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In metastatic lymph nodes, solid stress generated by metastatic growth prevents the infiltration of lymphocytes into the lesions.

The ability to genetically modify haematopoietic stem cells would allow the durable treatment of a diverse range of genetic disorders but gene delivery to the bone marrow has not been achieved. Here lipid nanoparticles that target and deliver mRNA to 14 unique cells within the bone marrow are presented.

Carbon–carbon bonds are ubiquitous in lignin, limiting monomer yields from current depolymerization strategies mainly targeting C–O bonds. Now, a bifunctional hydrocracking approach uses a Pt/zeolite catalyst to break C–C bonds in lignin waste, achieving monocyclic hydrocarbon yields up to 54 C%.

Several 17B-HSD13 variants have been identified as protective against NASH/MASH. However the protein’s endogenous function is unknown. Here authors describe sulfonamide-based inhibitors and synthetic substrates, then apply to multiple cellular systems revealing that the most prevalent IsoD variant maintains NAD-dependent catalytic activity.

AI-guided epigenetic classification is integral for accurate brain tumour diagnosis. Here, the authors introduce an interpretable framework to explain the AI process, revealing biological insights and potential therapeutic targets.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Solvating polar polymers with ionic liquids at appropriate concentrations can produce a unique class of materials called glassy gels with desirable properties of both glasses and gels.

Chan et al. report that 3′ UTR splicing is widespread and enhanced across different cancer types and is associated with more advanced tumour progression.

China’s dramatic demographic shift toward population aging raises challenges at the individual, familial and societal levels. Fang et al. review these challenges and emerging policies designed to promote healthy longevity in China.

Epstein-Barr virus (EBV) is associated with high risk for nasopharyngeal carcinoma (NPC). Here, the authors develop a comprehensive risk score that combines risk effects of EBV and human genetics for NPC risk stratification.

The organic geochemical biomarker IP₂₅ has been widely applied in the reconstruction of Arctic sea ice, yet its source remains undetermined. Here, the authors report the identification of IP₂₅in common pan-Arctic sea ice diatoms, thus establishing its applicability as a palaeo Arctic sea ice proxy.

A magnetic resonance imaging probe that binds specifically to neurotoxic amyloid-beta oligomers can potentially be used for early detection of Alzheimer's disease.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

G Protein-Coupled Receptors (GPCRs) can adopt different conformations, each linked to distinct cellular outcomes. Here the authors show that compound 17b, a novel agonist of the GPCR family member FPR, robustly activates cardioprotective but not detrimental FPR signalling, showing beneficial therapeutic effect in a mouse model of cardiac infarction.

A long- and short-read barley pan-transcriptome assembled from 20 diverse barley genotypes offers insights into genotype- and tissue-dependent gene expression and function.

Combining theoretical derivation and numerical simulations, this study predicts an ecological mechanism for maintaining microbial coexistence via dynamic neutrality enabled by horizontal gene transfer. This mechanism allows the emergence of microbial diversity beyond the limit predicted by previous theories.

Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing.

The generation and observation of strained cyclic alkynes is of fundamental importance to organic chemistry, as the deviations from ideal bond angles further our understanding of reactivity and stability. Here, the authors generate and trap three polycyclic strained carbocyclic compounds through the Fritsch–Buttenberg–Wiechell rearrangement, and discuss the trapped species in the context of computational investigations of the reaction coordinates.

Wang and colleagues show that miR-126 and miR-126^* suppress metastasis by inhibiting the production of the Sdf-1α cytokine in mouse mammary tumours, resulting in decreased recruitment of mesenchymal stem cells and inflammatory monocytes to the tumour stroma.

Polar microalgae have high zinc demand. Here, the authors use quantitative proteomics and transcriptomics of polar and non-polar model algae combined with cellular physiology to show that zinc plays an important role in supporting photosynthetic growth in eukaryotic polar phytoplankton.

Here the authors describe a method for remote magnetothermal stimulation of neurons that achieves subsecond behavioural responses in Drosophila fruit flies by combining magnetic nanoparticles with TRPA1-A, a rate-sensitive thermoreceptor. Tuning the properties of magnetic nanoparticles to respond to different magnetic field strengths and frequencies enables multichannel thermal magnetogenetic stimulation.

This mega-analysis of brain resting-state functional connectivity in young individuals with major depressive disorder scanned at six sites across four countries identified hub regions of the attentional and default mode networks as predictors of depression severity.

Genome-wide siRNA screens identify an essential function for sorting nexin 5 in virus-induced autophagy and immunity mediated via class III phosphatidylinositol-3-kinase complex 1.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

To understand the potential for seaweed as a Blue Carbon strategy, the authors quantify carbon burial under 20 globally distributed seaweed farms. They attribute an average of 1.06 ± 0.74 tCO₂e ha⁻¹ yr⁻¹ to seaweed farms, and show increased accumulation of carbon with farm age.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Conventional intermetallics are usually brittle and hard to manufacture. This work successfully develops a strong yet ductile chemically complex intermetallic alloy based on the 3D printing technique.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

A multi-ancestry genetic meta-analysis identifies 12 new loci associated with preeclampsia and gestational hypertension and proposes the integration of polygenic scores and clinical factors for disease prediction

Now a reactivity-based RNA profiling strategy can measure the global off-target transcriptome interactions of small-molecule drugs at single-nucleotide resolution. Using this approach, three FDA-approved drugs were evaluated, uncovering pervasive drug–RNA interactions and interactions that perturb RNA functions in cells.

Discovery of a biochemical mechanism through which lactate binds and inhibits the SUMO protease SENP1, stimulating timed degradation of cell cycle proteins, and resulting in mitotic exit.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Hydrogen-doping driven metal to ferroelectric phase transition in a complex oxide NdNiO₃ is demonstrated. Transient negative differential capacitance and implementation of polarization decay into neural network for learning are then presented.

Pseudomonas aeruginosa infections are increasingly difficult to treat due to the development of antimicrobial resistance. Here, the authors describe the synthesis, characterisation and efficacy of a quorum sensing inhibitor.

SCENT is a nonparametric method that models association between chromatin accessibility and gene expression in single-cell multimodal datasets, enabling construction of cell-type-specific enhancer–gene maps to aid mapping of candidate causal variants and genes for common diseases.

The underlying mechanisms driving colorectal cancer (CRC) through the serrated route are largely unknown. Here, the authors show that reduced aPKC levels increase cholesterol biosynthesis to promote aggressiveness in serrated tumours and targeting this pathway reduces tumourigenesis in preclinical models of serrated CRC.

The role of T cells in modulating the course of influenza infection in humans is not clear. Wilkinson et al. now report that, in the absence of strain-specific humoral immunity, preexisting cytotoxic CD4⁺ T cells limit the severity and duration of symptoms in humans challenged with influenza virus and suggest these CD4⁺ T cell responses might be harnessed in vaccine development.

Lam et al. show that conditional deletion of calcineurin B1 in cardiomyocytes and its inhibition using the US Food and Drug Administration-approved drug, FK506, promotes cardiomyocyte cell-cycle re-entry and increases cardiomyocyte numbers in adult mice

Grune et al. show that hypokalemic mice develop spontaneous ventricular tachycardia after myocardial infarction, and they use this model to dissect the role of immune cells in arrhythmia: neutrophils increase ventricular tachycardia, partly by promoting reactive oxygen species production, whereas efferocytic macrophages play a protective role.

In the context of succinate uptake to promote adipose tissue browning, Reddy, Winther et al. show how the directionality of succinate transport across membranes is coupled with metabolic flux-derived changes in pH gradients.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

This Review summarizes existing data, as well as crucial knowledge gaps, emerging from clinical trials involving NAD⁺ precursor supplementation in humans.

Mouse models often combine mutant alleles to accelerate cancer development, limiting oncogenic diversity. Here the authors show that sporadic MYC activation in Vk*MYC mice is sufficient to induce tumors with a variety of secondary mutations that mirror the genetic heterogeneity of human myeloma.