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Here, the authors elucidate TMPRSS2 protease recognition of the SARS-CoV-2 spike S₂′ cleavage site, revealing the molecular basis of activation of membrane fusion, and show that antibodies recognizing the S₂′ site or TMPRSS2 block viral entry by interfering with TMPRSS2 access.

Structural studies demonstrate that myosin generates forces that cause structural changes in actin, modulating cooperative binding by α-catenin and thus signal transduction and intercellular communication via adhesion complexes.

A large-scale proteomics analysis of the dark proteome by the TransCODE Consortium reveals many translated non-canonical open reading frames to encode microproteins and peptideins.

The anti-CRISPR protein AcrVA2 specifically interrupts Cas12a biogenesis by triggering co-translational mRNA degradation.

How early-life intestinal microenvironment shape colonic iNKT cell development to be further explored. The authors here identify an early-life enriched Wnt4⁺ stromal cells form a microbiota-regulated neonatal niche that drives iNKT expansion via BMP2-MAPK signaling and programs long term mucosal immune homeostasis.

Understanding the charge transfer at microbe–semiconductor interfaces in biohybrids is valuable for advancing solar-to-chemical conversion. Now, the reverse electron transfer in Shewanella–haematite hybrids is quantified using multimodal single-particle imaging, revealing facet-dependent efficiency.

Tree cover gains in the moist tropics (1982–2015) were 56% naturally regenerated forests and 27% managed tree systems, with forest type influencing carbon recovery. Effective forest restoration requires robust tracking of forest types established by restoration efforts.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Macrophages can sample antigens from living cells through a trogocytosis-like mechanism that routes ingested material away from degradation, a finding that delineates a previously unknown pathway for antigen presentation to CD8 T cells.

In this individual participant data meta-analysis, and across 321,345 smartphone-ratings of affective well-being and nearly 1 million hours of physical activity measurement, Rehder et al. clarify the nature and extent of activity–well-being relations and document their relevance in humans’ everyday life.

Here, authors demonstrate an ultrafast time-gating protocol using a sub-micron-thick layer of epsilon-near-zero indium-tin oxide, yielding a strong four-wave mixing signal while reducing scattering and scintillation.

Psychedelic-assisted therapy shows promise for psychiatric disorders, but therapeutic responses vary widely. Here a survey of therapists’ experience aimed to identify key predictors of successful outcomes, highlighting the importance of therapeutic alliance, social support, openness and active engagement, which could inform future screening and preparation practices to enhance therapeutic efficacy.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Genome-wide analyses identify genetic loci and plasma proteins associated with polycystic ovary syndrome (PCOS). This study highlights the hormonal and metabolic foundations of the disease and explores the impact of polygenic risk for PCOS in both sexes.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

A single-cell spatial atlas identifies a B cell-predominant microenvironment within the profibrotic tubular niche that marks a subset of patients with diabetic kidney disease with rapid progression.

How insects maintain precise vision during rapid motion remains unclear. Here, the authors show that motion-driven photoreceptor dynamics and synaptic high-frequency jumping enable hyperacute, minimal-delay visual encoding.

Prime assembly can initiate Gibson-like assembly in cells to generate gene insertions without double-stranded DNA breaks, recombinases or homology-directed repair.

By tuning graphene’s electronic density of states, the study shows electrode electronic structure—not just the electrolyte—dominates reorganization energy and thus controls outer-sphere electron-transfer rates at solid–liquid interfaces.

OBSCORE is a machine learning-based risk prediction tool that uses a set of clinical features to stratify individuals with a body mass index (BMI) of ≥ 27 kg m⁻² by their 10-year risk of obesity-related complications, outperforming existing models. OBSCORE is generalizable across diverse populations, supporting risk-based prioritization of obesity interventions that goes beyond simple BMI thresholds.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

This study reveals that the immune system has a role in driving ALS. These findings link blood immune changes to spinal cord damage and suggest personalized treatments targeting specific immune pathways.

This study is a small RNA genomics survey from global Aedes aegypti mosquito samples, and detected replicating viruses. This study then isolated several mosquito viruses into cell cultures to show that viral small RNA are active in gene silencing.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

mRNA vaccine efficacy is enhanced by silencing cell-type-specific expression.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Transmission of Plasmodium falciparum relies on the development of gametocytes, which undergo extensive cellular remodelling. Here, the authors demonstrate that the PfGID E3 ubiquitin ligase complex affects gametocyte development by regulating key proteins, producing defective cells that cannot infect mosquitoes.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

In this Resource paper, Krummel and colleagues provide analysis of 15 commonly used syngeneic mouse tumor models and compare these to the diversity of human tumor microenvironments.

Sulfation helps shape cartilage, bone and other biological functions. Here, the authors identify MESH1 as the 3′-phosphoadenosine-5′-phosphosulfate-degrading enzyme that controls sulfation in animals and show that blocking MESH1 restores sulfation-linked defects, revealing a potential therapeutic target.

Urea, the most widely used nitrogen fertilizer, has unknown impacts on freshwater ecosystems. This study demonstrates that urea additions in Canadian prairie agricultural reservoirs triple phytoplankton abundance without increasing cyanobacterial toxins, revealing considerable nitrogen loss to the atmosphere and highlighting potential global water quality degradation in phosphorus-rich agricultural regions.

The genetically encoded voltage indicators JEDI3sub and JEDI3hyp enhance monitoring of subthreshold neuronal activity in the awake mouse brain using a variety of two-photon microscopy techniques.

CRISPR screening shows that claudin-4 is a receptor for the pro-carcinogenic B. fragilis toxin on colonic epithelial cells, and that this interaction promotes cleavage of E-cadherin, leading to epithelial barrier disruption and inflammation.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Exfoliated flakes of van der Waals materials embedded in tailored electromagnetic environments can form intrinsic optical self-cavities, but the influence of this effect on their nonlinear optoelectronic properties at THz frequencies remains unexplored. Here, the authors report self-cavity-induced Purcell enhancement of directional edge photocurrents in WTe₂.

High-density single-neuron recordings in patients with epilepsy revealed interictal discharges are generated by structured laminar circuits. These circuits overlapped with cognitive circuits and could predict discharges up to 1 s in advance.

Methane is a potent greenhouse gas, but can also be used as a source for advanced carbon materials. This work shows a sustainable approach to produce high-value carbon fibres through methane pyrolysis.

Guan, Ocampo and colleagues report the discovery and mechanistic dissection of Al3Cas12f, a metagenome-derived miniature nuclease that retains notable genome-editing capacity. They engineer an RKK variant, which boosts editing and helps overcome the potency threshold that has limited compact editors.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Coherent exciton dynamics in antiferromagnetic CrSBr are studied by petahertz field-resolved spectroscopy, revealing how laser-imprinted exciton coherence persists beyond excitation and is modulated by spin and lattice modes.

Using electronic health records from over 140,000 children, the authors developed a neural network model that predicts attention deficit hyperactivity disorder diagnosis years before a typical clinical identification.

D’Ambrosio et al. screen 10,480 electrophilic compounds for senolytic effects and show that senolytic chloroacetamides or GPX4 inhibitors selectively kill senescent cells by ferroptosis.

Development of myeloid leukaemia in children with Down syndrome is a stepwise process. Here, the authors employ scRNA sequencing and phylogenetic analysis on patient samples from various disease stages to define the cellular and molecular features of this stepwise leukaemia development.

Single-variant and ultrarare variant burden analyses leveraging exome sequencing data from 22 cohorts identify new risk genes for amyotrophic lateral sclerosis and show cumulative effects of several rare variants on disease risk.

This paper identifies the ‘master regulators’ that maintain cell transcriptional states in diffuse midline gliomas and shows that targeting them in combination could represent a promising therapeutic avenue for the disease.

Over three decades, rapid expansion of the transposable element ISL3 has reshaped Enterococcus faecium, which helps to explain this pathogen’s growing clinical threat.

Beta-adrenergic signalling modulates histone variant H2A.Z deposition, chromatin accessibility and chromatin loop reorganization to regulate thermogenesis in mouse and human adipocytes.