44 research outputs found
Statistical analysis of geometrical parameters of corroded reinforcement
This paper reports an experimental work to investigate the pit corrosion of steel bars in chloride contaminated concrete. A total of 50 reinforcing steel bars with a length of 250 mm and a diameter of 14 mm were embedded in 10 concrete specimens, before they were subjected to accelerated corrosion. The geometric parameters of the corroded steel bars were then examined using 3D scanning method, before the characteristics of pitting corrosion of the corroded bars were analyzed accordingly. The results show that there is a weak correlation between the maximum pit depth and the mass loss rate. However, there is a strong correlation between the pitting factor and the mass loss rate. The relationship between the pitting factor and the mass loss rate has been developed as a reciprocal function
The transcriptional coactivator TAZ regulates reciprocal differentiation of T(h)17 cells and T(reg) cells
自身免疫性疾病是一类机体对自身抗原发生免疫反应而导致自身多器官、组织受累的慢性炎症性疾病。目前大量研究表明机体内促炎症的TH17细胞和抑制炎症Treg细胞在类群数量和活化状态的失衡是造成自身免疫疾病的主要致病因素。陈兰芬教授和周大旺教授团队的前期研究发现小鼠中Hippo信号通路中激酶Mst1/2缺失导致免疫缺陷,机体易受病原体感染并伴随着严重自身免疫疾病。该研究揭示了Hippo 信号通路转录共激活因子TAZ在决定CD4+初始T细胞分化为促进炎症的TH17效应细胞和抑制免疫反应的Treg调节性细胞过程中发挥着关键作用,拓展了当前对于Hippo信号通路的相关研究内容。
陈兰芬,博士,厦门大学生命科学学院教授。【Abstraact】An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under T
H17 cell–inducing conditions and was required for TH17 differentiation and TH17 cell–mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under T
regcell–skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors RORγt and Foxp3 promoted Treg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced Treg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed TH17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of Treg
cells and TH17 cells.J. Avruch for comments on the manuscript.Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), the National Natural Science Foundation of China (81422018 to L.C.; 31625010 and U1505224 to D.Z.; U1405225 and 81372617 to L.C.; J1310027 to D.Z.; 81472229 to L.H.; and 31600698 to J. Geng), the 111 Projects (B12001 and B06016), China's 1000 Young Talents Program (D.Z., and L.C.), the Fundamental Research Funds for the Central Universities of China-Xiamen University (20720160071 to D.Z. and 20720160054 to L.H.) and Major disease research projects of Xiamen (3502Z20149029 to L.C.)
Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2
大多数真核生物的体细胞是二倍体,即仅含有两组染色体,分别遗传自父本和母本。而一些特定组织如心脏、肝脏等就含有多倍体细胞,特别是肝脏组织含有较高比例的四、八倍体等多倍体细胞。肝脏是人体的重要解毒器官,同时酒精、肝炎病毒等毒性物质或毒性代谢物容易诱发肝细胞的基因突变,多倍体被认为有利于提供代偿性的正常基因来维持肝脏稳态。然而肝脏受损后,多倍体细胞将会受胁迫进行增殖,再生修复受损的肝组织。因此研究机体调控多倍体细胞产生及多倍体细胞进行细胞分裂的调控机理对于理解肝癌的发病机理和肝癌的治疗至关重要。Hippo信号通路在调节组织成体干细胞的分化和增殖,调控器官再生与尺寸大小中具有重要作用。深入研究发现, Hippo信号通路下游效应分子YAP通过AKT-SKP2信号促进二倍体细胞向多倍体转化及多倍体细胞的生长增殖。本项研究阐明了Hippo缺失及YAP激活促进多倍体细胞产生及增殖作为肝癌发生发展中的一个重要机制,为肝癌诊疗提供了新的策略。
周大旺,博士,厦门大学生命科学学院教授、副院长、国家杰出青年基金获得者。【Abstract】Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis. importantly, the depletion or inactivation of Akt or Skp2 abrogated Hippo signal deficiency-induced liver tumorigenesis, indicating their epistatic interaction. Thus, we conclude that Hippo-Yap signaling suppresses cell polyploidy and oncogenesis through Skp2.该研究工作获得了国家自然科学基金委、国家重点基础研究发展计划(973)项目、青年千人计划和中央高校基本科研基金的资助。
The Yap (S127A) transgenic mice were kindly provided by Dr. Fernando Camargo from Harvard Medical School, Boston, MA. D.Z. and L.C. were supported by the National Natural Science Foundation of China (31625010,U1505224, and J1310027 to D.Z.; 81422018, U1405225, and 81372617 to L.C.; 81472229 to L.H.), the National Basic Research Program (973) of China (2015CB910502 to L.C.), the Fundamental Research Funds for the Central Universities of China-Xiamen University (20720140551 to L.C. and 2013121034 and 20720140537 to D.Z.)
Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity
该研究成果揭示了吞噬性细胞内Hippo信号通路关键激酶Mst1和Mst2通过活化Rac家族蛋白来调节线粒体向吞噬小泡募集并释放ROS来清除病原体,这个生物学过程在天然免疫和宿主防御中发挥着重要作用。该成果解析了人的Mst1基因缺失或Rac2基因突变引发免疫缺陷综合症的致病机理,为研究人类感染性疾病提供了全新的视角。
该论文的主要工作由2012级博士生耿晶、2013级博士生孙秀峰以及王平、张世浩和王晓珍等学生共同承担,并与厦门市第一医院、台湾长庚大学、中国科学技术大学等单位合作完成,通讯作者为周大旺教授和陈兰芬教授。该研究工作获得了“青年千人计划”、国家自然科学基金委和科技部的资助。Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2D57N mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), China's 1000 Young Talents Program (D.Z. and L.C.), the 111 Projects (B12001 and B06016), the Fundamental Research Funds for the Central Universities of China-Xiamen University (CXB2014004 to J.Z.; 20720140551 to L.C.; and 2013121034 and 20720140537 to D.Z.), the National Natural Science Foundation of China (31270918, 81222030 and J1310027 to D.Z.; 81372617, 81422018 and U1405225 to L.C.; 81472229 to L.H.; and 81302529 to X.L.), the Natural Science Foundation of Fujian (2013J06011 to D.Z. and 2014D007 to X.L.), the US National Institutes of Health (RO1 CA136567 for J.A.) and institutional funds from Massachusetts General Hospital (for J.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
The Ets Transcription Factor GABP Is a Component of the Hippo Pathway Essential for Growth and Antioxidant Defense
这是周大旺教授继2009年首次发现了Hippo信号通路在哺乳动物中控制器官大小及肿瘤发生具有重要作用后的又一重大研究成果,该研究系统阐述了 YAP基因在转录调控水平上的的调控机理,进一步完善了人们对Hippo信号通路的认识,也为由YAP调控异常所引发的癌症提供了一个潜在的治疗靶点。
该论文的第一作者为博士生吴黉坦和硕士生肖玉波和张世浩, 通讯作者是周大旺教授和陈兰芬副教授,该工作是与厦门市中医院、中山医院和医学高等专科学校等单位合作完成的。周大旺教授是中央首批“青年千人计划”入选者并获得国家首批“优秀青年科学基金”资助。The transcriptional coactivator Yes-associated protein (YAP) plays an important role in organ-size control and tumorigenesis. However, how Yap gene expression is regulated remains unknown. This study shows that the Ets family member GABP binds to the Yap promoter and activates YAP transcription. The depletion of GABP downregulates YAP, resulting in a G1/S cell-cycle block and increased cell death, both of which are substantially rescued by reconstituting YAP. GABP can be inactivated by oxidative mechanisms, and acetaminophen-induced glutathione depletion inhibits GABP transcriptional activity and depletes YAP. In contrast, activating YAP by deleting Mst1/Mst2 strongly protects against acetaminophen-induced liver injury. Similar to its effects on YAP, Hippo signaling inhibits GABP transcriptional activity through several mechanisms. In human liver cancers, enhanced YAP expression is correlated with increased nuclear expression of GABP. Therefore, we conclude that GABP is an activator of Yap gene expression and a potential therapeutic target for cancers driven by YAP
Research on Microscopic Pore Structure and Permeability of Air-Entrained Fly–Ash Concrete Subjected to Freezing and Thawing Action
In this paper, rapid freezing and thawing test of air-entrained fly–ash concrete was carried out. Gas adsorption of concrete pores, mass loss, dynamic elastic modulus, and chloride diffusion coefficient of concrete after different freezing and thawing cycles was tested; scanning electron image was used to study the microscopic pore structure of the specimens. Results show that after certain freezing and thawing cycles, microscopic pores of the sample had a brittle failure, which results in sudden changes of cumulative desorption pore volume and cumulative desorption surface area obtained by Barrett, Joyner, and Halenda method. It was found that the variation of maximum cumulative desorption surface area is in good agreement with that of mass loss rate and chloride diffusion coefficient. At different stages of freezing and thawing, rate of mass loss shows a linear relationship with maximum cumulative desorption pore volume and maximum cumulative desorption surface area. In the range of freezing and thawing cycle between 0 and 150, chloride diffusion coefficient demonstrates a linear relationship with maximum cumulative desorption pore volume and maximum cumulative desorption surface area; in the range of freezing and thawing cycle between 200 and 300, this relationship becomes nonlinear
Applicability Analysis of Assessment Methods for Morphological Parameters of Corroded Steel Bars
The irregular and uneven residual sections along the length of a corroded steel bar substantially change its mechanical properties and significantly dominate the safety and performance of an existing concrete structure. As a result, it is important to measure the geometry and amount of corrosion of a steel bar in a structure properly to assess the residual bearing capacity and service life of the structure. This paper introduces and compares five different methods for measuring the geometry and amount of corrosion of a steel bar. A single 500 mm long and 14 mm diameter steel bar is the specimen that is subjected to accelerated corrosion in this protocol. Its morphology and the amount of corrosion were carefully measured before and after using mass loss measurements, a Vernier caliper, drainage measurements, 3D scanning, and X-ray micro-computed tomography (XCT). The applicability and suitability of these different methods were then evaluated. The results show that the Vernier caliper is the best choice for measuring the morphology of a non-corroded bar, while 3D scanning is the most suitable for quantifying the morphology of a corroded bar
The Hysteresis Performance and Restoring Force Model for Corroded Reinforced Concrete Frame Columns
A numerical simulation of the hysteresis performance of corroded reinforced concrete (RC) frame columns was conducted. Moreover, the results obtained were compared with experimental data. On this basis, a degenerated three-linearity (D-TRI) restoring force model was established which could reflect the hysteresis performance of corroded RC frame columns through theoretical analysis and data fitting. Results indicated that the hysteretic bearing capacity of frame columns decreased significantly due to corrosion of the rebar. In view of the characteristics of the hysteresis curve, the plumpness of the hysteresis loop for frame columns decreased and shrinkage increased with increasing rebar corrosion. All these illustrated that the seismic energy dissipation performance of frame columns reduced but their brittleness increased. As for the features of the skeleton curve, the trends for corroded and noncorroded members were basically consistent and roughly corresponded to the features of a trilinear equivalent model. Thereby, the existing Clough hysteresis rule can be used to establish the restoring force model applicable to corroded RC frame columns based on that of the noncorroded RC members. The calculated skeleton curve and hysteresis curve of corroded RC frame columns using the D-TRI model are closer to the experimental results
Deformation and Compressive Strength of Steel Fiber Reinforced MgO Concrete
To reduce the cracking caused by shrinkage and avoid the brittle behavior of concrete, MgO expansion agent and steel fibers were used in this paper. Firstly, the effect of MgO and steel fibers on the compressive strength of concrete was compared. The results showed that the compressive strength of steel fibers reinforced concrete (SC) and steel fiber reinforced MgO concrete (SMC) was significantly improved. Compared with ordinary concrete (OC), SMC’s 28 days compressive strength increased by 19.8%. Secondly, the influence of MgO and steel fibers with different contents on the self-volumetric deformation of concrete was compared through the experiment. The results showed that as a result of the hydration expansion of MgO, MC and SMC both showed obvious expansion, and their 190 days expansion was 335 μ ε and 288 μ ε , respectively. Lastly, through a scanning electron microscope (SEM) test, it was found that the constraint effect of steel fibers changed the expansion mode of MgO from outward expansion to inward extrusion, thus improving the interfacial bond strength of concrete