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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.

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.

Imposing shear flow on a cell layer induces an ordering transition. Now it is shown that an intermediate phase of ordering occurs driven by an interplay between cellular activity and the aligning field.

Nimbus, a deep learning model, uses a large multiplexed imaging dataset to predict the likelihood of marker positivity in single cells.

Biomolecular condensates (BCs) are ubiquitous compartments that regulate key functions in cells. Authors demonstrate that phase separation is suppressed with glycine by using model heterotypic condensates composed of nucleophosmin 1 and ribosomal ribonucleic acid.

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.

Analysis of crop yields, farmer income and bird species abundances identifies multiple positive outcomes of a large-scale Indian government-incentivized agroecology initiative.

In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS compared to standard of care in patients with phospho-mTOR activation.

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.

A coherent 909-Hz quasi-periodic oscillation was potentially detected in GRB 230307A, the second brightest gamma-ray burst to date, indicating that a millisecond magnetar formed after the merger powered the burst.

Research efforts to develop digital twins in medicine are rapidly increasing, with promising emerging applications in oncology, diabetes management and cardiovascular medicine. While medical digital twins hold great promise for personalized healthcare, their implementation is no easy feat. The field faces diverse challenges including collecting data, choosing computational model designs, ensuring safety and efficacy, and preventing biases. What can be learned from the successes achieved? Which are the most promising upcoming applications? We asked experts in the field for their thoughts.

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.

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.

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.

Vallentgoed et al. integrate clinical and multiomic data from persons with matched initial and recurrent IDH-mutant astrocytomas to identify progression-associated mechanisms and report a DNA methylation-based signature associated with survival.

Bruton tyrosine kinase (BTK) inhibitors can interrupt the crosstalk between follicular lymphoma FL cells and macrophages thereby inducing downregulation of pro-survival pathways in FL cells. Here this group reports a phase 2 single-arm trial evaluating the regimen of acalabrutinib with lenalidomide plus rituximab on twenty four patients with previously untreated FL.

The authors analyze rare coding variants in 1990 individuals with congenital kidney anomalies, finding diagnostic variants in 14.1% of cases. They identify two new causal genes, ARID3A and NR6A1, along with 38 candidate genes, providing evidence for shared genetics with other developmental disorders.

This Review highlights how terrestrial laser scanning is transforming forest research by enabling highly detailed 3D measurements of trees, supporting applications in forest ecology, carbon monitoring, and biodiversity assessment.

The blood-brain barrier (BBB) regulates the extracellular composition of the central nervous system (CNS), but it is not known whether its properties differ across CNS regions. Here, the authors show in mice that the BBB exhibits regional specializations, and that such specializations can be important for the function of specific neural circuits.

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.

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.

Virus-host protein-protein interactions are fundamental to viral pathogenesis, yet few are structurally resolved. Here, the authors combine cross-linking mass spectrometry, bio-orthogonal labeling and AlphaFold to reveal the structural virus-host interface from intact cells infected with HSV-1.

Salivary gland cancers (SGC) respond poorly to immunotherapies and new treatment strategies are needed. Here, the authors develop an integrated analysis of advanced SGC to characterize the immune microenvironment and identify potential therapeutic vulnerabilities.

A quantum kernel estimation by which feature data points are evaluated through the unitary evolution of two-boson Fock states is experimentally demonstrated on a photonic integrated processor. This model provides enhanced accuracy with respect to commonly used classical methods for several classification tasks.

The ability to encode and recall information about food is critical for survival. We reveal that ventral hippocampus projections to the lateral hypothalamus encode meal-related memories, and that disruption of this circuit promotes excessive eating.

Membrane proteins are involved in many critical cellular pathways. Here, authors use a combination of structural predictions, an algorithm for stabilizing membrane proteins, and molecular dynamics to reveal a putative mechanism for the action of ceramide synthases.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

Obesity leads to pathological expansion of white adipose tissue driving vascular dysfunction. Here, the authors utilize single-cell RNA sequencing to elucidate endothelial heterogeneity and demarcate key differences in obesity-associated vascular alterations in subcutaneous and visceral white adipose tissue.