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  • Molecular basis of ligand recognition and activation of succinate receptor

    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.

  • Reevaluating GPR30: A Paradigm Shift from Estrogen Receptor to Unique Hydrophilic Ligand Activation

    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.

  • Structural Insights into Ligand Recognition, Selectivity and Activation of the human Bombesin Receptor Subtype-3

    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.

  • Formation and ecological response of sand patches in the protection system of Shapotou section of the Baotou-Lanzhou railway, China

    分类: 地球科学 >> 地理学 提交时间: 2024-02-21 合作期刊: 《干旱区科学》

    摘要: The development of bare patches typically signifies a process of ecosystem degradation. Within the protection system of Shapotou section of the Baotou-Lanzhou railway, the extensive emergence of bare sand patches poses a threat to both stability and sustainability. However, there is limited knowledge regarding the morphology, dynamic changes, and ecological responses associated with these sand patches. Therefore, we analyzed the formation and development process of sand patches within the protection system and its effects on herbaceous vegetation growth and soil nutrients through field observation, survey, and indoor analysis methods. The results showed that sand patch development can be divided into three stages, i.e., formation, expansion, and stabilization, which correspond to the initial, actively developing, and semi-fixed sand patches, respectively. The average dimensions of all sand patch erosional areas were found to be 7.72 m in length, 3.91 m in width, and 0.32 m in depth. The actively developing sand patches were the largest, and the initial sand patches were the smallest. Throughout the stage of formation and expansion, the herbaceous community composition changed, and the plant density decreased by more than 50.95%. Moreover, the coverage and height of herbaceous plants decreased in the erosional area and slightly increased in the depositional lobe; and the fine particles and nutrients of soils in the erosional area and depositional lobe showed a decreasing trend. In the stabilization phases of sand patches, the area from the inlet to the bottom of sand patches becomes initially covered with crusts. Vegetation and 0–2 cm surface soil condition improved in the erosional area, but this improvement was not yet evident in the depositional lobe. Factors such as disturbance, climate change, and surface resistance to erosion exert notable influences on the formation and dynamics of sand patches. The results can provide evidence for the future treatment of sand patches and the management of the protection system of Shapotou section of the Baotou-Lanzhou railway.

  • Development and application of high-precision multifunction astronomical plate digitizers in China

    分类: 天文学 >> 天文仪器与技术 提交时间: 2024-02-07 合作期刊: 《天文技术与仪器(英文)》

    摘要:Before charge-coupled device detectors became widely employed in observational astronomy, for more than a hundred years, the main detection method was photography on astronomical glass plates. Recently, in order to preserve these historical data and maintain their usability, the International Astronomical Union has appealed to all countries for global digitization of astronomical plates by developing or adopting advanced digitization technology. Specialized digitizers with high precision and high measuring speed represent key equipment for this task. The Shanghai Astronomical Observatory and the Nishimura Co., Ltd in Japan cooperated between 2013 and 2016 to develop the first Chinese high-precision astronomical plate digitizer, which was then used for complete digitization of all nighttime-observation astronomical plates in China. Then, in 2019–2021, the Shanghai Astronomical Observatory independently developed new models of plate digitizers that enabled countries such as Uzbekistan and Italy to digitize their astronomical plates. Additionally, a new high-precision and multifunction digitizer was also used to digitize valuable microscope slides from the Shanghai Natural History Museum, providing a successful example of crossdomain application of high-precision digitization technology.

  • High-precision X-ray polarimeter based on channel-cut crystals

    分类: 物理学 >> 核物理学 提交时间: 2024-02-07

    摘要:    We report on using synthetic silicon for a high-precision X-ray polarimeter comprising a polarizer and an analyzer, each based on a monolithic channel-cut crystal used at multiple Brewster reflections with a Bragg angle very close to 45°. Experiments were performed at the BL09B bending magnet beamline of the Shanghai Synchrotron Radiation Facility using a Si(800) crystal at an X-ray energy of 12.914 keV. A polarization purity of 8.4×10-9 was measured. This result is encouraging, as the measured polarization purity is the best-reported value for the bending magnet source. Notably, this is the firstly systematic study on the hard X-ray polarimeter in China, which is crucial for exploring new physics, such as verifying vacuum birefringence.

  • A High-Mass Young Star-forming Core Escaping from Its Parental Filament

    分类: 天文学 >> 天体物理学 提交时间: 2023-12-29

    摘要: We studied the unique kinematic properties in massive filament G352.63-1.07 at 1000-AU spatial scale with the dense molecular tracers observed with the Atacama Large Millimeter/submillimeter Array (ALMA). We find the central massive core M1 (12 Msun) being separated from the surrounding filament with a velocity difference of v-v_sys=-2 km/s and a transverse separation within 3 arcsec. Meanwhile, as shown in multiple dense-gas tracers, M1 has a spatial extension closely aligned with the main filament and is connected to the filament towards its both ends. M1 thus represents a very beginning state for a massive young star-forming core escaping from the parental filament, within a time scale of ~4000 years. Based on its kinetic energy (3.5x10^44 erg), the core escape is unlikely solely due to the original filament motion or magnetic field, but requires more energetic events such as a rapid intense anisotropic collapse. The released energy also seems to noticeably increase the environmental turbulence. This may help the filament to become stabilized again.

  • Atypical radio pulsations from magnetar SGR 1935+2154

    分类: 天文学 >> 天文学 提交时间: 2023-12-29

    摘要: Magnetars are neutron stars with extremely strong magnetic fields, frequently powering high-energy activity in X-rays. Pulsed radio emission following some X-ray outbursts have been detected, albeit its physical origin is unclear. It has long been speculated that the origin of magnetars' radio signals is different from those from canonical pulsars, although convincing evidence is still lacking. Five months after magnetar SGR 1935+2154's X-ray outburst and its associated Fast Radio Burst (FRB) 20200428, a radio pulsar phase was discovered. Here we report the discovery of X-ray spectral hardening associated with the emergence of periodic radio pulsations from SGR 1935+2154 and a detailed analysis of the properties of the radio pulses. The complex radio pulse morphology, which contains both narrow-band emission and frequency drifts, has not been seen before in other magnetars, but is similar to those of repeating FRBs - even though the luminosities are many orders of magnitude different. The observations suggest that radio emission originates from the outer magnetosphere of the magnetar, and the surface heating due to the bombardment of inward-going particles from the radio emission region is responsible for the observed X-ray spectral hardening.

  • Design and commissioning of a wideband RF system for CSNS-II rapid-cycling synchrotron

    分类: 工程与技术科学 >> 工程物理学 分类: 核科学技术 >> 粒子加速器 提交时间: 2023-12-13

    摘要: The China Spallation Neutron Source (CSNS) upgrade project (CSNS-II) aims to enhance the beam power from 100 to 500 kW. A dual-harmonic accelerating method has been adopted to alleviate the stronger space-charge effect in rapid-cycling synchrotrons owing to the increased beam intensity. To satisfy the requirements of dual-harmonic acceleration, a new radiofrequency (RF) system based on a magnetic alloy-loaded cavity is proposed . This paper presents design considerations and experimental results regarding the performance evaluation of the proposed RF system through high-power tests and beam commissioning. The test results demonstrate that the RF system satisfies the desired specifications and affords significant benefits for CSNS-II .


     

  • Latest Developments in EUV Photoresist Evaluation Capability at Shanghai Synchrotron Radiation Facility

    分类: 核科学技术 >> 辐射物理与技术 提交时间: 2023-11-24

    摘要: Evaluating the comprehensive characteristics of extreme ultraviolet (EUV) photoresists is crucial for their application in EUV lithography, a key process in modern technology. This paper highlights the capabilities of the Shanghai Synchrotron Radiation Facility (SSRF) 08U1B beamline in advancing this field. Specifically, it demonstrates how this beamline can create fringe patterns with a 15-nm half-pitch (HP) on a resist using synchrotron-based EUV lithography (EUV-IL). This achievement is vital for evaluating EUV photoresists at the advanced 5-nm node. We provide a detailed introduction to the methods and experimental setup used at the SSRF 08U1B beamline to assess an EUV photoresist. A significant part of this research involved the fabrication of high-resolution hydrogen silsesquioxane (HSQ) mask gratings. These gratings, with an aspect ratio of approximately 3, were created using electron beam lithography (EBL) on an innovative mask framework. This framework was crucial in eliminating the impact of zeroth-order light on interference patterns. The proposed framework offers a new approach to mask fabrication, particularly beneficial for achromatic Talbot lithography and multicoherent-beam interference applications.

  • A multithreaded parallel upwind sweep algorithm for the SN transport equations discretized with discontinuous finite elements

    分类: 物理学 >> 核物理学 提交时间: 2023-11-22

  • The bio safety level-2 macromolecular crystallography beamline (BL10U2) at the Shanghai Synchrotron Radiation Facility

    分类: 物理学 >> 核物理学 提交时间: 2023-11-22

    摘要: BL10U2 is an undulator-based macromolecular crystallography (MX) beamline located at the 3.5-GeV Shanghai Synchrotron Radiation Facility. BL10U2 is specifically designed for conducting routine and bio safety level-2 (BSL-2) MX experiments utilizing high-flux tunable X-rays with energies from 7 to 18 keV, providing a beam spot size of 20 µm (horizontal) × 10 µm (vertical) at the sample point. Certification by the Shanghai Pudong Municipal Health Commission confirmed the capability to perform BSL-2 MX experiments. The beamline is currently equipped with an Eiger X 16M detector and two newly developed in-house high-precision diffractometers that can be switched to perform conventional or in situ crystal diffraction experiments. An automatic sample changer developed in-house allows fast sample exchange in less than 30s, supporting high-throughput MX experimentation and rapid crystal screening. Data collection from both the diffractometer and detector was controlled by an in-house developed data collection software (Finback) with a user-friendly interface for convenient operation. This study presents a comprehensive overview of the facilities, experimental methods, and performance characteristics of the BL10U2 beamline.

  • Environmental significance and hydrochemical characteristics of rivers in the western region of the Altay Mountains, China

    分类: 地球科学 >> 地理学 提交时间: 2023-10-17 合作期刊: 《干旱区科学》

    摘要: Analysis of environmental significance and hydrochemical characteristics of river water in mountainous regions is vital for ensuring water security. In this study, we collected a total of 164 water samples in the western region of the Altay Mountains, China, in 2021. We used principal component analysis and enrichment factor analysis to examine the chemical properties and spatiotemporal variations of major ions (including F–, Cl–, NO3–, SO42–, Li+, Na+, NH4+, K+, Mg2+, and Ca2+) present in river water, as well as to identify the factors influencing these variations. Additionally, we assessed the suitability of river water for drinking and irrigation purposes based on the total dissolved solids, soluble sodium percentage, sodium adsorption ratio, and total hardness. Results revealed that river water had an alkaline aquatic environment with a mean pH value of 8.00. The mean ion concentration was ranked as follows: Ca2+>SO42–>Na+>NO3–>Mg2+>K+>Cl–>F–>NH4+>Li+. Ca2+, SO42–, Na+, and NO3– occupied 83% of the total ion concentration. In addition, compared with other seasons, the spatial variation of the ion concentration in spring was obvious. An analysis of the sources of major ions revealed that these ions originated mainly from carbonate dissolution and silicate weathering. The recharge impact of precipitation and snowmelt merely influenced the concentration of Cl–, NO3–, SO42–, Ca2+, and Na+. Overall, river water was in pristine condition in terms of quality and was suitable for both irrigation and drinking. This study provides a scientific basis for sustainable management of water quality in rivers of the Altay Mountains.
     

  • Automatic Spectrum Recognition System for Charge State Analysis in Electron Cyclotron Resonance Ion Sources

    分类: 物理学 >> 核物理学 提交时间: 2023-10-13

    摘要: The Electron Cyclotron Resonance (ECR) ion source is a critical device for producing highly charged ion beams in various applications. Analyzing the charge-state distribution of the ion beams is essential, but the manual analysis is labor-intensive and prone to inaccuracies due to impurity ions. An automatic spectrum recognition system based on intelligent algorithms was proposed for rapid and accurate chargestate analysis of ECR ion sources. The system employs an adaptive window-length Savitzky-Golay (SG) filtering algorithm, an improved automatic multiscale peak detection (AMPD) algorithm, and a greedy matching algorithm based on the relative distance to accurately match different peaks in the spectra with the corresponding charge-state ion species. Additionally, a user-friendly operator interface was developed for ease of use. Extensive testing on the online ECR ion source platform demonstrates that the system achieves high accuracy, with an average root mean square error of less than 0.1 A for identifying charge-state spectra of ECR ion sources. Moreover, the system minimizes the standard deviation of the first-order derivative of the smoothed signal to 81.1846 A. These results indicate the capability of the designed system to identify ion beam spectra with mass numbers less than Xe, including Xe itself. The proposed automatic spectrum recognition system represents a significant advancement in ECR ion source analysis, offering a rapid and accurate approach for charge-state analysis while enhancing supply efficiency. The exceptional performance and successful implementation of the proposed system on multiple ECR ion source platforms at IMPCAS highlight its potential for widespread adoption in ECR ion source research and applications.
     

  • ID effects on beam dynamics in the SSRF-U storage ring

    分类: 物理学 >> 核物理学 提交时间: 2023-10-12

    摘要: This paper introduces the proposed Insertion Device (ID) scheme for the Shanghai Synchrotron Radiation Facility Upgrade (SSRF-U). Based on this scheme, the influences of the ID radiation on the Intra-Beam Scattering (IBS) emittance and energy spread were evaluated. Optical distortion caused by the IDs was comprehensively examined and compensated using both local and global corrections. Subsequently, a Frequency Map Analysis (FMA) method was used to identify potentially dangerous resonance lines. In addition, the dynamic aperture, energy acceptance, and Touschek lifetime were calculated after considering high-order magnetic field errors to ensure that the ID effect did not affect the operation of the storage ring.

     

  • Towards real-time digital pulse process algorithms for CsI(Tl) detector array at External Target Facility in HIRFL-CSR

    分类: 核科学技术 >> 核探测技术与核电子学 提交时间: 2023-09-14

    摘要: A fully digital data acquisition system based on a field-programmable gate array (FPGA) was developed for a CsI(Tl) array at the External Target Facility (ETF)in the Heavy Ion Research Facility in Lanzhou(HIRFL). To process the CsI(Tl) signals generated by γ-rays and light-charged ions, a scheme for digital pulse processing algorithms is proposed. Every step in the algorithms was benchmarked using standard γ and α sources. The scheme, which included a moving average filter, baseline restoration, leading-edge discrimination, moving window deconvolution and digital charge comparison was subsequently implemented on the FPGA. A good energy resolution of 5.7% for 1.33 MeV γ rays and excellent α-γ identification using the digital charge comparison method were achieved, which satisfies CsI(Tl) array performance requirements.
     

  • Comparison between 4D Robust Optimization Methods for Carbon-Ion Treatment Planning

    分类: 核科学技术 >> 核科学与技术 提交时间: 2023-08-27

    摘要: Intensity-modulated particle therapy (IMPT) with carbon ions is comparatively susceptible to various uncertainties caused by breathing motion, including range, setup, and target positioning uncertainties. To determine relative biological effectiveness-weighted dose (RWD) distributions that are resilient to these uncertainties, the reference phase-based four-dimensional (4D) robust optimization (RP-4DRO) and each phase-based 4D robust optimization (EP-4DRO) method in carbon-ion IMPT treatment planning were evaluated and compared. Based on RWD distributions, 4DRO methods were compared with 4D conventional optimization using planning target volume (PTV) margins (PTV-based optimization) to assess the effectiveness of the robust optimization methods. Carbon-ion IMPT treatment planning was conducted in a cohort of five lung cancer patients. The results indicated that the EP-4DRO method provided better robustness (P=0.080) and improved plan quality (P=0.225) for the clinical target volume (CTV) in the individual respiratory phase when compared with the PTV-based optimization. Compared with the PTV-based optimization, the RP-4DRO method ensured the robustness (P = 0.022) of the dose distributions in the reference breathing phase, albeit with a slight sacrifice of the target coverage (P=0.450). Both 4DRO methods successfully maintained the doses delivered to the organs at risk (OARs) below tolerable levels, which were lower than the doses in the PTV-based optimization (P<0.05). Furthermore, the RP-4DRO method exhibited significantly superior performance when compared with the EP-4DRO method in enhancing overall OAR sparing in either the individual respiratory phase or reference respiratory phase (P<0.05). In general, both 4DRO methods outperformed the PTV-based optimization in terms of OAR sparing and robustness.

  • Design of a rapid-cycling synchrotron for flash proton therapy

    分类: 核科学技术 >> 粒子加速器 提交时间: 2023-08-21

    摘要: The purpose of this study was to design a rapid cycling synchrotron, making it capable of proton beam ultra-high dose rate irradiation, inspired by laser accelerators. The design had to be cheap and simple. We consider our design from six aspects: the lattice, injection, extraction, space charge effects, eddy current effects and energy switching. Efficiency and particle quantity must be addressed when injected. The space charge effects at the injection could affect particles’ number. The eddy current effects in the vacuum chambers would affect the magnetic field itself and generate heat, all of which need to be taken into account. Fast extraction can obtain 1010 protons/pulse, equal to instantaneous dose rate up to 107 Gy/s in a very short time, while changing various extraction energies rapidly and easily to various deposition depths. In the further research we expect to combine a delivery system with this accelerator to realize the FLASH irradiation.

  • Long-term light grazing does not change soil organic carbon stability and stock in biocrust layer in the hilly regions of drylands

    分类: 生物学 >> 生态学 提交时间: 2023-08-15 合作期刊: 《干旱区科学》

    摘要: Livestock grazing is the most extensive land use in global drylands and one of the most extensive stressors of biological soil crusts (biocrusts). Despite widespread concern about the importance of biocrusts for global carbon (C) cycling, little is known about whether and how long-term grazing alters soil organic carbon (SOC) stability and stock in the biocrust layer. To assess the responses of SOC stability and stock in the biocrust layer to grazing, from June to September 2020, we carried out a large scale field survey in the restored grasslands under long-term grazing with different grazing intensities (represented by the number of goat dung per square meter) and in the grasslands strictly excluded from grazing in four regions (Dingbian County, Shenmu City, Guyuan City and Ansai District) along precipitation gradient in the hilly Loess Plateau, China. In total, 51 representative grassland sites were identified as the study sampling sites in this study, including 11 sites in Guyuan City, 16 sites in Dingbian County, 15 sites in Shenmu City and 9 sites in Ansai District. Combined with extensive laboratory analysis and statistical analysis, at each sampling site, we obtained data on biocrust attributes (cover, community structure, biomass and thickness), soil physical-chemical properties (soil porosity and soil carbon-to-nitrogen ratio (C/N ratio)), and environmental factors (mean annual precipitation, mean annual temperature, altitude, plant cover, litter cover, soil particle-size distribution (the ratio of soil clay and silt content to sand content)), SOC stability index (SI) and SOC stock (SOCS) in the biocrust layer, to conduct this study. Our results revealed that grazing did not change total biocrust cover but markedly altered biocrust community structure by reducing plant cover, with a considerable increase in the relative cover of cyanobacteria (23.1%) while a decrease in the relative cover of mosses (42.2%). Soil porosity and soil C/N ratio in the biocrust layer under grazing decreased significantly by 4.1%–7.2% and 7.2%–13.3%, respectively, compared with those under grazing exclusion. The shifted biocrust community structure ultimately resulted in an average reduction of 15.5% in SOCS in the biocrust layer under grazing. However, compared with higher grazing (intensity of more than 10.00 goat dung/m2), light grazing (intensity of 0.00–10.00 goat dung/m2 or approximately 1.20–2.60 goat/(hm2•a)) had no adverse effect on SOCS. SOC stability in the biocrust layer remained unchanged under long-term grazing due to the offset between the positive effect of the decreased soil porosity and the negative effect of the decreased soil C/N ratio on the SOC resistance to decomposition. Mean annual precipitation and soil particle-size distribution also regulated SOC stability indirectly by influencing soil porosity through plant cover and biocrust community structure. These findings suggest that proper grazing might not increase the CO2 release potential or adversely affect SOCS in the biocrust layer. This research provides some guidance for proper grazing management in the sustainable utilization of grassland resources and C sequestration in biocrusts in the hilly regions of drylands.
     

  • Deep learning for estimation of Kirkpatrick–Baez mirror alignment errors

    分类: 物理学 >> 核物理学 提交时间: 2023-07-09

    摘要: A deep learning-based automated Kirkpatrick–Baez mirror alignment method is proposed for synchrotron radiation. We trained a convolutional neural network (CNN) on simulated and experimental imaging data of a focusing system. Instead of learning directly from bypass images, we use a scatterer for X-ray modulation and speckle generation for image feature enhancement. The smallest normalized root mean square error on the validation set was 4%. Compared with conventional alignment methods based on motor scanning and analyzer setups, the present method simplified the optical layout and estimated alignment errors using a single-exposure experiment. Single-shot misalignment error estimation only took 0.13 s, significantly outperforming conventional methods. We also demonstrated the effects of the beam quality and pretraining using experimental data. The proposed method exhibited strong robustness, can handle high-precision focusing systems with complex or dynamic wavefront errors, and provides an important basis for intelligent control of future synchrotron radiation beamlines.