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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.

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.

Applications of optical laser-based techniques are limited by the long wavelengths of the lasers. Now, observations of phonons and thermal transport at nanometre length scales are reported with an all-hard X-ray transient-grating spectroscopy technique.

This study finds that native tree extinctions and alien naturalizations are pushing forests towards fast-growing, resource-demanding species. This global shift could affect carbon storage and ecosystem stability, highlighting the need to protect slow-growing trees.

New methods for targeted covalent protein modification at low reactivity aspartates and glutamates are of high interest. Here, the authors report a technique inspired by the HaloTag technology, which employs a covalent conjugation reaction between ligands with a reactive chloroalkane linker and a specific aspartic acid, and use it to covalently modify lipoprotein chaperone PDEδ at a binding site glutamic acid.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Discovery proteomics offers deep insights but is currently not applied clinically in diagnostics. Here, the authors present ADAPT-MS, a flexible machine learning framework that enables fast, personalized diagnostic and prognostic decisions directly from proteome-wide data.

The famous nebula Barnard 68 has been used as a giant cosmic-ray detector: cosmic-ray-excited vibrational H₂ emission has been observed by JWST, giving a direct measurement of the CR ionization rate.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

Fractional Chern insulators have been observed in moiré MoTe₂ at zero magnetic field, but the expected zero longitudinal resistance has not been demonstrated. Now it is shown that improving device quality allows this effect to appear.

The authors consider the changing sensitivity of the leaf-onset date to temperature (S_T) for boreal deciduous broadleaf forests. S_T increased between 1982–1996 and 1998–2012—potentially linked to enhanced chilling accumulation—but this increase is underestimated in phenology models.

Silicon anodes promise much higher battery capacity but are limited by poor storage life. This work identifies key ageing mechanisms and suggests ways to improve long-term stability.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

Quantum interference of sodium nanoparticles, which can each contain more than 7,000 atoms at masses greater than 170,000 Da, is demonstrated.

This study of magic-angle twisted trilayer graphene moiré superconductors using scanning tunnelling microscopy and spectroscopy identifies two energy gaps that develop from many-body resonance in this highly tunable class of materials.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

A generative AI approach is developed for predicting materials synthesis recipes—a complex challenge in materials science. Using this approach, the authors experimentally synthesized a material using AI-generated synthesis recipes.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

The presence of EGFR mutations and de novo MET aberrations limited response to EGFR inhibitors in patients with advance non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 randomised clinical trial investigating first-line osimertinib (EGFR inhibitor) plus savolitinib (c-MET inhibitor) in patients with MET-aberrant, EGFR-mutant advanced NSCLC.

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.

Single-particle tracking experiments in intact cells reveal dynamic co- and post-translational interactions of the TRiC–PFD chaperonin complex with client proteins during in vivo protein folding.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Many biological systems appear to organize their dynamics close to a critical point. Now it is shown that the protein array mediating Escherichia coli chemosensing is near-critical, enabling large signal amplification without compromising response speeds.

Integrating complex multi-omics data for individual patient decision making can be challenging. Here, the authors develop Knowledge Connector as a decision support system to generate and document Molecular Tumor Board recommendations and support medical decision-making.

Disease heterogeneity complicates precision medicine, which focuses on single conditions and ignores shared mechanisms. Here the authors introduce ‘pan-disease’ analysis using a deep learning model on multi-organ data, identifying 11 AI-derived biomarkers that reveal new therapeutic targets and pathways, enhancing patient stratification for disease risk monitoring and drug discovery.

In a double-blind, placebo-controlled phase 2 trial in patients with metastatic renal cell carcinoma treated with anti-PD-1 plus a VEGFR tyrosine kinase inhibitor, donor fecal microbial transplantation (FMT) from complete responders to immunotherapy did not significantly improve the primary endpoint of 12-month progression-free survival (PFS) but did significantly improve median PFS versus placebo FMT.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

JWST’s COSMOS-Web survey is used to create an ultra-high-detail dark matter map, revealing hidden filaments, clusters and distant structures. By tracing features out to z = 2, this map shows how dark and luminous matter build the cosmic web across cosmic time.

The Huayuan biota exhibits extraordinary biodiversity, illuminating the impact of the Phanerozoic mass extinction around 513 million years ago and offering critical insights into the transformation of global ecosystems in the early Cambrian.

This study uses single-cell DNA sequencing to analyze genomic evolution in pancreatic cancer using a cohort of multiregionally and longitudinally sampled patients’ tissues across various clinical contexts.

Muscularis macrophages, housekeepers of enteric nervous system integrity and intestinal homeostasis, modulate α-synuclein pathology and neurodegeneration in models of Parkinson’s disease, and understanding the accompanying mechanisms could pave the way for early-stage biomarkers.

In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship between environmental antigen exposure and subsequent allergy.

Guided by density functional theory, a commercially viable refractory alloy is developed, which exhibits excellent room-temperature ductility and strength, and high strength at elevated temperatures.

De novo domestication was performed on the brassica Thlaspi arvense (pennycress) by identifying and stacking CRISPR-induced mutations to create a new intermediate oilseed crop that can be grown in the off-season, with seed compositions similar to canola (low erucic acid and reduced glucosinolate).

Elite and viremic controllers of HIV can spontaneously regulate viral replication, but some lose this ability over time. In this longitudinal cohort study, 31% of viremic and 3% of elite HIV controllers lost viral control over 17 years. Specific T-cell– related proteins distinguish controller types and predict loss years in advance.

In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Juno radio occultations precisely redefine Jupiter’s shape, measuring a polar diameter of 66,842 km and an equatorial diameter of 71,488 km, both smaller than long-used values, bringing models of the planet’s interior into better agreement with observations.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

Large-scale computational and in vitro analyses identify commensal type III secretion systems and substrates in the human gut microbiome that can interact with human proteins to modulate immune pathways.

Iron is an essential micronutrient for plants and a lack of iron availability limits crop yield in many parts of the world. Here the authors show that natural variation in root growth ofArabidopsis plants under iron deficiency can be caused by allelic variation at the FRO2locus.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

Growth of wind and solar energy share demonstrates different dynamics between the initial phases of adoption as compared with the advanced stages. Cherp et al. study the growth dynamics of renewable energy and show that laggards may continue to struggle to achieve high growth rates despite learning from early adopters’ experience.

While the photoreceptor outer segments in the bird outer retina have access to oxygen, the inner retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.