Outd7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination

( Hongbo Hu ),( Hui Wang ),( Yichuan Xiao ),( Jin Jin ),( Jae Hoon Chang ),( Qiang Zou ),( Xiaopin Xie ),( Xuhong Cheng ),( Shao Cong Sun ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

Signal transduction from the T ceII receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitatinq TCR sig­naling. Upon TCR ligation, Olud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal sig­naling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Olud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phospha­tases SIs1 and Sts2. These findings establish Otud7b as a positive requlator of TCR-proximal signaling and T cell activation. highlighting the importance of deubiquitination in regulaling Zap70 function.

Pentagalloylglucose induces autophagy and caspase-independent programmed deaths in human PC-3 and mouse TRAMP-C2 prostate cancer cells.

Hu, Hongbo,Chai, Yubo,Wang, Lei,Zhang, Jinhui,Lee, Hyo Jeong,Kim, Sung-Hoon,Lü,, Junxuan American Association for Cancer Research, Inc 2009 Molecular Cancer Therapeutics Vol.8 No.10

<P>Penta-1,2,3,4,6-O-galloyl-beta-d-glucose (PGG) suppresses the in vivo growth of human DU145 and PC-3 prostate cancer xenografts in nude mice, suggesting potential utility as a prostate cancer chemotherapeutic or chemopreventive agent. Our earlier work implicates caspase-mediated apoptosis in DU145 and LNCaP prostate cancer cells as one mechanism for the anticancer activity. We show here that, in the more aggressive PC-3 prostate cancer cell line, PGG induced programmed cell deaths lacking the typical caspase-mediated apoptotic morphology and biochemical changes. In contrast, PGG induced patent features of autophagy, including formation of autophagosomes and lipid modification of light chain 3 after 48 hours of PGG exposure. The 'autophagic' responses were also observed in the murine TRAMP-C2 cells. Caspase inhibition exacerbated PGG-induced overall death. As for molecular changes, we observed a rapid inhibition of the phosphorylation of mammalian target of rapamycin-downstream targets S6K and 4EBP1 by PGG in PC-3 and TRAMP-C2 cells but not that of mammalian target of rapamycin itself, along with increased AKT phosphorylation. Whereas the inhibition of phosphatidylinositol 3-kinase increased PGG-induced apoptosis and autophagy, experiments with pharmacologic inducer or inhibitor of autophagy or by knocking down autophagy mediator Beclin-1 showed that autophagy provided survival signaling that suppressed caspase-mediated apoptosis. Knocking down of death receptor-interacting protein 1 kinase increased overall death without changing light chain 3-II or caspase activation, thus not supporting death receptor-interacting protein 1-necroptosis for PGG-induction of autophagy or other programmed cell death. Furthermore, PGG-treated PC-3 cells lost clonogenic ability. The induction by PGG of caspase-independent programmed cell death in aggressive prostate cancer cell lines supports testing its merit as a potential drug candidate for therapy of caspase-resistant recurrent prostate cancer.</P>

Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces p53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo.

Hu, Hongbo,Lee, Hyo-Jeong,Jiang, Cheng,Zhang, Jinhui,Wang, Lei,Zhao, Yan,Xiang, Qiu,Lee, Eun-Ok,Kim, Sung-Hoon,Lü,, Junxuan American Association for Cancer Research, Inc 2008 Molecular Cancer Therapeutics Vol.7 No.9

<P>Penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG) is a naturally occurring gallotannin from some Oriental herbs. Several cell culture studies suggested a potential for PGG as a novel agent for the chemoprevention and treatment of cancer. Here, we investigated the cell death signaling mechanisms induced by PGG in human prostate cancer cells of different p53 functional status. We observed the induction of G(1)- and S-phase arrests and caspase-mediated apoptosis in the androgen-dependent human LNCaP cells, which express wild-type p53, and in the androgen-independent, p53-mutant DU145 cells. In LNCaP cells, caspase-mediated apoptosis induction by PGG was associated with and mediated in major part by activation of p53 as established through small interfering RNA knockdown and dominant-negative mutant approaches. Intracellular reactive oxygen species production by PGG was found to be crucial for these molecular and cellular actions. In DU145 cells, which harbor constitutively active signal transducer and activator of transcription 3 (STAT3), caspase-mediated apoptosis induction by PGG was associated with an inhibition of STAT3 Tyr705 phosphorylation and the down-regulation of STAT3 transcriptional targets Bcl-XL and Mcl-1. Overexpression of Bcl-XL or knockdown of its binding partner Bak attenuated apoptosis induction. Furthermore, we provide, for the first time, in vivo data that PGG significantly inhibited DU145 xenograft growth in an athymic nude mouse model in association with an inhibition of pSTAT3. Our data support PGG as a multitargeting agent for chemoprevention and therapy of prostate cancer by activating the p53 tumor suppressor pathway and by inhibiting STAT3 oncogenic signaling.</P>

OTUD7B controls non-canonical NF-kB activation through deubiquitination of TRAF3

( Hongbo Hu ),( George C Brittain ),( Jae Hoon Chang ),( Nahum Puebla Osorio ),( Jin Jin ),( Anna Zal ),( Yichuan Xiao ),( Xuhong Cheng ),( Mikyoung Chang ),( Yang Xin Fu ),( Tomasz Zal ),( Chengming 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

The non-canonical NF-κB pathway forms a major arm of NF-κB signalling that mediates important biological functions, including lymphoid organogenesis, B-lymphocyte function, and cell growth and survival. Activation of the non-canonical NF-κB pathway involves degradation of an inhibitory protein, TNF receptor-associated factor 3 (TRAF3), but how this signalling event is controlled is still unknown. Here we have identified the deubiquitinase OTUD7B as a pivotal regulator of the non-canonical NF-κB pathway. OTUD7B deficiency in mice has no appreciable effect on canonical NF-κB activation but causes hyperactivation of non-canonical NF-κB. In response to non-canonical NF-κB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NF-κB activation. Consequently, the OTUD7Bdeficiency results in B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa, and elevated host-defence ability against an intestinal bacterial pathogen, Citrobacter rodentium. These findings establish OTUD7B as a crucial regulator of signal-inducednon-canonical NF-κB activation and indicate a mechanism of immune regulation that involves OTUD7B-mediated deubiquitination and stabilization of TRAF3.

Reinforcement of Circular Steel Tubes Using Welded Casings Under Axial Compression Loading

Hongbo Liu,Jie Hu,Zhi-Hua Chen,Longxuan Wang,W. A. H. Mashrah 한국강구조학회 2022 International Journal of Steel Structures Vol.22 No.3

To explore the mechanical behavior of circular steel tube components strengthened with welded casings, two groups of six specimens are designed, and two working conditions of zero-load reinforcement and load reinforcement are defi ned. Typical failure modes, ultimate bearing capacity, defl ection curves, and strain data of measuring points are obtained. The FE modeling method considering the thermal eff ect of the welding process is proposed and verifi ed. A total of 446 fi nite element models are established to explore the eff ects of the initial defects, the slenderness ratio, the boundary conditions, and the area ratio of the welded casing to the circular steel tube on the ultimate bearing capacity of the strengthened components. In addition, the ultimate bearing capacity equations for zero-load strengthened components is proposed using regression fi tting and considering the adverse eff ects of the residual stresses due to the rolling and welding processes. Moreover, equations for calculating the deformation and the ultimate bearing capacity of the load-strengthened components considering the eff ect of the welding heat are also derived. Finally, the experimental, numerical, and theoretical analyses results were consistent in high calculation validity and effi ciency.

Performance Analysis of Multi-hop Wireless Networks under Different Hopping Strategies with Spatial Diversity

( Hu Han ),( Zhu Hongbo ),( Zhu Qi ) 한국인터넷정보학회 2012 KSII Transactions on Internet and Information Syst Vol.6 No.10

This paper derives two main end-to-end performance metrics, namely the spatial capacity density and the average end-to-end delay of the multi-hop wireless ad hoc networks with multi-antenna communications. Based on the closed-form expressions of these performance metrics, three hopping strategies, i.e., the closest neighbor, the furthest neighbor and the randomly selected neighbor hopping strategies have been investigated. This formulation provides insights into the relations among node density, diversity gains, number of hops and some other network design parameters which jointly determine network performances, and a method of choosing the best hopping strategy which can be formulated from a network design perspective.

Design of the Linear Quadratic Structure Based Predictive Functional Control for Industrial Processes Against Partial Actuator Failures Using GA Optimization

Xiaomin Hu,Hongbo Zou,Limin Wang 제어·로봇·시스템학회 2019 International Journal of Control, Automation, and Vol.17 No.3

This paper addresses the genetic algorithm (GA) optimization and the linear quadratic (LQ) structurebased predictive functional control (PFC) for batch processes under non-repetitive unknown disturbances and partialactuator faults. First, by adopting the extended non-minimal state space (ENMSS) model in which the state variablesand the tracking error are united, the new state vector with more degrees is provided for the controller design. Inorder to enhance the ensemble control performance under the PFC structure, GA is adopted for the optimizationof the weighting matrix in the controller. The case study on the injection velocity control in an injection moldingmachine demonstrates the effectiveness of the proposed PFC scheme against various disadvantages.

Adjust band gap of IATO nanoparticles to obtain desirable optical property by one-step hydrothermal oxidati

Te Hu,Yuchang Su,Ian R. Baxendale,Jiang Tan,Hongbo Tang,Lihua Xiao,Feng Zheng,Ping Ning 한국물리학회 2017 Current Applied Physics Vol.17 No.4

Antimony-tin-doped indium oxide (IATO) as transparent conducting oxide (TCO) exhibits significant optical property on blocking UV and Infrared(IR) for wavelengths less ~400 nm and over ~1400 nm as well as appropriate transmissivity on visible wavelength in our work that can be as an optional idea optical material applying in shielding film or nanocomposite to achieve desired optical application. We have successfully developed an optimal synthesis system which allows for a single hydrothermal oxidation directly synthesizing IATO nanoparticles without high-temperature calcination. These nanoparticles show superior size, crystallinity, agglomeration and are free of intermediates In(OH)3 and InOOH. We also have demonstrated they give scope to desired optical property as a result of an altered IATO band gap energy. We highlight this approach due to the shortened preparation time, the reduced energy consumption and the decreased chemical usage which dramatically save on production costs and protect environment.

A Shared-bridge Converter with Reversed Current Direction for Active Magnetic Bearing Drive

Zaidong Hu,Dong Jiang,Hongbo Sun,Ronghai Qu 전력전자학회 2019 ICPE(ISPE)논문집 Vol.2019 No.5

Active magnetic bearing(AMB) is widely used in high speed rotating machinary, and the power electronic converter is a key technology of AMB[1]. A shared-bridge converter has been put forward for multi-axis AMB drive, which can make fully use of devices and reduce the cost[8]. However, the high current rating of shared-phase-leg brings challenge to the devices and the power losses of converter cannot be reduced by this topology. In this paper, a novel topology for AMB drive with reversed current direction is put forward. Comparing with the shared-bridge converter, the novel topology can significantly reduce the current stress of devices on the shared-phase leg by using one more power electronics switch and diode. Meanwhile, the power losses of the converter can be greatly reduced. The principle and the implementation method are introduced and compensation is applied to eliminate the effect of dead-time. Simulation results have successfully validated the feasibility of methods of modulation and dead-time compensation. Suspension and rotating tests have carried out on a 4-axis AMB test rig with the converter of novel topology. The experimental results have verified that the novel converter meets the requirements of AMB drive.

An ABA triblock copolymer strategy for intrinsically stretchable semiconductors

Peng, Rui,Pang, Bo,Hu, Daqing,Chen, Mengjie,Zhang, Guobing,Wang, Xianghua,Lu, Hongbo,Cho, Kilwon,Qiu, Longzhen The Royal Society of Chemistry 2015 Journal of Materials Chemistry C Vol.3 No.15

<▼1><P>A novel semiconductor–rubber–semiconductor triblock copolymer has been designed and prepared according to the principle of thermoplastic elastomers (TPEs). It behaves as a TPE and exhibits good electrical properties.</P></▼1><▼2><P>A novel semiconductor–rubber–semiconductor (P3HT–PMA–P3HT) triblock copolymer has been designed and prepared according to the principle of thermoplastic elastomers. It behaves as a thermoplastic elastomer with a Young's modulus (<I>E</I>) of 6 MPa for an elongation at break of 140% and exhibits good electrical properties with a carrier mobility of 9 × 10<SUP>−4</SUP> cm<SUP>2</SUP> V<SUP>−1</SUP> s<SUP>−1</SUP>. This novel semiconductor may play an important role in low-cost and large-area stretchable electronics.</P></▼2>