Utilizing an Animal Model to Identify Brain Neurodegeneration-Related Biomarkers in Aging

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.     

基于生物启发计算的警用流动人口分析系统

目前对流动人口的管理仅停留在数据查询比对和简单统计上,缺少对数据的深层次分析,难以对决策指挥提供支持。针对流动人口的分析问题,提出了构建一个基于生物启发计算的智能分析系统,用于发现流动人口中各类人员的流动模式以及流动人口的趋势性问题,找出异常的流动信息和模式。该系统综合运用了前沿的生物启发计算技术——基于多层染色体基因表达式编程算法、重叠基因表达进化算法、基于概念相似度神经网络分类模型和层次距离计算的聚类算法搭建了一个警用流动人口的分析平台。同时根据实际需求,提出了一种新的基于智能分析结果的分级报警模型。实验表明系统具有较高的性能和实用性。     

Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD⁺, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD⁺ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD⁺ production through the NAD⁺ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD⁺ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD⁺ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD⁺ biosynthesis pathways in mammals, the NAD⁺ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD⁺, have been developed so far. In this review, we will focus on the importance of NAD⁺ and the possible application of an activator of NAMPT to promote successive aging.     

A New Tool to Study Parkinsonism in the Context of Aging: MPTP Intoxication in a Natural Model of Multimorbidity

The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100β were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.     

ECAP制备的亚微米7050铝合金的力学性能和微观结构

采用等通道角挤压法 (ECAP法 )制备亚微米 70 5 0铝合金。为了提高合金的力学性能 ,在挤压过程中增加了固溶时效处理工艺 ,并对 70 5 0铝合金在不同处理工艺条件下的显微组织和力学性能的变化进行了研究。结果表明 :ECAP挤压后进行固溶和时效处理能明显提高合金的力学性能。退火态合金经过ECAP后 ,晶粒尺寸明显细化到亚微米级。将挤压一次的试样进行固溶处理和时效处理 ,合金的强度在 5 75MPa左右 ,而延伸率能达到2 5 .5 %左右 ;若经等通道角挤压过的试样在固溶处理后立即进行再次挤压 ,并配合时效处理 ,合金强度能迅速达到 6 16MPa ,延伸率为 16 .9%。     

热处理和锰含量对CuZnAl合金微观组织结构和宏观性能的影响

采用万能试验机、金相显微镜、扫描电子显微镜以及动态热机械分析仪,研究了时效时间以及Mn元素对CuZnAl合金微观组织结构、力学及阻尼性能的影响。结果表明:Mn元素可以改善材料微观组织结构,提高合金的阻尼性能和拉伸强度;微观组织结构中的针状马氏体和块状马氏体随时效热处理时间的增长发生显著变化,并由此影响材料的阻尼性能;阻尼性能与针状马氏体的长度和密度呈正相关,而与块状马氏体的数量呈负相关,但Mn含量过高时,例如达到10%,出现粗大的块状组织,合金力学性能会有明显下降。     

时效对2195铝锂合金腐蚀行为的影响

研究了2195铝锂合金在不同时效状态下的晶间腐蚀和剥落腐蚀行为.结果表明:2195合金在自然时效状态下具有较好的抗晶间腐蚀和剥落腐蚀能力,但随着在160℃时效时间的延长,其晶间腐蚀与剥落腐蚀倾向逐渐增加;在剥落腐蚀溶液中进行的极化曲线测试也表现出相同的趋势.透射电镜观察发现:2195合金主要析出相为T1相;随着时效时间延长,T1相逐渐粗化,在晶界处还会出现无析出带及平衡相.模拟相实验证实,由于T1相和无析出带的开路电位都明显低于铝基体的,在腐蚀性介质中作为阳极相优先溶解,从而导致2195合金产生晶间腐蚀及剥落腐蚀.过时效状态与峰时效状态相比,晶界平衡相增多,无析出带变宽,晶间腐蚀及剥落腐蚀程度将更加严重.     

熔体快淬Cu100-xCrx合金过饱和固溶体的时效分解及对电阻率的影响

用熔体快淬法制备了C11100-xCrx(x=2～35)合金带.研究表明:熔体快淬带的组织由Cr在Cu中的过饱和固溶体、富Cr溶质偏聚区、富Cr液相分解粒子组成;含Cr量增加,液相分解粒子体积分数增加,电阻率提高;过饱和固溶体在等温时效过程中短时间内(10 min)快速分解完毕,合金带的电阻率大幅下降,延长时效时间,富Cr沉淀相尺寸长大缓慢;时效温度升高,富Cr沉淀的尺寸略有增大,电阻率在600℃时效达到最小值.     

延缓与加速A1-Cu合金时效析出反应的研究

研究了溶质原子浓度、Si晶体第二相、残余形变、外加莫来石(Mullite)短纤维及其交互作用，对二元Al—Cu合金时效析出行为的影响。试验材料采用挤压铸造方法制备，复合材料中纤维体积分数为18％。实验结果表明：随溶质原子浓度的升高，A1-Cu二元合金中GP，θ″和θ′相的析出都得到了相应加快；Si含量超过一定值后，随Si含量增加，A1-Cu-Si合金中GP区形成受到抑制，而θ″和θ′相的析出得到加快；形变对GP区的抑制和对θ″，θ′和θ相的加速析出具有十分明显的作用；纤维本身除对GP区抑制和对θ″，θ′相的析出加速外，还会与溶质原子、合金元素或第二相以及残余形变交互作用，使GP区被抑制，而θ″，θ′甚至θ相被加速析出等现象进一步加强。用位错理论能较好地解释析出反应延缓与加速的微观机理。     

铝合金时效-屈服强度的实验与模型化研究

以析出热力学、长大动力学及位错理论为基础，研究了铝合金在时效过程中盘／片状、棒／针状析出相尺寸、体积分数对时效合金强化效果的影响，从微观-宏观相结合的角度建立了具有盘／片状、棒／针状细小时效强化相铝合金的时效工艺-屈服强度量化模型，并通过513K温度下时效Al-Cu-Mg合金和463K温度下时效Al-Mg-Si合金的实验结果对模型进行了验证，取得了较满意的吻合结果，并对本模型的模拟精度与时效析出相参数之间的关系进行了讨论。