分类: 生物学 >> 生物物理学 提交时间: 2016-05-05
摘要: Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Particularly, a large number of patients with CRC also have liver metastasis. Currently, there are just a few targeted drugs against these two kinds of tumors which can only benefit a very small population of patients. Therefore, the need of more effective therapeutic drugs or strategies for these two types of cancers is urgent. PS341 (Bortezomib) is the first proteasome inhibitor drug which has been approved in clinical treatment for multiple myeloma. Here we demonstrated that PS341 negatively regulated HCC and CRC both in vitro and in vivo, including the inhibition of cell proliferation, epithelial-mesenchymal transition (EMT), the expression of stemness-related genes, cell migration and invasiveness. Mechanically, PS341 upregulated the expression of FOXO3, which inhibited the transcriptional activation of CTNNB1. The downregualtion of CTNNB1 led to apoptosis, cell cycle arrest, and the inhibition of migration, invasion, self-renewal and tumor formation of these two cancer types. In sum, our findings shed light on the PS341 mediated targeted therapy against both HCC and CRC in the future.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: Using the analytic, static and spherically symmetric metric for a Schwarzschild black hole immersed in dark matter (DM) halos with Hernquist type density distribution, we derive analytic formulae for the orbital period and orbital precession, the evolutions of the semi-latus rectum and the eccentricity for eccentric EMRIs with the environment of DM halos. We show how orbital precessions are decreased and even reverse the direction if the density of DM halo is large enough. The presence of local DM halos slows down the decrease of the semi-latus rectum and the eccentricity. Comparing the number of orbital cycles with and without DM halos over one-year evolution before the merger, we find that DM halos with the compactness as small as $10^{-4}$ can be detected. By calculating the mismatch between GW waveforms with and without DM halos, we show that we can use GWs from EMRIs in the environments of galaxies to test the existence of DM halos and detect the compactness as small as $10^{-5}$.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: Using the analytic, static and spherically symmetric metric for a Schwarzschild black hole immersed in dark matter (DM) halos with Hernquist type density distribution, we derive analytic formulae for the orbital period and orbital precession, the evolutions of the semi-latus rectum and the eccentricity for eccentric EMRIs with the environment of DM halos. We show how orbital precessions are decreased and even reverse the direction if the density of DM halo is large enough. The presence of local DM halos slows down the decrease of the semi-latus rectum and the eccentricity. Comparing the number of orbital cycles with and without DM halos over one-year evolution before the merger, we find that DM halos with the compactness as small as $10^{-4}$ can be detected. By calculating the mismatch between GW waveforms with and without DM halos, we show that we can use GWs from EMRIs in the environments of galaxies to test the existence of DM halos and detect the compactness as small as $10^{-5}$.
分类: 光学 >> 量子光学 提交时间: 2023-02-19
摘要: Understanding the mechanism of photoacoustic generation at the nano-scale is key to developing more efficient photoacoustic devices and agents. Unlike the far-field photoacoustic effect that has been well employed in imaging, the near-field profile leads to a complex wave-tissue interaction but is under-studied. Here we show that the spatiotemporal profile of the near-field photoacoustic waves can be shaped by laser pulses, anisotropy, and nanoparticle(s) spatial arrangement. Using a gold nanorod as an example, we discovered that the near-field photoacoustic amplitude in the short axis is ~75% stronger than the long axis, and the anisotropic spatial distribution converges to an isotropic spherical wave at ~50 nm away from the nanorod's surface. We further extend the model to asymmetric gold nanostructures by arranging isotropic nanospheres anisotropically with broken symmetry to achieve a precisely controlled near-field photoacoustic "focus" largely within an acoustic wavelength.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: Purpose: To investigate the longitudinal brain regional homogeneity (ReHo) changes in nonhuman primate after spinal cord injury (SCI) by resting-state functional magnetic resonance imaging (fMRI). Methods: Three adult female rhesus monkeys underwent unilateral thoracic cord injury. A resting-state fMRI examination was performed in the healthy stage and 4, 8, and 12 weeks after the injury. The ReHo value of each voxel in the monkey brain was calculated and compared between pre- and post-SCI monkeys with paired t test. The regions of interest (ROIs) in the significantly changed ReHo regions were set. The correlations between the ReHo change and the time after injury were also determined. Results: Compared with those in healthy period, the ReHo values of the left premotor cortex and the anterior cingulate cortex (ACC) in post-SCI rhesus monkeys significantly increased in 4-week follow-up examinations. The ReHo values of posterior cingulate cortex, left precuneus, left temporal parietooccipital area, and bilateral superior parietal lobules decreased at 8-week follow-up examinations. In 12-week follow-up examinations, the ReHo values of the left postcentral gyrus, right caudate nucleus, and superior temporal gyrus increased. Correlation analysis showed positive correlations between left ACC and the postoperative time. Conclusion: SCI can change the regional synchronism of brain activity in sensorimotor system and the default mode network. These findings may help us to understand the potential pathophysiological changes in the central nervous system after SCI. (C) 2015 Elsevier Inc. All rights reserved.
分类: 光学 >> 量子光学 提交时间: 2023-02-19
摘要: Highly efficient terahertz (THz) wave sources based on difference frequency generation (DFG) process in nonlinear optical crystals play an important role for the applications of THz wave. In order to find more novel nonlinear crystals, here we theoretically investigate the generation of THz wave using the isomorphs of periodically poled $\mathrm{KTiOPO_4}$ (PPKTP), including periodically poled RTP, KTA, RTA and CTA. By solving the cascaded difference frequency coupled wave equations, it is found that the intensities of the THz wave generated from the cascaded difference frequency processes are improved by 5.27, 2.87, 2.82, 3.03, and 2.76 times from the non-cascaded cases for KTP, RTP, KTA, RTA and CTA, respectively. The effects of the crystal absorption, the phase mismatch and the pump intensity are also analyzed in detail. This study might help to provide a stronger THz radiation source based on the nonlinear crystals.
分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-11
摘要: Hereditary multiple exostosis (HME) is an autosomal inherited skeletal disease whose etiology is not fully understood. To further understand the genetic spectrum of the disease, we analyzed a five-generation Chinese family with HME that have observable inheritance. Exome sequencing was performed on three HME individuals and three unaffected individuals from the family. A downstream study confirmed a new C deletion at codon 442 on exon 5 of the exostosin-1 (EXT1) gene as the only pathogenic site which generated a stop codon and caused the truncation of the protein. We rediscovered the deletion in other affected individuals but not in the unaffected individuals from the family. Upon immunohistochemistry assay, we found that the EXT1 protein level of the patients with the novel mutation in our study was less than the level in the patients without the EXT1 mutation from another unrelated family. For a deeper understanding, we analyzed the mutation spectrum of the EXT1 gene. The present study should facilitate a further understanding of HME.
分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-11
摘要: Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3 beta and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3 beta/CTNNB1 pathway, and may contribute to progression and metastasis of RCC.
分类: 天文学 >> 天文学 提交时间: 2024-03-29 合作期刊: 《Research in Astronomy and Astrophysics》
摘要: Ground-based arrays of imaging atmospheric Cherenkov telescopes (IACTs) are the most sensitive γ-ray detectors for energies of approximately 100 GeV and above. One such IACT is the High Altitude Detection of Astronomical Radiation (HADAR) experiment, which uses a large aperture refractive water lens system to capture atmospheric Cherenkov photons (i.e., the imaging atmospheric Cherenkov technique). The telescope array has a low threshold energy and large field of view, and can continuously scan the area of the sky being observed, which is conducive to monitoring and promptly responding to transient phenomena. The process of γ-hadron separation is essential in very-high-energy (>30 GeV) γ-ray astronomy and is a key factor for the successful utilization of IACTs. In this study, Monte Carlo simulations were carried out to model the response of cosmic rays within the HADAR detectors. By analyzing the Hillas parameters and the distance between the event core and the telescope, the distinction between air showers initiated by γ-rays and those initiated by cosmic rays was determined. Additionally, a Quality Factor was introduced to assess the telescope's ability to suppress the background and to provide a more effective characterization of its performance.