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1Intramedullary schwannoma of the upper cervical spinal cord:a case study of identification in pathologic autopsy显示文摘Intramedullary schwannoma of the upper cervical spinal cord is rarely reported in forensic medicine.We herein report a case involving a patient who died of compression from an intramedullary schwannoma in the upper cervical spinal cord.A 30-year-old man initially presented with a five-day history of pain in the left chest that progressed to weakening in the left arm.Although the patient was treated with analgesic poultices,he developed inspiratory dyspnoea and died while working the next day without having undergone any medical imaging examination or surgical treatment.Anatomical and histopathological examinations revealed an intramedullary schwannoma in the left cervical spinal cord(C_(3)-C_(5))underneath the spinal nerve root.The cause of death might have been asphyxia secondary to the tumour,which interfered with the nerve function in the respiratory muscles.This finding suggests that an autopsy is essential for pathologists and medicolegists to comprehensively undertake their due obligation to obtain“the first evidence”,especially when there is a lack of directly related evidence.As part of the central nervous system,the spinal cord could be systematically included in a routine pathological autopsy in some cases.Xianxian Li Guangtao Xu Ruibing Su Junyao Lv Xiaoping Lai Xiaojun Yu 2017Forensic Sciences Research2017,2,1:2
2论当代生态电影批评的建构维度及其发展趋向显示文摘当代西方生态电影批评既来自生态批评、文学批评、文化研究、美学和电影学等学科的支撑和经验积淀,同时也在建构自身体系的过程中不断开拓和突破,呈现出对电影生态和整个人类文化发展态势的自觉关注,显示出极大的活力。在剖析西方生态电影批评发展历程的基础上,面对当下中国生态电影批评研究纷繁错杂、缺乏体系的状况,对当代生态电影批评理论资源的梳理,以及对其建构维度、发展趋向的考察,皆能为夯实中国生态电影批评的基础及进一步建设具有当代性的理论话语提供一定的参照。宋眉 2017浙江科技学院学报2017,29,2:2
3Derivatives of (phenylsulfonamido-methyl)nicotine and (phenylsulfonamido-methyl)thiazole as novel 11β-hydroxysteroid dehydrogenase type 1 inhibitors: synthesis and biological activities in vitro显示文摘Xu ZHANG Yang ZHOU Yu SHEN Li-li DU Jun-hua CHEN Ying LENG Jian-hua SHEN 2009Acta Pharmacologica Sinica2009,30,9:1
4Precise location of proton of beta-secretase for catalytic aspartates(Asp 32 and Asp 228)in Alzheimer’s patients显示文摘BACKGROUND:β-secretase(β-site APP cleavage rate-limiting enzyme,BACE) has been proposed as a promising therapeutic target for Alzheimer's disease(AD).BACE inhibition reduces production of β-amyloid peptide(Aβ) and promotes neural regeneration.Two catalytic aspartates(Asp 32 and Asp 228) exist in a monoprotonated state in the active BACE site,but the precise proton location remains unclear.OBJECTIVE:To explore the entire process of BACE enzymatic hydrolysis using quantum chemistry calculations,and to identify the precise proton location for Asp 32 and Asp 228 during the enzymatic process.DESIGN,TIME AND SETTING:According to protonation state of BACE,four tautomers were designed and quantum chemistry calculations were performed at the Department of Human Anatomy,Zhongshan School of Medicine,Sun Yat-sen University,China between October 2008 and March 2009.MATERIALS:Hardware:linux workstation(Department of Equipment,Sun Yat-sen University,China);software:QSITE,Glide,Maestro(Schrodinger LLC,USA),MOPAC 2007(CAChe Research LLC,USA),Triton 4.0(National Centre for Biomolecular Research,Czech Republic) were used.METHODS:Using crystal structures of BACE to build a catalytic model(enzyme,catalytic water,and substrate peptide EVNLAAEF) on the computer and superimposition,four BACE tautomers(32i,32o,228i,and 228o) in the monoprotonated state were developed with Schrodinger package.Hybrid quantum mechanical/molecular mechanic(QM/MM) calculations were performed at the B3LYP density functional theory level to identify the precise proton location for the dyad aspartic residues(Asp 32 and Asp 228).Using the most possible tautomer as the reactant,the entire enzymatic hydrolysis of substrate EVNL/AAEF was simulated at the semiempirical level.MAIN OUTCOME MEASURES:The precise proton location of was measured by analyzing co-planarities of 4 BACE tautomers(32i,32o,228i,and 228o) in the monoprotonated state,because the dihedral formed by the carboxyl oxygen atoms of the dyad aspartic residues.The transition state and the production state,as well as activation energies and reaction enthalpies,were measured by calculating geometric and energy changes during catalytic reaction of the system.RESULTS:In the 228o BACE tautomer,the dihedral angle of the four oxygen atoms in the catalytic aspartates was 8.7°,which was the lowest of four tautomers.The lowest activation energy and highest reaction enthalpy(Ea = 216.30 kJ/mol,H =-30.98 kJ/mol) were also found in 228o,among the four tautomers during the catalytic reaction.In addition,when the reaction proceeded to the transition state,followed by product generation,the proton location was reversed to the inner oxygen of Asp 32(32i) from the outer oxygen of Asp 228(228o).CONCLUSION:Results demonstrated the mechanism of Aβ generation.At beginning of BACE catalytic reaction,the precise proton location was preferred on the outer oxygen of Asp 228(228o).In this protonation state,catalytic reaction can proceed smoothly,with reduced active energy and heat release.When the reaction proceeded to the transition state and product generation,the proton location was reversed to the inner oxygen of Asp 32(32i).These results provide theoretical guidance for designing new drugs to protect neural cells and promote neural regeneration in Alzheimer's patients.Shu Liu Huaqiao Wang Lihua Zhou Zhibin Yao 2010Neural Regeneration Research2010,5,8:0
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