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

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 system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,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 loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To 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 assessments.Recently,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 proposed.Especially 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 barrier.In 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 sources.Additionally,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

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Excellentπ-Bowl Semiconductors Based on C_(70)Subunit

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CCS Chemistry 2024年第2期6卷 353-364页

作者： Meng Chen Yuxiao Duan Xinyue Liu Qian Zhan Hironobu Hayashi Kyohei matsuo Hiroko Yamada Guangpeng Gao Yonghao Zheng Lei Zhang Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical TechnologyBeijing 100029 School of Optoelectronic Science and Engineering University of Electronic Science and Technology of China(UESTC)Chengdu 610054 Division of Materials Science Nara Institute of Science and Technology(NAIST)IkomaNara 630-0192 Key Laboratory of Cluster Science of Ministry of Education Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion MaterialsSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081

As open substructures of fullerenes,aromaticπ-bowls are promising candidates as new organic semiconductors,as well as attractive hosts for fullerenes.We demonstrate herein the synthesis and characterization of a novel C_(2v)symmetricπ-bowl,pyracyleno[6,5,4,3,2,1-pqrstuv]pentaphene(3).Bowl 3 was equipped with two distinctive reactive sites,allowing for bromination and cross-coupling reactions to readily yield functionalized bowls with two 2,4,6-trimethylphenyl(5)and triethylsilyl(TES)-ethynyl(6)substituents,respectively.Variable-temperature 1H NMR analysis and density functional theory(DFT)calculations indicated bowl-to-bowl inversions of 3,5,and 6 at room temperature.By alternating the substituents,the crystal structures of the threeπ-bowls 3,5,and 6 could be controlled from 1D linear to 1D slipped to 2D herringbone packing motifs,providing insight into the packing behavior ofπ-bowls.1H NMR titration study indicated that the TES-ethynyl substituent enhanced the ability ofπ-bowl to bind C_(70)with an association constant of 2485 M−1.The C_(70)molecules withπ-bowls 3 and 6 formed 1:1 complexes,in which C_(70)molecules aggregated into zig-zag and 1D linear arrays,respectively.The hole mobility of 2.3 cm^(2)V^(−1)^s(−1)and electron mobility of 0.16 cm^(2)V^(−1)^s(−1)ofπ-bowl 3 and its complex with C_(70)were demonstrated,respectively,which proved a great value for the development of aromaticπ-bowl semiconductors with tunable properties for organic electronic devices.

关键词： organic semiconductor π-bowl fullerene crystal engineering mobility

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Operationally Simple Enantioselective Silane Reduction of Ketones by the [Ir(OMe)(cod)]₂/Azolium Catalytic System

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International Journal of Organic Chemistry 2024年第1期14卷 1-19页

作者： Satoshi Sakaguchi Chika Nagao Ryo Ichihara Shogo matsuo Department of Chemistry and Materials Engineering Faculty of Chemistry Materials and Bioengineering Kansai University Suita Japan

An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]2 (cod = 1,5-cyclooctadiene) (3) as a metal catalyst precursor. This reaction was driven by chiral hydroxyamide-functionalized azolium salt 2. The catalytic ESR reaction could be performed under benchtop conditions at room temperature. Treatment of 2 with 3 in THF yielded the monodentate IrCl(NHC)(cod) (NHC = N-heterocyclic carbene) complex 4 in 93% yield, herein the anionic methoxy ligand of 3 serves as an internal base that deprotonates the azolium ring of 2. The well-defined Ir complex 4 catalyzed the ESR reaction of propiophenone (6) with (EtO)2MeSiH using the pre-mixing reaction procedure. Based on this success, the catalytic ESR reaction was designed and implemented using an in situ-generated NHC/Ir catalyst derived from 2 and 3. Thus, a wide variety of aryl ketones could be reduced to the corresponding optically active alcohols in moderate to excellent stereoselectivities at room temperature without temperature control. Since the high catalytic activity of 3 was observed, we next evaluated several other transition metal catalyst precursors for the catalytic ESR reaction under the influence of 2. This evaluation revealed that Ir(acac)(cod) (acac = acetylacetonate) (28) and [IrCl(cod)]2 (5) can be successfully used as metal catalyst precursors in the ESR reaction.

关键词： Asymmetric Catalysis Enantioselective Reduction Hydrosilylation Reaction N-Heterocyclic Carbene Iridium

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Phosphorylated protein chip combined with artificial intelligence tools for precise drug screening

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Journal of Biomedical Research 2024年第3期38卷 195-205页

作者： Katsuhisa Horimoto Yuki Suyama Tadamasa Sasaki kazuhiko Fukui Lili Feng Meiling Sun Yamin Tang Yixuan Zhang Dongyin Chen Feng Han SOCIUM Inc. Tokyo 1350064Japan International Medical Center Saitama Medical UniversitySaitama 350-1298Japan Artificial Intelligence Research Center National Institute of Advanced Industrial Science and TechnologyTokyo 1350064Japan Department of Informatics and Data Science Sanyo-Onoda City UniversityYamaguchi 7560884Japan International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China Department of Physiology School of Basic Medical SciencesNanjing Medical UniversityNanjingJiangsu 211166China Gusu School Nanjing Medical UniversitySuzhouJiangsu 215001China National Vaccine Innovation Platform Nanjing Medical UniversityNanjingJiangsu 211166China

We have developed a protein array system,named"Phospho-Totum",which reproduces the phosphorylation state of a sample on the array.The protein array contains 1471 proteins from 273 known signaling pathways.According to the activation degrees of tyrosine kinases in the sample,the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions.In addition to measuring the phosphorylation levels of the 1471 substrates,we have developed and performed the artificial intelligence-assisted tools to further characterize the phosphorylation state and estimate pathway activation,tyrosine kinase activation,and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample.The Phospho-Totum system,which seamlessly links and interrogates the measurements and analyses,has the potential to not only elucidate pathophysiological mechanisms in diseases by reproducing the phosphorylation state of samples,but also be useful for drug discovery,particularly for screening targeted kinases for potential drug kinase inhibitors.

关键词： Phospho-Totum protein array signal transduction pathways artificial intelligence tools drug screening

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Kidney GATA3^(+) regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury

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Cellular & Molecular Immunology 2021年第5期18卷 1249-1261页

作者： Ryota Sakai Minako Ito Kyoko Komai Mana Iizuka-Koga kazuhiko matsuo Takashi Nakayama Osamu Yoshie Koichi Amano Hiroshi Nishimasu Osamu Nureki Masato Kubo Akihiko Yoshimura Department of Microbiology and Immunology Keio University School of Medicine35 ShinanomachiShinjuku-kuTokyo160-8582Japan Department of Rheumatology and Clinical Immunology Saitama Medical CenterSaitama Medical University1981 KamodaKawagoe350-8550Japan Medical Institute of Bioregulation Kyushu University 3-1-1 MaidashiHigashi-kuFukuoka812-8582Japan Division of Chemotherapy Kindai University Faculty of PharmacyHigashi-Osaka577-8502Japan The Health and Kampo Institute SendaiMiyagi981-3205Japan Department of Biological Science Graduate School of ScienceThe University of Tokyo7-3-1 HongoBunkyo-kuTokyo113-0033Japan Center for Animal Disease Models Research Institute for Biomedical ScienceTokyo University of Science2669 YamazakiNoda-shiChiba278-0022Japan

FoxP3^(+)regulatory T cells(Tregs)play crucial roles in peripheral immune tolerance.In addition,Tregs that reside or accumulate in nonlymphoid tissues,called tissue Tregs,exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and repair.In an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody,Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels(~30–35%of CD4^(+)T cells)during the late stage(days 21–90),which correlated with stable disease control.Treg depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells,suggesting that Tregs are essential for disease control during the convalescence stage.The Tregs that accumulated in the kidney showed tissue Treg phenotypes,including high expression of GATA3,ST2(the IL33 receptor subunit),amphiregulin(Areg),and PPARγ.Although T-bet^(+) Tregs and RORγt^(+) Tregs were observed in the kidney,GATA3^(+) Tregs were predominant during the convalescence stage,and a PPARγagonist enhanced the accumulation of GATA3^(+) Tregs in the kidney.To understand the function of specific genes in kidney Tregs,we developed a novel T cell transfer system to T cell-deficient mice.This experiment demonstrates that ST2,Areg,and CCR4 in Tregs play important roles in the accumulation of GATA3^(+) Tregs in the kidney and in the amelioration of renal injury.Our data suggest that GATA3 is important for the recruitment of Tregs into the kidney,which is necessary for convalescence after renal tissue destruction.

关键词： Tissue Tregs autoantibody GATA3 kidney IL-33

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Electroencephalogram Signal Correlations between Default Mode Network and Attentional Functioning

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Journal of Behavioral and Brain Science 2024年第4期14卷 119-134页

作者： Moemi matsuo Takashi Higuchi Toranosuke Abe Takuya Ishibashi Ayano Egashira Rio Kamashita Faculty of Rehabilitation Sciences Nishi Kyushu University Kanzaki Japan Department of Physical Therapy Osaka University of Human Sciences Settsu Japan Research Center for Child Mental Development Chiba University Chiba Japan

Attentional issues may affect acquiring new information, task performance, and learning. Cortical network activities change during different functional brain states, including the default mode network (DMN) and attention network. We investigated the neural mechanisms underlying attentional functions and correlations between DMN connectivity and attentional function using the Trail-Making Test (TMT)-A and -B. Electroencephalography recordings were performed by placing 19 scalp electrodes per the 10 - 20 system. The mean power level was calculated for each rest and task condition. Non-parametric Spearman’s rank correlation was used to examine the correlation in power levels between the rest and TMT conditions. The most significant correlations during TMT-A were observed in the high gamma wave, followed by theta and beta waves, indicating that most correlations were in the parietal lobe, followed by the frontal, central, and temporal lobes. The most significant correlations during TMT-B were observed in the beta wave, followed by the high and low gamma waves, indicating that most correlations were in the temporal lobe, followed by the parietal, frontal, and central lobes. Frontoparietal beta and gamma waves in the DMN may represent attentional functions.

关键词： Cortical Network Activities Electroencephalography Attention Default Mode Network

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Enhancement of Visual Attention by Color Revealed Using Electroencephalography

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Open Journal of Therapy and Rehabilitation 2024年第1期12卷 1-9页

作者： Moemi matsuo Takashi Higuchi Takuya Ishibashi Ayano Egashira Toranosuke Abe Hiroya Miyabara Faculty of Rehabilitation Sciences Nishikyushu University Kanzaki Japan Department of Physical Therapy Osaka University of Human Sciences Settsu Japan

Attention constitutes a fundamental psychological feature guiding our mental effort toward specific objects, concurrent with processes such as memory, reasoning, and imagination. Visual attention, crucial for selecting surrounding information, often decreases in older adults and patients with cerebrovascular disorders. Effective methods to enhance attention are scarce. Here, we investigated whether color information influences visual attention and brain activity during task performance, utilizing EEG. We examined 13 healthy young adults (seven women and six men;mean age: 21.2 ± 0.58 years) using 19-electrode electroencephalograms to assess the impact of color information on visual attention. The Clinical Assessment for Attention cancellation test was conducted under the black, red, and blue color conditions. Wilcoxon’s signed-rank test was used to assess differences in task performance (task time and error) between conditions. Spearman’s rank correlation was utilized to examine the correlation in power levels between task performance and color conditions. Significant variations in total task errors were observed among color conditions. The black condition exhibited the highest error frequency (0.7 ± 0.9 times), followed by the red condition (0.5 ± 0.8 times), with the lowest error frequency occurring in the blue (0.2 ± 0.4 times) condition (black vs. red: P = 0.03;black vs. blue: P = 0.00;red vs. blue: P = 0.032). No time difference was observed. The black condition showed negative delta and high-gamma correlations in the central electrodes. The red condition revealed positive alpha and low-gamma correlations in the frontal and occipital areas. Although no correlations were observed in the blue condition, it enhanced attentional performance. Positive alpha and low-gamma waves might be crucial for spotting attentional errors in key areas. Our findings provide insights into the effects of color information on visual attention and potential neural correlates associated with attentional processes. In conclusion, our

关键词： Attention Higher Brain Function Electroencephalography Neuroimaging Rehabilitation

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Light is an Important Limiting Factor for the Vertical Distribution of the Largest Extant Benthic Foraminifer Cycloclypeus carpenteri

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Journal of Earth Science 2022年第6期33卷 1460-1468页

作者： kazuhiko Fujita Yoji Kanda Takashi Hosono Department of Physics and Earth Sciences University of the RyukyusOkinawa903-0213Japan Tropical Biosphere Research Center University of the RyukyusOkinawa903-0213Japan Japan Agency for Marine-Earth Science and Technology(JAMSTEC) Global Oceanographic Data Center(GODAC)Kanagawa236-0001Japan

Cycloclypeus carpenteri is the largest extant benthic foraminifer,dwelling in the deep euphotic zone(a water depth between 60 and 130 m)of the warm oligotrophic Indo-West Pacific.This foraminifer harbors diatom endosymbionts and the foraminifer-microalgal association acts like a holobiont.To verify that light is an important limiting factor controlling the vertical(depth)distribution of living Cycloclypeus holobionts,their physiological responses to light intensity were examined by short-term metabolic measurements and long-term *** oxygen production(OP)rates measured under different light levels using an oxygen microelectrode indicate that Cycloclypeus holobionts are daily net primary producers adapted to low light levels,with slight photoinhibition(reduced net OP rates relative to a light-saturated rate)over 100μmol photons m^(−2)s^(−1).Long-term growth increments of asexually reproduced juveniles incubated for two months at different light levels ranging from 0 to 100μmol photons m^(−2)s^(−1) show that Cycloclypeus holobionts are adapted to a low light level(∼5μmol photons m^(−2)s^(−1)),but can be acclimatized to a certain low light ranges(<50μmol photons m^(−2)s^(−1)).These experimental results confirm that light is an important environmental gradient affecting the vertical distribution of Cycloclypeus holobionts.

关键词： algal symbiosis diatom large benthic foraminifer oxygen production photosynthesis

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Dorsal approach for isolated volar fracture-dislocation of the base of the second metacarpal:A case report

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世界临床病例杂志 2023年第28期11卷 6871-6876页

作者： Taketo Kurozumi Masato Saito kazuhiko Odachi Fumiaki Masui Trauma Center Toranomon HospitalTokyo 105-8470Japan Department of Orthopedic Surgery Chiba-Nishi General HospitalChiba 270-2251Japan

BACKGROUND We report a case with the displacement of an articular fracture fragment of the base of the second metacarpal from the ulnar to the volar side,treated via the dorsal approach.The dorsal approach can be a good option not only because it allows direct observation of ligament damage and fixation of bone fragments but also because the thin subcutaneous tissue makes the approach easier.CASE SUMMARY A 45-year-old man with a right hand injury visited the hospital.A small bone fragment was identified using plain radiography.Lateral radiography revealed the fragment as lying over the volar aspect of the carpometacarpal(CMC)joint.Computed tomography revealed that approximately one-third of the CMC joint surface of the second metacarpal was damaged.We provisionally diagnosed an intra-articular fracture with significant CMC joint instability and performed open reduction and internal fixation.We made a dorsal longitudinal incision over the CMC joint between the second and third metacarpals.The dorsal ligament of the third CMC joint was torn.We thought it had been dislocated to the volar side and spontaneously reduced to that position.There are only few reports of volar dislocation of CMC joint fractures,particularly of the second and third metacarpals;our report is unique as our patient had an intact interosseous ligament between the second and third metacarpals.CONCLUSION Although past reports have used a palmar approach,the dorsal approach is a good option for these cases.

关键词： Metacarpal bone Fracture-dislocation Mechanism Dorsal approach Carpometacarpal joint Case report

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Flexible Förster resonance energy transfer-assisted optical waveguide based on elastic mixed molecular crystals

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Aggregate 2023年第6期4卷 95-100页

作者： Takumi matsuo Koki Ikeda Shotaro Hayashi School of Engineering Science Kochi University of TechnologyKochiJapan

Flexible molecular crystal waveguides based on elastic molecular crystals(EMCs)are essential inﬂexible and compact optical materials.An increased loss coefﬁ-cientαdue to self-absorption is often a problem in optical waveguides(OWGs)ofﬂuorescent chemical materials waveguiding photons in active mode.Herein,the development of anthracene-based elastic mixed molecular crystals(EMMCs)is reported for Förster Resonance Energy Transfer(FRET)-assisted OWG.To yield a FRET crystal system based on elastic molecular crystals,1%–5%accep-tor doping forﬂuorescent molecular crystals of 9,10-dibromoanthracene 1 was successful by selecting the same regioisomer having electron-withdrawing group,9,10-diformylanthracene 2,as a dopant.In addition to conversion to the mixed system,there is a difference in the elastic modulus and hardness in EMC C1 and EMMC C2@1.However,the elastic behaviour was also shown in a few percent doping of the acceptor.Theαvalue of this EMMC,composed of 1 including 1%of 2(0.0077 dB/μm),is much lower than that of EMC composed of 1(0.1258 dB/μm)because of reducing self-absorption in the FRET system.An efﬁcient andﬂexible OWG was successfully developed by selecting an appropriate acceptor molecule and its low doping rate for mixed crystal construction.This method is a practical approach in various functional andﬂexible crystal systems.

关键词： anthracene elastic mixed molecular crystals ﬂexible Förster resonance energy transfer optical waveguide

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