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Abstract Neuropeptide Y (NPY), a 36‐amino‐acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]–NPY and [Leu31, Pro34]–NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N‐terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor‐selective drug development. In this study, we report three cryo‐electron microscopy (cryo‐EM) structures of Gi2‐coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]–NPY. Combined with cell‐based assays, our study not only reveals the conserved peptide‐binding mode of NPY receptors but also identifies an additional sub‐pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub‐pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.

Abstract G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms.

The three successive coronal mass ejections (CMEs) that erupted from 2023 November 27–28, provide the first opportunity to shed light on the entire process of a shock propagating through, sequentially compressing, and modifying two preceding CMEs using in situ data from Solar Orbiter, Wind, and STEREO-A. We describe the interaction of the three CMEs as follows: CME-1 and CME-2 interacted with each other at distances close to the Sun. Subsequently, the shock (S3) driven by CME-3 caught up with and compressed ICME-2 before 0.83 au, forming a typical shock–ICME interaction event observed by the Solar Orbiter. The S3 continued to propagate, crossing ICME-2 and propagating into ICME-1 as observed by Wind, and completely overtaking both ICME-1 and ICME-2 at STEREO-A. The interaction between S3 and the preceding two ICMEs leads to a clear compression of preceding ICMEs including an increase in magnetic field (∼150%) and a reduction in the interval of ICMEs. It presents direct and compelling evidence that a shock can completely traverse two preceding CMEs, accompanied by a significant decrease in shock strength (magnetic compression ratio decrease from 1.74 to 1.49). Even though the three ICMEs interact significantly in the heliosphere, their magnetic field configurations exhibit coherence at different observation points, especially for ICME-3. Those results highlight the significant implications of shock–CME interactions for CME propagation and space weather forecasting.

The Mars Orbiter MAGnetometer (MOMAG) is a scientific instrument onboard the orbiter of China’s first mission for Mars — Tianwen-1. Since November 13, 2021, it has been recording magnetic field data from the solar wind to the magnetic pile-up region surrounding Mars. Here we present its in-flight performance and first science results, based on its first one and one-half months’ data. Comparing these early MOMAG observations to the magnetic field data in the solar wind from NASA’s Mars Atmosphere and Volatile EvolutioN (MAVEN) mission, we report that the MOMAG magnetic field data are at the same level in magnitude, and describe the same magnetic structures with similar variations in three components. We recognize 158 clear bow shock (BS) crossings in these MOMAG data; their locations match well statistically with the modeled average BS. We also identify and compare five pairs of datasets collected when Tianwen-1’s orbiter and the MAVEN probe made simultaneous BS crossings. These BS crossings confirm the global shape of modeled BS, as well as the south-north asymmetry of the Martian BS. Two cases presented in this paper suggest that the BS is probably more dynamic at flank than near the nose. So far, MOMAG performs well, and provides accurate magnetic field vectors. MOMAG is continuously scanning the magnetic field surrounding Mars. Data from MOMAG’s measurements complement data from MAVEN and will undoubt edly advance our understanding of the plasma environment of Mars.

In order to study the antioxidant activity of Tricholoma matsutake polysaccharides (TMP), its antioxidant capacity in vitro was investigated using superoxide anion radical (O2－·) scavenging capacity, total reducing capacity and ABTS radical scavenging capacity as indicators; and then the mouse model of ethanol oxidative damage was established, and the antioxidant activity of Tricholoma matsutake polysaccharides in vivo were measured by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AKP) in the serum of mice and the activity of catalase (CAT), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver. In vitro antioxidant results showed that Tricholoma matsutake polysaccharides had better scavenging ability on superoxide anion free radical and ABTS free radical, and the scavenging rate reached 56.67% and 96.60% when the concentration was 1 mg/mL. However, the total reducing ability of Tricholoma matsutake polysaccharides was not obvious. When the concentration was 1 mg/mL, the absorbance value could reach 0.163. Animal experiment results showed that after four weeks of continuous gastric administration, compared with the model control group, Tricholoma matsutake polysaccharides could significantly reduce ALT, AST and AKP viability in mice serum (P

Abstract Carbon nanogels (CNGs) with dual ability of reactive oxygen species (ROS) imaging and photodynamic therapy have been designed with self‐assembled chemiluminescent carbonized polymer dots (CPDs). With efficient deep‐red/near‐infrared chemiluminescence (CL) emission and distinctive photodynamic capacity, the H2O2‐driven chemiluminescent CNGs are further designed by assembling the polymeric conjugate and CL donors, enabling an in vitro and in vivo ROS bioimaging capability in animal inflammation models and a high‐performance therapy for xenograft tumors. Mechanistically, ROS generated in inflammatory sites or tumor microenvironment can trigger the chemically initiated electron exchange luminescence in the chemical reaction of peroxalate and H2O2, enabling in vivo CL imaging. Meanwhile, part of the excited‐state electrons will transfer to the ambient H2O or dissolved oxygen and in turn lead to the type I and type II photochemical ROS production of hydroxyl radicals or singlet oxygen, endowing the apoptosis of tumor cells and thus enabling cancer therapy. These results open up a new avenue for the design of multifunctional nanomaterials for bioimaging and antienoplastic agents.

The magnetic orientation of coronal mass ejections (CMEs) is of great importance to understand their space weather effects. Although plenty of evidence suggests that CMEs can undergo significant rotation during the early phases of evolution in the solar corona, there are few reports that CMEs rotate in the interplanetary space. In this work, we use multispacecraft observations and a numerical simulation starting from the lower corona close to the solar surface to understand the CME event on 2021 December 4, with an emphatic investigation of its rotation. This event is observed as a partial halo CME from the back side of the Sun by coronagraphs and reaches the BepiColombo spacecraft and the Mars Atmosphere and Volatile EvolutioN/Tianwen-1 as a magnetic flux-rope-like structure. The simulation discloses that in the solar corona the CME is approximately a translational motion, while the interplanetary propagation process evidences a gradual change of axis orientation of the CME’s flux-rope-like structure. It is also found that the downside and the right flank of the CME moves with the fast solar wind, and the upside does in the slow-speed stream. The different parts of the CME with different speeds generate the nonidentical displacements of its magnetic structure, resulting in the rotation of the CME in the interplanetary space. Furthermore, at the right flank of the CME exists a corotating interaction region, which makes the orientation of the CME alter and also deviates from its route due to the CME. These results provide new insight into interpreting CMEs’ dynamics and structures during their traveling through the heliosphere.

Using the Stream Interaction Regions list from the Tianwen-1/Mars Orbiter Magnetometer (MOMAG) data between 2021 November and 2021 December and from Wind observations, we present an accurate prediction for the arrival time and in situ parameters of corotating interaction regions (CIRs) when the Earth and Mars have large longitudinal separations. Since CIRs were detected earlier at Earth than at Mars during the period examined, we employ Earth-based CIR detections for predicting CIR observations at Mars. The arrival time is calculated by the Parker spiral model under the assumption of steady corotation of the Sun and coronal holes, while the in situ parameters are derived from Wind data through radial dependent scaling laws. The CIR prediction results are compared to the actual observations obtained from the MOMAG and Mars Ion and Neutral Particle Analyzer instruments onboard Tianwen-1, as well as the Magnetometer and Solar Wind Ion Analyzer instruments onboard MAVEN. The predicted arrival time is close to the observed values with relative errors less than 10%, and the expected in situ data show a good consistency with the Martian measurements. The comparison results indicate that the prediction method has good performance and will be helpful for comparative analysis with Tianwen-1 observations at Mars in the future.

Combined with data assimilation methods, a three-dimensional magnetohydrodynamic (MHD) numerical model is an effective tool to explore the mechanism of space weather. As a driver of space weather, the dynamic development of stream interaction regions (SIRs) near the orbit of Mars is an area of active research. In this study, we use the interplanetary total variation diminishing (TVD) MHD model to simulate solar wind parameters and model SIRs near Mars from 2021 November 15 to 2021 December 31. In this model, the MHD equations are solved by the conservation TVD Lax–Friedrichs scheme in a rotating spherical coordinate system with six component meshes used on the spherical shell. Solar wind velocity, density, temperature, and magnetic field strength are given at the inner boundary due to the characteristic waves propagating outward. We compared modeled results with observations from Mars Atmospheric Volatile EvolutioN (MAVEN) and Tianwen-1 (China’s first Mars exploration mission). Statistical analysis shows that the simulated results can capture SIRs and are in good agreement with observations; moreover, the assimilated results based on the Kalman filter improve the accuracy of numerical prediction compared with simulated results. This paper is the first attempt to simulate SIR events combined with MAVEN and Tianwen-1 in situ observations. Our work demonstrates that using the MHD model with the Kalman filter to reconstruct solar wind parameters can help us study the characteristics of SIRs near Mars, improve the capabilities of space weather forecasting, and understand the background solar wind environment.

Planetary bow shocks noncollisionally dissipate the incident bulk flow energy of solar wind into some other forms. To what extent and how solar wind disturbances affect the energy dissipation processes at the bow shocks on different planets remain unclear. With the Chinese Tianwen-1 and American Mars Atmosphere and Volatile EvolutioN missions, we present the first observation of significant modifications by a solar wind stream interaction region to the Martian foreshock waves, which are an important energy dissipation product of the bow shock. After the stream interface hitting Mars, an unusual band of foreshock waves emerged, with a central frequency of ∼0.4 Hz and frequency width of ∼0.2 Hz. These waves exhibited highly distorted waveforms, with peak-to-peak amplitudes of 10–25 nT in contrast to a background magnetic field of 6–9 nT. They were approximately elliptically polarized with respect to the wavevector and propagated highly obliquely to the background magnetic field. These waves reported here differed greatly from the commonly known Martian foreshock “30 s waves” and “1 Hz waves,” but resembled, to some extent, the less frequently occurring terrestrial foreshock “3 s waves.” Our present findings may imply an unexpected energy dissipation pattern of the Martian bow shock to the disturbed solar wind, which needs further observational, theoretical, and numerical investigations.

We present two multipoint interplanetary coronal mass ejections (ICMEs) detected by the Tianwen-1 and Mars Atmosphere and Volatile Evolution spacecraft at Mars and the BepiColombo (0.56 au ∼0.67 au) upstream of Mars from 2021 December 5 to 31. This is the first time that BepiColombo is used as an upstream solar wind monitor ahead of Mars and that Tianwen-1 is used to investigate the magnetic field characteristics of ICMEs at Mars. The Heliospheric Upwind Extrapolation time model was used to connect the multiple in situ observations and the coronagraph observations from STEREO/SECCHI and SOHO/LASCO. The first fast coronal mass ejection event (∼761.2 km s ^−1 ), which erupted on December 4, impacted Mars centrally and grazed BepiColombo by its western flank. The ambient slow solar wind decelerated the west flank of the ICME, implying that the ICME event was significantly distorted by the solar wind structure. The second slow ICME event (∼390.7 km s ^−1 ) underwent an acceleration from its eruption to a distance within 0.69 au and then traveled with the constant velocity of the ambient solar wind. These findings highlight the importance of background solar wind in determining the interplanetary evolution and global morphology of ICMEs up to Mars distance. Observations from multiple locations are invaluable for space weather studies at Mars and merit more exploration in the future.

Abstract Carbon nanodots (CDs) have emerged as an alternative option for traditional nanocrystals due to their excellent optical properties and low toxicity. Nevertheless, high emission efficiency is a long‐lasting pursuit for CDs. Herein, CDs with near‐unity emission efficiency are prepared via atomic condensation of doped pyrrolic nitrogen, which can highly localize the excited states thus lead to the formation of bound excitons and the symmetry break of the π–electron conjugation. The short radiative lifetimes (

Abstract Solar wind stream interaction regions (SIRs) and corotating interaction regions (CIRs) can cause geomagnetic storms and change energetic particle environment, ionospheric composition on Earth. Therefore advanced warning of SIRs/CIRs is vital for mitigating the effect of space weather on critical infrastructures in modern society. Recently, several solar missions, for example, Vigil mission (Luntama et al., 2020) and Solar Ring mission (Wang et al., 2020), that can be served as a space weather monitor, have been proposed. To evaluate the capabilities of these future missions of predicting SIRs/CIRs, the Solar Terrestrial Relations Observatory (STEREO‐B) spacecraft is used to investigate the correlation between SIRs/CIRs detected by STEREO‐B and Wind spacecraft. The correlation coefficients of solar wind velocity in SIRs/CIRs are significantly higher than that of magnetic field intensity or plasma density. It indicates that the velocity structure of solar wind is more persistent than magnetic field and ion density. By assuming the SIR/CIR structures are stable and ideal corotation, 58.9% of SIRs/CIRs in the STEREO‐B CIR catalog can be used to predict CIR arrival time in near‐Earth space. With increasing longitudinal and latitudinal separations between STEREO‐B and Wind, the percentage of accurately predicted CIRs decreases gradually from 100% to 20%. If the separation angle between STEREO‐B and Wind is within 30° in longitude and approximately ±5° in latitude, more than 93.2% of SIRs/CIRs can be accurately predicted several days in advance. This demonstrates that a spacecraft situated 30° trailing Earth in its orbit, can optimize our space weather‐predicting capabilities for the Earth and lessen the risk of missing or “false alarms” CIRs.

As one of the seven scientific payloads on board the Tianwen-1 orbiter, the Mars Orbiter Magnetometer (MOMAG) will measure the magnetic fields of and surrounding Mars to study its space environment and the interaction with the solar wind. The instrument consists of two identical triaxial fluxgate magnetometer sensors, mounted on a 3.19 meter-long boom with a seperation of about 90 cm. The dual-magnetometers configuration will help eliminate the magnetic field interference generated by the spacecraft platform and payloads. The sensors are controlled by an electric box mounted inside the orbiter. Each magnetometer measures the ambient vector magnetic field over a wide dynamic range (to 10,000 nT per axis) with a resolution of 1.19 pT. Both magnetometers sample the ambient magnetic field at an intrinsic frequency of 128 Hz, but will operate in a model with alternating frequency between 1 and 32 Hz to meet telemetry allocations.

The Tianwen-1 spacecraft is China's first Mars exploration mission. The Mars Orbiter Magnetometer (MOMAG) is a scientific instrument on board the Tianwen-1 mission that is designed to study magnetic fields at Mars, including the solar wind to the magnetosheath and the ionosphere. Using the first Tianwen-1/MOMAG data that is publicly available, we present an interplanetary coronal mass ejection (ICME) and stream interaction region (SIR) list based on in situ observations at Mars between 2021 November 16 and 2021 December 31. We compared the magnetic field intensity and vector magnetic field measurements from Tianwen-1/MOMAG and Mars Atmospheric Volatile EvolutioN (MAVEN)/Magnetometer (MAG) during the ICME and SIR interval and found a generally good consistency between them. Due to MAVEN's orbital adjustment since 2019, the Tianwen-1/MOMAG instrument is almost unique in its status as an interplanetary magnetic field monitor currently at Mars. The observations indicate that the MOMAG instrument on Tianwen-1 is performing well and can provide accurate measurements of the vector magnetic field in the near-Mars solar wind space. The multipoint observations combining MOMAG, MINPA, and MEPA on board Tianwen-1 with MAG, SWIA, and STATIC on board MAVEN will help develop systematic studies of the characteristics of ICMEs and SIRs at Mars, and their influences on the Martian atmosphere and ionosphere.

Interplanetary coronal mass ejections (ICMEs) are solar transients that have significant effects on the upper atmosphere and ionosphere of Mars. The simultaneous spacecraft observations from Tianwen-1/MOMAG in solar wind and multiple instruments on board the Mars Atmosphere and Volatile Evolution (MAVEN) in the Martian upper atmosphere are used to study the response of Mars to an ICME. The ICME was observed at Mars by Tianwen-1 and MAVEN at 00:00 UT on 2021 December 10, which was earlier observed by BepiColombo upstream of Mars at 22:32 UT on 2021 December 6. During 2021 December 6–15, MAVEN measured the nightside ionosphere and Tianwen-1 measured the dayside ionosphere while both were inside the Martian bow shock. The rapid drop in densities of ionospheric ions and electrons, which is typically identified as the end of the ionosphere at altitudes between 300–800 km, is known as the ionopause. The altitude of the Martian ionopause location was lowered by the high dynamic pressure of the solar wind during the ICME passage. The depletion of the plasma density in the topside Martian ionosphere on the nightside reveals the presence of substantial ion and electron escape to space through the interaction between the ICME and Mars. The column abundance of plasma dramatically decreased, with 34% e ^− , 61% ${{\rm{O}}}_{2}^{+}$ , and 73% O ^+ reduced. This study highlights the significant impact of the space weather associated with the intense magnetic field and high dynamic pressure of the ICME on Mars’s atmosphere, which is particularly important for future human exploration missions to Mars.

The intensity of the southward component of the magnetic field (Bs) carried by Interplanetary Coronal Mass Ejections (ICMEs) is one of the most critical parameters in causing extreme space weather events, such as intense geomagnetic storms. In this work, we investigate three typical ICME events with extremely intense Bs in detail and present a statistical analysis of the origins of intense Bs in different types of ICMEs based on the ICME catalogue from 1995 to 2020. According to the in-situ characteristics, the ICME events with extremely high Bs are classified into three types: isolated ICMEs, multiple ICMEs, and shock-ICME interaction events with shocks inside ICMEs or shocks passing through ICMEs. By analyzing all ICME events with Bs ≥ 10nT and Bs ≥ 20nT, we find that 39.6% of Bs,mean ≥ 10nT events and 50% of Bs,mean ≥ 20nT events are associated with shock-ICME events. Approximately 35.7% of shock-ICME events have Bs,mean ≥ 10nT, which is much higher than the other two types (isoloted ICMEs: 7.2% and multiple ICMEs: 12.1%). Those results confirm that the ICMEs interaction events are more likely to carry extreme intense Bs and cause intense geomagntic storms. Only based on the in-situ observations at Earth, some interaction ICME events, such as shock-ICME interaction events with shocks passing through the preceding ICME or ICME cannibalism, could be classified as isolated ICME events. This may lead to an overestimate of the probability of ICME carrying extremely intense Bs. To further investigate such events, direct and multi-point observations of the CME propagation in the inner heliosphere from the Solar Ring Mission could be crucial in the future.

Maternal origins based on the bovine mitochondrial D-loop region are proven to have two main origins: Bos taurus and Bos indicus. To examine the association between the maternal origins of bovine and reproductive traits, the complete mitochondrial D-loop region sequences from 501 Chinese Holstein cows and 94 individuals of other breeds were analyzed. Based on the results obtained from the haplotype analysis, 260 SNPs (single nucleotide polymorphism), 32 indels (insertion/deletion), and 219 haplotypes were identified. Moreover, the nucleotide diversity (π) and haplotype diversity (Hd) were 0.024 ± 0.001 and 0.9794 ± 0.003, respectively, indicating the abundance of genetic resources in Chinese Holstein cows. The results of the median-joining network analysis showed two haplogroups (HG, including HG1 and HG2) that diverged in genetic distance. Furthermore, the two haplogroups were significantly (p < 0.05) correlated with the antral follicle (diameter ≥ 8 mm) count, and HG1 individuals had more antral follicles than HG2 individuals, suggesting that these different genetic variants between HG1 and HG2 correlate with reproductive traits. The construction of a neighbor-joining phylogenetic tree and principal component analysis also revealed two main clades (HG1 and HG2) with different maternal origins: Bos indicus and Bos taurus, respectively. Therefore, HG1 originating from the maternal ancestors of Bos indicus may have a greater reproductive performance, and potential genetic variants discovered may promote the breeding process in the cattle industry.

The activities of geomagnetic storms are generally controlled by solar activities. The current solar cycle (SC) 24 is found to be mild; compared to SCs 19–23, the storm occurrence and size derived by averaging the occurrence number and Dst around the solar maximum are reduced by about 50–82% and 36–61%, respectively. We estimate separately, for SC 19 to 24, the repeat intervals between geomagnetic storms of specific Dst, based on fits of power-law and log-normal distributions to the storm data for each SC. Repeat intervals between super geomagnetic storms with Dst≤–250 nT are found to be 0.36–2.95 year(s) for SCs 19–23, but about 20 years based on the data for SC 24. We also estimate the repeat intervals between coronal mass ejections (CMEs) of specific speed (VCME) since CMEs are known to be the main drivers of intense storms and the related statistics may provide information about the potential occurrence of super geomagnetic storms from the location of the Sun. Our analysis finds that a CME with VCME≥1860 km/s may occur once per 3 and 5 months in SC 23 and 24, respectively. Based on a VCME-Dst relationship, such a fast CME may cause a storm with Dst=–250 nT if arriving at the Earth. By comparing the observed geomagnetic storms to storms expected to be caused by CMEs, we derive the probability of CME caused storms, which is dependent on VCME. For a CME faster than 1860 km/s, the probability of a CME caused storm with Dst≤–250 nT is about 1/5 for SC 23 or 1/25 for SC 24. All of the above results suggest that the likelihood of the occurrence of super geomagnetic storms is significantly reduced in a mild SC.

When a CME arrives at the Earth, it will interact with the magnetosphere, sometimes causing hazardous space weather events. Thus, the study of CMEs which arrived at Earth (hereinafter, Earth-impacting CMEs) has attracted much attention in the space weather and space physics communities. Previous results have suggested that the three-dimensional parameters of CMEs play a crucial role in deciding whether and when they reach Earth. In this work, we use observations from the Solar TErrestrial RElations Observatory (STEREO) to study the three-dimensional parameters of 71 Earth-impacting CMEs from the middle of 2008 to the end of 2012. We find that the majority Earth-impacting CMEs originate from the region of [30S,30N] × [40E,40W] on the solar disk; Earth-impacting CMEs are more likely to have a central propagation angle (CPA) no larger than half-angular width, a negative correlation between velocity and acceleration, and propagation time is inversely related to velocity. Based on our findings, we develop an empirical statistical model to forecast the arrival time of the Earth-impacting CME. Also included is a comparison between our model and the aerodynamic drag model.

Solar eruptions provide opportunities to study magnetic flux ropes, a structure of fundamental importance for both plasma physics and space weather. Here the authors reveal the dynamic formation of a flux rope through its footprint on the solar surface, revealing a highly twisted core structure.