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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： daniel Adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

Wafer‑Scale Ag_(2)S‑Based Memristive Crossbar Arrays with Ultra‑Low Switching‑Energies Reaching Biological Synapses

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Nano-Micro Letters 2025年第3期17卷 328-339页

作者： Yuan Zhu Tomas Nyberg Leif Nyholm daniel primetzhofer Xun Shi Zhen Zhang Division of Solid‑State Electronics Department of Electrical EngineeringUppsala University75121 UppsalaSweden Department of Chemistry Uppsala UniversityUppsalaSweden Department of physics and Astronomy Uppsala UniversityUppsalaSweden State Key Laboratory of High performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050People’s Republic of China

Memristive crossbar arrays(MCAs)offer parallel data storage and processing for energy-efficient neuromorphic ***,most wafer-scale MCAs that are compatible with complementary metal-oxide-semiconductor(CMOS)technology still suffer from substantially larger energy consumption than biological synapses,due to the slow kinetics of forming conductive paths inside the memristive *** we report wafer-scale Ag_(2)S-based MCAs realized using CMOS-compatible processes at temperatures below 160℃.Ag_(2)S electrolytes supply highly mobile Ag+ions,and provide the Ag/Ag_(2)S interface with low silver nucleation barrier to form silver filaments at low energy *** further enhancing Ag+migration in Ag_(2)S electrolytes via microstructure modulation,the integrated memristors exhibit a record low threshold of approximately−0.1 V,and demonstrate ultra-low switching-energies reaching femtojoule values as observed in biological *** low-temperature process also enables MCA integration on polyimide substrates for applications in flexible ***,the intrinsic nonidealities of the memristive units for deep learning can be compensated by employing an advanced training *** impressive accuracy of 92.6%in image recognition simulations is demonstrated with the MCAs after the *** demonstrated MCAs provide a promising device option for neuromorphic computing with ultra-high energy-efficiency.

关键词： Wafer-scale Ag_(2)S films Reactive sputter Silver nucleation Ag^(+)migration Energy-efficient neuromorphic computing

Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan daniel Fulton Zubair Ahmed WMatthijs Blankesteijn Sébastien Foulquier Department of pharmacology and Toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-School for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma Sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-School for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands Department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel Jonathan Grossberg daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2969-2981页

作者： Mackenzie M.Spicer Jianqi Yang daniel Fu Alison N.DeVore Marisol Lauffer Nilufer S.Atasoy Deniz Atasoy Rory A.Fisher Department of Neuroscience and pharmacology University of Iowa Carver College of MedicineIowa CityIAUSA Iowa Neuroscience Institute University of Iowa Carver College of MedicineIowa CityIAUSA Interdisciplinary Graduate program in Molecular Medicine University of Iowa Carver College of MedicineIowa CityIAUSA Neural Circuits and Behavior Core University of Iowa Carver College of MedicineIowa CityIAUSA

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s *** hippocampal neurogenesis is reduced in patients with Alzheimer’s *** stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s ***,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly ***,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in ***,we generated novel RGS6fl/fl;App_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse *** found that voluntary running in App_(SWE) mice restored their hippocampal cognitive impairments to that of control *** cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal *** hippocampal neurogenesis was reduced in sedentary App_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor ***6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing ***,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in App_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

关键词： adult hippocampal neurogenesis Alzheimer’s disease dentate gyrus exercise learning/memory neural precursor cells regulator of G protein signaling 6(RGS6)

Challenges to Coordination: Understanding Intergovernmental Friction During Disasters

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International Journal of Disaster Risk Science 2019年第3期10卷 306-316页

作者： daniel p.Aldrich Department of political Science School of Public Policy and Urban Affairs Northeastern UniversityBoston

While idealized crisis response involves smooth coordination between relevant actors, friction between levels of government and between the state and civil society in responding to catastrophe may be more *** article builds a theory of cross-level friction during and after crisis by analyzing the conditions when discord is most likely. With a medium-N dataset(N = 18) of disaster responses from, among other countries, Chile, Haiti, Japan,North America, the philippines, and Somalia, I carry out quantitative and qualitative analysis of cases with a variety of levels of friction to investigate the conditions that lead to misalignment. Tobit regression, qualitative comparative analysis, and case studies that take into account levels of economic development, government structure, nongovernmental organization density, and levels of damage demonstrate that low levels of development, lower levels of economic costs from the crisis, and poor planning and logistical infrastructure correlate with a higher likelihood of friction between disaster response *** not definitive, these findings come with theoretical and practical implications as climate change makes extreme weather events and future disasters more likely and more powerful.

关键词： Bottom up culture Case studies Disaster coordination Qualitative comparative analysis Tobit regression analysis Top down institutions

New developments in the treatment of castration resistant prostate cancer

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Asian Journal of Andrology 2014年第4期16卷 555-560页

作者： Roxanne Wadia daniel p petrylak Department of Medicine Smilow Cancer Center Yale University School of Medicine Yale Comprehensive Cancer Center New Haven Connecticut USA

In the past 5 years, the treatment and understanding of metastatic castrate resistant prostate cancer （CRpC） have improved dramatically. Our understanding of the mechanisms of castration resistance has allowed for the development of new drugs to target prostate cancer, and our understanding of genetic mutations may give us new tools with which to more accurately diagnose and be able to predict the course of this heterogeneous disease. This article summarizes the recent advances in the understanding of the development of CRpC, as well as the new drugs and targets, which have evolved from this basic research.

关键词： castration resistant prostate cancer abiraterone enzalutamide chemotherapy docetaxel cabazitaxel pSMA antibody

Nanomechanical hydrodynamic force sensing using suspended microfluidic channels

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Microsystems & Nanoengineering 2023年第3期9卷 95-102页

作者： Alberto Martín-pérez daniel Ramos Optomechanics Lab Instituto de Ciencia de Materiales de Madrid(ICMMCSIC)3 Sor Juana Inés de la Cruz(Madrid)E-28049 MadridSpain

Microfluidics has demonstrated high versatility in the analysis of in-flow particles and can even achieve mechanical properties measurements of biological cells by applying hydrodynamic ***,there is currently no available technique that enables the direct measurement and tracking of these hydrodynamic forces acting on a flowing *** this work,we introduce a novel method for the direct measurement of the hydrodynamic force actuating on an in-flow particle based on the analysis of the induced resonance changes of suspended microchannel resonators(SMRs).This hydrodynamic force sensitivity depends on the device used;therefore,we considered the geometry and materials to advance this dependency on the SMR resonance frequency.

关键词： hydrodynamic applying flow

Managing water for life

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Frontiers of Environmental Science & Engineering 2012年第2期6卷 255-264页

作者： daniel p.LOUCKS Haifeng JIA Civil and Environmental Engineering Comell UniversityIthaca NY 14853USA School of Environment Tsinghua UniversityBeijing 100084China

Water is essential for life. In spite of the entire engineering infrastructure devoted to the treatment, regulation and beneficial uses of water, occasionally sufficient quantities and qualities of water become scarce. When this happens, just how do we decide how much less water to allocate to all of us and the activities we engage in to sustain and enhance our quality of life？ This paper addresses some of the complexities of answering such a question, especially as society increasingly recognizes the need to provide flow regimes that will maintain healthy aquatic and floodplain ecosystems that also impact the economic, physical and even the spiritual quality of our lives. For we depend on these ecosystems to sustain our wellbeing. We are indeed a part of our ecosystems. We depend upon on aquatic ecosystems to moderate river flow qualities and quantities, reduce the extremes of floods and droughts, reduce erosion, detoxify and decompose water- borne wastes, generate and preserve flood plain soils and renew their fertility, regulate disease carrying organisms, and to enhance recreational benefits of river systems. This question of deciding just how much water to allocate to each water user and for the maintenance of viable aquatic ecosystems, especially when there is not enough, is a complex, and largely political, issue. This issue is likely to become even more complex and political and contentious in the future as populations grow and as water quantities and their qualities become even more variable and uncertain.

关键词： water stress aquatic ecosystems sustainablewater resource allocations ecosystem water requirements