ACTA PHARMACOLOGICA SINICA
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2025
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IF 8.4
Feng Yue-yao,Hao Jing-ran,Zhang Yu-jie,Qiu Tong-tong,Zhang Meng-lin,Qiao Wei,Wu Jin-jin,Qiu Ping,Xu Chao-fan,Zhang Yin-liang,Du Chun-yuan,Pan Zhe,Chang Yong-sheng
The deposition of β-amyloid (Aβ) in the brain is a crucial factor in the pathogenesis of Alzheimer’s disease (AD). Insulin-degrading enzyme (IDE) plays a critical role in the balance between Aβ production and degradation. However, the regulatory mechanisms of IDE are not yet fully understood. Therefore, uncovering additional IDE regulatory mechanisms will help elucidate the pathogenesis of AD and identify key therapeutic targets for this disease. This study revealed that global Krüppel-like factor 9-mutant (Klf9 −/− ) mice exhibited impaired cognitive function. Additionally, we found that Klf9 expression in hippocampal tissue was reduced in APPswe/PS1dE9 (APP/PS1) mice. This study also showed that Klf9 stimulates IDE expression and promotes the Aβ degradation process by directly binding to IDE and activating its transcription. Silencing IDE blocked the Klf9-induced Aβ degradation process. We stereotactically injected an adeno-associated virus to selectively overexpress IDE (AAV-IDE) in the hippocampal neurons of Klf9 −/− mice and found that the overexpression of IDE in hippocampal neurons ameliorated cognitive deficits and reduced the Aβ content in Klf9 −/− mice. Additionally, we also stereotactically injected AAV-Klf9 into the hippocampal neurons of APP/PS1 mice and found that overexpression of Klf9 in hippocampal neurons ameliorated cognitive deficits and reduced Aβ levels in APP/PS1 mice. These findings suggest that downregulation of Klf9 may be a key factor in AD progression, as it reduces Aβ clearance by decreasing IDE expression. Overexpression or activation of Klf9 may be a potential strategy for preventing the pathogenesis of AD.
研究领域:
神经生物学
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分子生物学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER
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2024
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IF 4.1
Pei Zhang,Rulin Yang,Yuzhu Wang,Hongguang Sun,Guangqiang Xu,Qinggang Wang
The chemical recycling of plastics to monomers provides efficient assistance for sustainable development of plastics. For polyglycolide (PGA), it has gained widespread attention to be a highly promising plastic material due to its excellent performance. However, research on the ring-closing depolymerization of PGA has yet to break through. The depolymerization is mainly limited by the challenges brought by high crystallinity and melting point of PGA, and instability of glycolide (GL). In this work, a synergistic transesterification strategy is proposed to achieve efficient depolymerization of PGA to monomer GL. Utilizing the versatile catalyst zinc bis[bis(trimethylsilyl)amide] (Zn(HMDS)2) to promote simultaneous intramolecular and intermolecular transesterification, the random chain scission and back-biting depolymerization is achieved in succession. Therefore, the depolymerization product GL can be obtained in high yield and purity. This strategy will provide new research ideas for the chemical recycling of plastics.
研究领域:
材料科学
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化学工程
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Jian Zhang,Yuyu Zhang,Jayne Wu,Haochen Qi,Meiqi Zhao,Maoxiang Yi,Zhenmin Li,Lei Zheng
Cadmium ion (Cd 2+ ) is a highly toxic heavy metal pollutant with long biological half-life and strong bioaccumulation, which may cause irreversible damage to human health even at low-dose intake. Sensitive and specific detection of ultra-trace Cd 2+ is of great significance in food safety and environmental monitoring. In this work, a simple-to-use aptasensor to rapidly detect Cd 2+ in various liquid media is developed based on a DNA aptamer modified gold interdigitated electrode (IDE). Capacitance at the solid-liquid interface is utilized to reflect the change caused by adsorbed Cd 2+ . With the microfluidic enrichment by AC electrothermal (ACET) effect, Cd 2+ ions are sped up toward the IDE surface and captured by the probes instantaneously. Owing to the integration of target enrichment and capacitance detection, the sample-to-result time of this sensor is as short as 30 s. This aptasensor as a quantitative detector has a linear response range from 0.45 fM to 4.5 pM, with a limit of detection of 253.16 aM. The selectivity ratio reaches 2320: 1 against non-target metal ions. By detection of Cd 2+ spiked in tap water and olive oil as well as natural residual Cd 2+ in rice leaching solution, the sensor’s applicability and reliability in different practical liquid media are demonstrated.
研究领域:
环境科学
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分析化学
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食品安全
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生物技术
✓ 已验证
DOI
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2021
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IF 3.921
Ying Xu,Yunxia Dong,Cong Wang,Qian Jiang,Haichao Chu,Yue Tian
As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro . In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ 1-40 and Aβ 1-42 in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment.
研究领域:
神经科学
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药理学
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麻醉学
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老年医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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