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A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Talin is a well-known regulator of cell adhesion and intracellular force transmission in animals. Here, the authors demonstrate that talin’s mechanical function is evolutionarily conserved and already established in unicellular eukaryotes.

Risk stratification in non-small cell lung cancer (NSCLC) remains challenging. By combining multiplex immunofluorescence, H&E histology, and AI, the study identifies spatial “cell-niche” patterns that enhance survival prediction beyond UICC8 staging. These patterns reclassify many stage I patients as high risk, revealing potentially undertreated cases and establishing spatial tumor microenvironment features as clinically actionable biomarkers.

Eusociality evolved independently in Hymenoptera and in termites. Here, the authors sequence genomes of the German cockroach and a drywood termite and provide insights into the evolutionary signatures of termite eusociality.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Among many populations of blood cells, high dimensional analysis using mass cytometry reveals classical monocyte frequency as strong predictors of response to PD-1 blockade therapy of melanoma.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

Here, the authors show that MacroD1 is important for mitochondrial integrity and function. Lack of MacroD1 resulted in impaired cellular respiration which was particularly detrimental for cells and organs with high energetic requirements, such as skeletal muscle.

A mode of bidirectional microglia–neuron crosstalk through Hex–GM2–MGL2 and centred around GM2 ganglioside turnover is essential for homeostatic regulation of central nervous system membrane components.

53BP1 is marker of double-strand breaks and accumulates in nuclear foci. These foci are shown to accumulate in G1 at lesions generated by replication stress and may shield lesions from erosion.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.

Design strategies that possess both biological relevance and structural diversity may lead to compound collections that are enriched in diverse bioactivities. Now a diverse pseudo-natural product design principle has been established to efficiently explore biologically relevant chemical space. Through dearomatization reactions, a compound collection enriched in both structural and biological diversity was rapidly generated.

Platten and colleagues find that tryptophan metabolism by myeloid cells contributes to immunosuppressive microenvironment uniquely in IDH-mutant gliomas, which can be overcome by inhibiting this pathway in murine tumor models.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Genetic variation is key to species evolution. Here the authors sequence two phenotypically distinct populations of the ant Cardiocondyla obscurior, and find accumulations of transposable elements correlating with genetic variation that may have a role in differentiation, adaptation and speciation.

Muscle cells express an adhesion molecule called metavinculin, which has been associated with cardiomyopathies. Here, the authors employed molecular tension sensors to reveal that metavinculin expression modulates cell adhesion mechanics and they develop a mouse model to demonstrate that the presence of metavinculin is not as critical for heart muscle function as previously thought.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

Carbon sequestration in soils has rarely been observed at microscopic scales. Here the authors reveal the impact of soil moisture regimes in shaping carbon stabilization and mineralization patterns tied to the pore network.

Relapsed/refractory multiple myeloma (RRMM) is characterized by a remarkable heterogeneity and high drug resistance. Here, the authors analyse RRMM samples by single-cell RNA-sequencing, revealing molecular features associated with high-risk chromosomal 1q-gain and changes in the tumor microenvironment.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Dishevelled (DVL) is the key component of Wnt signaling pathway that acts as a signaling hub. Here, authors study the conformational dynamics of DVL3 in vivo using their engineered FlAsH-based FRET biosensors and describe how Wnt activation opens DVL and facilitates Frizzled recruitment.

Gliotoxin (GT), produced by the pulmonary pathogen A. fumigatus, induces detachment-induced apoptosis (anoikis) of lung epithelial cells and likely promotes invasion. Here, the authors show that GT covalently modifies integrins at the RGD binding site followed by activation of RhoA-ROCK-MKK4/7-JNK signalling leading to Bim-mediated anoikis.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

A FRET-based biosensor reveals a conformational change in the actin-binding domain of α-catenin during the maturation of epithelial adherens junctions.

Lehtiö and colleagues perform proteogenomic analysis of non-small cell lung cancer and identify molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets and validate their classification method in separate clinical cohorts.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

In the Arctic cryosphere, phytoplankton communities changed abruptly with variable sea ice cover and glacial ice loss in the last 14,000 years, according to organic geochemical biomarkers’ data from a sediment core in Svalbard.

In a phase I trial, highly individualized peptide vaccines against unmutated tumour antigens and neoepitopes elicited sustained responses in CD8⁺ and CD4⁺ T cells, respectively, in patients with newly diagnosed glioblastoma.

Ammar Al-Chalabi, Jan Veldink and colleagues perform a genome-wide association study for amyotrophic lateral sclerosis (ALS) in 15,156 cases and 26,242 controls. They identify three new genome-wide-significant variants and establish ALS as a complex trait with a polygenic architecture, but with a distinct and important role for low-frequency variants.

Residues of pesticides currently used in apple orchards were detected in soils and vegetation throughout the valley even at remote high-alpine ecosystems and conservation areas, according to a terrestrial landscape-scale field campaign in the European Alps.

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.