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The changing cellular, transcriptional, and genomic landscape of human lung aging can be characterized using single-cell RNA sequencing. Here, the authors show that lung aging is cell-type dyssynchronous, with alveolar epithelial and endothelial cells exhibiting the greatest changes in gene expression, transcriptional entropy, and a high level of somatic mutations.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

A statistical method to quantify crystallographic textures in aluminum alloys under additive manufacturing conditions is introduced. Experiments and simulations reveal interfacial energy anisotropy dominates texture selection and grain competition.

Core ionization of ions in solution leads to decay processes involving interaction with the environment. Here, the authors report a non-local X-ray emission process in core-ionized Na⁺ and Mg²⁺ that can be used to probe the ions’ solvation shells.

A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.

RAS-driven cancers depend on SHOC2–PP1C. Here, the authors reveal that KRAS forms a low-affinity SHOC2–PP1C complex with fewer contacts than MRAS and show that dual inhibition of KRAS- and MRAS-dependent assemblies strengthens SHOC2 suppression and may overcome resistance.

Biochemical screening and optimization identify small molecules that inhibit the formation of lipoprotein(a), and these inhibitors reduce the levels of Lp(a) in several animal models, suggesting that they could provide a therapeutic option in humans.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

Zonal positioning in the liver determines whether the CTNNB1 oncogene can induce liver cancer.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Marine spatial planning (MSP) and ecosystem restoration are effective approaches to address marine and coastal biodiversity loss and meet Global Biodiversity Framework targets, but have been applied separately to date. This Perspective outlines how ecoscape restoration and climate-smart MSP can be aligned to deliver reciprocal benefits and accelerate biodiversity recovery.

Engineering mammalian cellular functions requires a toolkit of orthogonal and well-characterized genetic components. Here the authors develop COMET: an ensemble of transcription factors, promoters, and accompanying models for the design and construction of genetic programs.

Mantle cell lymphoma (MCL) is a form of B-cell non-Hodgkin lymphoma with a high degree of genetic and clinical heterogeneity. Here, using a multi-omics approach, the authors investigate genetic alterations in association with the tumour microenvironment to identify potential therapeutic vulnerabilities.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

BANKSY is an algorithm with R and Python implementations that identifies both cell types and tissue domains from spatially resolved omics data by incorporating spatial kernels capturing microenvironmental information. It is applicable to a range of technologies and is scalable to millions of cells.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

The translocation channel of ClpXP, which must open for degradation, is closed by an axial pore-2 loop when recognizing the ssrA degron. Here the authors show that the channel is also closed in the absence of substrate in cryo-EM structures and find that mutational destabilization of the closed-channel conformation changes substrate specificity.

Mutations reducing the function of MYT1L, a neuron-specific transcription factor, are associated with a syndromic neurodevelopmental disorder, yet it remains unclear which cell types are most impacted by MYT1L loss. Here authors use single-nuclei RNA sequencing to profile the forebrains of MYT1L-deficient mice at three developmental stages and reveal MYT1L deficiency disrupts cortical neuron proportions and gene expression, primarily affecting excitatory neuron maturation programs.

Linking prior epigenetic status to future outcomes remains a challenge. Here, authors show recording neuronal enhancer activity across postnatal development in mice reveals loci that predict and can be manipulated to modify acute seizure response.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Post-drought rehydration triggers a preventive immune response in plants, revealing targets to enhance crop resilience by linking drought stress recovery with improved pathogen resistance.

Utilizing single-cell RNA sequencing, the authors here find that IL1B gene expression in peripheral blood monocytes associates with smaller HIV-1 reservoir size in people treated during acute infection, suggesting IL1B may be a natural latency reversing factor decreasing the reservoir via NF-κB activation.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

Single-cell DNA methylome profiling allows the study of epigenomic heterogeneity in tissues but has been impeded by library quality. Here the authors demonstrate snmC-seq2 which improves mapping, throughput and library complexity.

The neural mechanisms underlying the antidepressant effects of nitrous oxide remain poorly understood. This study reveals that specific activation of layer V pyramidal neurons in the cingulate cortex rescues stress-associated hypoactivity states and is driven by inhibition of calcium-sensitive potassium channels rather than NMDA-receptor antagonism.

Scaffolding protein ankyrin-B, implicated in cardiometabolic syndrome, enables mitochondrial fission and flexibility of nutrient utilization under energetic stress in skeletal muscle to support energy production and optimal exercise capacity.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

Human pathways acting on nuclear ncRNAs have been refractory to forward genetics. Here, the authors develop a forward genetic approach that identifies such pathways and show DDX59 is required for minor intron splicing, suggesting a mechanism for its association with Oral-Facial-Digital syndrome.

A study identifies public neoantigens generated by tumor-wide aberrant mRNA splicing activity across distinct cancer types.

This study combines lattice light sheet microscopy and single molecule imaging to study protein dynamics and chromatin structure in live cells. The authors describe how nucleosomes and proteins move and are organised in relation to chromatin density.

Independent of antigen presentation, migratory CCR7⁺ dendritic cells orchestrate the influx, proliferation and cytotoxic action of natural killer cells to control cancer cell growth in the leptomeninges.

Wildfire observations reveal that 21% of black carbon aerosols contain multiple cores, and accounting for this morphology increases global absorption by 19%, highlighting a missing source of radiative forcing in current models.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

This research investigates the neurobiological factors influencing weight gain, using brain scans from diverse cohorts to develop a predictive model. The findings indicate that BMIgap correlates with psychiatric conditions, suggesting its potential for identifying at-risk individuals and guiding personalized interventions.

Utricle, a component of the inner ear vestibular system, is essential for balance. This study maps the cells and genes in the adult human utricle. It identifies distinct non-sensory cell types and reveals early responses to damage, providing insight into potential strategies for restoring balance.

Microscopic colitis is a chronic inflammatory disease of the large intestine. Here the authors use single-cell RNA transcriptomic profiling and tissue localization studies to characterise the colon immune cell populations in MC, showing expansion of CD8 T cells with diverse TCR clonotypes and expression of CD4 T reg cell signatures.

Reduced GC-related content in the influenza A virus genome may be a necessary condition for sustained mammalian transmission and should be included in risk assessment tools for pandemic influenza.

Here, the authors characterize the gut plasmidome of a cohort of 34 mother-infant dyads showing that infants exhibit greater plasmid diversity compared to their mothers and other healthy adults, with Bacteroidota representing the primary host for gut plasmids and plasmid transfer.

Mitochondrial translational activators (TAs) facilitate transcript-specific translation. Using selective ribosome profiling and cryo-electron microscopy, the authors show that TAs bind to the 5′ untranslated region of their target transcript to position mitoribosomes for initiation.