分类： 药物科学 >> 生物化学 提交时间： 2024-06-14
Huixu Feng
Guobin Liu
Luhan Li
Xuelian Ren
Yue Jiang
Wanting Hou
Ruilong Liu
Kun Liu
Hong Liu
He Huang
摘要： Hyperlipidemia (HLP) is a prevalent systemic metabolic disorder characterized by disrupted lipid metabolism. Statin drugs have long been the primary choice for managing lipid levels, but intolerance issues have prompted the search for alternative treatments. Matrine, a compound derived from the traditional Chinese medicine Kushen, exhibits anti-inflammatory and lipid-lowering properties. Nevertheless, the mechanism by which matrine modulates lipid metabolism remains poorly understood. Here, we investigated the molecular mechanisms underlying matrine’s regulation of lipid metabolism. Employing quantitative proteomics, we discovered that matrine increases the expression of LDL receptor (LDLR) in HepG2 and A549 cells, with subsequent experiments validating its role in enhancing LDL uptake. Notably, in hyperlipidemic hamsters, matrine effectively lowered lipid levels without affecting body weight, which highlights LDLR as a critical target for matrine’s impact on hyperlipidemia. Moreover, matrine’s potential inhibitory effects on tumor cell LDL uptake hint at broader applications in cancer research. Additionally, Thermal Proteome Profiling (TPP) analysis identified lipid metabolism-related proteins that may interact with matrine. Together, our study reveals matrine’s capacity to upregulate LDLR expression and highlights its potential in treating hyperlipidemia. These findings offer insights into matrine’s mechanism of action and open new avenues for drug research and lipid metabolism regulation.
分类： 药物科学 >> 生物化学 提交时间： 2024-06-14
Yue Jiang
Xuelian Ren
Jing Zhao
Guobin Liu
Fangfang Liu
Xinlong Guo
Ming Hao
Hong Liu
Kun Liu
He Huang
摘要： Gemcitabine (GEM) is a potent chemotherapeutic agent widely employed in the treatment of various cancers, notably pancreatic cancer. Despite its clinical success, challenges related to GEM resistance and toxicity persist. Therefore, there is a pressing need for a deeper understanding of its intracellular mechanisms and potential targets. In this study, we utilized quantitative proteomics and thermal proteome profiling (TPP) to elucidate the effects of GEM. Our proteomic analysis revealed that GEM primarily affected DNA synthesis, leading to the upregulation of cell cycle and DNA replication proteins. Additionally, enrichment analysis highlighted the activation of the p53 pathway, shedding light on GEM-induced apoptosis mechanisms. Notably, we observed the upregulation S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator, in response to GEM treatment. Combining SKP2 inhibition with GEM showed synergistic effects in both cellular and animal models, suggesting SKP2 as a potential target for enhancing GEM sensitivity and overcoming chemoresistance. Furthermore, through TPP, we explored potential binding targets of GEM, which implies GEM’s broad anticancer effects. Together, these findings provide valuable insights into GEM’s molecular mechanisms and offer potential targets for improving treatment efficacy. This research holds the promise of advancing personalized treatment strategies and opening avenues for novel combination therapies to enhance outcomes in pancreatic cancer.
分类： 天文学 >> 天文学 提交时间： 2023-02-19
摘要： TianQin is a proposed space-based gravitational-wave detector mission to be deployed and operated in high Earth orbits. As a sequel to [Zhang et al. Phys. Rev. D 103, 062001 (2021)], we investigate a type of ``orbital noise'' in TianQin's range acceleration that is caused by gravitational perturbation associated with solar free oscillations. Frequencies of such oscillations are typically within TianQin's measurement band of 0.1 mHz--1 Hz, and the disturbance level needs careful assessment. By using high-precision orbit propagation and adding the Sun's time-variable oblateness $J_2$ to detailed gravity-field models, we examine the effect in the frequency domain and show that the solar free oscillation noise is expected to be two orders of magnitude lower than the noise requirement on single links and hence has little impact on the mission.
分类： 天文学 >> 天文学 提交时间： 2023-02-19
摘要： The errors of cosmological data generated from complex processes, such as the observational Hubble parameter data (OHD) and the Type Ia supernova (SN Ia) data, cannot be accurately modeled by simple analytical probability distributions, e.g. Gaussian distribution. To constrain cosmological parameters from these data, likelihood-free inference is usually used to bypass the direct calculation of the likelihood. In this paper, we propose a new procedure to perform likelihood-free cosmological inference using two artificial neural networks (ANN), the Masked Autoregressive Flow (MAF) and the denoising autoencoder (DAE). Our procedure is the first to use DAE to extract features from data, in order to simplify the structure of MAF needed to estimate the posterior. Tested on simulated Hubble parameter data with a simple Gaussian likelihood, the procedure shows the capability of extracting features from data and estimating posterior distributions without the need of tractable likelihood. We demonstrate that it can accurately approximate the real posterior, achieve performance comparable to the traditional MCMC method, and the MAF gets better training results for small number of simulation when the DAE is added. We also discuss the application of the proposed procedure to OHD and Pantheon SN Ia data, and use them to constrain cosmological parameters from the non-flat $\Lambda$CDM model. For SNe Ia, we use fitted light curve parameters to find constraints on $H_0,\Omega_m,\Omega_\Lambda$ similar to relevant work, using less empirical distributions. In addition, this work is also the first to use Gaussian process in the procedure of OHD simulation.
分类： 天文学 >> 天文学 提交时间： 2023-02-19
摘要： TianQin is a proposed space-based gravitational-wave detector mission to be deployed and operated in high Earth orbits. As a sequel to [Zhang et al. Phys. Rev. D 103, 062001 (2021)], we investigate a type of ``orbital noise'' in TianQin's range acceleration that is caused by gravitational perturbation associated with solar free oscillations. Frequencies of such oscillations are typically within TianQin's measurement band of 0.1 mHz--1 Hz, and the disturbance level needs careful assessment. By using high-precision orbit propagation and adding the Sun's time-variable oblateness $J_2$ to detailed gravity-field models, we examine the effect in the frequency domain and show that the solar free oscillation noise is expected to be two orders of magnitude lower than the noise requirement on single links and hence has little impact on the mission.
分类： 光学 >> 量子光学 提交时间： 2023-02-19
Yani Zuo
Shiying Cao
Shaoyang Dai
Yige Lin
Tao Yang
Baike Lin
Fei Meng
Weiliang Chen
Kun Liu
Fasong Zheng
Tianchu Li
Fang Fang
摘要： We report the construction and characterization of a narrow-linewidth laser system to interrogate the E2 clock transitions at 436 nm of ytterbium ions trapped in end-cap traps. The 871 nm seed laser at the fundamental frequency is referenced to a 10 cm long notched ULE cavity. The output of the laser system is delivered to a narrow-linewidth femtosecond fiber comb, which has been referenced to an ultrastable 698 nm laser, with a phase noise-canceled fiber link. The beat between the laser and the comb shows a sub-Hz linewidth, and with a stability better than 2E-15@1~100 s. The performance of the self-developed wavelength extension ports at 871 nm of the narrow linewidth erbium-doped fiber comb with single-point frequency-doubling technique is also verified.
分类： 光学 >> 量子光学 提交时间： 2023-02-19
摘要： Terahertz (THz) technology is a cutting-edge scheme with various promising applications, such as next generation telecommunication, non-destructive evaluation, security check, and in-depth characterization, owing to their sensitivity to material geometric change and good transparency. Even though tremendous progresses have been made during the past decade, exploration the mechanisms of THz-matter interaction microscopically is still in its infancy. In this work, we use thermodynamic theory to show how THz illumination deforms materials and use group-IV monochalcogenide compounds to illustrate it. According to our first-principles density functional theory calculations, THz light with intermediate intensity (~109 W/cm2) could yield elastic deformations on the order of ~0.1%, depending on laser polarization direction. Large anisotropic opto-mechanical responses are also revealed. Finally, we show that such strain can be detected via measuring the layer-resolved shift current under a probe light irradiation.
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