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Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes. Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of inflammatory diseases. Here authors report a cryoelectron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, which provides insights into PACAP27 binding and VIP receptor activation.

Objective This study aims to describe the epidemiological features of craniofacial soft tissue injuries in a major plastic emergency department in northwest China. Methods A retrospective review of emergency medical records (2019-2023) was conducted for craniofacial soft tissue injury patients. Demographic and clinical data were collected and analyzed, stratified by age and with consideration of the COVID-19 period. Results A total of 22,887 patients with 24,050 craniofacial soft tissue injuries were included. The mean age was 13.46±15.52 years, with a male to female ratio of 1.57. Collisions were the primary cause of injury (86.5%), and contusion and laceration were the most common types of wounds (97.4%). The most frequent injury locations were the forehead (24.4%), chin (13.8%), cheeks (13.0%), and supercilium (12.3%). Peak visiting times were in April, May, June, September, and October during the year, on weekends during the week, and in the afternoon and evening during the day. The average time interval between injury and hospital visit was 6.17±5.68 hours, with a median time of 4 hours. Epidemiological characteristics were also described for different age subgroups (underage [0-17 years], working-age [18-65 years], elderly [≥65 years]) and within each underage subgroup (infant-toddler [0-2 years], preschool [3-5 years], primary school [6-11 years], secondary school [12-17 years]). The COVID-19 pandemic led to a decrease in the frequency of facial injuries and a change in hospital visiting pattern, but had no apparent influence on other epidemiological characteristics. Conclusions This study provides a detailed epidemiological description of craniofacial soft tissue injuries in a large single-center retrospective cohort. The findings can contribute to optimizing treatment strategies, resource allocation, and the development of public health policies.

A bstract Despite the large baryon-anti-baryon asymmetry in the observable Universe, the closely related phenomenon — the violation of the combined charge and parity symmetry ( CP V) — has not been observed in the baryon sector in laboratories. In this paper, a new strategy for searching for CP V in heavy hadron multi-body decays is proposed, in which a set of novel observables measuring CP V in such decays — the partial wave CP asymmetries (PW CP As) — are introduced. This strategy is model-independent and applicable to multi-body decays of heavy hadrons with arbitrary spin configurations in both initial and final states, and with any number of particles in the final state. It is especially applicable for CP V investigations in multi-body decays of heavy baryons. As applications of this strategy, we suggest to measure the PW CP As in some decay channels of bottom baryons such as Λ b 0 → p π − π + π − , Λ b  →  pK − π + π − , Λ b 0 → p π − K + K − , Λ b 0 → Λ K + π − , and Λ b 0 → p π − K s .

As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide range of physiological processes. Extensive efforts of structural biology have been made on the study of GPCRs. However, a large portion of GPCR structures remain unsolved due to structural instability. Recently, AlphaFold2 has been developed to predict structure models of many functionally important proteins including all members of the GPCR family. Herein we evaluated the accuracy of GPCR structure models predicted by AlphaFold2. We revealed that AlphaFold2 could capture the overall backbone features of the receptors. However, the predicted models and experimental structures were different in many aspects including the assembly of the extracellular and transmembrane domains, the shape of the ligand-binding pockets, and the conformation of the transducer-binding interfaces. These differences impeded the use of predicted structure models in the functional study and structure-based drug design of GPCRs, which required reliable high-resolution structural information.

We use a near-threshold parameterization with explicit inclusion of the Castillejo–Dalitz–Dyson poles, which is more general than the effective range expansion, to study the bottomonium-like states Zb(10610) and Zb(10650). In terms of the partial-wave amplitude, we fit the event number distribution of B(∗)B¯∗ system to the experimental data for these resonances from Belle Collaboration. The data could be described very well in our method, which supports the molecular interpretation. Then the relevant physical quantities are obtained, including the B(∗)B¯∗ scattering length (a), effective range (r), and residue squared (γs2) of the pole in the complex plane. In particular, we find the compositeness can range from about 0.4 up to 1 for the BB¯∗ (B∗B¯∗) component in the resonance Zb(10610) (Zb(10650)).

G protein-coupled receptors (GPCRs) are critical drug targets involved in numerous physiological processes, yet many of their structures remain unresolved due to inherent flexibility and diverse ligand interactions. This study systematically evaluates the accuracy of AlphaFold3-predicted GPCR structures compared to experimentally determined structures, with a primary focus on ligand-bound states. Our analysis reveals that while AlphaFold3 shows improved performance over AlphaFold2 in predicting overall GPCR backbone architecture, significant discrepancies persist in ligand-binding poses, particularly for ions, peptides, and proteins. Despite advancements, these limitations constrain the utility of AlphaFold3 models in functional studies and structure-based drug design, where high-resolution details of ligand interactions are crucial. We assess the accuracy of predicted structures across various ligand types, quantifying deviations in binding pocket geometries and ligand orientations. Our findings highlight specific challenges in the computational prediction of ligand-bound GPCR structures, emphasizing areas where further refinement is needed. This study provides valuable insights for researchers using AlphaFold3 in GPCR studies, underscores the ongoing necessity for experimental structure determination, and offers direction for improving protein–ligand interaction predictions in future computational models.

A bstract The semileptonic decay of heavy flavor mesons offers a clean environment for extraction of the Cabibbo-Kobayashi-Maskawa (CKM) matrix elements, which describes the CP-violating and flavor changing process in the Standard Model. The involved form factors where the dynamical information is encoded play an essential role in achieving any conclusive statement. That is, the knowledge of the form factors should be under good control, requiring one to examine more observables in addition to the branching fraction. In this paper, we provide the mean value and the q 2 -dependent shape for further observables [differential decay distribution ( d Γ/ dq 2 ), forward-backward asymmetry A FB ls , longitudinal P L l and transverse P T l polarization of a charged lepton, longitudinal polarization of a vector meson in the final state F L l V , leptonic convexity parameter C F l , and trigonometric moments W i l in the decay of D ( s ) and B ( s ) to P / Vl + ν l ( l = e , μ or τ )], based on the predictions of the relevant form factors from the covariant light-front quark model. P and V denote the pseudoscalar and vector meson, respectively. As a comparison, we find a good agreement with the results from the covariant confining quark model and the relativistic quark model in the literature. As it has been observed that the P L l and F L l V are crucial quantities to discriminate various New Physics models, the reexamination of these observables from a different method is also essential and necessary.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, with many GPCRs having crucial roles in endocrinology and metabolism. Cryogenic electron microscopy (cryo-EM) has revolutionized the field of structural biology, particularly regarding GPCRs, over the past decade. Since the first pair of GPCR structures resolved by cryo-EM were published in 2017, the number of GPCR structures resolved by cryo-EM has surpassed the number resolved by X-ray crystallography by 30%, reaching >650, and the number has doubled every ~0.63 years for the past 6 years. At this pace, it is predicted that the structure of 90% of all human GPCRs will be completed within the next 5–7 years. This Review highlights the general structural features and principles that guide GPCR ligand recognition, receptor activation, G protein coupling, arrestin recruitment and regulation by GPCR kinases. The Review also highlights the diversity of GPCR allosteric binding sites and how allosteric ligands could dictate biased signalling that is selective for a G protein pathway or an arrestin pathway. Finally, the authors use the examples of glycoprotein hormone receptors and glucagon-like peptide 1 receptor to illustrate the effect of cryo-EM on understanding GPCR biology in endocrinology and metabolism, as well as on GPCR-related endocrine diseases and drug discovery. This Review highlights how cryo-electron microscopy has revolutionized our understanding of G protein-coupled receptor (GPCR) functions. Specific examples are outlined that provide insights into GPCR biology and drug discovery in endocrinology and metabolism. Key points Cryogenic electron microscopy (cryo-EM) has revolutionized G protein-coupled receptor (GPCR) drug discovery, providing detailed insights into GPCR structures, allosteric modulation and biased signalling, and advancing precision medicine for metabolic disorders. Biased ligands enable precise modulation of GPCR signalling, offering the possibility of tailored therapeutic strategies in the discovery of drugs for endocrine and metabolic diseases. Ligand binding to GPCRs induces key structural changes, activating GPCRs for signal transduction via G proteins and arrestins, as determined by transmembrane helix 6 movement and phosphorylation states. GPCRs are modulated by diverse allosteric ligands at various sites, offering insights into drug development and therapeutic strategies. GPCRs have a pivotal role in endocrine diseases and metabolic conditions, making them promising therapeutic targets; cryo-EM has provided a better understanding of GPCRs that will enhance the development of precision drugs.

In the perturbative QCD framework, we use the quasi-two-body method to study the CP violations and branching ratios in the B ¯ s → [ ϕ ( ρ 0 , ω ) → K + K - ] [ K ∗ 0 → K + π - ] and B ¯ s → [ ρ 0 ( ω , ϕ ) → ( π + π - ) ] [ K ∗ 0 → K + π - ] decay processes. Owing to the interference effects of ρ 0 , ω , and ϕ , new strong phases associated with vector mesons will be generated, resulting in relatively large CP violation within the interference region. Moreover, we provide numerical comparisons of CP violation from resonance effects and non-resonance contributions. In order to provide better theoretical predictions for future experiments, we integrate CP violation over invariant mass to obtain the regional CP violation value. Furthermore, we have calculated the polarization fractions and branching ratios for different intermediate states in the four-body decay process, which may be influenced by vector interference effects. Additionally, this study may provide valuable reference for the future exploration of the LHC experiment.

We interpret the X1(2900) as an S-wave D¯1K molecular state in the Bethe–Salpeter equation approach with the ladder and instantaneous approximations for the kernel. By solving the Bethe–Salpeter equation numerically with the kernel containing one-particle-exchange diagrams and introducing three different form factors (monopole, dipole, and exponential form factors) in the verties, we find the bound state exists. We also study the decay width of the decay X1(2900) to D-K+.