106 results on '"Daming, Gao"'
Search Results
2. Constructing a Ring-like Self-Aggregation SERS Sensor with the Coffee Ring Effect for Ultrasensitive Detection and Photocatalytic Degradation of the Herbicides Paraquat and Diquat
- Author
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Caiyu Ni, Jiadong Zhao, Xiaoxiao Xia, Zhihui Wang, Xiaoxiao Zhao, Junyu Yang, Nianxi Zhang, Yang Yang, Hui Zhang, and Daming Gao
- Subjects
General Chemistry ,General Agricultural and Biological Sciences - Abstract
A strategy for building ring-like deposit surface-enhanced Raman scattering (SERS) sensors with the coffee ring effect through the functional modification of the silica nanoparticle surface encapsulated by free-tagged Ag nanoparticles is addressed along with their applications in the SERS-based detection and degradation of target species, including paraquat, diquat, and their free radicals. The nanogap formed by two interparticles with SERS hotspots provides a gigantic amplification signal for the Raman scattering intensity of the analyte molecule located approximately at the hotspots. The enhanced Raman spectrum signals of these target analytes were achieved through the hotspot region of the surface plasmon resonance (SPR) located on the embankment formed by self-aggregation of SiO
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- 2022
3. An integrated framework for agricultural non-point source pollution control technology evaluation: Application of an improved multiple attribute decision making method
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Yao Ji, Daming Gao, Quanli Liu, Jing Su, Yue Liu, Jian Zhao, Yanmei Yang, Yu Fu, and Guohe Huang
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Artificial Intelligence ,General Engineering ,Computer Science Applications - Published
- 2023
4. Figure S1-4 and supplementary material and methods from SCFFBXW7/GSK3β-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells
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Daming Gao, Wenyi Wei, Zhiwei Wang, Jun Qin, Jianfei Huang, Hu Zhou, Hongwen Zhu, Junqiang Li, Yuxue Zhang, Binghai Cui, Min Chen, Kangjunjie Wang, Ran Chen, Long Li, and Xiaoling Kuai
- Abstract
Figure S1-GFI1 promotes GC cell proliferation and suppresses GKN2 expression.Figure S2-FBXW7 governs GFI1 stability.Figure S3-GSK3β destabilizes GFI1 and negatively regulates GFI1 expression. Figure S4-Spectrum of peptide containing GFI1 S94 phosphorylation.
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- 2023
5. Figure S1-S7 from FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2–Mediated Phosphorylation of CENP-A
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Qing Zhang, Wenyi Wei, Gary H. Karpen, Guohong Li, Kerry Bloom, Christopher J. Fry, Bo Zhai, Lianxin Hu, Ming Zhuang, Lixin Wan, Daming Gao, Hiroyuki Inuzuka, Zhouliang Yu, Taruho S. Kuroda, Aussie Suzuki, Weiguo Zhang, and Mamoru Takada
- Abstract
Supplemental Figures for "FBW7 loss promotes chromosomal instability and tumorigenesis via Cyclin E1/CDK2-mediated phosphorylation of CENP-A"
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- 2023
6. Table S1 from FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2–Mediated Phosphorylation of CENP-A
- Author
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Qing Zhang, Wenyi Wei, Gary H. Karpen, Guohong Li, Kerry Bloom, Christopher J. Fry, Bo Zhai, Lianxin Hu, Ming Zhuang, Lixin Wan, Daming Gao, Hiroyuki Inuzuka, Zhouliang Yu, Taruho S. Kuroda, Aussie Suzuki, Weiguo Zhang, and Mamoru Takada
- Abstract
Table S1: Antibodies used in this paper.
- Published
- 2023
7. Data from SCFFBXW7/GSK3β-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells
- Author
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Daming Gao, Wenyi Wei, Zhiwei Wang, Jun Qin, Jianfei Huang, Hu Zhou, Hongwen Zhu, Junqiang Li, Yuxue Zhang, Binghai Cui, Min Chen, Kangjunjie Wang, Ran Chen, Long Li, and Xiaoling Kuai
- Abstract
Gastric cancer is the third leading cause of cancer-related death worldwide. The regulatory mechanisms underlying gastric cancer cell proliferation are largely unclear. Here, we show that the transcription factor GFI1 is associated with advanced clinical gastric cancer progression and promoted gastric cancer cell proliferation partially through inhibition of gastrokine-2 (GKN2) transcription. GFI1 was a degrading substrate of FBXW7, whose loss was observed in gastric cancer. Mechanistically, GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation. A nondegradable GFI1 S94A/S98A mutant was more potent in driving gastric cancer cell proliferation and tumorigenesis than wild-type GFI1. Overall, this study reveals the oncogenic role of GFI1 in gastric cancer and provides mechanistic insights into the tumor suppressor function of FBXW7.Significance:These findings demonstrate the oncogenic role of the transcription factor GFI1 and the tumor suppressive function of FBXW7 in gastric cancer.
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- 2023
8. Data from FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2–Mediated Phosphorylation of CENP-A
- Author
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Qing Zhang, Wenyi Wei, Gary H. Karpen, Guohong Li, Kerry Bloom, Christopher J. Fry, Bo Zhai, Lianxin Hu, Ming Zhuang, Lixin Wan, Daming Gao, Hiroyuki Inuzuka, Zhouliang Yu, Taruho S. Kuroda, Aussie Suzuki, Weiguo Zhang, and Mamoru Takada
- Abstract
The centromere regulates proper chromosome segregation, and its dysfunction is implicated in chromosomal instability (CIN). However, relatively little is known about how centromere dysfunction occurs in cancer. Here, we define the consequences of phosphorylation by cyclin E1/CDK2 on a conserved Ser18 residue of centromere-associated protein CENP-A, an essential histone H3 variant that specifies centromere identity. Ser18 hyperphosphorylation in cells occurred upon loss of FBW7, a tumor suppressor whose inactivation leads to CIN. This event on CENP-A reduced its centromeric localization, increased CIN, and promoted anchorage-independent growth and xenograft tumor formation. Overall, our results revealed a pathway that cyclin E1/CDK2 activation coupled with FBW7 loss promotes CIN and tumor progression via CENP-A–mediated centromere dysfunction. Cancer Res; 77(18); 4881–93. ©2017 AACR.
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- 2023
9. Screening Ionic Liquids as Entrainers for Separation of Acetonitrile and Water Azeotropic Systems by Combining Theoretical and Experimental Investigationsscreening Ionic Liquids as Entrainers for Separation of Acetonitrile and Water Azeotropic Systems by Combining Theoretical and Experimental Investigations
- Author
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Yuan Cheng, Jing Wang, Daming Gao, Hui Zhang, Young Min Kwon, Xiaochen Wang, Anqiu Liu, Lingyun Zhang, and Chan Kyung Kim
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- 2023
10. An Amphiphilic Nitrogen-Doped Graphene Prepared by Ammonia Cold Plasma and its Supported Platinum Nanocatalyst for Aqueous-Phase Hydrogenation of Cinnamaldehyde
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Ping Wang, Xia Yi, Mohong Lu, Pengcheng Huang, Yuan Wang, Daming Gao, Yanan Wei, Xiaowei Xie, and Jie Zhu
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- 2023
11. Comprehensive Analysis of Sorafenib Druggable Targets on Differential Gene Expression and ceRNA Network in Hepatocellular Carcinoma
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Zhi Fu, Guang Yang, Tiezheng Wang, Daming Gao, Dongdong Lin, and Xiaoni Liu
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Health, Toxicology and Mutagenesis ,General Medicine ,Toxicology ,Pathology and Forensic Medicine - Published
- 2023
12. Nanostructured Shell-Layer Artificial Antibody with Fluorescence-Tagged Recognition Sites for the Trace Detection of Heavy Metal Ions by Self-Reporting Microsensor Arrays
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Xianfeng Du, Xiaoxiao Xia, Daming Gao, Yue Cai, En Yang, and Fei Chang
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Materials science ,Polymers ,Metal ions in aqueous solution ,Inorganic chemistry ,Nanoparticle ,Conjugated system ,Methacrylate ,Antibodies ,Fluorescence ,Molecular Imprinting ,Metal ,Biomimetic Materials ,Metals, Heavy ,Materials Testing ,Molecule ,General Materials Science ,Ions ,chemistry.chemical_classification ,Molecularly imprinted polymer ,Polymer ,Silicon Dioxide ,Nanostructures ,Spectrometry, Fluorescence ,chemistry ,visual_art ,visual_art.visual_art_medium ,Microtechnology ,Spectrophotometry, Ultraviolet - Abstract
Herein, a strategy for a metal ion-imprinted artificial antibody with recognition sites tagged by fluorescein was carried out to construct the selective sites with a sensitive optical response signal to the specific metal ion. The synthesized silica nanoparticles were modified by the derivative residue group of 3-aminopropyltriethoxysilane conjugated with a 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) molecule through the hydrolysis and condensation reactions. The as-prepared silica nanoparticles were encapsulated by metal ion (Cu2+, Cd2+, Hg2+, and Pb2+)-imprinted polymers with nanostructured layers through the copolymerization of ethyl glycol dimethyl methacrylate (EGDMA) as a cross-linker, AIBN as an initiator, metal ions as template molecules, AA as a functional monomer, and acetonitrile as a solvent. The layers of molecular imprinted polymers (MIPs) with a core-shell structure removed template molecules by EDTA-2Na to retain the cavities and spatial sizes to match the imprinted metal ions. The microsensor arrays were achieved by the self-assembly technique of SiO2@MIP nanoparticles on the etched silicon wafer with regular dot arrays. The nanostructured-shell layers with fluorescence-tagged recognition sites rebound metal ions by the driving force of concentration difference demonstrates the high selective recognition and sensitive detection to heavy metal ions through the decline of fluorescence intensity. The LOD concentration for four metal ions is down to 10-9 mol·L-1. The method will provide biomimetic synthesis, analyte screen, and detection of highly dangerous materials in the environment for theoretical foundation and technological support.
- Published
- 2021
13. USP10 strikes down β-catenin by dual-wielding deubiquitinase activity and phase separation potential
- Author
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Yinuo Wang, Aihua Mao, Jingwei Liu, Pengjie Li, Shaoqin Zheng, Tong Tong, Zexu Li, Haijiao Zhang, Lanjing Ma, Jiahui Lin, Zhongqiu Pang, Qing Han, Fukang Qi, Xinjun Zhang, Maorong Chen, Xi He, Xi Zhang, Teng Fei, Bi-Feng Liu, Daming Gao, Liu Cao, Qiang Wang, Yiwei Li, and Ren Sheng
- Abstract
Wnt/β-catenin signaling is a conserved pathway crucially governing development, homeostasis and oncogenesis. Discovery of novel regulators holds great values in both basic and translational research. Through screening, we identified a deubiquitinase (DUB) USP10 as a novel and critical modulator of β-catenin. Mechanistically, USP10 binds to key scaffold Axin1 via conserved motifs and stabilizes Axin1 through K48-linked deubiquitination, and surprisingly, tethers Axin1 and β-catenin physically while promoting phase separation for β-catenin suppression regardless of its enzymatic activity. Functionally, USP10 prominently regulates embryonic development and intestinal homeostasis by antagonizing β-catenin via DUB activity. In colorectal cancer, USP10 substantially represses cancer growth mainly through physical binding compensation and phase separation promotion and correlates with Wnt/β-catenin magnitude clinically. Collectively, we discovered USP10 functioning in multiple biological processes against β-catenin and unearthed a novel enzyme-dependent and -independent “dual-regulating” mechanism by which USP10 utilizes parallelly and context-dependently. USP10 inhibitor was suggested in treating certain Wnt-related diseases.
- Published
- 2022
14. Evolution for Composition Analysis and Pattern of Shouzhou Kiln Porcelain by Comparison of Sui and Tang Dynasties and the Contemporary Era
- Author
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Xiaoyang Liu and Daming Gao
- Abstract
Shouzhou kiln is located in the north of Anhui Province. Its porcelain was first fired in the Six Dynasties, peaked in the Sui and Tang Dynasties, but gradually declined in the late Tang Dynasty. Shouzhou kiln complied with the trend of the times and catered to the aesthetic taste of the public. In the Tang Dynasty, a new way was found, which laid a solid foundation for its great development and prosperity. In order to compare the differences between the Sui and Tang Dynasties and the modern Shouzhou kiln in the production process and composition, XRF and XRD were employed to analyze their compositions and structures. The results confirm that the main components are silica and alumina, which exist in the form of quartzite and mullite, indicating that the materials used for the body and glaze of Shouzhou kiln porcelain are relatively stable.
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- 2022
15. Multimodule characterization of immune subgroups in intrahepatic cholangiocarcinoma reveals distinct therapeutic vulnerabilities
- Author
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Jian Lin, Yuting Dai, Chen Sang, Guohe Song, Bin Xiang, Mao Zhang, Liangqing Dong, Xiaoli Xia, Jiaqiang Ma, Xia Shen, Shuyi Ji, Shu Zhang, Mingjie Wang, Hai Fang, Xiaoming Zhang, Xiangdong Wang, Bing Zhang, Jian Zhou, Jia Fan, Hu Zhou, Daming Gao, and Qiang Gao
- Subjects
Pharmacology ,Inflammation ,Proteomics ,Cancer Research ,Hepatitis B virus ,Immunology ,Cholangiocarcinoma ,Mice ,Bile Ducts, Intrahepatic ,Oncology ,Bile Duct Neoplasms ,Tumor Microenvironment ,Molecular Medicine ,Immunology and Allergy ,Animals ,Humans - Abstract
BackgroundImmune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications.MethodsWe performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues. We validated our findings through H&E staining (n=177), multiplex immunostaining (n=188), single-cell RNA sequencing (scRNA-seq) (n=10), in vitro functional studies, and in vivo transposon-based mouse models.ResultsIntegrated multimodule data identified three immune subgroups with distinct clinical, genetic, and molecular features, designated as IG1 (immune-suppressive, 25.1%), IG2 (immune-exclusion, 42.7%), and IG3 (immune-activated, 32.2%). IG1 was characterized by excessive infiltration of neutrophils and immature dendritic cells (DCs). The hallmark of IG2 was the relatively higher tumor-proliferative activity and tumor purity. IG3 exhibited an enrichment of adaptive immune cells, natural killer cells, and activated DCs. These immune subgroups were significantly associated with prognosis and validated in two independent cohorts. Tumors with KRAS mutations were enriched in IG1 and associated with myeloid inflammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures were both predominant in IG3. Hepatitis B virus (HBV)-related samples tended to be under-represented in IG1, and scRNA-seq analyses implied that HBV infection indeed alleviated myeloid inflammation and reinvigorated antitumor immunity.ConclusionsOur study elucidates that the immunogenomic traits of iCCA are intrinsically heterogeneous among patients, posing great challenge and opportunity for the application of personalized immunotherapy.
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- 2022
16. Correction to: A novel strategy for efficient disaccharides synthesis from glucose by β-glucosidase
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Kangle Niu, Zhengyao Liu, Yuhui Feng, Tianlong Gao, Zhenzhen Wang, Piaopiao Zhang, Zhiqiang Du, Daming Gao, and Xu Fang
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Renewable Energy, Sustainability and the Environment ,Biomedical Engineering ,Food Science ,Biotechnology - Published
- 2022
17. Combined Experimental and Theoretical Studies on the Prediction of the Isobaric Vapor–Liquid Association Phenomena for Binary and Ternary Mixtures of Water, Ethanoic Acid, and Propanoic Acid
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Xiaochen Wang, Chan Kyung Kim, Zhang Lingyun, Nasir Shahzad, Liu Anqiu, Xiaoxiao Xia, Daming Gao, Zhang Hui, Zhang Lidong, Young Min Kwon, Hong Chen, and Dechun Zhu
- Subjects
Ternary numeral system ,Materials science ,General Chemical Engineering ,Binary number ,Thermodynamics ,02 engineering and technology ,General Chemistry ,021001 nanoscience & nanotechnology ,Industrial and Manufacturing Engineering ,Chemical separation ,020401 chemical engineering ,Phase (matter) ,Non-random two-liquid model ,Isobaric process ,Vapor liquid ,0204 chemical engineering ,0210 nano-technology ,Ternary operation - Abstract
It is a considerable challenge for the phase behavior of chemical separation industry to correlate and predict the vapor–liquid equilibria (VLE) data of the binary and ternary systems containing as...
- Published
- 2020
18. Measurements and Correlation of Isobaric Vapor–Liquid Equilibrium Data for Binary Mixtures of Furan, Oxolane, and Furan-2-Carbaldehyde and Application of the Binary Model Parameters for Further Prediction of the Ternary System
- Author
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Liu Anqiu, Xiaochen Wang, Daming Gao, Zhang Hui, Zhang Lidong, Zhang Lingyun, Dechun Zhu, Chen Qianyun, and Hong Chen
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chemistry.chemical_compound ,Binary Independence Model ,Ternary numeral system ,Chemistry ,General Chemical Engineering ,Furan ,Vapor–liquid equilibrium ,Binary number ,Thermodynamics ,Isobaric process ,General Chemistry - Abstract
Depending on the available experimental data (T, p, x, y, and HE), the vapor–liquid equilibrium (VLE) data of the completely miscible isobaric systems at low pressure are accurately correlated and ...
- Published
- 2020
19. Constructed the Ring-Like Self-Aggregation Sers Sensor by Coffee Ring Effect for Ultrasensitive Detection and Photocatalytic Degradation of Herbicide Paraquat and Diquat
- Author
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Caiyu Ni, Jiadong Zhao, Xiaoxiao Xia, Zhihui Wang, Xiaoxiao Zhao, Junyu Yang, Nianxi Zhang, Hui Zhang, and Daming Gao
- Published
- 2022
20. scEMC10, a novel circulating inhibitor of adipocyte thermogenesis, is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity
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Xuanchun Wang, Guifen Qiang, YANLIANG LI, Kaihua Wang, Jiarong Dai, Maximilian McCann, Victoria Gil, Yifei Yu, Shengxian Li, Zhihong Yang, Shanshan XU, Jose Cordoba-Chacon, Dario F De Jesus, Bei Sun, Kuangyang Chen, Xiaoxia Liu, Qing Miao, Linuo Zhou, Renming Hu, Qiang Ding, Rohit Kulkarni, Daming Gao, Matthias Blüher, and Chong Wee Liew
- Abstract
Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterised secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in humans with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a novel circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.
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- 2021
21. Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice
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Xuanchun Wang, Yanliang Li, Guifen Qiang, Kaihua Wang, Jiarong Dai, Maximilian McCann, Marcos D. Munoz, Victoria Gil, Yifei Yu, Shengxian Li, Zhihong Yang, Shanshan Xu, Jose Cordoba-Chacon, Dario F. De Jesus, Bei Sun, Kuangyang Chen, Yahao Wang, Xiaoxia Liu, Qing Miao, Linuo Zhou, Renming Hu, Qiang Ding, Rohit N. Kulkarni, Daming Gao, Matthias Blüher, and Chong Wee Liew
- Subjects
Multidisciplinary ,General Physics and Astronomy ,Mice, Obese ,Membrane Proteins ,Biological Transport ,General Chemistry ,Antibodies, Neutralizing ,General Biochemistry, Genetics and Molecular Biology ,Diet ,Mice ,Humans ,Animals ,Obesity ,Insulin Resistance - Abstract
Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.
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- 2021
22. Editorial: Ubiquitin Code: From Cell Biology to Translational Medicine
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Cui Hua, Liu, Yu, Rao, Daming, Gao, Lixin, Wan, and Lingqiang, Zhang
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PROTAC technology ,Cell and Developmental Biology ,ubiquitin code ,disease ,Editorial ,ubiquitination ,deubiquitination - Published
- 2021
23. SCFFBXW7/GSK3β-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells
- Author
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Jianfei Huang, Hongwen Zhu, Long Li, Junqiang Li, Jun Qin, Min Chen, Wenyi Wei, Daming Gao, Ran Chen, Xiaoling Kuai, Hu Zhou, Binghai Cui, Zhiwei Wang, Yuxue Zhang, and Kangjunjie Wang
- Subjects
0301 basic medicine ,Cancer Research ,biology ,Cell growth ,Chemistry ,digestive, oral, and skin physiology ,medicine.disease_cause ,law.invention ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Ubiquitin ,law ,Transcription (biology) ,030220 oncology & carcinogenesis ,Cancer cell ,medicine ,biology.protein ,Cancer research ,Phosphorylation ,Suppressor ,Carcinogenesis ,Transcription factor - Abstract
Gastric cancer is the third leading cause of cancer-related death worldwide. The regulatory mechanisms underlying gastric cancer cell proliferation are largely unclear. Here, we show that the transcription factor GFI1 is associated with advanced clinical gastric cancer progression and promoted gastric cancer cell proliferation partially through inhibition of gastrokine-2 (GKN2) transcription. GFI1 was a degrading substrate of FBXW7, whose loss was observed in gastric cancer. Mechanistically, GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation. A nondegradable GFI1 S94A/S98A mutant was more potent in driving gastric cancer cell proliferation and tumorigenesis than wild-type GFI1. Overall, this study reveals the oncogenic role of GFI1 in gastric cancer and provides mechanistic insights into the tumor suppressor function of FBXW7. Significance: These findings demonstrate the oncogenic role of the transcription factor GFI1 and the tumor suppressive function of FBXW7 in gastric cancer.
- Published
- 2019
24. Crosstalk between signaling pathways and DNA damage response
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Kangjunjie Wang, Daming Gao, Long Li, and Yuxue Zhang
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body regions ,Crosstalk (biology) ,chemistry.chemical_compound ,Molecular level ,chemistry ,DNA damage ,Signal transduction ,Biology ,Human genetics ,DNA ,Signaling system ,Cell biology ,Genome stability - Abstract
Living organisms have developed a complex signaling system to sense diverse growth signals and co-ordinate intracellular bioprocesses, so that they survive in various conditions. Since organisms are often exposed to environmental and genomic threats which cause DNA damages, DNA damage response (DDR) and repair systems are important for maintenance of genome stability and integrity. A line of evidences has demonstrated that there is tight crosstalk between growth signaling pathways and DDR systems. In this review, we give a brief overview of recent reports dissecting the interaction between signaling pathways and DDR at molecular level, which may further expand the knowledge of the signaling network and provide clues for disease therapy.
- Published
- 2019
25. Identification of a USP9X Substrate NFX1-123 by SILAC-Based Quantitative Proteomics
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Yanting Zhou, Xiangling Chen, Jing Gao, Hu Zhou, Daming Gao, Hongwen Zhu, and Dayun Lu
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Proteomics ,0301 basic medicine ,Proteasome Endopeptidase Complex ,Immunoprecipitation ,Quantitative proteomics ,Apoptosis ,Biochemistry ,Deubiquitinating enzyme ,HeLa ,03 medical and health sciences ,Ubiquitin ,Stable isotope labeling by amino acids in cell culture ,Humans ,Cell Proliferation ,Gene knockdown ,030102 biochemistry & molecular biology ,biology ,Chemistry ,Ubiquitination ,General Chemistry ,biology.organism_classification ,Cell biology ,Repressor Proteins ,030104 developmental biology ,Gene Expression Regulation ,Gene Knockdown Techniques ,Nerve Degeneration ,biology.protein ,Ubiquitin Thiolesterase ,HeLa Cells ,Deubiquitination - Abstract
The deubiquitinase USP9X is involved in multiple diseases including neurodegeneration, epilepsy, and various types of tumors by targeting different substrates. In the present study, we aimed to explore the potential substrates of USP9X and performed SILAC-based quantitative proteomics to compare these substrates in USP9X-knockdown and wild-type HeLa cells. We consequently carried out Flag-NFX1-123 tag affinity-based mass spectrometry and confirmed that the X-box binding nuclear factor NFX1-123 interacted with USP9X. Moreover, immunoprecipitation assays verified a direct interaction between USP9X and NFX1-123. Further experiments confirmed that NFX1-123 could be modified by ubiquitination and that USP9X stabilized NFX1-123 via efficient deubiquitination of NFX1-123. Knockdown of USP9X resulted in decreased NFX1-123 protein levels compared with their unchanged corresponding mRNA levels in different cell lines. In summary, we found that NFX1-123 was a bona fide substrate of the deubiquitinase USP9X and that it could be degraded by the ubiquitin-proteasome system. The present study provided new insight into understanding the biological function of USP9X by targeting its substrate NFX1-123.
- Published
- 2019
26. Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma
- Author
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Liangqing Dong, Dayun Lu, Ran Chen, Youpei Lin, Hongwen Zhu, Zhou Zhang, Shangli Cai, Peng Cui, Guohe Song, Dongning Rao, Xinpei Yi, Yingcheng Wu, Nixue Song, Fen Liu, Yunhao Zou, Shu Zhang, Xiaoming Zhang, Xiaoying Wang, Shuangjian Qiu, Jian Zhou, Shisheng Wang, Xu Zhang, Yongyong Shi, Daniel Figeys, Li Ding, Pei Wang, Bing Zhang, Henry Rodriguez, Qiang Gao, Daming Gao, Hu Zhou, and Jia Fan
- Subjects
Cholangiocarcinoma ,Proteomics ,Cancer Research ,Bile Ducts, Intrahepatic ,Oncology ,Bile Duct Neoplasms ,Liver ,Mutation ,Tumor Microenvironment ,Humans ,Prognosis ,Proteogenomics - Abstract
We performed proteogenomic characterization of intrahepatic cholangiocarcinoma (iCCA) using paired tumor and adjacent liver tissues from 262 patients. Integrated proteogenomic analyses prioritized genetic aberrations and revealed hallmarks of iCCA pathogenesis. Aflatoxin signature was associated with tumor initiation, proliferation, and immune suppression. Mutation-associated signaling profiles revealed that TP53 and KRAS co-mutations may contribute to iCCA metastasis via the integrin-FAK-SRC pathway. FGFR2 fusions activated the Rho GTPase pathway and could be a potential source of neoantigens. Proteomic profiling identified four patient subgroups (S1-S4) with subgroup-specific biomarkers. These proteomic subgroups had distinct features in prognosis, genetic alterations, microenvironment dysregulation, tumor microbiota composition, and potential therapeutics. SLC16A3 and HKDC1 were further identified as potential prognostic biomarkers associated with metabolic reprogramming of iCCA cells. This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in iCCA.
- Published
- 2021
27. Detailed studies on the anticancer action of rosmarinic acid in human Hep-G2 liver carcinoma cells: evaluating its effects on cellular apoptosis, caspase activation and suppression of cell migration and invasion
- Author
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Boxun, Jin, Jinning, Liu, Daming, Gao, Ying, Xu, Li, He, Yunjin, Zang, Ning, Li, and Dongdong, Lin
- Subjects
Carcinoma, Hepatocellular ,Cell Survival ,Liver Neoplasms ,Antineoplastic Agents ,Apoptosis ,Hep G2 Cells ,Depsides ,Liver ,Proto-Oncogene Proteins c-bcl-2 ,Cell Movement ,Cinnamates ,Caspases ,Cell Line, Tumor ,Humans ,Cell Proliferation ,Signal Transduction - Abstract
Liver cancer is one of the most common and highly malignant cancers of the digestive system. The main aim of the present research work was to investigate the anticancer action of rosmarinic acid - a naturally occurring plant secondary metabolite. We also investigated its effects on cell apoptosis, caspase activation, cell migration and cell invasion.Cell viability of Hep-G2 liver cancer cells was evaluated by CCK-8 assay while apoptotic studies were carried out by fluorescence microscopy using Hoechst, acridine orange (AO)/ethidium bromide (EB) and Comet assays as well as using annexin-v/propidium iodide (PI) assay for apoptosis quantification. Western blot assay was used to study the effects of rosmarinic acid on apoptosis-related protein expressions including Bax, Bcl-2 and various caspases. In vitro wound healing assay was used to evaluate the effects on cell migration while transwell chambers assay with Matrigel was used to assess the effects of rosmarinic acid on cell invasion.Rosmarinic acid caused significant reduction in the viability of the human Hep-G2 liver carcinoma cells in a dose-dependent manner, exhibiting an IC50 of 14 µM in cancer cells. The AO/EB staining assay showed that rosmarinic acid suppressed the viability of cancer cells via induction of apoptotic cell death which was associated with rise in Bax and decrease in Bcl-2 levels. DAPI staining results also confirmed that rosmarinic acid induced apoptosis. The apoptotic cells increased from 5.8% in control to 24.68% at 28 µM concentration of rosmarinic acid. Rosmarinic acid also caused activation of caspase-3 and 9 along with suppressing liver cancer cell migration and invasion.The current study shows that rosmarinic acid has a potential to inhibit in vitro cancer cell growth in Hep-G2 cells by triggering apoptosis, caspase activation and suppressing cell migration and invasion and as such this molecule could be developed as a possible anticancer agent provided further studies are carried out.
- Published
- 2020
28. A novel strategy for efficient disaccharides synthesis from glucose by β-glucosidase
- Author
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Kangle Niu, Daming Gao, Zhiqiang Du, Tianlong Gao, Piaopiao Zhang, Zhenzhen Wang, Zhengyao Liu, Xu Fang, and Yuhui Feng
- Subjects
0301 basic medicine ,Sophorose ,Reverse hydrolysis reaction ,Stereochemistry ,Hydropathy index ,lcsh:Biotechnology ,Biomedical Engineering ,Cellobiose ,lcsh:Chemical technology ,01 natural sciences ,lcsh:Technology ,03 medical and health sciences ,chemistry.chemical_compound ,Hydrolysis ,lcsh:TP248.13-248.65 ,Monosaccharide ,lcsh:TP1-1185 ,Laminaribiose ,Disaccharide synthesis ,chemistry.chemical_classification ,Site-directed mutagenesis ,010405 organic chemistry ,Renewable Energy, Sustainability and the Environment ,lcsh:T ,Rational design ,0104 chemical sciences ,β-Glucosidase ,030104 developmental biology ,Enzyme ,chemistry ,Docking (molecular) ,Food Science ,Biotechnology - Abstract
Oligosaccharides have important therapeutic applications. A useful route for oligosaccharides synthesis is reverse hydrolysis by β-glucosidase. However, the low conversion efficiency of disaccharides from monosaccharides limits its large-scale production because the equilibrium is biased in the direction of hydrolysis. Based on the analysis of the docking results, we hypothesized that the hydropathy index of key amino acid residues in the catalytic site is closely related with disaccharide synthesis and more hydrophilic residues located in the catalytic site would enhance reverse hydrolysis activity. In this study, positive variants TrCel1bI177S, TrCel1bI177S/I174S, and TrCel1bI177S/I174S/W173H, and one negative variant TrCel1bN240I were designed according to the Hydropathy Index For Enzyme Activity (HIFEA) strategy. The reverse hydrolysis with TrCel1bI177S/I174S/W173H was accelerated and then the maximum total production (195.8 mg/mL/mg enzyme) of the synthesized disaccharides was increased by 3.5-fold compared to that of wildtype. On the contrary, TrCel1bN240I lost reverse hydrolysis activity. The results demonstrate that the average hydropathy index of the key amino acid residues in the catalytic site of TrCel1b is an important factor for the synthesis of laminaribiose, sophorose, and cellobiose. The HIFEA strategy provides a new perspective for the rational design of β-glucosidases used for the synthesis of oligosaccharides.
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- 2020
29. Efficient Synthesis of Rare Disaccharides by Engineered β-Glucosidase Based on Hydropathy Index
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Zhenzhen Wang, Yuhui Feng, Piaopiao Zhang, Xu Fang, Daming Gao, Zhiqiang Du, Tianlong Gao, Kangle Niu, and Zhengyao Liu
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chemistry.chemical_classification ,chemistry.chemical_compound ,Hydrolysis ,Enzyme ,chemistry ,Sophorose ,Stereochemistry ,Rational design ,Monosaccharide ,Cellobiose ,Hydrophobicity scales ,Laminaribiose - Abstract
Oligosaccharides have important therapeutic applications. A useful route for oligosaccharides synthesis, especially rare disaccharides, is reverse hydrolysis by β-glucosidase. However, the low conversion efficiency of disaccharides from monosaccharides limits its large-scale production because the equilibrium is biased in the direction of hydrolysis. Based on the analysis of the docking results, we hypothesized that the hydropathy index of key amino acid residues in the catalytic site is closely related with disaccharide synthesis and more hydrophilic residues located in the catalytic site would enhance reverse hydrolysis activity. In this study, positive variants TrCel1bI177S, TrCel1bI177S/I174S, and TrCel1bI177S/I174S/W173H, and one negative variant TrCel1bN240I were designed according to the Hydropathy Index For Enzyme Activity (HIFEA) strategy. The reverse hydrolysis with TrCel1bI177S/I174S/W173H was accelerated and then the maximum total production (195.8 mg/ml/mg enzyme) of the synthesized disaccharides was increased 3.5-fold compared to that of wildtype. On the contrary, TrCel1bN240I lost reverse hydrolysis activity. The results demonstrate that the average hydropathy index of the key amino acid residues in the catalytic site of TrCel1b is an important factor for the synthesis of laminaribiose, sophorose, and cellobiose. The HIFEA strategy provides a new perspective for the rational design of β-glucosidases used for the synthesis of oligosaccharides.
- Published
- 2020
30. Development of A Novel Highly Selective TLR8 Agonist for Cancer Immunotherapy
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Huanming Yang, L. Wang, Xin Sun, Daming Gao, Yiming Zeng, Peng George Wang, Y. Wang, Xin Lin, Fu G, Suwen Zhao, Haitao Li, Peng Zhang, and Yu-Tang Gao
- Subjects
Agonist ,Innate immune system ,Immune system ,Cancer immunotherapy ,In vivo ,medicine.drug_class ,Chemistry ,Pathogen-associated molecular pattern ,medicine.medical_treatment ,medicine ,Cancer research ,TLR8 ,Ex vivo - Abstract
Toll-like receptors (TLRs) are a family of proteins that recognize pathogen associated molecular patterns (PAMPs). Their primary function is to activate innate immune responses while also involved in facilitating adaptive immune responses. Different TLRs exert distinct functions by activating varied immune cascades. Several TLRs are being pursued as cancer drug targets. We discovered a novel, highly potent and selective small molecule TLR8 agonist DN052. DN052 exhibited strong in vitro cellular activity with EC50 at 6.7 nM and was highly selective for TLR8 over other TLRs including TLR4, 7 and 9. The selectivity profile distinguished DN052 from all other TLR agonists currently in clinical development. DN052 displayed excellent in vitro ADMET and in vivo PK profiles. DN052 potently inhibited tumor growth as a single agent. Moreover, combination of DN052 with the immune checkpoint inhibitor, selected targeted therapeutics or chemotherapeutic drugs further enhanced efficacy of single agents. Mechanistically, treatment with DN052 resulted in strong induction of pro-inflammatory cytokines in ex vivo human PBMC assay and in vivo monkey study. GLP toxicity studies in rats and monkeys demonstrated favorable safety profile. This led to the advancement of DN052 into phase I clinical trials.
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- 2020
31. Additional file 1 of A novel strategy for efficient disaccharides synthesis from glucose by β-glucosidase
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Kangle Niu, Zhengyao Liu, Yuhui Feng, Tianlong Gao, Zhenzhen Wang, Piaopiao Zhang, Zhiqiang Du, Daming Gao, and Fang, Xu
- Abstract
Additional file 1: Fig. S1. The phylogenetic tree of TrCel1b and other GH1 family β-glucosidases. Fig. S2. The 3-D model of TrCel1b predicted by SWISS-MODEL (A) and I-TASSER (B) using β-glucosidase 6KHT as template. Fig. S3. Analysis of the disaccharides with HPLC. Fig. S4. The disaccharides synthesis of β-glucosidase and its variants under different concentrations of glucose. Fig. S5. SDS-PAGE analysis of purification of TrCel1b and its variants. Fig. S6. Effects of pH value on disaccharides synthesis. Fig. S7. The interaction profiles between TrCel1b (A), TrCel1bI177SI174SW173H (B) or TrCel1bN240I (C) and cellobiose analyzed by Discovery Studio 4.5, respectively. Table S1. The comparison of the production of laminaribiose and sophorose synthesized by β-glucosidase from different species. Table S2. Primers used in this study.
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- 2020
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32. Ubiquitin-like proteins and their Chinese nomenclatures
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Cui Hua Liu, Chengwei Yang, Lingqiang Zhang, Yongchao Zhao, Jun Zhu, Hui-Hua Li, Yi Sun, Zhijie Chang, Mian Wu, Jun Zhou, Qiao Wu, Daming Gao, Tian-Xia Jiang, Shiying Miao, Rentian Feng, Ping Wang, Bo Yang, Hongbing Zhang, Feng Rao, Hong Zhang, Wenyi Wei, Cheng Cao, Chen Wang, Meidan Ying, Yu Shang, Ceshi Chen, Jianping Jin, Jinke Cheng, Linfang Wang, Zhanxin Wang, Zhi-Heng Xu, Yong Wan, Leina Ma, Ronggui Hu, Hengbing Wang, Xuan Liu, Quan Chen, Songbo Xie, Zhiyin Song, Xiao-Bo Qiu, Wei Li, Ping Xu, Qi Xie, Lijun Jia, and Zhiping Xie
- Subjects
Multidisciplinary ,Biochemistry ,Ubiquitin-Like Proteins ,Biology - Published
- 2018
33. Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma
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Yang Shi, Qiang Gao, Zhen-Bin Ding, Liangqing Dong, Liu-Xiao Yang, Zhi-Chao Wang, Bohao Zheng, Daming Gao, Zhao Zhang, Xiaoying Wang, Meng Duan, Shu Zhang, Jia Fan, Ai-Wu Ke, Jian Zhou, Ruibin Xi, Long-Zi Liu, Lijie Ma, and Ke Yuan
- Subjects
Male ,0301 basic medicine ,Biology ,medicine.disease_cause ,Somatic evolution in cancer ,Metastasis ,Cholangiocarcinoma ,Clonal Evolution ,03 medical and health sciences ,0302 clinical medicine ,Chromosomal Instability ,Chromosome instability ,medicine ,Humans ,Exome ,Exome sequencing ,Intrahepatic Cholangiocarcinoma ,Aged ,Mutation ,Hepatology ,High-Throughput Nucleotide Sequencing ,DNA, Neoplasm ,Middle Aged ,medicine.disease ,Bile Ducts, Intrahepatic ,030104 developmental biology ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,KRAS ,Carcinogenesis - Abstract
Background & Aims Intrahepatic cholangiocarcinoma (ICC) is the second-most lethal primary liver cancer. Little is known about intratumoral heterogeneity (ITH) and its impact on ICC progression. We aimed to investigate the ITH of ICC in the hope of helping to develop new therapeutic strategies. Methods We obtained 69 spatially distinct regions from six operable ICCs. Patient-derived primary cancer cells (PDPCs) were established for each region, followed by whole-exome sequencing (WES) and multi-level validation. Results We observed widespread ITH for both somatic mutations and clonal architecture, shaped by multiple mechanisms, like clonal “illusion”, parallel evolution and chromosome instability. A median of 60.3% of mutations were heterogeneous, among which 85% of the driver mutations were located on the branches of tumor phylogenetic trees. Many truncal and clonal driver mutations occurred in tumor suppressor genes, such as TP53, SMARCB1 and PBRM1 that are involved in DNA repair and chromatin-remodeling. Genome doubling occurred in most cases (5/6) after the accumulation of truncal mutations and was shared by all intratumoral sub-regions. In all cases, ongoing chromosomal instability is evident throughout the evolutionary trajectory of ICC. The recurrence of ICC1239 provided evidence to support the polyclonal metastatic seeding in ICC. The change of mutation landscape and internal diversity among subclones during metastasis, such as the loss of chemoresistance mediator, can be used for new treatment strategies. Targeted therapy against truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, was developed in 5/6 patients. Conclusions Integrated investigations of spatial ITH and clonal evolution may provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ICC. Lay summary We applied multiregional whole-exome sequencing to investigate the evolution of intrahepatic cholangiocarcinoma (ICC). The results revealed that many factors, such as parallel evolution and chromosome instability, may participate and promote the branch diversity of ICC. Interestingly, in one patient with primary and recurrent metastatic tumors, we found evidence of polyclonal metastatic seeding, indicating that symbiotic communities of multiple clones existed and were maintained during metastasis. More realistically, some truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, could be promising treatment targets in patients with ICC.
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- 2018
34. Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress
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Qinrun Li, Ivan Dikic, Jiao Yang, Juan Du, Yongning He, Xuemin Zhang, Xiaoduo Xie, Hai Rao, Masaaki Komatsu, Byung-Hoon Lee, Ronggui Hu, Qin Xia, Daniel Finley, Daming Gao, Tao Zhang, Qing You, Jian Hou, Hongyan Wang, Wen Han, Tianrang Li, Hong Peng, Ying Huang, Lijian Hui, Guangyi Li, and Rong Zeng
- Subjects
0301 basic medicine ,biology ,Autophagy ,HEK 293 cells ,Cell Biology ,Plasma protein binding ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Ubiquitin ,Downregulation and upregulation ,biology.protein ,Phosphorylation ,Heat shock ,Receptor ,Molecular Biology - Abstract
Alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. Here we report that autophagy receptor p62/sequestosome-1 interacts with E2 Ub conjugating enzymes, UBE2D2 and UBE2D3. Endogenous p62 undergoes E2-dependent ubiquitylation during upregulation of Ub homeostasis, a condition termed as Ub+ stress, that is intrinsic to Ub overexpression, heat shock or prolonged proteasomal inhibition by bortezomib, a chemotherapeutic drug. Ubiquitylation of p62 disrupts dimerization of the UBA domain of p62, liberating its ability to recognize polyubiquitylated cargoes for selective autophagy. We further demonstrate that this mechanism might be critical for autophagy activation upon Ub+ stress conditions. Delineation of the mechanism and regulatory roles of p62 in sensing Ub stress and controlling selective autophagy could help to understand and modulate cellular responses to a variety of endogenous and environmental challenges, potentially opening a new avenue for the development of therapeutic strategies against autophagy-related maladies.
- Published
- 2017
35. Extracellular Signal-regulated Kinases (ERKs) Phosphorylate Lin28a Protein to Modulate P19 Cell Proliferation and Differentiation
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Long Li, Xiangyuan Liu, Min Chen, Daming Gao, Liyan Gong, and Hu Zhou
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0301 basic medicine ,MAPK/ERK pathway ,Embryonal Carcinoma Stem Cells ,Cellular differentiation ,Biology ,Biochemistry ,Mice ,03 medical and health sciences ,Animals ,Humans ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Cell Proliferation ,Kinase ,RNA-Binding Proteins ,Cell Differentiation ,Cell Biology ,Embryonic stem cell ,Cell biology ,030104 developmental biology ,P19 cell ,Accelerated Communications ,Mitogen-Activated Protein Kinases ,Stem cell ,Signal transduction ,HeLa Cells ,Signal Transduction - Abstract
Lin28a, originally discovered in the nematode Caenorhabditis elegans and highly conserved across species, is a well characterized regulator of let-7 microRNA (miRNA) and is implicated in cell proliferation and pluripotency control. However, little is known about how Lin28a function is modulated at the post-translational level and thereby responds to major signaling pathways. Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. By editing lin28a gene with the CRISPR/Cas9-based method, we generated P19 mouse embryonic carcinoma stem cells expressing Lin28a-S200A (phospho-deficient) and Lin28a-S200D (phospho-mimetic) mutants, respectively, to study the functional impact of Ser-200 phosphorylation. Lin28a-S200D-expressing cells, but not Lin28a-S200A-expressing or control P19 embryonic carcinoma cells, displayed impaired inhibition of let-7 miRNA and resulted in decreased cyclin D1, whereas Lin28a-S200A knock-in cells expressed less let-7 miRNA, proliferated faster, and exhibited differentiation defect upon retinoic acid induction. Therefore our results support that ERK kinase-mediated Lin28a phosphorylation may be an important mechanism for pluripotent cells to facilitate the escape from the self-renewal cycle and start the differentiation process.
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- 2017
36. Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis
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L Zhou, Qing-Hai Ye, Huiyong Yin, Daming Gao, Jun Qin, Xiangyuan Liu, Wenwei Zhu, Hu Zhou, Yongzhen Tao, Min Chen, Liyan Gong, Long Li, Hongli Hu, and Dan Ye
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0301 basic medicine ,education.field_of_study ,Hepatology ,biology ,Cell growth ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Acetylation ,Cancer cell ,Sirtuin ,Cancer research ,medicine ,biology.protein ,Cyclic adenosine monophosphate ,Liver cancer ,Carcinogenesis ,Phosphoglycerate kinase 1 ,education - Abstract
Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein-binding protein-associated factor (PCAF) and Sirtuin 7 as the enzymes regulating K323 acetylation from both directions in liver cancer cells. Conclusion These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515-528).
- Published
- 2016
37. Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors
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Caicun Zhou, Jian Zhang, Zhonglin Jiang, Liang Hu, Yujuan Jin, Chenchen Guo, Jun Qin, Fei Li, Hua Wang, Hsin-Yi Huang, Lei Deng, Dong Gao, Daming Gao, Fuming Li, Luonan Chen, Dan Sun, Xiangkun Han, Cheng Li, Kwok-Kin Wong, Hongbin Ji, Tao Jiang, Liu Yang, Chao Zheng, Shenda Hou, Yuetong Wang, and Shengxiang Ren
- Subjects
Drug ,biology ,business.industry ,media_common.quotation_subject ,Drug resistance ,medicine.disease ,respiratory tract diseases ,Downregulation and upregulation ,Cancer cell ,Cancer research ,biology.protein ,Medicine ,Epigenetics ,Epidermal growth factor receptor ,business ,Lung cancer ,Reprogramming ,media_common - Abstract
SUMMARYDrug resistance is a significant hindrance to effective cancer treatment. Although resistance mechanisms of epidermal growth factor receptor (EGFR)-mutant cancer cells to lethal EGFR tyrosine kinase inhibitors (TKI) treatment have been investigated intensively, how cancer cells orchestrate adaptive response under sublethal drug challenge remains largely unknown. Here we find that 2-hour sublethal TKI treatment elicits a transient drug-tolerant state in EGFR-mutant lung cancer cells. Continuous sublethal treatment reinforces this tolerance and eventually establishes long-term TKI resistance. This adaptive process involves H3K9 demethylation-mediated epigenetic upregulation of branched-chain amino acid aminotransferase 1 (BCAT1) and subsequent metabolic reprogramming, which promotes TKI resistance through attenuating reactive oxygen species (ROS) accumulation. Combinational treatment with TKI and ROS-inducing reagents overcomes this drug resistance in preclinical mouse models. Clinical information analyses support the correlation of BCAT1 expression with EGFR TKI response. Collectively, our findings reveal the importance of epigenetically regulated BCAT1-engaged metabolism reprogramming in TKI resistance in lung cancer.HIGHLIGHTSSublethal EGFR TKI treatment induces transient drug-tolerant state and long-term resistance in EGFR-mutant lung cancer cellsEpigenetically regulated BCAT1-mediated metabolic reprogramming orchestrates EGFR TKI-induced drug resistanceCombinational treatment with TKI and ROS-inducing agents overcomes the drug resistance induced by EGFR TKI treatment
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- 2019
38. Author Correction: Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis
- Author
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Shavali Shaik, Pengda Liu, Byeong Mo Kim, Min Yuan, Suchithra Menon, Brendan D. Manning, Dou Liu, Wenjian Gan, John M. Asara, Hiroyuki Inuzuka, Bo Zhai, Wenyi Wei, Daming Gao, Tae Ho Lee, Lixin Wan, Yonghao Yu, Steven P. Gygi, Omotooke Arojo, John Blenis, Bing Su, and Adam S. Lazorchak
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0303 health sciences ,Cell signaling ,Akt signalling ,Chemistry ,Cell Biology ,medicine.disease_cause ,mTORC2 ,Cell biology ,Blot ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,medicine ,Phosphorylation ,Whole cell lysate ,Carcinogenesis ,PI3K/AKT/mTOR pathway ,030304 developmental biology - Abstract
In the version of this Article originally published, the labels for Rictor and mTOR in the whole cell lysate (WCL) blots were swapped in Fig. 3b and the mTOR blot was placed upside down. Unprocessed blots of mTOR were also missing from Supplementary Fig. 9. The corrected Figs are shown below. In addition, control blots for the mTOR antibody (Cell Signalling Technology #2972) were also missing. These are now provided below, as Fig. 9, and show that the lower band is likely non-specific.
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- 2019
39. Effects of Catechins on N
- Author
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Ye, Jiao, Wei, Quan, Zhiyong, He, Daming, Gao, Fang, Qin, Maomao, Zeng, and Jie, Chen
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Plant Leaves ,Models, Chemical ,Molecular Structure ,Tea ,Food Handling ,Lysine ,Pyruvaldehyde ,Camellia sinensis ,Catechin - Abstract
The effects of catechins on N
- Published
- 2019
40. TGF-β1/P65/MAT2A Pathway Regulates Liver Fibrogenesis via Intracellular SAM
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Shanhua Fang, Lihong Hu, Xiaoning Wang, Hongwen Zhu, Jing Gao, Qian Liu, Kuifeng Wang, Hu Zhou, Daming Gao, Ping Liu, Zhenyun Zhu, Jia-Sheng Wu, Feihong Ji, Yueming Ma, Xu Shen, and Jiansheng Zhu
- Subjects
Gene knockdown ,Downregulation and upregulation ,Fibrosis ,Hepatic stellate cell ,Cancer research ,medicine ,Biology ,Signal transduction ,Hepatic fibrosis ,medicine.disease ,Intracellular ,Transforming growth factor - Abstract
Background: Hepatic stellate cell (HSC) activation induced by transforming growth factor β1 (TGF-β1) plays a pivotal role in fibrogenesis, while the complex downstream mediators of TGF-β1 in such process are largely unknown. Methods: We performed proteomic profiling of mice liver tissues from control, carbon tetrachloride (CCl4)-induced fibrosis and NPLC0393 administrated groups. Our target Mat2a was overexpressed and knocked down in vivo by tail vein injection of AAV vectors. We examined NF-κB transcriptional and MAT2A promoter activation via luciferase assay. Intracellular SAM contents were analyzed by LC/MS method. Findings: We found that methionine adenosyltransferase 2A (MAT2A) is significantly upregulated in the CCl4-induced fibrosis mice model and application of NPLC0393, a known small molecule inhibitor of TGF-β1 signaling pathway, inhibits the upregulation of MAT2A. Mechanistically, TGF-β1 induces phosphorylation of p65 and activation of NF-κB, thereby promoting mRNA transcription and protein expression of MAT2A and reduces S-adenosylmethionine (SAM) concentration in HSCs. Consistently, in vivo and in vitro knockdown of MAT2A alleviates CCl4- and TGF-β1-induced HSC activation, whereas in vivo overexpression of MAT2A facilitates hepatic fibrosis and abolishes therapeutic effect of NPLC0393. Interpretation: This study identifies TGF-β1/p65/MAT2A pathway that is involved in the regulation of intracellular SAM concentration and liver fibrogenesis, suggesting that this pathway is a potential therapeutic target for hepatic fibrosis. Funding: This work was supported by National Natural Science Foundation of China (No. 81500469, 81573873 and 81774196), Zhejiang Provincial Natural Science Foundation of China (No. Y15H030004), the National Key Research and Development Program from the Ministry of Science and Technology of China (No. 2017YFC1700200) and the Key Program of National Natural Science Foundation of China (No. 8153000502). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The animal experiment was approved by Science and Technology Commission of Shanghai Municipality, and all experimental procedures were performed according to the ethical guidelines of Animal care and use committee, Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
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- 2019
41. SCF
- Author
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Xiaoling, Kuai, Long, Li, Ran, Chen, Kangjunjie, Wang, Min, Chen, Binghai, Cui, Yuxue, Zhang, Junqiang, Li, Hongwen, Zhu, Hu, Zhou, Jianfei, Huang, Jun, Qin, Zhiwei, Wang, Wenyi, Wei, and Daming, Gao
- Subjects
Male ,F-Box-WD Repeat-Containing Protein 7 ,Glycogen Synthase Kinase 3 beta ,Ubiquitination ,Mice, Nude ,Xenograft Model Antitumor Assays ,DNA-Binding Proteins ,Stomach Neoplasms ,Serine ,Animals ,Humans ,Phosphorylation ,Carrier Proteins ,Cell Proliferation ,Transcription Factors - Abstract
Gastric cancer is the third leading cause of cancer-related death worldwide. The regulatory mechanisms underlying gastric cancer cell proliferation are largely unclear. Here, we show that the transcription factor GFI1 is associated with advanced clinical gastric cancer progression and promoted gastric cancer cell proliferation partially through inhibition of gastrokine-2 (GKN2) transcription. GFI1 was a degrading substrate of FBXW7, whose loss was observed in gastric cancer. Mechanistically, GSK3β-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation. A nondegradable GFI1 S94A/S98A mutant was more potent in driving gastric cancer cell proliferation and tumorigenesis than wild-type GFI1. Overall, this study reveals the oncogenic role of GFI1 in gastric cancer and provides mechanistic insights into the tumor suppressor function of FBXW7. SIGNIFICANCE: These findings demonstrate the oncogenic role of the transcription factor GFI1 and the tumor suppressive function of FBXW7 in gastric cancer.
- Published
- 2018
42. Anticorrosive behavior of epoxy coating modified with hydrophobic nano-silica on phosphatized carbon steel
- Author
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Minghua Li, Liu Anqiu, Daming Gao, Shufen Wang, Yangshuhan Xu, Qiang Dong, Liu Qiao, and Xiaochen Wang
- Subjects
Materials science ,Carbon steel ,General Chemical Engineering ,02 engineering and technology ,engineering.material ,010402 general chemistry ,01 natural sciences ,Corrosion ,Contact angle ,chemistry.chemical_compound ,Materials Chemistry ,Thermal stability ,Trimethylolpropane ,Composite material ,Organic Chemistry ,Epoxy ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Surfaces, Coatings and Films ,chemistry ,visual_art ,Diethylenetriamine ,visual_art.visual_art_medium ,engineering ,Wetting ,0210 nano-technology - Abstract
Corrosion existing in many fields brings lots of troubles to our life. In this work, epoxy coatings modified by hydrophobic nano-silica and hydrophilic nano-silica were fabricated to provide corrosion protection for phosphatized Q235 carbon steel. The traditional epoxy coating was prepared by the polymerization of trimethylolpropane triglycidyl ether and diethylenetriamine. The modified epoxy coating was fabricated by the polymerization and mixing of trimethylolpropane triglycidyl ether, diethylenetriamine and nano-silica. The microscopic morphologies of various epoxy coatings were investigated by SEM. Wettability of epoxy coatings was measured by static contact angle measurement instrument. Thermal stability was tested by thermo gravimetric analyzer. Corrosion behaviors was investigated by electrochemical workstation. Adhesion was reflected by cross-cut test and pull-off test. Equivalent circuits were used to fit the electrochemical impedance spectrum (EIS). According to experimental results, modified epoxy coatings present good hydrophobicity, good thermal stability at 250 °C with only about 3 % weight loss and the ca. 10 μm modified epoxy coating added with the most hydrophobic nano-silica shows the best anticorrosive performance with impedance of 5.25 × 105 Ω•cm2 (0.01 Hz) at 0 h immersion. The anticorrosive performance of epoxy coating is significantly improved when hydrophobic nano-silica is added into epoxy matrix. Adding hydrophobic nano-silica can effectively prolong the diffusion path of water-soluble corrosive medium and the hydrophobicity is able to retard the diffusion of water.
- Published
- 2021
43. Hierarchically nanoporous copolymer with built-in carbene-CO2 adducts as halogen-free heterogeneous organocatalyst towards cycloaddition of carbon dioxide into carbonates
- Author
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Liu Anqiu, Daming Gao, Yuting Wen, Qiang Dong, Wu Yun, Xiaochen Wang, Xu Zezhong, Guojian Chen, Zhouyang Long, Ye Chaojie, and Yangshuhan Xu
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Reaction mechanism ,Chemistry ,Nanoporous ,General Chemical Engineering ,Radical polymerization ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Industrial and Manufacturing Engineering ,Cycloaddition ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Styrene oxide ,Polymer chemistry ,Copolymer ,Environmental Chemistry ,Dimethyl carbonate ,0210 nano-technology - Abstract
A serial of porous polymers incorporating N‑heterocyclic carbene-CO2 adducts (designated as NHC-CO2 adducts) were facilely synthesized via radical polymerization of N-vinylimidazolate and ethyleneglycol dimethacrylate plus post-treatment with dimethyl carbonate (DMC). The polymers possessed tunable chemical structure, large surface area along with abundant meso-macropores and enhanced CO2 uptake which functioned as metal-halogen-free heterogeneous organocatalysts for solvent-free cycloaddition of CO2 to styrene oxide under 10 bar CO2 pressure, exhibiting highly catalytic activity and stable recyclability. Further, turnover frequency (TOF) of 7.1 h−1 (94.3% yield, 12 h) was obtainable under ambient condition, much higher than those of reported metal-halogen-free heterogeneous catalysts, even comparable with existing halogen-containing ones. Furthermore, the catalyst could efficiently convert various epoxides including internal epoxides into corresponding cyclic carbonates under mild condition (1 bar, 70–120 °C). The excellent catalytic performance was ascribed to the appropriate proportion of NHC-CO2 adducts in porous skeleton structure triggered by DMC. A plausible reaction mechanism was proposed to understand NHC-catalyzed fixation of CO2. This study highlights porous organic polymer is a versatile platform of NHC-CO2 adducts to construct eco-friendly solid catalyst towards efficient CO2 conversion.
- Published
- 2021
44. Exportin-5 SUMOylation promotes hepatocellular carcinoma progression
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Guangming Li, Zhaobo Liu, Dongdong Lin, Tiezheng Wang, Zhi Fu, Guang Yang, Yadong Wang, and Daming Gao
- Subjects
0301 basic medicine ,PLCB1 ,Carcinoma, Hepatocellular ,Carcinogenesis ,Phospholipase C beta ,SUMO protein ,SUMO2 ,Karyopherins ,Biology ,XPO5 ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Nuclear export signal ,Cell Proliferation ,Cell growth ,Liver Neoplasms ,Sumoylation ,Cell Biology ,medicine.disease ,Phenotype ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research - Abstract
Increasing evidence has shown that abnormal expression of XPO5 is found in many human cancers and acts as an oncoprotein in certain cancers. However, its functional role in hepatocellular carcinoma (HCC) remains unexplored. In our study, we found that XPO5 was highly expressed in HCC, which was associated with SUMO modification. Moreover, we found that XPO5 was SUMOylated by SUMO2 at K125. Functional experiments revealed that XPO5 SUMOylation could promote MHCC97H cell proliferation, migration and invasion. In addition, we found that the nuclear export of pre-miR-3184 was suppressed by SUMOylated XPO5. Moreover, PLCB1 was identified as the common target of miR-3184-5p and miR-3184-3p. The suppressed phenotype induced by miR-3184-5p and miR-3184-3p could be rescued by overexpression of PLCB1. Bioinformatics analysis showed that PLCB1 expression had a negative relationship with HCC patient survival. The inhibitory effects of MHCC97H cells resulted from abnormal XPO5 SUMO modification could be blocked by miR-3184 inhibitor or PLCB1 overexpression. In conclusion, our findings demonstrate a novel mechanism of XPO5 in HCC, that is, the SUMOylated XPO5 acts as an "oncogenic" role in MHCC97H cells proliferation, migration and invasion by controlling the nuclear-cytoplasm transportation of miR-3184, thus up-regulating PLCB1 expression.
- Published
- 2020
45. Surgical treatment of extensive hepatic alveolar echinococcosis using a three-dimensional visualization technique combined with allograft blood vessels
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Ning Li, Tiezheng Wang, Dongdong Lin, Zhi Fu, Daming Gao, and Guangming Li
- Subjects
Male ,Echinococcosis, Hepatic ,medicine.medical_specialty ,reconstruction ,surgical treatment ,Vena Cava, Inferior ,Inferior vena cava ,03 medical and health sciences ,Imaging, Three-Dimensional ,0302 clinical medicine ,three-dimensional visualization technique ,medicine.artery ,medicine ,Hepatectomy ,Humans ,Aorta, Abdominal ,Clinical Case Report ,030212 general & internal medicine ,Vein ,medicine.diagnostic_test ,business.industry ,Abdominal aorta ,stenosis ,General Medicine ,Middle Aged ,hepatic alveolar echinococcosis ,Allografts ,medicine.disease ,Echinococcosis ,Stenosis ,medicine.anatomical_structure ,medicine.vein ,030220 oncology & carcinogenesis ,Angiography ,Vascular Grafting ,Radiology ,Tomography, X-Ray Computed ,business ,Research Article ,Blood vessel ,Abdominal surgery - Abstract
Rationale: Hepatic alveolar echinococcosis (HAE) presents a high pathogenicity and case fatality rate. The main treatment for HAE is surgical resection. Giant lesions in the liver and invasion of the pathogen into the retrohepatic inferior vena cava are usually associated with a poor prognosis when radical resection cannot be performed. Patient concerns: A 56-year-old man who underwent hydatidectomy 7 years prior noted a recurrence of HAE. He was subsidized and admitted to our hospital for the purpose of surgical treatment. Diagnosis: By computed tomography, angiography and three-dimensional (3D) computed tomography reconstruction images, multiple, giant HAE with 75% stenosis was confirmed. Interventions: With the 3D visualization technique, we designed the surgical plan and performed radical resection of the lesions, including the invaded inferior vena cava, and maximized retention of normal liver tissue. The abdominal aorta of an organ donor was used for vascular allograft reconstruction. Outcomes: The patient recovered gradually after the operation. He was followed up for 3 months, and the reconstructed vein patency was good. Lessons: The 3D visualization technique combined with a blood vessel allograft allowed us to expand indications for radical resection of extensive HAE.
- Published
- 2020
46. Formation of N
- Author
-
Ye, Jiao, Jialiang, He, Zhiyong, He, Daming, Gao, Fang, Qin, Mingyong, Xie, Maomao, Zeng, and Jie, Chen
- Subjects
Plant Leaves ,Tea ,Food Handling ,Gallic Acid ,Lysine ,Polyphenols ,Glyoxal ,Pyruvaldehyde ,Camellia sinensis ,Catechin ,Food Analysis - Abstract
This study selected common processing methods for orthodox black tea and investigated changes in the levels of N
- Published
- 2018
47. Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma
- Author
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Yansheng Liu, Liangqing Dong, Ran Chen, Qian Liu, Yanting Zhou, Zhijian Song, Hongwen Zhu, Li Ding, Bing Zhang, Xiaowei Dong, Junqiang Li, Bo Wen, Weiwei Shi, Jia Fan, Daming Gao, Emily S. Boja, Xiaoying Wang, Pei Wang, Qiang Gao, Henry Rodriguez, Hu Zhou, Lijie Ma, Jian Zhou, Chen Huang, Weiping Ma, Ana I. Robles, and Yize Li
- Subjects
Male ,Hepatitis B virus ,Carcinoma, Hepatocellular ,Biology ,medicine.disease_cause ,Proteomics ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Mice ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Fructose-Bisphosphate Aldolase ,Tumor Microenvironment ,medicine ,Animals ,Humans ,beta Catenin ,Cell Proliferation ,Proteogenomics ,030304 developmental biology ,Mice, Inbred BALB C ,0303 health sciences ,Cell growth ,Proteomic Profiling ,Gene Expression Profiling ,Liver Neoplasms ,Hep G2 Cells ,Middle Aged ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Hepatocellular carcinoma ,Proteome ,Cancer research ,Female ,Signal transduction ,030217 neurology & neurosurgery - Abstract
We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.
- Published
- 2019
48. Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis
- Author
-
Yang Li, Lin Yuan, Guichun Xing, Haidong Gao, Wenyi Wei, Lijing Wang, Yanrong Lv, Yuan Zhang, Xiangzhen Kong, Yuxin Yin, Fuchu He, Li Hongchang, Zhi-Xiong Xiao, Daming Gao, Tao Zhou, Lingqiang Zhang, and Shanshan Song
- Subjects
Carcinogenesis ,Transgene ,Regulator ,Mice, Nude ,Breast Neoplasms ,Mice, Transgenic ,medicine.disease_cause ,law.invention ,Ubiquitin ,law ,Cell Line, Tumor ,medicine ,Animals ,Humans ,PTEN ,Mice, Inbred BALB C ,Mutation ,biology ,Protein Stability ,PTEN Phosphohydrolase ,Ubiquitination ,Cell Biology ,Cell biology ,Cancer research ,biology.protein ,Suppressor ,Female ,Ubiquitin-Specific Proteases ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Neoplasm Transplantation ,Signal Transduction - Abstract
PTEN is one of the most frequently mutated tumour suppressors and reduction in PTEN protein stability also plays a role in tumorigenesis. Although several ubiquitin ligases for PTEN have been identified, the deubiquitylase for de-polyubiquitylation and stabilization of PTEN is less defined. Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN. Depletion of OTUD3 leads to the activation of Akt signalling, induction of cellular transformation and cancer metastasis. OTUD3 transgenic mice exhibit higher levels of the PTEN protein and are less prone to tumorigenesis. Reduction of OTUD3 expression, concomitant with decreased PTEN abundance, correlates with human breast cancer progression. Furthermore, we identified loss-of-function OTUD3 mutations in human cancers, which either abolish OTUD3 catalytic activity or attenuate the interaction with PTEN. These findings demonstrate that OTUD3 is an essential regulator of PTEN and that the OTUD3-PTEN signalling axis plays a critical role in tumour suppression.
- Published
- 2015
49. Effects of Calcination Temperature on the Structural and Magnetic Properties of NiFe2O4Nanoparticles
- Author
-
Ganhong Zheng, Lingyun Zhang, Daming Gao, Chang Li, and Hong Chen
- Subjects
Materials science ,Nanoparticle ,Coercivity ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials ,law.invention ,Magnetization ,Crystallinity ,Nuclear magnetic resonance ,Chemical engineering ,Control and Systems Engineering ,law ,Materials Chemistry ,Ceramics and Composites ,Particle ,Microemulsion ,Calcination ,Electrical and Electronic Engineering ,Crystallization - Abstract
NiFe2O4 nanoparticles have been synthesized by water-in-oil microemulsion method. Effects of calcination temperature varying from 600 to 1200°C on the structural and magnetic properties of NiFe2O4 nanoparticles have been investigated. Studies carried out using XRD, SEM and VSM techniques. Results indicated that magnetic properties of NiFe2O4 nanoparticles showed great dependence on the variation of the crystallinity and particle sizes caused by the calcination temperature. The crystallization, saturation magnetization Ms and remenant magnetization Mr increased as the calcination temperature increased. But the variation of coercivity Hc was not in accordance with that of Ms and Mr, indicating that Hc was not determined only by the crystallinity and size of NiFe2O4 nanoparticles.
- Published
- 2015
50. ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer
- Author
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Quanxing Ni, Chen Liu, Jiang Long, Dingkong Liang, Paul J. Chiao, Hongli Hu, Daming Gao, Yi Qin, Haijun Zhou, Si Shi, Jing Gao, Liang Liu, Wenyan Xu, Jin Xu, Hu Zhou, Xianjun Yu, Xiangyuan Liu, Bo Zhang, Shunrong Ji, and Jiang Liu
- Subjects
MAPK/ERK pathway ,Proteasome Endopeptidase Complex ,F-Box-WD Repeat-Containing Protein 7 ,Ubiquitin-Protein Ligases ,pancreatic cancer ,Cell Cycle Proteins ,Biology ,Real-Time Polymerase Chain Reaction ,medicine.disease_cause ,law.invention ,Proto-Oncogene Proteins p21(ras) ,Mice ,law ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Pancreatic cancer ,KRAS ,medicine ,Animals ,Humans ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Molecular Biology ,Cell Proliferation ,Mutation ,F-Box Proteins ,Ubiquitination ,Cancer ,Cell Biology ,medicine.disease ,Pancreatic Neoplasms ,ERK ,Ubiquitin ligase complex ,ras Proteins ,FBW7 ,Cancer research ,Suppressor ,Original Article ,Carcinogenesis ,Protein Binding - Abstract
F-box and WD repeat domain-containing 7 (FBW7) is the substrate recognition component of the Skp1-Cul1-F-box (SCF) ubiquitin ligase complex and functions as a major tumor suppressor by targeting various oncoproteins for degradation. Genomic deletion or mutation of FBW7 has frequently been identified in many human cancers but not in pancreatic ductal adenocarcinoma. Thus it is important to know how the tumor suppressive function of FBW7 is impaired in pancreatic cancer. In this study, we first observed that low FBW7 expression correlated significantly with ERK activation in pancreatic cancer clinical samples, primarily due to KRAS mutations in pancreatic cancer. We further showed that ERK directly interacted with FBW7 and phosphorylated FBW7 at Thr205, which sequentially promoted FBW7 ubiquitination and proteasomal degradation. Furthermore, the phospho-deficient T205A FBW7 mutant is resistant to ERK activation and could significantly suppress pancreatic cancer cell proliferation and tumorigenesis. These results collectively demonstrate how the oncogenic KRAS mutation inhibits the tumor suppressor FBW7, thus revealing an important function of KRAS mutations in promoting pancreatic cancer progression.
- Published
- 2015
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