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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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Acute effects of human protein S administration after traumatic brain injury in mice

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Neural Regeneration Research 2020年第11期15卷 2073-2081页

作者： Xiaowei Wang Jing tong Xiaodi han Xiaoming Qi Jun Zhang Erxi Wu jason h.huang Center for Translational Neuromedicine University of RochesterRochesterNYUSA Department of Neurosurgery 4th Affiliated Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery Tiantan HospitalBeijingChina Department of Neurosurgery Baylor Scott&White HealthTempleTXUSA Department of Neurosurgery PLA General HospitalBeijingChina College of Medicine Texas A&M Health Science CenterTempleTXUSA

Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain *** impediment to successful drug development is entangled secondary injury *** we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve *** subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous *** 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue *** and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated *** targeting CD11 b showed limited leukocyte infiltration in the protein S-treated ***,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing *** results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury *** Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval ***-2008-102 R)on November 12,2013.

关键词： apoptosis aquaporin-4 controlled cortical impact edema inflammation protein S TBI therapy traumatic brain injury

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Multiple description coding with spatial-temporal hybrid interpolation for video streaming in peer-to-peer networks

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2006年第5期7卷 894-899页

作者： YAO jason ChEN homer h Graduate Institute of Communication Engineering

In this paper, we present an innovative design of multiple description coding with spatial-temporal hybrid interpola- tion (MDC-SThI) for peer-to-peer (P2P) video streaming. MDC can be effective in P2P networks because the nature of overlay routing makes path diversity more feasible. however, most MDC schemes require a redesign of video coding systems and are not cost-effective for wide deployment. We base our work on multiple state video coding, a form of MDC that can utilize standard codecs. Two quarter-sized video bit streams are generated as redundancies and embedded in the original-sized streams. With MDC-SThI, the nodes in P2P network can adjust the streaming traffic to satisfy the constraints of their devices and network environment. By design, the redundancies are used to compensate for missing frames, and can also be streamed independently to fulfill certain needs of low rate, low resolution applications. For better error concealment, optimal weights for spatial and temporal interpolation are determined at the source, quantized, and included in redundancies.

关键词： P2P streaming, Multiple state video coding, Multiple description coding (MDC)

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Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第41期12卷 6620-6626页

作者： Myron J tong Lawrence M Blatt Jia-horng Kao jason Tzuying Cheng William G Corey The Liver Center Huntington Medical Research InstitutesPasadenaCaliforniaUnited States The Pfleger Liver InstituteDavid Geffen Schoolof Medicine at the University of California in Los AngelesCaliforniaUnited States Intermune Inc.BrisbaneCaliforniaUnited States The hepatitis Research Center National TaiwanUniversity HospitalTaipeiTaiwanChina The Liver Center Huntington Medical Research InstitutesPasadenaCaliforniaUnited States

AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METhODS： The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA （hBV DNA） level and hepatitis B e antigen （hBeAg） were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS： During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio： 95.74 （12.13-891.31）, P 〈 0.0001], male sex [odds ratio： 7.61 （2.20-47.95）; P = 0.006], and higher Iogzo hBV DNA [odds ratio： 4.69 （1.16-20.43）; P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio： 26.51 （2.36-381.47）; P = 0.007], presence of precore mutants [odds ratio： 4.23 （1.53-19.58）, P = 0.02] and presence of basal core promoter mutants [odds ratio： 2.93 （1.24-7.57）; P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION： Our results show that high levels of baseline serum hBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.

关键词： Basal core promoter mutants Precore mutants hepatitis B viral genotypes hepatitis B viral DNA hepatitis B e antigen Liver failure hepatocellular carcinoma

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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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Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures

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Neural Regeneration Research 2017年第3期12卷 401-402页

作者： Buqing Liang jason h.huang Department of Neurosurgery Neuroscience InstituteBaylor Scott&White HealthCentral DivisionTempleTXUSA Department of Surgery Texas A&M University Health ScienceCenterCollege of MedicineTempleTXUSA

As a leading cause for morbidity and mortality in young adults,traumatic brain injury（TBI）,along with the poorly understood TBI-related seizures inducing their predispositions,pose a major health and socioeconomic p... 详细信息

关键词： TBI Elevated NKCC1 transporter expression facilitates early post-traumatic brain injury seizures Cl TGF

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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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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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Sorption of inorganic nanoparticles in woven cellulose fabrics

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Particuology 2009年第2期7卷 121-128页

作者： Dan h. Marsh D. jason Riley David York Andrew Graydon School of Chemistry University of NottinghamUniversity ParkNottinghamNG7 the School of Chemistry University of BristolCantocks CloseBristolBS8 1TSUK.2RDUK Department of Materials Imperial College LondonExhibition RoadLondonSW7 2AZUK the School of Chemistry University of BristolCantocks CloseBristolBS8 1TSUK. Procter & Gamble Technical Centres Ltd. Newcastle Upon TyneNE12 9TSUK

Titanium dioxide was deposited from aqueous suspension onto cellulosic surfaces. Titania was sourced from Degussa （P25TM, 70：30 anatase：rutile）. Dry uptake of particles was shown to be rapid and dominant with one-third of the deposition occurring in less than 30 s and over one-half in the first minute. Isotherms were recorded to compare the rate of titanium deposition on dry and pre-wetted cotton. In the dry case uptake reached a maximum in 30 min whereas in the pre-wetted case the uptake was seen to continue beyond 180 min. A broad trend of higher deposition occurring at lower ph was seen, corresponding to the region where surface charges were opposite and thus attractive. Dry pickup was less significant at high ph. The response to varying ionic strength was complex and was attributed to the combined effect of charge screening, particle aggregation and consequent particle entrapment or occlusion. Titania deposition into the interstices of woven cotton sheets resulted in the formation of inorganic, nanoparticulate skeletons which could be isolated by controlled combustion of the cellulose and thus cotton was suggested to have potential for the templated synthesis of high surface area semiconductor materials.

关键词： Titania Cellulose Sorption Zeta potential Templated material

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