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Forests are essential for both climate change mitigation and biodiversity conservation, yet how to balance these goals in managed forests remains unclear. Here, using a Europe-wide dataset, the authors find that biodiversity increases with carbon stocks, but mostly when deadwood is included.

Remote sensed information and population data for continental Africa are used to assess how migration acts as an adaptation response after drought event. The effect on mobility is amplified with drought frequency and poverty.

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

Kornfeld-Sylla et al reveal how alpha brainwaves are altered in children and adults with Fragile X Syndrome (FXS) and find parallel changes in alpha-like rhythms in juvenile and adult FXS model mice, showing their use for testing potential therapies.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

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.

Broadly neutralizing antibodies (bNAbs) can offer strong protection against HIV. Here, the authors demonstrate that rare resistant variants of SHIV are capable of abrogating bNAb protective efficacy, causing productive infection in rhesus macaques challenged with virus that is over 99.9% sensitive to the antibody.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Covalent inhibitors are powerful entities in drug discovery. Now the amino acid selectivity and reactivity of a diverse electrophile library have been assessed proteome-wide using an unbiased workflow. This comparative analysis and the probes described could help guide the discovery and design of covalent ligands targeting residues beyond cysteine.

Fishmeal and oil derived from forage fish are critical vulnerabilities for stable aquaculture feed supply. A shortfall impact model and scenario analysis explores options for bridging forage fish deficits with alternative aquaculture feeds.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

A CRISPR screen reveals that loss of structural components of the SAGA complex derails hematopoiesis by decoupling epigenetic control. This halts stem cell maturation, triggers a pathogenic interferon program and boosts human MDS-L cell growth.

Natural products inspire the development of pseudo-natural products through combinations of fragments of compound classes that are chemically and biologically distinct. Here, the authors report a library of 244 pseudo-natural products, evaluate them in the cell painting essays and identify the phenotypic role of individual fragments.

WIN332 is an HIV-1 Env protein designed to elicit a new class of Asn332-glycan-independent antibodies (type II) to the V3-glycan site of Env. WIN332 immunization rapidly induces type-II V3-glycan antibodies with low inhibitory activity indicative of a neutralization activity in macaques.

A spatial and single-cell transcriptomics study across multiple mammalian species identifies epidermal BMP signalling as a functional requirement for rete ridge formation, providing insight into mechanisms underlying hair density loss and wound healing.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

The relative contribution of lipid catabolism on fasting-induced longevity was unknown. Authors showed lifespan extension from fasting depend on silencing lipid catabolism upon nutrient replenishment through phosphorylation of NHR-49 by KIN-19.

Using a non-human primate model, the authors identified the tissue sites of initial viral rebound after discontinuation of antiretroviral therapy, demonstrating that such rebound preferentially occurs in the gastrointestinal tract-associated lymphoid tissues.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.

Wise management is critical to sustaining fisheries. This study finds that rebuilding plans, ratification of international agreements and harvest control rules yield strong benefits and that these are cumulative.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

The dopamine motivating animals to perform a current behavior also desensitizes local D₂ dopamine receptors. Dopamine signaling is less effective in subsequent rounds, resulting in repetition-induced devaluation of behavior.

The developmental dynamics of distinct cell types across brain regions remain poorly understood. Here authors generate DevAtlas, a high-resolution developmental 3D atlas, mapping region and cell type-specific growth in GABAergic cells and microglia in early postnatal mouse brains.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

Multi-omics and genetic models show that CGG repeat toxicity in GABAergic neurons drives FXTAS pathology and identify PRKCG as a critical modifier and potential therapeutic target.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

How individual neurons in the human lateral occipital complex respond to perceptually suppressed visual input remains unclear. Here, the authors demonstrate that while most neurons track perceptual awareness in a graded fashion, a smaller subset instead encodes the visual input itself.

Roßmann and colleagues report a simple strategy to generate a panel of fluorescent HaloTag Ligands that enable visualisation of cell surface proteins at low concentrations and with brief incubation times. They use these probes to label neuromodulatory receptors in neurons, allowing for the distinction of surface versus internal receptors of the presynaptic terminal.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, but platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, the authors design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone, which exhibit the activity of both parent anticancer compounds and can overcome drug efflux effectively due to covalent binding to intracellular biomolecules.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

Although climate change is known to abruptly shift ecosystem functions, the response of belowground ecosystem multifunctionality to climate scenarios is less understood. This study predicts that climate change will reduce global belowground ecosystem multifunctionality.

The phase 2/3 DEVOTE trial demonstrated that high-dose nusinersen significantly improved motor function and was safe in patients with spinal muscular atrophy, compared with a matched sham control.

Studies of the G-protein-coupled receptor NTSR1 show that the G protein selectivity of this receptor can be modified by small molecules, enabling the design of drugs that work by switching receptor subtype preference.