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A spatiotemporally adaptive targeting strategy ensures sequentially reprogramming metabolism of inflammatory macrophages and senescent stem cells via intracellular NAD⁺ replenishment, accelerating bone and skin tissue regeneration.

Here, the authors show that Msx2 deficiency prevents osteoclast fusion and enhances type H vessel- mediated osteogenesis. Mechanically, MSX2 protects PU.1 from FBXW7 mediated degradation and targeting Msx2 serves as an anabolic therapy in pre-clinical models of osteoporosis.

Pulmonary veno-occlusive disease (PVOD) is a fatal disease characterised by remodelling of pulmonary veins and haemosiderin accumulation in macrophages. Here the authors examine the lack of GCN2 in PVOD as this has been observed in human disease and deficiency of GCN2 in mouse and rat PVOD models alters transcriptome profiles and increases macrophage ferroptosis.

Sequencing the genome and microbiome of about 1,500 tick samples from regions across China revealed host–microbe associations in ticks that could have implications for controlling ticks and tick-borne diseases.

Osteoarthritis is closely linked to obesity. Here, the authors show that lipid overload in chondrocytes boosts fatty acid oxidation, fueling disease progression via SOX9 degradation and epigenetic dysregulation.

High-entropy nanocarbides (HENCs) containing 5–22 metal elements are synthesized through a nanoconfined impulse synthetic strategy enabled by Joule heating-induced in situ reactions in carbon nanotube films. These HENCs exhibit multi-element effects and enhanced electrocatalytic activities due to their nanoscale size and modified catalytic sites.

In a phase 1/2 trial in patients with advanced non-small-cell lung cancer (NSCLC), followed by a phase 2 trial in an EGFR-mutant selected population, treatment with the TROP2-targeting antibody–drug conjugate sacituzumab tirumotecan led to encouraging clinical response rates, especially in patients with EGFR-mutant NSCLC, which was supported by mechanistic data.

Mechanical force is critical for the development and remodeling of bones. Here the authors report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine via regulating the expression of the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 in osteoblasts.

The roles of liver-specific genes in hepatocellular carcinoma (HCC) remain to be explored. Here the authors report that PGRMC1, localized to the endoplasmic reticulum (ER) membrane, functions as a tumor suppressor in HCC by inhibiting c-Myc protein translation via activation of PERK independent of ER stress.

Fan, Shang, Song, Chen et al. identify the Integrator–PP2A complex (INTAC) as a key regulator of cancer cell sensitivity to BET inhibitors through directly interacting with the RACK7–KDM5 complex to orchestrate epigenetic silencing in a catalytic-independent manner.

Chen, Hu, Zhao, Fang and colleagues show that the ribosomal large subunit protein Rpl12 functions as a conserved ribophagy receptor in multiple organisms.

Immune checkpoint blockade therapy improved the survival rates of non-small cell lung cancer but only a proportion of patients benefit. Here authors follow the humoral and cellular immunological parameters of patients undergoing anti-PD1 therapy longitudinally and find that levels and functional properties of cytotoxic T cells, and especially CD8⁺CD101^hiTIM3⁺ cells determine the response.

Interactions among insects, plants, and microorganisms are fundamental for ecosystem function. This study focuses on the attraction of oriental armyworm moths to yeast-fermented nectar and finds that isoamyl alcohol, a yeast-derived compound, activates specific olfactory neurons in the moths, enhancing yeast dispersal and moth reproduction.

The CAPItello-291 phase 3 study reported that capivasertib (an AKT inhibitor) and fulvestrant (a selective estrogen receptor degrader) improved progression free survival in patients with HR-positive/HER2-negative advanced breast cancer. Here, the authors report the results of an extended Chinese cohort recruited as part of the original global CAPItello-291 study.

Proof of concept of the viability of a plant-derived photosynthetic system based on nanothylakoid units encapsulated in a chondrocyte membrane to enhance cell anabolism in chondrocytes is demonstrated.

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.

ARAF uniquely enhances RAS activity via N-terminal disordered sequence, forming membrane ARAF–RAS condensates that shield RAS from negative regulation and drive cancer drug resistance.

Osteoarthritis is a prevalent age-related disease. Here, the authors show that that CircRREB1 is highly expressed in second generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression.

Fibrous capsule formation limits the lifetime of implanted devices. Here, the authors report on an elastomer designed to reduce the immune response which shows enhanced device utility in both mice and non-human primate models, including in an insulin infusion catheter model.

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.

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

The identification of cross-linked peptides at a proteome scale for interactome analyses represents a complex challenge. Here the authors report an efficient and reliable search engine pLink 2 for proteome-scale cross-linking mass spectrometry analyses, and demonstrate how to systematically evaluate the credibility of search engines.

Using cryo-electron microscopy, the authors report the structures of G-protein-coupled bile acid receptor–G_s complexes and reveal the structural basis of bile acid recognition.

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.

The mechanism of cold-activated TRPM8 channel activation remains unclear. Here, authors have determined structures of mouse TRPM8 in apo or ligand-bound states, providing insights into the activation of TRPM8 structures in different states.

Arabidopsis thaliana PIN3 structures reveal the molecular mechanisms of the transport of indole-3-acetic acid and the inhibition of polar auxin transport by N-1-naphthylphthalamic acid.

DNA damage results in the acetylation of the cell-cycle checkpoint kinase WEE1 at Lys177 enabling activation. The deacetylase SIRT1 directly associates with and modifies WEE1 to inactivate it enabling resistance to WEE1 inhibition in cancer cells.

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.

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.

High-entropy ceramic dielectrics show promise for capacitive energy storage but struggle due to vast composition possibilities. Here, the authors propose a generative learning approach for finding high-energy-density high-entropy dielectrics in a practically infinite exploration space of over 10¹¹ combinations.

In a randomized, double-blind, placebo-controlled phase 3 trial, the anti-vascular endothelial growth factor receptor small-molecule inhibitor fruquintinib plus chemotherapy significantly extended progression-free survival, but not overall survival, as second-line therapy in patients with advanced gastric or gastroesophageal junction cancers.

The transcription-independent function of trimethylation of histone H3 (H3K4me) in cell division is unclear. Here, Heng-Yu Fan and colleagues report that CFP1, a subunit of the H3K4 methyltransferase, is required for oocyte meiosis, being phosphorylated and degraded during cell cycle transition.

The NF-kB pathway is strictly regulated to prevent excessive inflammatory and immune responses. Here, Li et al. describe an alternative pathway of negative regulation of p65- driven gene expression.

The retention time and toxicity of synthetic NIR-II fluorophores limit long-term application. Here the authors use infrared fluorescent proteins (iRFPs) as NIR-II probes for prolonged continuous imaging in mice, and generate a transgenic mouse model which they use to image liver and pancreas.

The mechanisms through which multigenerational paternal obesity affects spermatogenesis in offspring remain poorly understood. Here, the authors show that it affects Wt1 m6A modifications, decreasing the fertility of offspring.

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.

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.

Touch can positively modulate cognitive performance and emotional response. Here the authors demonstrate that enriched tactile experience improves memory and reduces anxiety in adult mice by remodelling the pathway from the primary somatosensory cortex to the dentate gyrus.

Age-dependent decline in remyelination in the CNS is associated with declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). Here, the authors show nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing in mouse OPCs. β-nicotinamide mononucleotide (β-NMN) supplement delays myelin aging and enhances remyelination in the aged mice.

Pregestational hyperglycaemia in mothers increases the probability of glucose intolerance in the offspring, an effect controlled by TET3-dependent DNA demethylation of genes involved in insulin secretion.

This study shows that dietary supplementation with B. adolescentis increases the activity of the catalase enzyme and improves the healthspan and lifespan in multiple animal models. Deletion of the catalase enzyme in worms abolished the beneficial effects of the bacterium.

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.

The number of edge channels in quantum anomalous Hall insulators is controlled by varying either the magnetic dopant concentration or the interior spacer layer thickness, yielding Chern numbers up to 5.