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Role of myeloid cells in neural repair after brain tissue injury

Clinical and Experimental Neuroimmunology 2024年第4期15卷 215-221页

作者： Koyama, Ryuki Shichita, Takashi Department of Neuroinflammation and Repair Medical Research Institute Tokyo Medical and Dental University Tokyo Japan Core Research for Evolutional Science and Technology (CREST) Japan Agency for Medical Research and Development (AMED) Tokyo Japan

Stroke and traumatic brain injury leave many survivors with permanent neurological disabilities, and the development of therapeutics to enhance functional recovery is needed. Both residential and infiltrating immune cells participate in the acute inflammation after brain injury, exacerbating functional outcomes;however, some immune cells have been reported to alter their characteristic to a reparative phenotype. This review focused on the recent findings of the reparative immunity of myeloid cells. Functional recovery after injury is achieved through the combination of resolution of inflammation, reorganization of neuronal network, white matter repair, angiogenesis and extracellular matrix reorganization. In each process, myeloid cells play vital roles in leading to functional recovery. Further research on the diversity of immune cells implicated in neural repair will be promising to develop therapeutics enhancing functional recovery after brain tissue injuries. © 2024 Japanese Society for Neuroimmunology.

关键词： brain injury functional recovery myeloid neuronal repair tissue repair

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Effects of CPAP on Atherosclerotic Coronary Plaques in Patients with Sleep-Disordered Breathing: The ENTERPRISE Trial

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JACC: Asia 2024年第11期4卷 875-878页

作者： Fukase, Tatsuya Dohi, Tomotaka Kasai, Takatoshi Yanagisawa, Naotake Endo, Hirohisa Okazaki, Shinya Minamino, Tohru Department of Cardiovascular Biology and Medicine Juntendo University Graduate School of Medicine Tokyo Japan Cardiovascular Respiratory Sleep Medicine Juntendo University School of Medicine Tokyo Japan Sleep and Sleep-Disordered Breathing Center Juntendo University Hospital Tokyo Japan Medical Technology Innovation Center Juntendo University Tokyo Japan Department of Cardiology Juntendo University Shizuoka Hospital Sizuoka Japan Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST) Japan Agency for Medical Research and Development Tokyo Japan

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Spatial prisoner's dilemma optimally played in small-world networks

arXiv

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arXiv 2024年

作者： Masuda, Naoki Aihara, Kazuyuki Department of Complexity Science and Engineering Graduate School of Frontier Sciences The University of Tokyo Bunkyo-ku 7-3-1 Hongo Tokyo113-8656 Japan Core Research for Evolutional Science and Technology Japan Science and Technology Corporation 4-1-8 Hon-cho Saitama Kawaguchi332-0012 Japan

Cooperation is commonly found in ecological and social systems even when it apparently seems that individuals can benefit from selfish behavior. We investigate how cooperation emerges with the spatial prisoner's dilemma played in a class of networks ranging from regular lattices to random networks. We find that, among these networks, small-world topology is the optimal structure when we take into account the speed at which cooperative behavior propagates. Our results may explain why the small-world properties are self-organized in real networks. © 2024, CC BY.

关键词： Small-world networks

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Determination of spin Hall angle in the Weyl ferromagnet Co2MnGa by taking into account the thermoelectric contributions

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Physical Review Materials 2022年第8期6卷 084411-084411页

作者： Hironari Isshiki Zheng Zhu Hayato Mizuno Ryota Uesugi Tomoya Higo Satoru Nakatsuji YoshiChika Otani Institute for Solid State Physics University of Tokyo Kashiwa Chiba 277-8581 Japan Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) Saitama 332-0012 Japan Department of Physics The University of Tokyo Bunkyo-ku Tokyo 113-0033 Japan Trans-scale Quantum Science Institute University of Tokyo Bunkyo-ku Tokyo 113-0033 Japan Center for Emergent Matter Science RIKEN Wako Saitama 51-0198 Japan

The spin Hall effects of various materials, including Weyl semimetals, have been studied by the spin absorption method with the nonlocal spin valve structures. Here, we study Co2MnGa (CMG) by using the standard spin absorption method. A considerable amount of thermoelectric signal superimposes on the inverse spin Hall signal in the measurement configuration: the applied electric current between the spin injector (permalloy) and bridge (copper) wires produces heating or cooling at the interface via the Peltier effect, which causes an out-of-plane temperature gradient in CMG. As a result, a voltage signal induced by the anomalous Nernst effect (ANE) of CMG comes into the inverse spin Hall signal. We quantitatively separate these signals by combining the experiment and a numerical simulation. About 75% of the detected signal is found attributable to the thermoelectric effects. The superposing thermoelectric contribution is a general and unavoidable problem in this method when the spin Hall materials exhibit ANE. After eliminating the thermoelectric signal, the spin Hall angle of CMG turns out to be θ=−0.09 at room temperature.

关键词： Inverse spin Hall effect Spin Hall effect Spin current Spin generation Spin

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Prognostic values of proteinuria in patients with acute heart failure

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Journal of Cardiology 2025年

作者： Akama, Yuka Matsue, Yuya Maeda, Daichi Dotare, Taishi Sunayama, Tsutomu Iso, Takashi Fujimoto, Yudai Nakade, Taisuke Yatsu, Shoichiro Ishiwata, Sayaki Nakamura, Yutaka Suda, Shoko Kato, Takao Hiki, Masaru Kasai, Takatoshi Minamino, Tohru Department of Cardiovascular Biology and Medicine Juntendo University Graduate School of Medicine Tokyo Japan Cardiovascular Respiratory Sleep Medicine Juntendo University Graduate School of Medicine Tokyo Japan Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST) Japan Agency for Medical Research and Development Tokyo Japan

Background: Renal dysfunction is significantly associated with poor prognosis in patients with heart failure. However, the prognostic significance of proteinuria as a potential marker of an impaired glomerular filtration barrier in acute heart failure (AHF) remains unclear. We aimed to investigate the prognostic value of urinary protein/creatinine ratio (PCR) in patients with AHF. Methods: Urinary protein levels measured at admission were adjusted for urinary creatinine concentrations in 346 patients (75 ± 13 years;61 % men) with AHF. Patients were categorized based on urinary PCR, adhering to the Japanese chronic kidney disease (CKD) guideline cut-offs for CKD staging: A1 (<0.15 g/gCr), A2 (0.15–0.49 g/gCr), and A3 (≥0.5 g/gCr). The primary endpoint was all-cause mortality. Results: Overall, there were 85, 126, and 135 patients in the A1, A2, and A3 groups, respectively. Groups A2 and A3 were associated with lower hemoglobin levels, higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide levels, and poor renal function. Moreover, groups A2 and A3 had high cystatin C, alpha 1 microglobulin, and urinary liver-type fatty acid-binding protein (L-FABP) levels. Urinary PCR correlated more with tubular markers, alpha 1-microglobulin, and L-FABP than with the glomerular marker cystatin C. Over a median follow-up period of 434 (interquartile range: 89–753) days, 72 deaths occurred. Elevated urinary PCR was associated with higher mortality rates (log-rank test, p < 0.001), even after adjusting for other variables [A2 vs. A1: hazard ratio (HR) 2.59, 95 % confidence interval (CI) 0.71–9,55, p = 0.15;A3 vs. A1: HR 4.40, 95 % CI 1.17–16.6, p = 0.029]. Conclusions: Elevated urinary PCR is more prevalent in patients with AHF and is associated with a higher risk of all-cause mortality, independent of covariates, including glomerular function. Thus, urinary PCR at admission should provide prognostic information independent of glomerular function. © 2024 Elsevier Ltd

关键词： Glomerular function Heart failure Proteinuria Renal dysfunction Urinary protein/creatinine ratio

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Identification of a molecular resistor that controls UCP1-independent Ca²⁺ cycling thermogenesis in adipose tissue

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Cell Metabolism 2025年第6期37卷 1311-1325.e9页

作者： Auger, Christopher Li, Mark Fujimoto, Masanori Ikeda, Kenji Yook, Jin-Seon Caycedo, María Paula Huertas Xiaohan, Cai Oikawa, Satoshi Verkerke, Anthony R.P. Shinoda, Kosaku Griffin, Patrick R. Inaba, Kenji Stimson, Roland H. Kajimura, Shingo Division of Endocrinology Diabetes and Metabolism Beth Israel Deaconess Medical Center and Harvard Medical School and Howard Hughes Medical Institute Boston MA United States Department of Molecular Endocrinology and Metabolism Tokyo Medical and Dental University Tokyo Japan Department of Molecular Medicine The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology Jupiter FL United States University/BHF Centre for Cardiovascular Science University of Edinburgh Queen's Medical Research Institute Edinburgh United Kingdom Medical Institute of Bioregulation Kyushu University Fukuoka 812-8582 Japan Core Research for Evolutional Science and Technology (CREST) Japan Agency for Medical Research and Development (AMED) Tokyo Japan Departments of Medicine and Molecular Pharmacology Albert Einstein College of Medicine Bronx New York NY United States

Adipose tissue thermogenesis contributes to energy balance via mitochondrial uncoupling protein 1 (UCP1) and UCP1-independent pathways. Among UCP1-independent thermogenic mechanisms, one involves Ca²⁺ cycling via SERCA2b in adipose tissue;however, the underlying molecular basis remains elusive. Here, we report that an endoplasmic reticulum (ER) membrane-anchored peptide, C4orf3 (also known as another regulin [ALN]), uncouples SERCA2b Ca²⁺ transport from its ATP hydrolysis, rendering the SERCA2b-C4orf3 complex exothermic. Loss of C4orf3/ALN improved the energetic efficiency of SERCA2b-dependent Ca²⁺ transport without affecting SERCA2 expression, thereby reducing adipose tissue thermogenesis and increasing the adiposity of mice. Notably, genetic depletion of C4orf3 resulted in compensatory activation of UCP1-dependent thermogenesis following cold challenge. We demonstrated that genetic loss of both C4orf3 and Ucp1 additively impaired cold tolerance in vivo. Together, this study identifies C4orf3 as the molecular resistor to SERCA2b-mediated Ca²⁺ import that plays a key role in UCP1-independent thermogenesis and energy balance. © 2025

关键词： Ca2+ cycling energy balance obesity thermogenesis UCP1-independent

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Exploring diamondlike lattice thermal conductivity crystals via feature-based transfer learning

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Physical Review Materials 2021年第5期5卷 053801-053801页

作者： Shenghong Ju Ryo Yoshida Chang Liu Stephen Wu Kenta Hongo Terumasa Tadano Junichiro Shiomi Department of Mechanical Engineering The University of Tokyo 7-3-1 Hongo Bunkyo Tokyo 113-8656 Japan National Institute for Materials Science (NIMS) 1-2-1 Sengen Tsukuba Ibaraki 305-0047 Japan Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) 4-1-8 Kawaguchi Saitama 332-0012 Japan and RIKEN Center for Advanced Intelligence Project 1-4-1 Nihonbashi Chuo-ku Tokyo 103-0027 Japan

Ultrahigh lattice thermal conductivity materials hold great importance since they play a critical role in the thermal management of electronic and optical devices. Models using machine learning can search for materials with outstanding higher-order properties like thermal conductivity. However, the lack of sufficient data to train a model is a serious hurdle. Herein we show that big data can complement small data for accurate predictions when lower-order feature properties available in big data are selected properly and applied to transfer learning. The connection between the crystal information and thermal conductivity is directly built with a neural network by transferring descriptors acquired through a pretrained model for the feature property. Successful transfer learning shows the ability of extrapolative prediction and reveals descriptors for lattice anharmonicity. The resulting model is employed to screen over 60000 compounds to identify novel crystals that can serve as alternatives to diamond. Even though most materials in the top list are superhard materials, we reveal that superhard property does not necessarily lead to high lattice thermal conductivity. Large hardness means high elastic constants and group velocity of phonons in the linear dispersion regime, but the lattice thermal conductivity is determined also by other important factors such as the phonon relaxation time. What is more, the average or maximum dipole polarizability and the van der Waals radius are revealed to be the leading descriptors among those that can also be qualitatively related to anharmonicity.

关键词： Lattice thermal conductivity Phonons Thermal conductivity

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Mid-infrared dielectric response of Fermi-degenerate electron-hole droplets in diamond

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Physical Review B 2022年第23期106卷 235205-235205页

作者： J. Omachi N. Naka K. Yoshioka M. Kuwata-Gonokami Department of Applied Physics School of Engineering The University of Tokyo Hongo Bunkyo-ku Tokyo 113-0033 Japan Photon Science Center School of Engineering The University of Tokyo Yayoi Bunkyo-ku Tokyo 113-8656 Japan Core Research for Evolutional Science and Technology Agency Kawaguchi-shi Saitama 332-0012 Japan Department of Physics Kyoto University Kitashirakawa Sakyo-ku Kyoto 606-8502 Japan Department of Physics School of Science The University of Tokyo Hongo Bunkyo-ku Tokyo 113-0033 Japan

Exploring the properties of a highly quantum-degenerate electron-hole (e-h) state as a many-body system is an interesting problem in solid-state physics. Electron-hole droplets (EHDs) offer a potential platform for investigating such a state of Fermi-degenerate carriers at an extremely high density. Herein we present dielectric response measurements of carriers in the mid-infrared (MIR) region for a definitive evaluation of the dynamic properties of the e-h state of EHDs in diamond. With photoexcitation across the band-gap energy by using the two-photon absorption process, we performed time-resolved differential transmission spectroscopy by using MIR probe light and time-resolved photoluminescence spectroscopy in the deep-ultraviolet region. By linking the two temporal profiles, we overcame the problem of previous ambiguous PL analyses and elucidated the MIR dielectric response that reveals the surface plasmon resonance (SPR) of EHDs and the effect of the e-h Coulomb interaction on the dynamic dielectric response. Thus, we found that the carrier density inside EHDs remained constant at 8×1019cm−3 up to 2 ns, whereas a decay time of 1 ns of the condensed volume was found and the AC conductivity relaxation rate of 2×1014s−1 maintained during this nanosecond timescale was the highest among group-IV semiconductors. We predicted a strong dependence of the e-h scattering rate on the probe frequency in the high-frequency region in which SPR appeared, suggesting that—when probed in the low-frequency region—dynamical relaxation does not interfere with the order formation expected in quantum-degenerate e-h systems at ultralow temperatures.

关键词： Carrier dynamics Dielectric properties Excitons Time-resolved photoluminescence Ultrafast pump-probe spectroscopy

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Prevalence and Prognostic Implications of Changes in Tricuspid Regurgitation Severity in Acute Heart Failure

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Journal of Cardiac Failure 2025年第5期31卷 781-788页

作者： KOBAYASHI, TETSUYA MATSUE, Y.U.Y.A. FUJIMOTO, YUDAI MAEDA, DAICHI KIDA, KEISUKE KITAI, TAKESHI KAGIYAMA, NOBUYUKI YAMAGUCHI, TETSUO OKUMURA, TAKAHIRO MIZUNO, ATSUSHI OISHI, SHOGO INUZUKA, YASUTAKA AKIYAMA, EIICHI SUZUKI, SATOSHI YAMAMOTO, MASAYOSHI TAMURA, YUICHI MINAMINO, TOHRU Department of Cardiovascular Biology and Medicine Juntendo University Graduate School of Medicine Tokyo Japan Department of Cardiology Tokyo Bay Medical Center Urayasu Japan Department of Pharmacology St. Marianna University School of Medicine Kawasaki Japan Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Osaka Japan Department of Cardiology Cardiovascular Center Toranomon Hospital Tokyo Japan Department of Cardiology Nagoya University Graduate School of Medicine Nagoya Japan Department of Cardiovascular Medicine St. Luke's International Hospital Tokyo Japan Department of Cardiology Mahoshi Hospital Kobe Japan Department of Cardiology Shiga Medical Center for Adults Moriyama Japan Division of Cardiology Yokohama City University Medical Center Yokohama Japan Department of Cardiovascular Medicine Fukushima Medical University Fukushima Japan Cardiovascular Division Faculty of Medicine University of Tsukuba Tsukuba Japan Department of Cardiology International University of Health and Welfare Mita Hospital Tokyo Japan Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST) Japan Agency for Medical Research and Development Tokyo Japan

Background: Tricuspid regurgitation (TR), prevalent in acute heart failure (AHF), has a poor prognosis;however, the dynamics of TR severity during hospitalization and its prognostic implications remain unclear. We investigated TR dynamism during hospitalization and its prognostic impact in AHF. Methods and Results: This is a post hoc analysis of a prospective multicenter study of patients with AHF who underwent echocardiographic TR severity evaluation at admission and before discharge. The primary end point was a combined of 1-year all-cause mortality and HF rehospitalization after discharge. Among 1079 participants, TR severity changed dynamically, with 60.3% of those with moderate TR and 29.6% of those with severe TR at admission being diagnosed as no or mild TR at discharge. In 3 groups stratified by changes in TR severity, the persistent TR groups had a higher incidence of the primary end point than the resolution and absence groups. In adjusted analyses, the persistent group (hazard ratio, 1.37;95% confidence interval, 1.04–1.80), but not the resolution group (hazard ratio, 1.07;95% confidence interval, 0.79–1.44), had a higher primary end point incidence than the absence group. Conclusions: TR severity at admission in patients with AHF can change dynamically and is associated with subsequent prognosis. Significant TR that remains even after decongestive therapy might be a target for further treatment in hospitalized patients with AHF. © 2024 Elsevier Inc.

关键词： acute heart failure prognosis Tricuspid regurgitation

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Functional production of human antibody by the filamentous fungus Aspergillus oryzae

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Fungal Biology and Biotechnology 2020年第1期7卷 7页

作者： Huynh, Hung Hiep Morita, Naoki Sakamoto, Toshihiro Katayama, Takuya Miyakawa, Takuya Tanokura, Masaru Chiba, Yasunori Shinkura, Reiko Maruyama, Jun-Ichi Department of Biotechnology University of Tokyo Tokyo Japan Laboratory of Immunology and Infection Control Institute for Quantitative Biosciences University of Tokyo Tokyo Japan Collaborative Research Institute for Innovative Microbiology University of Tokyo Tokyo Japan Department of Applied Biological Chemistry University of Tokyo Tokyo Japan Biotechnology Research Institute for Drug Discovery National Institute of Advanced Industrial Science and Technology (AIST) Tsukuba Ibaraki Japan Core Research for Evolutional Science and Technology Japan Agency for Medical Research and Development Tokyo Japan

Background: Monoclonal antibodies (mAbs) as biopharmaceuticals take a pivotal role in the current therapeutic applications. Generally mammalian cell lines, such as those derived from Chinese hamster ovaries (CHO), are used to produce the recombinant antibody. However, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. Aspergillus oryzae, a filamentous fungus recognized as a GRAS (Generally Regarded As Safe) organism, has an ability to secrete a large amount of proteins into the culture supernatant, and thus the fungus has been used as one of the cost-effective microbial hosts for heterologous protein production. Pursuing this strategy the human anti-TNFα antibody adalimumab, one of the world's best-selling antibodies for the treatment of immune-mediated inflammatory diseases including rheumatoid arthritis, was chosen to produce the full length of mAbs by A. oryzae. Generally, N-glycosylation of the antibody affects immune effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) via binding to the Fc receptor (FcγR) on immune cells. The CRISPR/Cas9 system was used to first delete the Aooch1 gene encoding a key enzyme for the hyper-mannosylation process in fungi to investigate the binding ability of antibody with FcγRIIIa. Results: Adalimumab was expressed in A. oryzae by the fusion protein system with α-amylase AmyB. The full-length adalimumab consisting of two heavy and two light chains was successfully produced in the culture supernatants. Among the producing strains, the highest amount of antibody was obtained from the ten-protease deletion strain (39.7 mg/L). Two-step purifications by Protein A and size-exclusion chromatography were applied to obtain the high purity sample for further analysis. The antigen-binding and TNFα neutralizing activities of the adalimumab produced by A. oryzae were comparable with those of a commercial product Humira^®. No apparent binding wit

关键词： Antibody Aspergillus oryzae Fc receptor N-linked glycan Neutralization

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