請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101466完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王兆麟 | zh_TW |
| dc.contributor.advisor | Jaw-Lin Wang | en |
| dc.contributor.author | 劉倩嘉 | zh_TW |
| dc.contributor.author | Janet Lau | en |
| dc.date.accessioned | 2026-02-03T16:29:59Z | - |
| dc.date.available | 2026-02-04 | - |
| dc.date.copyright | 2026-02-03 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2026-01-21 | - |
| dc.identifier.citation | 1. Hablitz, L.M. and M. Nedergaard, The Glymphatic System: A Novel Component of Fundamental Neurobiology. J Neurosci, 2021. 41(37): p. 7698–7711.
2. Fatima, G., et al., Vascular and glymphatic dysfunction as drivers of cognitive impairment in Alzheimer's disease: Insights from computational approaches. Neurobiol Dis, 2025. 208: p. 106877. 3. Xiong, Y., et al., Advances in the study of the glymphatic system and aging. CNS Neurosci Ther, 2024. 30(6): p. e14803. 4. Silva, I., et al., Glymphatic system, AQP4, and their implications in Alzheimer's disease. Neurol Res Pract, 2021. 3(1): p. 5. 5. Gao, Y., K. Liu, and J. Zhu, Glymphatic system: an emerging therapeutic approach for neurological disorders. Front Mol Neurosci, 2023. 16: p. 1138769. 6. Jessen, N.A., et al., The Glymphatic System: A Beginner's Guide. Neurochem Res, 2015. 40(12): p. 2583–99. 7. Stark, R.J., H. Choi, and F.S. Lamb, Neuronal ASIC1A As a Cerebral pH Sensor: Bringing the Flow. Circ Res, 2019. 125(10): p. 921–923. 8. Lai, K., et al., Glutamate acts on acid-sensing ion channels to worsen ischaemic brain injury. Nature, 2024. 631(8022): p. 826–834. 9. Qi, X., et al., Pharmacological Validation of ASIC1a as a Druggable Target for Neuroprotection in Cerebral Ischemia Using an Intravenously Available Small Molecule Inhibitor. Front Pharmacol, 2022. 13: p. 849498. 10. Lim, J., Tai, H.-H., Liao, W.-H., Chu, Y.-C., Hao, C.-M., Huang, Y.-C., Lee, C.-H., Lin, S.-S., Hsu, S., Chien, Y.-C., Lai, D.-M., Chen, W., Chen, C.-C., & Wang, J.-L., ASIC1a is required for neuronal activation via low-intensity ultrasound stimulation in mouse brain. eLife, 2021. 10. 11. Papadopoulos, E.S. and R. Mani, The Role of Ultrasound Therapy in the Management of Musculoskeletal Soft Tissue Pain. Int J Low Extrem Wounds, 2020. 19(4): p. 350–358. 12. Tyler, W.J., et al., Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound. PLoS One, 2008. 3(10): p. e3511. 13. Kim, T., et al., Effect of Low Intensity Transcranial Ultrasound Stimulation on Neuromodulation in Animals and Humans: An Updated Systematic Review. Front Neurosci, 2021. 15: p. 620863. 14. Wu, C.H., et al., Very Low-Intensity Ultrasound Facilitates Glymphatic Influx and Clearance via Modulation of the TRPV4-AQP4 Pathway. Adv Sci (Weinh), 2024. 11(47): p. e2401039. 15. Cloutier, G., et al., Quantitative ultrasound imaging of soft biological tissues: a primer for radiologists and medical physicists. Insights Imaging, 2021. 12(1): p. 127. 16. Xin, Z., et al., Clinical applications of low-intensity pulsed ultrasound and its potential role in urology. Transl Androl Urol, 2016. 5(2): p. 255–66. 17. Darrow, D.P., Focused Ultrasound for Neuromodulation. Neurotherapeutics, 2019. 16(1): p. 88–99. 18. Cox, S.S., et al., A Comprehensive Review of Low-Intensity Focused Ultrasound Parameters and Applications in Neurologic and Psychiatric Disorders. Neuromodulation, 2025. 28(1): p. 1–15. 19. Ventre, D.M. and A.N. Koppes, The Body Acoustic: Ultrasonic Neuromodulation for Translational Medicine. Cells Tissues Organs, 2016. 202(1-2): p. 23–41. 20. Song, M., et al., Ultrasonic neuromodulation mediated by mechanosensitive ion channels: current and future. Front Neurosci, 2023. 17: p. 1232308. 21. Kim, Y.H., et al., Acoustic radiation force for analyzing the mechanical stress in ultrasound neuromodulation. Phys Med Biol, 2023. 68(13). 22. Patra, S. and S.B. Grover, Physical Principles of Elastography: A Primer for Radiologists. Indographics, 2023. 01(01): p. 027–040. 23. Chu, Y.C., et al., Activation of Mechanosensitive Ion Channels by Ultrasound. Ultrasound Med Biol, 2022. 48(10): p. 1981–1994. 24. <Analytical modelling of ultrasonically induced tissue heating.pdf>. 25. Collins, M.N. and K.A. Mesce, A review of the bioeffects of low-intensity focused ultrasound and the benefits of a cellular approach. Front Physiol, 2022. 13: p. 1047324. 26. Humphrey, V.F., Ultrasound and matter--physical interactions. Prog Biophys Mol Biol, 2007. 93(1-3): p. 195–211. 27. Thomas R. Nelson PhD, J. Brian Fowlkes PhD, and C.C.C.P. Jacques S. Abramowicz MD, Ultrasound Biosafety Considerations for the Practicing Sonographer and Sonologist. Journal of Ultrasound in Medicine, 2009. 28. Jin, J., et al., Transcranial focused ultrasound precise neuromodulation: a review of focal size regulation, treatment efficiency and mechanisms. Front Neurosci, 2024. 18: p. 1463038. 29. Li, H., et al., Effects of skull properties on continuous-wave transcranial focused ultrasound transmission. J Acoust Soc Am, 2025. 157(4): p. 2336–2349. 30. Pan, Y., et al., A transcranial multiple waves suppression method for plane wave imaging based on Radon transform. Ultrasonics, 2024. 143: p. 107405. 31. Zhu, Z., et al., Syncing the brain's networks: dynamic functional connectivity shifts from temporal interference. Front Hum Neurosci, 2024. 18: p. 1453638. 32. Shimokawa, H., et al., Pivotal trial of low-intensity pulsed ultrasound therapy for early Alzheimer's disease: Rationale and design. J Alzheimers Dis Rep, 2025. 9: p. 25424823241312108. 33. Liu, T., et al., Sonogenetics: Recent advances and future directions. Brain Stimul, 2022. 15(5): p. 1308–1317. 34. Karageorgou, M.-A., K. Tsakmakidis, and D. Stamopoulos, Ferroelectric/Piezoelectric Materials in Energy Harvesting: Physical Properties and Current Status of Applications. Crystals, 2024. 14(9). 35. Shrout, T.R. and S.J. Zhang, Lead-free piezoelectric ceramics: Alternatives for PZT? Journal of Electroceramics, 2007. 19(1): p. 113–126. 36. Jiang, X., et al., A Review of Low-Intensity Pulsed Ultrasound for Therapeutic Applications. IEEE Trans Biomed Eng, 2019. 66(10): p. 2704–2718. 37. Xu, A., J. Yuan, and J. Gao, Leveling Method of Working Platform Based on PZT Electromechanical Coupling Effect. Micromachines (Basel), 2025. 16(7). 38. Li, T., R.Y. Gianchandani, and Y.B. Gianchandani, Micromachined bulk PZT tissue contrast sensor for fine needle aspiration biopsy. Lab Chip, 2007. 7(2): p. 179–85. 39. Jiang, X., W.T. Ng, and J. Chen, A Miniaturized Low-Intensity Ultrasound Device for Wearable Medical Therapeutic Applications. IEEE Trans Biomed Circuits Syst, 2019. 13(6): p. 1372–1382. 40. Lee, W., et al., All-in-one low-intensity pulsed ultrasound stimulation system using piezoelectric micromachined ultrasonic transducer (pMUT) arrays for targeted cell stimulation. Biomed Microdevices, 2017. 19(4): p. 86. 41. Reskal, H., et al., Modeling high-frequency ultrasonic transducers incorporating piezoelectric multilayers using equivalent circuits. Engineering Research Express, 2025. 7(3). 42. Hu, Y.Y., et al., Transcranial low-intensity ultrasound stimulation for treating central nervous system disorders: A promising therapeutic application. Front Neurol, 2023. 14: p. 1117188. 43. Iliff, J.J., et al., A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med, 2012. 4(147): p. 147ra111. 44. Ding, Z., et al., The glymphatic system: a new perspective on brain diseases. Front Aging Neurosci, 2023. 15: p. 1179988. 45. Corbali, O. and A.I. Levey, Glymphatic system in neurological disorders and implications for brain health. Front Neurol, 2025. 16: p. 1543725. 46. Bohr, T., et al., The glymphatic system: Current understanding and modeling. iScience, 2022. 25(9): p. 104987. 47. Iliff, J.J., et al., Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci, 2013. 33(46): p. 18190–9. 48. Duan, W., Y. Zhou, and H. Liu, The glymphatic system in Huntington's disease. J Huntingtons Dis, 2025. 14(3): p. 279–290. 49. Liu, K., et al., Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus. JCI Insight, 2021. 6(17). 50. Carlstrom, L.P., et al., A clinical primer for the glymphatic system. Brain, 2022. 145(3): p. 843–857. 51. Nedergaard, M. and S.A. Goldman, Glymphatic failure as a final common pathway to dementia. Science, 2020. 370(6512): p. 50–56. 52. Rook, M.L., M. Musgaard, and D.M. MacLean, Coupling structure with function in acid-sensing ion channels: challenges in pursuit of proton sensors. J Physiol, 2021. 599(2): p. 417–430. 53. Wang, Y., et al., The Role of ASIC1a in Inflammatory Immune Diseases: A Potential Therapeutic Target. Front Pharmacol, 2022. 13: p. 942209. 54. Tolino, L.A., et al., Insights into the mechanism of pore opening of acid-sensing ion channel 1a. J Biol Chem, 2011. 286(18): p. 16297–307. 55. M Nedergaard, et al., Dynamics of interstitial and intracellular pH in evolving brain infarct. American Journal of Physiology, 1991. 260(3). 56. Liu, S., et al., Acid-sensing ion channels: potential therapeutic targets for neurologic diseases. Transl Neurodegener, 2015. 4: p. 10. 57. Jasti, J., et al., Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature, 2007. 449(7160): p. 316–23. 58. Krauson, A.J., A.C. Rued, and M.D. Carattino, Independent contribution of extracellular proton binding sites to ASIC1a activation. J Biol Chem, 2013. 288(48): p. 34375–83. 59. Yang, H., et al., Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating mechanism. PLoS Biol, 2009. 7(7): p. e1000151. 60. Sherwood, T.W., E.N. Frey, and C.C. Askwith, Structure and activity of the acid-sensing ion channels. Am J Physiol Cell Physiol, 2012. 303(7): p. C699–710. 61. Sun, A.W., et al., The Role of Zinc in Modulating Acid-Sensing Ion Channel Function. Biomolecules, 2023. 13(2). 62. Liu, Y., et al., Molecular determinants of ASIC1 modulation by divalent cations. Sci Rep, 2024. 14(1): p. 2320. 63. Joeres, N., et al., Functional and pharmacological characterization of two different ASIC1a/2a heteromers reveals their sensitivity to the spider toxin PcTx1. Sci Rep, 2016. 6: p. 27647. 64. Zhang, Z., et al., Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention. Cell Death Discov, 2023. 9(1): p. 330. 65. Song, N., et al., Acid-sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis. J Cell Mol Med, 2019. 23(5): p. 3429–3440. 66. Wang, Y.Z., et al., Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction. Elife, 2015. 4. 67. Armstrong, A., et al., Inhibition of ASIC1a Improves Behavioral Recovery after Stroke. eNeuro, 2024. 11(2). 68. Ruan, N., et al., Acid-Sensing Ion Channels and Mechanosensation. Int J Mol Sci, 2021. 22(9). 69. Chu, X.P., K.A. Grasing, and J.Q. Wang, Acid-sensing ion channels contribute to neurotoxicity. Transl Stroke Res, 2014. 5(1): p. 69–78. 70. Chien, Y.C., et al., Lacking ASIC1a in ASIC4-positive amygdala/bed nucleus of the stria terminalis (BNST) neurons reduces anxiety and innate fear in mice. J Biomed Sci, 2025. 32(1): p. 43. 71. Liao, W.-H., et al., Enhancing glymphatic function with very low-intensity ultrasound via the transient receptor potential vanilloid-4-aquaporin-4 pathway. 2023. 72. Vullo, S. and S. Kellenberger, A molecular view of the function and pharmacology of acid-sensing ion channels. Pharmacol Res, 2020. 154: p. 104166. 73. Nakada, T., et al., Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow. Int J Mol Sci, 2017. 18(8). 74. Yoo, S., et al., Focused ultrasound excites cortical neurons via mechanosensitive calcium accumulation and ion channel amplification. Nat Commun, 2022. 13(1): p. 493. 75. Uria-Avellanal, C. and N.J. Robertson, Na(+)/H(+) exchangers and intracellular pH in perinatal brain injury. Transl Stroke Res, 2014. 5(1): p. 79–98. 76. Hersh, D.S., et al., Pulsed ultrasound expands the extracellular and perivascular spaces of the brain. Brain Res, 2016. 1646: p. 543–550. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/101466 | - |
| dc.description.abstract | 超音波長期以來已廣泛應用於診斷與治療領域。近年來，低強度超音波（low-intensity ultrasound, LIUS）逐漸成為腦部研究中一種非侵入性的神經調控策略。越來越多的研究證據顯示，LIUS 可作為治療腦部疾病的非侵入性神經調控方法；其能以機械力精準作用於腦組織，同時避免造成不可逆的組織損傷與熱效應累積。
膠淋巴系統（glymphatic system）是大腦的清除途徑，負責腦脊髓液（cerebrospinal fluid, CSF）與腦間質液（interstitial fluid, ISF）之間的交換，以及代謝廢物的清除。而此過程高度依賴水通道蛋白四型（aquaporin-4, AQP4）的功能。膠淋巴系統功能受損已被認為與多種神經系統疾病的發生相關。 本研究探討酸敏感離子通道一型（Acid-Sensing Ion Channel 1a, ASIC1a）在膠淋巴系統功能中的角色，以及其是否可受到 LIUS 調控。研究中使用 ASIC1a 基因剔除（knockout, KO）小鼠與野生型（wild-type, WT）小鼠，並在有或無 LIUS 刺激的條件下，進行以螢光示蹤劑為基礎的腦脊髓液流動分析。 研究結果顯示，ASIC1a 會透過降低 AQP4 所介導的液體運輸而調節膠淋巴系統功能（初步可見趨勢為抑制）；相對地，LIUS 能夠對抗此抑制趨勢，並促進膠淋巴清除功能。這些結果指出，LIUS 可能作為一種調控 ASIC1a 介導之膠淋巴功能障礙的潛在工具，為與腦部清除功能受損相關的神經系統疾病提供一項具前景的治療策略。 | zh_TW |
| dc.description.abstract | Ultrasound has been in diagnostic and therapeutic use for a long while. In recent focus, low-intensity ultrasound (LIUS) has come into the non-invasive neuromodulation strategy in brain research. Growing evidence indicates that LIUS has emerged as a non-invasive neuromodulation approach to treating brain disorders. It has the ability to target brain tissue with mechanical force without causing irreversible damage and thermal accumulation.
The glymphatic system is the brain’s clearance pathway responsible for cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange and metabolic waste removal, where aquaporin-4 (AQP4) channels are a major factor of the mechanism. Glymphatic function dysfunction is critical in culmination of neurological disorders. This study seeks to identify how Acid-Sensing Ion Channel 1a (ASIC1a) impact on glymphatic system function and its modulation by LIUS. ASIC1a knockout (KO) and wild-type (WT) mice are subjected to fluorescent tracer–based CSF flow analysis with or without LIUS stimulation. Our results demonstrate that ASIC1a is involved in modulating glymphatic function, with an inhibitory tendency, by reducing AQP4-mediated fluid transport. On the other hand, LIUS alleviates this inhibitory tendency and promotes glymphatic clearance. These findings establish LIUS as a potential modulator of ASIC1a in glymphatic dysfunction, offering a promising therapeutic strategy for neurological disorders associated with impaired brain clearance. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2026-02-03T16:29:59Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2026-02-03T16:29:59Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
Acknowledgement ii 中文摘要 iv Abstract v List of Contents vi List of Figures x List of Tables xiii List of Symbols and Technical Abbreviations xiv Chapter 1 Introduction 1 1-1 Research Background 1 1-1-1 Glymphatic System 1 1-1-2 Importance of Brain Research in Glymphatic System 1 1-1-3 Acid Sensing Ion Channel 1a 2 1-1-4 Low Intensity Ultrasound 2 1-2 Literature Review 3 1-2-1 Low Intensity Ultrasound 3 1-2-1-1 Basics of Ultrasound 3 1-2-1-2 Types of Mechanical Waves in Ultrasound 3 1-2-1-3 Key Principle & Mechanism of Low Intensity Ultrasound 4 1-2-1-4 Acoustic Mechanism 4 1-2-1-5 Biological Mechanism 6 1-2-1-6 Physical Mechanism 7 1-2-1-7 Low-Intensity Ultrasound Attenuation in Biological Tissue 7 1-2-1-7 1 Transmission and reflection at interfaces 8 1-2-1-8 Ultrasound Parameters 8 1-2-1-9 Factors Affecting Low Intensity Ultrasound Efficacy 12 1-2-2 Piezoelectricity 13 1-2-2-1 The Piezoelectric Effect 13 1-2-2-2 The Reverse Piezoelectric Effect 13 1-2-2-3 Use of Piezoelectric Ultrasound Transducer in Low-Intensity Ultrasound Research 13 1-2-3 Glymphatic System 14 1-2-3-1 Glymphatic System Mechanism 14 1-2-3-2 Factors Affecting Glymphatic System 15 1-2-3-3 Role of Glymphatic System in Pathology 16 1-2-4 Acid Sensing Ion Channel 1a (ASIC1a) 18 1-2-4-1 ASIC1a Mechanism 18 1-2-4-2 Regulators of ASIC1a 22 1-2-4-3 ASIC1a’s Role in Apoptosis 23 1-2-4-4 Mechanical Modulation of ASIC1a Activation 23 1-2-4-5 Pathological Role of ASIC1a 23 1-3 Aims of Research 24 Chapter 2 Material 25 2-1 Experimental Equipment 25 2-1-1 Function Generator And Amplifier 25 2-1-2 Piezoelectric Ceramic Ultrasonic Transducer 26 2-1-3 Syringe Pump 27 2-1-4 Stereotactic Instrument 28 2-1-5 Gas Anaesthesia Unit 29 2-1-6 Specimen Slicer 30 2-1-7 Fluorescent Microscope with Power Supply and Camera 31 2-2 Animals Tested 32 2-3 Chemicals 33 2-4 Software Application for Analysis 34 2-4-1 Software Application for Image Analysis 34 2-4-2 Software Application For Result Analysis and Statistical Analysis 35 Chapter 3 Experimental Design and Method 36 3-1 Experimental Framework 36 3-2 Experiment 1: Determine ASIC1a Effect On CSF Penetration As A Study Of Glymphatic System 36 3-2-1 Anaesthesia and Preparation 37 3-2-2 Procedure for Cannulation 38 3-2-3 Surgical Procedure and Fluorescent Tracer Injection 39 3-2-4 Experimental Set – Up For No Ultrasound Stimulation Group 40 3-2-5 Euthanasia and Perfusion 41 3-2-6 Brain Extraction 41 3-2-7 Brain Sectioning 42 3-2-8 Mounting of Brain Section Onto Microscope Slides 42 3-2-9 Fluorescent Imaging 44 3-2-10 Image Analysis 44 3-3 Experiment 2: Determine How Low Intensity Ultrasound Stimulation Modulates ASIC1a On CSF Penetration, Determine Low Intensity Ultrasound ‘s Direct Effect On CSF Penetration, As A Study of Glymphatic System 46 3-3-1 Tracer Injection 46 3-3-2 Ultrasound Stimulation 46 Chapter 4 Experimental Results 49 4-1 Significance of Fluorescent Imaging Results 50 4-2 Fluorescence Analysis 50 4-2-1 Percentage Area Analysis 51 4-2-2 Statistical Analysis of Percentage Area Results 53 4-2-3 Overall Intensity Analysis 54 4-2-4 Statistical Analysis of Overall Intensity Results 56 4-2-5 Normalized Sectioned Intensity Analysis 57 4-2-6 Statistical Analysis of Normalized Sectioned Intensity Results 59 Chapter 5 Results Discussion 60 5-1 ASIC1a’s Involvement In Modulating Glymphatic System Function 60 5-2 Role of Aquaporin-4 (AQP4) In Inhibitory Tendency 61 5-3 Effect of Low Intensity Ultrasound On Glymphatic Function And ASIC1a As A Modulator 62 Chapter 6 Conclusion and Future Direction 65 List of References 67 | - |
| dc.language.iso | en | - |
| dc.subject | 低強度超音波 | - |
| dc.subject | 膠淋巴系統 | - |
| dc.subject | 酸敏感離子通道一型 | - |
| dc.subject | 神經退化性疾病 | - |
| dc.subject | ASIC1a | - |
| dc.subject | Low-Intensity Ultrasound | - |
| dc.subject | Glymphatic System | - |
| dc.subject | Neurodegenerative Diseases | - |
| dc.title | 低強度超音波作為酸敏感離子通道一型對膠淋巴系統功能的調節因子 | zh_TW |
| dc.title | Low Intensity Ultrasound as A Modulator of ASIC1a on Glymphatic System | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 陳志成;陳文翔 | zh_TW |
| dc.contributor.oralexamcommittee | Chih-Cheng Chen;Wen-Shiang Chen | en |
| dc.subject.keyword | 低強度超音波,膠淋巴系統酸敏感離子通道一型神經退化性疾病 | zh_TW |
| dc.subject.keyword | ASIC1a,Low-Intensity UltrasoundGlymphatic SystemNeurodegenerative Diseases | en |
| dc.relation.page | 71 | - |
| dc.identifier.doi | 10.6342/NTU202600158 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2026-01-22 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| dc.date.embargo-lift | 2026-02-04 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-114-1.pdf 授權僅限NTU校內IP使用（校園外請利用VPN校外連線服務） | 3.25 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。