Hong Kong Zhuhai Macao Link

AbstractThe Hong Kong Zhuhai Macao Link will be built across the mouth of the Pearl River Delta linking Hong Kong, Zhuhai and Macao in the south of China. The link will comprise of a dual 3-lane with hardshoulder motorway with a total length of approximately 42km, of which approximately 30km will be in mainland territory and approximately 12km will be within Hong Kong territory. The link will comprise of Border Crossing Facilities on reclaimed land in Zhuhai and Hong Kong, approximately 30km of sea-crossing bridges, approximately 5km of immersed tunnel, two artificial islands, approximately 2km of at-grade road and approximately 2km of cut and cover tunnel. The preliminary design of the link on the mainland side has been carried out by a joint venture of HPDI+ARUP+COWI+SHTDI+FHCL and on the Hong Kong side by ARUP alone. The division of work is as follows:•HPDI-Lead•ARUP-Bridges•COWI-Tunnel•SHTDI-Islands•FHCL-Electrical & MechanicalThis paper describes the design of the bridges on the link. The client for the link on the mainland side comprises the governments of the Guangdong Province PRC, Hong Kong SAR and Macao SAR. The client on the Hong Kong side is the Highways Department of the Hong Kong SAR

2-HG通过上调RIP3启动子的甲基化水平抑制细胞坏死

文章简介在异柠檬酸脱氢酶1/2(IDH1/2)突变的细胞中,高浓度的2-羟基戊二酸(2-HG)通过抑制TET2的活性增强了DNA的甲基化。在本研究中,课题组发现2-HG可通过直接激活DNA甲基转移酶DNMT1的作用而促进RIP3启动子的国家基础研究计划基金(973 Program;2015CB553800,2013CB944903,2014CB541804);;国家自然科学基金项目(91029304,31420103910,31330047,81630042,81372702,81402285,31571473);;中央高校基本科研专项资金(20720140552,10120100002);;国家基础科学人才培养基金(Grant No.J1310027)的资

IDH1突变体通过抑制JNK的激活减少生长因子缺失诱导的细胞凋亡

文章简介抵抗凋亡和能在血清营养因子缺乏的情况下生长是肿瘤细胞的两个主要特征。JNK的激活是血清饥饿诱导的细胞凋亡所必须的因素。目前研究表明IDH1突变体产生的致癌代谢物2-羟基戊二酸(2-HG)是突变的导致肿瘤形成的主要原因。然而目前尚不清楚2-HG是否能抑制JNK的激活,进而使细胞抵抗血清饥饿诱导的凋亡。课题组以IDH1 R132Q的基因敲入MEF为研究对象

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn2+ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn2+ chelator to create an EBNA1-specific inhibitor (ZRL5P4). ZRL5P4 by itself is sufficient to reactivate EBV from its latent infection. ZRL5P4 is able to emit unique responsive fluorescent signals once it binds with EBNA1 and a Zn2+ ion. ZRL5P4 can selectively disrupt the EBNA1 oligomerization and cause nasopharyngeal carcinoma (NPC) tumor shrinkage, possibly due to EBV lytic induction. Dicer1 seems essential for this lytic reactivation. As can been seen, EBNA1 is likely to maintain NPC cell survival by suppressing viral reactivation

Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11

PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G1 and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolu

Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease

BackgroundNon-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD) represents the largest subgroup with heterogeneous liver fibrosis risk. Metabolic dysfunction promotes liver fibrosis. Here, we investigated whether incorporating additional metabolic risk factors into clinical evaluation improved liver fibrosis risk stratification among individuals with non-diabetic overweight/obese MAFLD.Materials and methodsComprehensive metabolic evaluation including 75-gram oral glucose tolerance test was performed in over 1000 participants from the New Hong Kong Cardiovascular Risk Factor Prevalence Study (HK-NCRISPS), a contemporary population-based study of HK Chinese. Hepatic steatosis and fibrosis were evaluated based on controlled attenuation parameter and liver stiffness (LS) measured using vibration-controlled transient elastography, respectively. Clinically significant liver fibrosis was defined as LS ≥8.0 kPa. Our findings were validated in an independent pooled cohort comprising individuals with obesity and/or polycystic ovarian syndrome.ResultsOf the 1020 recruited community-dwelling individuals, 312 (30.6%) had non-diabetic overweight/obese MAFLD. Among them, 6.4% had LS ≥8.0 kPa. In multivariable stepwise logistic regression analysis, abnormal serum aspartate aminotransferase (AST) (OR 7.95, p<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5 (OR 5.01, p=0.008) were independently associated with LS ≥8.0 kPa, in a model also consisting of other metabolic risk factors including central adiposity, hypertension, dyslipidaemia and prediabetes. A sequential screening algorithm using abnormal AST, followed by elevated HOMA-IR, was developed to identify individuals with LS ≥8.0 kPa, and externally validated with satisfactory sensitivity (>80%) and negative predictive value (>90%).ConclusionA sequential algorithm incorporating AST and HOMA-IR levels improves fibrosis risk stratification among non-diabetic overweight/obese MAFLD individuals

Ernest Armstrong McCulloch

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