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Dysregulation of autophagy is associated with the neurodegenerative processes in Alzheimer's disease (AD), yet it remains controversial whether autophagy is a cause or consequence of AD. We have previously expressed the full‐length human APP in Drosophila and established a fly AD model that exhibits multiple AD‐like symptoms. Here we report that depletion of CHIP effectively palliated APP‐induced pathological symptoms, including morphological, behavioral, and cognitive defects. Mechanistically, CHIP is required for APP‐induced autophagy dysfunction, which promotes Aβ production via increased expression of BACE and Psn. Our findings suggest that aberrant autophagy is not only a consequence of abnormal APP activity, but also contributes to dysregulated APP metabolism and subsequent AD pathogenesis.  相似文献   
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Washing is a standard step for enzyme‐linked immunosorbent assays (ELISA) performed on a paper‐based chip, in which nonspecific‐binding antibodies and antigens should be removed completely from the paper surface. In this study, a novel three‐dimensional (3D) washing strategy using a heating ring‐oven was carried out on a paper‐based chip. Compared with a plane washing mode by a ring‐oven, this 3D washing strategy obtained a lower background, as gravity played an important role in the washing step. The paper‐based chip was placed on a 3D plastic holder and the waste area was connected to a heating ring. Use of a heating waste area meant that the nonspecific‐binding protein was continuously carried to the waste area through gravity and capillary action. The angle between the plastic holder and the ring plane was carefully selected. The effect of washing on different parts of the detection area was investigated by upconversion fluorescence and chemiluminescence (CL). This novel 3D washing strategy was performed for carcinoembryonic antigen detection through CL and a lower detection limit of 2 pg ml?1 was obtained. This approach provides an effective washing strategy to remove nonspecific‐binding antibody from a paper‐based immunodevice.  相似文献   
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为探讨大别山森林群落的构建和演替机制, 本文基于安徽鹞落坪落叶阔叶林11.56 ha动态监测样地的定位监测资料, 采用最近邻分析和O-ring函数、Monte Carlo拟合和零模型选取的方法, 分析了落叶阔叶林蔷薇科主要树种水榆花楸(Sorbus alnifolia)、山樱花(Cerasus serrulata)和中华石楠(Photinia beauverdiana)不同年龄阶段的空间分布格局及种间关联性。结果表明: (1)在整个样地中3个树种的小树和成年树阶段都为聚集分布, 且随年龄增加聚集性减弱, 在老树阶段转为随机和均匀分布。(2)在0-50 m尺度范围内, 以完全随机模型(complete spatial randomness, CSR)为零假设时, 3个树种整体及小树都在小尺度(≤ 10 m)上呈聚集分布, 成年树与老树多为随机分布。以异质性泊松模型(heterogeneous Poisson, HP)为零假设时, 树种的聚集与生境异质性间呈负相关, 3个树种只在≤ 4 m尺度上出现聚集现象。(3) 3个树种种内各个年龄段之间在较大范围内多为负相关和无显著相关性, 同时各树种及不同年龄段之间受种间竞争和密度制约效应影响在小尺度上(≤ 10 m)多为负相关, 随尺度增加相关性减弱。综合而言, 大别山落叶阔叶林中蔷薇科植物的分布格局整体上多为聚集分布, 随树龄增加聚集性减弱, 在中大尺度上受生境异质性效应的影响显著, 在小尺度上多为负相关, 各树种内部各龄级相互之间也多为负相关。  相似文献   
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Ethnopharmacological relevance: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis.Objective: The present study aimed to examine GLXBBX’s preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats.Materials and methods: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats’ plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected.Results: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1).Conclusion: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.  相似文献   
149.
肺部微生物组存在于呼吸道和实质组织中,通过菌群紊乱、代谢产物、炎症反应、免疫反应、基因毒性等方面介导肺部损伤。随着肺部微生物组的深入研究,发现肺部微生物组的相关活动与慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)和肺癌息息相关,能够促使COPD向肺癌的转变。本文主要介绍了肺部微生物组稳态及其通过炎症反应导致COPD和肺癌,重点探讨了肺部微生物组如何通过炎症反应介导COPD转化为肺癌,以期为COPD和肺癌的临床预防、优化治疗以及新型药物设计提供新的理论依据。  相似文献   
150.
ABSTRACT

The role of the serotonin 7 receptor (5-HT7 receptor) subtype in a number of domains has been widely recognized, but its role in the regulation of changes of the circadian rhythm after anesthesia is still unclear. We used intraperitoneal injection of 5-HT7 receptor agonist LP-211 or antagonist SB-269970 in mice to influence the level of 5-HT7 receptor protein in the SCN and to observe the role of this receptor on circadian rhythm changes after isoflurane anesthesia. Our results show the appropriate dose of SB-269970 significantly alleviated the circadian rhythm disorder induced by isoflurane anesthesia, while LP-211 significantly aggravated it after anesthesia, which is different from the phase shift that can be caused by the administration of LP-211 before anesthesia. These findings may indicate the 5-HT7 receptor plays a complex role in the regulation of circadian rhythm after anesthesia. Our findings may provide some positive significance for alleviating circadian rhythm disorder in patients after anesthesia and ultimately promoting rapid postoperative recovery.  相似文献   
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