogenation. This work highlights new opportunities in using machine learning to guide morphology engineering of nMOFs and other nanomaterials.
- Published
- 2020
29. Frequency-selectable microwave generation based on on-chip switchable spectral shaping and wavelength-to-time mapping
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Yu Sun, Dongyu Wang, Chunyu Deng, Mengjia Lu, Wanghua Zhu, Binfeng Yun, Guohua Hu, and Yiping Cui
- Subjects
Atomic and Molecular Physics, and Optics - Abstract
We propose and experimentally demonstrate a scheme for the photonic generation of pulsed microwave signals with selectable frequency based on spectral shaping and wavelength-to-time mapping (WTTM) technique. The frequency selectivity is realized by channel switching on an integrated silicon-on-insulator (SOI) spectral shaping chip. The incident signal is spectrally shaped by the asymmetric Mach-Zehnder interferometer (MZI) in the selected channel, and an optical spectrum with uniform free spectral range (FSR) can be generated in a broad bandwidth up to dozens of nanometers, implying large microwave signal duration after WTTM if a pulse light source with matched bandwidth is available. Microwave pulses of frequency from 3.6 GHz to 28.4 GHz with a fixed interval are experimentally generated respectively. The realization of eight microwave frequencies selectable with only one shared dispersive element (DE) required indicates high expansibility in the frequency cover range of our scheme by tuning the dispersion value in WTTM.
- Published
- 2023
30. Single cell sequencing analysis identifies genetics-modulated ORMDL3+ cholangiocytes having higher metabolic effects on primary biliary cholangitis
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Jingjing Li, Fei Qiu, Yunlong Ma, Bingyu Xiang, Xiuli Lin, Jianzhong Su, Huifang Zhang, Mingqin Lu, Chunyu Deng, Yijun Zhou, Yukuan Huang, and Shanshan Li
- Subjects
Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Biology ,PBC ,Applied Microbiology and Biotechnology ,Liver cells ,Medical technology ,Humans ,GWAS ,RNA-Seq ,R855-855.5 ,Biliary Tract ,Cells, Cultured ,Genetics ,Primary (chemistry) ,Liver Cirrhosis, Biliary ,Research ,ORMDL3 ,Membrane Proteins ,Single cell sequencing ,Metabolic effects ,Molecular Medicine ,Single-Cell Analysis ,Risk genes ,TP248.13-248.65 ,Biotechnology ,Genome-Wide Association Study ,Single cell sequencing analysis - Abstract
Background Primary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear. Results We constructed a powerful computational framework to integrate GWAS summary statistics with scRNA-seq data to uncover genetics-modulated liver cell subpopulations for PBC. Based on our multi-omics integrative analysis, 29 risk genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. By combining GWAS summary statistics with scRNA-seq data, we found that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals (Permuted P ORMDL3 showed the highest expression proportion in cholangiocytes than other liver cells (22.38%). The ORMDL3+ cholangiocytes have prominently higher metabolism activity score than ORMDL3− cholangiocytes (P = 1.38 × 10–15). Compared with ORMDL3− cholangiocytes, there were 77 significantly differentially expressed genes among ORMDL3+ cholangiocytes (FDR ORMDL3+ cholangiocytes exhibited relatively high communications with macrophage and monocyte. Compared with ORMDL3− cholangiocytes, the VEGF signaling pathway is specific for ORMDL3+ cholangiocytes to interact with other cell populations. Conclusions To the best of our knowledge, this is the first study to integrate genetic information with single cell sequencing data for parsing genetics-influenced liver cells for PBC risk. We identified that ORMDL3+ cholangiocytes with higher metabolism activity play important immune-modulatory roles in the etiology of PBC. Graphical Abstract
- Published
- 2021
31. The genetic source tracking of human urinary exosomes
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Jiaoyuan Li, Meng Li, Jianzhong Su, Liu Huang, Qinsi Yang, Xianjun Dong, Chunyu Deng, Yong Wang, Liming Cheng, Qingfu Zhu, Fei Liu, and Luke P. Lee
- Subjects
Multidisciplinary ,Monocyte ,Cancer ,Dendritic cell ,Biology ,medicine.disease ,Microvesicles ,Cell biology ,Immune system ,medicine.anatomical_structure ,medicine ,Liquid biopsy ,Biomarker discovery ,Gene - Abstract
The genetic origins of nanoscale extracellular vesicles in our body fluids remains unclear. Here, we perform a tracking analysis of urinary exosomes via RNA sequencing, revealing that urine exosomes mostly express tissue-specific genes for the bladder and have close cell-genetic relationships to the endothelial cell, basal cell, monocyte, and dendritic cell. Tracking the differentially expressed genes of cancers and corresponding enrichment analysis show urine exosomes are intensively involved in immune activities, indicating that they may be harnessed as reliable biomarkers of noninvasive liquid biopsy in cancer genomic diagnostics and precision medicine.
- Published
- 2021
32. Combination of single cell sequencing data and GWAS summary statistics reveals genetically-influenced liver cell types for primary biliary cholangitis
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Yunlong Ma, Jingjing Li, Mingqin Lu, Chunyu Deng, Shanshan Li, Bingyu Xiang, Xiuli Lin, and Huifang Zhang
- Subjects
Transcriptome ,Genetics ,medicine.anatomical_structure ,Single cell sequencing ,Liver cell ,T cell ,Expression quantitative trait loci ,medicine ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Genetic association - Abstract
ImportancePrimary biliary cholangitis (PBC) is a classical autoimmune disease, which is highly influenced by genetic determinants. Many genome-wide association studies (GWAS) have reported that numerous genetic loci were significantly associated with PBC susceptibility. However, the effects of genetic determinants on liver cells and its immune microenvironment for PBC remain unclear.ObjectiveTo identify genetics-modulated functional liver cell subsets involved in the pathogenesis of PBC.Design, Setting, and ParticipantsIn this present study, 13,239 European participants were collected from IEU open GWAS project on PBC. There were 1,124,241 qualified SNPs used for GWAS analysis. Expression quantitative trait loci (eQTL) data across 49 tissues were downloaded from the GTEx database. Two single cell RNA sequencing (scRNA-seq) profiles and two bulk-based RNA transcriptomes were downloaded from the GEO database. Data collection and analyses were performed from August 2020 to June 2021.Main outcomes and measuresWe constructed a powerful computational framework to integrate GWAS summary statistics with scRNA-seq data to uncover genetics-modulated liver cell subpopulations.ResultsBased on our multi-omics integrative analysis, we found that 29 risk genes including ORMDL3, GSNK2B, and DDAH2 were significantly associated with PBC susceptibility. Gene-property analysis revealed that four immune cell types, including Cst3+ dendritic cell, Chil3+ macrophage, Trbc2+ T cell, and Gzma+ T cell, were significantly enriched by PBC-risk genes. By combining GWAS summary statistics with scRNA-seq data, we found that cholangiocytes exhibited a notable enrichment by PBC-related genetic association signals (Permuted P < 0.05). The risk gene of ORMDL3 showed the highest expression proportion in cholangiocytes than other liver cells (22.38%). Compared with ORMDL3+ cholangiocytes, there were 71 significantly highly-expressed genes among ORMDL3- cholangiocytes (FDR < 0.05), such as inflammatory cytokine genes CXCL8, CCL3, IFI16, and IRF1. These highly-expressed genes were significantly enriched in numerous biological pathways and functional terms associated with autoimmune diseases (FDR < 0.05).Conclusions and relevanceTo the best of our knowledge, this is the first study to integrate genetic information with single cell sequencing data for parsing genetics-influenced liver cells for PBC risk. We identified that ORMDL3- cholangiocytes play important immune-modulatory roles in the etiology of PBC.Key pointsQuestionAre genetics factors influenced liver cell subpopulations and its immune microenvironment for PBC?FindingsIn this comprehensive genomics study based on multi-omics data, genetic determinants were significantly enriched in cholangiocytes and immune cells including subsets of macrophage, dendritic cells, and T cells. ORMDL3- cholangiocytes have crucial immune-modulatory roles in developing PBC.MeaningFindings suggest that integration of single cell sequencing data with GWAS summary statistics contribute to pinpoint PBC-relevant cell types and risk genes.
- Published
- 2021
33. Integrating single-cell sequencing data with GWAS summary statistics reveals CD16+monocytes and memory CD8+T cells involved in severe COVID-19
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Yunlong Ma, Fei Qiu, Chunyu Deng, Jingjing Li, Yukuan Huang, Zeyi Wu, Yijun Zhou, Yaru Zhang, Yichun Xiong, Yinghao Yao, Yigang Zhong, Jia Qu, and Jianzhong Su
- Subjects
Sequence Analysis, RNA ,Quantitative Trait Loci ,Receptors, IgG ,Receptors, CCR1 ,COVID-19 ,Computational Biology ,CD8-Positive T-Lymphocytes ,GPI-Linked Proteins ,Severity of Illness Index ,Monocytes ,Genetics ,Molecular Medicine ,Humans ,Genetic Predisposition to Disease ,Single-Cell Analysis ,Molecular Biology ,Genetics (clinical) ,Genome-Wide Association Study ,Megakaryocyte Progenitor Cells ,Receptors, CXCR6 - Abstract
Background Understanding the host genetic architecture and viral immunity contributes to the development of effective vaccines and therapeutics for controlling the COVID-19 pandemic. Alterations of immune responses in peripheral blood mononuclear cells play a crucial role in the detrimental progression of COVID-19. However, the effects of host genetic factors on immune responses for severe COVID-19 remain largely unknown. Methods We constructed a computational framework to characterize the host genetics that influence immune cell subpopulations for severe COVID-19 by integrating GWAS summary statistics (N = 969,689 samples) with four independent scRNA-seq datasets containing healthy controls and patients with mild, moderate, and severe symptom (N = 606,534 cells). We collected 10 predefined gene sets including inflammatory and cytokine genes to calculate cell state score for evaluating the immunological features of individual immune cells. Results We found that 34 risk genes were significantly associated with severe COVID-19, and the number of highly expressed genes increased with the severity of COVID-19. Three cell subtypes that are CD16+monocytes, megakaryocytes, and memory CD8+T cells were significantly enriched by COVID-19-related genetic association signals. Notably, three causal risk genes of CCR1, CXCR6, and ABO were highly expressed in these three cell types, respectively. CCR1+CD16+monocytes and ABO+ megakaryocytes with significantly up-regulated genes, including S100A12, S100A8, S100A9, and IFITM1, confer higher risk to the dysregulated immune response among severe patients. CXCR6+ memory CD8+ T cells exhibit a notable polyfunctionality including elevation of proliferation, migration, and chemotaxis. Moreover, we observed an increase in cell-cell interactions of both CCR1+ CD16+monocytes and CXCR6+ memory CD8+T cells in severe patients compared to normal controls among both PBMCs and lung tissues. The enhanced interactions of CXCR6+ memory CD8+T cells with epithelial cells facilitate the recruitment of this specific population of T cells to airways, promoting CD8+T cell-mediated immunity against COVID-19 infection. Conclusions We uncover a major genetics-modulated immunological shift between mild and severe infection, including an elevated expression of genetics-risk genes, increase in inflammatory cytokines, and of functional immune cell subsets aggravating disease severity, which provides novel insights into parsing the host genetic determinants that influence peripheral immune cells in severe COVID-19.
- Published
- 2021
34. Synthesis of single-crystalline Pb(Zr0.52Ti0.48)O3 nanocrystals by hydrothermal method
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Yang Ju, Lianmeng Zhang, Dongyun Guo, Xuedong Zhou, Zhixiong Huang, Xinyi Li, Chunyu Deng, Shaoqing Li, and Chaoran Qin
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reaction time ,010302 applied physics ,Thesaurus (information retrieval) ,Materials science ,Mechanical Engineering ,naoh concentration ,Nanotechnology ,02 engineering and technology ,reaction temperature ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,pbzr0.52ti0.48o3 nanocrystal ,01 natural sciences ,Hydrothermal circulation ,Nanomaterials ,Nanocrystal ,hydrothermal method ,Mechanics of Materials ,0103 physical sciences ,TA401-492 ,General Materials Science ,0210 nano-technology ,Science, technology and society ,Materials of engineering and construction. Mechanics of materials - Abstract
PbZr0.52Ti0.48O3 nanocrystals were synthesized by a hydrothermal method. The effect of NaOH concentration, reaction temperature and time on nucleation and growth of PbZr0.52Ti0.48O3 nanocrystals was investigated. As the 0.05 mol/L PbZr0.52Ti0.48O3 precursors were heated at 200 °C for 21 h with NaOH concentration of 0.5 mol/L, the tetragonal PbZr0.52Ti0.48O3 nanocrystals were formed, and the grain size was more than 20 nm. With increasing the NaOH concentration from 0.5 to 1.5 mol/L, the grain size of PbZr0.52Ti0.48O3 nanocrystals decreased. When the precursors were heated at different temperatures (140 °C to 200 °C) for 21 h with 1.0 mol/L NaOH, single-phase PbZr0.52Ti0.48O3 nanocrystals were obtained at 160 °C to 200 °C. With increasing the reaction temperature from 160 °C to 200 °C, the grains size of PbZr0.52Ti0.48O3 nanocrystals increased from 5 nm to 9 nm. When the precursors were heated at 160 °C in different reaction times from 6 h to 21 h, the evolution from amorphous to crystalline PbZr0.52Ti0.48O3 nanocrystals in correlation with the reaction time was observed. Single crystalline PbZr0.52Ti0.48O3 nanocrystals with narrow size distribution (from 5 nm to 9 nm) were synthesized by controlling the NaOH concentration, reaction temperature and time. The obtained results can find potential application in preparing PbZr0.52Ti0.48O3 thin films on flexible substrates.
- Published
- 2019
35. Identifying Cancer Driver lncRNAs Bridged by Functional Effectors through Integrating Multi-omics Data in Human Cancers
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Liwen Xu, Jing Bai, Gaoming Liao, Yun Xiao, Tao Luo, Aimin Xie, Yong Zhang, Xinxin Zhang, Xia Li, Min Yan, Zhilin Long, and Chunyu Deng
- Subjects
0301 basic medicine ,Somatic cell ,Regulatory T cell ,Computational biology ,Biology ,medicine.disease_cause ,Article ,long non-coding RNAs ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,immunosuppression ,copy number alterations ,Effector ,cancer drivers ,lcsh:RM1-950 ,medicine.disease ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Molecular Medicine ,Adenocarcinoma ,DECIPHER ,Multi omics ,cancer hallmarks ,Human genome ,Carcinogenesis - Abstract
The accumulation of somatic driver mutations in the human genome enables cells to gradually acquire a growth advantage and contributes to tumor development. Great efforts on protein-coding cancer drivers have yielded fruitful discoveries and clinical applications. However, investigations on cancer drivers in non-coding regions, especially long non-coding RNAs (lncRNAs), are extremely scarce due to the limitation of functional understanding. Thus, to identify driver lncRNAs integrating multi-omics data in human cancers, we proposed a computational framework, DriverLncNet, which dissected the functional impact of somatic copy number alteration (CNA) of lncRNAs on regulatory networks and captured key functional effectors in dys-regulatory networks. Applying it to 5 cancer types from The Cancer Genome Atlas (TCGA), we portrayed the landscape of 117 driver lncRNAs and revealed their associated cancer hallmarks through their functional effectors. Moreover, lncRNA RP11-571M6.8 was detected to be highly associated with immunotherapeutic targets (PD-1, PD-L1, and CTLA-4) and regulatory T cell infiltration level and their markers (IL2RA and FCGR2B) in glioblastoma multiforme, highlighting its immunosuppressive function. Meanwhile, a high expression of RP11-1020A11.1 in bladder carcinoma was predictive of poor survival independent of clinical characteristics, and CTD-2256P15.2 in lung adenocarcinoma responded to the sensitivity of methyl ethyl ketone (MEK) inhibitors. In summary, this study provided a framework to decipher the mechanisms of tumorigenesis from driver lncRNA level, established a new landscape of driver lncRNAs in human cancers, and offered potential clinical implications for precision oncology. Keywords: cancer drivers, long non-coding RNAs, copy number alterations, cancer hallmarks, immunosuppression
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- 2019
36. TIP: A Web Server for Resolving Tumor Immunophenotype Profiling
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Xia Li, Yun Xiao, Wei Liu, Xinxin Zhang, Zhilin Long, Tingting Zhao, Feng Li, Huating Yuan, Bo Pang, Min Yan, Peng Cheng, Gaoming Liao, Liwen Xu, and Chunyu Deng
- Subjects
0301 basic medicine ,Anticancer immunity ,Cancer Research ,Web server ,Computer science ,medicine.medical_treatment ,Computational biology ,Web Browser ,computer.software_genre ,Immunophenotyping ,03 medical and health sciences ,Immune system ,Cancer immunotherapy ,Neoplasms ,Cancer genome ,Biomarkers, Tumor ,medicine ,Humans ,Profiling (information science) ,Computational Biology ,Immunotherapy ,030104 developmental biology ,Oncology ,computer ,Software - Abstract
Systematically tracking the tumor immunophenotype is required to understand the mechanisms of cancer immunity and improve clinical benefit of cancer immunotherapy. However, progress in current research is hindered by the lack of comprehensive immune activity resources and easy-to-use tools for biologists, clinicians, and researchers to conveniently evaluate immune activity during the “cancer-immunity cycle.” We developed a user-friendly one-stop shop web tool called TIP to comprehensively resolve tumor immunophenotype. TIP has the capability to rapidly analyze and intuitively visualize the activity of anticancer immunity and the extent of tumor-infiltrating immune cells across the seven-step cancer-immunity cycle. Also, we precalculated the pan-cancer immunophenotype for 11,373 samples from 33 The Cancer Genome Atlas human cancers that allow users to obtain and compare immunophenotype of pan-cancer samples. We expect TIP to be useful in a large number of emerging cancer immunity studies and development of effective immunotherapy biomarkers. TIP is freely available for use at http://biocc.hrbmu.edu.cn/TIP/. Significance: TIP is a one-stop shop platform that can help biologists, clinicians, and researchers conveniently evaluate anticancer immune activity with their own gene expression data. See related commentary by Hirano, p. 6536
- Published
- 2018
37. Residential Demand Response Strategy Based on Deep Deterministic Policy Gradient
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Kehe Wu and Chunyu Deng
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Computer science ,020209 energy ,Bioengineering ,02 engineering and technology ,lcsh:Chemical technology ,Demand response ,lcsh:Chemistry ,Electric power system ,deep deterministic policy gradient ,0202 electrical engineering, electronic engineering, information engineering ,Chemical Engineering (miscellaneous) ,Reinforcement learning ,Electricity market ,lcsh:TP1-1185 ,Consumption (economics) ,deep reinforcement learning ,business.industry ,Process Chemistry and Technology ,Environmental economics ,power consumption strategy optimization ,Incentive ,Smart grid ,lcsh:QD1-999 ,demand response ,020201 artificial intelligence & image processing ,Electricity ,business - Abstract
With the continuous improvement of the power system and the deepening of electricity market reform, the trend of users’ active participation in power distribution is more and more significant. Demand response has become the promising focus of smart grid research. Providing reasonable incentive strategies for power grid companies and demand response strategies for customers plays a crucial role in maximizing the benefits of different participants. To meet different expectations of multiple agents in the same environment, deep reinforcement learning was adopted. The generative model of residential demand response strategy under different incentive policies can be trained iteratively through real-time interactions with the environmental conditions. In this paper, a novel optimization model of residential demand response strategy, based on a deep deterministic policy gradient (DDPG) algorithm, was proposed. The proposed work was validated with the actual electricity consumption data of a certain area in China. The results showed that the DDPG model could optimize residential demand response strategy under certain incentive policies. In addition, the overall goal of peak load-cutting and valley filling can be achieved, which reflects promising prospects of the electricity market.
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- 2021
38. Systematic Assessment of Transcriptomic Biomarkers for Immune Checkpoint Blockade Response in Cancer Immunotherapy
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Jiali Zhu, Liwen Xu, Linyun Wan, Bo Pang, Yun Xiao, Shuting Zhou, Zhilin Long, Lin Pang, Xinxin Zhang, Shangqin Sun, and Chunyu Deng
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,comparative analysis ,medicine.medical_treatment ,transcriptomic biomarkers ,lcsh:RC254-282 ,Article ,immune response ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cancer immunotherapy ,Internal medicine ,Medicine ,business.industry ,Melanoma ,Cancer ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immune checkpoint ,immune checkpoint blockade (ICB) ,030104 developmental biology ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,immunotherapy ,business - Abstract
Simple Summary The aim of our study was to evaluate the predictive performance of transcriptomic biomarkers to immune response. The study collected 22 transcriptomic biomarkers and constructed multiple benchmark datasets to evaluate their predictive performance of immune checkpoint blockade (ICB) response in pre-treatment patients with distinct ICB agents in diverse cancers. We found “Immune-checkpoint molecule” biomarkers PD-L1, PD-L2, CTLA-4 and IMPRES and the “Effector molecule” biomarker CYT showed significant associations with ICB response and clinical outcomes. These immune-checkpoint biomarkers and another immune effector IFN-gamma presented predictive ability in melanoma, urothelial cancer and clear cell renal-cell cancer. Interestingly, for anti-PD-1 therapy and anti-CTLA-4 therapy, the top-performing response biomarkers were usually mutually exclusive even though in the same biomarker category and most of biomarkers with outstanding predictive power were observed in patients with combined anti-PD-1 and anti-CTLA-4 therapy. Abstract Background: Immune checkpoint blockade (ICB) therapy has yielded successful clinical responses in treatment of a minority of patients in certain cancer types. Substantial efforts were made to establish biomarkers for predicting responsiveness to ICB. However, the systematic assessment of these ICB response biomarkers remains insufficient. Methods: We collected 22 transcriptome-based biomarkers for ICB response and constructed multiple benchmark datasets to evaluate the associations with clinical response, predictive performance, and clinical efficacy of them in pre-treatment patients with distinct ICB agents in diverse cancers. Results: Overall, “Immune-checkpoint molecule” biomarkers PD-L1, PD-L2, CTLA-4 and IMPRES and the “Effector molecule” biomarker CYT showed significant associations with ICB response and clinical outcomes. These immune-checkpoint biomarkers and another immune effector IFN-gamma presented predictive ability in melanoma, urothelial cancer (UC) and clear cell renal-cell cancer (ccRCC). In non-small cell lung cancer (NSCLC), only PD-L2 and CTLA-4 showed preferable correlation with clinical response. Under different ICB therapies, the top-performing biomarkers were usually mutually exclusive in patients with anti-PD-1 and anti-CTLA-4 therapy, and most of biomarkers presented outstanding predictive power in patients with combined anti-PD-1 and anti-CTLA-4 therapy. Conclusions: Our results show these biomarkers had different performance in predicting ICB response across distinct ICB agents in diverse cancers.
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- 2021
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39. Residential appliance detection based on attention-based deep convolutional neural network
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Binbin Wang, Kehe Wu, and Chunyu Deng
- Subjects
Consumption (economics) ,Computer science ,Smart meter ,business.industry ,Deep learning ,Energy consumption ,Machine learning ,computer.software_genre ,Convolutional neural network ,Electronic, Optical and Magnetic Materials ,General Energy ,Electricity market ,Artificial intelligence ,Electrical and Electronic Engineering ,Hidden Markov model ,business ,computer ,Efficient energy use - Abstract
Improving energy efficiency management has become an important task for current electricity market participating entities, and monitoring consumption of pivotal appliances plays an important role in many applications. This paper focuses on detecting whether a residence hold a certain type appliance based on their electricity consumption. We propose a data-driven deep learning approach with attention mechanism to detect residential appliances from low-resolution aggregate energy consumption data. Firstly, the historical consumption profile of each user is divided into a specific length and labeled with the status of an appliance to generate training and test samples; Then a deep convolutional neural network model with attention mechanism is trained, and the trained model is utilized to classify the test samples; Finally, we obtain appliance status in a residence based on classification of multiple samples. Experiments are conducted on a low-frequency smart meter data set sampled once every 30 minutes, whose results show our proposed model performs better than hidden Markov model based algorithms and has good application prospects.
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- 2020
40. Post Evaluation of Power Grid Project Based on Rough Set and Improved Multi-Level Extension Assessment
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Chunyu Deng and Hao Li Wenjing Chen
- Abstract
Post evaluation of power grid investment and construction project is an important part of power grid construction project. The effect of post evaluation will directly affect the quality level of project construction. Therefore, this paper proposes an improved post evaluation system based on rough set and fuzzy multi-level extension. Firstly, the main factors affecting the function effect of power grid construction project are analyzed. Then, the improved fuzzy multi-level extension evaluation model is constructed by combining fuzzy comprehensive evaluation theory with multi-level extension evaluation method. Finally, a 220 kV substation construction project is taken as an example to verify the validity and rationality of the model.
- Published
- 2022
41. CancerSEA: a cancer single-cell state atlas
- Author
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Liwen Xu, Gaoming Liao, Xia Li, Huating Yuan, Haoteng Yan, Chunyu Deng, Guanxiong Zhang, Aiai Shi, Tao Luo, Wei Liu, Yun Xiao, Zhilin Long, Tingting Zhao, and Min Yan
- Subjects
DNA repair ,Angiogenesis ,RNA-Seq ,Computational biology ,Biology ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Single-cell analysis ,Neoplasms ,Databases, Genetic ,Genetics ,medicine ,Humans ,Database Issue ,Gene ,030304 developmental biology ,0303 health sciences ,Proteins ,Cell cycle ,medicine.disease ,Cancer cell ,RNA, Long Noncoding ,Single-Cell Analysis ,030217 neurology & neurosurgery - Abstract
High functional heterogeneity of cancer cells poses a major challenge for cancer research. Single-cell sequencing technology provides an unprecedented opportunity to decipher diverse functional states of cancer cells at single-cell resolution, and cancer scRNA-seq datasets have been largely accumulated. This emphasizes the urgent need to build a dedicated resource to decode the functional states of cancer single cells. Here, we developed CancerSEA (http://biocc.hrbmu.edu.cn/CancerSEA/ or http://202.97.205.69/CancerSEA/), the first dedicated database that aims to comprehensively explore distinct functional states of cancer cells at the single-cell level. CancerSEA portrays a cancer single-cell functional state atlas, involving 14 functional states (including stemness, invasion, metastasis, proliferation, EMT, angiogenesis, apoptosis, cell cycle, differentiation, DNA damage, DNA repair, hypoxia, inflammation and quiescence) of 41 900 cancer single cells from 25 cancer types. It allows querying which functional states are associated with the gene (or gene list) of interest in different cancers. CancerSEA also provides functional state-associated PCG/lncRNA repertoires across all cancers, in specific cancers, and in individual cancer single-cell datasets. In summary, CancerSEA provides a user-friendly interface for comprehensively searching, browsing, visualizing and downloading functional state activity profiles of tens of thousands of cancer single cells and the corresponding PCGs/lncRNAs expression profiles.
- Published
- 2018
42. CellMarker: a manually curated resource of cell markers in human and mouse
- Author
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Aiai Shi, Tao Luo, Feng Li, Yujia Lan, Liwen Xu, Tingting Zhao, Yanyan Ping, Yun Xiao, Min Yan, Xinxin Zhang, Jing Bai, Erjie Zhao, Gaoming Liao, Chunyu Deng, Xia Li, Fei Quan, and Jinyuan Xu
- Subjects
Cell marker ,0303 health sciences ,Cell type ,Cell ,Computational biology ,Biology ,Stem cell marker ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Databases, Genetic ,Genetics ,medicine ,Animals ,Humans ,Database Issue ,Tissue type ,Single-Cell Analysis ,Sequence Analysis ,Software ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
One of the most fundamental questions in biology is what types of cells form different tissues and organs in a functionally coordinated fashion. Larger-scale single-cell sequencing and biology experiment studies are now rapidly opening up new ways to track this question by revealing substantial cell markers for distinguishing different cell types in tissues. Here, we developed the CellMarker database (http://biocc.hrbmu.edu.cn/CellMarker/ or http://bio-bigdata.hrbmu.edu.cn/CellMarker/), aiming to provide a comprehensive and accurate resource of cell markers for various cell types in tissues of human and mouse. By manually curating over 100 000 published papers, 4124 entries including the cell marker information, tissue type, cell type, cancer information and source, were recorded. At last, 13 605 cell markers of 467 cell types in 158 human tissues/sub-tissues and 9148 cell makers of 389 cell types in 81 mouse tissues/sub-tissues were collected and deposited in CellMarker. CellMarker provides a user-friendly interface for browsing, searching and downloading markers of diverse cell types of different tissues. Furthermore, a summarized marker prevalence in each cell type is graphically and intuitively presented through a vivid statistical graph. We believe that CellMarker is a comprehensive and valuable resource for cell researches in precisely identifying and characterizing cells, especially at the single-cell level.
- Published
- 2018
43. A pan‐cancer atlas of cancer hallmark‐associated candidate driver lncRNAs
- Author
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Chunyu Deng, Xinxin Zhang, Tingting Zhao, Yulan Deng, Gaoming Liao, Shangyi Luo, Yun Xiao, Yujia Lan, Huating Yuan, Xia Li, Chaoxia Zou, Liwen Xu, and Xu Gao
- Subjects
0301 basic medicine ,Cancer genome sequencing ,Cancer Research ,copy number alteration ,Computational biology ,cancer hallmark ,Biology ,Mutually exclusive events ,medicine.disease_cause ,lcsh:RC254-282 ,Metastasis ,03 medical and health sciences ,Breast cancer ,Neoplasms ,driver lncRNA ,mutual exclusivity ,Databases, Genetic ,Genetics ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Neoplasm ,Gene ,Research Articles ,Pan cancer ,General Medicine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Molecular Medicine ,Adenocarcinoma ,RNA, Long Noncoding ,pan‐cancer atlas ,Carcinogenesis ,Research Article - Abstract
Substantial cancer genome sequencing efforts have discovered many important driver genes contributing to tumorigenesis. However, very little is known about the genetic alterations of long non‐coding RNAs (lncRNAs) in cancer. Thus, there is a need for systematic surveys of driver lncRNAs. Through integrative analysis of 5918 tumors across 11 cancer types, we revealed that lncRNAs have undergone dramatic genomic alterations, many of which are mutually exclusive with well‐known cancer genes. Using the hypothesis of functional redundancy of mutual exclusivity, we developed a computational framework to identify driver lncRNAs associated with different cancer hallmarks. Applying it to pan‐cancer data, we identified 378 candidate driver lncRNAs whose genomic features highly resemble the known cancer driver genes (e.g. high conservation and early replication). We further validated the candidate driver lncRNAs involved in ‘Tissue Invasion and Metastasis’ in lung adenocarcinoma and breast cancer, and also highlighted their potential roles in improving clinical outcomes. In summary, we have generated a comprehensive landscape of cancer candidate driver lncRNAs that could act as a starting point for future functional explorations, as well as the identification of biomarkers and lncRNA‐based target therapy.
- Published
- 2018
44. Review on the research and practice of deep learning and reinforcement learning in smart grids
- Author
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Chunyu Deng, Dongxia Zhang, and Xiaoqing Han
- Subjects
Developmental stage ,business.industry ,Status quo ,Computer science ,lcsh:T ,020209 energy ,Deep learning ,media_common.quotation_subject ,02 engineering and technology ,Data science ,lcsh:Technology ,lcsh:QC1-999 ,Electronic, Optical and Magnetic Materials ,Electric power system ,General Energy ,Smart grid ,0202 electrical engineering, electronic engineering, information engineering ,Reinforcement learning ,Artificial intelligence ,Electrical and Electronic Engineering ,business ,lcsh:Physics ,media_common - Abstract
Smart grids are the developmental trend of power systems and they have attracted much attention all over the world. Due to their complexities, and the uncertainty of the smart grid and high volume of information being collected, artificial intelligence techniques represent some of the enabling technologies for its future development and success. Owing to the decreasing cost of computing power, the profusion of data, and better algorithms, AI has entered into its new developmental stage and AI 2.0 is developing rapidly. Deep learning (DL), reinforcement learning (RL) and their combination-deep reinforcement learning (DRL) are representative methods and relatively mature methods in the family of AI 2.0. This article introduces the concept and status quo of the above three methods, summarizes their potential for application in smart grids, and provides an overview of the research work on their application in smart grids.
- Published
- 2018
45. Capturing functional long non-coding RNAs through integrating large-scale causal relations from gene perturbation experiments
- Author
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Yun Xiao, Aiming Xie, Liwen Xu, Gaoming Liao, Jian Huang, Xia Li, Aiai Shi, Jinyuan Xu, Tao Luo, Chunyu Deng, Zhilin Long, and Min Yan
- Subjects
0301 basic medicine ,Technology research ,medicine.medical_treatment ,Cancer metastasis ,Translational research ,Computational biology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Open Reading Frames ,03 medical and health sciences ,Basic research ,Immune infiltration ,Neoplasms ,medicine ,Humans ,Neoplasm Metastasis ,Gene ,Gene Expression Profiling ,Causal relations ,Cell Cycle ,Immunity ,Computational Biology ,General Medicine ,Immunotherapy ,medicine.disease ,Immune therapy ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Scale (social sciences) ,RNA, Long Noncoding ,Psychology ,Coding (social sciences) - Abstract
Characterizing functions of long noncoding RNAs (lncRNAs) remains a major challenge, mostly due to the lack of lncRNA-involved regulatory relationships. A wide array of genome-wide expression profiles generated by gene perturbation have been widely used to capture causal links between perturbed genes and response genes. Through annotating more than 600 gene perturbation profiles, over 354,000 causal relationships between perturbed genes and lncRNAs were identified. This large-scale resource of causal relations inspired us to develop a novel computational approach LnCAR for inferring lncRNAs' functions, which showed a higher accuracy than the co-expression based approach. By application of LnCAR to the cancer hallmark processes, we identified 38 lncRNAs involved in distinct carcinogenic processes. The "activating invasion & metastasis" related lncRNAs were strongly associated with metastatic progression in various cancer types and could act as a predictor of cancer metastasis. Meanwhile, the "evading immune destruction" related lncRNAs showed significant associations with immune infiltration of various immune cells and, importantly, can predict response to anti-PD-1 immunotherapy, suggesting their potential roles as biomarkers for immune therapy. Taken together, our approach provides a novel way to systematically reveal functions of lncRNAs, which will be helpful for further experimental exploration and clinical translational research of lncRNAs. Funding: This work was supported in part by the National High Technology Research and Development Program of China [863 Program, Grant Nos. 2014AA021102], the National Program on Key Basic Research Project [973 Program, Grant Nos. 2014CB910504], the National Natural Science Foundation of China [Grant Nos. 91439117, 61473106, 61573122], the China Postdoctoral Science Foundation (2016M600260), Wu lien-teh youth science fund project of Harbin medical university [Grant Nos. WLD-QN1407], Special funds for the construction of higher education in Heilongjiang Province [Grant Nos. UNPYSCT-2016049], and the Heilongjiang Postdoctoral Foundation (LBH-Z16098). Declaration of Interest: We declare that we have no competing financial interests regarding this work. There are no relationships with industry.
- Published
- 2018
46. Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy
- Author
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Ji-Yan Chen, Qian-jie Tang, Xiao-hong Li, Yong-heng Fu, Yubi Lin, Wang-sheng Sheng, Heping Lei, Chunyu Deng, Shi-Long Zhong, Ya-ling Han, and Hong Wu
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Heart Diseases ,medicine.medical_treatment ,Hemorrhage ,Coronary Artery Disease ,Article ,Coronary artery disease ,03 medical and health sciences ,Percutaneous Coronary Intervention ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Vascular Diseases ,cardiovascular diseases ,Prospective cohort study ,Aged ,Aged, 80 and over ,Pharmacology ,Aspirin ,business.industry ,Hazard ratio ,Percutaneous coronary intervention ,General Medicine ,Middle Aged ,Prognosis ,Clopidogrel ,medicine.disease ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Conventional PCI ,Female ,business ,Biomarkers ,Platelet Aggregation Inhibitors ,Mace ,medicine.drug - Abstract
MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30–2.59) at a false discovery rate of
- Published
- 2018
47. The Exploratory Research on Reform and Innovation of Project Management in Grid Enterprises under the Changing Circumstances
- Author
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Haiqing Xu, Jiandong Kang, Chunyu Deng, Junhui Li, Xiao Han, and Huaguang Yan
- Subjects
Process management ,business.industry ,Management system ,Exploratory research ,Business ,Power grid ,Project management system ,Project management ,Grid ,Organizational performance ,PATH (variable) - Abstract
At present, the management systems and enterprises demand have already changed because of the environments-changing, which puts new requirements and directions for grid enterprises. This research comprehensively analyzes the current situation and problems of the project management, and then explores the profound impact of the new situation to the project management system in power grid enterprises. After that, this research also summarizes the reforms and innovation experiences of the power grid enterprises in the project management, and extracts the project management characteristics of the grid enterprises under the new situation. At the same time, based on the project management practices, we provide a new method and implementation path for grid enterprises. This method and path provide theoretical and methodological support for relevant grid enterprises to improve their management efficiency and improve organizational performance.
- Published
- 2021
48. Broadband and compact polarization beam splitter in LNOI hetero-anisotropic metamaterials
- Author
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Ruohu Zhang, Mengjia Lu, Binfeng Yun, Chunyu Deng, Yu Sun, Lei Huang, Guohua Hu, Yiping Cui, and Dongyu Wang
- Subjects
Materials science ,Birefringence ,Extinction ratio ,business.industry ,Bandwidth (signal processing) ,Physics::Optics ,Metamaterial ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Polarization (waves) ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,010309 optics ,Transverse plane ,Optics ,0103 physical sciences ,Insertion loss ,0210 nano-technology ,Anisotropy ,business - Abstract
In this paper, theoretical modeling and numerical simulations of a high-performance polarization beam splitter (PBS) based on hetero-anisotropic metamaterials are proposed on the lithium-niobate-on-insulator (LNOI) platform. The hetero-anisotropic metamaterials constructed by sub-wavelength gratings (SWGs) can be regarded as effective anisotropy medium, which exhibits strong birefringence without breaking the geometrical symmetry, contributing to the formation of PBS. Rather than the principle of PBS based on beat-length difference of transverse electric (TE) polarization and transverse magnetic (TM) polarization, the device can realize polarization beam splitting in single beat length, and the footprint of the proposed PBS can be reduced to 8 µm × 160 µm (with S-bend). The simulation results show that the bandwidth is 185 nm (1450∼1634 nm) for TE polarization while the bandwidth is 85 nm (1490∼1575 nm) for TM polarization when the polarization extinction ratio is >20 dB. Furthermore, the insertion loss is less than 1 dB in the range of 1450 to 1650 nm, for both TE and TM polarization. Additionally, the proposed device proves strong robustness of the fabrication tolerance.
- Published
- 2021
49. Plasmonic nanocavity for obtaining bound state in the continuum in silicon waveguides
- Author
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Yiping Cui, Pengfei Zheng, Lilong Zhao, Wang Feng, Ying Li, Guohua Hu, Bo Liu, Chunyu Deng, and Zhipeng Qi
- Subjects
Physics ,Quantum optics ,Silicon ,business.industry ,Nanophotonics ,Physics::Optics ,chemistry.chemical_element ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,010309 optics ,Optics ,chemistry ,Electric field ,Q factor ,0103 physical sciences ,Bound state ,Optoelectronics ,Nanorod ,0210 nano-technology ,business ,Plasmon - Abstract
Bound states in the continuum (BICs) have become a new trend in the area of metaoptics and nanophotonics. Strong interactions in electromagnetic fields are analogous to electron transitions in atoms, giving rise to BICs with vanishing radiative losses. However, it is still a great challenge to realize BICs in the lossy plasmonic systems. For this problem, we propose a supercavity-like plasmonic nanocavity consisting of an Au nanorod deposited inside an Au symmetric split ring, and explore the possibility of exciting quasi-BICs that own finite but high quality (Q) factors. In such hybrid configuration, the excited resonances can be easily engineered by modifying the rotation angle or the length of the Au nanorod. With the integration of such nanocavity in silicon (Si) waveguides, sharp transmission spectra could be achieved with fiber-chip in-parallel excitations and detections. Besides, the ultracompact geometry of this plasmonic nanocavity provides a route to boost enhanced electric fields, thus improving sensing performances significantly. Our study not only offers a novel platform for the realization of chip-scale quasi-BICs, but extends functionalities of photonic-plasmonic hybrid circuits.
- Published
- 2021
50. Dexmedetomidine inhibits vasoconstriction via activation of endothelial nitric oxide synthase
- Author
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Jue Ma, Lidan Nong, Chunyu Deng, Jianxiu Cui, Songsong Mao, Haifeng Li, and Guangyan Zhang
- Subjects
Serotonin ,Physiology ,030204 cardiovascular system & hematology ,Pharmacology ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,030202 anesthesiology ,Enos ,medicine.artery ,polycyclic compounds ,Medicine ,Human pulmonary arteries ,biology ,business.industry ,biology.organism_classification ,Yohimbine ,Nitric oxide synthase ,chemistry ,Vasoconstriction ,Anesthesia ,Pulmonary artery ,biology.protein ,Original Article ,Cyclooxygenase ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists ,Dexmedetomidine ,Myograph ,medicine.drug - Abstract
Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10(-8)~10(-6) mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10(-9) mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α2-adrenoceptor and nitric oxide synthase.
- Published
- 2016
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