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The evolving.roles of Wnt sig.aling.in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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g.nes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu kevin Qin Jiaming.Fan g.ozhi Zhao Piao Zhao Wei Zeng.Connie Chen Annie Wang.Yong.ui Wang.jiamin Zhong.Yi Zhu William Wag.taff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong.Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncolog. Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diag.ostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surg.ry The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urolog. The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surg.ry Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biolog. and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurolog. The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt sig.aling.pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified sig.aling.molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt sig.aling.*** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt sig.aling.*** sig.aling.has emerg.d as an important factor in stem cell biolog. and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,g.t,neural,and epidermal stem *** sig.aling.has also been implicated in tumor cells that exhibit stem cell-like *** sig.aling.is crucial for bone formation and presents a potential targ.t for the development of therapeutics for bone *** surprising.y,aberrant Wnt sig.aling.is also associated with a wide variety of diseases,including.*** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing.of dysreg.lated Wnt sig.aling.in disease have paved the way for the development of novel therapeutics that targ.t components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledg. of Wnt sig.aling.in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targ.ting.the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targ.ted therapy Wnt sig.aling

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Comparison of a Manual and an Automated Tracking.Method for Tibetan Plateau Vortices

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Advances in Atmospheric Sciences 2018年第8期35卷 69-84页

作者： Julia CURIO Yong.en CHEN Reinhard SCHIEMANN Andrew g. TURNER Kai Chi WONg.kevin HODg.S Yueqing.LI NCAS-Climate University of Reading Reading RG6 6BB UK Department of Meteorolog. University of Reading Reading RG6 6BB UK Institute of Plateau Meteorolog. China Meteorological Administration Chengdu 610072 China Heavy Rain and Droug.t-Flood Disasters in Plateau and Basin Key Laboratory of Sichuan Province Chengdu 610072 China

Tibetan Plateau vortices （TPVs） are mesoscale cyclones orig.nating.over the Tibetan Plateau （TP） dnring.the extended summer season （April-September）. Most TPVs stay on the TP, but a small number can move off the TP to the east. TPVs are known to be one of the main precipitation-bearing.systems on the TP and moving.off TPVs have been associated with heavy precipitation and flooding.downstream of the TP （e.g., in Sichuan province or over the Yang.ze River Valley）. Identifying.and tracking.TPVs is difficult because of their comparatively small horizontal extent （400-800 kin） and the limited availability of sounding. over the TP, which in turn constitutes a challeng. for short-term predictions of TPV-related impacts and for the climatolog.cal study of TPVs. In this study, （i） manual tracking.（MT） results using.radiosonde data from a network over and downstream of the TP are compared with （ii） results obtained by an automated tracking.（AT） alg.rithm applied to ERA-Interim data. Ten MT-TPV cases are selected based on method （i） and matched to and compared with the corresponding.AT-TPVs identified with method （ii）. Conversely, ten AT-TPVs are selected and compared with the corresponding.MT-TPVs. In g.neral, the comparison shows g.od results in cases where the underlying.data are in g.od ag.eement, but considerable differences are also seen in some cases and explained in terms of differences in the tracking.methods, data availability/coverag. and disag.eement between sounding.and ERA-Interim data. Recommendations are g.ven for future efforts in TPV detection and tracking. including.in an operational weather forecasting.context.

关键词： Tibetan Plateau Vortices Yearbook of TPVs TRACK mesoscale cyclones manual tracking automated tracking

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Comparison of Cog.itive Reg.stration Transrectal Ultrasound-g.ided Targ.ted Biopsy of Prostate to Systematic 12-Core Biopsy: A Retrospective, Multicentre Study

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Open Journal of Urolog. 2024年第7期14卷 381-390页

作者： kevin Chang.Yue Wei Lee Say Bob Devindran Manoharan Liong.Men Long.Teoh Sze Yong.Teo Rui Ling.Chua Zi Wei Department of Urolog. Hospital Pulau Pinang George Town Malaysia Department of Urolog. Georgetown Specialist Hospital George Town Malaysia Department of Radiolog. Hospital Pulau Pinang George Town Malaysia Department of Radiolog. Georgetown Specialist Hospital George Town Malaysia

Introduction: Prostate cancer (PCa) is the third most prevalent cancer among.Malaysian males, often diag.osed at advanced stag.s, leading.to suboptimal outcomes. While transrectal ultrasound-g.ided systematic biopsy (TRUS-SB) is the primary diag.ostic method, prebiopsy multiparametric mag.etic resonance imag.ng.(mpMRI) is g.ining.popularity in identifying.suspicious lesions. This study addresses the lack of comprehensive investig.tions into the efficacy of cog.itive reg.stration TRUS targ.ted biopsy (COg.TB) compared to conventional TRUS-SB, considering.the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antig.n (PSA) level of more than 4 ng.mL who underwent both COg.TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopatholog.cal outcomes, including.g.eason score. Results: COg.TB showed a hig.er overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically sig.ificant cancer detection rates were similar between COg.TB and TRUS-SB (37.1%). Further analysis revealed that both COg.TB and TRUS-SB detected clinically sig.ificant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting.finding. in 16 patients (p Conclusion: COg.TB and TRUS-SB have comparable detection rates for clinically sig.ificant prostate cancer, with COg.TB showing.a hig.er tendency to detect insig.ificant prostate cancer. Further studies comparing.these methods are warranted.

关键词： Prostate Cancer Multiparametric MRI Targ.ted Biopsy Cog.itive Fusion Transrectal Ultrasound-g.ided Biopsy

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The HIF-1α/PLOD2 axis integ.ates extracellular matrix org.nization 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 g.o Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pag.ni 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 Org.nog.nesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surg.ry 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 Biolog. and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Patholog. Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic sig.aling.has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)org.nization 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 prog.nitor cells(MPCs)contributes to patholog.c bone formation remain to ***,we used a proven mouse injury-induced HO model to investig.te the role of HIF-1αon aberrant cell ***-cell RNA sequencing.scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collag.n ECM org.nizationis the most hig.ly up-reg.lated biolog.cal process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))sig.ificantly mitig.ted HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collag.n cross-linking.as downstream of the HIF-1αreg.lation of ***,our scRNA-seq data and mechanisticstudies further uncovered that g.ucose metabolism in MPCs is most hig.ly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor sig.ificantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssig.ificantly decreased osteog.nic differentiation and g.ycolytic *** sug.ests that the HIF-1α/PLOD2/LOX axis linked tometabolism reg.lates HO-forming.MPC *** results sug.est that the HIF-1α/PLOD2/LOX pathway represents a promising.trateg. to mitig.te HO formation.

关键词： metabolism skeletal aberrant

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M+博物馆

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世界建筑导报 2024年第3期39卷 96-99页

作者： Virg.le Simon Bertrand(摄) kevin Mak(摄) 不详

M+博物馆是西九文化区的一大文化中心,为20世纪和21世纪的艺术、设计、建筑和动态影像的展示场所。仅仅20年前,西九文化区所处之地还是海港的一部分。一块接一块地填海造地,将天然港湾改造成为陆地。现在,这片人工填海的土地是西九文化... 详细信息

M+博物馆是西九文化区的一大文化中心,为20世纪和21世纪的艺术、设计、建筑和动态影像的展示场所。仅仅20年前,西九文化区所处之地还是海港的一部分。一块接一块地填海造地,将天然港湾改造成为陆地。现在,这片人工填海的土地是西九文化区新建筑的建设场地。有意思的是,恰好是另一项曾被视为场地规划的阻碍工程,即机场快线的地下隧道,定义了这片区域的特殊性,成为M+博物馆项目设计的起点。

关键词：文化区场地规划建设场地填海造地动态影像博物馆地下隧道 21世纪

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从BRDF到BPDF:遥感反演基础模型的演进初探

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中国科学：信息科学 2024年第8期54卷 2001-2020页

作者：尚可晏磊张飞舟褚君浩杨彬刘思远 kevin TANSEY 贾秀萍 Oleg.DUBOVIK 张子晗李飞北京大学地球与空间科学学院遥感与地理信息系统研究所北京大学空间信息集成与3S工程应用北京市重点实验室北京100871 中国科学院上海技术物理研究所红外物理国家重点实验室上海200083 湖南大学电气与信息工程学院长沙410082 中国兵器工业导航与控制技术研究所北京100089 School of g.og.aphy Geologyand the EnvironmentUniversity of LeicesterLeicester LE17RHUK School of Eng.neering.and Technolog. The University of New South WalesCanberra ACT 2600Australia Laboratoire d'Optique Atmospherique CNRS/UniversitéLilleVilleneuve d'Ascq 59655France

光的本质是横波电磁波矢量,以双向反射分布函数BRDF (bidirectional reflectance distribution function)为基础模型的标量遥感体系只利用植被反射光的整体强度信息,无法进一步区分反射辐射蕴含的叶表、叶内和冠层结构信息;在标量遥感... 详细信息

光的本质是横波电磁波矢量,以双向反射分布函数BRDF (bidirectional reflectance distribution function)为基础模型的标量遥感体系只利用植被反射光的整体强度信息,无法进一步区分反射辐射蕴含的叶表、叶内和冠层结构信息;在标量遥感基础上考虑垂直于电磁波传播方向的二维偏振矢量特性(强度+方向)就能深化为矢量遥感体系,从而有望精确刻画反射光中蕴含的多种信息,提升植被参数反演精度.刻画偏振反射空间分布的双向偏振分布函数BPDF目前存在精度低、泛化性差等问题,因此进一步探索矢量遥感基础理论,构建通用性强的植被矢量遥感基础模型具有迫切的现实需求.本文旨在利用光子与植被元素的相互作用构建通用性较强的植被BPDF物理模型.首先基于光子–植被元素相互作用的光谱不变原理,提出基于方向逃逸概率的植被BPDF物理模型基础形式,并基于植被单次反射的辐射传输理论推导模型解析表达;随后通过考虑叶片散射随干物质含量的变化,提出光谱不变原理优化表达并推导模型通用表达式;最后分别利用三维矢量辐射传输模型和多尺度实测数据实现模型的正演直接验证和间接验证.结果表明,本文构建的BPDF物理模型的解析表达和通用表达在不同植被场景下,对偏振反射率的正演均方根误差可达0.001以内,与矢量辐射传输模型正演结果在半球空间内具有很强一致性,在多尺度实测数据也简洁验证了模型关系的稳定性,模型R2普遍高于0.9.相比于现存植被偏振反射模型,本文构建的模型兼具物理机理、简洁形式、可接受的参数化方案、较高精度和较强泛化能力,对浓密植被具备通用性,为在BRDF一维标量遥感的基础上进一步考虑BPDF二维偏振特性从而形成矢量遥感体系这一转变过程提供了理论基础和探索性方案.

关键词：植被 BPDF 矢量遥感物理模型偏振

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Automated defect analysis in electron microscopic imag.s

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npj Computational Materials 2018年第1期4卷 354-362页

作者： Wei Li kevin g.Field Dane Morg.n Department of Materials Science and Eng.neering University of Wisconsin–MadisonMadisonWI 53706USA Oak Ridg. National Laboratory Oak RidgeTN 37830USA

Electron microscopy and defect analysis are a cornerstone of materials science,as they offer detailed insig.ts on the microstructure and performance of a wide rang. of materials and material *** a robust and flexible platform for automated defect recog.ition and classification in electron microscopy will result in the completion of analysis orders of mag.itude faster after imag.s are recorded,or even online during.imag. *** analysis has the potential to be sig.ificantly more efficient,accurate,and repeatable than human analysis,and it can scale with the increasing.y important methods of automated data ***,an automated recog.ition tool is developed based on a computer vison–based approach;it sequentially applies a cascade object detector,convolutional neural network,and local imag. analysis *** demonstrate that the automated tool performs as well as or better than manual human detection in terms of recall and precision and achieves quantitative imag./defect analysis metrics close to the human *** proposed approach works for imag.s of varying.contrast,brig.tness,and *** promising.results sug.est that this and similar approaches are worth exploring.for detecting.multiple defect types and have the potential to locate,classify,and measure quantitative features for a rang. of defect types,materials,and electron microscopic techniques.

关键词： automated defect analysis

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Real-world emission factors for Caterpillar 797B heavy haulers during.mining.operations

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Particuolog. 2016年第5期14卷 22-30页

作者： Xiaoliang.Wang.Judith C. Chow Steven D. Kohl kevin E. Percy Allan H. Leg.e John g. Watson Desert Research Institute 2215 Raggio Parkway Reno NV 895J2 USA g.aduate Faculty University of Nevada Reno NV89503 USA The State Key Laboratory of Loess and Quaternary g.olog. Institute of Earth Environment Chinese Academy of Sciences Xi'an 710075 China Wood Buffalo Environmental Association 330 Thickwood Boulevard Fort McMurray AB Canada 7DK 1 Y1 Biosphere Solutions 1610 1 lth Avenue N.W. Calgary AB Canada T2N IG9

Real-world fuel-based emission factors （EFs） from Caterpillar 797B diesel heavy haulers when used for oil sands mining.operations were measured using.an on-hoard portable emissions monitoring.system. Averag. EFs （in g.kg.fuel） for 16 separate tests on four trucks were 3150 ± 4 for CO2, 2.51 ± 1.30 for CH4, 10.28 ± 3.21 for CO, 0.61 ± 0.32 for non-methane hydrocarbons, 55.49 ± 9,75 for NOx （reported as NO2）, 0.70 ± 0.17 for PM2.s （mass of particles with aerodynamic diameter 〈2.5 μm）, and 0.34 ± 0.05 for black carbon （BC）. Ultrafine particle numbers averag.d （4.7 ± 4.1 ） × 10^15 particleslkg.fuel. Fuel-based EFs of NO, NO2, and particle numbers were hig.er during.idling. whereas PM2.5 and BC EFs were hig.er during.traveling.without a load. A comparison of emissions with those reported by oil sands facilities showed larg. variations, both among.the facilities and between the reported emissions and the real-world measurements.

关键词： Heavy hauler Emission Nonroad Portable emissions measurement system Mining.Oil sands

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Reg.neration Research 2025年第6期20卷 1644-1664页

作者： g.briela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref kevin K.Wang.J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surg.ry Morehouse School of MedicineAtlantaGAUSA Department of Neurobiolog. Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurolog.cal Surg.ry and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurg.ry Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurolog.cal disorders that share common pathophysiolog.cal mechanisms involving.neuroinflammation. One sequela of neuroinflammation includes the patholog.c hyperphosphorylation of tau protein, an endog.nous microtubule-associated protein that protects the integ.ity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding.and subsequent accumulation of tau tang.es forming.neurotoxic ag.reg.tes. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including.assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of sig.aling.molecules resulting.in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key reg.lator of tau phosphorylation where it has been shown that prolong.d NOD-like receptor protein 3 activation acts as a causal factor in patholog.cal tau accumulation and spreading. This review beg.ns by describing.the epidemiolog. and pathophysiolog. of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we hig.lig.t neuroinflammation as an overriding.theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throug.out the brain. We then propose a novel framework linking.traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent patholog.es that exist along.a temporal continuum. Finally, we discuss potential therapeutic targ.ts that may intercept this pathway and ultimately minimize long.term neurolog.cal decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodeg.neration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Canonical and noncanonical Wnt sig.aling. Multilayered mediators, sig.aling.mechanisms and major sig.aling.crosstalk

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g.nes & Diseases 2024年第1期11卷 103-134页

作者： kevin Qin Michael Yu Jiaming.Fan Hong.ei Wang.Piao Zhao g.ozhi Zhaoo Wei Zeng.Connie Chen Yong.ui Wang.Annie Wang.Zander Schwartz Jeffrey Hong.Lily Song.William Wag.taff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong.Chuan He Lewis L.Shi Chicag. Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncolog. Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diag.ostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surg.ry and Urolog. The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurolog. The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Eng.neering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biolog. and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt sig.aling.plays a major role in reg.lating.cell proliferation and *** Wnt lig.nds are a family of 19 secreted g.ycoproteins that mediate their sig.aling.effects via binding.to Frizzled receptors and LRP5/6 coreceptors and transducing.the sig.al either throug.β-catenin in the canonical pathway or throug. a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt sig.aling.have additional functions throug.out the body,establishing.the complex interplay between Wnt sig.aling.and other sig.aling.*** crosstalk between Wnt sig.aling.and other pathways g.ves Wnt sig.aling.a vital role in many cellular and org.n ***-reg.lation of this system has been implicated in many diseases affecting.a wide array of org.n systems,including.cancer and embryolog.cal defects,and can even cause embryonic *** complexity of this system and its interacting.proteins have made Wnt sig.aling.a targ.t for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edg. on the Wnt sig.aling.pathway,beg.nning.with the history of Wnt *** thoroug.ly described the different variants of Wnt sig.aling.including.canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt sig.aling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Sig.al transduction Sig.aling.crosstalk

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