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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 | Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4’-Phosphatase, PGN_0524显示文摘Aim To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis (P. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin B. Methodology A genetic screen of P. gingivalis clones generated by a Tn4400’-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B (PMB, 50 μg-mL-1). Results P. gingivalis (ATCC 33277) is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations (200 μg-mL-1). Approximately 2,700 independent Tn4400’-derived mutants of P. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose (50 μg-mL-1). A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400’ transposon was integrated into the gene encoding the lipid A 4’-phosphatase, PGN_0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400’, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural (MALDI-TOF MS) analyses revealed that lipid A isolates from 0524-Tn4400’ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P. gingivalis lipid A spectrum. Finally, intact 0524- Tn4400’ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 (TLR4)-dependent E-selectin expression in human endothelial cells relative to intact wild-type P. gingivalis or its corresponding LPS isolate. Conclusion The combined molecular evidence provided in this report suggests that PGN_0524, a lipid A 4’-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR4 sensing. | Stephen R. Coats Thao T. To Sumita Jain Pamela H. Braham Richard P. Darveau | 2009 | International Journal of Oral Science2009，1，3： | 2 |
| 3 | Allergic dis- ease and asthma: a major global health concern显示文摘 | Pawankar RU Giorgio WH Stephen TO | | Curr Opin Allergy Clin Immunol0，12，6： | 1 |
| 4 | Phase Transitions and Structures of Poly(ethylene-co-chlorotrifluoroethylene)显示文摘Poly(ethylene- co -chlorotrifluoroethylene) with a 1∶1 molar ratio of ethylene and chlorotrifluoroethylene in composition, PECTFE, is a statistically alternating copolymer widely used in cable coating industry. PECTFE has been commonly characterized as a semicrystalline polymer with crystals melting at 238 ℃. Differential scanning calorimetry, thermal mechanical analysis and dynamic mechanical analysis indicated that PECTFE undergoes a reversible solid-solid transition during cooling and heating in the temperature range between 100 ℃ and 200 ℃. Based on detailed structural analysis via wide angle X-ray diffraction and electron diffraction techniques, we proposed that PECTFE possesses a hexagonal phase above 200 ℃( a =0 60 nm, c =0 49 nm) and an orthorhombic phase( a =0 99 nm, b =0 57 nm, c =0 49 nm) at room temperature. | J.M.DEITZEL, Bojie WANG, Ping HUANG, L.Lawrence CHAPOY, Stephen Z.D.CHENG * (The Maurice Morton Institute and Department of Polymer Science, The University of Akron,Akron Ohio 44325-3909,U.S.A.) Dedicated to the Occasion of the 80th Birthday of P | 2001 | 应用化学2001，18，5： | 1 |
| 5 | 8台马尼托瓦克Potain系列起重机建设福建省最大的金融综合体显示文摘福建省厦门市海两会谷广场包括酒店、办公楼和商业中心等,面积达43万m2,总投资额约30亿元,建成后将成为福建省厦门市最大的金融综合体。据了解,海西金谷广场金融综合体采用竹简式设计,由4座高达46层的高楼组成,以及2个占地面积为1000m2的金融交易大厅。 | Stephen To Ben Shaw | 2015 | 工程机械2015，46，9： | 0 |
| 6 | 马尼托瓦克新型塔式起重机 将在bauma China 2014首次亮相显示文摘在bauma China2014上,马尼托瓦克将携两款新型Potain系列平头式塔机和1台Grove品牌KT890E型移动式越野起重机盛装亮相。Potain系列塔机是马尼托瓦克中国张家港工厂的最近创新成果。 | Stephen To | 2014 | 工程机械2014，45，11： | 0 |
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