77 results on '"Guiming Li"'
Search Results
2. Supplementary Figure Legends from Dietary Resveratrol Prevents Development of High-Grade Prostatic Intraepithelial Neoplastic Lesions: Involvement of SIRT1/S6K Axis
- Author
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Addanki P. Kumar, Rita Ghosh, Robert L. Reddick, Dinesh Thapa, Roble Bedolla, Paul Rivas, and Guiming Li
- Abstract
PDF file - 55KB
- Published
- 2023
3. Supplementary Figure 2 from Dietary Resveratrol Prevents Development of High-Grade Prostatic Intraepithelial Neoplastic Lesions: Involvement of SIRT1/S6K Axis
- Author
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Addanki P. Kumar, Rita Ghosh, Robert L. Reddick, Dinesh Thapa, Roble Bedolla, Paul Rivas, and Guiming Li
- Abstract
PDF file - 60KB, Apoptosis in SIRT1 knockdown DU145 cells
- Published
- 2023
4. Supplementary Figure 3 from Dietary Resveratrol Prevents Development of High-Grade Prostatic Intraepithelial Neoplastic Lesions: Involvement of SIRT1/S6K Axis
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Addanki P. Kumar, Rita Ghosh, Robert L. Reddick, Dinesh Thapa, Roble Bedolla, Paul Rivas, and Guiming Li
- Abstract
PDF file - 79KB, Effect of RES on the protein levels of p4E-BP1 and FOXO-3 in prostate cancer cells
- Published
- 2023
5. Layout Design of Satellite Star Sensor Fixed to Rotation Platform
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Guiming Li, Zhihui Li, Rui Liu, Jianfu Zhang, Yushuang Wang, and Ao Chen
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- 2023
6. A Time Sequence Design for Improving the Output Frequency and Accuracy of Star Sensor Under High Dynamic Conditions
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Rui Liu, GuiMing Li, ZhiHui Li, and JianFu Zhang
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- 2023
7. Modeling and Analysis of Satellite with a Large Inertia Rotating Load
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Guiming Li, Shixuan Liu, Zhihui Li, Xinyan Wu, Kui Zou, and Rui Liu
- Published
- 2023
8. Anticancer Activity and Molecular Mechanism of Momordica cochinchinensis Seed Extract in Chronic Myeloid Leukemia Cells
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Zhengdong Ai, Chong Ma, Ruiming Wan, Jingyi Yin, Guiming Li, Yan Li, and Li Chen
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Cancer Research ,Nutrition and Dietetics ,Oncology ,Medicine (miscellaneous) - Published
- 2021
9. Overexpression of a ceramide synthase gene,GhCS1, inhibits fiber cell initiation and elongation by promoting the synthesis of ceramides containing dihydroxy LCB and VLCFA
- Author
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Guiming Li, Qiaoling Wang, Qian Meng, Guanhua Wang, Fan Xu, Qian Chen, Fang Liu, Yulin Hu, and Ming Luo
- Subjects
Plant Science - Abstract
Cotton is an important natural fiber crop worldwide. Cotton fiber cell is regarded as an ideal material for studying the growth and development of plant cells. Sphingolipids are important components of biomembrane and bioactive molecules which participate in many processes such as plant growth, development regulation, stimulus sensing, and stress response. However, the functions of sphingolipids in the cotton fiber development are still unclear. In the present study, we identified a cotton ceramide synthase gene, GhCS1, which is predominantly expressed in fiber cell. The GhCS1 is located in the endoplasmic reticulum and has the conserved domains of ceramide synthase. Overexpression of GhCS1 gene inhibited both vegetative and reproductive growth in cotton. Importantly, the fiber cell initiation and elongation were severely inhibited when compared with control. Comparison of the sphingolipid profile in the 0-DPA (days past anthesis) ovule (with fiber cell) between control and transgenic cotton plants showed that the content of sphingosines (Sph) decreased significantly in transgenic ovules, whereas the content of phyto-sphingosines (Phyto-Sph) had no change. Meanwhile, the content of ceramide containing Sph and very-long-chain fatty acid (VLCFA) increased significantly in transgenic ovules, while ceramide containing Phyto-Sph and long-chain fatty acids (LCFA)/VLCFA significantly decreased. These results indicated that GhCS1 was a functional ceramide synthase, which preferentially used Sph and VLCFA as substrates and was different from the Arabidopsis ceramide synthase AtLOH1/AtLOH3, which preferentially used Phyto-Sph and VLCFA as substrates, and also different from AtLOH2, which preferentially used Sph and LCFA as substrates. It is suggested that GhCS1 might be a new ceramide synthase gene in the plant, play some roles in the development of fiber cells and cotton plants.
- Published
- 2022
10. Overexpression of a ceramide synthase gene
- Author
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Guiming, Li, Qiaoling, Wang, Qian, Meng, Guanhua, Wang, Fan, Xu, Qian, Chen, Fang, Liu, Yulin, Hu, and Ming, Luo
- Abstract
Cotton is an important natural fiber crop worldwide. Cotton fiber cell is regarded as an ideal material for studying the growth and development of plant cells. Sphingolipids are important components of biomembrane and bioactive molecules which participate in many processes such as plant growth, development regulation, stimulus sensing, and stress response. However, the functions of sphingolipids in the cotton fiber development are still unclear. In the present study, we identified a cotton ceramide synthase gene
- Published
- 2022
11. Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent pleuromutilin derivatives with a substituted piperazine moiety
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Yunpeng Yi, Shifa Yang, Yueyue Liu, Bin Yin, Zengcheng Zhao, Guiming Li, Zhongli Huang, Lei Chen, Fei Liu, Ruofeng Shang, and Shuqian Lin
- Subjects
Organic Chemistry ,Drug Discovery ,Molecular Biology ,Biochemistry - Published
- 2023
12. Anticancer Activity and Molecular Mechanism of
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Zhengdong, Ai, Chong, Ma, Ruiming, Wan, Jingyi, Yin, Guiming, Li, Yan, Li, and Li, Chen
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Plant Extracts ,Fusion Proteins, bcr-abl ,Antineoplastic Agents ,Apoptosis ,Xenograft Model Antitumor Assays ,Mice ,Drug Resistance, Neoplasm ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Imatinib Mesylate ,Animals ,Humans ,Myeloid Cell Leukemia Sequence 1 Protein ,Momordica ,Cell Proliferation - Abstract
Targeting Bcr-Abl is the key to the treatment of chronic myeloid leukemia. Despite great progress in the treatment of patients with chronic CML, advanced CML patients are still unable to obtain effective and safe drugs.
- Published
- 2021
13. Ginsenoside Rg1 exerts anti‑apoptotic effects on non‑alcoholic fatty liver cells by downregulating the expression of SGPL1
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Guiming Li, Hongqing Xie, Xiaodie Cao, Chong Ma, Yan Li, and Li Chen
- Subjects
Cancer Research ,Oncology ,Ginsenosides ,Non-alcoholic Fatty Liver Disease ,Genetics ,Molecular Medicine ,Humans ,Panax ,Apoptosis ,Molecular Biology ,Biochemistry ,Aldehyde-Lyases - Abstract
Non‑alcoholic fatty liver disease (NAFLD) has a high incidence, and can lead to liver cirrhosis and even hepatocellular carcinoma in severe cases. To the best of our knowledge, there is currently no safe and effective treatment for the management of this disease. Ginsenoside Rg1 (Rg1) is an active monomer derived from ginseng and notoginseng. In the present study, HHL‑5 hepatocytes were used to establish an
- Published
- 2021
14. Comparative Metabolomics Analysis Reveals Sterols and Sphingolipids Play a Role in Cotton Fiber Cell Initiation
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Fan Xu, Qian Meng, Guiming Li, Li Huang, Caixia Ma, Qian Chen, Qiaoling Wang, and Ming Luo
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Ceramide ,QH301-705.5 ,Campesterol ,Gene Expression ,Genes, Plant ,cotton ,fiber cell ,Catalysis ,Article ,Inorganic Chemistry ,chemistry.chemical_compound ,sterol ,Gene Expression Regulation, Plant ,Metabolomics ,Cotton Fiber ,Biology (General) ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Spectroscopy ,Plant Proteins ,Ovule ,Gossypium ,Stigmasterol ,sphingolipids ,Gene Expression Profiling ,Organic Chemistry ,Sterol ester ,Wild type ,Phytosterols ,General Medicine ,differentiation ,Sphingolipid ,Sterol ,Computer Science Applications ,initiation ,Chemistry ,Sterols ,chemistry ,Biochemistry ,Fiber cell ,sphingolipid metabolism ,Carbohydrate Metabolism ,lipids (amino acids, peptides, and proteins) ,Transcriptome - Abstract
Cotton fiber is a seed trichome that protrudes from the outer epidermis of cotton ovule on the day of anthesis (0 day past anthesis, 0 DPA). The initial number and timing of fiber cells are closely related to fiber yield and quality. However, the mechanism underlying fiber initiation is still unclear. Here, we detected and compared the contents and compositions of sphingolipids and sterols in 0 DPA ovules of Xuzhou142 lintless-fuzzless mutants (Xufl) and Xinxiangxiaoji lintless-fuzzless mutants (Xinfl) and upland cotton wild-type Xuzhou142 (XuFL). Nine classes of sphingolipids and sixty-six sphingolipid molecular species were detected in wild-type and mutants. Compared with the wild type, the contents of Sphingosine-1-phosphate (S1P), Sphingosine (Sph), Glucosylceramide (GluCer), and Glycosyl-inositol-phospho-ceramides (GIPC) were decreased in the mutants, while the contents of Ceramide (Cer) were increased. Detail, the contents of two Cer molecular species, d18:1/22:0 and d18:1/24:0, and two Phyto-Cer molecular species, t18:0/22:0 and t18:0/h22:1 were significantly increased, while the contents of all GluCer and GIPC molecular species were decreased. Consistent with this result, the expression levels of seven genes involved in GluCer and GIPC synthesis were decreased in the mutants. Furthermore, exogenous application of a specific inhibitor of GluCer synthase, PDMP (1-phenyl-2-decanoylamino-3-morpholino-1-propanol), in ovule culture system, significantly inhibited the initiation of cotton fiber cells. In addition, five sterols and four sterol esters were detected in wild-type and mutant ovules. Compared with the wild type, the contents of total sterol were not significantly changed. While the contents of stigmasterol and campesterol were significantly increased, the contents of cholesterol were significantly decreased, and the contents of total sterol esters were significantly increased. In particular, the contents of campesterol esters and stigmasterol esters increased significantly in the two mutants. Consistently, the expression levels of some sterol synthase genes and sterol ester synthase genes were also changed in the two mutants. These results suggested that sphingolipids and sterols might have some roles in the initiation of fiber cells. Our results provided a novel insight into the regulatory mechanism of fiber cell initiation.
- Published
- 2021
15. Effect of Mahuang Fuzi and Shenzhuo Decoction on Idiopathic Membranous Nephropathy: A Multicenter, Nonrandomized, Single-Arm Clinical Trial
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Zhaocheng Dong, Haoran Dai, Yu Gao, Hanxue Jiang, Meiqi Liu, Fei Liu, Wenbin Liu, Zhendong Feng, Xiaoyan Zhang, Aijie Ren, Xiaolan Li, Hongliang Rui, Xuefei Tian, Guiming Li, and Baoli Liu
- Subjects
medicine.medical_specialty ,Serum albumin ,Renal function ,idiopathic membranous nephropathy ,Decoction ,RM1-950 ,Gastroenterology ,Membranous nephropathy ,Internal medicine ,objective performance criteria ,medicine ,Pharmacology (medical) ,Adverse effect ,Original Research ,Pharmacology ,Mahuang Fuzi and Shenzhuo Decoction ,single-arm clinical trial ,biology ,business.industry ,Albumin ,medicine.disease ,Clinical trial ,Regimen ,herbal medicine ,biology.protein ,Therapeutics. Pharmacology ,business - Abstract
Objective: To explore the clinical effect of Mahuang Fuzi and Shenzhuo Decoction on idiopathic membranous nephropathy.Methods: This study is a multicenter, nonrandomized, single-arm clinical trial carried out as per the objective performance criteria, with the target being set at 35.0%. 184 cases of patients suffering from idiopathic membranous nephropathy with Shaoyin Taiyin syndrome were collected. These patients were treated with Mahuang Fuzi and Shenzhuo Decoction with a follow-up period of 3 years. The 24-hour urine protein and blood albumin were observed, and the remission rates of the patients were compared with the target.Results: The mean follow-up time was 18 (12.5, 30) months, and the remission rate was 61.4%, which is a statistically significant difference from the target group of 35%. The remission rates for patients who had and had not used immunosuppressive therapy were 59.6 and 65.5%, respectively, but the difference was not statistically significant (p = 0.254). However, the albumin before the treatment and the course of treatment of the patients was significantly correlated with the disease remission (p < 0.05). However, the albumin before the treatment and the course of treatment of the patients was significantly correlated with the disease remission (p < 0.05). There were no significant changes in renal function before and after treatment, and no severe adverse events occurred during treatment.Conclusion: Mahuang Fuzi and Shenzhuo Decoction have significant effects on idiopathic membranous nephropathy, and has the same effect on patients with membranous nephropathy who are newly treated as well as those who have been treated with immunosuppressive therapy without remission. In addition, the efficacy of this regimen is related to the albumin and the duration of the therapy, but not to 24-hour urine protein or other factors.
- Published
- 2021
16. Sphingolipid Profile during Cotton Fiber Growth Revealed That a Phytoceramide Containing Hydroxylated and Saturated VLCFA Is Important for Fiber Cell Elongation
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Qian Meng, Qian Chen, Suo Xiaodong, Guiming Li, Caixia Ma, Ming Luo, Qiaoling Wang, Li Wang, Li Huang, and Fan Xu
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Ceramide ,Cell division ,elongation ,Ceramides ,Hydroxylation ,Biochemistry ,Microbiology ,cotton ,fiber cell ,Article ,Fatty Acids, Monounsaturated ,chemistry.chemical_compound ,VLCFA ,Gene Expression Regulation, Plant ,Myriocin ,Fiber ,Cotton Fiber ,Molecular Biology ,Gossypium ,Sphingolipids ,Sphingosine ,Chemistry ,Gene Expression Profiling ,Serine C-palmitoyltransferase ,Fatty Acids ,Sphingolipid ,QR1-502 ,Cell biology ,Biosynthetic Pathways ,Fiber cell ,lipids (amino acids, peptides, and proteins) ,sphingolipid ,secondary cell wall - Abstract
Cotton fiber is a single-celled seed trichrome that arises from the epidermis of the ovule’s outer integument. The fiber cell displays high polar expansion and thickens but not is disrupted by cell division. Therefore, it is an ideal model for studying the growth and development of plant cells. Sphingolipids are important components of membranes and are also active molecules in cells. However, the sphingolipid profile during fiber growth and the differences in sphingolipid metabolism at different developmental stages are still unclear. In this study, we detected that there were 6 classes and 95 molecular species of sphingolipids in cotton fibers by ultrahigh performance liquid chromatography-MS/MS (UHPLC-MS/MS). Among these, the phytoceramides (PhytoCer) contained the most molecular species, and the PhytoCer content was highest, while that of sphingosine-1-phosphate (S1P) was the lowest. The content of PhytoCer, phytoceramides with hydroxylated fatty acyls (PhytoCer-OHFA), phyto-glucosylceramides (Phyto-GluCer), and glycosyl-inositol-phospho-ceramides (GIPC) was higher than that of other classes in fiber cells. With the development of fiber cells, phytosphingosine-1-phosphate (t-S1P) and PhytoCer changed greatly. The sphingolipid molecular species Ceramide (Cer) d18:1/26:1, PhytoCer t18:1/26:0, PhytoCer t18:0/26:0, PhytoCer t18:1/h20:0, PhytoCer t18:1/h26:0, PhytoCer t18:0/h26:0, and GIPC t18:0/h16:0 were significantly enriched in 10-DPA fiber cells while Cer d18:1/20:0, Cer d18:1/22:0, and GIPC t18:0/h18:0 were significantly enriched in 20-DPA fiber cells, indicating that unsaturated PhytoCer containing hydroxylated and saturated very long chain fatty acids (VLCFA) play some role in fiber cell elongation. Consistent with the content analysis results, the related genes involved in long chain base (LCB) hydroxylation and unsaturation as well as VLCFA synthesis and hydroxylation were highly expressed in rapidly elongating fiber cells. Furthermore, the exogenous application of a potent inhibitor of serine palmitoyltransferase, myriocin, severely blocked fiber cell elongation, and the exogenous application of sphingosine antagonized the inhibition of myriocin for fiber elongation. Taking these points together, we concluded that sphingolipids play crucial roles in fiber cell elongation and SCW deposition. This provides a new perspective for further studies on the regulatory mechanism of the growth and development of cotton fiber cells.
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- 2021
17. 1.5 T Nuclear Magnetic Resonance Imaging System Failure Treatment and Rectification Summary
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Guiming, Li, Yongsheng, Wang, Xiang, Xiao, and Jianbo, Zhu
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Magnets ,Helium ,Magnetic Resonance Imaging - Abstract
Quench of magnetic resonance imaging system refers to the process that the superconducting condition inside the magnet is destroyed due to some reason. The large current stored in the coil is quickly converted into heat at the place where the resistance is formed, and a large amount of liquid helium in the magnet is evaporated. If it happens, it will cause huge loss to the user. We introduce the real cases of 1.5 T magnetic resonance imaging system's quench fault, maintenance treatment and management improvement, which can be used for reference by various medical institutions, so as to better strengthen the operation and maintenance management of magnetic resonance imaging system, so as to avoid the occurrence of out of tolerance fault, and do a good job in the guarantee work after the out of tolerance fault.
- Published
- 2021
18. Down-regulating a fiber-specific KCR like gene GhKCRL1 suppressed fiber elongation through blocking the synthesis of sphingolipids in fiber cell
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Qian Meng, Qiaoling Wang, Fan Xu, Qian Chen, Caixia Ma, Li Huang, Guiming Li, Fang Liu, and Ming Luo
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Agronomy and Crop Science - Published
- 2022
19. Overexpression of miR-4433 by suberoylanilide hydroxamic acid suppresses growth of CML cells and induces apoptosis through targeting Bcr-Abl
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Jingyi Yin, Haiyan Wu, Yan Li, Li Chen, Guiming Li, and Zhengdong Ai
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0301 basic medicine ,medicine.drug_class ,growth ,03 medical and health sciences ,0302 clinical medicine ,Nude mouse ,hemic and lymphatic diseases ,microRNA ,medicine ,Viability assay ,neoplasms ,miR-4433 ,biology ,Chemistry ,Histone deacetylase inhibitor ,apoptosis ,SAHA ,medicine.disease ,biology.organism_classification ,chronic myelogenous leukemia ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Signal transduction ,Research Paper ,Bcr-Abl ,Chronic myelogenous leukemia ,K562 cells - Abstract
Background: Targeting Bcr-Abl is the key for the treatment of CML. Although great progress has been achieved for the treatment of CML patients in chronic stage, effective drugs with good safety are not available for those in advanced stages of CML patients. In present study, a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was used to screen for microRNA that can target Bcr-Abl. Methods: RT-qPCR was used to determine Bcr-Abl and miR-4433 transcription level in CML cells. In CML cells, Proteins including PARP, caspase-3, acetyl-histone 3, histone 3 and Bcr-Abl, as well as Bcr-Abl downstream proteins were detected using western blot. Cell viability and apoptosis were monitored respectively by MTS assay and flow cytometry. The correlation between miR-4433 and Bcr-Abl was determined by luciferase reporter assay. The anti-tumor effect of miR-4433 to K562 cells was evaluated by nude mouse xenograft model in vivo. Results: SAHA up-regulated the acetylation level of histone 3, and effectively inhibited Bcr-Abl mRNA level and its downstream signal transduction pathway, while inhibiting the growth of CML cells and inducing apoptosis. Furthermore, bioinformatics tools predicted that miR-4433 is a putative microRNA targeting Bcr-Abl and that the expression level of miR-4433 was significantly increased after SAHA treatment in K562 cells. Luciferase activity analysis revealed that miR-4433 directly targets Bcr-Abl. Additionally, transient expression of miR-4433 abrogated Bcr-Abl activity and its downstream signaling pathways while inducing apoptosis in K562 cells. Moreover, stable expression of miR-4433 suppressed Bcr-Abl and its downstream signaling pathway, and inhibited the growth of K562 cells in vitro and the growth of K562-xenografts in nude mice. Conclusion: miR-4433 was identified as a microRNA targeting Bcr-Abl, which may be subject to epigenetic regulation of SAHA, a histone deacetylase inhibitor that has been approved by the US FDA for the treatment of cutaneous T-cell lymphoma. The findings of this study provide a molecular basis from another angle for the use of SAHA in the treatment of CML.
- Published
- 2019
20. GhCYP710A1 Participates in Cotton Resistance to Verticillium Wilt by Regulating Stigmasterol Synthesis and Plasma Membrane Stability
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Li Huang, Guiming Li, Qiaoling Wang, Qian Meng, Fan Xu, Qian Chen, Fang Liu, Yulin Hu, and Ming Luo
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Inorganic Chemistry ,Organic Chemistry ,cotton ,sterol C22-desaturase ,lipid raft ,JA ,phytosterol ,stigmasterol ,General Medicine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Cotton is an important economic crop. Cotton Verticillium wilt caused by Verticillium dahliae seriously damages production. Phytosterols play roles in plant-pathogen interaction. To explore the function and related mechanism of phytosterols in the interaction between Verticillium dahliae and cotton plants, and the resistance to Verticillium wilt, in this study, we analyzed the changes of sterol composition and content in cotton roots infected by Verticillium dahliae, and identified the sterol C22-desaturase gene GhCYP710A1 from upland cotton. Through overexpressing and silencing the gene in cotton plant, and ectopically expressing the gene in Arabidopsis, we characterized the changes of sterol composition and the resistance to Verticillium wilt in transgenic plants. The infection of Verticillium dahliae resulted in the content of total sterol and each sterol category decreasing in cotton root. The ratio of stigmasterol to sitosterol (St/Si) increased, indicating that the conversion of sitosterol to stigmasterol was activated. Consistently, the expression level of GhCYP710A1 was upregulated after infection. The GhCYP710A1 has the conservative domain that is essential for sterol C22-desaturase in plant and is highly expressed in root and stem, and its subcellular location is in the endoplasmic reticulum. The ectopic expression of GhCYP710A1 gene promoted the synthesis of stigmasterol in Arabidopsis. The St/Si value is dose-dependent with the expression level of GhCYP710A1 gene. Meanwhile, the resistance to Verticillium wilt of transgenic Arabidopsis increased and the permeability of cell membrane decreased, and the content of ROS decreased after V991 (a strain of Verticillium dahliae) infection. Consistently, the resistance to Verticillium wilt significantly increased in the transgenic cotton plants overexpressing GhCYP710A1. The membrane permeability and the colonization of V991 strain in transgenic roots were decreased. On the contrary, silencing GhCYP710A1 resulted in the resistance to Verticillium wilt being decreased. The membrane permeability and the colonization of V991 were increased in cotton roots. The expression change of GhCYP710A1 and the content alteration of stigmasterol lead to changes in JA signal transduction, hypersensitivity and ROS metabolism in cotton, which might be a cause for regulating the Verticillium wilt resistance of cotton plant. These results indicated that GhCYP710A1 might be a target gene in cotton resistance breeding.
- Published
- 2022
21. Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells
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Johanna Villarreal, Mei Qiao, Greco Hernández, Caihong Yi, Dmitri N. Ivanov, Mitzli X. Velasco, Luiz O. F. Penalva, Zhonghua Wang, Matthew J. Hart, Yogesh K. Gupta, Christopher G. Hubert, Soni Kaundal, and Guiming Li
- Subjects
0301 basic medicine ,Cell Survival ,Cancer therapy ,Nerve Tissue Proteins ,RNA-binding protein ,Biology ,Piperazines ,Small Molecule Libraries ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Line, Tumor ,Radiation, Ionizing ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Luteolin ,Molecular Biology ,Cell Proliferation ,RNA-Binding Proteins ,RNA ,Cancer ,Cell Biology ,medicine.disease ,Combined Modality Therapy ,Phenotype ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,chemistry ,Cancer research ,Phthalazines ,Glioblastoma ,Research Paper - Abstract
RNA binding proteins have emerged as critical oncogenic factors and potential targets in cancer therapy. In this study, we evaluated Musashi1 (Msi1) targeting as a strategy to treat glioblastoma (GBM); the most aggressive brain tumor type. Msi1 expression levels are often high in GBMs and other tumor types and correlate with poor clinical outcome. Moreover, Msi1 has been implicated in chemo- and radio-resistance. Msi1 modulates a range of cancer relevant processes and pathways and regulates the expression of stem cell markers and oncogenic factors via mRNA translation/stability. To identify Msi1 inhibitors capable of blocking its RNA binding function, we performed a ~ 25,000 compound fluorescence polarization screen. NMR and LSPR were used to confirm direct interaction between Msi1 and luteolin, the leading compound. Luteolin displayed strong interaction with Msi1 RNA binding domain 1 (RBD1). As a likely consequence of this interaction, we observed via western and luciferase assays that luteolin treatment diminished Msi1 positive impact on the expression of pro-oncogenic target genes. We tested the effect of luteolin treatment on GBM cells and showed that it reduced proliferation, cell viability, colony formation, migration and invasion of U251 and U343 GBM cells. Luteolin also decreased the proliferation of patient-derived glioma initiating cells (GICs) and tumor-organoids but did not affect normal astrocytes. Finally, we demonstrated the value of combined treatments with luteolin and olaparib (PARP inhibitor) or ionizing radiation (IR). Our results show that luteolin functions as an inhibitor of Msi1 and demonstrates its potential use in GBM therapy.
- Published
- 2018
22. Effect of surface oxygen vacancy sites on ethanol synthesis from acetic acid hydrogenation on a defective In2O3(110) surface
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Jiatao Liu, Yifei Chen, Guiming Li, Minhua Zhang, Haoxi Jiang, and Huisheng Lyu
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Surface oxygen ,Ethanol ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,engineering.material ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,Oxygen ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Acetic acid ,chemistry ,Catalytic cycle ,Vacancy defect ,engineering ,Noble metal ,Physical and Theoretical Chemistry ,0210 nano-technology - Abstract
Developing a new type of low-cost and high-efficiency non-noble metal catalyst is beneficial for industrially massive synthesis of alcohols from carboxylic acids which can be obtained from renewable biomass. In this work, the effect of active oxygen vacancies on ethanol synthesis from acetic acid hydrogenation over defective In2O3(110) surfaces has been studied using periodic density functional theory (DFT) calculations. The relative stabilities of six surface oxygen vacancies from Ov1 to Ov6 on the In2O3(110) surface were compared. D1 and D4 surfaces with respective Ov1 and Ov4 oxygen vacancies were chosen to map out the reaction paths from acetic acid to ethanol. A reaction cycle mechanism between the perfect and defective states of the In2O3 surface was found to catalyze the formation of ethanol from acetic acid hydrogenation. By H2 reduction the oxygen vacancies on the In2O3 surface play key roles in promoting CH3COO* hydrogenation and C–O bond breaking in acetic acid hydrogenation. The acetic acid, in turn, benefits the creation of oxygen vacancies, while the C–O bond breaking of acetic acid refills the oxygen vacancy and, thereby, sustains the catalytic cycle. The In2O3 based catalysts were shown to be advantageous over traditional noble metal catalysts in this paper by theoretical analysis.
- Published
- 2018
23. Insights into the mechanism of acetic acid hydrogenation to ethanol on Cu(111) surface
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Minhua Zhang, Yifei Chen, Guiming Li, Haoxi Jiang, and Rui Yao
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Reaction mechanism ,Ethanol ,Acetaldehyde ,General Physics and Astronomy ,02 engineering and technology ,Surfaces and Interfaces ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Dissociation (chemistry) ,0104 chemical sciences ,Surfaces, Coatings and Films ,Catalysis ,chemistry.chemical_compound ,Acetic acid ,Adsorption ,chemistry ,Organic chemistry ,0210 nano-technology ,Bond cleavage - Abstract
Density functional theory (DFT) calculations were employed to theoretically explain the reaction mechanism of acetic acid hydrogenation to ethanol on Cu catalyst. The activation barriers of key elementary steps and the adsorption configurations of key intermediates involved in acetic acid hydrogenation on Cu(111) surface were investigated. The results indicated that the direct dissociation of acetic acid to acetyl (CH3COOH → CH3CO + OH) is the rate-determined step. The activation barrier of acetic acid scission to acetyl and the adsorption energy of acetic acid are two descriptors which could determine the conversion of acetic acid. The descriptors might have effects on the ethanol selectivity including: the adsorption energy of acetaldehyde and the activation barriers for O H bond formation of C2-oxygenates (CH3CO + H → CH3COH, CH3CHO + H → CH3CHOH and CH3CH2O + H → CH3CH2OH). These proposed descriptors could be used as references to design new Cu-based catalysts that have excellent catalytic performance.
- Published
- 2017
24. Catalytic activity of transition metal doped Cu(111) surfaces for ethanol synthesis from acetic acid hydrogenation: a DFT study
- Author
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Yifei Chen, Minhua Zhang, Haoxi Jiang, Rui Yao, and Guiming Li
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General Chemical Engineering ,Inorganic chemistry ,Doping ,Acetaldehyde ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,Catalysis ,Acetic acid ,chemistry.chemical_compound ,Adsorption ,chemistry ,Transition metal ,Density functional theory ,0210 nano-technology ,Bond cleavage - Abstract
Transition metal (Co, Ni, Ru, Rh, Pd and Pt) doped Cu(111) models are selected to examine the effects of transition metals on Cu surface for ethanol synthesis from acetic acid hydrogenation using density functional theory (DFT) calculations. On these surfaces, the adsorption of the main intermediates and reaction barriers of key elementary steps are investigated. The calculation results indicate that oxophilic metals are projected to be more active in acetic acid adsorption and acetaldehyde adsorption compared to less-oxophilic metals. Those metals with larger C adsorption energies generally have better C–OH bond cracking activity. Additionally, a good linear Bronsted–Evans–Polanyi (BEP) correlation is established for predicting the preferences of C–OH bond scission of acetic acid on other metals. Finally, O–H bond formation in C2-oxygenates (CH3CO, CH3CHO, CH3CH2O) hydrogenation is examined on all these surfaces. The reactions are more likely to occur on less-oxophilic metal-doped Cu surfaces. Therefore, it appears to involve an intricate balance between C–OH cracking and O–H bond formation reactions. That means those metal-doped Cu-based catalysts that are capable of preferentially activating C–OH bond without considerably inhibiting O–H bond formation of C2-oxygenates are predicted to achieve optimum catalytic activity for ethanol synthesis from acetic acid hydrogenation. The results can provide theoretical guidance for related experiments as well as the designing of Cu-based catalysts for ethanol synthesis.
- Published
- 2017
25. Insights into the mechanism of ethanol synthesis and ethyl acetate inhibition from acetic acid hydrogenation over Cu2In(100): a DFT study
- Author
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Huisheng Lyu, Yifei Chen, Minhua Zhang, Jiatao Liu, Haoxi Jiang, and Guiming Li
- Subjects
Ethanol ,Chemistry ,Ethyl acetate ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Copper ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Acetic acid ,Adsorption ,Organic chemistry ,Physical and Theoretical Chemistry ,0210 nano-technology ,Bimetallic strip ,Indium - Abstract
Developing low-cost and high-efficiency non-noble metal catalysts is beneficial for industrially massive synthesis of ethanol from acetic acid, which can be obtained from renewable biomass. Understanding the detailed mechanism of the reaction from a molecular level provides insights that can be used to tailor catalysts to improve their performance. In this study, alternative mechanisms for ethanol synthesis from acetic acid hydrogenation over Cu2In(100) have been investigated using periodic density functional theory (DFT) calculations. The pathway of CH3COOH → CH3COO → CH3CHOO → CH3CHO → CH3CH2O → CH3CH2OH was found to be most favorable. The high activation barriers for CH3COO hydrogenation to CH3CHOO (1.33 eV) and CH3CH2O hydrogenation to CH3CH2OH (1.04 eV) indicate that these two steps are the rate-limiting steps. In addition, the results also show that there are probably two more active intermediate species of CH3CO and CH3CH(OH)O besides CH3COO. Furthermore, the synergy and the role of copper and indium in the Cu–In bimetallic catalyst were discussed. The adsorption strength of copper will be improved by indium. Indium, however, has high chemical inertness in Cu2In. They evenly divided the surface into small reaction areas which could significantly inhibit ethyl acetate formation through the hindrance effect.
- Published
- 2017
26. Passive mode locking in fiber lasers due to the polarization-dependent losses
- Author
-
Luming Zhao, Guiming Li, Xiaohong Yan, and Jian Kong
- Subjects
Materials science ,business.industry ,Polarization (waves) ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,010309 optics ,Optics ,Mode-locking ,Fiber laser ,0103 physical sciences ,Dispersion (optics) ,Electrical and Electronic Engineering ,Polarization dependent ,business ,Engineering (miscellaneous) - Abstract
Weak polarization dependence exists in most fiber components. We numerically demonstrated passive mode locking in fiber lasers based on weak polarization dependence down to polarization-dependent loss of 1.76 dB. Different polarization dependences are investigated to unveil its role for achieving passive mode locking. The anomalous dispersion region and the normal dispersion regime are both tested. It is found that, independent of operating dispersion regime, stronger gain is required for achieving mode locking with lower polarization dependence. Our numerical demonstration confirms previous experimental results and broadens the knowledge on additive-pulse mode locking.
- Published
- 2020
27. In Vitro Assessment of Combinations of Enterovirus Inhibitors against Enterovirus 71
- Author
-
Yizhuo Wang, Qianqian Gao, Ralf Altmeyer, Shilin Yuan, Gang Zou, Ke Lan, and Guiming Li
- Subjects
0301 basic medicine ,Indoles ,Drug resistance ,Viral Nonstructural Proteins ,Virus Replication ,medicine.disease_cause ,Protein Structure, Secondary ,Myoblasts ,Chlorocebus aethiops ,Enterovirus 71 ,Pharmacology (medical) ,Cytotoxicity ,Pathogen ,Drug Synergism ,Valine ,Pyrrolidinones ,Molecular Docking Simulation ,Drug Combinations ,Infectious Diseases ,Pyrazines ,Itraconazole ,Protein Binding ,medicine.drug ,Phenylalanine ,Suramin ,030106 microbiology ,Favipiravir ,Biology ,Antiviral Agents ,03 medical and health sciences ,Phenols ,Cell Line, Tumor ,Drug Resistance, Viral ,medicine ,Animals ,Humans ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,Vero Cells ,Pharmacology ,Binding Sites ,Sequence Homology, Amino Acid ,Isoxazoles ,biology.organism_classification ,Amides ,Virology ,Enterovirus A, Human ,030104 developmental biology ,Viral replication ,Mutation ,Enterovirus ,Sequence Alignment - Abstract
Enterovirus 71 (EV-A71) is a major causative pathogen of hand, foot, and mouth disease (HFMD) epidemics. No antiviral therapies are currently available for treating EV-A71 infections. Here, we selected five reported enterovirus inhibitors (suramin, itraconazole [ITZ], GW5074, rupintrivir, and favipiravir) with different mechanisms of action to test their abilities to inhibit EV-A71 replication alone and in combination. All selected compounds have anti-EV-A71 activities in cell culture. The combination of rupintrivir and ITZ or favipiravir was synergistic, while the combination of rupintrivir and suramin was additive. The combination of suramin and favipiravir exerted a strong synergistic antiviral effect. The observed synergy was not due to cytotoxicity, as there was no significant increase in cytotoxicity when compounds were used in combinations at the tested doses. To investigate the potential inhibitory mechanism of favipiravir against enterovirus, two favipiravir-resistant EV-A71 variants were independently selected, and both of them carried an S121N mutation in the finger subdomain of the 3D polymerase. Reverse engineering of this 3D S121N mutation into an infectious clone of EV-A71 confirmed the resistant phenotype. Moreover, viruses resistant to ITZ or favipiravir remained susceptible to other inhibitors. Most notably, combined with ITZ, rupintrivir prevented the development of ITZ-resistant variants. Taken together, these results provide a rational basis for the design of combination regimens for use in the treatment of EV-A71 infections.
- Published
- 2016
28. Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus
- Author
-
Ralf Altmeyer, Liu Wang, Rui Cui, Yizhuo Wang, Guiming Li, Gang Zou, and Ke Lan
- Subjects
Gene Expression Regulation, Viral ,0301 basic medicine ,Indoles ,Thapsigargin ,viruses ,030106 microbiology ,Calcium-Transporting ATPases ,Respiratory Syncytial Virus Infections ,Biology ,Pharmacology ,Virus Replication ,Antiviral Agents ,Calcium in biology ,Cell Line ,Small Molecule Libraries ,03 medical and health sciences ,chemistry.chemical_compound ,Virology ,Animals ,Humans ,Biological Products ,Dose-Response Relationship, Drug ,Calcium channel ,Calcium Ionophores ,High-Throughput Screening Assays ,Tetrandrine ,Calcium ATPase ,030104 developmental biology ,chemistry ,Respiratory Syncytial Virus, Human ,Ionomycin ,Calcium ,Sodium-Potassium-Exchanging ATPase ,Cyclopiazonic acid - Abstract
Human respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants and young children worldwide, yet no vaccine or effective antiviral treatment is available. To search for new anti-RSV agents, we developed a cell-based assay that measures inhibition of RSV-induced cytopathic effect (CPE) and identified cyclopiazonic acid (CPA), an intracellular calcium ATPase inhibitor as a RSV inhibitor (EC50 values 4.13 μM) by screening of natural product library. CPA inhibited the replication of RSV strains belonging to both A and B subgroups and human parainfluenza virus type 3, but not Enterovirus 71. Mechanism of action study by time-of-addition assay and minigenome assay revealed that CPA acts at the step of virus genome replication and/or transcription. Moreover, two other calcium ATPase inhibitors (Thapsigargin and BHQ) and calcium ionophores (A23187 and ionomycin), but not calcium channel blockers (nifedipine, nimodipine, and tetrandrine), also had similar effect. These results indicate that an increase in intracellular calcium concentration is detrimental to RSV replication. Thus, our findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration.
- Published
- 2016
29. Identification of Positively Charged Residues in Enterovirus 71 Capsid Protein VP1 Essential for Production of Infectious Particles
- Author
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Qianqian Gao, Shilin Yuan, Yizhuo Wang, Guiming Li, Ying Wang, Gang Zou, Rui Cui, and Ralf Altmeyer
- Subjects
0301 basic medicine ,viruses ,Static Electricity ,030106 microbiology ,Immunology ,Mutant ,Mutagenesis (molecular biology technique) ,Virus Replication ,medicine.disease_cause ,Microbiology ,03 medical and health sciences ,Suppression, Genetic ,Virology ,Chlorocebus aethiops ,medicine ,Animals ,Vero Cells ,Mutation ,biology ,Structure and Assembly ,virus diseases ,RNA virus ,biology.organism_classification ,Reverse Genetics ,Enterovirus A, Human ,Entry inhibitor ,030104 developmental biology ,Amino Acid Substitution ,Capsid ,Viral replication ,Virion assembly ,Insect Science ,Mutagenesis, Site-Directed ,Capsid Proteins ,Mutant Proteins ,medicine.drug - Abstract
Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) in children, which can cause severe central nervous system disease and death. The capsids of EV71 consist of 60 copies of each of four viral structural proteins (VP1 to VP4), with VP1, VP2, and VP3 exposed on the surface and VP4 arranged internally. VP1 plays a central role in particle assembly and cell entry. To gain insight into the role of positively charged residues in VP1 function in these processes, a charged-to-alanine scanning analysis was performed using an infectious cDNA clone of EV71. Twenty-seven mutants containing single charged-to-alanine changes were tested. Sixteen of them were not viable, seven mutants were replication defective, and the remaining four mutants were replication competent. By selecting revertants, second-site mutations which could at least partially restore viral infectivity were identified within VP1 for four defective mutations and two lethal mutations. The resulting residue pairs represent a network of intra- and intermolecular interactions of the VP1 protein which could serve as a potential novel drug target. Interestingly, mutation K215A in the VP1 GH loop led to a significant increase in thermal stability, demonstrating that conditional thermostable mutants can be generated by altering the charge characteristics of VP1. Moreover, all mutants were sensitive to the EV71 entry inhibitor suramin, which binds to the virus particle via the negatively charged naphthalenetrisulfonic acid group, suggesting that single charged-to-alanine mutation is not sufficient for suramin resistance. Taken together, these data highlight the importance of positively charged residues in VP1 for production of infectious particles. IMPORTANCE Infection with EV71 is more often associated with neurological complications in children and is responsible for the majority of fatalities. No licensed vaccines or antiviral therapies are currently available for the prevention or treatment of EV71 infection. Understanding the determinants of virion assembly and entry will facilitate vaccine development and drug discovery. Here, we identified 23 out of 27 positively charged residues in VP1 which impaired or blocked the production of infectious particles. The defect could be rescued by second-site mutations within the VP1 protein. Our findings highlight the importance of positively charged residues in VP1 during infectious particle production and reveal a potential strategy for blocking EV71 infections by inhibiting intra- or intermolecular interactions of the VP1 protein.
- Published
- 2016
30. Controlled synthesis of highly dispersed and nano-sized Ru catalysts supported on carbonaceous materials via supercritical fluid deposition
- Author
-
Minhua Zhang, Yimin Zhang, Haoxi Jiang, and Guiming Li
- Subjects
Materials science ,General Chemical Engineering ,Inorganic chemistry ,Nanoparticle ,02 engineering and technology ,General Chemistry ,Carbon nanotube ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Supercritical fluid ,0104 chemical sciences ,law.invention ,Catalysis ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Nitric acid ,law ,Particle size ,Temperature-programmed reduction ,0210 nano-technology ,High-resolution transmission electron microscopy - Abstract
Highly dispersed Ru nanoparticles (NPs) supported on carbonaceous materials were fabricated by supercritical fluid deposition technology and characterized by various methods including high-resolution transmission electron microscopy (HRTEM), and X-ray photoelectron spectroscopy (XPS). The mean particle size was controlled in the range from 0.42 to 3.66 nm by changing the carbonaceous support or the pretreatment method of the supports. Ru NPs supported on carbon nanotubes (CNTs) presented smaller particle size, higher dispersion and catalytic activity than those on activated carbon (AC). The interactions between Ru precursors and different carbonaceous supports were characterized by hydrogen temperature programmed reduction (TPR). The ultrasonication-assisted nitric acid oxidation pretreatment method for CNTs is favorable for the dispersion of Ru NPs. The appropriate ultrasound time and the dosage of nitric acid are the prerequisites of its good performance. The optimized pretreatment conditions are ultrasound time 20 min and nitric acid dosage 1/14 (the mass ratio of CNTs to HNO3).
- Published
- 2016
31. Investigation of the dithering-like cycles induced by deuterium pellet injection during ELMy H-mode plasmas on EAST
- Author
-
Y.M. Wang, F. Wen, T. Zhang, Z. Zhou, Guiming Li, M.F. Wu, L. Wang, Jilei Hou, Junchao Huang, Y. K. Liu, Ge Zhuang, Kangning Geng, H.M. Xiang, J.S. Hu, K.X. Ye, F.B. Zhong, J.B. Liu, Y. Q. Liu, East Team, and He Liu
- Subjects
Nuclear and High Energy Physics ,Materials science ,Deuterium ,Pellet ,Mode (statistics) ,Dither ,Plasma ,Atomic physics ,Condensed Matter Physics - Published
- 2020
32. A novel cold-regulated protein isolated from Saussurea involucrata confers cold and drought tolerance in transgenic tobacco (Nicotiana tabacum)
- Author
-
Ning Liu, Guiming Li, Xinyong Guo, Zhihua Xu, Gaoquan Dong, Jianbo Zhu, Li Zhang, and Aiying Wang
- Subjects
Saussurea ,0106 biological sciences ,0301 basic medicine ,Acclimatization ,Nicotiana tabacum ,Transgene ,Drought tolerance ,Plant Science ,Genetically modified crops ,01 natural sciences ,03 medical and health sciences ,Gene Expression Regulation, Plant ,Tobacco ,Gene expression ,Genetics ,Amino Acid Sequence ,Gene ,Phylogeny ,Plant Proteins ,biology ,fungi ,food and beverages ,Plant physiology ,General Medicine ,Plants, Genetically Modified ,biology.organism_classification ,Droughts ,Cell biology ,Cold Temperature ,030104 developmental biology ,Transcription Factor Gene ,Sequence Alignment ,Agronomy and Crop Science ,010606 plant biology & botany - Abstract
Adverse environmental conditions, such as cold and drought, can inhibit plant growth, development, and productivity. The isolation and characterization of stress response genes from stress-tolerant plants can provide a better understanding of the underlying adaptive mechanisms. In this study, a novel cold-regulated gene, SikCOR413PM1, was isolated from Saussurea involucrata Kar. et Kir., which is a plant that survives at the high altitudes and in the low temperatures of alpine slopes in northwestern China. SikCOR413PM1 was induced in response to cold and drought in S. involucrata, and phylogenetic analysis revealed that the gene groups with a COR gene encoding a COR413PM protein family member. Subcellular localization of a SikCOR413PM1-green fluorescent fusion protein showed that SikCOR413PM1 was localized to the plasma membrane. A transgenic tobacco (Nicotiana tabacum) system was employed to investigate the possible role of SikCOR413PM1 in cold and drought tolerance. Analyses of growth, germination and survival rates, relative water content, malondialdehyde content, relative electrolyte leakage, and maximal photochemical efficiency of photosystem II showed that transgenic tobacco plants expressing SikCOR413PM1 were more tolerant to cold and drought stresses than WT plants. SikCOR413PM1 overexpression was also accompanied by constitutive activation of NtDREB1 and NtDREB3, two cold-responsive transcription factor genes, and NtERD10A and NtERD10B, two cold-induced genes. The expression levels of downstream transcription factor genes NtDREB3, NtERD10C, NtERD10D, and NtLEA5 were also induced in SikCOR413PM1-expressing transgenic plants under drought conditions. Our results suggest that the overexpression of SikCOR413PM1 induces changes in tobacco plants, and facilitates enhanced tolerance to cold and drought stresses.
- Published
- 2019
33. Passive mode locking resulting from weak polarization dependence based on evanescent field interaction with a monolayer graphene absorber
- Author
-
Xiaohong Yan, Yuan Chen, Guiming Li, and Luming Zhao
- Subjects
Materials science ,Graphene ,business.industry ,Saturable absorption ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Laser ,Polarization (waves) ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,law.invention ,010309 optics ,Light intensity ,Optics ,Mode-locking ,law ,Fiber laser ,0103 physical sciences ,Electrical and Electronic Engineering ,0210 nano-technology ,business ,Engineering (miscellaneous) ,Light field - Abstract
Weak polarization dependence based on evanescent field interaction with a monolayer graphene absorber is demonstrated. By covering single-layer graphene on the top of a fiber taper, the symmetry of the light field propagation was destroyed. Polarization-dependent loss (PDL) of 2 dB was obtained, and no saturable absorption was observed. Passive mode locking was achieved by using the graphene-covered fiber taper in a fiber laser. It is found that the weak PDL down to 2 dB is capable for achieving mode locking in a fiber laser. Therefore, the claim of saturable absorption of any graphene or two-dimensional materials in a fiber laser needs to be made with care.
- Published
- 2018
34. Effect of surface oxygen vacancy sites on ethanol synthesis from acetic acid hydrogenation on a defective In
- Author
-
Huisheng, Lyu, Jiatao, Liu, Yifei, Chen, Guiming, Li, Haoxi, Jiang, and Minhua, Zhang
- Abstract
Developing a new type of low-cost and high-efficiency non-noble metal catalyst is beneficial for industrially massive synthesis of alcohols from carboxylic acids which can be obtained from renewable biomass. In this work, the effect of active oxygen vacancies on ethanol synthesis from acetic acid hydrogenation over defective In
- Published
- 2018
35. Hematopoietic knockdown of PPARδ reduces atherosclerosis in LDLR−/− mice
- Author
-
C Chen, K C Biju, Guiming Li, S D Laing, Robert A. Clark, Robert L. Reddick, Clive Ballard, and Senlin Li
- Subjects
0301 basic medicine ,CCR2 ,Receptors, CCR2 ,Interleukin-1beta ,Down-Regulation ,Inflammation ,Biology ,Article ,Mice ,03 medical and health sciences ,Downregulation and upregulation ,Genetics ,medicine ,Animals ,PPAR delta ,Molecular Biology ,Aorta ,Chemokine CCL2 ,Mice, Knockout ,Gene knockdown ,Interleukin-6 ,Macrophages ,Monocyte ,Genetic Therapy ,Atherosclerosis ,Hematopoietic Stem Cells ,Plaque, Atherosclerotic ,Transplantation ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Matrix Metalloproteinase 9 ,Gene Knockdown Techniques ,LDL receptor ,Cancer research ,Molecular Medicine ,Female ,Bone marrow ,medicine.symptom ,ATP Binding Cassette Transporter 1 - Abstract
PPARδ (peroxisome proliferator-activated receptor δ) mediates inflammation in response to lipid accumulation. Systemic administration of a PPARδ agonist can ameliorate atherosclerosis. Paradoxically, genetic deletion of PPARδ in hematopoietic cells led to a reduction of atherosclerosis in murine models, suggesting that downregulation of PPARδ expression in these cells may mitigate atherogenesis. To advance this finding forward to potential clinical translation through hematopoietic stem cell transplantation-based gene therapy, we employed a microRNA (miRNA) approach to knock down PPARδ expression in bone marrow cells followed by transplantation of the cells into LDLR −/− mice. We found that knockdown of PPARδ expression in the hematopoietic system caused a dramatic reduction in aortic atherosclerotic lesions. In macrophages, a key component in atherogenesis, knockdown of PPARδ led to decreased expression of multiple pro-inflammatory factors, including monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β and IL-6. Expression of CCR2, a receptor for MCP-1, was also decreased. The downregulation of pro-inflammatory factors is consistent with significant reduction of macrophage presence in the lesions, which may also be attributable to elevation of ABCA1 (ATP-binding cassette, subfamily A, member 1) and depression of adipocyte differentiate-related protein. Furthermore, the abundance of both MCP-1 and matrix metalloproteinase-9 proteins was reduced in plaque areas. Our results demonstrate that miRNA-mediated PPARδ knockdown in hematopoietic cells is able to ameliorate atherosclerosis.
- Published
- 2015
36. High activity ordered mesoporous carbon-based solid acid catalyst for the esterification of free fatty acids
- Author
-
Anxia Sun, Haoxi Jiang, Minhua Zhang, Guiming Li, Yonglu Meng, and Lingtao Wang
- Subjects
Acid value ,Carbonization ,Inorganic chemistry ,chemistry.chemical_element ,General Chemistry ,Condensed Matter Physics ,Catalysis ,chemistry.chemical_compound ,Adsorption ,chemistry ,Mechanics of Materials ,General Materials Science ,Methanol ,Mesoporous material ,High-resolution transmission electron microscopy ,Carbon ,Nuclear chemistry - Abstract
Sulfonated mesoporous carbon catalysts were synthesized using a carbonization–sulfonation method and employed to the pre-esterification of free fatty acids contained in high acid value oil. Various synthesis parameters, such as composition of carbon precursor, carbonization and sulfonation temperature, were systematically investigated. The catalysts were characterized by N2 adsorption, small angle XRD, HRTEM, FT-IR and strong acid density analysis. The results indicated that they have a high surface area, uniform pore size, large mesopore volume, high acid density and good catalytic activity. Among them, MC600-S160 exhibited a highest activity and good stability for the esterification of FFA with methanol, the FFA conversion reached 94.6% after reaction for 3 h.
- Published
- 2015
37. Catalytic Performance of Biomass Carbon-Based Solid Acid Catalyst for Esterification of Free Fatty Acids in Waste Cooking Oil
- Author
-
Anxia Sun, Lingtao Wang, Haoxi Jiang, Guiming Li, Minhua Zhang, and Yonglu Meng
- Subjects
inorganic chemicals ,Biodiesel ,Acid value ,Carbonization ,organic chemicals ,Industrial catalysts ,chemistry.chemical_element ,General Chemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Organic chemistry ,Methanol ,Bagasse ,Carbon ,Nuclear chemistry - Abstract
A series of carbon-based solid acid catalysts were prepared from bagasse using a carbonization–sulfonation method and employed to catalyze esterification of oil with methanol to produce biodiesel. The physical and chemical properties of the biomass carbon catalysts were characterized by FTIR. The pretreatment of bagasse, carbonization temperature, sulfonation temperature and time, as well as the catalytic performance were systematically investigated. The results indicated that the catalysts prepared from bagasse with dilute acid hydrothermal treatment showed the best performance. For the catalysts, the acid value of waste cooking oils was decreased to 1 mg KOH/g, and FFA conversion reached 94.4 % after reaction for 4 h under optimized reaction conditions. The catalysts also showed better stability than traditional homogeneous catalysts.
- Published
- 2014
38. Ordered mesoporous carbon supported ferric sulfate: A novel catalyst for the esterification of free fatty acids in waste cooking oil
- Author
-
Xiuqin Dong, Haoxi Jiang, Guiming Li, Lingtao Wang, and Minhua Zhang
- Subjects
inorganic chemicals ,Biodiesel ,Chemistry ,organic chemicals ,General Chemical Engineering ,Inorganic chemistry ,Energy Engineering and Power Technology ,Catalysis ,chemistry.chemical_compound ,Fuel Technology ,Adsorption ,Pyridine ,medicine ,Ferric ,Lewis acids and bases ,Methanol ,Mesoporous material ,medicine.drug ,Nuclear chemistry - Abstract
Ordered mesoporous carbon (OMC) supported ferric sulfate (FS) catalysts were prepared by impregnation, and their catalytic activity for the esterification of the free fatty acids (FFAs) in waste cooking oil (WCO) with methanol was evaluated. The FS/OMC catalysts were characterized by N 2 adsorption–desorption, powder X-ray diffraction and transmission electron microscopy. The results indicated that catalysts retained the ordered mesoporous structure, and the FS was well dispersed on the surface of the OMC. The FT-IR spectrum of pyridine adsorbed on the FS/OMC catalysts showed the presence of strong Lewis acid sites on the surface of the catalysts. The FS/OMC catalysts exhibited excellent catalytic performances for FFA esterification. In addition, the process variables that influence the esterification of FFAs, such as the FS loading, the amount of catalyst, the molar ratio of methanol to FFAs, the reaction temperature and the reaction time, were investigated and optimized. The FS/OMC catalysts are reusable and maintained their original catalytic activities after six uses.
- Published
- 2014
39. The action mechanism of ethanol in preparation of supported nano-sized Ru catalyst via supercritical fluid deposition
- Author
-
Guiming Li, Yanhui Wang, Yimin Zhang, Minhua Zhang, and Haoxi Jiang
- Subjects
Ethanol ,Process Chemistry and Technology ,Inorganic chemistry ,Butanone ,General Chemistry ,Catalysis ,Supercritical fluid ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,medicine ,Particle ,Deposition (phase transition) ,Particle size ,Activated carbon ,medicine.drug - Abstract
Ru catalysts supported on activated carbon (AC) were prepared by supercritical fluid deposition (SFD) with ethanol added and their catalytic performance in butanone hydrogenation was investigated. The effects of ethanol amount on Ru particle size were systematically studied. As the amount of ethanol increased, Ru mean particle sizes always decreased firstly, then increased. And the minimum mean particle size of Ru was obtained at 10 ml ethanol. The catalysts with smaller Ru mean particle size presented higher catalytic activity. These results demonstrated that the role of ethanol may not be only co-solvent but also anti-solvent and extractant during the preparation of Ru/AC.
- Published
- 2014
40. Phosphorylated ordered mesoporous carbon as a novel solid acid catalyst for the esterification of oleic acid
- Author
-
Lingtao Wang, Xiuqin Dong, Haoxi Jiang, Guiming Li, and Minhua Zhang
- Subjects
endocrine system ,Carbonization ,Process Chemistry and Technology ,Phosphorus ,chemistry.chemical_element ,General Chemistry ,Catalysis ,chemistry.chemical_compound ,Oleic acid ,chemistry ,Mesoporous carbon ,Phosphorylation ,Organic chemistry ,Methanol ,Phosphoric acid ,hormones, hormone substitutes, and hormone antagonists - Abstract
A novel phosphorylated ordered mesoporous carbon (POMC) solid acid catalyst has been prepared by modifying mesoporous carbon with phosphoric acid, and was employed to catalyze the esterification oleic acid with methanol. The effects of the carbonization temperature on the type of phosphorus species formed, the phosphorus content and the amount of acid in the POMC were investigated. A mechanism for the phosphorylation of the ordered mesoporous carbon is proposed. The POMCs have good catalytic activity for the esterification of oleic acid and showed good reusability.
- Published
- 2014
41. Insights into the mechanism of ethanol synthesis and ethyl acetate inhibition from acetic acid hydrogenation over Cu
- Author
-
Jiatao, Liu, Huisheng, Lyu, Yifei, Chen, Guiming, Li, Haoxi, Jiang, and Minhua, Zhang
- Abstract
Developing low-cost and high-efficiency non-noble metal catalysts is beneficial for industrially massive synthesis of ethanol from acetic acid, which can be obtained from renewable biomass. Understanding the detailed mechanism of the reaction from a molecular level provides insights that can be used to tailor catalysts to improve their performance. In this study, alternative mechanisms for ethanol synthesis from acetic acid hydrogenation over Cu
- Published
- 2017
42. Characterization of three small molecule inhibitors of enterovirus 71 identified from screening of a library of natural products
- Author
-
Lili Wang, Ralf Altmeyer, Ke Lan, Qianqian Gao, Shilin Yuan, Guiming Li, Feifei Yin, and Gang Zou
- Subjects
0301 basic medicine ,viruses ,030106 microbiology ,Biology ,medicine.disease_cause ,Virus Replication ,Virus ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Viral entry ,Coumarins ,Virology ,Cricetinae ,Chlorocebus aethiops ,Drug Discovery ,Drug Resistance, Viral ,medicine ,Enterovirus 71 ,Enterovirus Infections ,Formononetin ,Animals ,Humans ,Yangonin ,Vero Cells ,Enterovirus ,Pharmacology ,Biological Products ,Haplorhini ,Virus Internalization ,biology.organism_classification ,Genistein ,Isoflavones ,Enterovirus A, Human ,High-Throughput Screening Assays ,030104 developmental biology ,Capsid ,chemistry ,Pyrones ,Mutation ,Auraptene ,Capsid Proteins ,Sequence Alignment - Abstract
Enterovirus 71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD). Infection with EV-A71 is more often associated with neurological complications in children and is responsible for the majority of fatalities, but currently there is no approved antiviral therapy for treatment. Here, we identified auraptene, formononetin, and yangonin as effective inhibitors of EV-A71 infection in the low-micromolar range from screening of a natural product library. Among them, formononetin and yangonin selectively inhibited EV-A71 while auraptene could inhibit viruses within the enterovirus species A. Time of addition studies showed that all the three inhibitors inhibit both attachment and postattachment step of entry. We found mutations conferring the resistance to these inhibitors in the VP1 and VP4 capsid proteins and confirmed the target residues using a reverse genetic approach. Interestingly, auraptene- and formononetin-resistant viruses exhibit cross-resistance to other inhibitors while yangonin-resistant virus still remains susceptible to auraptene and formononetin. Moreover, auraptene and formononetin, but not yangonin protected EV-A71 against thermal inactivation, indicating a direct stabilizing effect of both compounds on virion capsid conformation. Finally, neither biochanin A (an analog of formononetin) nor DL-Kavain (an analog of yangonin) exhibited anti-EV-A71 activity, suggesting the structural elements required for anti-EV-A71 activity. Taken together, these compounds could become potential lead compounds for anti-EV-A71 drug development and also serve as tool compounds for studying virus entry.
- Published
- 2017
43. A DFT Study of Ethanol Adsorption and Dehydrogenation on Cu/Cr2O3 Catalyst
- Author
-
Yingzhe Yu, Guiming Li, Yanping Huang, Minhua Zhang, and Ruzhen Li
- Subjects
Ethanol ,Inorganic chemistry ,chemistry.chemical_element ,General Chemistry ,Copper ,Catalysis ,chemistry.chemical_compound ,Adsorption ,chemistry ,Cluster (physics) ,Molecule ,Dehydrogenation ,Organometallic chemistry - Abstract
In this work, DFT simulation method was used to study the adsorption and dehydrogenation of ethanol on Cu/Cr2O3 catalyst. Firstly, the stable configuration of Cu4 cluster adsorbed on Cr2O3(001) surface was studied. Secondly, the adsorption and dehydrogenation of ethanol on Cr2O3(001) surface and Cu/Cr2O3 were calculated. A part of the charge transfers to Cr2O3 from Cu4 cluster after Cu4 cluster is adsorbed on Cr2O3(001) surface. It is easier for Cu/Cr2O3 catalyst to supply electrons than pure copper catalyst. Adsorption energy of ethanol molecules on Cr2O3(001) surface is 0.94 eV, suggesting a chemisorptions process. The adsorption energy of ethanol on pure copper is only 0.34 eV. The interface of Cu4 cluster and Cr2O3 provides the appropriate ethanol adsorption sites. The adsorption energy of the most stable configuration of ethanol is 0.80 eV, and the adsorbed ethanol molecule bonds with Cu atom. There is a charge transfer process among ethanol, Cu cluster and Cr2O3, which can enhance the adsorption stability of ethanol molecules. In this work, DFT simulation method was used to study the adsorption and dehydrogenation of ethanol on Cu/Cr2O3 catalyst. Firstly, the stable configuration of Cu4 cluster adsorbed on Cr2O3(001) surface was studied. Secondly, the adsorption and dehydrogenation of ethanol on Cr2O3(001) surface and Cu/Cr2O3 were calculated. A part of the charge transfers to Cr2O3 from Cu4 cluster after Cu4 cluster is adsorbed on Cr2O3(001) surface. It is easier for Cu/Cr2O3 catalyst to supply electrons than pure copper catalyst. Adsorption energy of ethanol molecule on Cr2O3(001) surface is 0.94 eV, suggesting a chemisorptions process. The adsorption energy of ethanol on pure copper is only 0.34 eV. The interface of Cu4 cluster and Cr2O3 provides the appropriate ethanol adsorption sites. The adsorption energy of the most stable configuration of ethanol is 0.80 eV, and the adsorbed ethanol molecule bonds with Cu atom. There is a charge transfer process among ethanol, Cu cluster and Cr2O3, which can enhance the adsorption stability of ethanol molecules.
- Published
- 2014
44. Synthesis of MnOx–CeO2·NOx catalysts by polyvinylpyrrolidone-assisted supercritical antisolvent precipitation
- Author
-
Guiming Li, Li Kuang, Minhua Zhang, Huiqin Wang, and Haoxi Jiang
- Subjects
Materials science ,Precipitation (chemistry) ,Mechanical Engineering ,Oxide ,chemistry.chemical_element ,Selective catalytic reduction ,Condensed Matter Physics ,Supercritical fluid ,law.invention ,Catalysis ,Cerium ,chemistry.chemical_compound ,chemistry ,Mechanics of Materials ,law ,General Materials Science ,Calcination ,NOx ,Nuclear chemistry - Abstract
A series of MnOx–CeO2 binary oxide catalysts were synthesized by polyvinylpyrrolidone-assisted supercritical antisolvent precipitation and the effects of the manganese (Mn)/cerium (Ce) molar ratio and calcination temperature on the structure and properties of MnOx–CeO2 were investigated. A solid solution was obtained at each experimental condition and the highest surface area of 107.6 m2/g was obtained at the Mn/Ce molar ratio of 3:5 and the calcination temperature of 400 °C. Low-temperature selective catalytic reduction of emissions of nitrogen oxides, namely NO, NO2, and N2O (deNOx) with ammonia (NH3) to convert them into nitrogen and water, was used as model reaction to evaluate MnOx–CeO2 catalytic performance. It is found that the activity first increased and then decreased with increasing Mn content and decreased with increasing calcination temperature. The highest catalytic activity (93.3% NO conversion and 100% N2 selectivity) was obtained at the Mn/Ce molar ratio of 1/1 and the calcination temperature of 400 °C, which was attributed to the combination of high surface area and high redox performance of the catalyst.
- Published
- 2014
45. Preparation of a novel carbon-based solid acid from cassava stillage residue and its use for the esterification of free fatty acids in waste cooking oil
- Author
-
Xiuqin Dong, Guiming Li, Haoxi Jiang, Minhua Zhang, and Lingtao Wang
- Subjects
Acid value ,Hot Temperature ,Manihot ,Environmental Engineering ,Esterification ,Renewable Energy, Sustainability and the Environment ,Carbonization ,food and beverages ,Bioengineering ,Sulfuric acid ,General Medicine ,Fatty Acids, Nonesterified ,Raw material ,Carbon ,Catalysis ,Cold Temperature ,chemistry.chemical_compound ,Residue (chemistry) ,chemistry ,Organic chemistry ,Cooking ,Stillage ,Methanol ,Oils ,Waste Management and Disposal - Abstract
A novel carbon-based solid acid catalyst was prepared by the sulfonation of incompletely carbonized cassava stillage residue (CSR) with concentrated sulfuric acid, and employed to catalyze the esterification of methanol and free fatty acids (FFAs) in waste cooking oil (WCO). The effects of the carbonization and the sulfonation temperatures on the pore structure, acid density and catalytic activity of the CSR-derived catalysts were systematically investigated. Low temperature carbonization and high temperature sulfonation can cause the collapse of the carbon framework, while high temperature carbonization is not conducive to the attachment of SO3H groups on the surface. The catalyst showed high catalytic activity for esterification, and the acid value for WCO is reduced to below 2mg KOH/g after reaction. The activity of catalyst can be well maintained after five cycles. CSR can be considered a promising raw material for the production of a new eco-friendly solid acid catalyst.
- Published
- 2014
46. Relationships between Serotoninergic System and Skin Fibrotic
- Author
-
Chaodi Huang, Qiying Gong, Jianguo Huang, and Guiming Li
- Subjects
Serotonin ,Connective Tissue Disorder ,medicine.medical_treatment ,Immunology ,Cell Growth Processes ,Biology ,Serotonergic ,Scleroderma ,Mediator ,Fibrosis ,medicine ,Animals ,Humans ,Immunology and Allergy ,Precision Medicine ,Lisuride ,Receptor ,Skin ,Pharmacology ,Scleroderma, Systemic ,Growth factor ,General Medicine ,medicine.disease ,Dopamine Agonists ,Receptor, Serotonin, 5-HT1A ,Selective Serotonin Reuptake Inhibitors - Abstract
Cutaneous fibrosis seen in systemic sclerosis (SSc) is a generalized connective tissue disorder, characterized by a wide spectrum of microvascular and immunological abnormalities. Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter and immune modulator, is also an important mediator of bidirectional interactions between the vasoactive amines and the skin.5-HT, a commonly secreted amine, is a known inducer of fibrosis, although the mechanistic basis for it and growth factors regulating fibrosis and proliferation in the microenvironment are unclear. We review that as serotonin has powerful vasodilator, immunomodulator, and growth factor actions, this pathway could be involved in skin fibrotic. Since serotoninergic system play a role in skin fibrotic, and 5-HTs drugs, an usual treatment for this type of patients. These provides a future perspective for research and drug development.
- Published
- 2014
47. Measurement of Serum Monoamine Oxidase in Lichen Planus Patients and Its Clinical Significance
- Author
-
Guiming Li, Qiying Gong, and Jianguo Huang
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Monoamine oxidase ,Immunology ,Biology ,Gastroenterology ,Young Adult ,stomatognathic system ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Clinical significance ,skin and connective tissue diseases ,Monoamine Oxidase ,Aged ,Pharmacology ,integumentary system ,Lichen Planus ,General Medicine ,Middle Aged ,Prognosis ,stomatognathic diseases ,Disease Progression ,Female - Abstract
To study the role of serum Monoamine oxidase (MAO) in Lichen planus(LP).82 cases of Lichen planus patients and 35 healthy controls were selected in the investigation. The total serum MAO levels were measured.The levels of serum MAO in Lichen planus patients were significantly higher than those in healthy controls (P0.01). The severity of Lichen planus was not correlated with serum MAO levels (r =0.4873, t=0.73, p0.05).According to the findings, there might be a coincidence of MAO and lichen planus. However, further studies are required to clarify the immunological mechanisms which are responsible for MAO synthesis during immunoreaction.
- Published
- 2014
48. Robust Adaptive Coordinated Attitude Control Problem with Unknown Communication Delays and Uncertainties
- Author
-
Liangdong Liu and Guiming Li
- Subjects
Lemma (mathematics) ,Spacecraft ,business.industry ,General Medicine ,Term (time) ,Attitude control ,Nonlinear system ,Control theory ,Bounded function ,Constant (mathematics) ,Quaternion ,business ,Engineering(all) ,Mathematics - Abstract
We address the robust adaptive coordinated attitude control problem (CACP) for formation spacecraft with model and disturbance uncertainties, and with unknown constant time delays existing in the information exchanged channels. Here, spacecraft attitude is described via quaternion, and the local relative attitude is obtained in non-convex space, i.e., on the nonlinear manifold-Lie Group. Unlike in existing designs, where constant delays must be explicit and bounded, our novel laws, by injecting a nonlinear term, solve the CACP with disturbances and unknown/large constant communication delays. To overcome model uncertainties, the adaptive method is adopted. The closed-loop systems are investigated based on the Lyapunov-Krasovskii theory and Barbalat Lemma, and a spacecraft formation is conducted to demonstrate the effectiveness of theoretical results.
- Published
- 2012
49. Preparation and evaluation of MnO –CeO2 nanospheres via a green route
- Author
-
Guiming Li, Haoxi Jiang, Dongyu Jiang, and Minhua Zhang
- Subjects
Materials science ,Process Chemistry and Technology ,No conversion ,chemistry.chemical_element ,Selective catalytic reduction ,Nanotechnology ,General Chemistry ,Oxygen ,Catalysis ,Supercritical fluid ,Active oxygen ,Chemical engineering ,chemistry ,Solid solution - Abstract
Hollow and solid MnO x –CeO 2 nanospheres have been successfully prepared with a supercritical anti-solvent process and used for the selective catalytic reduction of NO with NH 3 . Solid solution structures are detected for these nanospheres. The hollow MnO x –CeO 2 nanospheres have more oxygen vacancies than the solid ones. And they also present a better NO conversion in the low-temperature range of 100–200 °C. Higher surface area, better oxygen mobility and richer surface active oxygen species are responsible for the better performance of the hollow sample. Therefore, the supercritical anti-solvent preparation of the nanospheres with the hollow structure is more favorable for the low-temperature selective catalytic reduction of NO.
- Published
- 2012
50. Macrophage-mediated GDNF Delivery Protects Against Dopaminergic Neurodegeneration: A Therapeutic Strategy for Parkinson's Disease
- Author
-
James L. Roberts, William W. Morgan, Guiming Li, K.C. Biju, Syed Z Imam, Robert A. Clark, Senlin Li, and Qing Zhou
- Subjects
Male ,Dopamine ,animal diseases ,Neurotoxins ,Enzyme-Linked Immunosorbent Assay ,Substantia nigra ,Pharmacology ,Biology ,Neuroprotection ,Eating ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Neurotrophic factors ,Drug Discovery ,Genetics ,medicine ,Glial cell line-derived neurotrophic factor ,Animals ,Glial Cell Line-Derived Neurotrophic Factor ,Molecular Biology ,Cells, Cultured ,Chromatography, High Pressure Liquid ,030304 developmental biology ,0303 health sciences ,Tyrosine hydroxylase ,Macrophages ,MPTP ,Body Weight ,Neurodegeneration ,Parkinson Disease ,Anatomy ,Flow Cytometry ,medicine.disease ,3. Good health ,Mice, Inbred C57BL ,Substantia Nigra ,Transplantation ,nervous system ,chemistry ,1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ,Nerve Degeneration ,biology.protein ,Molecular Medicine ,Original Article ,030217 neurology & neurosurgery - Abstract
Glial cell line-derived neurotrophic factor (GDNF) has emerged as the most potent neuroprotective agent tested in experimental models for the treatment of Parkinson's disease (PD). However, its use is hindered by difficulties in delivery to the brain due to the presence of the blood-brain barrier (BBB). In order to circumvent this problem, we took advantage of the fact that bone marrow stem cell-derived macrophages are able to pass the BBB and home to sites of neuronal degeneration. Here, we report the development of a method for brain delivery of GDNF by genetically modified macrophages. Bone marrow stem cells were transduced ex vivo with lentivirus expressing a GDNF gene driven by a synthetic macrophage-specific promoter and then transplanted into recipient mice. Eight weeks after transplantation, the mice were injected with the neurotoxin, MPTP, for 7 days to induce dopaminergic neurodegeneration. Macrophage-mediated GDNF treatment dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and TH(+) terminals in the striatum, stimulated axon regeneration, and reversed hypoactivity in the open field test. These results indicate that macrophage-mediated GDNF delivery is a promising strategy for developing a neuroprotective therapy for PD.
- Published
- 2010
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