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Nonalcoholic fatty liver disease (NAFLD) has limited dietary treatment options. Here, the authors show that torularhodin, a microbial carotenoid, alleviates NAFLD by enriching Akkermansia muciniphila and promoting adenosylcobalamin synthesis, which reduces ceramides via HIF-2α inhibition.

Dipterocarp trees are iconic but severely threatened species in Asian rainforests. This study assembles high-quality genomes of seven dipterocarp species to reveal the molecular basis of key adaptations and identifies a recent sharp population decline coinciding with local human activity.

Evidence for the treatment of patients with mild-to-moderate COPD is limited. Here, the authors show that long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improve lung function in patients with mild-tomoderate COPD.

P2X3 activation requires tightening the inner pocket of the head ___domain (IP-HD) following ATP binding. Here the authors demonstrate that targeting the IP-HD with allosteric small molecules presents a potential strategy for the development of therapeutics for refractory chronic cough without taste abnormalities.

Euglena gracilis is a model organism of the eukaryotic supergroup Discoba, single-celled organisms containing mitochondria with discoid cristae. Here, the authors report structures of Euglena’s transport chain supercomplex to reveal their distinctive architecture and working mechanisms.

The authors highlight the role of acyl coenzyme A binding protein (encoded by DBI) in Cushing’s syndrome by using six different inhibition methods and mapping the physiological effects.

A heteroepitaxial-strain-based strategy for enhancing the stability of perovskite quantum dots for spectrally narrow (pure) red LEDs is reported.

LYCHOS is a lysosome-localized cholesterol sensor involved in mTORC1 activity regulation. Here, the authors report the three-dimensional structure of LYCHOS bound to cholesterols, revealing the recognition mechanism for this molecule.

Toxin B (TcdB) is a major exotoxin responsible for diseases associated with C. difficile infection. Here, Tian et al. show that several TcdB subtypes do not recognize the established FZD receptors, and identify a different host protein (TFPI) as a receptor for subtypes TcdB4 and TcdB10.

The mechanisms of stalled fork degradation in BRCA1/2-deficient cells remain unclear. UFL1, an UFM1-specific E3 ligase, was found to catalyze PTIP UFMylation at lysine 148, promoting stalled fork degradation by the MRE11 nuclease.

Safe haemodialysis is essential for patients with acute kidney injury and renal failure. Here the authors present a DNA origami-based approach with high affinity and specificity to thrombin, inhibiting coagulation.

How excitatory neurons (EN) acquire senescence is unclear. Here, the authors show that GDF11 in ENs slows EN senescence, brain ageing, cognitive decline and maintains lifespan, revealing a mechanism underlying EN senescence and brain ageing.

Tumour cell behaviour is an underdeveloped target for cancer intervention. Here the authors report on a spatiotemporal interaction between tumour cells and osteoclasts in initial bone metastases and propose a behaviour-targeting therapy with an in situ physical killing strategy.

PRS-CSx is a polygenic risk score construction method that improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations.

The alternative mechanisms of innate immunity in tumorigenesis of colorectal cancers are unclear. Here, the authors report a non-canonical function of IRF3, a mediator of innate immune signalling, in the suppression of colorectal tumorigenesis and this is via the inhibition of Wnt/β-catenin pathway.

Hsc70 (heat shock protein family A member 8) is a cytoplasmic chaperone protein involved in endosomal micro-autophagy and chaperone-mediated autophagy. Here the authors report that Hsc70 promotes lysosomal degradation of PD-L1 and that its overexpression promotes anti-tumor immune responses in preclinical cancer models.

Candidalysin is a toxin secreted by Candida albicans. Although critical for pathogenesis, its intracellular targets are not well mapped. Here, Zhang et al screen for interacting proteins and identify that candidalysin can modulate the DNA damage repair pathway to promote fungal infection.

In a randomized phase 2 trial comparing anti-PD-1 plus anti-VEGF plus an HDAC inhibitor versus anti-PD-1 plus an HDAC inhibitor in patients with MSS/pMMR colorectal cancer, the triplet combination led to significantly better 18-week progression-free survival.

Biocompatible afterglow materials have potential in imaging applications, but are challenging to prepare. Here the authors report the development of carbon nanodots with near-infrared afterglow, and demonstrate their use in imaging for tumour resection.

The glucagon-like peptide-1 (GLP-1) receptor is a key regulator of glucose homeostasis and a drug target for type 2 diabetes but available GLP-1R agonists are suboptimal due to several side-effects. Here authors report the cryo-EM structure of GLP-1R bound to an ago-allosteric modulator in complex with heterotrimeric G_s which offers insights into the molecular details of ago-allosterism.

In the CNS, glutamatergic neurons directly control functional hyperemia via synaptic-like transmission onto arteriolar smooth muscle cells. Inhibiting this process reduces brain atrophy following cerebral ischemia.

Multi-targeting agonists at GIPR, GLP-1R or GCGR are pursued vigorously. Here, the authors report cryo-EM structures of tirzepatide-bound GIPR and GLP-1R, peptide 20-bound GIPR, GLP-1R and GCGR, revealing the molecular basis of their multiplexed pharmacological actions.

The central circadian circuit’s role in integrating temperature changes is not fully understood. Here, the authors demonstrate that temperature-sensitive DN1a circadian neurons in the Drosophila brain bidirectionally influence downstream circadian neurons, regulating temperature-dependent physiological activities.

Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.

A subcutaneous hydrogel electrostatically entrapping live Zika virus recruited immune cells at the injection site and provided mice with effective protection against a lethal challenge.

Tetrahymena thermophila possesses tubular mitochondrial cristae and a highly divergent electron transport chain. Here the authors report cryo-EM structures of its half ring-shaped ~8 MDa megacomplex IV₂ + (I + III₂ + II)₂ and ~10.6 MDa megacomplex (IV₂ + I + III₂+ II)₂ adapted to the cristae membrane curvature.

The authors report on the structure of a glucocorticoid-bound adhesion G-protein-coupled receptor–G protein complex.

scAtlasVAE is a deep learning-based model for cross-atlas integration. Here it enables the development of a large-scale human CD8⁺ T cell atlas with integrated T cell receptor data.

Xu et al. report structures of the Arabidopsis cytokinin importer AZG1 in the apo, trans-zeatin-bound, 6-benzyleaminopurine-bound and kinetin-bound states, and elucidate an elevator transport model for the AZG1-mediated cytokinin uptake.

In a prespecified interim analysis of the multicenter, randomized, phase 3 FLAMES trial, maintenance therapy with a PARP inhibitor in patients with ovarian cancer showed prolonged progression-free survival compared with placebo in all subgroups defined by BRCA or homologous recombination status.

Recently, the theory of Hawking radiation of a black hole has been tested in several analogue platforms. Shi et al. report a fermionic-lattice model realization of an analogue black hole using a chain of superconducting transmon qubits with tuneable couplers and show the stimulated Hawking radiation.

Helicobacter pylori FabX, a dehydrogenase/isomerase flavoprotein, is required for unsaturated fatty acid synthesis. Here, the authors characterize FabX substrate recognition and catalytic mechanism, and reveal that it contains an atypical [4Fe-4S] cluster, which is essential and participates in the catalytic cycle.

The Nemo-like kinase (NLK) plays a regulatory role in immune responses. Here, the authors show that NLK inhibits antiviral IFN responses by phosphorylating the mitochondrial antiviral-signaling protein MAVS and describe a MAVS-derived peptide that exhibits antiviral effects both in vitro and in mice.

Bacteriophage Q protein serves as a model regulator for the study of transcription elongation. Here the authors report a cryo-EM structure of an intact Q-engaged arrested complex, revealing the interactions responsible for σ-dependent pause, Q engagement, and Q-mediated transcription antitermination.

An effective-gate-voltage-programmed graded-doping method can be used to reconfigure a single-gate molybdenum ditelluride device to different states, including a polarity-switchable diode, memory, Boolean logic and artificial synapse.

A mouse model of gliomagenesis reveals that olfaction can directly regulate the genesis of gliomas, showing that sensory experience and gliomagenesis are linked and providing insight into the neural circuitry involved.