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The evolving roles of wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao wei Zeng Connie Chen Annie wang Yonghui wang jiamin Zhong Yi Zhu william wagstaff 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 Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)wnt signaling *** 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 signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant wnt signaling 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 dysregulated wnt signaling in disease have paved the way for the development of novel therapeutics that target 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 knowledge of wnt signaling in stem cells,aberrations to the wnt pathway associated with diseases,and novel therapeutics targeting the wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical wnt Disease Non-canonical wnt Stem cells Targeted therapy wnt signaling

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

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela 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 Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery 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 Neurosurgery 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 neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. 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 signaling 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 regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight 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 throughout the brain. we then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

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

Canonical and noncanonical wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： kevin Qin Michael Yu Jiaming Fan Hongwei wang Piao Zhao Guozhi Zhaoo wei Zeng Connie Chen Yonghui wang Annie wang Zander Schwartz Jeffrey Hong Lily Song william wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

wnt signaling plays a major role in regulating cell proliferation and *** wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical wnt signaling have additional functions throughout the body,establishing the complex interplay between wnt signaling and other signaling *** crosstalk between wnt signaling and other pathways gives wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the wnt signaling pathway,beginning with the history of wnt *** thoroughly described the different variants of wnt signaling,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 signaling.

关键词： β-catenin Canonical wnt Noncanonical wnt Signal transduction Signaling crosstalk

A stock assessment for Illex argentinus in Southwest Atlantic using an environmentally dependent surplus production model

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Acta Oceanologica Sinica 2018年第2期37卷 94-101页

作者： wANG Jintao CHEN Xinjun kevin w.Staples CHEN Yong College of Marine Sciences Shanghai Ocean University Shanghai 201306 China National Distant-water Fisheries Engineering Research Center Shanghai Ocean University Shanghai 201306 China key Laboratory of Sustainable Exploitation of Oceanic Fisheries Resources of Ministry of Education Shanghai Ocean University Shanghai 201306 China School of Marine Sciences University of Maine Orono Maine 04469 USA Collaborative Innovation Center for National Distant-water Fisheries Shanghai 201306 China

The southern Patagonian stock（SPS） of Argentinian shortfin squid, Illex argentinus, is an economically important squid fishery in the Southwest Atlantic. Environmental conditions in the region play an important role in regulating the population dynamics of the I. argentinus population. This study develops an environmentally dependent surplus production（EDSP） model to evaluate the stock abundance of I. argentines during the period of 2000 to 2010. The environmental factors（favorable spawning habitat areas with sea surface temperature of 16–18°C） were assumed to be closely associated with carrying capacity（K） in the EDSP model. Deviance Information Criterion（DIC） values suggest that the estimated EDSP model with environmental factors fits the data better than a Schaefer surplus model without environmental factors under uniform and normal *** EDSP model estimated a maximum sustainable yield（MSY） from 351 600 t to 685 100 t and a biomass from 1 322 400 t to1 803 000 t. The fishing mortality coefficient of I. argentinus from 2000 to 2010 was smaller than the values of F（0.1） and F（MSY）. Furthermore, the time series biomass plot of I. argentinus from 2000 to 2010 shows that the biomass of *** and this fishery were in a good state and not presently experiencing overfishing. This study suggests that the environmental conditions of the habitat should be considered within squid stock assessment and management.

关键词： Illex argentinus stock assessment Schaefer surplus production model environmental factors Southwest Atlantic

Mixed ion and electron transport theory and application in solid oxide conductors

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International Journal of Minerals,Metallurgy and Materials 2022年第4期29卷 870-875页

作者： kevin Huang Department of Mechanical engineering University of South CarolinaColumbiaSC 292201USA

Mixed ions and electron conductors(MIECs)are an important family of electrocatalysts for electrochemical devices,such as reversible solid oxide cells,rechargeable metal-air batteries,and oxygen transport *** ionic and electronic transports in these materials play a key role in electrocatalytic *** in-depth fundamental understanding of the transport phenomena is critically needed to develop better *** this brief review,we introduced generic ionic and electronic transport theory based on irreversible thermodynamics and applied it to practical oxide-based materials with oxygen vacancies and electrons/holes as the predominant *** oxide systems,namely CeO_(2)-based and La CrO_(3)-based materials,are selected as case studies to illustrate the utility of the transport theory in predicting oxygen partial pressure distribution across MIECs,electrochemical electronic/ionic leakage currents,and the effects of external load current on the leakage currents.

关键词： irreversible thermodynamics diffusivity charge neutrality electrochemical potential electrostatic potential

A Potential Risk Index Dataset for Landfalling Tropical Cyclones over the Chinese Mainland(PRITC dataset V1.0)

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Advances in Atmospheric Sciences 2021年第10期38卷 1791-1802页

作者： Peiyan CHEN Hui YU kevin K.w.CHEUNG Jiajie XIN Yi LU Shanghai Typhoon Institute China Meteorological AdministrationShanghai 200030China key Laboratory of Numerical Modeling for Tropical Cyclone of China Meteorological Administration Shanghai 20030China The Joint Laboratory for Typhoon Forecasting Technique Applications between Shanghai Typhoon Institute and wenzhou Meteorological Bureau Wenzhou 325027China Climate and Atmospheric Science NSW Department of Planning Industry and EnvironmentSydney 2000Australia

A dataset entitled“A potential risk index dataset for landfalling tropical cyclones over the Chinese mainland”(PRITC dataset V1.0)is described in this paper,as are some basic statistical *** the severity of the impacts of tropical cyclones(TCs)that make landfall on the Chinese mainland based on observations from 1401 meteorological stations was proposed in a previous study,including an index combining TC-induced precipitation and wind(IPwT)and further information,such as the corresponding category level(CAT_IPwT),an index of TC-induced wind(IwT),and an index of TC-induced precipitation(IPT).The current version of the dataset includes TCs that made landfall from 1949-2018;the dataset will be extended each ***-term trend analyses demonstrate that the severity of the TC impacts on the Chinese mainland have increased,as embodied by the annual mean IPwT values,and increases in TC-induced precipitation are the main contributor to this *** winnie(1997)and TC Bilis(2006)were the two TCs with the highest IPwT and IPT values,*** PRITC V1.0 dataset was developed based on the China Meteorological Administration’s tropical cyclone database and can serve as a bridge between TC hazards and their social and economic impacts.

关键词： tropical cyclone risk dataset China

New Record Ocean Temperatures and Related Climate Indicators in 2023

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Advances in Atmospheric Sciences 2024年第6期41卷 1068-1082页

作者： Lijing CHENG John ABRAHAM kevin E.TRENBERTH Tim BOYER Michael EMANN Jiang ZHU Fan wANG Fujiang YU Ricardo LOCARNINI John FASULLO Fei ZHENG Yuanlong LI Bin ZHANG Liying wAN Xingrong CHEN Dakui wANG Licheng FENG Xiangzhou SONG Yulong LIU Franco RESEGHETTI Simona SIMONCELLI Viktor GOURETSKI Gengxin CHEN Alexey MISHONOV Jim REAGAN Karina VON SCHUCKMANN Yuying PAN Zhetao TAN Yujing ZHU wangxu wEI Guancheng LI Qiuping REN Lijuan CAO Yayang LU International Center for Climate and Environment Sciences Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China University of St.Thomas School of EngineeringMinnesota 55105USA NSF National Center for Atmospheric Research BoulderColorado 80307USA University of Auckland Auckland 1010New Zealand National Oceanic and Atmospheric Administration National Centers for Environmental InformationSilver SpringMaryland 20910USA Department of Earth and Environmental Science University of PennsylvaniaPhiladelphiaPennsylvania 19104USA Institute of Oceanology Chinese Academy of SciencesQingdao 266071China National Marine Environmental Forecasting Center Ministry of Natural Resources of ChinaBeijing 100081China Oceanographic Data Center Chinese Academy of SciencesQingdao 266071China College of Oceanography Hohai UniversityNanjing 210098China National Marine Data and Information Service Tianjin 300171China Italian National Agency for New Technologies Energy and Sustainable Economic DevelopmentS.Teresa Research CenterLerici 19032Italy Istituto Nazionale di Geofisica e Vulcanologia Sede di BolognaBologna 40128Italy South China Sea Institute of Oceanology Chinese Academy of SciencesGuangzhou 510301China ESSIC/CISESS-MD University of MarylandCollege ParkMD20740USA Mercator Ocean International Toulouse 31400France Eco-Environmental Monitoring and Research Center Pearl River Valley and South China Sea Ecology and Environment AdministrationMinistry of Ecology and EnvironmentPRCGuangzhou 510611China National Meteorological Information Center China Meteorological AdministrationBeijing 100081China International Research Center of Big Data for Sustainable Development Goals Beijing 100094China

The global physical and biogeochemical environment has been substantially altered in response to increased atmospheric greenhouse gases from human *** 2023,the sea surface temperature(SST)and upper 2000 m ocean heat content(OHC)reached record *** 0–2000 m OHC in 2023 exceeded that of 2022 by 15±10 ZJ(1 Zetta Joules=1021 Joules)(updated IAP/CAS data);9±5 ZJ(NCEI/NOAA data).The Tropical Atlantic Ocean,the Mediterranean Sea,and southern oceans recorded their highest OHC observed since the *** with the onset of a strong El Niño,the global SST reached its record high in 2023 with an annual mean of~0.23℃ higher than 2022 and an astounding>0.3℃ above 2022 values for the second half of *** density stratification and spatial temperature inhomogeneity indexes reached their highest values in 2023.

关键词： ocean heat content salinity stratification global warming climate

E-pO^(2–) diagram for rare earth elements in molten salt

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Journal of Rare Earths 2017年第2期35卷 187-192页

作者： Yixing(kevin) Shen Jinsuo Zhang Niuclear Engineering Program Department of Mechanical and Aerospace Engineering The Ohio State University US

Electro-reduction of spent nuclear oxide fuels in molten salt was the key step of pyroprocessing for oxide fuel treatment. In the present study, the E-pO^2- diagram for rare earth elements in molten Li Cl-KCl at 450 oC were developed based available experimental data. E-pO^2- diagrams could show the stability of each chemical compound in the salt, and therefore, the diagrams could be applied to predict experimental conditions for electro-reduction of spent nuclear fuel efficiently. Compared with the available E-pO^2-diagrams, the present study concerned the activity coefficient of the element studied in the molten salt in all reactions, which made the diagram be more reliable and accurate.

关键词： E-pO^2- Diagram molten salt pyroprocessing fuel cycle rare earths

JUMPING INSTABILITIES IN THE POST-BUCKLING OF A BEAM ON A PARTIAL NONLINEAR FOUNDATION

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Acta Mechanica Solida Sinica 2013年第5期26卷 500-513页

作者： Yin Zhang kevin D Murphy State key Laboratory of Nonlinear Mechanics (LNM) Institute of Mechanics Chinese Academy of Sciences Department of Mechanical Engineering University of Connecticut

Mode jumping is an instability phenomenon in the post-buckling region, which causes a sudden change in the equilibrium configuration and is thus harmful to structure. The con- figuration of a partial elastic foundation can directly induce mode coupling from the buckling stage and through the whole post-buckling region. The mode coupling effect due to the configuration of partial foundation on mode jumping is investigated and demonstrated to be an important factor of determining mode jumping. By properly choosing the partial elastic foundation configuration, mode jumping can be avoided.

关键词： instability mode jumping tertiary jumping buckling beam elastic foundation