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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan juan Alec C.Bancroft ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard juhoon Lee Sowmya Ramesh Aaron W.james david Hudson Kevin N.Dalby Lin Xu Robert j.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

不同Nb含量X80钢管环焊热影响区的微观组织与韧性

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焊接学报 2024年第3期45卷 75-81,I0007页

作者：何小东杨耀彬陈越峰张永青 david Han 中国石油集团工程材料研究院有限公司石油管材及装备材料服役行为与结构安全国家重点实验室西安710077 国际焊接研究中心西安710077 中信金属股份有限公司北京100004

为研究Nb含量对焊接热影响区微观组织和性能的影响,采用熔化极气体保护焊(gas metal arc welding,GMAW)和手工焊条电弧焊(shielded metal arc welding,SMAW)对0.055%Nb和0.075%Nb含量的X80钢管进行环焊.采用夏比冲击试验和金相分析方法... 详细信息

为研究Nb含量对焊接热影响区微观组织和性能的影响,采用熔化极气体保护焊(gas metal arc welding,GMAW)和手工焊条电弧焊(shielded metal arc welding,SMAW)对0.055%Nb和0.075%Nb含量的X80钢管进行环焊.采用夏比冲击试验和金相分析方法,研究热影响区的微观组织差异和夏比冲击韧性.并借助扫描电镜和超高温激光共聚焦显微镜分析不同Nb含量X80管体的微观组织对热影响区性能的影响.结果表明,在0℃和-20℃时,0.075%Nb和0.055%Nb的X80钢管GMAW环焊接头热影响区均具有较高的冲击韧性,其平均冲击吸收能量均高于150 j.其中0.055%Nb略高于0.075%Nb的GMAW环焊接头热影响区夏比冲击吸收能量;焊接热输入较低时,0.055%Nb低于0.075%Nb的X80环焊接头粗晶区的韧脆转变温度,具有更好的低温韧性.焊接热输入较高时,0.075%Nb的X80环焊接头粗晶区具有更高的上平台冲击吸收能量,且上平台温度和韧脆转变温度也更低,其低温韧性也更优异;还发现了X80环焊接头热影响区的冲击韧性不仅与热输入量和热影响区马氏体-奥氏体组织(M-A)的形状、大小、分布有关,而且还受管体中Nb含量、原始的强度与韧性、微观组织状态的遗传影响.

关键词：含铌X80钢管环焊接头热影响区冲击韧性 M-A组织

Evaluation of corneal parameter changes under different accommodative stimuli with Scheimpflug imaging-based tomography

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国际眼科杂志 2024年第9期24卷 1357-1366页

作者： Farid j Bedrán-García david P Piñero Department of Optics Pharmacology and AnatomyUniversity of AlicanteAlicante 03690Spain

AIM:To evaluate the reliability of measurements of corneal changes with accommodation in healthy eyes using a Scheimpflug imaging-based system and how these measurements distribute in the normal ***:Prospective,non-randomized,comparative study including 27 healthy subjects(54 eyes),including emmetropia(13 eyes),myopia(17 eyes),hyperopia(4 eyes)and astigmatism(20 eyes)*** all cases,a complete eye examination was performed,including the analysis of corneal changes with different accommodative stimuli(+2.00,0.00 and-3.00 D)using the Pentacam AXL *** investigation was structured in 2 phases:repeatability analysis and characterization of accommodation-related corneal changes in healthy ***:In the repeatability analysis,the index of height asymmetry(IHA)showed the greatest variability with the three accommodative stimuli,being the results for the rest of parameters *** group of emmetropes showed significant differences with accommodative changes in the position of maximum keratometry(Kmax;P<0.05),whereas in the astigmatism group,significant changes were not only observed in the position of Kmax,but also in minimum corneal thickness(MCT),corneal spherical aberration,and total and low order aberration root mean square(all P<0.05).Likewise,a significant difference was found in the displacement of the X position of Kmax with+2.00 D and-3.00 D in the myopia group(P=0.033)as well as in changes with+2.00 D and-3.00 D in the magnitude of the position vector of Kmax in the emmetropia group(P<0.05).No significant changes were found between accommodative stimuli in the displacement of coordinates of MCT(P≥0.109).CONCLUSION:The position of Kmax and MCT in healthy corneas can change significantly when presenting different accommodative stimuli using the accommodation mode of the Pentacam system,with different trends in these accommodation-related corneal changes between refractive ***,the consistency of the measurement

关键词： corneal biomechanics keratometry corneal thickness pachymetry corneal aberrations Pentacam accommodation

Molecular Characterization of Gastrointestinal Stromal Tumors (Gist) and Contribution of Immunohistochemistry in Congolese from Kinshasa

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Open journal of Gastroenterology 2024年第4期14卷 109-116页

作者： Rive Lukuaku jérémie Okumadi Fabrice Bokambandja Andy Mbangama Vincent Mbatu Georges Mvumbi jean-Louis Mumbere david Azako Serge Pezo Dieudonné Mvumbi Faculty of Medicine Bel Campus Technological University Kinshasa DR Congo Department of Anatomy and Pathological Cytology University Clinics of Kinshasa Kinshasa DR Congo Department of Gyneco-Obstetrics University Clinics of Kinshasa Kinshasa DR Congo Molecular Biology Department Faculty of Medicine University of Kinshasa Kinshasa DR Congo Institute of Medical Immunology Free University of Brussels Ixelles Belgium

Introduction: The differentiation of digestive tumors very often requires the use of techniques currently not widely in use in the Democratic Republic of Congo (DRC), such as immunohistochemistry. This is perfectly verified for GISTs whose precise, or at least highly certain, diagnosis can only be made using immunohistochemical markers. This underuse of these techniques due to lack of equipment and human skills explains the limited epidemiological data available to date, thus leading to untargeted and too often late treatment of patients. Research question: What contribution can immunohistochemical markers make to the diagnosis of digestive tract tumours? Objective: Discuss the contribution of immunohistochemical markers in the diagnosis of GIST and provide basic data on the epidemiology of these nosological entities in Kinshasa. Methodology: This was a retrospective study carried out at the LEBOMA private anatomy and pathological cytology centre. The main inclusion criterion was any digestive tract block or slide whose diagnosis of GIST had been requalified after review by at least 2 pathologists. An immuhistochemical study was performed using an automated technique (with a Ventana XT machine) using a panel of antibodies: CD-117 and DOG-1 which are listed in the literature as strongly correlated with the occurrence of GIST, all slides were made at Hj Hospital using an OLYMPUS BX41 co-observation microscope. Results: Of 601 cases of digestive tumors recorded during the concerned period, 32 (5.32%) concerned GIST. This prevalence was confirmed by our immunohistochemical results where the expression of CD117 and that of DOG-1 were positive in 90.6% and 100% of cases which prevalence is high compared with the worldwide prevalence according to the literature, respectively. The distribution of the patients concerned was made with a sex ratio of 1.6 women/men with a median age of 53 years. Most cases (81%) had a gastric location and were fusiform GISTs. Conclusion: Gastro

关键词： Digestive Tumors GIST Immunohistochemistry CD117 DOG-1

Tantalum pentoxide:a new material platform for high-performance dielectric metasurface optics in the ultraviolet and visible region

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Light(Science & Applications) 2024年第1期13卷 142-152页

作者： Cheng Zhang Lu Chen Zhelin Lin junyeob Song Danyan Wang Moxin Li Okan Koksal Zi Wang Grisha Spektor david Carlson Henri j.Lezec Wenqi Zhu Scott Papp Amit Agrawal School of Optical and Electronic Information&Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China National Institute of Standards and Technology GaithersburgMD 20899USA University of Maryland College ParkMD 20742USA National Institute of Standards and Technology BoulderCO 80305USA

Dielectric metasurfaces,composed of planar arrays of subwavelength dielectric structures that collectively mimic the operation of conventional bulk optical elements,have revolutionized the field of optics by their potential in constructing high-efficiency and multi-functional optoelectronic systems on *** performance of a dielectric metasurface is largely determined by its constituent material,which is highly desired to have a high refractive index,low optical loss and wide bandgap,and at the same time,be fabrication ***,we present a new material platform based on tantalum pentoxide(Ta2O5)for implementing high-performance dielectric metasurface optics over the ultraviolet and visible spectral *** wide-bandgap dielectric,exhibiting a high refractive index exceeding 2.1 and negligible extinction coefficient across a broad spectrum,can be easily deposited over large areas with good quality using straightforward physical vapor deposition,and patterned into high-aspect-ratio subwavelength nanostructures through commonly-available fluorine-gas-based reactive ion *** implement a series of highefficiency ultraviolet and visible metasurfaces with representative light-field modulation functionalities including polarization-independent high-numerical-aperture lensing,spin-selective hologram projection,and vivid structural color generation,and the devices exhibit operational efficiencies up to 80%.Our work overcomes limitations faced by scalability of commonly-employed metasurface dielectrics and their operation into the visible and ultraviolet spectral range,and provides a novel route towards realization of high-performance,robust and foundry-manufacturable metasurface optics.

关键词： dielectric optics ultraviolet

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周年生物钟:赋予动物预知季节的能力

Science Bulletin 2024年第12期69卷 1839-1843页

作者：陈君凤吴蔚龙娟刘鑫 david Hazlerigg 詹祥江 Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Arctic Seasonal Timekeeping Initiative(ASTI) Department of Arctic and Marine Biology UiTThe Arctic University of NorwayTromsø9037Norway Cardiff University-Institute of Zoology joint Laboratory for Biocomplexity Research Chinese Academy of SciencesBeijing 100101China Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China

Seasonal changes in climate and animal behaviors have been depicted in Chinese literature since ancient times,such as the classical poem"HuìChóng Ch-un jiang Wǎn jǐng"by Su *** now know that the intricate interpla... 详细信息

关键词： periodic behaviors 生物钟

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

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World journal of Gastrointestinal Surgery 2024年第3期16卷 740-750页

作者： Phillip Gu Shishir Dube Norman Gellada So Yung Choi Susan Win Yoo jin Lee Shaohong Yang Talin Haritunians Gil Y Melmed Eric A Vasiliauskas Niru Bonthala Gaurav Syal Andres j Yarur david Ziring Shervin Rabizadeh Phillip Fleshner Cindy Kallman Suzanne Devkota Stephan R Targan Dalin Li Dermot PB McGovern Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Imaging Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Biostatistics Shared Resource Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Internal Medicine Keimyung University School of MedicineDaegu 42601South Korea Department of Medicine University of California at Los AngelesLos AngelesCA 90095United States Department of Medicine University of California at San DiegoSan DiegoCA 92093United States Department of Pediatrics Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory ***,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional *** advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential ***,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after *** strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off ***,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee Yj and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting

关键词： Crohn’s disease Surgery Visceral adipose tissue Mesenteric adipose tissue Creeping fat Computed tomography

High-speed silicon photonic electro-optic Kerr modulation

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Photonics Research 2024年第1期12卷 51-60页

作者： jONATHAN PELTIER WEIWEI ZHANG LEOPOLD VIROT CHRISTIAN LAFFORGUE LUCAS DENIEL DELPHINE MARRIS-MORINI GUY AUBIN FARAH AMAR DENH TRAN XINGZHAO YAN CALLUM G.LITTLEjOHNS CARLOS ALONSO-RAMOS KE LI david j.THOMSON GRAHAM REED LAURENT VIVIEN University Paris-Saclay CNRSCentre for Nanoscience and Nanotechnology(C2N)Palaiseau 91120France University Grenoble Alpes CEALETIGrenoble 38000France Optoelectronics Research Centre Zepler Institute for Photonics and NanoelectronicsFaculty of Engineering and Physical SciencesUniversity of SouthamptonSouthampton SO171BJUK

Silicon-based electro-optic modulators contribute to easing the integration of high-speed and low-power consumption circuits for classical optical communications and data *** the plasma dispersion modulation,an alternative solution in silicon is to exploit the DC Kerr effect,which generates an equivalent linear electro-optical effect enabled by applying a large DC electric *** some theoretical and experimental studies have shown its existence in silicon,limited contributions relative to plasma dispersion have been achieved in high-speed modulation so *** paper presents high-speed optical modulation based on the DC Kerr effect in silicon PIN *** contributions of both plasma dispersion and Kerr effects have been analyzed in different waveguide configurations,and we demonstrated that the Kerr induced modulation is dominant when a high external DC electric field is applied in PIN ***-speed optical modulation response is analyzed,and eye diagrams up to 80 Gbit/s in NRZ format are obtained under a *** of 30 *** work paves the way to exploit the Kerr effect to generate high-speed Pockels-like optical modulation.

关键词： waveguide dispersion effect

Natural products and drug discovery

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National Science Review 2022年第11期9卷 37-57页

作者： david j.Newman NIH Special Volunteer

This review covers the recent history of a series of very important natural products and their derivatives that are currently in use or under evaluation in the areas of anti-infectives, important cancer treatments that include antibody drug conjugates, followed by a discussion of type 2 diabetes(T2DM) drugs and angiotensin converting enzyme inhibitors. The current structures of the agents are shown, though in the case of some peptides used in T2DM drugs the standard single leTher abbreviation for an amino acid is used.

关键词： artemisinin glycopeptides anthracyclines dolastatin diabetes 2 ACE inhibitors