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This study reports widespread loss of mountain vegetation worldwide from 2000 to 2020, with ∼89% attributable to human expansion, primarily agriculture. Over half of this loss occurred within protected areas and other biodiversity-rich areas, threatening conservation efforts.

In a phase II–III trial, a novel antibody targeting IL-6 receptor α (IL-6Rα), sarilumab, conferred clinical, functional and structural benefits in rheumatoid arthritis. These results, though, seem quite similar to those for tocilizumab, the existing anti-IL-6Rα antibody, as well as for other agents currently in development that target this same pathway.

A novel natural ribozyme has been discovered in the 5′ noncoding region of the glmS mRNA. Surprisingly, glmS ribozyme activity is modulated by a cellular metabolite. The glmS ribozyme thus represents the first example of an novel regulatory mechanism in bacteria.

Pl@ntBERT is a language-based AI model that learned the ‘syntax’ of plant assemblages, predicting likely species and inferring habitats by modelling biotic relationships.

Consensus guidelines for patient management can increase disease awareness and education, and facilitate evidence-based clinical decision-making. Nevertheless, new gout recommendations leave a 'déjà vu' impression. Novel evidence from clinical trials is needed to robustly advance patient care and build the next generation of guidelines.

Cell-cell adhesions coordinate collective movement by linking neighboring cells. Here, the authors use artificial photoswitchable adhesions to show that increased membrane tension can drive collective migration.

The authors report on the implementation of a data-efficient machine learning approach to predict plasma dynamics. This enables offline design of robust trajectories to terminate the plasma without disruptive instabilities. Experimental results at the TCV tokamak show statistically significant improvements in key figures of merit and the ability to a priori predict the dynamics of key plasma properties.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Alfonsa et al. show that wakefulness causes shifts in cortical EGABA_A, weakening synaptic inhibition and resulting in markers of local sleep pressure, and identify Cl⁻ regulation as a link between sleep–wake history, cortical activity and behavior.

A global multi-taxon extinction risk assessment of freshwater fauna for The IUCN Red List of Threatened Species finds one-quarter of species to be at high risk of extinction.

How the brain combines sensory with non-sensory information is unknown. Here, the authors find that sensory input from the thalamus to the apical dendrites of the main cortical output neurons enables the first stage of this combination process.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

The second Global Amphibian Assessment finds that the status of amphibians is continuing to deteriorate globally, driven predominantly by climate change, disease and habitat loss.

Here the authors present a method to transform polygenic scores into disorder probabilities using only GWAS summary statistics, genotype data and a prior - no tuning sample is needed. The method enables individualized, well-calibrated predictions.

Climate change is a major threat to biodiversity. This study predicts that climate change will reshape Neotropical frog diversity, causing losses in phylogenetic diversity and phylogenetic endemism, with many species facing severe range contractions by 2050.

Single-cell intracellular recordings have been used as the primary tool for estimating driving forces across inhibitory receptors within the nervous system. Here, the authors present ORCHID as an all-optical method to measure inhibitory receptor driving forces in targeted brain cell types.

Many species of reptiles are threatened with extinction. This analysis on 259 species of turtles, tortoises and crocodilians identifies anthropogenic threats that disproportionally affect species with certain life history strategies and others that affect all species similarly.

Vitrimers are malleable networks based on thermally triggered associative exchange reactions and thus can be used for processing, recycling and self-healing materials. Here the authors show how acids and bases affect the exchange kinetics and in turn rationalize these effects mechanistically.

The M₅ muscarinic acetylcholine receptor represents a promising therapeutic target for neurological disorders. Here, the authors reveal a 2.1 Å cryo-EM structure of the M₅ bound to a selective positive allosteric modulator site that enables structure-based drug design.

Invertebrate-derived eDNA (iDNA) is an emerging tool for taxonomic and spatial biodiversity monitoring. Here, the authors use metabarcoding of leech-derived iDNA to estimate vertebrate occupancy over an entire protected area, the Ailaoshan Nature Reserve, China.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Assessing the conservation status of 1,020 European marine fishes reveals half of large (>1.5 m) fishes are threatened with extinction and stock status diverges geographically: almost all Mediterranean stock is overfished, most northern European stock is not.

Madagascar is a threatened biodiversity hotspot. Here, using a newly assembled dataset and island biogeography models, the authors estimate how many millions of years of evolutionary history have been lost since human colonisation and may be further lost in the future for Malagasy mammals.

Jordan and colleagues show the role of increased fatty acid metabolism in AML stem cells, in both intrinsic and acquired resistance to combination venetoclax and azacitidine, and find that cells can be re-sensitized by inhibiting fatty acid oxidation.

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.

A genome-wide siRNA screen on patient-derived Fanconi anemia pathway-deficient head-and-neck squamous-cell-carcinoma (HNSCC) cell lines identifies RBBP9 as a candidate therapeutic target.

The mechanism of currently prescribed antidepressants is incompletely understood. Here, the study identifies associations between antidepressant use and DNA methylation, highlighting shared signals across datasets, and tissue enrichment in the amygdala.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

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.

Functional roles of natural acetylcholine (ACh) dynamics are not fully understood. This study reveals dynamic changes in ACh release across the mouse striatum during learning and extinction, identifying how and where release dynamics shape brain plasticity to gate learning and promote extinction of cue-reward associations.

Using in silico neuroscience, Gifford et al. developed a neural control algorithm to modulate the representational relationships between visual cortical areas, revealing how these areas jointly represent the world as an interconnected network.

FLAMES is a machine learning approach combining variant fine-mapping, SNP-to-gene annotations and convergence-based gene prioritization scores to identify candidate effector genes at genome-wide associated loci with high accuracy.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.