Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.

Inhibition of calcitonin gene-related peptide (CGRP) or its cognate CGRP receptor (CGRPR) has arisen as a major breakthrough in the treatment of migraine. However, a second CGRP-responsive receptor exists, the amylin (Amy) 1 receptor (AMY1R), yet its involvement in the pathology of migraine is poorly understood. AMY1R and CGRPR are heterodimers consisting of receptor activity-modifying protein 1 (RAMP1) with the calcitonin receptor (CTR) and the calcitonin receptor-like receptor (CLR), respectively. Here, we present the structure of AMY1R in complex with CGRP and Gs protein and compare it with the reported structures of the AMY1R complex with rat amylin (rAmy) and the CGRPR in complex with CGRP. Despite similar protein backbones observed within the receptors and the N- and C-termini of the two peptides bound to the AMY1R complexes, they have distinct organization in the peptide midregions (the bypass motif) that is correlated with differences in the dynamics of the respective receptor extracellular domains. Moreover, divergent conformations of extracellular loop (ECL) 3, intracellular loop (ICL) 2, and ICL3 within the CTR and CLR protomers are evident when comparing the CGRP bound to the CGRPR and AMY1R, which influences the binding mode of CGRP. However, the conserved interactions made by the C-terminus of CGRP to the CGRPR and AMY1R are likely to account for cross-reactivity of nonpeptide CGRPR antagonists observed at AMY1R, which also extends to other clinically used CGRPR blockers, including antibodies.

Highly Sensitive Gas Sensor for Detection of Air Decomposition Pollutant (CO, NOx): Popular Metal Oxide (ZnO, TiO2)-Doped MoS2 Surface.

When partial discharges occur in air-insulated equipment, the air decomposes to produce a variety of contamination products, resulting in a reduction in the insulation performance of the insulated equipment. By monitoring the concentration of typical decomposition products (CO, NO, and NO2) within the insulated equipment, potential insulation faults can be diagnosed. MoS2 has shown promising applications as a gas-sensitive semiconductor material, and doping metal oxides can improve the gas-sensitive properties of the material. Therefore, in this work, MoS2 has been doped using the popular metal oxides (ZnO, TiO2) of the day, and its gas-sensitive properties to the typical decomposition products of air have been analyzed and compared using density functional theory (DFT) calculations. The stability of the doped system was investigated using molecular dynamics methods. The related adsorption mechanism was analyzed by adsorption configuration, energy band structure, density of states (DOS) analysis, total electron density (TED) analysis, and differential charge density (DCD) analysis. Finally, the practical application of related sensing performance is evaluated. The results show that the doping of metal oxide nanoparticles greatly improves the conductivity, gas sensitivity, and adsorption selectivity of MoS2 monolayer to air decomposition products. The sensing response of ZnO-MoS2 for CO at room temperature (25 °C) reaches 161.86 with a good recovery time (0.046 s). TiO2-MoS2 sensing response to NO2 reaches 3.5 × 106 at 25 °C with a good recovery time (0.108 s). This study theoretically solves the industrial challenge of recycling sensing materials and provides theoretical value for the application of resistive chemical sensors in air-insulated equipment.

Structural insight into selectivity of amylin and calcitonin receptor agonists.

Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.

Grazing practices affect soil microbial networks but not diversity and composition in alpine meadows of northeastern Qinghai-Tibetan plateau.

Livestock grazing is the primary practice in alpine meadows and can alter soil microbiomes, which is critical for ecosystem functions and services. Seasonal grazing (SG) and continuous grazing (CG) are two kinds of different grazing practices that dominate alpine meadows on the Qinghai-Tibetan Plateau (QTP), and how they affect soil microbial communities remains in-depth exploration. The present study was conducted to investigate the effects of different grazing practices (i.e., SG and CG) on the diversity, composition, and co-occurrence networks of soil bacteria and fungi in QTP alpine meadows. Soil microbial α- and ß-diversity showed no obvious difference between SG and CG grasslands. Grazing practices had little impact on soil microbial composition, except that the relative abundance of Proteobacteria and Ascomycota showed significant difference between SG and CG grasslands. Soil microbial networks were more complex and less stable in SG grasslands than that in CG grasslands, and the bacterial networks were more complex than fungal networks. Soil fungal diversity was more strongly correlated with environmental factors than bacteria, whereas both fungal and bacterial structures were mainly influenced by soil pH, total nitrogen, and ammonium nitrogen. These findings indicate that microbial associations are more sensitive to grazing practices than microbial diversity and composition, and that SG may be a better grazing practice for ecological benefits in alpine meadows.

Quantifying changes in soil organic carbon density from 1982 to 2020 in Chinese grasslands using a random forest model.

China has the second-largest grassland area in the world. Soil organic carbon storage (SOCS) in grasslands plays a critical role in maintaining carbon balance and mitigating climate change, both nationally and globally. Soil organic carbon density (SOCD) is an important indicator of SOCS. Exploring the spatiotemporal dynamics of SOCD enables policymakers to develop strategies to reduce carbon emissions, thus meeting the goals of "emission peak" in 2030 and "carbon neutrality" in 2060 proposed by the Chinese government. The objective of this study was to quantify the dynamics of SOCD (0-100 cm) in Chinese grasslands from 1982 to 2020 and identify the dominant drivers of SOCD change using a random forest model. The results showed that the mean SOCD in Chinese grasslands was 7.791 kg C m-2 in 1982 and 8.525 kg C m-2 in 2020, with a net increase of 0.734 kg C m-2 across China. The areas with increased SOCD were mainly distributed in the southern (0.411 kg C m-2), northwestern (1.439 kg C m-2), and Qinghai-Tibetan (0.915 kg C m-2) regions, while those with decreased SOCD were mainly found in the northern (0.172 kg C m-2) region. Temperature, normalized difference vegetation index, elevation, and wind speed were the dominant factors driving grassland SOCD change, explaining 73.23% of total variation in SOCD. During the study period, grassland SOCS increased in the northwestern region but decreased in the other three regions. Overall, SOCS of Chinese grasslands in 2020 was 22.623 Pg, with a net decrease of 1.158 Pg since 1982. Over the past few decades, the reduction in SOCS caused by grassland degradation may have contributed to soil organic carbon loss and created a negative impact on climate. The results highlight the urgency of strengthening soil carbon management in these grasslands and improving SOCS towards a positive climate impact.

A small fishing vessel recognition method using transfer learning based on laser sensors.

The management of small vessels has always been key to maritime administration. This paper presents a novel method for recognizing small fishing vessels based on laser sensors. Using four types of small fishing vessels as targets, a recognition method for small fishing vessels based on Markov transition field (MTF) time-series images and VGG-16 transfer learning is proposed. In contrast to conventional methods, this study uses polynomial fitting to obtain the contours of a fishing vessel and transforms one-dimensional vessel contours into two-dimensional time-series images using the MTF coding method. The VGG-16 model is used for the recognition process, and migration learning is applied to improve the results. The UCR time-series public dataset is used as a transfer learning dataset for the MTF time-series image encoding. The experiment demonstrates that the proposed method exhibits higher accuracy and performance than 1D-CNN and other general neural network models, and the highest accuracy rate is 98.92%.

Wavefront shaping with nonlinear four-wave mixing.

Wavefront manipulations have enabled wide applications across many interdisciplinary fields ranging from optics and microwaves to acoustics. However, the realizations of such functional surfaces heavily rely on micro/nanofabrication to define the structured surfaces, which are fixed and only work within a limited spectrum. To address these issues, previous attempts combining tunable materials like liquid crystal or phase-change ones onto the metasurfaces have permitted extra tunability and working spectra, however, these additional layers bring in inevitable loss and complicate the fabrication. Here we demonstrate a fabrication-free tunable flat slab using a nonlinear four-wave mixing process. By wavefront-shaping the pump onto the flat slab, we can successfully tune the effective nonlinear refraction angle of the emitting FWM beams according to the phase-matching condition. In this manner, a focusing and a defocusing nonlinear of FWM beam through the flat slab have been demonstrated with a converging and a diverging pump wavefronts, respectively. Furthermore, a beam steering scheme over a 20° angle has been realized through a non-degenerate four-wave mixing process by introducing a second pump. These features open up a door to manipulating light propagation in an all-optical manner, paving the way to more functional and tunable flat slab devices in the applications of imaging and all-optical information.

New Insights into the Structure and Function of Class B1 GPCRs.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors. Class B1 GPCRs constitute a subfamily of 15 receptors that characteristically contain large extracellular domains (ECDs) and respond to long polypeptide hormones. Class B1 GPCRs are critical regulators of homeostasis, and, as such, many are important drug targets. While most transmembrane proteins, including GPCRs, are recalcitrant to crystallization, recent advances in cryo-electron microscopy (cryo-EM) have facilitated a rapid expansion of the structural understanding of membrane proteins. As a testament to this success, structures for all the class B1 receptors bound to G proteins have been determined by cryo-EM in the past 5 years. Further advances in cryo-EM have uncovered dynamics of these receptors, ligands, and signaling partners. Here, we examine the recent structural underpinnings of the class B1 GPCRs with an emphasis on structure-function relationships.

Response of leaf stoichiometry of Potentilla anserina to elevation in China's Qilian Mountains.

Plants adapt to changes in elevation by regulating their leaf ecological stoichiometry. Potentilla anserina L. that grows rapidly under poor or even bare soil conditions has become an important ground cover plant for ecological restoration. However, its leaf ecological stoichiometry has been given little attention, resulting in an insufficient understanding of its environmental adaptability and growth strategies. The objective of this study was to compare the leaf stoichiometry of P. anserina at different elevations (2,400, 2,600, 2,800, 3,000, 3,200, 3,500, and 3,800 m) in the middle eastern part of Qilian Mountains. With an increase in elevation, leaf carbon concentration [(C)leaf] significantly decreased, with the maximum value of 446.04 g·kg-1 (2,400 m) and the minimum value of 396.78 g·kg-1 (3,500 m). Leaf nitrogen concentration [(N)leaf] also increased with an increase in elevation, and its maximum and minimum values were 37.57 g·kg-1 (3,500 m) and 23.71 g·kg-1 (2,800 m), respectively. Leaf phosphorus concentration [(P)leaf] was the highest (2.79 g·kg-1) at 2,400 m and the lowest (0.91 g·kg-1) at 2,800 m. The [C]leaf/[N]leaf decreased with an increase in elevation, while [N]leaf/[P]leaf showed an opposite trend. The mean annual temperature, mean annual precipitation, soil pH, organic carbon, nitrogen, and phosphorus at different elevations mainly affected [C]leaf, [N]leaf, and [P]leaf. The growth of P. anserina in the study area was mainly limited by P, and this limitation was stronger with increased elevation. Progressively reducing P loss at high elevation is of great significance to the survival of P. anserina in this specific region.

Formation of Cr-based layered double hydroxide: effect of the amendments.

Chromium is one of the eight most popular inorganic soil pollutants in China, and its bioavailability is determined by the chemical states. Amendments, which are able to change the chemical forms of chromium and decrease its bioavailability, have received considerable attention in recent years. In this work, the formation of Cr-based layered double hydroxides (LDHs) and the immobilization of Cr in solution and soil were systemically investigated. The formation of Cr-based LDHs is strongly depended on the layer charges, aging temperatures and reaction time, as identified by X-ray diffraction (XRD), transmission electron microscope (TEM) and X-ray absorption fine structure (XAFS) spectrum. According to the pot experiment results, the concentration of Cr in the overground part of Brassica Chinensis L. was significantly decreased to 1.50-2.03 µg kg- 1 in the present of amendments. In total, the finding of LDHs formation on amendments and the thermodynamic stability of LDHs provides a new insight into the remediation of Cr-polluted soils.

The effects of grazer exclosure duration on soil microbial communities on the Qinghai-Tibetan Plateau.

While determining the response of soil microbes to grazer exclosure duration is critical to understanding ecosystem restoration processes, few studies have focused on this issue. With seasonal grazing as a control, microbes of alpine grassland soils under 5, 13, 22, and 39 years of grazer exclosure situated in the eastern part of the Qinghai-Tibetan Plateau, were examined. Microbial diversity was determined through Illumina high-throughput sequencing of the 16S rRNA gene and an internal transcription spacer (ITS). We found that soil bacterial α-diversity showed insignificant differences between seasonal grazing and grazer exclosure and among the grazer exclosures of different durations, while fungal α-diversity under the 5-year grazer exclosure was significantly different from those under the other treatments. Soil microbial community profiles under the 13-, 22-, and 39-year grazer exclosures were significantly different compared to those under the seasonal grazing or 5-year grazer exclosure. Briefly, longer exclosure durations led to a higher relative abundance of multiple copiotrophic microbial lineages (e.g., ß-Proteobacteria, Rhizobiales, and Frankiales), whereas several oligotrophic microbial lineages (e.g., Chloroflexi, Leotiomycetes, and Xylariales) gradually and significantly decreased. Functional predictions suggest that as grazer exclosure duration was extended, the relative abundance of nitrogen fixers increased, while the proportions of plant pathogenic fungi decreased. This indicates that long-term grazer exclosure duration may contribute to enhanced soil nitrogen fixation and grassland health by maintaining plant growth and decreasing the risk of plant disease. However, this may have a resource cost as plant productivity and soil organic carbon both decreased with the extension of grazer exclosure duration. Therefore, the agroecology effect of grazer exclosure duration on the diversity and abundance of soil nitrogen fixing bacteria and plant pathogen fungi, should be given more attention in the cold and humid portion of the Qinghai-Tibetan Plateau.

Analyzing the Effect of Badminton on Physical Health and Emotion Recognition on the account of Smart Sensors.

Emotional ability is an important symbol of human intelligence. Human's understanding of emotions, from subjective consciousness to continuous or discrete emotional dimensions, and then to physiological separability, has shown a trend of gradually diverging from psychological research to the field of intelligent human-computer interaction. This article is aimed at studying the effects of smart sensor-based emotion recognition technology and badminton on physical health. It proposes a method of using smart sensor technology to recognize badminton movements and emotions during the movement. And the impact of emotion recognition based on smart sensors and badminton sports on physical health is carried out in this article. Experimental results show that the emotion recognition technology based on smart sensors can well recognize the changes in people's emotions during badminton sports, and the accuracy of emotion recognition is higher than 70%. At the same time, experiments show that badminton can greatly improve people's physical fitness and strengthen people's physique.

A structural basis for amylin receptor phenotype.

Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMY1R, AMY2R, and AMY3R. Selective AMYR agonists and dual AMYR/CTR agonists are being developed as obesity treatments; however, the molecular basis for peptide binding and selectivity is unknown. We determined the structure and dynamics of active AMYRs with amylin, AMY1R with salmon CT (sCT), AMY2R with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. The conformation of amylin-bound complexes was similar for all AMYRs, constrained by the RAMP, and an ordered midpeptide motif that we call the bypass motif. The CT-bound AMYR complexes were distinct, overlapping the CT-bound CTR complexes. Our findings indicate that activation of AMYRs by CT-based peptides is distinct from their activation by amylin-based peptides. This has important implications for the development of AMYR therapeutics.

Broadband achromatic metalens for linearly polarized light from 450 to 800 nm.

Metalens is a planar optical component that uses nanostructures with a thickness on the order of the wavelength to manipulate the wavefront of the incident light. A key problem, especially in color imaging and display applications, is the correction of chromatic aberration, which is an inherent effect caused by the dispersion of periodic lattices and resonance modes. However, the current achromatic metalenses either use the PB phase method that is only valid for circularly polarized light or nanostructures with complex cross sections that are difficult to manufacture. Here, we designed a broadband achromatic metalens for linearly polarized light from 450 to 800 nm. Rectangular titanium dioxide nanofins of various lengths and widths were applied to modulate the phase and dispersion of the incident light. The metalens can fulfill three target phases simultaneously by using an optimization method. The designed metalens has a stable focus from 450 to 800 nm with an average focusing efficiency of 64%. It can be potentially applied in microscopes, lithography machines, sensors, and displays.

Structure and dynamics of the CGRP receptor in apo and peptide-bound forms.

G protein-coupled receptors (GPCRs) are key regulators of information transmission between cells and organs. Despite this, we have only a limited understanding of the behavior of GPCRs in the apo state and the conformational changes upon agonist binding that lead to G protein recruitment and activation. We expressed and purified unmodified apo and peptide-bound calcitonin gene-related peptide (CGRP) receptors from insect cells to determine their cryo-electron microscopy (cryo-EM) structures, and we complemented these with analysis of protein conformational dynamics using hydrogen-deuterium exchange mass spectrometry and three-dimensional variance analysis of the cryo-EM data. Together with our previously published structure of the active, Gs-bound CGRP receptor complex, our work provides insight into the mechanisms of class B1 GPCR activation.

Characterization of chemical components in the Guanxinning injection by liquid chromatography-mass spectrometry.

Guanxinning injection (GXNI) is widely used in the treatments of cerebral thrombosis, cerebral hemorrhage, sequela, coronary disease, stenocardia, arrhythmia, and so on. For the herbal injections, more components should be characterized and quantified as much as possible to guarantee the drug safety. However, large numbers of the chemical constituents in the GXNI still remain unknown. In this study, ultrahigh performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q Orbitrap HRMS), in combination of nuclear magnetic resonance (NMR), was used to identify the components in GXNI, which led to the identification of 194 compounds. With the aid of solvent partition, more phthalides, diterpenoid quinines, and salvianolic acids were tentatively identified, and minor compounds with the other structural types were also detected. The structural diversity of phthalides and diterpenoid quinones were revealed by the structural network, and six phthalides and 13 diterpenoid quinones were further detected in GXNI with the help of the characteristic fragmentation pattern and structural network. In addition, NMR also revealed the presence of a series of primary metabolites in the GXNI, which could be used as a complimentary approach for the rapid identification of the chemical components in the traditional Chinese medicines (TCM). However, the unknown NMR signals of GXNI needed to be further identified to guarantee the drug safety.

Seasonal Dynamics of Leaf Stoichiometry of Phragmites australis: A Case Study From Yangguan Wetland, Dunhuang, China.

Leaf stoichiometry can enhance our understanding of leaf elements' (C, N and P) concentrations and their corresponding ratios in an ecosystem with seasonal environment changes. This study quantified the seasonal dynamics of leaf stoichiometry of P. australis from Yangguan wetland, Dunhuang, China as a case study example. The leaf C concentration (LC) of P. australis changed between seasons and was 392.26 (g×kg-1), 417.35 (g×kg-1) and 392.58 (g×kg-1) in spring, summer and autumn, respectively. Leaf N and P concentrations (LN and LP) were 23.49 (g×kg-1), and 17.54 (g×kg-1) and 5.86 (g×kg-1), and 1.00 (g×kg-1), 0.75 (g×kg-1) and 0.16 (g×kg-1), respectively, in the three seasons. The maximum (77.68) and the minimum values (17.00) of LC:LN were observed in the autumn and spring, respectively. Seasonal variations in LC:LP also showed a similar trend, with the greatest value of 3015.91 in autumn and the lowest value of 429.39 in spring. However, the highest (45.67) and the lowest values (24.18) of LN:LP were observed in autumn and summer, respectively, indicating that the growth of P. australis was mainly affected by P. Based on these results, it can be concluded that P. australis adopted a competition strategy during the early growth stage but took on a defense life strategy at the late growth stage to cope with various environments.

Rumor detection based on propagation graph neural network with attention mechanism.

Rumors on social media have always been an important issue that seriously endangers social security. Researches on timely and effective detection of rumors have aroused lots of interest in both academia and industry. At present, most existing methods identify rumors based solely on the linguistic information without considering the temporal dynamics and propagation patterns. In this work, we aim to solve rumor detection task under the framework of representation learning. We first propose a novel way to construct the propagation graph by following the propagation structure (who replies to whom) of posts on Twitter. Then we propose a gated graph neural network based algorithm called PGNN, which can generate powerful representations for each node in the propagation graph. The proposed PGNN algorithm repeatedly updates node representations by exchanging information between the neighbor nodes via relation paths within a limited time steps. On this basis, we propose two models, namely GLO-PGNN (rumor detection model based on the global embedding with propagation graph neural network) and ENS-PGNN (rumor detection model based on the ensemble learning with propagation graph neural network). They respectively adopt different classification strategies for rumor detection task, and further improve the performance by including attention mechanism to dynamically adjust the weight of each node in the propagation graph. Experiments on a real-world Twitter dataset demonstrate that our proposed models achieve much better performance than state-of-the-art methods both on the rumor detection task and early detection task.

Driving Factors and Future Prediction of Land Use and Cover Change Based on Satellite Remote Sensing Data by the LCM Model: A Case Study from Gansu Province, China.

Land use and cover change (LUCC) is an important issue affecting the global environment, climate change, and sustainable development. Detecting and predicting LUCC, a dynamic process, and its driving factors will help in formulating effective land use and planning policy suitable for local conditions, thus supporting local socioeconomic development and global environmental protection. In this study, taking Gansu Province as a case study example, we explored the LUCC pattern and its driving mechanism from 1980 to 2018, and predicted land use and cover in 2030 using the integrated LCM (Logistic-Cellular Automata-Markov chain) model and data from satellite remote sensing. The results suggest that the LUCC pattern was more reasonable in the second stage (2005 to 2018) compared with that in the first stage (1980 to 2005). This was because a large area of green lands was protected by ecological engineering in the second stage. From 1980 to 2018, in general, natural factors were the main force influencing changes in land use and cover in Gansu, while the effects of socioeconomic factors were not significant because of the slow development of economy. Landscape indices analysis indicated that predicted land use and cover in 2030 under the ecological protection scenario would be more favorable than under the historical trend scenario. Besides, results from the present study suggested that LUCC in arid and semiarid area could be well detected by the LCM model. This study would hopefully provide theoretical instructions for future land use planning and management, as well as a new methodology reference for LUCC analysis in arid and semiarid regions.

Immunoassay-type biosensor based on magnetic nanoparticle capture and the fluorescence signal formed by horseradish peroxidase catalysis for tumor-related exosome determination.

A sandwich-type fluorescent biosensor for the determination of tumor-related exosome was designed. It is based on magnetic nanoparticle (MNP) capture and horseradish peroxidase (HRP) catalysis. MNPs were used as the substrate to capture exosomes by modifying the CD63 antibody on MNPs surface. After that, the biotinylated epithelial cell adhesion molecule (EpCAM) antibody was used to capture the tumor-related exosomes, which specifically express EpCAM. A novel method for the fluorescence measurement of tumor-associated exosome was achieved, with a detection limit as low as 200 (± 9) particles mL-1. The analytical range of this method is from 576 (± 15) particles mL-1 to 5.76 × 107 (± 5.1 × 105) particles mL-1. For the fluorescence measurement, the excitation wavelength was set to 320 nm. Fluorescent spectra were collected at emission wavelength in the range 370 to 550 nm; the data shown in the calibration plot were studied by using the fluorescence intensity at 406 nm. This sensor was also able to successfully detect the exosomes from the plasma of patients with hepatocellular carcinoma (HCC) and healthy humans. Graphical abstract Schematic representation of the sensing process of immunoassay-type biosensor based on magnetic nanoparticle capture and the fluorescence signal formed by the horseradish peroxidase (HRP) catalysis for tumor-related exosome determination.