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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman jason h.tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi hou Andrew M.Intlekofer Richard M.higashi Teresa W.M.Fan Andrew N.Lane Kevin h.Eng Brahm h.Segal Elizabeth A.Repasky Kelvin P.Lee Scott h.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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Astrocytic calcium waves:unveiling their roles in sleep and arousal modulation

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Neural Regeneration Research 2024年第5期19卷 984-987页

作者： Erxi Wu Dan Qi Damir Nizamutdinov jason h.huang Department of Neurosurgery and Neuroscience Institute Baylor Scott&White HealthTempleTXUSA Texas A&M University School of Medicine TempleTXUSA Texas A&M University School of Pharmacy College StationTXUSA LIVESTRONG Cancer Institutes and Department of Oncology Dell Medical Schoolthe University of Texas at AustinAustinTXUSA Department of Neurosurgery Baylor College of MedicineTempleTXUSA

Neuron-astrocyte interactions are vital for the brain’s *** astrocyte activities is crucial for comprehending the complex neural network,particularly the population-level functions of neurons in different cortical states and associated behaviors in *** on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between ***,outnumbering neurons by nearly fivefold,support and regulate neuronal and synaptic *** research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel *** summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep,wakefulness,and arousal levels,exploring the involvement of noradrenaline signaling,ion channels,and glutamatergic signaling in different cortical *** findings highlight the significant impact of astrocytes on large-scale neuronal networks,influencing brain activity and *** astrocytic signaling pathways shows promise for treating sleep disorders and arousal *** research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states,requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep-and arousal-related disorders.

关键词： arousal astrocyte calcium waves locus coeruleus neuron-astrocyte interaction norepinephrine sleep wakefulness

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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

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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

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Construction of a novel six-gene signature to predict tumour response to induction chemotherapy and overall survival in locoregionally advanced laryngeal and hypopharyngeal carcinoma

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Genes & Diseases 2024年第3期11卷 148-150页

作者： Chen Tan Lingwa Wang Yifan Yang Shizhi he George G.Chen jason YK.Chan Michael CF.tong C.A.van hasselt Wenbin Xu Ling Feng Ru Wang Jugao Fang Department of Otolaryngology head and Neck Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Key Laboratory of Otolaryngology head and Neck Surgery(Ministry of Education of China) Beijing Institute of OtolaryngologyBeijing 100730China Department of Otorhinolaryngology Head and Neck SurgeryThe Chinese University of Hong KongPrince of Wales HospitalHongKong SAR999077China Department of Medical Genetics Institute of Basic Medical ScienceChinese Academy of Medical Science&Peking Union Medical CollageBeijing 100730China

Locoregionally advanced laryngeal and hypopharyngeal cancers(LA-LhCs)are traditionally treated with surgery followed by postoperative radiotherapy,which impairs speech and swallowing functions and reduces the quality of life.^(1,2)The use of induction chemotherapy(IC)as a larynxpreserving approach for LA-LhCs has been verified and refined.^(3)however,the short-term tumor response to IC varies,non-responders usually show poor survival and little benefit.

关键词： chemotherapy laryngeal surgery

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Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(Linum L.)

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Oil Crop Science 2024年第2期9卷 121-130页

作者： Kenyon J. Nisbett Abida Alokozai Su hyun Elizabeth Ko G. Adam Mott jason C.L. Browna Department of Biological Sciences University of Toronto ScarboroughTorontoONCanada Department of Cell&Systems Biology University of TorontoTorontoONCanada Centre for the Analysis of Genome Evolution&Function University of TorontoTorontoONCanada

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 *** proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple *** differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular *** present study evaluated this hypothesis using annual and perennial flax(Linum L.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar h2O2spraying)and complete prolonged *** chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our *** predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to *** levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using *** chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as *** plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,ch

关键词： Ageing Life history Maximum lifespan Oxidative stress Somatic maintenance

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Dynamics of self-hybridized exciton–polaritons in 2D halide perovskites

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Light(Science & Applications) 2024年第1期13卷 13-22页

作者： Surendra B.Anantharaman jason Lynch Christopher E.Stevens Christopher Munley Chentao Li Jin hou hao Zhang Andrew Torma Thomas Darlington Francis Coen Kevin Li Arka Majumdar PJames Schuck Aditya Mohite hayk harutyunyan Joshua R.hendrickson Deep Jariwala Department of Electrical and Systems Engineering University of PennsylvaniaPhiladelphiaPA19104USA KBR Inc. BeavercreekOH45431USA Air Force Research Laboratory Sensors DirectorateWright-Patterson Air Force BaseOH45433USA Department of Physics University of WashingtonSeattleWA98195USA Department of Physics Emory UniversityAtlantaGA30322USA Department of Chemical and Biomolecular Engineering Rice UniversityHoustonTX77005USA Department of Materials Science and Nanoengineering Rice UniversityHoustonTX77005USA Applied Physics Program Smalley‐Curl InstituteRice UniversityHoustonTX77005USA Department of Mechanical Engineering Columbia UniversityNew YorkNY10027USA Department of Electrical and Computer Engineering University of WashingtonSeattleWA98195USA

Excitons,bound electron–hole pairs,in two-dimensional hybrid organic inorganic perovskites(2D hOIPs)are capable of forming hybrid light-matter states known as exciton-polaritons(E–Ps)when the excitonic medium is confined in an optical *** the case of 2D hOIPs,they can self-hybridize into E–Ps at specific thicknesses of the hOIP crystals that form a resonant optical cavity with the ***,the fundamental properties of these self-hybridized E–Ps in 2D hOIPs,including their role in ultrafast energy and/or charge transfer at interfaces,remain ***,we demonstrate that>0.5µm thick 2D hOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E–P *** E–Ps have high Q factors(>100)and modulate the optical dispersion for the crystal to enhance sub-gap absorption and *** varying excitation energy and ultrafast measurements,we also confirm energy transfer from higher energy E–Ps to lower energy E–***,we also demonstrate that E–Ps are capable of charge transport and transfer at *** findings provide new insights into charge and energy transfer in E–Ps opening new opportunities towards their manipulation for polaritonic devices.

关键词： charge polar excitation

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Meter-scale variation within a single transect demands attention to taxon accumulation curves in riverine microbiome studies

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Frontiers of Environmental Science & Engineering 2022年第5期16卷 115-125页

作者： Bingdi Liu Lin Zhang jason h.Knouft Fangqiong Ling Department of Energy Environmental and Chemical EngineeringWashington University in St.LouisSt.LouisMO 63130USA Department of Biology Saint Louis UniversitySt.LouisMO 63103USA National Great Rivers Research and Education Center East AltonMO 62035USA Department of Computer Science and Engineering Washington University in St.LouisSt.LouisMO 63130USA Division of Biological and Biomedical Sciences Washington University in St.LouisSt.LouisMO 63110USA Division of Computational and Data Science Washington University in St.LouisSt.LouisMO 63130USA

Microbial communities inhabiting river ecosystems play crucial roles in global biogeochemical cycling and pollution *** variations in local microbial assemblages are important for detailed understanding of community assembly and developing robust biodiversity sampling ***,we intensely analyzed twenty water samples collected from a one-meter spaced transect from the near-shore to the near-center in the Meramec River in eastern Missouri,USA and examined the microbial community composition with 16S rRNA gene amplicon *** microbiomes across the transect exhibited extremely high similarity,with Pearson’s correlation coefficients above 0.9 for all pairwise community composition ***,despite the high similarity,PERMANOVA revealed significant spatial differences between near-shore and nearcenter communities(p=0.001).Sloan’s neutral model simulations revealed that within-transect community composition variation was largely explained by demographic stochasticity(R^(2)=0.89).Despite being primarily explained by neutral processes,LefSe analyses also revealed taxa from ten families of which relative abundances differed directionally from the bank to the river center,indicating an additional role of environmental ***,the local variations within a river transect can have profound impacts on the documentation of alpha ***-accumulation curves indicated that even twenty samples did not fully saturate the sampling effort at the genus level,yet four,six and seven samples were able to capture 80%of the phylum-level,family-level,and genus-level diversity,*** study for the first time reveals hyperlocal variations in riverine microbiomes and their assembly mechanisms,demanding attention to more robust sampling strategies for documenting microbial diversity in riverine systems.

关键词： Microbiome Freshwater Taxon accumulation curve Community assembly

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Transcranial photobiomodulation with near-infrared light:a promising therapeutic modality for Alzheimer's disease

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Neural Regeneration Research 2023年第9期18卷 1944-1945页

作者： hanli Liu Damir Nizamutdinov jason h.huang Bioengineering Department the University of Texas at ArlingtonArlingtonTXUSA Neurosurgery Neuroscience InstituteBaylor Scott and White HealthTempleTXUSA Neurosurgery College of MedicineTexas A&M UniversityTempleTXUSA

Transcranial photobiomodulation(tPBM) is a noninvasive neuromodulation technique that delivers near-infrared(NIR) light with low irradiance(i.e.,power density in mW/cm2) in the wavelength range of 800-1070 *** recently published books or collected literature(hamblin,2019;GonzalezLima,2021) and papers(Nizamutdinov et al. 2022)offer comprehensive reviews of the mechanism of action and potential clinical translations of tPBM for the treatment of a variety of diseases,including neurodegenerative diseases(Alzheimer’s disease(AD),and Parkinson’s disease),traumatic brain injury.

关键词： Alzheimer diseases

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Engineered nucleus-free mesenchymal stem cells (MSCs) for the targeted delivery of therapeutics to disease site

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Genes & Diseases 2023年第2期10卷 310-312,I0001页

作者： Zander Schwartz Piao Zhao Annie Wang Guozhi Zhao Wei Zeng Yonghui Wang hue h. Luu Rex C. haydon tong-Chuan he Russell R. Reid jason Strelzow School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.

关键词： targeted delivery sought

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