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External Control Arm methods for clinical trials were developed to compare the efficacy of a treatment to a control group that is built with data from external sources. Here, the authors present FedECA, a privacy-enhancing method for analyzing treatment effects across institutions, streamlining multi-centric trial design and thereby accelerating drug development while minimizing patient data exposure.

Hammerhead is a compact high-voltage vacuum bushing designed, simulated, and tested to 330 kV. It significantly increases voltage holdoff per volume compared to other designs and operates stably at 300 kV with leakage current below 10 μA without requiring ultra-high vacuum or polishing.

During filamentous growth in the human fungal pathogen Candida albicans, a reduction in ribosome concentration leads to a decrease in macromolecular crowding. Inhibition of ribosome biogenesis can trigger filamentous growth in this pathogen.

The authors found that the Alzheimer’s disease-associated protein tau, widely considered pathogenic when hyperphosphorylated, has a natural function as part of the innate immune system in the brain and can protect against herpes simplex virus 1.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

Combining high-resolution mapping of foliar and herbivore faecal sodium concentrations across Africa, the authors show that plant-derived sodium availability constrains megaherbivore densities at a continental scale.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The impact of the COVID pandemic restrictions on Mycobacterium tuberculosis transmission is not well understood. Here, the authors analyse tuberculin skin test results from school children in Jiangsu Province, China and find evidence of declined transmission during the pandemic compared to the years before.

Risk stratification in non-small cell lung cancer (NSCLC) remains challenging. By combining multiplex immunofluorescence, H&E histology, and AI, the study identifies spatial “cell-niche” patterns that enhance survival prediction beyond UICC8 staging. These patterns reclassify many stage I patients as high risk, revealing potentially undertreated cases and establishing spatial tumor microenvironment features as clinically actionable biomarkers.

Here, the authors show that Mycobacterium tuberculosis manipulates lipid metabolism to overcome host restriction, by remodelling its lipidome and utilising host lipids as an alternative phosphate source.

Caspase 8 protein expression is largely absent in small cell lung cancer (SCLC) patients. Here, the authors generate a caspase 8 deletion SCLC mouse model and show that it promotes a neuronal progenitor-like cell state and pre-tumoral immunosuppression triggered by necroptosis that promotes metastasis.

A dynamic interconversion of three nickel states in lithium nickel oxide is demonstrated using evidence from x-ray spectroscopic data and first-principles calculations, which explains many physical properties of this and similar materials.

Sepsis may progress into lethal septic shock, but the cellular mechanisms are still unclear. Here the authors show that, in septic mice, platelets activate perivascular mast cells to cause systemic hypotension and vascular pathology, while inhibiting platelets or mast cell activation suppresses septic shock induction, thereby implicating potential therapy targets.

Biomass-derived monomers are a renewable resource for the production of polymers. Robertet al. develop an auto-tandem catalytic transformation for the synthesis of aliphatic polyesters—'activated' monomers are prepared from dicarboxylic acids, which can be copolymerized with epoxides.

Zhou, Jay et al. report that in mantle cell lymphoma and T cell leukaemia, lineage-determining transcription factors share a mechanism to regulate how multiple enhancers control oncogene expression through topological conformation and interaction.

Marine cloud reflectivity declined by 2.8%/decade (2003-2022) over the NE Pacific and North Atlantic, enhancing shortwave absorption beyond climate model projections. Here, the authors use an improved aerosol-climate model and show that aerosol reductions may account for 69% of the cloud reflectivity decline.

Analyses of whole-genome sequencing data from UK Biobank and All of Us identify rare variant burden signals associated with metabolic health, including effects of protein-truncating variants in IRS2 on type 2 diabetes and chronic kidney disease risk.

Imputation of genotypes is central to genetic studies but remains limited for several data types. Here the authors present QUILT2, a scalable and read-aware method that enables imputation from short reads, long reads, and cell-free DNA from non-invasive prenatal testing.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

This work presents a degradable ionizable lipid, AMG1541, for mRNA vaccines that significantly enhances potency and enables similar protective immunity at doses 100-fold lower than current standards, while also reducing toxicity and improving clearance in vivo.

This study presents a scalable reinforcement learning framework that accelerates the discovery of bioactive peptides by efficiently screening vast peptide libraries with demonstrated activity towards breast cancer.

ATGL is a key enzyme in intracellular lipolysis. Here, the authors use deep mutational scanning to define the determinants of protein interaction between ATGL and its regulatory partners, gaining insights into lipolysis mechanisms in cells.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Using intracranial electroencephalography from patients with epilepsy during spatial attention tasks, this study shows that high-frequency bursts facilitate fast communications in brain networks and support attentional information routing.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Here authors report dopamine D2 receptor-driven mediation of striatal acetylcholine signaling regulates cocaine consumption by activating muscarinic M4 receptors in medium spiny neurons and controlling KAT5 expression and histone H4K8 acetylation.

Methods used to date a network of marine sediment cores reveal that rapid retreat of the Ross Ice Shelf was contemporaneous with the lowering of nearby outlet glaciers, implicating warm ocean waters as a driver of Antarctic deglaciation.

Chiral organic materials hold significant potential in optoelectronics, sensing, and catalysis, with macrocycles potentially offering enhanced chiroptical properties thanks to their preorganisation. Here, the authors synthesize bis-perylene diimide-based macrocycles with multiple sources of chirality, revealing the dominant influence of chromophore helical chirality on chiroptical properties and enabling chirality induction in achiral guests.

A system based on trapped rubidium atoms for generating quantum secure keys between distant users is presented, which could operate in a device-independent fashion.

Cas12a3 nucleases constitute a distinct clade of type V CRISPR–Cas bacterial immune systems that preferentially cleave the 3′ tails of tRNAs after recognition of target RNA to induce growth arrest and block phage dissemination.

Across 13 longitudinal studies (3,737 adults), the authors show that brain atrophy parallels memory loss, with a stronger coupling in later life. APOE ε4 increases decline, yet genetic risk does not modify the brain–memory relationship.

Wang, Xiao and colleagues develop and validate organ-specific proteomic aging clocks across large population cohorts in the UK, the USA and China, which show strong performance in tracking organ aging and predicting the risk of morbidity and mortality.

Pocock et al. reveal that transient activation of 5′ AMP-activated protein kinase and estrogen-related receptor drives robust maturation of multicellular human cardiac organoids, enabling modeling of desmoplakin cardiomyopathy dysfunction, which could be rescued using the bromodomain and extra-terminal inhibitor INCB054329.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Sustainable aviation fuels production scale-up is slow. By 2024, only 24% of the capacity planned to be in production had been realized and more than 40% of year 2030 plans risk delays. Even with a solar/wind-like rapid scale-up, global and EU SAF capacity will miss 2030 and 2050 policy targets.

Current single-cell RNA sequencing methods struggle to comprehensively profile transcriptomes, with many lowly expressed transcripts remaining undetected. Here authors present a workflow for enhancing the detection of both transcripts and regions of interest in combination with a standard transcriptome profile.

Khawaja et al. show sex-specific differences in neuronal-activity regulation by chaperone-mediated autophagy and that loss of chaperone-mediated autophagy leads to defective neuronal physiology and increased seizure susceptibility, linking chaperone-mediated autophagy to neuronal excitability.

In the phase 3 STAR trial, subretinal administration of the AAV2-based gene therapy timrepigene emparvovec in patients with choroideremia did not lead to a significant difference in the primary endpoint of 15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) improvement in visual acuity from baseline compared to untreated controls.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Instrumental to the migration of antigen-scavenging immune cells, the lymphatic vessel entry receptor LYVE-1 interacts with the hyaluronan glycocalyx, anchored by the leucocyte hyaluronan receptor CD44. Here, dynamic force spectroscopy, crystal structures and MD simulations provide mechanistic insights.

The mechanism(s) controlling CD8+ virtual memory T cell (TVM) development are still under investigation. Here, using uninfected or IAV-challenged Ikzf3-deficient mice, the authors identify the transcription factor Aiolos as a negative regulator of TVM cell development by repressing Eomes and IL-15/STAT5 signaling.

Sodium-ion batteries are promising low-cost alternatives to lithium-ion systems yet limited by underperforming anodes. This Review highlights advances and challenges in hard carbon and alloy-based anodes, outlining design strategies to boost capacity, stability and commercial viability of next-generation high-energy sodium-ion batteries.

Somatic instability plays a role in Huntington’s disease. Here, the authors show that lowering HTT levels by transcriptional repression suppresses somatic instability. This can also be done without affecting HTT levels by direct CAG repeat binding.