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Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling

Acta Pharmaceutica Sinica B 2022年第7期12卷 3073-3084页

作者： Ziying Sun Qianqian Liu Zhongyang Lv Jiawei Li Xingquan Xu Heng Sun Maochun Wang Kuoyang Sun Tianshu Shi Zizheng Liu Guihua Tan Wenqiang Yan Rui Wu Yannick Xiaofan Yang shiro ikegawa Qing Jiang Yang Sun Dongquan Shi State Key Laboratory of Pharmaceutical Biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Laboratory for Bone and Joint Disease Model Animal Research Center(MARC)Nanjing UniversityNanjing 210093China State Key Laboratory of Pharmaceutical Biotechnology Department of Biotechnology and Pharmaceutical SciencesSchool of Life ScienceNanjing UniversityNanjing 210023China Drum Tower of Clinical Medicine Nanjing Medical UniversityNanjing 210008China Laboratory for Bone and Joint Diseases RIKEN Center for Integrative Medical Science(IMSRIKEN)Tokyo 108-8639Japan

Osteoarthritis(OA),in which M1 macrophage polarization in the synovium exacerbates disease progression,is a major cause of cartilage degeneration and functional *** strategies of OA designed to interfere with the polarization of macrophages have rarely been ***,we report that SHP099,as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2(SHP2),attenuated osteoarthritis progression by inhibiting M1 macrophage *** demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model *** to wild-type(WT)mice,myeloid lineage conditional Shp2 knockout(c KO)mice showed decreased M1 macrophage polarization and attenuated severity of synovitis,an elevated expression of cartilage phenotype protein collagen II(COL2),and a decreased expression of cartilage degradation markers collagen X(COL10)and matrix metalloproteinase3(MMP3)in OA *** mechanistic analysis showed that SHP099 inhibited lipopolysaccharide(LPS)-induced Toll-like receptor(TLR)signaling mediated by nuclear factor kappa B(NF-κB)and PI3K—AKT ***,intra-articular injection of SHP099 also significantly attenuated OA progression,including joint synovitis and cartilage *** results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

关键词： SHP2 SHP099 Osteoarthritis Synovitis Toll-like receptor signaling Macrophage Cartilage degradation M1 macrophage polarization

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History of Western Philosophy and Quantum Language (Including Quantum Mechanics, Statistics, Fuzzy Logic, etc.)

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Journal of Applied Mathematics and Physics 2024年第5期12卷 1769-1795页

作者： shiro Ishikawa Department of Mathematics Faculty of Science and Technology Keio University Yokohama Japan

Although there are many different types of philosophy, many philosophers agree that the mainstream of Western philosophy (Socrates, Plato, Aristotle, Descartes, Kant, Wittgenstein) developed toward the perfection of Socrates’ absolutism. But can the absolutism maintain its central position after analytic philosophy? There are pessimistic views on this problem, such as that of R. Rorty, the standard-bearer of neo-pragmatism. Recently, I proposed quantum language (which is including quantum mechanics, statistics, fuzzy sets, etc.). I think that that this theory is not only one of the most fundamental scientific theories, but also the scientific final destination of Western philosophy. If so, Socrates’ dream has come true. The purpose of this paper is to discuss the above and to inform readers that quantum language has the power to create a paradigm shift from the classical mechanical world view to the quantum mechanical worldview.

关键词： Quantum Language Linguistic Copenhagen Interpretation Fuzzy Logic

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Population-based X-ray gastric cancer screening in Hiroshima prefecture, Japan

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World Journal of Clinical Oncology 2024年第2期15卷 271-281页

作者： Nhu Thi Hanh Vu Yuji Urabe Duc Trong Quach shiro Oka Toru Hiyama Department of Internal Medicine University of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh 700000Viet Nam Department of Endoscopy Hiroshima University HospitalHiroshima 734-8551Japan Department of Gastrointestinal Endoscopy and Medicine Hiroshima University HospitalHiroshima 734-8551Japan Department of Gastroenterology Hiroshima University HospitalHiroshima 734-8551Japan Health Service Center Hiroshima UniversityHigashihiroshima 739-8514Japan

BACKGROUND X-ray gastric cancer(GC)screening has been shown to decrease ***-based X-ray GC screening has been performed in Hiroshima Prefe-cture,Japan,since 1983 but time trends and the efficacy of the method over 39 years have not been *** This was a population-based retrospective *** data were derived from aggregated data of the Hiroshima Regional Health Medical Promotion Organization,including the number and rate of participants and those requiring esophagogastroduodenoscopies(EGDs),the number and rate of participants diagnosed as having GC,and the positive predictive value of the abnormal findings detected by X-ray and confirmed by *** number and rate of esophageal cancers were also ***,the cost of detecting one GC was *** The number of participants has decreased during the last four decades,from 39925 in 1983 to 12923 in *** rate of those requiring EGDs decreased significantly in recent years(P<0.001).The number of participants diagnosed as having GC has also declined,from 76 to 10 ***,the rate of cases diagnosed as GC among the participants remained around 0.1%.The positive predictive value increased significantly in recent years except during *** number and rate of accidentally detected esophageal cancers have risen recently,from 0%in 2008 to 0.02%in 2021,one-fifth of the diagnosis rate of *** GC diagnosis costs approximately 4200000 Japanese Yen(30000 United States Dollars)for the X-ray screenings and *** X-ray GC screening in Hiroshima has been efficient,but one challenge is the *** cancers may also need to be considered because they have gradually increased in recent years.

关键词： Population Retrospective studies X-ray Gastric cancer Screening

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Which characteristics are associated with changes in medication status for lower urinary tract symptoms among patients with prostate cancer receiving external beam radiotherapy?

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Current Urology 2024年第2期18卷 122-127页

作者： Yuki Kyoda Kohei Hashimoto Atsushi Takahashi TakeshiMaehana Kimihito Tachikawa Takashi Muranaka Shuichi Kato Tomoyo Kurisug Fumimasa Fukuta Takahiro Kirisawa Manabu Okada Ko Kobayashi Toshiaki Tanaka shiro Hinotsu Naoya Masumoria Department of Urology SapporoMedical University School of MedicineSapporoJapan Department of Urology Hakodate Goryoukaku HospitalHakodateJapan Department of Urology Muroran City General HospitalMuroranJapan Department of Urology NTT-East Sapporo HospitalSapporoJapan Department of Urology Sunagawa City Medical CenterSunagawaJapan Department of Urology Oji General HospitalTomakomaiJapan Department of Urology Steel Memorial Muroran HospitalMuroranJapan Department of Urology Obihiro Kyokai HospitalObihiroJapan Department of Medical Statistics Sapporo Medical University School of MedicineSapporoJapan

Background:We clarified the predictive factors for changes in the status ofmedications for lower urinary tract symptoms(LUTS)2 years after local radiotherapy for nonmetastatic prostate *** and methods:We retrospectively included patients who underwent local external radiotherapy for nonmetastatic prostate cancer in 8 institutions between April 2001 and March *** were divided into themedication and no-medication group based on the use of drugs for LUTS before *** defined improvement of LUTS as when the patient did not require medication for LUTS at 24 months after radiotherapy in the medication group and as deterioration whenmedication was required in the no-medication *** regression analysis was used to evaluate predictive factors for changes in medication ***:Altogether,505 patients were divided into a no-medication group(n=352)and a medication group(n=153).The number of patients with deterioration and improvement in LUTS was 49(14%)and 36(23%),*** the multivariate analysis,the predictive variables for deterioration were the International Prostate SymptomScore(≥8;odds ratio[OR],2.21;p=0.014)and the biopsy Gleason score(≤3+4=7;OR,2.430;p=0.008)in the no-medication group,whereas those for improvement were age(<75 years old;OR,5.81;p=0.002),the quality of life score(<3;OR,3.15;p=0.028),and a positive biopsy core rate(≥50%;OR,2.530;p=0.027)in the medication ***:These predictive factors for changes in the status ofmedications for LUTS at 2 years after external radiotherapymay help determine the definitive therapy for nonmetastatic prostate cancer.

关键词： Prostate cancer Radiotherapy Lower urinary tract symptoms Medications

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High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1487-1496页

作者： Nao Furuya Atsushi Yamaguchi Naohiro Kato Syuhei Sugata Takuro Hamada Takeshi Mizumoto Yuzuru Tamaru Ryusaku Kusunoki Toshio Kuwai Hirotaka Kouno Kazuya Kuraoka Yoshiyuki Shibata Sho Tazuma Takeshi Sudo Hiroshi Kohno shiro Oka Department of Gastroenterology National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKure 737-0023HiroshimaJapan Department of Gastroenterology Hiroshima University HospitalHiroshima 734-8551HiroshimaJapan Department of Pathology National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKure 737-0023HiroshimaJapan Department of Surgery National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKure 737-0023HiroshimaJapan

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination ***,it can be diagnosed by pancreatic juice cytology from indirect *** previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic *** revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD ***,course observation was *** 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic *** performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology *** performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade *** parenchyma invasion was not observed,and curative resection was *** High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

关键词： Pancreatic cancer Pancreatic intraepithelial neoplasm High-grade pancreatic intraepithelial neoplasm Magnetic resonance cholangiopancreatography Carcinoma in situ Case report

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Cellulose decomposition behavior in hot-compressed aprotic solvents

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Science China Chemistry 2008年第5期51卷 479-486页

作者： shiro SAKA Department of Socio-Environmental Energy Science Graduate School of Energy ScienceKyoto University

Microcrystalline cellulose (avicel) is treated in hot-compressed aprotic solvents, sulfolane and 1,4-dioxane, using a batch-type reaction system with a molten tin bath in a range from 290 to 390°C. The corresponding densities of the solvent are 0.25–1.26 g/cm3 and 0.21–1.03 g/cm3 for sulfolane and 1,4-dioxane, respectively. As a result, in both solvents, more than 90% of cellulose is found to be decomposed to the solvent-soluble portion in which levoglucosan is the main component with the highest yield of about 35% on original cellulose basis. The decomposition rate to levoglucosan is, however, faster in sulfolane than in 1,4-dioxane, while levoglucosan is more stable in 1,4-dioxane. In addition, its yield is found to be solvent-density dependent to be highest around 0.4–0.5 g/cm3 for both solvents. To elucidate these decomposition behaviors, the results obtained in this study with aprotic solvents are compared with protic solvents such as water and methanol in previous works.

关键词： cellulose aprotic solvent solvent density decomposition behavior

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Pancreatic cancer early detection:Expanding higher-risk group with clinical and metabolomics parameters

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World Journal of Gastroenterology 2015年第6期21卷 1707-1717页

作者： shiro Urayama Division of Gastroenterology and Hepatology Department of Internal Medicine University of California Davis

Pancreatic ductal adenocarcinoma(PDAC)is the fourth and fifth leading cause of cancer death for each gender in developed *** lack of effective treatment and screening scheme available for the general population,the mortality rate is expected to increase over the next several decades in contrast to the other major malignancies such as lung,breast,prostate and colorectal *** ultrasound,with itshighest level of detection capacity of smaller pancreatic lesions,is the commonly employed and preferred clinical imaging-based PDAC detection *** molecular biomarkers have been investigated for characterization of the disease,but none are shown to be useful or validated for clinical utilization for early *** seen from studies of a small subset of familial or genetically high-risk PDAC groups,the higher yield and utility of imaging-based screening methods are demonstrated for these *** recent studies on the unique cancer metabolism including PDAC,demonstrate the potential for utility of the metabolites as the discriminant markers for this *** order to generate an early PDAC detection screening strategy available for a wider population,we propose to expand the population of higher risk PDAC group with combination clinical and metabolomics parameters.

关键词： Pancreatic cancer Endoscopic ultrasound Metabolomi

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Role of Salix reinii patches in spatio-temporal patterns of cohabitants on a Japanese volcano

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Journal of Plant Ecology 2022年第1期15卷 71-84页

作者： Miyuki Matsuda shiro Tsuyuzaki Division of Integrated Environmental Science Graduate School of Environmental Earth ScienceHokkaido UniversitySapporo 060-0810Japan IDEA Consultants Inc. 3-15-1 KomazawaSetagaya WardTokyo 154-8585Japan

Shrub patches often support the colonizers particularly under stressful and/or disturbed *** intensities of stresses and disturbances on mountains are often related to an elevation gradient and are decreased by shrub patches(canopy and litter).We aim to clarify these relationships by using shrub patches at different elevations on a *** monitored all shoots in plots established inside and outside of patches of Salix reinii(Salicaceae)and their related environments,such as temperature,light,moisture and chemistry,at three elevations on Mount Koma(1131 m a.s.l.),northern Japan,from early spring in 2005 to summer in *** patch structures were evaluated by area,branch density and litter *** structures of shrub patches did not differ among the *** patches increased the diversity of rare species,by an overall increase in plant species *** moisture,nitrogen and phosphate contents in the patches were higher than outside of *** effects of shrub patches on the cohabitants were overall positive,although the effects were negative on seedling abundance,shoot survival and *** results suggest that the growth patterns of shrub patches determine the plant community structures and facilitate plant diversity.

关键词： elevational difference interspecific interaction litter accumulation microenvironment shrub patch

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Changes in microbial community composition in the leaf litter of successional communities after volcanic eruptions of Mount Usu, northern Japan

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Journal of Mountain Science 2016年第9期13卷 1652-1662页

作者： Michiru OTAKI Fumiko TAKEUCHI shiro TSUYUZAKI Graduate School of Environmental Science Hokkaido University

Changes in the fungal and bacterial biomass and community structure in litter after the volcanic eruptions of Mount Usu, northern Japan were investigated using a chronosequence approach, which is widely used for analyzing vegetation succession. The vegetation changed from bare ground （10 years after the eruptions） with little plant cover and poor soil to monotonic grassland dominated by Polygonum sachalinense with undeveloped soil （33 years） and then to deciduous broad-leaved forest dominated by Populus maximowiczii with diverse species composition and well-developed soil （100 years）. At three chronosequential sites, we evaluated the compositions of phospholipid fatty acids （PLFAs）, carbon （C） and nitrogen （N） contents and the isotope ratios of C （δ13C） and N （δ15N） in the litter of two dominant species, Polygonum sachalinense and Populus maximowiezii. The C/N ratio, δ13C and δ15N in the litter of these two species were higher in the forest than that in the bare ground and grassland. The PLFAs gradually increased from the bare ground to the forest, showing that microbial biomass increased with the development of the soil and/or vegetation. The fungi-to-bacteria ratio of PLFA was constant at 5.3 ± 1.4 in all three sites, suggesting that fungi were predominant. A canonical correspondence analysis suggested that the PLFA comoosition was related to the successional ages and the developing soil properties （P 〈 0.05, ANOSIM）. The chrono- sequential analysis effectively detected the successional changes in both microbial and plant communities.

关键词： Volcanic succession Fungi-to-bacteriaratio Litter decomposition Microbial community Phospholipid fatty acids (PLFAs) Primary succession

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Centrifuge modeling of buried continuous pipelines subjected to normal faulting

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Earthquake Engineering and Engineering Vibration 2013年第1期12卷 155-164页

作者： Majid Moradi Mahdi Rojhani Abbas Galandarzadeh shiro Takada School of Civil Engineering College of EngineeringUniversity of Tehran

Seismic ground faulting is the greatest hazard for continuous buried *** the years,researchers have attempted to understand pipeline behavior mostly via numerical modeling such as the finite element *** lack of well-documented field case histories of pipeline failure from seismic ground faulting and the cost and complicated facilities needed for full-scale experimental simulation mean that a centrifuge-based method to determine the behavior of pipelines subjected to faulting is best to verify numerical *** paper presents results from three centrifuge tests designed to investigate continuous buried steel pipeline behavior subjected to normal *** experimental setup and procedure are described and the recorded axial and bending strains induced in a pipeline are presented and compared to those obtained via analytical *** influence of factors such as faulting offset,burial depth and pipe diameter on the axial and bending strains of pipes and on ground soil failure and pipeline deformation patterns are also ***,the tensile rupture of a pipeline due to normal faulting is investigated.

关键词： centrifuge models buried pipeline normal faulting earthquake permanent ground deformation

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