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Post-acute infection syndromes often have heterogeneous symptoms that are difficult to interpret. Here, the authors develop a latent trajectory analysis framework designed to categorise complex relationships in longitudinal data into distinct disease phenotypes and analyse transitions between them.

In this study, the authors present optimization and efficacy testing of apolipoprotein-based lipid nanoparticles for delivering various nucleic acid therapeutics in vivo to immune cells and their progenitors in the bone marrow.

Some individuals who are infected with both HIV and an opportunistic pathogen develop immune reconstitution inflammatory syndrome (IRIS) when CD4⁺T cell numbers are restored. This reaction may arise from a hyper-responsiveness of innate immune cells to the newly reconstituted T cell help, and may apply to other cases of inflammatory pathology.

Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

Langstein-Skora, Schmid, Huth et al. propose that intrinsically disordered region functionality can be driven by the interplay between linear binding motifs and contextual chemical characteristics such as charge and hydrophobicity.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.

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.

A distinctive population with high hunter-gatherer ancestry persisted 3,000 years later than in most European regions, contributing to later Lower Rhine–Meuse Bell Beaker users.

Selecting for varieties of commercial crops with enhanced nutritional quality is important in agriculture. Here, the authors identify alleles of a gene in tomatoes that give rise to increased levels of vitamin E and find that the promoter of the gene is differentially methylated.

Lamin A/C in the nuclear lamina is identified as a regulator of cysteine catabolic flux, necessary for cell fate decisions and function.

Here, the authors demonstrate that large reasoning models can autonomously plan and execute persuasive multi-turn attacks to systematically bypass safety mechanisms in widely used AI systems.

A label-free, DNA-based proximity ligation assay that uses ligatable staple pairs enables the longitudinal quantification of DNA origami structural stability dynamics in vivo, with single-helix resolution for both wireframe and lattice designs.

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.

The lesion network mapping method links diverse brain lesions to similar functional brain networks, reflecting general brain organization rather than disorder-specific circuits.

Here the authors show that transient cell cycle arrest reprograms CD8⁺ T cells into a highly energized state, increasing proliferation and antitumor activity and boosting efficacy of immunotherapies in cancer models.

North Atlantic waters have been aging over the past three decades, indicating a slowdown in ocean ventilation. By combining observations with models, this slowdown is likely driven by climate change.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

R-type contractile bacteriocins are natural-occurring nanomachines that kill bacteria. Here the authors report the atomic structures of a bacteriocin, called diffocin, that has been engineered to kill Gram-positive bacterium Clostridioides difficile.

Wearable data from 7,013 participants in the All of Us Research Program show that park accessibility across 53 US cities is positively associated with daily step counts, providing a mechanism for how urban green space can improve health.

Dermatoscopy is a common method to aid in diagnosis of melanoma, however, its utility in predicting metastasis is not fully known. Here, the authors leverage a cohort of 30 dermatologists to develop models to predict prognosis from dermatoscopic images.

An implantable vagus nerve-targeted device safely reduces disease activity and joint damage in rheumatoid arthritis, offering a new nondrug treatment for patients who do not respond to or cannot tolerate medication.

An intestinal organoid model recapitulates human microfold (M) cell function and transcriptomic profiling and biochemical assays demonstrate that M cells uptake and present antigens to the immune system via the class II major histocompatibility complex.

Here the authors show that two conserved transcription factors are required for heat stress memory in barley by mediating proper induction of heat-response genes after recurring heat stress. Overexpressing one of them increases heat tolerance without affecting growth.

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 serotonin transporter (SERT) is a key antidepressant target. Here, authors present a cryo-EM structure where the antidepressant vilazodone spans the main SERT binding site toward a secondary pocket and provide further insights into ligand binding.

This study shows that historical precipitation variability shapes current and future record-breaking precipitation probabilities, with regions with low current records being more at risk. High-risk regions are abundant around the world, leading to a quarter billion people facing potential precipitation disasters by 2050.

Intratumor heterogeneity (ITH) has been mainly studied at the genomic level. Here, the authors integrate multi-region proteomics of 280 tumor regions from 33 patients, exome sequencing, and imaging-based immune and stromal profiling to investigate functional spatial proteomic ITH in breast cancer and the interactions of cancer cells and the tumor microenvironment during cancer progression.

The idea that NK cells can distinguish aberrant cells by recognizing 'absence of the expected', rather than 'presence of the unexpected' emerged more than 25 years ago. Klas Kärre recapitulates how the idea took shape, and the first five years of experimental work to test its general predictions.

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.

Physical activity has the potential to combat the negative mental health effects of social isolation. Its benefit is particularly high in people at increased neural and psychological risk for affective disorders.

Proving sustainable chemical plastic recycling must rely on realistic feedstocks and sustainability-driven catalyst design. Here, the authors report titania-supported Ru–Ni alloy nanoparticles achieving up to 55% liquid (C6 to C45) products for low-carbon and profitable polyethylene hydrogenolysis and determine a metric for sustainable product distributions.