21 research outputs found

    Fangchinoline alleviates cognitive impairments through enhancing autophagy and mitigating oxidative stress in Alzheimer’s disease models

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    Introduction: Alzheimer’s disease (AD) is a debilitating, progressive, neurodegenerative disorder characterized by the deposition of amyloid-β (Aβ) peptides and subsequent oxidative stress, resulting in a cascade of cytotoxic effects. Fangchinoline (Fan), a bisbenzylisoquinoline alkaloid isolated from traditional Chinese herb Stephania tetrandra S. Moorec, has been reported to possess multiple potent biological activities, including anti-inflammatory and antioxidant properties. However, the potential neuroprotective efficacy of Fan against AD remains unknown.Methods: N2AAPP cells, the mouse neuroblastoma N2A cells stably transfected with human Swedish mutant APP695, were served as an in vitro AD model. A mouse model of AD was constructed by microinjection of Aβ1–42 peptides into lateral ventricle of WT mice. The neuroprotective effects of Fan on AD were investigated through a combination of Western blot analysis, immunoprecipitation and behavioral assessments.Results and discussion: It was found that Fan effectively attenuated the amyloidogenic processing of APP by augmenting autophagy and subsequently fostering lysosomal degradation of BACE1 in N2AAPP cells, as reflected by the decrease in P62 levels, concomitant with the increase in Beclin-1 and LC3-II levels. More importantly, Fan significantly ameliorated cognitive impairment in an Aβ1–42-induced mouse model of AD via the induction of autophagy and the inhibition of oxidative stress, as evidenced by an increase in antioxidants including glutathione reductase (GR), total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase-1 (SOD-1) and a decrease in pro-oxidants including hydrogen peroxide (H2O2) and inducible nitric oxide synthase (i-NOS), coupled with a reduction in apoptosis marker, cleaved caspase-3. Taken together, our study demonstrate that Fan ameliorates cognitive dysfunction through promoting autophagy and mitigating oxidative stress, making it a potential therapeutic agent for AD

    Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Function and Synaptic Plasticity in APP23/PS45 Mouse Model of Alzheimer’s Disease

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    Alzheimer’s disease (AD) is a chronic neurodegenerative disease leading to dementia, which is characterized by progressive memory loss and other cognitive dysfunctions. Recent studies have attested that noninvasive repetitive transcranial magnetic stimulation (rTMS) may help improve cognitive function in patients with AD. However, the majority of these studies have focused on the effects of high-frequency rTMS on cognitive function, and little is known about low-frequency rTMS in AD treatment. Furthermore, the potential mechanisms of rTMS on the improvement of learning and memory also remain poorly understood. In the present study, we reported that severe deficits in spatial learning and memory were observed in APP23/PS45 double transgenic mice, a well known mouse model of AD. Furthermore, these behavioral changes were accompanied by the impairment of long-term potentiation (LTP) in the CA1 region of hippocampus, a brain region vital to spatial learning and memory. More importantly, 2-week low-frequency rTMS treatment markedly reversed the impairment of spatial learning and memory as well as hippocampal CA1 LTP. In addition, low-frequency rTMS dramatically reduced amyloid-β precursor protein (APP) and its C-terminal fragments (CTFs) including C99 and C89, as well as β-site APP-cleaving enzyme 1 (BACE1) in the hippocampus. These results indicate that low-frequency rTMS noninvasively and effectively ameliorates cognitive and synaptic functions in a mouse model of AD, and the potential mechanisms may be attributed to rTMS-induced reduction in Aβ neuropathology

    A fine recognition method of strawberry ripeness combining Mask R-CNN and region segmentation

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    As a fruit with high economic value, strawberry has a short ripeness period, and harvesting at an incorrect time will seriously affect the quality of strawberries, thereby reducing economic benefits. Therefore, the timing of its harvesting is very demanding. A fine ripeness recognition can provide more accurate crop information, and guide strawberry harvest management more timely and effectively. This study proposes a fine recognition method for field strawberry ripeness that combines deep learning and image processing. The method is divided into three stages: In the first stage, self-calibrated convolutions are added to the Mask R-CNN backbone network to improve the model performance, and then the model is used to extract the strawberry target in the image. In the second stage, the strawberry target is divided into four sub-regions by region segmentation method, and the color feature values of B, G, L, a and S channels are extracted for each sub-region. In the third stage, the strawberry ripeness is classified according to the color feature values and the results are visualized. Experimental results show that with the incorporation of self-calibrated convolutions into the Mask R-CNN, the model’s performance has been substantially enhanced, leading to increased robustness against diverse occlusion interferences. As a result, the final average precision (AP) has improved to 0.937, representing a significant increase of 0.039 compared to the previous version. The strawberry ripeness classification effect is the best on the SVM classifier, and the accuracy under the combined channel BGLaS reaches 0.866. The classification results are better than common manual feature extraction methods and AlexNet, ResNet18 models. In order to clarify the role of the region segmentation method, the contribution of different sub-regions to each ripeness is also explored. The comprehensive results demonstrate that the proposed method enables the evaluation of six distinct ripeness levels of strawberries in the complex field environment. This method can provide accurate decision support for strawberry refined planting management

    Vanadium Pentoxide Nanofibers/Carbon Nanotubes Hybrid Film for High-Performance Aqueous Zinc-Ion Batteries

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    Aqueous zinc-ion batteries (ZIBs) with the characteristics of low production costs and good safety have been regarded as ideal candidates for large-scale energy storage applications. However, the nonconductive and non-redox active polymer used as the binder in the traditional preparation of electrodes hinders the exposure of active sites and limits the diffusion of ions, compromising the energy density of the electrode in ZIBs. Herein, we fabricated vanadium pentoxide nanofibers/carbon nanotubes (V2O5/CNTs) hybrid films as binder-free cathodes for ZIBs. High ionic conductivity and electronic conductivity were enabled in the V2O5/CNTs film due to the porous structure of the film and the introduction of carbon nanotubes with high electronic conductivity. As a result, the batteries based on the V2O5/CNTs film exhibited a higher capacity of 390 mAh g−1 at 1 A g−1, as compared to batteries based on V2O5 (263 mAh g−1). Even at 5 A g−1, the battery based on the V2O5/CNTs film maintained a capacity of 250 mAh g−1 after 2000 cycles with a capacity retention of 94%. In addition, the V2O5/CNTs film electrode also showed a high energy/power density (e.g., 67 kW kg−1/267 Wh kg−1). The capacitance response and rapid diffusion coefficient of Zn2+ (~10−8 cm−2 s−1) can explain the excellent rate capability of V2O5/CNTs. The vanadium pentoxide nanofibers/carbon nanotubes hybrid film as binder-free cathodes showed a high capability and a stable cyclability, demonstrating that it is highly promising for large-scale energy storage application

    Lack of interferon regulatory factor 3 leads to anxiety/depression-like behaviors through disrupting the balance of neuronal excitation and inhibition in mice

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    Disrupting the balance of neuronal excitation and inhibition (E/I) is an important pathogenic mechanism of anxiety and depression. Interferon regulatory factor 3 (IRF3) plays a key role in the innate immune response, and activation of IRF3 triggers the expression of type I interferons and downstream interferon-stimulated genes, which are associated with anxiety and depression. However, whether IRF3 participates in the pathogenesis of anxiety/depression by regulating E/I balance remains poorly understood. Here, we reported that global knockout (KO) of IRF3 (IRF3−/−) significantly increased anxiety/depression-like behaviors, but did not affect normal spatial learning and memory. Compared with wild type (WT) control mice, the E/I balance was disrupted, as reflected by enhanced glutamatergic transmission and decreased GABAergic transmission in the neurons of hippocampal CA1 and medial prefrontal cortex (mPFC) in IRF3-KO mice. Importantly, genetic rescue of IRF3 expression by adeno-associated virus (AAV) was sufficient to alleviate anxiety/depression-like behaviors and restore the neuronal E/I balance in IRF3-KO mice. Taken together, our results indicate that IRF3 is critical in maintaining neuronal E/I balance, thereby playing an essential role in ensuring emotional stability

    Presentation1_Fangchinoline alleviates cognitive impairments through enhancing autophagy and mitigating oxidative stress in Alzheimer’s disease models.pdf

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    Introduction: Alzheimer’s disease (AD) is a debilitating, progressive, neurodegenerative disorder characterized by the deposition of amyloid-β (Aβ) peptides and subsequent oxidative stress, resulting in a cascade of cytotoxic effects. Fangchinoline (Fan), a bisbenzylisoquinoline alkaloid isolated from traditional Chinese herb Stephania tetrandra S. Moorec, has been reported to possess multiple potent biological activities, including anti-inflammatory and antioxidant properties. However, the potential neuroprotective efficacy of Fan against AD remains unknown.Methods: N2AAPP cells, the mouse neuroblastoma N2A cells stably transfected with human Swedish mutant APP695, were served as an in vitro AD model. A mouse model of AD was constructed by microinjection of Aβ1–42 peptides into lateral ventricle of WT mice. The neuroprotective effects of Fan on AD were investigated through a combination of Western blot analysis, immunoprecipitation and behavioral assessments.Results and discussion: It was found that Fan effectively attenuated the amyloidogenic processing of APP by augmenting autophagy and subsequently fostering lysosomal degradation of BACE1 in N2AAPP cells, as reflected by the decrease in P62 levels, concomitant with the increase in Beclin-1 and LC3-II levels. More importantly, Fan significantly ameliorated cognitive impairment in an Aβ1–42-induced mouse model of AD via the induction of autophagy and the inhibition of oxidative stress, as evidenced by an increase in antioxidants including glutathione reductase (GR), total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase-1 (SOD-1) and a decrease in pro-oxidants including hydrogen peroxide (H2O2) and inducible nitric oxide synthase (i-NOS), coupled with a reduction in apoptosis marker, cleaved caspase-3. Taken together, our study demonstrate that Fan ameliorates cognitive dysfunction through promoting autophagy and mitigating oxidative stress, making it a potential therapeutic agent for AD.</p
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