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Evaluation of the Immunoregulatory Capacities of Feed Microbial Materials in Porcine Intestinal Immune and Epithelial Cells

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Open Journal of Veterinary Medicine 2014年第3期4卷 15-28页

作者： Naosuke Kumagae Julio Villena Yohsuke Tomosada Hisakazu Kobayashi Paulraj Kanmani Hisashi Aso Takashi Sasaki Motohiko Yoshida Hiroshi Tanabe Isao Shibata Tadao Saito haruki Kitazawa Cell Biology Laboratory Graduate School of Agricultural Science Tohoku University Sendai Japan Food and Feed Immunology Group Tohoku University Sendai Japan Food and Feed Immunology Group Tohoku University Sendai Japan Japan Society for the Promotion of Science (JSPS) Tokyo Japan Food and Feed Immunology Group Tohoku University Sendai Japan Laboratory of Immunobiotechnology Reference Centre for Lactobacilli (CERELA-CONICET) Tucuman Argentina Food and Feed Immunology Group Tohoku University Sendai Japan Scientific Feed Laboratory Co. Ltd. Tokyo Japan Scientific Feed Laboratory Co. Ltd. Tokyo Japan

The establishment of drug-free feeding systems has been required for secure and healthy livestock production. Although functional feed materials containing microorganisms as alternatives to enhance intestinal immunity are expected to be beneficial for reducing diarrhoea caused by pathogens in weaned piglets, the effects of such materials on porcine intestinal cells have not been investigated in detail. Therefore, this work evaluated the immunoregulatory functions of microbial feed materials in porcine intestinal immune and epithelial cells. Porcine immune cells isolated from Peyer’s patches and mesenteric lymph nodes were stimulated with six different feed materials containing microorganisms, and evaluated for lymphocyte mitogenicity and cytokine inductions. In addition, porcine intestinal epithelial cells were stimulated with the materials before treatment with heat-killed enterotoxigenic Escherichia coli (ETEC), and analyzed for the proinflammatory cytokine expressions. The material containing Bifidobacterium thermophilum significantly augmented lymphocytes’ mitogenicity and also induced a high expression of IL-2, IL-6 and IFN-γ in immune cells, and inhibited ETEC-induced overexpression of IL-6 and IL-8 via regulation of Toll-like receptor signaling. These results suggest that this feed material stimulates intestinal epithelial and immune cells to exert immunoregulation, suggesting that this feed is expected to contribute to promoting the health of piglets without using antimicrobial feed materials.

关键词： Feed Microbial Material Immunoregulatory Effect Porcine Intestinal Epitheliocytes Porcine Immune Cells

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Real-world Effectiveness and Tolerability of Interferonfree Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C:A Multinational Cohort Study

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 646-658页

作者： Fanpu Ji Sally Tran Eiichi Ogawa Chung-Feng Huang Takanori Suzuki Yu Jun Wong Hidenori Toyoda Dae Won Jun Liu Li haruki Uojima Akito Nozaki Makoto Chuma Cheng-Hao Tseng Yao-Chun Hsu Masatoshi Ishigami Takashi Honda Masanori Atsukawa Hiroaki Haga Masaru Enomoto Huy Trinh Carmen Monica Preda Phillip Vutien Charles Landis Dong Hyun Lee Tsunamasa Watanabe Hirokazu Takahashi Hiroshi Abe Akira Asai Yuichiro Eguchi Jie Li Xiaozhong Wang Jia Li Junping Liu Jing Liang Carla Pui-Mei Lam Rui Huang Qing Ye Hongying Pan Jiajie Zhang Dachuan Cai Qi Wang Daniel Q.Huang Grace Wong Vincent Wai-Sun Wong Junyi Li Son Do Norihiro Furusyo Makoto Nakamuta Hideyuki Nomura Eiji Kajiwara Eileen L.Yoon Sang Bong Ahn Koichi Azuma Kazufumi Dohmen Jihyun An Do Seon Song Hyun Chin Cho Akira Kawano Toshimasa Koyanagi Aritsune Ooho Takeaki Satoh Kazuhiro Takahashi Ming-Lun Yeh Pei-Chien Tsai Satoshi Yasuda Yunyu Zhao Yishan Liu Tomomi Okubo Norio Itokawa Mi Jung Jun Toru Ishikawa Koichi Takaguchi Tomonori Senoh Mingyuan Zhang Changqing Zhao Raluca Ioana Alecu Wei Xuan Tay Pooja Devan Joanne Kimiko Liu Ritsuzo Kozuka Elena Vargas-Accarino Ai-Thien Do Mayumi Maeda Wan-Long Chuang Jee-Fu Huang Chia-Yen Dai Ramsey Cheung Maria Buti Junqi Niu Wen Xie Hong Ren Seng Gee Lim Chao Wu Man-Fung Yuen Jia Shang Qiang Zhu Yoshiyuki Ueno Yasuhito Tanaka Jun Hayashi Ming-Lung Yu Mindie H.Nguyen Department of Infectious Diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxiChina Division of Gastroenterology and Hepatology Department of MedicineStanford University Medical CenterPalo AltoCAUSA Department of General Internal Medicine Kyushu University HospitalFukuokaJapan Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung Hepatitis Research Center College of Medicine and Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiung Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical SciencesNagoyaJapan Gastroenterology&Hepatology Changi General HospitalSinghealthSingapore Singhealth Duke-NUS Medicine Academic Clinical Program Singapore Department of Gastroenterology Ogaki Municipal HospitalOgakiJapan Department of Internal Medicine Hanyang UniversityCollege of MedicineSeoulKorea Hanyang Institute of Bioscience and Biotechnology Hanyang UniversitySeoulKorea Department of Hepatology The Third People's Hospital of Kunming CityKunmingYunnanChina Department of Gastroenterology Internal MedicineKitasato University School of MedicineSagamiharaJapan Gastroenterological Center Yokohama City University Medical CenterYokohamaJapan Division of Gastroenterology and Hepatology Department of Internal MedicineE-Da Cancer HospitalKaohsiung Department of Gastroenterology and Hepatology Nagoya University Graduate School of MedicineNagoyaJapan Division of Gastroenterology and Hepatology Nippon Medical SchoolTokyoJapan Department of Gastroenterology Yamagata University Faculty of MedicineYamagataJapan Department of Transfusion Medicine and Department of Hepatology Osaka Metropolitan University Graduate School of MedicineOsakaJapan San Jose Gastroenterology San JoseCAUSA Gastroenterology&Hepatology Department Clinic Fundeni InstituteBucharestRomania Division of Gastroenterology and Hepatology University of WashingtonSeattleWAUSA Department of

Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination *** study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and ***:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/***:The mean age was 62±13 years,with 49.6%*** demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/***,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for ***12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for ***12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis *** multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving ***:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/***12 for GT3/6 with cirrhosis and TE was lower but st

关键词： Hepatitis C virus Liver cirrhosis Hepatocellular carcinoma Genotype DAA REAL-C

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Bifidobacteria Upregulate Expression of Toll-Like Receptor Negative Regulators Counteracting Enterotoxigenic <i>Escherichia coli</i>Mediated Inflammation in Bovine Intestinal Epitheliocytes

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Open Journal of Veterinary Medicine 2013年第2期3卷 143-155页

作者： Kozue Murata Julio Villena Yohsuke Tomosada Risa Hara Eriko Chiba Tomoyuki Shimazu Hisashi Aso Yoshihito Suda Noriyuki Iwabuchi Jin-Zhong Xiao Tadao Saito haruki Kitazawa Food and Feed Immunology Group Laboratory of Animal Products Chemistry Graduate School of Agricultural Science Tohoku University Sendai Japan

We previously established a bovine intestinal epithelial cell line (BIE cells) and showed that BIE cells are useful in vitro model system for the study of interactions between pathogenic and beneficial microorganisms and bovine intestinal epithelial cells (IECs). In the present study, we aimed to select potential immunomodulatory bifidobacteria that may be used to beneficially modulate the inflammatory response in bovine IECs. We also aimed to gain insight into the molecular mechanisms involved in the anti-inflammatory effect of bifidobacteria by evaluating the role of Toll-like receptor (TLR)-2 and TLR negative regulators in the regulation of proinflammatory cytokines production and MAPK, NF-κB and PI3K pathways activation in BIE cells. Five bifidobacteria strains were evaluated in this study and according to their capacity to modulate the inflammatory response of BIE cells. Despite the unique effect of each strain, four common points were found when comparing the effect of the high and moderate anti-inflammatory strains: 1) Upregulation of TLR negative regulators and the intensity of that upregulation was related to the different immunomodulatory capacity of each bifidobacteria strain;2) The balance between MAPK activation and MKP-1 upregulation affected the anti-inflammatory effect of bifidobacteria in BIE cells;3) The inhibition of PI3K pathway was related to the anti-inflammatory effect of bifidobacteria;4) The immunoregulatory effect of bifidobacteria in BIE cells is partially dependent on TLR2. This study shows that BIE cells can be used for the selection of immunoregulatory bifidobacteria and for studying the mechanisms involved in the protective activity of immunobiotics against TLR4-induced inflammatory damage. In addition, we have demonstrated that the anti-inflammatory effect of bifidobacteria was achieved by a complex interaction of multiple TLRs negative regulators as well as the inhibition/activation of multiple signaling pathways.

关键词： Bovine Intestinal Epithelial Cells Bifidobacteria ETEC TLRs Negative Regulators

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Cytosolic chaperonin CCT possesses GTPase activity

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American Journal of Molecular Biology 2011年第3期1卷 123-130页

作者： Susumu Noguchi Kazuyoshi Toyoshima Soh Yamamoto Toshio Miyazaki Michiro Otaka Sumio Watanabe Katsunori Imai haruki Senoo Ryoji Kobayashi Mitsutoshi Jikei Yasushi Kawata Hiroshi Kubota Hideaki Itoh 不详

Cytosolic chaperonin CCT (also known as TRiC) is a hetero-oligomeric cage-like molecular chaperone that assists in protein folding by ATPase cycle-dependent conformational changes. However, role of the nucleo-tide binding and hydrolysis in CCT-assisted protein folding is still poorly understood. We purified CCT by using ATP-Sepharose and other columns, and found that CCT possesses ability to hydrolyze GTP, with an activity level very similar to the ATPase activity. CCT was more resistant to proteinase K treatment in the presence of GTP or ATP. These results suggest that the GTPase activity of CCT may play a role in chaperone-assisted protein folding.

关键词： Chaperonin Molecular Chaperone Protein Folding Gtp

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Design of the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS): A Multidisciplinary Observational Epidemiological Study

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Open Journal of Endocrine and Metabolic Diseases 2013年第2期3卷 144-156页

作者： Toshitaka Muneyuki Kaname Suwa haruki Oshida Tomoya Takaoka Ayano Kutsuma Tsukasa Yoshida Masafumi Saito Yumiko Hori Yoshihiko Kannno Eiichiro Kanda Masafumi Kakei Shin-Ichi Momomura Kei Nakajima Division of Clinical Nutrition Department of Medical Dietetics Faculty of Pharmaceutical Sciences Josai University Sakado Japan

Background: In the past few decades, the incidence of cardiometabolic diseases and disorders of the liver, kidney, pancreas, heart, and lung, have been increasing in Western and Asian countries, including Japan. Numerous factors, including abnormal body weight (obesity, overweight, or underweight), infrequent exercise, and other unfavorable lifestyle factors (e.g., smoking and heavy alcohol drinking) have been proposed as risk factors for the development and the progression of diseases, such as type 2 diabetes, hypertension, and dyslipidemia, which ultimately lead to impaired organ function and possibly death. However, the mechanisms that link these risk factors with diseases are still poorly understood, and the potential treatments, including pharmacotherapy and diet, have not been fully evaluated. Methods: In 2011, we established a new collaborative research program, the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS). This multidisciplinary observational epidemiological research study was designed to cover several high-profile diseases and some traditional fields of internal medicine, as well as apparently unrelated fields and particular lifestyle factors, such as unhealthy eating behaviors. In a series of studies, apparently healthy subjects who underwent a regular medical checkup were retrospectively identified based on the results of their medical checkups. In this way, the incidence, prevalence, causality, and clinical relevance of specific conditions and diseases have been investigated in cross-sectional analyses of 100,000 - 200,000 adults, and in longitudinal studies of several thousand subjects who underwent medical checkups multiple times. Discussion: This article describes the background, rationale, purpose, and methods of the SCDOIS. Using data obtained from annual medical checkups, our goals are to 1) establish criteria or identify clinical features that would enable clinicians to detect the presence of abnormal conditions associat

关键词： Obesity Cardiometabolic Risks Organ Impairments Asians Diabetes Nutrition Saitama Checkup

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Condyloma acuminatum of the anal canal,treated with endoscopic submucosal dissection

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World Journal of Gastroenterology 2016年第8期22卷 2636-2641页

作者： Akiko Sasaki Takeshi Nakajima Hideto Egashira Kotaro Takeda Shinnosuke Tokoro Chikamasa Ichita Sakue Masuda haruki Uojima Kazuya Koizumi Takeshi Kinbara Taku Sakamoto Yutaka Saito Makoto Kako Gastroenterology Medicine Center Shonan Kamakura General Hospital 1370-1 Okamoto Kamakura Endoscopy Division National Cancer Center Hospital5-1-1 Tsukiji Chuoku Diagnostic Pathology Shonan Kamakura General Hospital 1370-1 Okamoto Kamakura

Condyloma acuminatum(CA) is a common sexually transmitted disease caused by human papilloma virus infection. Not all individuals develop persistent, progressive disease, but careful follow up is required with moderate-to-severe dysplasia to prevent progression to malignancy. Standard therapies include surgical treatments(trans-anal resection and transanal endoscopic microsurgery) and immunotherapeutic and topical methods(topical imiquimod); however, local recurrence remains a considerable problem. Here, we report a case with superficial CA of the anal canal, treated with endoscopic submucosal dissection(ESD). A 28-year-old man presented with a chief complaint of hematochezia. Digital exam did not detect a tumor. Screening colonoscopy revealed 10-mm long, whitish condyles extending from the anal canal to the lower rectum. The lesion covered almost the whole circumference, and only a small amount of normal mucosa remained. Magnifying endoscopy with narrow band imaging showed brownish hairpin-shaped, coiled capillaries. Although histopathological diagnosis by biopsy revealed CA, accurate histological differentiation between CA, papilloma, and squamous cell carcinoma can be difficult with a small specimen. Therefore, weperformed diagnostic ESD, which provides a complete specimen for precise histopathological evaluation. The pathological diagnosis was CA, with moderate dysplasia(anal intraepithelial neoplasia 2). There was no recurrence at 16 mo after the initial ESD. Compared to surgical treatment, endoscopic diagnosis and resection could be performed simultaneously and the tumor margin observed clearly with a magnifying chromocolonoscopy, resulting in less recurrence. These findings suggest that endoscopic resection may be an alternative method for CA that prevents recurrence.

关键词： Condylomata acuminate Recurrence Endoscopy Dissection Carcinoma in situ

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隔震橡胶垫极限性能足尺试验结果与评价

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世界地震工程 2008年第1期24卷 82-87页

作者：马华北村春幸李振宝周锡元北京工业大学工程抗震与结构诊治北京市重点实验室北京100022 东京理科大学理工学部建筑学科

针对隔震建筑中使用的天然橡胶类叠层橡胶垫、高阻尼叠层橡胶垫和铅芯叠层橡胶垫,调查了日本叠层橡胶垫制造公司持有的极限性能足尺试验结果,并对这三类叠层橡胶垫进行了新的足尺极限性能试验。调查与试验结果表明,ISO标准采用的叠层橡... 详细信息

针对隔震建筑中使用的天然橡胶类叠层橡胶垫、高阻尼叠层橡胶垫和铅芯叠层橡胶垫,调查了日本叠层橡胶垫制造公司持有的极限性能足尺试验结果,并对这三类叠层橡胶垫进行了新的足尺极限性能试验。调查与试验结果表明,ISO标准采用的叠层橡胶垫极限性能预测公式是合理可行的。

关键词：隔震叠层橡胶垫极限性能

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Effects of Neuroticism on Partial and Whole Body Reactions under Stress

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Journal of Sports Science 2015年第4期3卷 155-164页

作者： Kanaka Yatabe Hiroto Fujiya Naoko Yui Keisuke Tateishi Yuka Murofushi Fumiko Terawaki Atsuhiro Yoshida Hirotaka Yoshioka Koh Terauchi Hajime Kobayashi Takaaki Kudo Mahiro Ohno Aya Uchino Hisao Miyano Tadasu Oyama haruki Musha Department of Sports Medicine St. Marianna University School of Medicine Kawasaki 216-8511 Japan Department of Sports Medicine St. Marianna University Graduate School of Medicine Kawasaki 216-8511 Japan Research Division National Center for University Entrance Examinations Tokyo 153-8501 Japan Department of Psychology College of Humanities and Sciences Nihon University Tokyo 156-8550 Japan

Effects of neuroticism on partial and whole body reaction times were investigated under stress, or choking conditions in student participants （N = 127）. We measured simple and choice reaction times of parts of the body and choice reaction times of the whole body in the participants with high and low neuroticism such as depression, cyclic tendency, inferiority feelings, and nervousness under the controlled stress scenario of being in front of people. Results indicated significant differences in reaction times of partial body, discriminative decisions and choice reaction times of participants in the high neuroticism group. Results of whole body reaction times were opposite to that of partial body reactions. However, a two-way factorial analysis of variance indicated neither a significant main effect, nor interactions between reaction times and personality traits. Whole body reactions suggest that the effects of stimulus transduction process from motor commands to motor outputs via motor neurons has a greater effect in the central nervous system than recognition and decision-making. However, it is possible that changes in the intracortical mechanisms related to cognitions and emotions could be correlated in partial body movements with nearly no muscular activity. Our findings suggested that delays indiscrimination, decision-making, and choice times could affect the performance of individuals.

关键词： Personality traits stress reaction.

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Alterations of Blood Immune Cells in Elderly Patients with COVID-19 and with or without Pre-Existing Type 2 Diabetes

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Open Journal of Immunology 2022年第2期12卷 41-63页

作者： Susana Salva Yanina Kolling Nicolás Argañaraz María Pía Rocchia Novillo María del Milagro Rocchia Novillo Leonardo Albarracin Jacqueline Charubi Alejandra Casen Nadia Gobbato Mirta Rachid Susana Alvarez haruki Kitazawa Julio Villena Juan Carlos Valdez Laboratory of Immunobiotechnology Reference Centre for Lactobacilli (CERELA-CONICET) Tucuman Argentina Laboratory of Immunology Faculty of Biochemistry Chemistry and Pharmacy National University of Tucuman Tucuman Argentina Hospital Centro de Salud “Zenon Santillan” Tucuman Argentina Instituto de Maternidad “Ntra. Sra. De las Mercedes” Tucuman Argentina Food and Feed Immunology Group Laboratory of Animal Food Function Graduate School of Agricultural Science Tohoku University Sendai Japan Livestock Immunology Unit International Education and Research Center for Food and Agricultural Immunology (CFAI) Graduate School of Agricultural Science Tohoku University Sendai Japan

Elderly individuals, especially those with pre-existing conditions like type 2 diabetes mellitus (T2DM), have a high risk for developing severe cases of COVID-19. The aim of this work was to characterize the alterations of blood immune cells (BIC) in patients with symptomatic COVID-19 and confirmed SARS-CoV-2 infection, ≥60 years and who needed hospitalization in the Centro de Salud Hospital of Tucuman, Argentina, during the second peak of the pandemic in Argentina. Ten patients were enrolled from December 2020 to May 2021. Blood samples were taken at the time of admission (day 0) and five days after (day 5) for routine laboratory tests and the characterization of BIC by flow cytometry. Most of the patients were men (70%) aged between 60 and 78 years. The 70% of patients had T2DM while 50% had arterial hypertension. At day 0, all the patients had increased neutrophils and inflammatory markers (C reactive protein and D-dimers) and reduced numbers of lymphocytes, HLA-DRhi monocytes, CD16+CD56+ NK cells, CD3+HLA−DR+CD25+ cells, CD4+ and CD8+ T cells in blood. Patients received a standard treatment for COVID-19 care (O2, corticosteroids and antibiotics). The hospital treatment normalized the levels of BIC (day 5) in 30% of patients who were those with no comorbidities. In patients with T2DM, BIC recovery was variable. In T2DM patients who required administration of plasma (30%), prolonged O2 therapy (40%) or referral to the intensive care unit (10%) significant reductions of CD16+CD56+, CD3+HLA−DR+CD25+, CD4+ and CD8+ cells were observed between days 0 and 5. In line with previous studies, our results show that absolute counts of major lymphocyte subsets in blood are significantly and substantially decreased during the course of severe COVID-19 disease

关键词： COVID-19 SARS-CoV-2 Diabetes Elderly Blood Leukocytes Immune Response

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“剧场”商店

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现代装饰 2021年第4期 16-23页

作者： haruki Oku(设计) Yuriko Yagi(设计) Kazumass Takada(设计) Kenji Seo(摄影) Crazy.Inc(摄影) 范嘉苑(编译) 日本haruki OKU DESIGN 丹麦PAN-PROJECTS 不详

“剧场”商店位于日本东京繁华时尚的青山区(Aoyama),是一个三层建筑的全新改造项目。建筑的一层和二层是英国时装品牌店,三层是婚礼及活动策划公司的专属大厅。设计团队面临的挑战是要重新考量实体零售商店的现有功能,并设想出后疫情... 详细信息

“剧场”商店位于日本东京繁华时尚的青山区(Aoyama),是一个三层建筑的全新改造项目。建筑的一层和二层是英国时装品牌店,三层是婚礼及活动策划公司的专属大厅。设计团队面临的挑战是要重新考量实体零售商店的现有功能,并设想出后疫情时代的新商业空间模式。全球新冠疫情显著地加快了社会的数字化进程,持续的快速发展预示着未来的购物体验趋势将愈发地往虚拟世界转移。如果说人们更喜欢在线购物,那我们应该要重新思考,当实体商店从以展示及储存为主要空间功能的模式中解放出来后,它还能给用户提供哪些体验?

关键词：活动策划数字化进程时装品牌虚拟世界购物体验在线购物空间功能改造项目

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