Crystal structures of agonist-bound human cannabinoid receptor CB.

Cannabinoid receptor 1 (CB) is the primary target of the partial agonist Δ-tetrahydrocannabinol (Δ-THC), the psychoactive constituent of marijuana. Here we report two agonist-bound crystal structures of human CB in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841). The two CB-agonist complexes reveal important conformational changes in the overall structure relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G protein-binding region.

The Role of and AMPK Signaling Pathway in Sarcopenia.

Objective: To identify the hub genes involved in sarcopenia and analyze their correlation with lipid metabolism.

Methods: Differentially expressed genes (DEGs) from sarcopenia/non-sarcopenia cohorts in and datasets were cross-analyzed with diabetes-related genes (GeneCards). Key genes underwent functional enrichment and protein-protein interaction (PPI) network analysis.

Comparison of pharmacokinetic similarity, immunogenicity, and safety of mepolizumab and BAT2606 in healthy Chinese men in a double-blinded, randomized, single-dose, three-arm parallel-group phase I trial.

Objective: To evaluate the similarity of BAT2606 and mepolizumab, including pharmacokinetic profiles, immunogenicity, and safety, in healthy Chinese men.

Methods: This randomized, double-blind, parallel three-arm, single-dose Phase I clinical study enrolled 207 subjects. All subjects enrolled in this study were randomly assigned to receive BAT2606 or mepolizumab (European-sourced Nucala [Nucala-EU] and US-sourced Nucala [Nucala-US]) at a 1:1:1 ratio.

Metagenomic Investigation of Pathogenic RNA Viruses Causing Diarrhea in Sika Deer Fawns.

Diarrhea is a common disease in sika deer. The causes of diarrhea in sika deer are complex and involve a variety of pathogens. Additionally, new virulent pathogens are continuously emerging, which poses a serious threat to deer's health and particularly affects fawns' survival rate.

Structural and functional characterization of human sweet taste receptor.

Sweet taste perception influences dietary choices and metabolic health. The human sweet taste receptor, a class C G-protein-coupled receptor (GPCR) heterodimer composed of TAS1R2 and TAS1R3 (refs. ), senses a wide range of sweet compounds-including natural sugars, artificial sweeteners and sweet proteins-and affects metabolic regulation beyond taste.

Green synthesis of PVA-LS-MXene composite conductive hydrogel for high-performance skin wound dressings.

Polyvinyl alcohol (PVA)-based hydrogels have been demonstrated to possess excellent biocompatibility and hydrophilicity. Nevertheless, their restricted mechanical resilience and antimicrobial properties have substantially constrained their utility in advanced wound care applications. To address these critical limitations, we constructed a conductive composite hydrogel as a potential wound dressing through strategic incorporation of lignin (LS) and MXene nanosheets into a PVA matrix.

[Surgical strategies for osteotomy correction of severe lower limb deformities in hypophosphatemic rickets].

Objective: To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets.

Methods: A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females.

Human induced neural progenitor cells generated from three-dimensional aggregate-based culture significantly improve post-stroke recovery in tMCAO mice.

Background: Despite the high prevalence of cerebral ischemic stroke, effective clinical treatments remain limited. With the development of regenerative medicine, induced neural progenitor cells (iNPCs) demonstrate ideal potential and good availability for autologous transplantation therapy. However, current differentiation protocols for iNPCs still have room for improvement in terms of purity, reproducibility, scalability and differentiation potential.

A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.

Cryo-electron microscopy (cryo-EM) is a transformative imaging technology that enables near-atomic resolution 3D reconstruction of target biomolecule, playing a critical role in structural biology and drug discovery. Cryo-EM faces significant challenges due to its extremely low signal-to-noise ratio (SNR) where the complexity of data processing becomes particularly pronounced. To address this challenge, foundation models have shown great potential in other biological imaging domains.

A phage-displayed nanobody-based competitive immunoassay for the detection of African swine fever virus antibodies.

African swine fever (ASF) is a highly infectious and devastating disease that poses a significant threat to the global swine industry. The rapid spread of ASF and its ongoing pandemics continue to impact pig farming worldwide. The absence of an effective vaccine, coupled with the complexity of the African swine fever virus (ASFV), makes the control and eradication of ASF a formidable challenge.

Neoadjuvant with low-dose radiotherapy, tislelizumab, albumin-bound paclitaxel, and cisplatin for resectable locally advanced head and neck squamous cell carcinoma: phase II single-arm trial.

Although pathological complete response (pCR) and major pathological response (MPR) rates of neoadjuvant immunotherapy combined with chemotherapy in head and neck squamous cell carcinoma (HNSCC) trials remain suboptimal, emerging evidence highlights the synergistic potential of combining low-dose radiotherapy with immunotherapy to promote the efficacy of immunotherapy. This phase II, open-label, single-arm, multicenter trial (NCT05343325) enrolled 28 patients with untreated stage III-IVB HNSCC (NeoRTPC02). Patients received neoadjuvant low-dose radiotherapy, the programmed death-1 (PD-1) inhibitor tislelizumab, albumin-bound paclitaxel, and cisplatin for two cycles, followed by radical resection ~4 weeks after treatment completion.

TNFRSF11B-modified umbilical cord mesenchymal stem cells as a novel strategy for bone-related diseases by suppressing osteoclast activity.

Background And Objective: Mesenchymal stem cells (MSCs), possessing multilineage potential, are capable of differentiating into osteoblasts and thus serve as suitable seed cells for bone regeneration. Tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) gene encodes osteoprotegerin (OPG), which has a critical role in repressing osteoclast differentiation and has been reported to influence the adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Nevertheless, the impact of TNFRSF11B on the osteogenic differentiation of umbilical cord mesenchymal stem cells (UCMSCs) remains unclear.

Influence of UV Radiation on the Appearance Quality of Fair-Faced Concrete and Mitigation Approaches.

Fair-faced concrete has garnered substantial attention in recent years owing to its aesthetic appeal and eco-friendly attributes. However, as a construction material, its long-term performance is highly dependent on its service environment, particularly ultraviolet (UV) radiation. This research focuses on examining the influence of UV exposure and managing the admixtures employed in concrete and investigating the effects of UV radiation on the appearance quality, pore distribution, and micro-composition of fair-faced concrete.

Noncovalent Soft Composites with Superior Thermal Conductivity and Photothermal Efficiency for Advanced Thermal Management.

Soft materials with elevated thermal conductivity are highly sought after for efficient, adaptable thermal management in contemporary electronics, yet their fabrication remains challenging. We describe a soft composite created by integrating tannic acid-mediated liquid metals and graphene nanosheets into a polyurethane matrix through a noncovalent assembly approach that involves multiple interfacial supramolecular interactions. This composite demonstrates remarkable toughness (90.

Large low-field-driven electrocaloric effect in organic-inorganic hybrid TMCM-CdCl.

Due to environmental-friendliness and high-efficiency, electrocaloric effect (ECE) is widely regarded as a refrigeration technology for tomorrow. Herein, utilizing organic-inorganic hybridization strategy, we achieve the largest low-field-driven ECE and highest directly-measured electrocaloric strength (ECS) via packing sphere-like organic cation (CH)NCHCl (TMCM) into inorganic one-dimension (1-D) CdCl chain framework. Single-crystal X-ray (SC-XRD) diffraction combined with Raman Spectra reveals that the simultaneous order-disorder transition of organic cations and dramatic structure change of inorganic framework are responsible for the large ECE.

Genome phylogenetic analysis of Brucella melitensis in Northwest China.

Brucellosis poses a severe threat to public health in Northwest China; however, the genome phylogeny and transmission pattern of Brucella melitensis from sheep and yaks in this region remain unclear. In this study, bacteriology, conventional biototyping, and whole-genome single-nucleotide polymorphism (WGS-SNP) were applied to depict the phylogenetic profiles of strains from Northwest China. A total of 46 Brucella strains were identified as B.

Structural basis of stepwise proton sensing-mediated GPCR activation.

The regulation of pH homeostasis is crucial in many biological processes vital for survival, growth, and function of life. The pH-sensing G protein-coupled receptors (GPCRs), including GPR4, GPR65 and GPR68, play a pivotal role in detecting changes in extracellular proton concentrations, impacting both physiological and pathological states. However, comprehensive understanding of the proton sensing mechanism is still elusive.

Giant energy density nitride dielectrics enabled by a paraelectric-metaparaelectric phase transition.

Electrostatic dielectric capacitors are foundational to advance the electronics and electric power devices due to their ultrafast charging/discharging capability and high-power density. However, the low energy density limits the potential for next generation devices in terms of miniaturization and integration. We propose a strategy that relies on inducing a field-driven phase transition that we denote paraelectric-metaparaelectric, which yields an ultrahigh energy density in III-nitrides.

LMCBert: An Automatic Academic Paper Rating Model Based on Large Language Models and Contrastive Learning.

The acceptance of academic papers involves a complex peer-review process that requires substantial human and material resources and is susceptible to biases. With advancements in deep learning technologies, researchers have explored automated approaches for assessing paper acceptance. Existing automated academic paper rating methods primarily rely on the full content of papers to estimate acceptance probabilities.

Microbiome-metabolomic insights into the systemic regulation in Fangxian Huangjiu fermentation.

Metabolic forces drive microecological succession in Huangjiu fermentation. This study investigates the dynamic metabolic-microbial interplay during Fangxian Huangjiu fermentation. Temporal changes of metabolome and microbiome revealed a syntropic relationship that purified the microbial community with convergent metabolic patterns.

Application of Phosphogypsum in Ultra-High-Performance Concrete (UHPC) Matrix for Strength Enhancement and Shrinkage Reduction.

Ultra-high-performance concrete is a high-strength and durable material widely used in infrastructure, but its high cement content raises environmental concerns, particularly in terms of CO₂ emissions and resource consumption. Phosphogypsum, an industrial by-product of phosphoric acid production, presents a sustainable alternative by partially replacing cement, thereby reducing cement demand and addressing solid waste disposal issues. This study investigates the effects of PG incorporation (0-40%) on hydration kinetics, mechanical properties, and volume stability in UHPC.

Electret-Inspired Charge-Injected Hydrogel for Scar-Free Healing of Bacterially Infected Burns Through Bioelectrical Stimulation and Immune Modulation.

In this study, an electret-inspired, charge-injected hydrogel called QOSP hydrogel (QCS/OD/SDI/PANI/PS/Plasma) that promotes scar-free healing of bacteria-infected burns through bioelectrical stimulation and immune modulation, is presented. The hydrogel, composed of quaternized chitosan (QCS), oxidized dextran (OD), sulfadiazine (SDI), polystyrene (PS), and polyaniline nanowires (PANI), forms a conductive network capable of storing and releasing electric charges, emulating an electret-like mechanism. This structure delivers bioelectrical signals continuously, enhancing wound healing by regulating immune responses and minimizing fibrosis.

GPX modulation promotes regenerative axonal fusion and functional recovery after injury through PSR-1 condensation.

Axonal fusion represents an efficient way to recover function after nerve injury. However, how axonal fusion is induced and regulated remains largely unknown. We discover that ferroptosis signaling can promote axonal fusion and functional recovery in C.

On-Chip Stimulated Raman Scattering Imaging and Quantification of Molecular Diffusion in Aqueous Microfluidics.

Numerous chemical reactions and most life processes occur in aqueous solutions, where the physical diffusion of small molecules plays a vital role, including solvent water molecules, solute biomolecules, and ions. Conventional methods of measuring diffusion coefficients are often limited by technical complexity, large sample consumption, or significant time cost. Here, we present an optical imaging method to study molecular diffusion by combining stimulated Raman scattering (SRS) microscopy with microfluidics: a "Y"-shaped microfluidic channel forming two laminar flows with a stable concentration gradient across the interface.