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Here proteomic chromatome analysis shows metabolic enzymes widely localize to chromatin in cancer in a tissue-specific manner. Nuclear enzymes affect DNA damage/repair and transcription, revealing non-canonical nuclear metabolic roles in cancer.

The authors performed computational and experimental analyses to reveal how Smoothened directly inhibits PKA through an intrinsically disordered region, defining a central step in Hedgehog signaling and a mechanism of G-protein-coupled receptor–kinase regulation.

This study develops a platform that enables simultaneous, multiplexed tracing of 30 nitrogen isotope-labelled metabolites, uncovering differences in pyrimidine synthesis pathway choice between primitive and differentiated cells.

Analysis of 128 high-coverage Indigenous American genomes shows extensive diversity shaped by several South American dispersals, ancient Australasian admixture, archaic introgression and long-term adaptation, indicating a far more complex evolutionary history than 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.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

Dutta et al. demonstrate that the tumor suppressor complex BRCA1–BARD1 physically interacts with the RNA–DNA helicase Senataxin (SETX) and upregulates the activity of SETX to resolve harmful R-loops crucial for the avoidance of transcription–replication conflicts.

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.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Mapping DNA variants that modulate mortality using a starting population of 6,438 young mice defined 29 distinct loci that influence lifespan and mortality with divergent age- and sex-specific effects, as well as 30 loci that specifically couple body mass with longevity.

A single-cell multiomic atlas of the human maternal–fetal interface across pregnancy reveals cell types, states and spatial niches, developmental tissue architectures and transcriptional programmes, and identifies cell types with roles in pre-eclampsia, spontaneous preterm birth and miscarriage.

Genomic deletions upstream of PITX2 are strongly associated with atrial fibrillation, the most common cardiac arrhythmia. Here, the authors report that ectopic PITX2 expression dosage-dependently disrupts pacemaker cell state and function, and atrial rhythm, linking chromatin conformation of the PITX2 locus to both sinus node dysfunction and atrial fibrillation.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

N-acetyltransferase 10 (NAT10) is an N⁴‐acetylcytidine (ac⁴C) writer, which catalyzes RNA acetylation at cytidine N⁴ position on RNAs. Here, the authors show that NAT10 catalyzes ac⁴C addition to a long non-coding RNA encoded by the oncogenic DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency, which promotes NAT10 recruitment of IFI16 mRNA, resulting in inflammasome activation.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

The mechanisms driving reversible dedifferentiation events towards a drug-tolerant persister (DTP) state remain to be explored. Here, multi-omics, information-theoretic approaches and dynamic systems modelling highlight the role of the oxidative-stress–mediated NF-κB/RelA axis in driving the transition towards DTP across multiple cancer types.

This study found COVID-19 vaccination offers added protection against reinfection in children and adolescents with prior infection but variable effectiveness across variants. Findings support vaccination benefits beyond infection-acquired immunity.

Barone et al. identify a fetal-restricted wave of hematopoietic progenitors that emerge from the hemogenic endothelium before hematopoietic stem cells and substantially contribute to embryonic lympho-myelopoiesis.

Leigh syndrome is a severe, currently untreatable mitochondrial neurological disorder. Menacho, Okawa et al. developed a deep-learning drug screening pipeline in brain organoids, identifying azole compounds as promising therapeutic candidates.

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.

Young, cognitively normal APOE4 mice display hippocampal network hyperactivity that predicts later memory decline. This phenotype is driven by neuronal APOE4 expression, which causes hyperexcitability of hippocampal neurons and can be reversed by targeting Nell2.

An autonomous robot system, Ace, combines event-based vision and reinforcement learning to compete with elite human table tennis players, highlighting the potential of physical AI agents to perform complex, real-time interactive tasks.

Higher-order interactions are shown to contribute to the decrease in species diversity from low to high latitudes in global forests, potentially explaining why this intricate phenomenon cannot be adequately explained by pairwise interactions alone.

Nasopharyngeal carcinoma (NPC) screening in southern China uses EBV serology, but its positive predictive value is low. Here, the authors introduce a swab-based E-CpMQ method in high-risk individuals, achieving better specificity.

Sunlight and iron scarcity can limit ocean algae that fuel marine food webs. This study defines iron- and light-responsive physiology, transcripts, and proteins in the abundant pelagophyte Pelagomonas calceolate and validates these responses using metatranscriptomes.

Seismic tremors can be used to distinguish plate boundaries. Analysis of tremors occurring deep beneath the San Andreas Fault may identify the boundary between the North American Plate and the preserved remnant of a subducted slab.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Spinster homolog 2 (SPNS2) exports sphingosine-1- 26 phosphate (S1P) out of cells. Here, the authors show that SPNS2 has antiporter-like activity, exporting S1P while importing glucose, revealing a mechanism linking SPNS2 to glucose homeostasis with clinical implications.

Here, by integrating host gene expression and airway microbiome data, the authors distinguish true lower respiratory infection from incidental pathogen carriage, and identify biologically distinct patterns that improve diagnostic precision beyond pathogen detection alone

The two species of African elephants are facing severe declines. Here, authors assess their continent-wide genomic diversity, identifying differences in their evolutionary histories and highlighting the formative role of gene flow.

Lim et al. identify CD34 as a surface marker of the heart’s sinoatrial node pacemaker cells, enabling their isolation from stem cell differentiation cultures, advancing future disease modeling, drug discovery, and biological pacemaker applications.

Response to next-generation selective oestrogen receptor-α (ERα) antagonist/degraders (SERDs) in ER+ breast cancer patients can be promising, but responses in advanced, pre-treated disease are heterogenous. Here, using samples from breast cancer patients pre-and post-SERD treatment, the authors identify loss of luminal lineage and subsequent ERα independence as a driver of SERD resistance.

Wan et al. develop a deep loop profiling to uncover how sequence diversity in the complementarity-determining regions of single-domain antibodies shapes folding fitness, thereby enabling the design of more robust synthetic antibody libraries.

Most bacteria use a flagellum, to swim and disseminate in their environment, and it is essential for virulence. In Vibrio, the flagellum is surrounded by a sheath, a membrane-like shield that protects the bacterium from the host’s immune system. Here, authors have obtained a view of the sheathed flagellum to atomic levels, revealing the molecular details of how the flagellum rotates within the sheath.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

The Scalesia plant radiation displays striking leaf-shape variation within Galápagos microclimates. Genome-wide analyses shows that lobed leaves evolved repeatedly through diversifying selection on diverse developmental regulators.

Gene editing technologies enable precise DNA modifications but remain limited by efficiency, precision of intended edits, and flexibility. Here, authors develop chimeric oligonucleotide-directed and Cas polymerase-based systems that enhance programmable gene correction across cells and embryos.

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

A Hemostatic Tough Adhesive (HTA) is developed and evaluated, achieving hemostasis in both liver and spleen injuries within an in vivo preclinical porcine model.

The study identifies novel genetic variants linked to core cerebrospinal fluid Alzheimer’s Disease biomarkers using a genome-wide analysis, showing how endophenotypes can identify genes and disease mechanisms not captured by case-control studies.

Genomic analyses of DNA from modern individuals show that, about 800 years ago, pre-European contact occurred between Polynesian individuals and Native American individuals from near present-day Colombia, while remote Pacific islands were still being settled.

The foreign body response involves immune cell activation and fibrosis, understanding the connection of the two is important for the biomedical engineering field. Here the authors show in a mouse biomaterial implant model that γδ T cell interactions with stromal cells shape fibrosis with differential involvement of type-1 and type-17 effector γδ T cell subsets in the acute and chronic phases of the response.

Stable and cell-specific transgene expression can be achieved through in vivo site-specific integration of large DNA payloads using a two-vector system of enveloped delivery vehicles and adeno-associated viruses.

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.