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| 1 | Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver显示文摘Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of obesity.Although cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains obscure.Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor immunosurveillance.Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients.Notably,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development.Moreover,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell depletion.Mechanistically,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and NAFLD-HCC.This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic. | Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng Haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hanyong Sun Xiaoyu Tian Philip Chun Yeung Yong Hou Heung Man Lee Candice C.H.Lam Howard H.W.Leung Anthony W.H.Chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.Cheng | 2022 | Cellular & Molecular Immunology2022，19，7： | 3 |
| 2 | Dendritic cells efficiently acquire and present antigen derived fromlung cancer cells and induce antigen-specific T cell responses 显示文摘 | Zhou Y McEarchern JA Howard E | 2003 | Cancer Immunol Immunother2003，52，7： | 1 |
| 3 | In vitro generated ThI7 cells support the expansion and phenotypic stability of CD4+ Foxp3+ regulatory T cells in vivo显示文摘 | Zhou Q Hu Y Howard OM | 2014 | Cytokine2014，65，1： | 1 |
| 4 | A full description of a simple and scalable fabrication process for electrowetting displays显示文摘 | K Zhou J Heikenfeld K A Dean E M Howard M R Johnson | 2009 | Journal of Micromechanics and Microengineering2009，，： | 1 |
| 5 | Adenomyoma Arising in a Meckel Diverticulum: Case Report and Review of the Literature显示文摘 | Jorge L. Yao Hong Zhou Kevin Roche Babu S. Bangaru Howard Ginsburg M. Alba Greco | 2000 | Pediatric and Developmental Pathology2000，，5： | 1 |
| 6 | Identification of a cell wall peroxidase in red calli of Prunus incisa Thunb.显示文摘 | S. Zhou R. Sauve E. Howard | 2002 | Plant Cell Reports2002，，4： | 1 |
| 7 | Direct contacts of microglia on myelin sheath and Ranvier’s node in the corpus callosum in rats显示文摘Over the recent years, it has been found that microglia pseudopodia contact synapses, detect sick ones and prune them, even in adult animals. Myelinated nerves also carry out plasticity in which microglia remove myelin debris by phagocytosis. However, it remains unknown whether microglia explore structures on nerve fibers, such as Ranvier’s node(RN) or myelin sheath, before they become debris. By double or triple staining RNs or myelin sheathes and microglia in healthy rat corpus callosum, this study unveiled direct contacts of microglia pseudopodia with RNs and with para-and inter-nodal myelin sheathes, which was then verified by electron microscopic observations. Our data indicated that microglia also explore unmyelinated nerve fibers. Furthermore, we used the animals with matured white matter;therefore, microglia may be actively involved in plasticity of matured white matter tracts as it does for synapse pruning, instead of only passively phagocytize myelin debris. | Jingdong Zhang Xinglong Yang You Zhou Howard Fox Huangui Xiong | 2019 | The Journal of Biomedical Research2019，33，3： | 1 |
| 8 | Malaria mosquito control using edible fish in western Kenya: preliminary findings of a controlled study显示文摘 | Howard AF Zhou GF Omlin FX | 2007 | BMC Public Health2007，7，： | 1 |
| 9 | Pericellular proteolysis by leukocytes and tumor cells on substrates: focal activation and the role of urokinase-type plasminogen activator显示文摘 | Andrei L. Kindzelskii Imran Amhad Donald Keller M.-J. Zhou Richard P. Haugland B. A. Garni-Wagner Margaret R. Gyetko Robert F. Todd Howard R. Petty | 2004 | Histochemistry and Cell Biology2004，，4： | 1 |
| 10 | Identification of a cell wall peroxidase in red calli of Prunus incisa Thunb显示文摘 | Zhou S Sauve R Howard E | 2002 | Plant Cell Reports2002，21，4： | 1 |
| 11 | Phase-field simulations of interfacial dynamics in viscoelastic fluids using finite elements with adaptive meshing显示文摘 | Pengtao Yue Chunfeng Zhou James J. Feng Carl F. Ollivier-Gooch Howard H. Hu | 2006 | Journal of Computational Physics2006，，1： | 1 |
| 12 | ARID1A/ BAF250a as a prognostic marker for gastric carcinoma: a study of two cohorts显示文摘 | Kimberly C. Wiegand Keiyan Sy Steve E. Kalloger Hector Li-Chang Ryan Woods Aalok Kumar Catherine J. Streutker Sara Hafezi-Bakhtiari Chen Zhou Howard J. Lim David G. Huntsman Blaise Clarke David F. Schaeffer | 2014 | Human Pathology2014，，： | 1 |
| 13 | A full description of a simple and scalable fabrication process for electrowetting display显示文摘 | K Zhou J Heikenfeld K A Dean E M Howard M R Johnson | | 0，，： | 1 |
| 14 | Post-combustion CO 2 capture using super-hydrophobic, polyether ether ketone, hollow fiber membrane contactors显示文摘 | Shiguang Li Dennis J. Rocha S. James Zhou Howard S. Meyer Benjamin Bikson Yong Ding | 2012 | Journal of Membrane Science2012，，： | 1 |
| 15 | Terrain synthesis from digital elevation models 显示文摘 | Howard Zhou Jie Sun Greg Turk | 2007 | IEEE Trans on Visualization and Computer Graphics2007，13，4： | 1 |
| 16 | Application of a particle-in-cell method to solid mechanics显示文摘 | SULSKY D ZHOU SJ HOWARD LS | 1995 | Computers Physics Communications1995，87，： | 1 |
| 17 | 3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists显示文摘 | Walsh SP Severino A Zhou C He J Liang GB Tan CP Cao J Eiermann GJ Xu L Salituro G Howard AD Mills SG Yang L | | 0，，11： | 1 |
| 18 | Structural studies of the ferroelectric phase transition in Bi4Ti3O12 显示文摘 | ZHOU Qingdi BRENDAN J Kennedy HOWARD Christopher J | 2003 | Chem Mater2003，15，： | 1 |
| 19 | Terrain synthesis from digital elevation models 显示文摘 | Zhou Howard Sun Jie Turk G | 2007 | IEEE Transactions on Visualization and Computer Graphics2007，13，4： | 1 |
| 20 | A cellular and proteomic approach to assess proteins extracted from cryopreserved human amnion in the cultivation of corneal stromal keratocytes for stromal cell therapy显示文摘Background:Human corneal stromal keratocytes propagated in culture media supplemented with human amnion extract(AME)can correct early corneal haze in an animal model.Clinical application of cultivated keratocytes is limited by infectious disease screening before amnion products can be used in humans.It remains unclear if AME from cryopreserved versus fresh human amnion can support human keratocyte propagation,and which components of the extract promote keratocyte growth.Methods:Three placentas were collected for the preparation of fresh and cryopreserved amnion tissues followed by homogenization and protein extraction.AME protein profiles were studied using isobaric tagging for relative and absolute quantitation(iTRAQ)proteomics.Enriched gene ontology(GO)terms and functional classes were identified.Primary human keratocytes from 4 donor corneas were cultured in media supplemented with fresh AME(F-AME)or cryopreserved AME(C-AME).Cell viability,proliferation and keratocyte marker expression were examined by confocal immunofluorescence and flow cytometry.Results:AME proteomics revealed 1385 proteins with similar expression levels(between 0.5-and 2-fold)between Fand C-AME,while 286 proteins were reduced(less than 0.5-fold)in C-AME.Enriched GO term and biological pathway analysis showed that those proteins with comparable expression between F-AME and C-AME were involved in cell metabolism,epithelial-mesenchymal transition,focal adhesion,cell-extracellular matrix interaction,cell stress regulation and complement cascades.Human corneal stromal keratocytes cultured with F-AME or C-AME showed similar morphology and viability,while cell proliferation was mildly suppressed with C-AME(P>0.05).Expression of aldehyde dehydrogenase 3A1(ALDH3A1)and CD34 was similar in both cultures.Conclusion:AME from cryopreserved amnion had limited influence on keratocyte culture.It is feasible to use protein extract from cryopreserved amnion to propagate human keratocytes for potential translational applications. | Beau J.Fenner Nur Zahirah B.M.Yusoff Matthias Fuest Lei Zhou Francisco Bandeira Howard Y.Cajucom-Uy H.K.Tan Jodhbir S.Mehta Gary H.F.Yam | 2019 | Eye and Vision2019，6，1： | 0 |
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