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The apelin receptor regulates heart and metabolic health via G-protein and β-arrestin signaling pathways. Here, authors present receptor-β-arrestin complex structures with distinct stoichiometries that provide insight into biased signaling, guiding targeted drug design.

The reaction between Criegee intermediates and water vapour greatly impacts atmospheric chemistry and climate, yet its dynamics remain poorly understood. Now it has been shown that syn-CH₃CHOO reacts with water vapour at rates much higher than previously estimated, through a roaming mechanism that enhances reactivity and challenges conventional understanding of atmospheric OH radical production.

The apelin receptor (APJR) is a drug target for cardiovascular and metabolic health. Here, authors reveal how ligand binding, receptor dimerization, and G protein coupling cooperate to regulate APJR signaling pathway, providing insight for drug discovery.

A large-scale photonic accelerator comprising more than 16,000 components integrated on a single chip to process MAC operations is described, demonstrating ultralow latency and reduced computing time compared with a commercially available GPU.

Full-dimensional dynamics simulations using a machine learning-based potential energy surface reveal that the Cl + C₂H₂→C₂H + HCl reaction predominantly follows two roaming mechanisms—chlorine roaming (Cl-roaming) and hydrogen roaming (H-roaming)—rather than the expected direct abstraction via the traditional transition state.

Data from two large longitudinal cohorts in China, in which the participants were clustered into five groups based on their metabolic characteristics, show that a signature of microbiome age modulates the risk of cardiovascular disease in metabolically unhealthy individuals.

The African swine fever virus represents a threat to global pig production. Here, the authors determine the cryo-EM structures of ASFV RNA polymerase, and suggest that the M1249L subunit may modulate polymerase activity in cells.

Structural analysis of Crenotalea thermophila SPARTA reveals that guide-mediated target binding releases the auto-inhibition of SPARTA imposed by an acidic tail and triggers substantial conformational changes, resulting in the oligomerization of short Ago and TIR for SPARTA activation.

GPRC5D is an atypical Class C orphan GPCR and an attractive target for therapeutic interventions. Here, the authors present the cryo-EM structure of the human GPRC5D and scFv complex, and elucidate the precise antibody binding mode and recpetor dimerization interface.

Psoriasis is a common inflammatory disease, and the overproduction of reactive oxygen species (ROS) in skin lesions plays a critical role in the progress of psoriasis. Here, the authors report the use of multienzyme-inspired biomimetic iron single-atom catalysts (FeN₄O₂-SACs) with broad-spectrum ROS-scavenging capability for psoriasis treatment and relapse prevention via related gene restoration.

Bladder urothelial carcinoma is one of the most prevalent urogenital cancer types with limited therapeutic options. Here, the authors characterize the tumor immune microenvironment of bladder cancer using single cell RNA sequencing and suggest a role for inflammatory cancer-associated fibroblasts in tumor progression.

Studying the cell composition of acral melanoma at the single-cell level could provide some clues about its poor response to immunotherapy. Here, the authors analyse acral and cutaneous melanoma patient samples using single-cell RNA-sequencing, and reveal a severe immunosuppressive state in acral melanomas

Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-G_i complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.

Structure determination followed by targeted engineering of the popular photoactivatable fluorescent protein monomeric (m)Eos2 yields mEos3 versions that are more monomeric and less disruptive in protein fusions and also exhibit higher labeling density, brightness and other beneficial properties.

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. Here, the authors report a machine learning model using mass spectrometry-based liquid biopsy data for pan-cancer screening and classification.

Matye el al. show that coenzyme-A and glutathione deficiency in NAFLD limits fatty acid oxidation and antioxidant defence capacity. The nutrient sensing transcription factor EB induces autophagy–lysosome proteolysis and methionine cycle-transsulfuration to maintain hepatic cysteine, coenzyme-A and glutathione availability.

Multi-omic analysis of 100 clear cell renal cell carcinomas identifies four transcriptomic subgroups (IM1–IM4). IM4 is a high-risk subtype characterized by specific metabolic changes and a loss of lipid droplets.

The self-assembly of molecular knots in water is challenging. Here, authors report the self-assembly of a trefoil knot in water via imine condensation, without relying on external templates; the handedness of the trefoil knot is determined by the chirality of the bisamino precursor.

Traditional RNA sequencing data may fail to detect the exact cellular changes in tumor cells. With comprehensively single-cell and traditional RNA-seq data, these authors detected and compared differentially expressed genes in lung adenocarcinoma. These results may improve our understanding of cellular and molecular differences between cancerous and non-malignant tissue and provide tumor markers as well as potential therapeutic targets.

Here, the authors report the direct growth of periodic arrays of 2D semiconductor ribbons by exploiting the step edges of high-miller-index Au facets, showing potential for 2D electronic devices. The synthesized ribbons could also be merged to obtain wafer-scale single-crystal monolayers.

A spin excitation continuum across a large region of the Brillouin zone that persists at near-zero temperatures provides evidence for a quantum spin liquid state with a spinon Fermi surface in YbMgGaO₄.

Glycerol monolaurate in a microbicide is shown to protect monkeys from infection after intra-vaginal exposure to high doses of SIV. The suppressive activity may be due to the inhibition of target cell recruitment due to glycerol-monolaurate-mediated inhibition of epithelial cell signalling and inflammatory cytokine expression.