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In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

This study reveals how 3D genome architecture and super-enhancers coordinate transcriptional programs that drive muscle fiber-type specification and transformation through STARD7 and epigenetic remodeling.

Dysregulated R-loops can compromise genome stability, leading to pathological consequences. Li et al. demonstrate that R-loop-induced poly(ADP-ribose) polymerase 1 activation orchestrates exonuclease 3′–5′ ___domain-containing 2-mediated R-loop resolution, thereby safeguarding genomic integrity.

Frequencies for motor kinematics are encoded by the cerebellum through population tuning of firing probabilities, which leads to cerebellar oscillations and corresponding motions.

Understanding the genetic factors that regulate panicle architecture is important for improving rice yields. In this study, Li et al. demonstrate that the gene PTB1is critical for regulating panicle seed setting rate and pollen tube growth.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

Liu et al. developed a platform to identify transcription factors (TFs) that turn stem cells into desired cell types. They discovered six key TFs that produce microglia efficiently, enhancing cell differentiation methods.

Undefined vacuole-like ultrastructures between epididymal cells have been observed. Here, the authors reveal that these structures contain organelle residues and protein aggregates that suggest a reservoir for protein recycling.

Wang, Wang, Pan and colleagues uncover a C864–C869 disulfide linkage stimulated by viral RNA that drives RIG-I activation, phase separation and stimulates downstream innate immune signalling.

Quantum entanglement contains important information about quantum systems, but its calculation is challenging. Here the authors develop a quantum Monte Carlo technique for full tomography on microscopic subregions of a system, enabling extraction of multipartite quantum entanglement in large scale models.

Metal-free catalysts offer a sustainable option for water oxidation but typically underperform compared to metal-based ones. Here, the authors report an all-organic catalyst that uses a rare oxide pathway to achieve high efficiency and long-term stability, comparable to metal-based systems.

Single atom catalysts offer a promising approach for CO₂ electroreduction to CO, but achieving high efficiency remains challenging. Here, the authors report lanthanide single atom catalysts with the transition ability from bridge to linear adsorption that exhibit efficient CO production.

Yang et al. developed a new method, BEPH, a foundation model trained on TCGA WSI images. BEPH improves cancer recognition, classification, and survival prediction across subtypes, potentially reducing reliance on expert annotations.

It is challenging to purify and prepare large amount of methacrylated proteins from cells. Here, the authors develop genetic code expansion technology to site-specifically incorporate ε-N-Methacryllysine into proteins and identify the post-translational modification ε-N-methyl-ε-N-methacrylation.

Baseline performance, benchmarks, and guidance for LLMs in biomedicine are limited. The authors assess four LLMs on 12 tasks, establish baselines, examine hallucinations, and provide recommendations for optimal LLM use.

Rat hepatitis E virus (HEV) can infect humans, but the extent of spillover isn’t well studied. Here the authors develop a serological test that distinguishes exposure to rat HEV from other HEV infection and show substantial spillover in a biodiversity hotspot in China. The method can support surveillance of rat HEV.

Monolithic SiC metasurface is demonstrated to engineer arbitrary 3D perfect vector vortex beam and implement an optical anticounterfeiting scheme by using such beams. This method paves the way for advanced optical trapping and information security.

Interferon-γ (IFNγ)-activated calcium/calmodulin-dependent protein kinase II (CAMK2) phosphorylates phosphoserine aminotransferase 1 (PSAT1) at serine 337 (S337), enabling glutathione peroxidase 4 (GPX4) interaction, promoting α-ketoglutarate-dependent PHD3-mediated GPX4 proline 159 (P159) hydroxylation and stabilizing GPX4 to counteract ferroptosis.

Lu et al. perform systematic functional analyses using data from the TRACERx cohort of patients with non-small-cell lung cancer and delineate how FAT1 regulates homologous recombination repair, chromosomal instability and whole-genome doubling with distinct mechanisms.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Effectiveness of the hepatitis E vaccine HEV 239 amongst high-risk groups isn’t well studied. Here, Zhuang et al. analyse a decade of surveillance data (2007–2017) from Dongtai, China, and estimate HEV 239 effectiveness of 72% amongst hepatitis B virus infected people.

Here the authors present a large genetic study in East Asians that identifies 97 genetic regions linked to kidney function. These findings aim at better understanding chronic kidney disease in diverse populations.

Cancer subtypes may have distinct metabolic vulnerabilities that can be exploited for therapeutic interventions. Here, the authors show that in lung cancer, genetic activation of distinct oncogenic receptor tyrosine kinases results in unique metabolic liabilities and, in particular, EGFR aberrant cancers rely on the serine biosynthetic pathway while FGFR aberrant cancers rely on glycolysis.

Crystalline dispersoids are commonly used to strengthen metals by obstructing dislocation movement, but this often comes at the cost of ductility. Here, the authors demonstrate that amorphous nanoparticles, introduced via additive manufacturing, enhance both the tensile strength and fatigue resistance of metallic materials.

Dendritic cells play pivotal roles in the immune response to viral infection but are targeted by flaviviruses resulting in evasion of the host response. Here the authors show Zika but not Dengue virus limits the NF-κB response in monocyte derived dendritic cells diminishing their ability to activate T cells.

Treating myocardial reperfusion injury via nanotherapy is challenging due to clearance by the mononuclear phagocyte system. Here, the authors target the spleen to reduce acute heart injury and improve long-term cardiac function via transient IRF7 inhibition.

MAT2A/MAT2B induction is required for hepatic stellate cell activation and FOXM1 is implicated in liver inflammation and fibrosis, but whether they crosstalk in liver disease is unknown. Here, the authors show that upregulation of the FOXM1/MAT2A/MAT2B axis drives liver inflammation and fibrosis.

Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.

Overcoming the suppressive tumor microenvironment (TME) is crucial to improving the efficacy of cancer therapy. Here the authors show that, in mouse cancer models, administration of exogenous IL-16 establishes a Th1-dominant TME via regulation of glutamine catabolism and triggers a Th1 cell-macrophage crosstalk, enhancing anti-tumor immune responses and the efficacy of immunotherapy.

The unique structure and mechanism of chanoclavine synthase (EasC), a haem catalase that uses superoxide for substrate transformation in ergot alkaloid biosynthesis, are revealed in this study, challenging established catalase mechanisms.

Saturated N-heterocyclic pyrrolidines are common in natural products and medicinal compounds, but reconstruction of their skeletal structures to access new chemical space is a challenging. Here, the authors report a skeletal modification strategy for conversion of polar cyclic pyrrolidines into nonpolar linear dienes through a N-atom removal and deconstruction process.

Chondritic meteorites formed in the early solar system and may tell us about primary processes at that time. Here, Zhang et al. report an absolute ²⁰⁷Pb/²⁰⁶Pb isochron age (4,450±50 Ma) of apatite from a carbonaceous chondrite constraining timing of fluid activity in meteorites.

Here, the authors report immunogenicity and safety of AR-MPXV5, a penta-component mRNA vaccine, in naive and simian immunodeficiency virus infected nonhuman primates (NHPs), and demonstrate protection in naïve male NHPs after immunization with two doses of AR-MPXV5.

The anti-CRISPR protein IF9 (AcrIF9) specifically inhibits the type I-F CRISPR adaptive immune system. Here, the authors present the cryo-EM structure of AcrIF9 in complex with the type I-F CRISPR RNA-guided surveillance complex (Csy) and a dsDNA bound Csy-AcrIF9 structure, and find that AcrIF9 binding to the Csy complex triggers non-sequence specific dsDNA binding to Csy-AcrIF9, which might sequester the complex from its target DNA.

Creating and maintaining a superior microenvironment is challenging for electrocatalytic CO₂ reduction reaction. Here the authors report an in situ activation method to deliver silver nanoparticles within the gas diffusion layer, constructing a feasible and stable interfacial microenvironment.

In this work, the authors present novel PLpro inhibitors, with lead compound GZNL-P36 showing potent activity against SARS-CoV-2 variants, improving survival and reducing lung viral loads in a mouse model, offering promise for COVID−19 therapies.