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Small cell lung carcinoma (SCLC) neuroendocrine (NE) subtypes often transdifferentiate to the more aggressive non-NE cell state during disease progression. Here, the authors discover that eIF6 is a regulator of SCLC plasticity, driving non-NE transdifferentiation via regulation of the CD104/FAK complex.

Meningiomas are common brain tumors with variable behavior. This study reveals high STING expression across multiple cell types in the meningioma microenvironment. STING agonism triggers tumor cell death via programmed necrosis and pyroptosis, enhancing survival in preclinical models.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Scanning nitrogen-vacancy microscopy unveils super-moiré spin textures emerging in twisted double-bilayer CrI₃ and provides real-space evidence of antiferromagnetic Néel-type skyrmions spanning multiple moiré cells.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

This research identifies two neural factors linked to externalizing and internalizing symptoms through a longitudinal imaging-genetic cohort. Distinct neural configurations and cognitive-behavioral relevance highlight the need for tailored therapeutic strategies addressing psychiatric comorbidity across developmental stages.

Multi-omics and genetic models show that CGG repeat toxicity in GABAergic neurons drives FXTAS pathology and identify PRKCG as a critical modifier and potential therapeutic target.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis involving evasion of immune control. Here, the authors perform a comprehensive analysis of single-cell multi-omic data revealing either a myeloid-enriched or adaptive-enriched tumour microenvironment, linked to distinct B and T cell clonal selection and differentiation, distinct overall survival, and potential therapeutic approaches.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

The Evaluation and Enhancement (EVEN) method optimizes automatically the quality of multichannel microscopy images affected by uneven illumination, enabling accurate visual interpretation and image analysis in challenging imaging scenarios.

WIN332 is an HIV-1 Env protein designed to elicit a new class of Asn332-glycan-independent antibodies (type II) to the V3-glycan site of Env. WIN332 immunization rapidly induces type-II V3-glycan antibodies with low inhibitory activity indicative of a neutralization activity in macaques.

Standard approaches for identifying pleiotropic genetic variants may lead to spurious results. Here the authors present a new statistical method and show that it uncovers five genes linked to metabolites in METSIM participants, which were previously undetected by existing methods.

SpatialZ generates virtual single-cell spatial transcriptomics slices between experimentally measured sections, enabling accurate and efficient building of 3D cell atlases of different tissues.

Iniquitate quantifies the effects of cell type imbalance on single-cell RNA sequencing data integration.

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.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Placental inflammation is sometimes associated with health outcomes later in life. Here, the authors find that expression of genes associated with the homeostatic function of Hofbauer cells, a placenta-specific macrophage, are associated with protection from adult cardiovascular and depressive disorders

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Engineered, bifunctional receptors present antigens and initiate signaling in response to binding to the cognate T cell receptor. Libraries built with SABRs can screen thousands of epitopes for the discovery of T cell target antigens.

The impact of placental transcriptomics on fetal traits throughout development is not well understood. Here, the authors apply distal-SNP-enriched transcriptome-wide association studies to detect genetic contributions, mediated through fetal placental genomics, to developmental programming of complex traits across the life course.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Intracellular redox state orchestrates a self-reinforcing circuit connecting hypoxia inducible factor 1α-dependent signalling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1 to govern intestinal stem cell fate.

Charge transport and extraction in polycrystalline perovskite films are often hindered by inefficient carrier transfer across grain domain boundaries (GDBs). Here, authors employ supramolecular assisted Rb+ delivery for in-situ GDB bridging, achieving efficiency of 26.02% for perovskite solar cells.

The origin and dispersal of the chicken across Eurasia is unclear. Here, the authors examine eggshell fragments from southern Central Asia with paleoproteomics to identify chicken eggshells, suggesting that chickens may have been an important dietary component as early as 400BCE.

GRB2 is known for its role in Receptor Tyrosine Kinase and RAS signaling. Here the authors unveil a GRB2 function and mechanism for DNA replication fork protection. GRB2 alleviates oncogenic replication stress, and in doing so, averts cancer immune destruction by inhibiting cGAS/STING and pro-inflammatory cytokine production.

Peng and colleagues present SpatialTopic, a scalable computational method that decodes spatial tissue structure from large-scale multiplexed images, thereby enabling rapid, integrative analysis of millions of cells across multiple tissue slides.

Urban populations ebb and flow as the pulse of human mobility reshapes the cityscape. This paper shows a spatiotemporal scaling laws revealing hidden patterns in these dynamic shifts, linking them to the urban fabric’s structure, density, and functionality.

Cells can sense mitochondrial damage through signalling via an unimported mitochondrial targeting sequence.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Here, the authors find that relative abundances of stress-sensitive gastrointestinal microbes at age 2 years predicts internalizing symptoms in middle childhood through altered emotion-related brain network connectivity.

Genomic deletions in poxviruses are not well understood, the authors found large deletions in >2% of Mpox virus genomes during routine surveillance, highlighting their role in poxvirus evolution and potential impact on diagnostics and therapeutics.

Oat is an important food crop, but the genetic diversity within the gene pool remains unclear. Here, the authors report the analyses of worldwide diversity and population structure of hexaploid oat, and identify signatures of structural rearrangements within the germplasm collection.

A multi-omic analysis of pancreatic cancer identifies spatially resolved, heterogeneous cell populations including transitional cell types. Analysis of primary samples identifies treatment-related changes in cross-talk between tumor and stromal cells.

A super-pangenome analysis incorporating 123 newly sequenced bryophyte genomes reveals that bryophytes exhibit a larger number of unique and lineage-specific gene families than vascular plants.

Using a near-field transducer with efficient optical energy transfer, researchers demonstrate proof-of-principle heat-assisted magnetic recording with multi-track data density of ∼375 Tb m⁻².

Zeolites are industrially important materials, functioning as separation media and catalyst supports. Here, the authors use a large-scale, multi-step computational screening process to identify promising zeolites for challenging separations, namely ethanol purification and alkane adsorption.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

The primary entry route of vanilloid ligands to the vanilloid-binding site in transient receptor potential vanilloid 1 (TRPV1) is found to be a distinct and targetable hydrophobic pathway at the TRPV1–cell membrane interface rather than through direct membrane penetration.

The authors develop a supervised and unsupervised learning algorithm Signature. Machine learning and network model analysis of Hi-C datasets across 62 2n genomes suggest that inter-chromosomal contacts demarcate genome topology along a spatial gradient of genome activity.

Bacteroides strains have multiple operons for biosynthesis of diverse capsular polysaccharides, but most cells express only one operon at a time due to tight regulation of transcription elongation by locus-specific UpxY and UpxZ proteins. Here, Saba et al. provide insight into the mechanisms by which UpxY distinguishes among cognate operons and how UpxZ inhibits only noncognate UpxY proteins.