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| 1 | Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis显示文摘The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer types.Although a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely understood.Here,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive microenvironment.Using an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)cells.Depletion of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,respectively.Mechanistically,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic mice.Accordingly,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation donors.In summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic immunosurveillance.Our findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention. | Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai Anthony Wing-Hung Chan Ka Fai To Stephen Lam Chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 2 | High-performance oxygen reduction and evolution carbon catalysis: From mechanistic studies to device integration显示文摘能容易集成于存在的高效、便宜的氧减小和进化催化剂的发展设备为利用 O 2-H2 O 化学,例如再生燃料房间和金属空气电池。此处,我们报导 NH 3-activated 做 N 的层次碳(NHC ) 催化剂经由一条可伸缩的线路综合了,并且表明它的设备集成。NHC 催化剂为氧减小反应(ORR ) 和氧进化反应(OER ) 展出了好性能,当综合时,借助于电气化学的研究和评估示威了进一个再生燃料房间的氧电极。为 ORR 和 OER 观察的活动比得上最先进的磅和红外催化剂在碱的环境完成的那些。我们进一步通过密度为电气化学的活动作为活跃地点识别了碳缺点的关键角色功能的理论计算和高分辨率的 TEM 可视化。这个工作加亮 NHC 的潜力在再生燃料房间并且可能代替商业宝贵金属为断断续续的可更新的精力的划算的存储的金属空气电池。 | John W. F. To Jia Wei Desmond Ng Samira Siahrostami Ai Leen Koh Yangjin Lee Zhihua Chen Kara D. Fong Shucheng Chen Jiajun He Won-Gyu Bae Jennifer Wilcox Hu Young Jeong Kwanpyo Kim Felix Studt Jens K. Nфrskov Thomas F. Jaramillo Zhenan Bao | 2017 | Nano Research2017，10，4： | 4 |
| 3 | 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 |
| 4 | Esophageal varices on computed tomography and subsequent variceal hemorrhage显示文摘 | Ma Somsouk Katherine To’o Mujtaba Ali Eric Vittinghoff Benjamin M. Yeh Judy Yee Alex Monto John M. Inadomi Rizwan Aslam | 2014 | Abdominal Imaging2014，，2： | 1 |
| 5 | Cryptosporidium erinacei n. sp. (Apicomplexa: Cryptosporidiidae) in hedgehogs显示文摘 | Martin Kvá? Lada Hofmannová Lenka Hlásková Dana Květoňová Ji?í Vítovec John McEvoy Bohumil Sak | 2014 | Veterinary Parasitology2014，，： | 1 |
| 6 | Functional connectivity in late-life de- pression using resting-state functional magnetic resonance imaging 显示文摘 | Eva RK M Res John TO | 2010 | Am J Geriatr Psychiatry2010，18，7： | 1 |
| 7 | Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1‐mediated G<sub>0</sub>/G<sub>1</sub> cell cycle arrest and apoptosis显示文摘 | Winnie Lai Ting Kan Chun Yin Hong Xi Xu Gang Xu Kenneth Kin Wah To Chi Hin Cho John Anthony Rudd Ge Lin | 2012 | Int J Cancer2012，，3： | 1 |
| 8 | Optical trapping,field enhaneement and laser cooling in photonic crystals显示文摘 | TO(DER O JOHN S BUSCH K | | 0，，03： | 1 |
| 9 | Mozambique Tilapia (Oreochromismossambicus) to salinitx acclimation显示文摘 | John D Sakamo to MT Gordon G E | 1997 | Compantive Biochem''s try and Physiology Part: Physiology1997，117，3： | 1 |
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