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Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

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Neural Regeneration Research 2024年第9期19卷 1954-1960页

作者： Kinya Matsuo hideaki Nshihara Yamaguchi University Graduate School of Medicine YamaguchiJapan Department of Neurotherapeutics Yamaguchi UniversityUbeJapan

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous ***-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s ***,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal ***,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective *** elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional ***,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been *** in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain *** this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell ***,we discuss the potential future directions for blood-brain barrier research.

关键词： Alzheimer’s disease blood-brain barrier human induced pluripotent stem cells

Fragile Link Structure in Page Rank Computation

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Fragile Link Structure in Page Rank Computation

Joint 48th IEEE Conference on Decision and Control and 28th Chinese Control Conference

作者： hideaki ishii Roberto Tempo Department of Computational Intelligence and Systems Science Tokyo Institute of Technology IEIIT-CNR Politecnico di Torino

In this paper,we study the so-called Page Rank algorithm used at Google that determines the importance of each *** first provide a brief overview of this ***,we consider the problem of computing the changes in Page Rank values when the web data contains erroneous link *** on interval matrix techniques,we develop an efficient centralized algorithm using linear *** theoretical results are verified by means of extensive simulations for a small web with 150 pages and a larger web of 1,200 pages.

关键词： Fragile links Interval matrices Page Rank algorithm Search engines

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用于旋翼飞机开发研究的多分野解析框架

Transactions of Nanjing University of Aeronautics and Astronautics 2024年第1期41卷 43-52页

作者： TANABE Yasutada SUGAWARA hideaki KIMURA Keita 日本宇宙航空研究开发机构航空技术部日本东京181-0015

介绍了日本宇宙航空研究开发机构研发的用于旋翼飞机的多分野解析框架。Heli Design是在各种旋翼飞机初期概念设计时使用的软件;rFlight可以提供在各种飞行条件下的平衡解析和线性化飞行模型;rBET/RMT是基于叶片要素理论的低保真度空力... 详细信息

介绍了日本宇宙航空研究开发机构研发的用于旋翼飞机的多分野解析框架。Heli Design是在各种旋翼飞机初期概念设计时使用的软件;rFlight可以提供在各种飞行条件下的平衡解析和线性化飞行模型;rBET/RMT是基于叶片要素理论的低保真度空力解析软件,和rMode提供的结构模型结合,可以推测旋转翼的弹性变形和各种飞行条件下的空力负载;rFlow3D是基于CFD计算的高保真度数值模拟软件;rGrid系列自动网格构造工具为其提供简单的网格生成;基于rFlow3D的计算结果,r Noise可以预测在任何观测点的噪声。这些软件已经广泛地被应用在各种新型旋翼飞机的开发研究中,其计算精度也已被各种实验结果所应证。

关键词：旋翼飞机多分野解析高保真模拟设计工具

Synergy of Prediction Rule and Total Synthesis in Solving the Stereochemical Puzzle of Valactamides

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Precision Chemistry 2024年第3期2卷 120-126页

作者： Tao Zhang Jiaxuan Feng hideaki Oikawa Yian Guo Tao Ye State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate SchoolShenzhen 518055China Innovation Center of Marine Biotechnology and Pharmaceuticals School of Biotechnology and Health SciencesWuyi UniversityJiangmen 529020China QianYan(Shenzhen)Pharmatech.Ltd. Shenzhen 518172China

Natural products with diverse functional groups and stereo-genic centers have inspired therapeutics and underpin the modern drug discovery *** three-dimensional molecular structures need to be unambiguously determined in order to be realized as clinical candidates or to achieve further activity-guided structural *** recent advances in spectroscopic methods have made it possible for researchers to determine the structures of microgram samples of complex natural products,there is no universally accepted method for determining the relative and absolute configuration of a naturally occurring *** report the determination of the full stereostructure of valactamide A,an eight-stereogenic-center-containing fungal metabolite by the synergy of prediction rule-guided analysis and chemical *** expedient total synthesis resulted in unambiguous verification of the predicted stereochemistry for valactamide A.

关键词： stereochemistry configuration prediction total synthesis valactamide A

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~*** statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in *** surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has *** 38,000 people died of cancer in *** National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

Cellular response against cytosolic leakage of mitochondrial DNA: insights into the pathology of Parkinson’s disease

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Neural Regeneration Research 2022年第12期17卷 2682-2684页

作者： Akiko Sakai hideaki Matsui Department of Neuroscience of Disease Brain Research InstituteNiigata UniversityNiigataJapan

Mitochondria are important organelles for cellular metabolism and homeostasis,and their abnormalities are implicated in various *** mitochondria originate from protobacterium,their components are easily recognized by pathogen sensors called pattern-recognition receptors as foreign substances in the *** is prominent for mitochondrial DNA(mtDNA)which has different properties from nuclear DNA,such as low,if any,methylation status,vulnerability to oxidation due to the proximity to the oxidative phosphorylation machinery,and its circular *** studies indicate that perturbations in mitochondrial function and homeostasis cause mtDNA to leak into the cytoplasm,where it triggers the innate immune response(West and Shadel,2017).Although inflammatory response is a cellular strategy to resist viral infections,it can also lead to undesirable outcomes by damaging own cells and tissues.

关键词： homeostasis metabolism insight

Factors other than fibrosis that increase measured shear wave velocity

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World Journal of Gastroenterology 2022年第46期28卷 6512-6521页

作者： Hiroko Naganuma hideaki Ishida Department of Gastroenterology Yokote Municipal HospitalYokote 013-8602Japan Department of Gastroenterology Akita Red Cross HospitalAkita 010-1495Japan

Shear wave elastography(SWE)is now becoming an indispensable diagnostic tool in the routine examination of liver *** particular,accuracy is required for shear wave propagation velocity measurement,which is directly related to diagnostic *** is generally accepted that the liver shear wave propagation velocity reflects the degree of fibrosis,but there are still few reports on other factors that increase the shear wave propagation *** this study,we reviewed such factors in the literature and examined their *** SWE measures propagation velocity based on the assumption that the medium has a homogeneous structure,uniform density,and is purely ***,the measurement is subject to *** other(confounding)factors that we routinely experience are primarily:(1)Conditions that appear to increase the viscous component;and(2)Conditions that appear to increase tissue ***,the former includes acute hepatitis,congested liver,biliary obstruction,etc,and the latter includes diffuse infiltration of malignant cells,various storage diseases,tissue necrosis,*** any case,it is important to evaluate SWE in the context of the entire clinical picture.

关键词： Liver Shear wave elastography Propagation velocity Viscoelasticity Artifact Ultrasound

A potential new tool to enhance translational success rate in stroke research by backcrossing techniques in transgenic mice

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Neural Regeneration Research 2023年第1期18卷 107-108页

作者： Takayuki Nakagomi hideaki Nishie Toshinori Sawano Akiko Nakano-Doi Institute for Advanced Medical Sciences Hyogo College of MedicineHyogoJapan Department of Therapeutic Progress in Brain Diseases Hyogo College of MedicineHyogoJapan Department of Biomedical Sciences Ritsumeikan UniversityShigaJapan

Ischemic stroke is a leading disease of the central nervous system,frequently coupled to severe damage and dysfunction in *** models mimicking human stroke provide useful tools for studying the pathomechanisms(e.g.,inflammation,neuroprotection,and neural regeneration),the treatment efficiency of various materials(e.g.,bioactive molecules or drugs),and transplantation usefulness by various cell types[e.g.,neural stem/progenitor cells(NSPCs),and mesenchymal or hematopoietic stem cells]under ischemic stroke.

关键词： inflammation damage neural