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    Inosine exerts dopaminergic neuroprotective effects via mitigation of NLRP3 inflammasome activation

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    Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD). Transformation of pro-interleukin (IL)-1β into a mature IL-1β via active inflammasome may be related to the progression of PD. Therefore, the modification of inflammasome activity may be a potential therapeutic strategy for PD. Inosine has been shown to exert anti-inflammatory effects in various disease models. In this study, we evaluated inosine's inhibitory effects on the microglial NLRP3 inflammasome, which may be related to the dopaminergic neuroprotective effects of inosine. Inosine suppresses lipopolysaccharides (LPS)-induced NLRP3 inflammasome activation in BV-2 microglial cells dose dependently. When SH-SY5Y cells were treated with conditioned medium from BV-2 cells treated with LPS and inosine, an NLRP3 inhibitor, or a caspase-1 inhibitor, the viability of SH-SY5Y cells was reduced indicating that LPS-induced microglial inflammasome activation could contribute to neuronal death. Inosine's modulatory effect on NLRP3 inflammasome activity appears to rely on the adenosine A2A and A3 receptors activation, as A2A or A3 receptor antagonists reversed the amelioration of NLRP3 activation by inosine. In addition, inosine treatment attenuated intracellular and mitochondrial ROS production mediated by LPS and this effect might be related to attenuation of NLRP3 inflammasome activity, as the antioxidant, N-acetyl cysteine ameliorated LPS-induced activation of the inflammasome. Finally, we assessed the inosine's neuroprotective effects via inflammasome activity modulation in mice receiving an intranigral injection of LPS. Immunohistochemical analysis revealed that LPS caused a significant loss of nigral dopaminergic neurons, which was mitigated by inosine treatment. LPS increased NLRP3 expression in IBA1-positive microglial cells, which was attenuated by inosine injection. These findings indicate that inosine can rescue neurons from LPS-induced injury by ameliorating NLRP3 inflammasome activity. Therefore, inosine could be applied as an intervention for neuroinflammatory diseases such as Parkinson's disease. © 2024 Elsevier LtdFALSEsciescopu

    High-Intensity focused ultrasound linear array and system for dermatology treatment

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    Dermatological lesions are typically located just a few millimeters below the surface of the skin, which constrains the efficacy of optical-based therapeutic methods such as photothermal and photodynamic therapy due to limited therapeutic depth caused by optical scattering. As an alternative, high-intensity focused ultrasound (HIFU) has been explored for its potential to treat a variety of dermatological conditions because it offers greater flexibility in terms of treatment depth. Since dermatological lesions have a small thickness ranging from 1.5 to 2.0 mm, high-frequency ultrasound (3–10 MHz or higher) is preferred as the focal area is proportional to the operating frequency. However, due to the difficulty in fabricating HIFU array transducers at this frequency range, the majority of HIFU treatments for dermatology rely on single element transducers. Despite the advantages of HIFU, single-element-based HIFU systems are limited in prevalent use for dermatology treatment due to their fixed focal length and mechanical movement for treatment, which can be time-consuming and unsuitable for treating multiple lesions. To address this, we present a newly developed HIFU linear array and 128-channel driving electronics specifically designed for dermatology treatment. This array consists of 128 elements, has a center frequency of 3.7 MHz, an elevation focal length of 28 mm, and an F-number of 1.27 in the elevation direction. The array has a footprint of 71.6 mm by 22 mm. Experiments using a tissue-mimicking phantom have demonstrated that the HIFU linear array and system are capable of transmitting sufficient ultrasound energy to create coagulation inside the phantom. © 2024 Elsevier B.V.FALSEsciescopu

    Engineering a membrane protein chaperone to ameliorate the proteotoxicity of mutant huntingtin

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    Toxic protein aggregates are associated with various neurodegenerative diseases, including Huntington’s disease (HD). Since no current treatment delays the progression of HD, we develop a mechanistic approach to prevent mutant huntingtin (mHttex1) aggregation. Here, we engineer the ATP-independent cytosolic chaperone PEX19, which targets peroxisomal membrane proteins to peroxisomes, to remove mHttex1 aggregates. Using yeast toxicity-based screening with a random mutant library, we identify two yeast PEX19 variants and engineer equivalent mutations into human PEX19 (hsPEX19). These variants effectively delay mHttex1 aggregation in vitro and in cellular HD models. The mutated hydrophobic residue in the α4 helix of hsPEX19 variants binds to the N17 domain of mHttex1, thereby inhibiting the initial aggregation process. Overexpression of the hsPEX19-FV variant rescues HD-associated phenotypes in primary striatal neurons and in Drosophila. Overall, our data reveal that engineering ATP-independent membrane protein chaperones is a promising therapeutic approach for rational targeting of mHttex1 aggregation in HD.TRUEsci

    Update on Strategies to Reduce Early Brain Injury after Subarachnoid Hemorrhage

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    Purpose of Review: Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH) is the most influential clinical determinant of outcomes. Despite significant advances in understanding of the pathophysiology of EBI, currently no treatments to target EBI have been developed. This review summarizes recent advances in EBI research over the past five years with a focus on potential therapeutic targets. Recent Findings: Mechanism-specific translational studies are converging on several pathophysiologic pathways: improved antioxidant delivery and the Sirt1/Nrf2 pathway for reactive oxygen species; NLRP3 inflammasome and microglial polarization for inflammation; and the PI3K/Akt pathway for apoptosis. Recently identified mechanistic components, such as microcirculatory failure and ferroptosis, need particular attention. Clinical studies developing radiographic markers and mechanism-specific, biofluid markers are attempting to bridge the translational therapeutic gap. Summary: There has been an exponential growth in EBI research. Further clinical studies which address specific pathophysiology mechanisms need to be performed to identify novel therapeutic approaches. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.FALSEsciescopu

    고해상도 및 고효율 Noise-Shaping SAR 기반 생체 신호 획득 시스템

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    Noise-shaping SAR, Bio-potential acquisition systemⅠ. Introduction 1 1.1 Motivation for Bio-Potential Acquisition System Development 1 1.2 Characteristics of Bio-Potential and Design Requirements 4 1.3 Overview of the Thesis 7 Ⅱ. Design Methodologies for Bio-Potential Acquisition 9 2.1 Review of Prior Bio-Potential Acquisition Systems 9 2.1.1 Low Noise Amplifier with Moderate Resolution ADC 9 2.1.2 High-Resolution ADCs for Direct Bio-Potential Acquisition 11 2.2 The Need for Noise-Shaping SAR in Bio-Potential Acquisition 15 2.2.1 Background of Noise-Shaping SAR 15 2.2.2 General System Model of Noise-Shaping SAR 21 2.2.3 Comparison between Noise-Shaping SAR and DSM 24 Ⅲ. Noise-Shaping SAR for Bio-Potential Acquisition 27 3.1 Overall Architecture 27 3.1.1 Conceptual Overview of the System 27 3.1.2 Architecture of the System 29 3.1.3 2nd-Order Noise-Shaping Loop Filter Design 32 3.1.4 The Model of the System 39 3.1.5 Noise Analysis of the System 41 3.2 Input Impedance and System Linearity 45 3.2.1 Input Impedance Enhancing Technique 45 3.2.2 CLA-Based DAC Element Matching 49 3.3 Measurement Results 53 3.4 Summary and Conclusion 60 Ⅳ. Noise-Shaping SAR with Multi-Tasking Integrator 61 4.1 Background of Sampling Noise 61 4.2 Overall Architecture 65 4.2.1 Architecture of the System 65 4.2.2 The Model and Noise Analysis of the System 67 4.3 Operation Principle of the System 72 4.3.1 Input Double Sampling and kT/C Noise Cancellation 72 4.3.2 2nd-Order Integration by Hardware Recycling and CLS 76 4.3.3 Input Impedance Boosting 81 4.4 Measurement Results 82 4.5 Summary and Conclusion 87 Ⅴ. Multi-Channel Bio-Potential Acquisition System 88 5.1 Review of Prior Multi-Channel Systems 88 5.2 TDM-NS-SAR for Multi-Channel Bio-Potential Acquisition 91 5.2.1 Architecture of the System 91 5.2.2 The Model and Noise Analysis of the System 94 5.3 TDM-Based 3rd-Order Residue Integration 98 5.4 Input Impedance and System Linearity 101 5.4.1 Input Impedance Boosting with Input Tracking 101 5.4.2 Time-Division CLA-Based Element Matching 103 5.5 Measurement Results 105 5.6 Summary and Conclusion 112 Ⅵ. Conclusion and Future Work 113 6.1 Conclusion of the Works 113 6.2 Future Work 116 References 117 Summary (in Korean) 123DoctordCollectio

    미세아교세포 활성화의 뇌 영역별 및 시간적 동역학 연구: NLRP3 염증복합체의 조절 이상이 뇌 기능에 미치는 영향

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    신경염증, 미세아교세포, 사이토카인, NLRP3, 시냅스, NMDA 수용체Ⅰ. INTRODUCTION 1 1.1 General introduction: Diversity building up the brain 1 1.2 Core structure of excitatory and inhibitory synapses and their diversity 3 1.3 Contribution of microglia to sophisticated brain function 4 1.4 Neuroinflammation and its impact on microglial function 5 1.5 Regulatory mechanisms of the NLRP3 inflammasome and the pathological contribution of its dysregulation 5 II. MATERIALS & METHODS 7 2.1 Animals 7 2.2 Drug treatment 7 2.3 Antibodies 7 2.4 Immunohistochemistry (IHC) 8 2.5 Microglial analyses using slide scanner 9 2.6 Microglial morphology analyses 9 2.7 Microglial 3D analyses 9 2.8 Preparation and titration of AAVs 10 2.9 Stereotaxic injections 10 2.10 Analysis of microglial engulfment using a synapse engulfment reporter virus 10 2.11 Preparation of brain lysates and quantification of cytokine expression levels 11 2.12 Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) 11 2.13 Primary microglia culture 12 2.14 Culture, immunostaining, and image analysis of cultured neurons 13 2.15 Behavior tests 13 2.16 Data analysis and statistics 15 III. RESULTS 16 3.1 Brain region-specific microglial response to LPS-induced neuroinflammation 16 3.2 Temporal dynamics of microglial activity and its impact on GABAergic synapses in LPS-induced neuroinflammation 19 3.3 NLRP3 dysregulation in microglia induced exaggerated and prolonged neuroinflammation to disrupt normal brain functions. 21 IV. DISCUSSION & CONCLUSION 28 4.1. Regional discrepancy in microglial activation during neuroinflammation 28 4.1.1 Susceptibility of Hb to mild neuroinflammation 28 4.1.2 Different clusters of brain regions show relatively severe responses to two daily doses of LPS 29 4.1.3 Different clusters of brain regions show relatively higher CD68 expression in response to a single dose of LPS. 30 4.1.4 Regional discrepancy in cytokine expression 30 4.2. Investigation of temporal dynamics of microglial activation 32 4.2.1 Microglial activation resolves across time. 32 4.2.2 Inhibitory synapse-specific impairment upon systemic LPS administration ·· 33 4.3 Effects of NLRP3-Dependent neuroinflammation on brain function 34 4.3.1 Abnormal microglial phenotypes induced by NLRP3 dysregulation lead to prolonged and intensive neuroinflammation. 35 4.3.2 Excitatory postsynaptic structures and properties get altered in severe neuroinflammation but not in mild neuroinflammation. 36 4.3.3 Excessive NMDAR response in neuroinflammatory brain dictates abnormal repetitive behavior of mice. 37 V. REFERENCE 87DoctordCollectio

    셀룰로오스 면에 고정된 폴리피롤(PPy) 광열 입자 기반 3차원 사다리형 태양열 증발기의 성능

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    Solar evaporation, DesalinationSolar evaporation, utilizing the most abundant and clean energy source solar energy has shown promising potential in addressing global water scarcity. To improve the performance of solar evaporation systems, interfacial solar evaporators have been introduced. In this study, we propose an efficient and eco-friendly solution by integrating a 3D system inspired by ladder for interfacial solar evaporation. The structure of the ladder facilitates the vertical alignment of polypyrrole (PPy)-coated non-woven cotton fabric, enabling evaporation to occur within the spaces between the fibers. This arrangement enhances convective flow from side evaporation, thereby accelerating the evaporation process and improving overall efficiency. Under standard 1 kW m² solar irradiation, the evaporation rate reached a maximum of 2.115 kg m-² h⁻¹ based on total surface area and 3.359 kg m-² h⁻¹ based on effective surface area. Outdoor tests demonstrated impressive results, with daily freshwater production reaching 50.898 kg m-² day⁻¹ and 80.838 kg m-² day⁻¹, respectively. By harnessing natural energy, interfacial evaporation offers a sustainable solution to the high energy costs and environmental impacts associated with conventional desalination technologies. |본 논문은 태양 에너지는 가장 풍부하고 깨끗한 에너지원으로, 이를 활용한 태양 증발은 전 세계적인 물 부족 문제를 해결하는 데 유망한 가능성을 보여주고 있습니다. 태양 증발 시스템의 성능을 향상시키기 위해, 계면 태양 증발기가 도입되었습니다. 본 연구에서는 계면 태양 증발을 위해 사다리에서 영감을 얻은 3D 시스템을 통합한 효율적이고 친환경적인 해결책을 제안합니다. 사다리의 구조는 폴리피롤(PPy)로 코팅된 부직포 면직물을 수직으로 배열하여 섬유 사이 공간에서 증발이 일어나도록 하였습니다. 이 배열은 측면 증발로 인한 대류 흐름을 촉진하여 증발 과정을 가속화하고 전반적인 효율성을 향상시킵니다. 표준 1 kW m² 태양광 조사 하에서 총 표면적 기준 최대 증발 속도는 2.115 kg m-² h⁻¹, 유효 표면적 기준으로는 3.359 kg m-² h⁻¹에 도달했습니다. 실외 테스트에서도 놀라운 결과가 나타났으며, 일일 담수 생산량은 각각 50.898 kg m- ² day⁻¹ 및 80.838 kg m- ² day⁻¹에 도달했습니다. 자연 에너지를 활용함으로써 계면 증발은 기존의 담수화 기술과 관련된 높은 에너지 비용과 환경 영향을 줄일 수 있는 지속 가능한 해결책을 제공합니다.Ⅰ. Theoretical background 1 1.1 Theoretical background 1 1.2 Solar-driven interfacial evaporation 2 1.2.1 Photothermal Conversion 2 1.2.2 Photothermal materials 2 1.2.3 Black body 3 1.3 Three-dimensional Solar evaporation device 3 1.4 Natural Convection 3 1.5 Water transporting support matrix 4 II. Introduction 5 2.1 Introduction 5 III. Experimental section 11 3.1 Materials 11 3.2 Characterization 11 3.3 Preparation of photothermal cotton fabric decorated with PPy (P-NCF) 11 3.4 Fabrication of 2D and 3D P-NCF experimental solar evaporators (PLE) 12 3.5 Simulated laboratorial open evaporation experiments 12 3.6 Convection measurement by evaporation of LSE 13 3.7 Outdoor Solar Evaporation Experiment with Ladder Solar Evaporator (LSE) 13 IV. Results and Discussions 14 4.1 3D ladder type solar evaporator fabrication strategy using 2D natural fabric 14 4.2 Solar evaporation behavior of the LSE at various intervals and heights 20 4.3 Measurement of convection flow according to the Spacing and Height of the LSE 29 4.4 Outdoor Experiment Using a Solar Evaporator 33 V. Conclusion 40 5.1 Conclusion 40 VI. References 42MasterdCollectio

    예쁜 꼬마 선충을 이용한 환경 변화에 따른 걸음걸이 전환을 조절하는 신경회로적 분자적 기작 연구

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    C. elegans, Gait transition, SMB neuron, unc-29, unc-79List of Contents Abstract i List of contents ii List of tables iv List of figures v Ⅰ. INTRODUCTION 1.1 Locomotion in animals 1 1.2 Gait transition in animals 1 1.3 Locomotion in C. elegans 3 1.4 Gait transition in C. elegans 5 1.5 Summary 6 Ⅱ. MATERIALS AND METHODS Ⅲ. RESULTS 3.1 Characteristics of different types of locomotive strategies in C. elegans 25 3.2 Gait transition is mediated by the head motor neuron SMB and SMD 31 3.3 The SMB neurons control head muscle activity to restrict head locomotion 42 3.4 Isolation of mutant strains that exhibit abnormal gait transition and swimming behavior 47 3.5 NCA complex protein UNC-79 regulates gait transition and swimming behavior 53 3.6 Acetylcholine receptor protein UNC-29 has a role in gait transition and swimming behavior 64 3.7 Gait transition-induced calcium activity of body muscles is mediated by nAChR 73 3.8 unc-29 may act downstream of SMB-mediated head muscle control in gait transition and swimming 77 3.9 Candidate neurotransmitter in gait transition 79 3.10 Candidate sensory neurons in gait transition 79 Ⅳ. DISCUSSIONS 4.1 Crawling-to-Swimming transition is regulated by head motor neurons: SMB and SMD 84 4.2 NCA channel subunit gene unc-79 regulates body locomotion to mediate gait transition and sustenance of gaits. 85 4.3 nAChR subunit unc-29 gene in muscles regulates Ca2+ activity to mediate proper gaits 86 4.4 Selecting gaits are regulated by complex neural circuit mechanisms in C. elegans 87 Ⅴ. REFERENCES Ⅵ. SUMMARY IN KOREANS VII. APPENDIX A FMRFamide-like neuropeptide FLP-12 signaling regulates head locomotive behaviors in Caenorhabditis elegans 99DoctordCollectio

    Optimized Red Blood Cell Segmentation in Holographic Imaging through Integration of Self-Supervised Learning and Diffusion Models

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    Red blood cells, Digital Holography, Deep Learning, Diffusion Model, Self-Supervised learningI. INTRODUCTION 1 II. METHODOLOGY 6 2.1 Data Acquisition 6 2.2 Digital Holographic Microscopy 7 2.3 Synthetic RBC Image Generation Using Diffusion Model 9 2.4 Self-Supervised Learning for Pretrained Model 13 2.5 Watershed Algorithm 16 2.6 Evaluation Metrics 17 III. EXPERIMENTAL SETUPS 18 3.1 Datasets 18 3.2 Implementation Setups 18 IV. RESULTS 20 4.1 Generated Synthetic RBC Data 20 4.2 Semantic Segmentation 21 4.3 Effectiveness of Losses in Self-Supervised Learning 24 4.4 Experiments on the Effect of SSCRL in Limited Training Data 25 4.5 Phenotypical Assessment of Red Blood Cells 26 V. CONCLUSION 27MasterdCollectio

    단순 수포성 표피박리증과 암에서 케라틴의 구조-기능 상관관계 연구

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    Keratin 5/14 (K5/K14), Keratin 8/19 (K8/K19), Epidermolysis Bullosa Simplex (EBS), Cancer, GSK3β, 14-3-3, Phosphorylation, Filament assembly, Protein interactionsⅠ. Introduction 1 1.1 Keratin5/Keratin14 and Epidermolysis Bullosa Simplex (EBS) 2 1.2 Keratin8/Keratin19 and Cancer 4 II. Methods and Materials 6 2.1 EBS mutant scoring and correlation analysis 6 2.1.1 Homology modeling by MODELLER 6 2.1.2 Aggregation scoring and correlation analysis 8 2.2 Plasmids and Protein expression 8 2.2.1 Mutagenesis and cloning 8 2.2.2 Transformation and protein expression 10 2.3 Protein purification 11 2.3.1 Purification of keratin 11 2.3.2 Purification of GSK3β and GST 12 2.3.3 Purification of 14-3-3 13 2.4 Assembly of Keratin filament 13 2.5 Assessing keratin filament assembly and bundling 14 2.5.1 Sedimentation assay 14 2.5.2 Transmission Electron Microscopy (TEM) 14 2.6 Measurement of material properties of K5/K14 15 2.7 Binding assay of K8/K19 filament with other protein 16 2.7.1 Co-sedimentation assay 16 2.7.2 Nuclear Magnetic Resonance (NMR) 16 III. Results 17 3.1 K5/K14 filaments show altered material properties in EBS mutants 17 3.1.1 Homology modeling 17 3.1.2 Correlation analysis between aggregation score and severity 21 3.1.3 Mutagenesis results 35 3.1.4 Protein purification 36 3.1.5 Sedimentation assay 38 3.1.6 TEM 39 3.1.7 Rheology Analysis 41 3.2 Functional differences between K8/K19 and K8/K19(S35E) 43 3.2.1 Protein purification 43 3.2.2 Sedimentation Assay 47 3.2.3 Comparison of wild-type and mutants (TEM, NMR) 49 3.2.4 Interaction with 14-3-3 (TEM, NMR, co-Sedimentation) 51 3.2.5 Interaction with GSK3β (TEM, NMR, co-Sedimentation) 56 IV. Discussion and Conclusion 61 V. Acknowledgement 65 VI. References 66 Abstract in Korean 70MasterdCollectio

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