21 results on '"Duan, Zheng"'
Search Results
2. Effect of Zener-Hollomon parameter on quench sensitivity of 7085 aluminum alloy
- Author
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Chengbo Li, Shengdan Liu, Zhaojun Shan, Duan-zheng Zhang, Shaolin Wang, and Xinming Zhang
- Subjects
010302 applied physics ,Quenching ,Materials science ,Mechanical Engineering ,Zener–Hollomon parameter ,Metallurgy ,Alloy ,Metals and Alloys ,Nucleation ,chemistry.chemical_element ,Recrystallization (metallurgy) ,Thermodynamics ,02 engineering and technology ,engineering.material ,021001 nanoscience & nanotechnology ,01 natural sciences ,chemistry ,Mechanics of Materials ,Aluminium ,0103 physical sciences ,Materials Chemistry ,engineering ,Grain boundary ,0210 nano-technology - Abstract
The effect of Zener-Hollomon (Z) parameter on quench sensitivity of 7085 aluminum alloy was investigated. With the increase of Z parameter from 2.67E10 to 4.79E16, quench sensitivity relative to hardness tends to decrease first and then increase, and it may be minimised in the range from 2.67E12 to 2.24E13. The reason was discussed mainly on the effect of Z parameter on recrystallization fraction, which changes the amount of nucleation sites of heterogeneous precipitation during slow quenching. Quench-induced η phase with little strengthening effect tends to form preferentially at grain boundaries and on the Al 3 Zr dispersoids with a size larger than about 23 nm in the recrystallized grains. The increase in the number of recrystallized grains can increase the amount of such grain boundaries and Al 3 Zr dispersoids, and therefore a larger amount of quench-induced phase; consequently, quench sensitivity increases.
- Published
- 2016
3. Synthesis of Several New 1-arylpyrazolo[3,4-d]Pyrimidines Containing an Amide Moiety
- Author
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Duan-Zheng Song, Ju Liu, Xin-wei Zhang, Zhou Yunpeng, and Cai Zhiqiang
- Subjects
Pyrimidine ,010405 organic chemistry ,Condensation ,General Chemistry ,010402 general chemistry ,Triethyl orthoformate ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Ammonium hydroxide ,chemistry ,Amide ,Polymer chemistry ,Moiety ,Molecule ,Tetrahydrofuran - Abstract
A series of novel 1-arylpyrazolo[3,4-d]pyrimidine derivatives, containing an amide moiety, was synthesised by condensation of different acids with 1-(2,4-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. This intermediate was prepared from 5-amino-1-(2,4-dichlorophenyl)-1H-pyrazole-4-carbonitrile by condensation with triethyl orthoformate and then cyclisation with ammonium hydroxide solution in tetrahydrofuran at room temperature. In addition, the molecular structure of a 1-arylpyrazolo[3,4-d]pyrimidine containing an amide moiety was determined by single crystal X-ray diffraction.
- Published
- 2016
4. Synthesis, Crystal Structure and bIological Activity of 5-(4-fluorophenyl)-N,N-dimethyl-7-(trifluoromethyl)Pyrazolo[1,5-a]Pyrimidine-3-carboxamide
- Author
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Xin-Wei Zhang, Yue-Fei Bai, Ju Liu, Dan Wang, Duan-Zheng Song, and Yan-Qiu Tian
- Subjects
Trifluoromethyl ,Pyrimidine ,010405 organic chemistry ,medicine.drug_class ,Stereochemistry ,Carboxamide ,Biological activity ,General Chemistry ,Crystal structure ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,medicine - Abstract
The title compound, 5-(4-fluorophenyl)-N,N-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide, has been synthesised by condensation of dimethylamine with 5-(4-fluorophenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid. This intermediate was prepared from ethyl 5-amino-1H-pyrazole-4-carboxylate by cyclisation with 4,4,4-trifluoro-1-(4-fluorophenyl)butane-1,3-dione and then saponification with sodium hydroxide. The crystal structure of the title compound was determined. The compound possesses distinct effective inhibition on the proliferation of some cancer cell lines.
- Published
- 2016
5. The chemistry of phosphirane-substituted phosphinidene complexes.
- Author
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Wang, Min, Yang, Tingting, Tian, Rongqiang, Wei, Donghui, Duan, Zheng, and Mathey, François
- Subjects
CHEMISTRY ,THERMOLYSIS - Abstract
Thermolysis of the 1,1′-biphosphirane pentacarbonylmetal complex offers access to 3,4-dihydro-1,2-diphosphete and diphosphorus (P
2 ) intermediates. A control reaction proves that this step-wise reaction is initiated by the dissociation of a W(CO)5 group. DFT calculations predict that further transformations proceed via a transient phosphiranylphosphinidene complex. The formation of the 3,4-dihydro-1,2-diphosphete derivative is thermodynamically favored, while a kinetic process provides the diphosphorus (P2 ) complex. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
6. ChemInform Abstract: Synthesis of Several New 1-Arylpyrazolo[3,4-d]pyrimidines Containing an Amide Moiety
- Author
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Xin-wei Zhang, Duan-Zheng Song, Ju Liu, Zhou Yunpeng, and Cai Zhiqiang
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chemistry.chemical_compound ,Ammonium hydroxide ,chemistry ,Pyrimidine ,Amide ,Condensation ,Polymer chemistry ,Molecule ,Moiety ,General Medicine ,Triethyl orthoformate ,Tetrahydrofuran - Abstract
A series of novel 1-arylpyrazolo[3,4-d]pyrimidine derivatives, containing an amide moiety, was synthesised by condensation of different acids with 1-(2,4-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine. This intermediate was prepared from 5-amino-1-(2,4-dichlorophenyl)-1H-pyrazole-4-carbonitrile by condensation with triethyl orthoformate and then cyclisation with ammonium hydroxide solution in tetrahydrofuran at room temperature. In addition, the molecular structure of a 1-arylpyrazolo[3,4-d]pyrimidine containing an amide moiety was determined by single crystal X-ray diffraction.
- Published
- 2016
7. A concise review of low coordinated organophosphorus compounds
- Author
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Mathey Francois and Duan Zheng
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chemistry.chemical_compound ,chemistry ,Phosphaalkyne ,Phosphinidene ,Computational chemistry ,General Chemical Engineering ,Phosphorus ,Materials Chemistry ,chemistry.chemical_element ,Phosphaalkene ,General Chemistry ,Biochemistry - Abstract
Organophosphorus chemistry is organized around σ 3 and σ 4 phosphorus compounds and their derivatives. For a long time, this represented the core of phosphorus chemistry and, still today, the bulk of the work on phosphorus concerns this domain. Starting in the 1960s, a new realm of P-chemistry started to emerge. It concerns σ 1 and σ 2 phosphorus compounds. The aim of this concise review is to summarize the main advances in this new field.
- Published
- 2010
8. Morphological, physical and chemical properties of aeolian sandy soils in northern China
- Author
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Xiao Honglang, Dong Zhibao, Sam Drake, Wang Gang, and Duan Zheng-hu
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chemistry.chemical_classification ,Ecology ,Soil science ,Vegetation ,Arid ,Physical property ,chemistry ,Soil water ,Aeolian processes ,Pedology ,Organic matter ,Ecology, Evolution, Behavior and Systematics ,Geology ,Entisol ,Earth-Surface Processes - Abstract
The morphological and physico-chemical properties of four pedons representing the major aeolian sandy soils in the arid and semi-arid regions of China were studied for their potential for amelioration and utilization. The aeolian sandy soils of this area show wide variation in their morphological and physico-chemical properties as a result of differences in mean annual precipitation, parent material, vegetation and topography where they are found. The characteristics of and differences among aeolian sandy soils are described in detail. The processes forming these sandy soils are characterized by: (1) fine particle accumulation; (2) crust formation; (3) organic matter accumulation; (4) soil water physical property changes; and (5) total chemical composition changes. The four pedons are classified into four taxonomic groups, based on soil genetic theory. They are Hyperaripsamments, Aripsamments, Semiaripsamments, and Ustpsamments.
- Published
- 2007
9. Reduction of Dislocations in GaN Epilayer Grown on Si (111) Substrates using a GaN Intermedial Layer
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Zhang Baoshun, Wang Jianfeng, Zhu Jian-Jun, Zhang Ji-Cai, Jiang De-Sheng, Chen Jun, Yang Hui, Yao Duan-zheng, Wang Yu-Tian, and Liu Wei
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Threading dislocations ,Materials science ,Silicon ,business.industry ,General Physics and Astronomy ,chemistry.chemical_element ,Chemical vapor deposition ,Reflectivity ,Stress (mechanics) ,chemistry ,Transmission electron microscopy ,Optoelectronics ,Dislocation ,business ,Layer (electronics) - Abstract
GaN intermedial layers grown under different pressures are inserted between GaN epilayers and AlN/Si(111) substrates. In situ optical reflectivity measurements show that a transition from the three-dimensional (3D) mode to the 2D one occurs during the GaN epilayer growth when a higher growth pressure is used during the preceding GaN intermedial layer growth, and an improvement of the crystalline quality of GaN epilayer will be made. Combining the in situ reflectivity and transmission electron microscopy (TEM) measurements, it is suggested that the lateral growth at the transition of growth mode is favourable for bending of dislocation lines, thus reducing the density of threading dislocations in the epilayer.
- Published
- 2006
10. Estimate of total CO2 output from desertified sandy land in China
- Author
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He Xingdong, Dong Zhibao, Duan Zheng-hu, Xiao Honglang, and Wang Gang
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Hydrology ,Total organic carbon ,Atmospheric Science ,media_common.quotation_subject ,chemistry.chemical_element ,Global change ,Carbon cycle ,chemistry.chemical_compound ,chemistry ,Desertification ,Greenhouse gas ,Soil water ,Carbon dioxide ,Environmental science ,Carbon ,General Environmental Science ,media_common - Abstract
Soil is an important factor in regional and global carbon budgets because it serves as a reservoir of large amount of organic carbon. In our study, using remote sensing data of different periods we analyzed the development and reversion of desertification in China, calculated the variations of organic carbon contents of the desertified lands in China. The results showed that the total storage of organic carbon in 0–50 cm soil layer of the desertified lands is 855 Mt. In recent 40 yr, the total CO 2 amount released by land desertification processes to the atmosphere was 150 Mt, while the CO 2 amount sequestered by desertification reversing processes corresponded to 59 Mt C. Hence, the net CO 2 amount released from desertified lands of China corresponded to 91 Mt C, about 68.42% of the 133 Mt C of annual CO 2 release in the global temperate and frigid zones. Simultaneously, it indicated that CO 2 amount sequestered by desertification reversing processes in desertified land had greater potential than the other soils.
- Published
- 2001
11. Effects of soil properties on ammonia volatilization
- Author
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Duan Zheng-hu and Xiao Honglang
- Subjects
chemistry.chemical_classification ,Volatilisation ,Soil organic matter ,Soil Science ,Mineralogy ,Soil classification ,Plant Science ,Ammonia volatilization from urea ,chemistry ,Environmental chemistry ,Soil pH ,Soil water ,Cation-exchange capacity ,Organic matter - Abstract
By using a small culture dish located above a large-sized closed dish with soil samples to trap emissions as well as applying multivariate analysis methods, the influence of soil properties on ammonia volatilization and their correlation was studied. The results showed that the ammonia volatilization rates were positively correlated with the soil pH, CaCO3, and total salt contents but negatively correlated with the organic matter content, CEC, and clay content. Of the three negative correlation factors, the CEC was most highly correlated with ammonia volatilization, while among the three positive correlation factors, the pH predominated. These results enabled to assess the magnitude of ammonia volatilization from soils. According to the correlation equation of ammonia volatilization versus pH and CEC, the potential of ammonia volatilization of some soils in China was determined and the soils were divided into four groups. It was concluded that by increasing the application rate of organic matter ...
- Published
- 2000
12. Caspase inhibition with XIAP as an adjunct to AAV vector gene-replacement therapy: improving efficacy and prolonging the treatment window
- Author
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Debra A. Thompson, Ashley Moncrief, Naheed W. Khan, David N. Zacks, William W. Hauswirth, Qiong Duan Zheng, Jingyu Yao, and Lin Jia
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Retinal degeneration ,Light ,Mouse ,Genetic enhancement ,lcsh:Medicine ,Pharmacology ,Mice ,chemistry.chemical_compound ,Molecular Cell Biology ,lcsh:Science ,Multidisciplinary ,medicine.diagnostic_test ,Retinal Degeneration ,Gene Therapy ,Genomics ,Animal Models ,Dependovirus ,Caspase Inhibitors ,XIAP ,medicine.anatomical_structure ,Medicine ,Retinal Disorders ,Photoreceptor Cells, Vertebrate ,Research Article ,Genetic Vectors ,X-Linked Inhibitor of Apoptosis Protein ,Biology ,Inhibitor of apoptosis ,Model Organisms ,Genomic Medicine ,Electroretinography ,Genetics ,medicine ,Animals ,Cyclic guanosine monophosphate ,Clinical Genetics ,Cyclic Nucleotide Phosphodiesterases, Type 6 ,Retina ,lcsh:R ,Human Genetics ,Genetic Therapy ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Ophthalmology ,chemistry ,Immunology ,Adjunctive treatment ,lcsh:Q - Abstract
Purpose AAV-mediated gene therapy in the rd10 mouse, with retinal degeneration caused by mutation in the rod cyclic guanosine monophosphate phosphodiesterase β-subunit (PDEβ) gene, produces significant, but transient, rescue of photoreceptor structure and function. This study evaluates the ability of AAV-mediated delivery of X-linked inhibitor of apoptosis (XIAP) to enhance and prolong the efficacy of PDEβ gene-replacement therapy. Methods Rd10 mice were bred and housed in darkness. Two groups of animals were generated: Group 1 received sub-retinal AAV5-XIAP or AAV5-GFP at postnatal age (P) 4 or 21 days; Group 2 received sub-retinal AAV5-XIAP plus AAV5- PDEβ, AAV5-GFP plus AAV5- PDEβ, or AAV- PDEβ alone at age P4 or P21. Animals were maintained for an additional 4 weeks in darkness before being moved to a cyclic-light environment. A subset of animals from Group 1 received a second sub-retinal injection of AAV8-733-PDEβ two weeks after being moved to the light. Histology, immunohistochemistry, Western blots, and electroretinograms were performed at different times after moving to the light. Results Injection of AAV5-XIAP alone at P4 and 21 resulted in significant slowing of light-induced retinal degeneration, as measured by outer nuclear thickness and cell counts, but did not result in improved outer segment structure and rhodopsin localization. In contrast, co-injection of AAV5-XIAP and AAV5-PDEβ resulted in increased levels of rescue and decreased rates of retinal degeneration compared to treatment with AAV5-PDEβ alone. Mice treated with AAV5-XIAP at P4, but not P21, remained responsive to subsequent rescue by AAV8-733-PDEβ when injected two weeks after moving to a light-cycling environment. Conclusions Adjunctive treatment with the anti-apoptotic gene XIAP confers additive protective effect to gene-replacement therapy with AAV5-PDEβ in the rd10 mouse. In addition, AAV5-XIAP, when given early, can increase the age at which gene-replacement therapy remains effective, thus effectively prolonging the window of opportunity for therapeutic intervention.
- Published
- 2012
13. Autophagy Activation in the Injured Photoreceptor Inhibits Fas-Mediated Apoptosis
- Author
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Cagri G. Besirli, David N. Zacks, Nicholas D. Chinskey, and Qiong Duan Zheng
- Subjects
Retinal degeneration ,Male ,Programmed cell death ,Time Factors ,genetic structures ,Blotting, Western ,Apoptosis ,Biology ,Caspase 8 ,Cathepsin D ,Autophagy-Related Protein 5 ,Cathepsin B ,Cell Line ,chemistry.chemical_compound ,Rats, Inbred BN ,medicine ,Autophagy ,Animals ,Protein Isoforms ,fas Receptor ,RNA, Small Interfering ,Retina ,Retinal pigment epithelium ,Adenine ,Retinal Detachment ,Proteins ,Retinal ,Articles ,medicine.disease ,Fas receptor ,Immunohistochemistry ,eye diseases ,Cell biology ,Rats ,Enzyme Activation ,medicine.anatomical_structure ,chemistry ,sense organs ,Microtubule-Associated Proteins ,Photoreceptor Cells, Vertebrate - Abstract
Separation of the retina from the retinal pigment epithelium (RPE) is a common form of injury that may occur alone (retinal detachment) or as a result of other blinding disease processes such as age-related macular degeneration or diabetic retinopathy. Despite significant advances in the medical and surgical management of retina–RPE separation, patients often lose vision, primarily due to the death of photoreceptors.1,2 We previously showed that the main event causing photoreceptor death is the activation of the Fas receptor and the downstream cascade of caspases 8, 3, 7, and 9.3–5 Preventing Fas pathway activity provides significant protection against separation-induced death of the photoreceptors. Although Fas-mediated apoptosis is activated rapidly after retina–RPE separation, a surprising number of photoreceptors survive for extended periods of time. This is best exemplified by the clinical observation that patients with retinal detachments affecting central vision generally recover near-normal vision if the detachment is repaired within 1 week.6,7 If repair is delayed beyond 1 week, visual outcomes become significantly poorer. This suggests that early in the course of the detachment, antiapoptotic pathways are activated within the retina to counteract the effect of proapoptotic signals and that they are responsible for the therapeutic window of opportunity for reattachment.8 Autophagy is a complex process that results in the autovacuolization of damaged or redundant cellular components. These vacuoles (i.e., autophagosomes) fuse with lysosomes and their contents are enzymatically degraded and released back into the cell.9 Autophagy activation typically occurs during periods of metabolic stress, usually serving as a cytoprotective process.10 Autophagy has been shown to occur in photoreceptors as part of basal processing of rod outer segments11 as well as in animal models of hereditary retinal degeneration and in models of oxidative stress.12–14 The role of autophagy in these settings is not well defined. We examined the role of autophagy and its control of photoreceptor apoptosis using a well-established rodent model of experimental retina–RPE separation. Our findings demonstrate that retinal detachment results in the activation of autophagy in photoreceptors. Similar to apoptosis, detachment-induced autophagy activity is Fas dependent. In detached retinas, autophagy acts as a prosurvival pathway through negative inhibition of apoptosis. Our data suggest a novel mechanism by which autophagy can be activated and regulate photoreceptor apoptosis.
- Published
- 2011
14. Interleukin-6 as a Photoreceptor Neuroprotectant in an Experimental Model of Retinal Detachment
- Author
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David N. Zacks, Linda Zhang, Christopher S. Boehlke, Deborah Y. Chong, Qiong Duan Zheng, and Ying Han
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Male ,Time Factors ,Apoptosis ,Cell Count ,Biology ,Neuroprotection ,Retinal ganglion ,Article ,Antibodies ,Drug Administration Schedule ,Retina ,chemistry.chemical_compound ,Mice ,Rats, Inbred BN ,medicine ,Animals ,Humans ,Mice, Knockout ,TUNEL assay ,Retinal pigment epithelium ,Interleukin-6 ,Retinal Detachment ,Retinal detachment ,Retinal ,Anatomy ,medicine.disease ,eye diseases ,Cell biology ,Rats ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Neuroprotective Agents ,chemistry ,Retinal ganglion cell ,sense organs ,Photoreceptor Cells, Vertebrate - Abstract
Retinal detachment (RD), defined as the separation of the neurosensory retina from subjacent retinal pigment epithelium (RPE), results in the apoptotic death of photoreceptor cells.1-4 Rodent and feline models of RD have demonstrated the activation of proapoptotic pathways nearly immediately after the retina becomes separated from the RPE.1-4 Histologic markers of apoptosis, such as terminal deoxynucleotidyl transferase nick-end label (TUNEL) staining, reach a peak at approximately 3 days after RD, with apoptotic activity and progressive cell death persisting for the duration of the detachment period. Clinical experience in the repair of retinal detachments, however, has demonstrated that there is a window of opportunity for repair with preservation of good visual acuity. Retrospective case series have demonstrated that significant numbers of patients with macula-off RDs repaired within 5 to 10 days after onset of detachment can retain relatively good visual function but that visual acuity drops significantly as the time between detachment and repair extends.5-7 The delayed time between the activation of proapoptosis pathways and the clinical onset of visual loss suggests that intrinsic neuroprotective factors may become activated within the neural retina and may serve to counterbalance the effects of the proapoptotic pathways activated by retinal–RPE separation. Previous work in our laboratory using gene microarray analysis of experimental detachment in rats revealed the increased expression of genes involved in stress–response pathways.8 Of particular interest was the increased transcription and translation of interleukin (IL)-6 and downstream components of its associated signal transduction pathway. IL-6 is a pleiotropic cytokine with a role in inflammation, hematopoiesis, angiogenesis, cell differentiation, and neuronal survival.9-11 In the central nervous system, IL-6 is synthesized by microglia, astrocytes, and neurons.12,13 In the retina, IL-6 is synthesized by Muller cells and the RPE.14,15 A neuroprotective role for IL-6 has been previously suggested in different models of ocular injury. In rat models of retinal ischemia–reperfusion injury, IL-6 protein levels are upregulated within 8 hours after injury.16 Furthermore, intravitreal injection of exogenous IL-6 immediately after ischemia–reperfusion injury or before N-methyl-d-aspartate (NMDA)-induced toxicity increases survival of retinal ganglion cells.16,17 In vitro studies have shown that IL-6 increases the duration of rat retinal ganglion cell survival in primary tissue culture.18,19 Collectively, these data suggest that IL-6 upregulation after injury may serve to function as a neuronal survival factor. The goal of this study is to test the hypothesis that IL-6 functions as an inhibitor of photoreceptor apoptosis after RD. Understanding the effect of IL-6 on photoreceptor survival may provide insight into potential therapeutic strategies for protecting photoreceptors during periods of photoreceptor–RPE separation.
- Published
- 2008
15. Role of the Fas-signaling pathway in photoreceptor neuroprotection
- Author
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Ayo Lynn Richards, David N. Zacks, Christopher S. Boehlke, and Qiong Duan Zheng
- Subjects
Opsin ,Mice, Inbred MRL lpr ,Rhodopsin ,genetic structures ,Cell Survival ,Immunoblotting ,Apoptosis ,Cell Count ,Biology ,chemistry.chemical_compound ,Mice ,Rats, Inbred BN ,medicine ,In Situ Nick-End Labeling ,Animals ,Photopigment ,fas Receptor ,RNA, Small Interfering ,Outer nuclear layer ,Antibodies, Blocking ,Fluorescent Antibody Technique, Indirect ,Retina ,Retinal pigment epithelium ,Reverse Transcriptase Polymerase Chain Reaction ,Retinal Detachment ,Rod Opsins ,Retinal ,eye diseases ,Cell biology ,Rats ,Mice, Inbred C57BL ,Ophthalmology ,medicine.anatomical_structure ,chemistry ,Immunology ,biology.protein ,Fas signaling pathway ,RNA ,sense organs ,Photoreceptor Cells, Vertebrate ,Signal Transduction - Abstract
Objective To determine whether inhibiting the Fas proapoptosis pathway will result in increased photoreceptor survival after separation of the retina from the retinal pigment epithelium (RPE). Methods Retina/RPE separation was induced in rat and mouse eyes by the subretinal injection of hyaluronic acid, 1%. Fas-pathway signaling was inhibited by the concomitant injection of a Fas receptor–neutralizing antibody, small inhibitory RNA against the Fas-receptor transcript (siFAS), or the use of the Fas-receptor defective mouse strain LPR. Indices of photoreceptor death included terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, cell counts, and retinal thickness measurements. Retinas were immunostained with antibodies against rhodopsin and cone opsin to evaluate rod and cone photopigment production, respectively. Results Inhibition of Fas signaling using Fas receptor–neutralizing antibody, siFas, or LPR mice resulted in a significant reduction in the number of TUNEL-positive photoreceptor cells as well as in a significant preservation of outer nuclear layer cell counts and thickness as compared with retina/RPE separation in eyes with intact Fas signaling. Fas-pathway inhibition resulted in preservation of both rhodopsin- and cone opsin–positive cells. Conclusions Inhibition of the Fas proapoptosis pathway results in significant photoreceptor preservation after retinal separation from the RPE. Clinical Relevance Fas-pathway inhibition might serve as a novel mechanism for preserving photoreceptor cells during retinal disease.
- Published
- 2007
16. Reaction of Zirconacyclopentadienes with Electrophiles such as Benzaldehyde, Methyl Methacrylate and 1-Bromo-2-butyne After Treatment with RLi
- Author
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Takashi Seki, Wen-Hua Sun, Tamotsu Takahashi, Duan Zheng, and Yoshinori Noguchi
- Subjects
chemistry.chemical_classification ,Addition reaction ,Nucleophilic addition ,Organic Chemistry ,Propargyl chloride ,General Medicine ,Biochemistry ,Medicinal chemistry ,Aldehyde ,Benzaldehyde ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Electrophile ,Butyllithium ,Michael reaction ,Organic chemistry ,Methyllithium - Abstract
Zirconacyclopentadienes reacted with electrophiles after treatment with alkyllithium. For example, the reaction with benzaldehyde after treatment with methyllithium to give a nucleophilic addition product of a dienyl moiety to aldehyde, dienylcarbinol, in a moderate yield. Similar reaction of a zirconacyclopentadiene using butyllithium with methyl methacrylate afforded a Michael addition product in a good yield. Treatment of zirconacyclopentadienes with n-BuLi followed by 1-bromo-2-butyne gave a mono-propargylated diene derivative in 95% yield after hydrolysis. When propargyl chloride was treated with n-BuLi first and then added to zirconacyclopentadienes, penta-substituted benzene derivatives were formed in high yields.
- Published
- 2005
17. Inhibition of Retinal Detachment-Induced Apoptosis in Photoreceptors by a Small Peptide Inhibitor of the Fas Receptor
- Author
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Cagri G. Besirli, Nicholas D. Chinskey, Qiong Duan Zheng, and David N. Zacks
- Subjects
Male ,genetic structures ,Cell Survival ,Blotting, Western ,Cell Culture Techniques ,Apoptosis ,Cell Count ,Caspase 3 ,Caspase 8 ,chemistry.chemical_compound ,Rats, Inbred BN ,In Situ Nick-End Labeling ,medicine ,Animals ,fas Receptor ,Caspase ,Caspase-9 ,Retina ,TUNEL assay ,biology ,Retinal Detachment ,Retinal ,Articles ,Molecular biology ,eye diseases ,Caspase 9 ,Rats ,Cell biology ,medicine.anatomical_structure ,Terminal deoxynucleotidyl transferase ,chemistry ,biology.protein ,sense organs ,Oligopeptides ,Photoreceptor Cells, Vertebrate - Abstract
Purpose. To test the effect of a small peptide inhibitor (Met12) of the Fas receptor on the activation of extrinsic and intrinsic apoptosis pathways after retinal detachment. Methods. Retinal-RPE separation was created in Brown Norway rats by subretinal injection of 1% hyaluronic acid. Met12, derived from the Fas-binding extracellular domain of the oncoprotein Met, was injected into the subretinal space at the time of separation. A mutant peptide and vehicle administered in a similar fashion acted as inactive controls. The extrinsic apoptotic pathway was induced in 661W cells using a Fas-activating antibody in the presence or absence of Met12. Caspase 3, caspase 8, and caspase 9 activities were measured with calorimetric and luminescent assays in retinal extracts and cell lysates. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was performed in retinal sections 3 days after separation. Histology was performed in retinal sections 2 months after retinal detachment. Results. Met12 inhibited Fas-induced caspase 8 activation in 661W cells. Similarly, administration of Met12 into the subretinal space inhibited the activation of caspase 3, caspase 8, and caspase 9 after retinal detachment. This corresponded to a decreased level of TUNEL-positive staining of photoreceptors after retinal-RPE separation in animals that received Met12, but not inactive mutant, peptide treatment. After 2 months, the outer nuclear layer was significantly thicker, and the photoreceptor count was higher in animals treated with subretinal Met12. Conclusions. The small peptide Met12 may serve as a photoreceptor-protective agent in the setting of retinal-RPE separation.
- Published
- 2010
18. Effects on XIAP Retinal Detachment–Induced Photoreceptor Apoptosis
- Author
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Laura A. Zadro-Lamoureux, Adam N. Baker, William W. Hauswirth, David N. Zacks, Qiong Duan Zheng, and Catherine Tsilfidis
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Retina ,Retinal pigment epithelium ,genetic structures ,Retinal detachment ,Retinal ,Exudative retinal detachment ,Anatomy ,Biology ,Inhibitor of apoptosis ,medicine.disease ,eye diseases ,Cell biology ,XIAP ,Retinal Tear ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,medicine ,sense organs - Abstract
Retinal detachment involves a separation of the neural retina from the underlying retinal pigment epithelium (RPE). It is a common form of retinal injury and a significant cause of visual loss,1,2 especially if it involves the macula. The incidence of retinal detachment is approximately 1 in 10,000 people per year, with a lifetime prevalence of 1 in 300.3 Risk increases dramatically when factors such as trauma, myopia, cataract surgery, previous retinal detachment, or family history are considered.4 Retinal detachment may also be associated with ocular disorders such as age-related macular degeneration (AMD), diabetic retinopathy, retinopathy of prematurity, retinoschisis, and central serous retinopathy among others. Rhegmatogenous detachment is the most common type; it involves a retinal tear that allows vitreal fluid to leak into the subretinal space and to detach the retina from the underlying RPE. In tractional detachment, fibrovascular tissue caused by injury, inflammation, or neovascularization pulls the neurosensory retina away from the RPE. Exudative retinal detachment results from subretinal fluid accumulation in the absence of a retinal tear. Recovery of vision after retinal separation from the RPE depends on the nature, severity, and duration of the detachment. The primary retinal cell types affected by detachment are the photoreceptors. These cells undergo characteristic changes such as shortening of the outer segments, retraction of rod terminals from the outer plexiform layer,5 and opsin redistribution.6 In addition, synapses of second-order neurons are remodeled and retinal glial cells proliferate.7 Some of these changes are significant obstacles to recovery but may be reversible after reattachment of the retina.8 However, the primary cause of visual loss is most likely photoreceptor death by apoptosis.1,9 In animal studies, apoptosis is initiated within 24 hours after retinal detachment and peaks at 3 days.2,8 Apoptosis most often involves the activation of cysteine proteases, called caspases, which are involved in the proteolytic digestion of the cell and its contents. Retinal detachment causes cell death through the activation of caspases 3, 7, and 9.2 X-linked inhibitor of apoptosis (XIAP) is a key member of the inhibitors of apoptosis (IAP) gene family. Members of this family all share at least one baculoviral IAP repeat (BIR) domain, so named because it was first discovered in baculoviruses. XIAP has three BIR domains, which, in combination with the linker regions between them, are involved in binding to and suppressing the activity of caspases 3, 7, and 9.10 XIAP also contains a carboxyl-terminal RING zinc finger domain that has E3 ubiquitin ligase activity. This domain determines the fate of XIAP or the cell, or both, depending on the severity of the cellular insult. Under conditions of severe cellular stress, XIAP will undergo auto-ubiquitination and degrade, allowing the apoptotic cascade to culminate in the death of the cell. Under lower apoptotic stress, XIAP will promote the ubiquitination and degradation of the caspases, leading to cell survival through the suppression of apoptosis.10 In disease models, XIAP has been shown to confer protection in forebrain ischemia,11 in methyl-phenyl-tetrahydropyridine–induced Parkinson disease,12,13 and in cisplatin-induced ototoxicity.14–16 In gene therapy studies in the eye, XIAP protects ganglion cells after axotomy of the optic nerve,17,18 increased intraocular pressure,19 and retinal ischemia.20 It also protects photoreceptors from chemotoxic insult21,22 and in genetic models of retinitis pigmentosa.23 The present study examines the protective effects of XIAP delivered through an adenoassociated virus (AAV) vector on retinal detachment–induced photoreceptor apoptosis. XIAP is an ideal therapeutic agent because it suppresses caspases 3, 7, and 9, whose activation has previously been shown to be responsible for apoptotic cell death in animal studies of retinal detachment.2
- Published
- 2009
19. FAS-Mediated Apoptosis and Its Relation to Intrinsic Pathway Activation in an Experimental Model of Retinal Detachment
- Author
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David N. Zacks, Ying Han, Joan W. Miller, Rita N. Bakhru, and Qiong Duan Zheng
- Subjects
Male ,Programmed cell death ,Fas Ligand Protein ,Time Factors ,Apoptosis ,Biology ,Caspase 8 ,Antibodies ,chemistry.chemical_compound ,Rats, Inbred BN ,medicine ,Animals ,RNA, Messenger ,fas Receptor ,Enzyme Inhibitors ,Retina ,Membrane Glycoproteins ,Caspase 3 ,Cytochrome c ,Intrinsic apoptosis ,Retinal Detachment ,Cytochromes c ,Retinal detachment ,Retinal ,medicine.disease ,Caspase Inhibitors ,Caspase 9 ,Peptide Fragments ,Rats ,Cell biology ,medicine.anatomical_structure ,chemistry ,Caspases ,Immunology ,biology.protein ,Carrier Proteins ,Oligopeptides ,BH3 Interacting Domain Death Agonist Protein - Abstract
PURPOSE. To determine whether the FAS-mediated apoptosis pathway becomes activated in the retina after retinal detachment and to investigate the temporal relationship between the activation of the FAS-pathway and the intrinsic apoptosis pathway involving caspase-9 and cytochrome c. METHODS. Experimental retinal detachments were created in Brown-Norway rats by injecting 10% hyaluronic acid into the subretinal space. Retinal tissue was harvested at 2, 4, 8, 24, 72, and 168 hours after creation of the detachment. Immunoprecipitation was performed to assess for FAS-receptor/FAS-ligand complex formation, and activation of caspase-8 and BID (a member of the Bcl-2 family of proteins) was assessed by Western blot analysis. A caspase-9 activity assay and immunoprecipitation of the caspase-9/cytochrome c complex were performed at these same time points. Specific pathway inhibition was performed with the caspase-9 inhibitor zLEHD.fmk or neutralizing antibodies against either the FAS-receptor or FAS-ligand. Transcription levels of FAS and intrinsic pathway intermediates were assessed as a function of time after retinal detachment by using quantitative real-time polymerase chain reaction. RESULTS. Retinal detachment resulted in the time-dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak of caspase-9 activity and caspase-9/cytochrome c complex formation. Cleavage of caspase-8 and truncation of BID were also observed. Injection of zLEHD.fmk into the subretinal space of a detached retina resulted in decreased caspase-9 activity, as did injection of anti-FAS-receptor antibody into either the subretinal space or the vitreous. Retinal detachment resulted in the transcriptional upregulation of the FAS-receptor, FAS-ligand, caspase-8 and BID, but not caspase-9 and cytochrome c. CONCLUSIONS. The FAS-mediated apoptosis pathway becomes activated and transcriptionally upregulated after retinal detachment. The peak of FAS activation precedes that of the intrinsic pathway, and inhibition of FAS activation can decrease caspase-9 activity.
- Published
- 2004
20. The zinc finger protein A20 interacts with p50 and regulates Nod2- and RICk-induced NF-kB activation
- Author
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Chuan-Min Chen, Yusong Gong, Jian-Jun Chen, and Qiong-Duan Zheng
- Subjects
Zinc finger ,RING finger domain ,P50 ,Hepatology ,Chemistry ,NOD2 ,Gastroenterology ,Cell biology - Published
- 2003
21. Human tumor cells do not express CD95 ligand (FasL)
- Author
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John Y. Kao, Jian-Jun Chen, Qiong-Duan Zheng, Wenying Song, and Chuan-Min Chen
- Subjects
Human tumor ,Cd95 ligand ,Hepatology ,Chemistry ,Cancer research ,Gastroenterology ,Fas ligand - Published
- 2001
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