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PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

Mycobacterium tuberculosis uses five ESX systems to secrete multiple effector proteins that are essential for the pathogen’s growth and virulence. Here, Nair et al. identify a protein complex that is required for outer-membrane localization and for secretion of all ESX-dependent proteins into the cytosol of infected macrophages.

Integrating an electronic device with a cavity can cause the electrons to couple to photons strongly enough to form hybrid modes. Now, the cavity effects induced by intrinsic graphite gates are shown to modify the low-energy properties of graphene.

SMC complexes are ring-shaped motors that fold DNA by extruding loops, but how they navigate large DNA obstacles is unclear. Here, Liu et al., show that SMC complexes bypass obstacles by threading obstacle linkers through a selective hinge channel, enabling translocation on crowded chromatin.

It is unclear whether the linkage between tree species richness and insect herbivory is consistent across climates and forest types. Here, the authors analyse data from forest biodiversity experiments to show a generally positive tree growth–insect herbivory relationship that is modulated by leaf traits.

Coufal and colleagues generated microglia from human iPS cells to examine mechanistic roles of the transcription factor MEF2C and how these roles might relate to the autism phenotype seen following the loss of MEF2C in human microglia.

Quintana and colleagues describe the engineering of oncolytic viruses armed with multiple immunomodulators and with targeted tropism for tumor cells for glioblastoma immunotherapy.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving 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.

Basidiomycete fungi typically have two mating-type loci located on different chromosomes. Here, Lucotte et al. report the convergent loss-of-function of mating-type genes across several species of phytopathogenic fungi of the genus Microbotryum.

Understanding the factors that control island orientation in the growth of two-dimensional materials is likely to improve their quality. Here, using low-energy electron microscopy, the authors show that post-nucleation annealing of 2D materials can improve rotational order.

This work uses differentiable simulations and reinforcement learning to design interpretable genetic networks, enabling simulated cells to self-organize into emergent developmental patterns by responding to local chemical and mechanical cues.

Convergent selection between crops can help to identify genetic variants with important roles in adaptation as a source of diversity for the improvement of cultivated species through the concept of inter-crop translational research for breeding.

Guidance is lacking on how to best integrate sex, gender and social and structural determinants of health into neuroscience research on brain resilience in ageing and dementia. In this Roadmap article, Rajah et al. propose a way forward for conducting more inclusive research in this field.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Several moons in the outer Solar System have oceans encased beneath an ice shell. If the ice shell thins, ocean pressure decreases. Modelling shows that on Mimas, Enceladus, and Miranda, the ocean can boil. On larger bodies, instead, compressional forces form tectonic features.

Engineering structurally and functionally complex synthetic cells remains a key challenge. Here DNA condensate synthetic cells combine phase separation and DNA nanostructures to reveal how switchable artificial cytoskeletons assemble in viscoelastic confinements. These cytoskeletons improve the mechanical properties of synthetic cells and enable stable mechano-interfaces with mammalian cells.

Chapman, Klaourakis and colleagues reveal that a lymphatic vasculature with poor clearance capacity in perinatal, regeneration-competent mouse hearts is required to retain pro-reparative macrophages and allow cardiac regeneration.

Municipal solid waste (MSW) could power sustainable aviation fuel (SAF), but costs and technical hurdles such as gasification hinder its adoption. A study now shows that MSW can be turned into SAF with 80–90% lower lifecycle emissions while offering a 16% reduction in aviation greenhouse gas emissions.

Multiple types of cell elongation have been described in bacteria, but little is known about how these strategies vary across species. Here, the authors use fluorescent D-amino acids to track the spatiotemporal dynamics of bacterial cell elongation, revealing unsuspected diversity of elongation modes among closely related species of the family Caulobacteraceae.

The notion that catalysts are static entities that barely change under operation is still prevalent although it is often not true. Here, a range of operando and in situ techniques reveals the dynamic nature of Co₃O₄ during the oxidation of 2-propanol to acetone, unveiling a network of interconnected solid-state processes, such as exsolution, diffusion or void formation, that govern the catalytic performance.

Here, Pickard et al. found that amino acids can disrupt the gut microbiota’s resistance, allowing Salmonella to grow, while removing protein from the diet restored this defense, suggesting diet changes could help protect against infections after antibiotics.

Yang–Mills theory is the basis of the standard model of particle physics. The Yang–Mills Millennium Prize problem, to show that the theory is mathematically well defined and that it has the mass gap property, is one of the great challenges of mathematical physics. This Review explores the problem from both physical and mathematical points of view and surveys promising approaches from recent years.

EXO1 performs multiple roles in DNA replication and DNA damage repair (DDR), but its role in DDR-deficient cancers remains unclear. Here, the authors find EXO1 loss as synthetic lethal with many DDR genes involved in various cancers, including genes from Fanconi Anaemia pathway, BRCA1-A complex, and spliceosome factor ZRSR2; such interactions represent potential clinical targets.

Surface acoustic waves have previously been used, in conjunction with electric currents and assisting magnetic fields, to manipulate magnetization. Here, Rivelles, Yanes, and coauthors succeed in driving magnetic domain walls solely with surface acoustic waves, an important milestone in acoustically controlled spintronic devices.’

Nature Biotechnology’s annual survey highlights academic startups that are, among other things, designing circular RNA therapeutics, tackling cancer with arenaviruses, creating psychedelics without the trip, editing genes and cells in vivo, harnessing the power of autoantibodies and editing the epigenome.

Seagrass genomes of the deep-water Zostera pacifica and shallow-water Z. marina from the Eastern Pacific Ocean provide evidence for low-light adaptation exemplified in the wild hybrid Z. marina × pacifica subjected to low-light stress in aquaria.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

A method termed ac⁴C-seq is introduced for the transcriptome-wide mapping of the RNA modification N⁴-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.

Indium selenides, InSe and In₂Se₃, exhibit high electron mobility, high thermal velocity, thickness-tunable bandgaps and unique phase-dependent ferroelectric properties. Addressing their challenges of scalable synthesis, phase control and oxidation could be the basis for next-generation, low-power computing.

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.

Observed 730 Myr after the Big Bang, a little red dot is found to anchor an overdensity of eight galaxies and seems to be embedded in a massive host dark matter halo.

Single-photon sources are important for quantum optical technologies, although achieving efficient light extraction from them with waveguides is limited in top-down approaches. Reimeret al. show a high extraction efficiency using a bottom-up method to grow quantum dots on the axis of nanowire waveguides.

Growth of high-quality III–V semiconductors for electronics and optoelectronics usually requires an atomic-lattice matched substrate. Here, the authors use templated liquid-phase crystal growth to create single-crystalline III–V material up to ten micrometres across on an amorphous substrate.

This study highlights a unique drug target for trypanosomatid parasitic protozoa and a new chemical tool for investigating the function of their divergent kinetochores.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Membrane trafficking is essential for organelle biogenesis. Here, the authors discover an alternative assembly of the Commander trafficking complex and show its role in melanosome biogenesis and in a subtype of albinism.

Entacapone, a Parkinson’s disease medication, sequesters iron resulting in a selective inhibition of gut microbial activity.

The authors show that regenerating liver requires de novo pyrimidine synthesis and it uses ammonia as precursors differentially as it traverses the liver zones. Tracing studies and spatial metabolomics reveal that assimilation periportally is via the urea cycle, and pericentrally through conversion into glutamine.

GROWdb defines US river microbiomes at the genome level.

BPTF is known to regulate chromatin accessibility and self-renewal in mammary epithelial stem cells. Here, the authors discover that BPTF inhibition delays tumor formation, re-activates ERα expression, increases sensitivity to tamoxifen treatment, and inhibits metastatic development.