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Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Filamentous fungi are a valuable source of natural therapeutic products such as antibiotics. Here the authors engineer monocellularS. cerevisiaeto perform complex secondary metabolism typical of multicellular fungi in order to demonstrate biosynthesis and secretion of bioactive penicillin.

Elevated extrinsic tissue-scale forces can drive pathological foreign-body responses to implants, mediated by the Rac2-mediated activation of a subpopulation of mechanoresponsive myeloid cells.

Chemically induced dimerization (CID) systems allow control over cellular processes. Here, the authors present a proof-of-principle demonstration that a complete CID system can be de novo designed, reporting a designed ligand and protein pair where a protein homodimer is induced by a macrocyclic peptide.

Protein synthesis is tightly regulated by the integrated stress response, but therapeutic activation remains challenging. Here, the authors identify a drug‑like allosteric inhibitor, an ISRAC, that stabilises inactive eIF2B, mimicking stress‑induced eIF2α phosphorylation to activate the ISR, establishing eIF2B as a tractable target for ISR modulation.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Computationally designing proteins with interfaces that bind small molecules has posed a long-standing challenge. Here, authors combine deep learning and physics-based approaches to design proteins that bind small molecules, and demonstrate their approach by designing a cortisol biosensor.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

This Perspective reviews tools developed over the past five years in the macromolecular modeling, docking and design software Rosetta.

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.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Allosteric biosensors are constructed by combining reporter proteins with machine-learning-designed receptor domains.

In a phase 1 basket trial, the small interfering RNA zodasiran, targeting ANGPTL3, lowered triglycerides in patients with severe hypertriglyceridemia and lowered both triglycerides and low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolemia.

C-terminal α-amidated peptides are attractive therapeutic targets, but preparative methods to access amidated pharmaceuticals are limited both on lab and manufacturing-scale. Here, the authors report a straightforward and scalable approach to the C-terminal α-amidation of peptides and proteins from cysteine-extended polypeptide precursors.

Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

The cortex fuels essential physiological processes with glucose-derived carbon, while gliomas fuel their aggressiveness by rerouting glucose carbon pathways and scavenging alternative carbon sources such as environmental amino acids, providing a potential therapeutic target.

Metabolic labeling experiments on fermenting yeast revealed that ethanol is oxidized to acetaldehyde and acetyl-CoA and is also a major source of NADH and NADPH, demonstrating that ethanol can be consumed as a TCA cycle and redox fuel.

Zuhra and Petrosino et al. report evidence that cyanide acts as a regulatory gasotransmitter in mammalian cells, where it is shown to affect cellular bioenergetics, most likely via protein S-cyanylation.

A Review of de novo protein design highlights key methodological advances and achievements, current challenges and future applications.

The Amazon faces worsening droughts, yet little is known about large-scale variation in the physiological limits of Amazon trees. Here, the authors reveal family-level conservatism in embolism resistance and estimate that Brazilian and Guiana shield forests are more resistant than Western Amazonia forests.

Manipulating chemical interactions is crucial in protein assembly. Here, the authors highlight the importance of accounting for solvent forces mediated by interfacial hydration structures when designing protein assemblies at liquid-crystal interfaces.

Laser performance is constrained by various factors. Here, the authors show theoretically that the linewidth can be reduced below the standard quantum limit by engineering the output coupling of a laser to reduce noise, and discuss the potential practical implementation of this approach.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

The association between Central Atlantic Magmatic Province (CAMP) eruption volatiles and the end-Triassic mass extinction remains ambiguous. Here, the authors present mercury and palaeontological evidence from the same archive and show that significant biotic recovery did not begin until CAMP eruptions ceased.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Tham and Bernardo et al. show that cardiomyocyte-specific knockout of estrogen receptor alpha induces increased adiposity and tissue metabolic alterations specifically in female mice, likely in part due to changes in the proteomic content of the heart-derived extracellular vesicles.