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Detection of Femtomolar Amyloid-β Peptides for Early-Stage Identification of Alzheimer’s Amyloid-β Aggregation with Functionalized Gold Nanoparticles

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ACS Applied Materials and Interfaces 2024年第3期16卷 3819-3828页

作者： Chang, Yu-Jen Chien, Yi-Hsin Chang, Chieh-Chun Wang, Pei-Ning Chen, Yun-Ru Chang, Yun-Chorng Genomics Research Center Academia Sinica Taipei115 Taiwan Taiwan International Graduate Program in Interdisciplinary Neuroscience National Taiwan University and Academia Sinica Taipei115 Taiwan Research Center for Applied Sciences Academia Sinica Taipei115 Taiwan Department of Physics National Taiwan University Taipei106 Taiwan Nano Science and Technology Program Taiwan International Graduate Program Academia Sinica and National Taiwan University Taipei115 Taiwan Brain Research Center National Yang Ming Chiao Tung University Taipei112 Taiwan Division of General Neurology Department of Neurological Institute Taipei Veterans General Hospital Taipei112 Taiwan

Progressive amyloid-β (Aβ) fibrillar aggregates have long been considered as the pathogenesis of Alzheimer’s disease (AD). Biocompatible and stable cysteine-Aβ peptide-conjugated gold nanoparticles (Cys-Aβ@AuNP) are demonstrated as suitable materials for detecting subfemtomolar Aβ peptides in human plasma. Incubation with Aβ peptides causes the Cys-Aβ@AuNP to aggregate and changes its absorption spectra. The spectral change is especially apparent and noticeable when detecting subfemtomolar Aβ peptides, and the aggregates contain only two or three AuNPs. Cys-Aβ@AuNP can also be used to identify early-stage Aβ oligomerization, which is not possible using the conventional method, in which the fluorescence of thioflavin-T is measured. The ability to detect Aβ oligomerization can facilitate therapeutics for AD. In addition, the binding of Aβ peptides by Cys-Aβ@AuNP in combination with centrifugation redirects the conventional Aβ aggregation pathway and can effectively inhibit the formation of toxic Aβ oligomers or fibrils. Therefore, the proposed Cys-Aβ@AuNP can also be used to develop effective therapeutic agents to inhibit Aβ aggregation. The results obtained in this study are expected to open revolutionary ways to both detect and inhibit Aβ aggregation at an early stage. © 2024 American Chemical Society

关键词： Oligomers

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Equilibrative nucleoside transporter 3 supports microglial functions and protects against the progression of Huntington's disease in the mouse model

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brain, Behavior, and Immunity 2024年 120卷 413-429页

作者： Lu, Ying-Sui Hung, Wei-Chien Hsieh, Yu-Ting Tsai, Pei-Yuan Tsai, Tsai-Hsien Fan, Hsiu-Han Chang, Ya-Gin Cheng, Hui-Kuei Huang, Shen-Yan Lin, Hsin-Chuan Lee, Yan-Hua Shen, Tzu-Hsiang Hung, Bing-Yu Tsai, Jin-Wu Dzhagalov, Ivan Cheng, Irene Han-Juo Lin, Chun-Jung Chern, Yijuang Hsu, Chia-Lin Institute of Microbiology and Immunology National Yang Ming Chiao Tung University Taipei Taiwan Taiwan International Graduate Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan Institute of Brain Science National Yang Ming Chiao Tung University Taipei Taiwan Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Taiwan International Graduate Program in Interdisciplinary Neuroscience National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei Taiwan Brain Research Center National Yang Ming Chiao Tung University Taipei Taiwan School of Pharmacy College of Medicine National Taiwan University Taipei Taiwan

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3^−/− mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes. © 2024 The Authors

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An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning

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National science Review 2024年第5期11卷 186-201页

作者： Mingyue Lv Ruyi Cai Renzimo Zhang Xiju Xia Xuelin Li Yipan Wang Huan Wang Jianzhi Zeng Yifei Xue Lanqun Mao Yulong Li State Key Laboratory of Membrane Biology School of Life SciencesPeking University State Key Laboratory of Brain and Cognitive Science Institute of Biophysics Chinese Academy of Sciences PKU-IDG/Mc Govern Institute for Brain Research Yuanpei College Peking University Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Peking University–Tsinghua University–National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary Studies Peking University Institute of Molecular Physiology Shenzhen Bay Laboratory College of Chemistry Beijing Normal University Chinese Institute for Brain Research

Octopamine（OA）,analogous to norepinephrine in vertebrates,is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions,including olfactory associative ***,the spatial and temporal dynamics of OA in vivo remain poorly understood due to limitations associated with the currently available methods used to detect *** overcome these limitations,we developed a genetically encoded GPCR activation-based（GRAB） OA sensor called *** sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular *** GRABOA1.0,we monitored OA release in the Drosophila mushroom body（MB）,the fly's learning center,and found that OA is released in response to both odor and shock stimuli in an aversive learning *** OA release requires acetylcholine（ACh） released from Kenyon cells,signaling via nicotinic ACh ***,we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octβ1R in dopaminergic neurons,leading to alterations in synaptic plasticity within the ***,our new GRABOA1.0sensor can be used to monitor OA release in real time under physiological conditions,providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.

关键词： octopamine dopamine GRAB sensor learning and memory

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Over the Quantum Rainbow: Explaining Hybrid Quantum Reinforcement Learning

Over the Quantum Rainbow: Explaining Hybrid Quantum Reinforc...

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Quantum Computing and Engineering (QCE), IEEE International Conference on

作者： Junghoon Park Jiook Cha Samuel Yen-Chi Chen Shinjae Yoo Huan-Hsin Tseng Interdisciplinary Program in Artificial Intelligence Seoul National University Department of Psychology Seoul National University Department of Brain and Cognitive Sciences Seoul National University Graduate School of Data Science Seoul National University Wells Fargo Computational Science Initiative Brookhaven National Laboratory

ISBN: (数字)9798331541378

ISBN: (纸本)9798331541385

In the realm of artificial intelligence, deep rein-forcement learning (RL) agents struggle with generalizability and require substantial computational resources, unlike humans who easily adapt and generalize across tasks. To address these challenges, we introduce Quantum Rainbow, a hybrid algorithm that leverages the neural mechanisms of human decision-making and the efficiency of quantum computing. Quantum Rainbow combines variational quantum circuits with the Rainbow Deep Q-Network (DQN) model to create a novel approach in rein-forcement learning that integrates quantum principles into deep learning paradigms. We evaluate our model using behavioral experiments through the Iowa Gambling Task and 4-Armed Bandit Task. Our investigations reveal a significant relationship between the architecture of quantum circuits and the performance of quantum RL agents. Specifically, using causal discovery methods, we demonstrate the critical role of quantum entanglement in enhancing model performance. These findings not only show promising results but also pave the way for future explorations into optimizing quantum circuit architectures for reinforcement learning applications. This study underscores the potential of quantum-enhanced algorithms to achieve “quantum advantage” by addressing fundamental limitations in conventional deep RL methods.

关键词： Analytical models Quantum computing Quantum algorithm Quantum advantage Quantum entanglement Computational modeling Reinforcement learning Quantum state Integrated circuit modeling Quantum circuit

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Biomedical data and AI

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science China Life sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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VEGF family in cortical development

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Discover Neuroscience 2025年第1期20卷 1-20页

作者： Halim, Alexander Kuo, Hung-Chih Hou, Pei-Shan Taiwan International Graduate Program in Interdisciplinary Neuroscience College of Life Sciences National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan Institute of Cellular and Organismic Biology Academia Sinica Taipei Taiwan Institute of Anatomy and Cell Biology College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Graduate Institute of Medical Genomics and Proteomics College of Medicine National Taiwan University Taipei Taiwan Institute of Brain Science College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan Brain Research Center National Yang Ming Chiao Tung University Taipei Taiwan

Vascular endothelial growth factor (VEGF) has been extensively recognized as a crucial angiogenic factor that regulates both physiological and pathological blood vessel development in vascular endothelial cells (ECs). Emerging evidence indicates that VEGF and its receptors are also expressed in various non-EC types. Studies have shown that VEGF is secreted by neuroepithelial cells during neural tube formation in mouse embryonic day 8.5. This suggests that VEGF may have functions beyond angiogenesis, particularly in brain development. Additionally, the disruption of VEGF signaling has been linked to the development of cerebral cortical malformations, further supporting the potential role of VEGF in brain development. In this review, we summarize studies that elucidate the roles of VEGF signaling in regulating embryonic cortical neural progenitor expansion during early embryogenesis. We then explore the VEGF functions in promoting cortical neurogenesis and discuss the impact of the VEGF family on the regulation of the cerebrovascular system and cortical gliogenesis. Finally, we elaborate on the significance of the VEGF family in cortical-related disorders, noting that both deficiency and excessive expression of VEGF can adversely affect cortical development, resulting in cortical malformations. Overall, this review presents an updated and comprehensive understanding of the multifaceted regulatory roles of the VEGF family in the embryonic brain, offering insights into the underlying mechanisms of brain development.

关键词： Vascular endothelial growth factor (VEGF) Corticogenesis Neurogenesis Angiogenesis Cortical malformation

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A nigroincertal projection mediates aversion and enhances coping responses to potential threat

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FASEB Journal 2023年第12期37卷 e23322-e23322页

作者： Ho, Ping-Chen Hsiao, Fu-Yun Chiu, Shi-Hong Lee, Syun-Ruei Yau, Hau-Jie The Laboratory for Neural Circuits and Behaviors Graduate Institute of Brain and Mind Sciences National Taiwan University Taipei Taiwan School of Medicine National Taiwan University Taipei Taiwan Neurobiology and Cognitive Science Center National Taiwan University Taipei Taiwan Taiwan International Graduate Program in Interdisciplinary Neuroscience National Taiwan University and Academia Sinica Taipei Taiwan Ph.D. Program in Translational Medicine National Taiwan University and Academia Sinica Taipei Taiwan

Recent studies have shown that the non-DA neurons in the ventral tegmental area (VTA) and substantia nigra (SN) not only modulate motivational behaviors but also regulate defensive behaviors. While zona incerta (ZI) is a threat-responsive substrate and receives innervations from the ventral midbrain, the function of the ventral midbrain-to-ZI connection remains poorly defined. Here, we demonstrate that the ZI receives heterogenous innervations from the ventral midbrain. By utilizing a retrograde AAV preferentially labeling non-DA neurons in the ventral midbrain, we found that ZI-projecting non-DA cells in the ventral midbrain are activated by restraint stress. We focused on the SN and found that SN-to-ZI GABAergic input is engaged by a predatory odor. Sustained pan-neuronal SN-to-ZI activation results in aversion and enhances defensive behaviors, likely through a disinhibition mechanism to recruit downstream brain regions that regulate defensive behaviors. Collectively, our results reveal a novel role of nigroincertal projection in mediating negative valence and regulating defensive behaviors. © 2023 Federation of American Societies for Experimental Biology.

关键词： defensive behavior stress substantia nigra ventral tegmental area zona increta

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brain MRI Synthesis from Amyloid PET/CT via Enhanced Denoising Diffusion Probabilistic Model

Brain MRI Synthesis from Amyloid PET/CT via Enhanced Denoisi...

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IEEE Symposium on Nuclear science (NSS/MIC)

作者： Y.J. Seol H.B. Yoo E.J. Yoon Y.K. Kim J.S. Lee Integrated Major in Innovative Medical Science Seoul National University Seoul Republic of Korea Seoul National University Interdisciplinary Program in Bioengineering Seoul Republic of Korea Department of Nuclear Medicine and WCU Department of Brain and Cognitive Sciences Seoul National University Seoul Republic of Korea Department of Nuclear Medicine Seoul National University-Seoul Metropolitan Government Boramae Medical Center Seoul Republic of Korea Department of Nuclear Medicine Seoul National University Seoul Republic of Korea Brightonix Imaging Inc Seoul Republic of Korea

ISBN: (数字)9798350388152

ISBN: (纸本)9798350388169

In this study, we presents a novel method for generating synthetic brain MRI images from amyloid PET/CT scans using an enhanced Denoising Diffusion Probabilistic Model (DDPM) conditioned with the joint probability distribution. We explored the use of early and late-phase 18 F -Florbetaben PET scans to guide the synthesis process within our DDPM framework, verifying that early-phase scans significantly improved the quality of synthetic MRI generation compared to other deep learning models. In addition, the proposed DDPMs using early-phase PET/CT suggest promising results, particularly for enhancing the accuracy of regional gray matter volume measurements and facilitating PET partial volume corrections in settings where traditional MRI is unavailable.

关键词： Temperature measurement Temperature distribution Microwave integrated circuits Semiconductor detectors Magnetic resonance imaging Volume measurement Noise reduction

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Theoretical foundations of studying criticality in the brain

arXiv

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arXiv 2023年

作者： Tian, Yang Tan, Zeren Hou, Hedong Li, Guoqi Cheng, Aohua Qiu, Yike Weng, Kangyu Chen, Chun Sun, Pei Department of Psychology Tsinghua Laboratory of Brain and Intelligence Tsinghua University Beijing100084 China Laboratory of Advanced Computing and Storage Central Research Institute 2012 Laboratories Huawei Technologies Co. Ltd. Beijing100084 China Institute for Interdisciplinary Information Science Tsinghua University Beijing100084 China UFR de Mathématiques Université de Paris Paris75013 France Institute of Automation Chinese Academy of Science Beijing100190 China University of Chinese Academy of Science Beijing100049 China Tsien Excellence in Engineering Program School of Aerospace Engineering Tsinghua University Beijing100084 China

Criticality is hypothesized as a physical mechanism underlying efficient transitions between cortical states and remarkable information processing capacities in the brain. While considerable evidence generally supports this hypothesis, non-negligible controversies persist regarding the ubiquity of criticality in neural dynamics and its role in information processing. Validity issues frequently arise during identifying potential brain criticality from empirical data. Moreover, the functional benefits implied by brain criticality are frequently misconceived or unduly generalized. These problems stem from the non-triviality and immaturity of the physical theories that analytically derive brain criticality and the statistic techniques that estimate brain criticality from empirical data. To help solve these problems, we present a systematic review and reformulate the foundations of studying brain criticality, i.e., ordinary criticality (OC), quasi-criticality (qC), self-organized criticality (SOC), and self-organized quasi-criticality (SOqC), using the terminology of neuroscience. We offer accessible explanations of the physical theories and statistic techniques of brain criticality, providing step-by-step derivations to characterize neural dynamics as a physical system with avalanches. We summarize error-prone details and existing limitations in brain criticality analysis and suggest possible solutions. Moreover, we present a forward-looking perspective on how optimizing the foundations of studying brain criticality can deepen our understanding of various neuroscience questions. © 2023, CC BY.

关键词： brain

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Bioluminescence-Activated Proximity Labeling for Spatial Multi-Omics

SSRN

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SSRN 2024年

作者： Wang, Ruixiang Fang, Yuxin Hu, Youyue Liu, Yanjun Chen, Peng R. Zou, Peng College of Chemistry and Molecular Engineering Synthetic and Functional Biomolecules Center Beijing National Laboratory for Molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering Ministry of Education PKU-IDG/McGovern Institute for Brain Research Peking University Beijing100871 China Peking-Tsinghua-NIBS Joint Graduate Program Peking University Beijing100871 China National Key Laboratory of Crop Genetic Improvement Hubei Hongshan Laboratory Huazhong Agricultural University Wuhan430070 China Academy for Advanced Interdisciplinary Studies PKU-Tsinghua Center for Life Science Peking University Beijing100871 China Beijing102206 China

Mapping the spatial organization of proteins and cellular interactions is crucial for understanding their biological functions. Herein, we report a biocompatible, multi-functional luminescence-activated proximity labeling (LAP) strategy for profiling subcellular proteomes and cell-cell interactions in live cells and animals. Our method capitalizes on fusing the photocatalyst miniSOG to NanoLuc luciferase, whose bioluminescence activates miniSOG via a resonance energy transfer mechanism, generating reactive oxygen species in situ to mediate proximity labeling. We demonstrated the high spatial specificity of LAP in a C57BL6/N mouse model transplanted with MC38 cells. Our data revealed tumor microenvironment-dependent remodeling of secretome. LAP was further applied to identify ligand-receptor mediated cell-cell interactions both in vitro and in vivo. We also achieved local transcriptome profiling by combining LAP with next-generation sequencing. Overall, LAP was proved to be a versatile PL technique with strong biocompatibility for spatial multi-omic applications. © 2024, The Authors. All rights reserved.

关键词： Bioluminescence

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