分类： 生物学 >> 生物物理学 >> 免疫学 提交时间： 2016-05-12
Chen, Jun
Hao, Lu
Li, Chong
Ye, Buqing
Du, Ying
Zhang, Honglian
Zhu, Pingping
Liu, Benyu
Yang, Liuliu
Fan, Zusen
Chen, Jun
Hao, Lu
Long, Bo
Long, Bo
Li, Peifeng
Tian, Yong
摘要： NK cells play a pivotal role in innate immune responses against pathogenic infections. However, the underlying mechanisms driving defined NK functions remain largely elusive. In this study, we identified a novel endoplasmic reticulum (ER) membrane protein, ER adaptor protein (ERAdP), which is constitutively expressed in human and mouse NK cells. ERAdP is expressed at low levels in peripheral NK cells of hepatitis B virus-associated hepatocellular carcinoma patients. We show that ERAdP initiates NK cell activation through the NF-kappa B pathway. Notably, ERAdP interacts with ubiquitin-conjugating enzyme 13 (Ubc13) to potentiate its charging activity. Thus, ERAdP augments Ubc13-mediated NF-kappa B essential modulator ubiquitination to trigger the Ubc13-mediated NF-kappa B pathway, leading to NK cell activation. Finally, ERAdP transgenic mice display hyperactivated NK cells that are more resistant to pathogenic infections. Therefore, understanding the mechanism of ERAdP-mediated NK cell activation will provide strategies for treatment of infectious diseases.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Zhu, Pingping
Wang, Yanying
Huang, Guanling
Du, Ying
Zhang, Geng
Yan, Xinlong
Xia, Pengyan
Ye, Buqing
Wang, Shuo
Hao, Lu
Wu, Jiayi
Fan, Zusen
He, Lei
Huang, Guanling
Hao, Lu
Wu, Jiayi
Fan, Zusen
摘要： Liver cancer stem cells (CSCs) have been identified and shown to have self-renewal and differentiation properties; however, the biology of these hepatic CSCs remains largely unknown. Here, we analyzed transcriptome gene expression profiles of liver CSCs and non-CSCs from hepatocellular carcinoma (HCC) cells lines and found that the transcription factor (TF) ZIC2 is highly expressed in liver CSCs. ZIC2 was required for the self-renewal maintenance of liver CSCs, as ZIC2 depletion reduced sphere formation and xenograft tumor growth in mice. We determined that ZIC2 acts upstream of the TF OCT4 and that ZIC2 recruits the nuclear remodeling factor (NURF) complex to the OCT4 promoter, thereby initiating OCT4 activation. In HCC patients, expression levels of the NURF complex were consistent with clinical severity and prognosis. Moreover, ZIC2 and OCT4 levels positively correlated to the clinicopathological stages of HCC patients. Altogether, our results indicate that levels of ZIC2, OCT4, and the NURF complex can be detected and used for diagnosis and prognosis prediction of HCC patients. Moreover, these factors may be potential therapeutic targets for eradicating liver CSCs.
分类： 物理学 >> 核物理学 提交时间： 2025-03-10
摘要： Ultrabright femtosecond X-ray pulses generated by X-ray free-electron lasers (XFELs) enable the high-resolution determination of nanoparticle structures without crystallization or freezing. As each particle that interacts with the pulse is destroyed, an aerodynamic lens (ADL) is used to update the particles by focusing them into a narrow beam in real time. Current single-particle imaging (SPI) experiments are limited by an insufficient number of diffraction patterns; therefore, optimized ADLs are required to improve the hit rate and signal-to-noise ratio, particularly for small particles. Herein, an efficient and simple method for designing ADLs and a new ADL specifically designed for SPI using this method are presented. A new method is proposed based on the functional relationship between a key parameter and its influencing parameters in the ADL, which is established through theoretical analysis and numerical simulations. A detailed design process for the new ADL is also introduced. Both simulations and experiments are performed to characterize the behavior of the particles in the ADL. The results show that particles with diameters ranging from 30 to 500 nm can be effectively focused into a narrow beam. In particular, particles smaller than 100 nm exhibit better performance at lower flow rates than the injector currently used in SPI. The new ADL increases the beam density and reduces the gas background noise. This new method facilitates the design of ADLs for SPI and has potential applications in other fields that utilize focused aerosol beams.
分类： 光学 >> 量子光学 提交时间： 2023-02-19
摘要： We propose a new architecture, double-pass multiple-plate continuum (DPMPC), for nonlinear pulse compression. In addition to smaller footprint, a double-pass configuration is designed to achieve substantial bandwidth broadening without incurring noticeable higher-order dispersion, thus improving the temporal contrast over those of traditional single-pass geometry when only quadratic spectral phase can be compensated. In our proof-of-concept experiment, 187~\muJ, 190-fs Yb-based laser pulse is compressed to 20~fs with high throughput (75%), high Strehl ratio (0.76) and excellent beam homogeneity by using DPMPC. Subsequently generated octave-spanning spectrum exhibits a significantly raised blue tail compared with that driven by pulses from a single-pass counterpart.
点击量
待评议
点击量
下载量
评论
