分类: 核科学技术 >> 核科学与技术 提交时间: 2023-12-10
摘要: X-ray photon correlation spectroscopy (XPCS) has emerged as a powerful tool for probing nanoscale dynamics of soft condensed matter and strongly correlated materials, offering high spatial resolution and high penetration capability. This technique requires high brilliance and beam coherence, which are not directly available at modern synchrotron beamlines in China. To pave the way for future XPCS experiments, we first modified the optical setup of the newly commissioned BL10U1 USAXS beamline at the Shanghai Synchrotron Radiation Facility (SSRF). Subsequently, we carried out XPCS measurements on silica suspensions of glycerol, which were opaque in appearance due to high concentrations. Image series were collected by a high frame-rate area detector. Comprehensive analysis was carried out, yielding the correlation functions and several key dynamic parameters. All results agree well with the theory of Brownian motion, demonstrating the feasibility of XPCS at SSRF. Eventually, by carefully optimizing the setup and analyzing algorithms, we achieved a time resolution of 2 ms, enabling characterization of millisecond dynamics in opaque systems.
分类: 核科学技术 >> 核科学技术其他学科 提交时间: 2024-05-08
摘要: In this study, to efficiently remove Pb(II) from aqueous environments, a novel L-serine-modified polyethylene/polypropylene nonwoven fabric sorbent (NWF-serine) was fabricated through the radiation grafting of glycidyl methacrylate and subsequent L-serine modification. The effect of the absorbed dose was investigated in the range of 5–50 kGy. NWF-serine was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. Batch adsorption tests were conducted to investigate the influences of pH, adsorption time, temperature, initial concentration, and sorbent dosage on the Pb(II) adsorption performance of NWF-serine. The results indicated that Pb(II) adsorption onto NWF-serine was an endothermic process, following the pseudo-second-order kinetic model and Langmuir isotherm model. The saturated adsorption capacity was 198.1 mg/g. NWF-serine exhibited Pb(II) removal rates of 99.8% for aqueous solutions with initial concentrations of 100 mg/L and 82.1% for landfill leachate containing competitive metal ions such as Cd, Cu, Ni, Mn, and Zn. Furthermore, NWF-serine maintained 86% of its Pb(II) uptake after five use cycles. The coordination of the carboxyl and amino groups with Pb(II) was confirmed using X-ray photoelectron spectroscopy and extended X-ray absorption fine structure analysis.
分类: 物理学 >> 核物理学 提交时间: 2024-11-19
摘要: This study investigates photonuclear reaction (\gamma,n) cross-sections using Bayesian neural network (BNN) analysis. After determining the optimal network architecture, which features two hidden layers, each with 50 hidden nodes, training was conducted for 30,000 iterations to ensure comprehensive data capture. By analyzing the distribution of absolute errors positively correlated with the cross-section for the isotope ^{159}Tb, as well as the relative errors unrelated to the cross-section, we confirmed that the network effectively captured the data features without overfitting. Comparison with the TENDL-2021 Database demonstrated the BNN’s reliability in fitting photonuclear cross-sections with lower average errors. The predictions for nuclei with single and double giant dipole resonance peak cross-sections, the accurate determination of the photoneutron reaction threshold in the low-energy region, and the precise description of trends in the high-energy cross-sections further demonstrate the network’s generalization ability on the validation set. This can be attributed to the consistency of the training data. By using consistent training sets from different laboratories, Bayesian neural networks can predict nearby unknown cross-sections based on existing laboratory data, thereby estimating the potential differences between other laboratories’ existing data and their own measurement results. Experimental measurements of photonuclear reactions on the newly constructed SLEGS beamline will contribute to clarifying the differences in cross-sections within the existing data.
分类: 物理学 >> 核物理学 提交时间: 2022-06-13
摘要: Shanghai Laser Electron Gamma Source (SLEGS) is a powerful gamma source to provide MeV gamma-ray beams for nuclear science and technology. It is developed as one of the sixteenbeamline stations in Phase II Project of the Shanghai Synchrotron Radiation Facility (SSRF). Theslant-scattering mode is for the first time systematically employed in the laser Compton scattering (LCS) at SLEGS to produce energy-tunable quasi-monoenergetic gamma-ray beams. SLEGS officially completed its commissioning from July to December 2021. Gamma-rays in energy range of 0.25 - 21.7 MeV with the flux of 2.1 104 - 1.2 107 photons/s and the energy spread of 2 15 % are produced during the test. This paper reports results of the commissioning of the SLEGS beamline.
分类: 药物科学 >> 结构生物学 提交时间: 2024-04-27
摘要: The norepinephrine transporter (NET) plays a pivotal role in regulating neurotransmitter balance and is critical for normal physiology and neurobiology. Dysfunction of NET has been implicated in numerous neuropsychiatric diseases including depression, anxiety, attention deficit hyperactivity disorder, and Parkinson’s disease. Here we report cryo-EM structures of NET in apo and substrate-bound forms, as well as complexes with six antidepressants. The structures reveal an unexpected NET dimer interface predominantly mediated by cholesterol and lipid molecules. The substrate norepinephrine is found to bind deep within the central binding pocket, with its amine group interacting with a conserved aspartate. The structures also provide insight into antidepressant recognition, including how subtle differences in binding poses confer selectivity over other monoamine transporters. Together these breakthrough findings significantly advance our understanding of NET regulation and inhibition, providing templates for designing improved antidepressants to treat neuropsychiatric disorders.
分类: 核科学技术 >> 辐射物理与技术 提交时间: 2025-04-07
摘要: A Monte Carlo simulation code and an analytical calculation code for polarization study were developed at Shanghai Laser Gamma Source (SLEGS), employing the unique laser Compton slant scattering (LCSS) mode. The intensity of spatial distributions and its Stokes parameters are simulated for LCSS of linearly/circularly polarized laser photons and unpolarized relativistic electrons. The polarization degree of the incident photon is almost completely transferred to the scattered gamma rays for any incident angle. For a linearly polarized laser incident in a fixed direction, the direction of polarization of the scattered gamma-ray changes with the scattering angle. The measured polarization direction and size of the scattered gamma spatial distribution are in general agreement with the simulation in the linearly polarized laser case.
分类: 药物科学 >> 结构生物学 提交时间: 2024-02-29
摘要: Succinic acid, a tricarboxylic acid (TCA) cycle intermediate, significantly influences mitochondrial reactive oxygen species homeostasis through the G protein-coupled succinate receptor (SUCR1, also called GPR91), linking it to various physiological and pathological processes. Despite SUCR1’s pivotal role in mediating effects leading to liver fibrosis, hypertension, angiogenesis, inflammation, and offering a therapeutic target for multiple diseases, its activation mechanism by diverse ligands and interaction with downwards G protein remains poorly understood. This study presents the cryo-electron microscopy (cryo-EM) structures of SUCR1 in complex with inhibitory G protein (Gi) bound to succinic acid, maleic acid, and compound 31, a high-affinity agonist. These structures elucidate the distinct ligand binding modes, uncover the activation signal cascade, and detail the G protein coupling mechanism of SUCR1. Our findings provide a comprehensive structural basis for SUCR1 activation, paving the way for structure-based drug design aimed at SUCR1-related pathologies.
分类: 物理学 >> 核物理学 提交时间: 2023-07-06
摘要: Proton computed tomography (CT) has a distinct practical significance in clinical applications. It eliminates 35% errors caused by the transformation of Hounsfield unit (HU) to relative stopping power (RSP) valueswhen using X-ray CT for positioning andtreatment planning systems (TPSs). Following the development of FLASH proton therapy, there are increased requirements for accurate and rapid positioning in TPSs. Thus, anewrapid proton CT imaging mode is proposed based on sparsely sampled projections. The proton beam wasboosted to 350 MeV by a compact proton linear accelerator (linac). In this study,thecomparisons of the proton scattering with the energyof 350 MeV and 230 MeV are conducted based on GEANT4simulations.Asthe sparsely sampledinformation associated with beam acquisitions at 12angles is not enough for reconstruction, X-ray CT is used as a prior image. The RSP map generated by converting the X-ray CT was constructed based onMonte Carlo simulations. Consideringtheestimationof the most likely path (MLP), the prior image-constrained compressed sensing (PICCS) algorithm isused to reconstruct images from twodifferent phantoms using sparse protonprojections of 350 MeV parallel proton beam. The results show that it is feasible to realize the proton image reconstruction with the rapid protonCT imaging proposed in this paper. It can produce RSP maps withmuchhigher accuracy for TPSs and fast positioning to achieve ultra-fast imaging for real-time image-guided radiotherapy(IGRT) in clinical proton therapyapplications.
分类: 药物科学 >> 结构生物学 提交时间: 2024-02-21
摘要: Bombesin receptor subtype-3 (BRS3) is an important orphan G protein-coupled receptor that regulates energy homeostasis and insulin secretion. As a member of the bombesin receptor (BnR) family, which includes neuromedin B receptor (NMBR) and gastrin-releasing peptide receptor (GRPR), the lack of known endogenous ligands and high-resolution structure has impeded understanding of BRS3 signaling and function. Here, we present cryogenic electron microscopy (cryo-EM) structures of BRS3 in complex with heterotrimeric Gq protein in three states: apo, bound to the pan-BnR agonist, BA1, and bound to the synthetic BRS3-specific agonist MK-5046. These structures reveal the architecture of the orthosteric ligand pocket underpinning molecular recognition. Comparisons with BnR members provide insights into the structural basis for BRS3’s selectivity and low affinity for bombesin peptides. Examination of conserved micro-switches suggests a shared activation mechanism among BnRs. Together our results enable deeper exploration of BRS3’s ligand selectivity, signaling, and therapeutic targeting for diabetes and obesity.
分类: 药物科学 >> 生物化学 提交时间: 2024-06-14
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 >> 结构生物学 提交时间: 2024-02-24
摘要: The orphan receptor GPR30, previously classified as a G protein-coupled estrogen receptor (GPER), has been a subject of debate regarding its ligand specificity. Through an integrative approach combining structure elucidation, biochemical binding, and cell signaling assays, we demonstrate that estrogen does not directly bind to or activate GPR30. Cryo-EM structures of GPR30 reveal an unexpected hydrophilic ligand-binding pocket, with striking differences from classical hydrophobic steroid-binding sites, inconsistent with estrogen binding. We further confirmed hydrophilic agonists like Lys05 as true activators of GPR30, providing structural insights into their binding mechanism and receptor activation. Our findings necessitate a paradigm shift in defining GPR30’s role in estrogen signaling, indicating that its activation occurs through mechanisms independent of estrogen binding. This study opens new avenues for developing targeted GPR30 ligands and reinterpreting its role in estrogen-mediated processes.