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Efficacy of chimeric antigen receptor (CAR)-T in solid tumors are limited by the antigen heterogeneity and tumor microenvironment (TME) induced exhaustion. The authors here manifested that Nr2f6-deficient CAR-T cells have superior anti-tumor effect compared with traditional CAR-T cells, which is associated with enhanced cytotoxic function, followed by durable response due to epitope spreading.

Structural features of DNA double-strand break (DSB) ends play key roles in determining DNA repair pathway usage and outcomes. Here, the authors identify ERCC6L2, a poorly characterized ATPase, as playing a minimal role in blunt end DSB repair but crucial for repair of staggered end DSBs.

The mitochondrial pathway of apoptosis requires coordinated protein–lipid signals. Here, Gelles et al. show that a BAX lipid-binding cavity for 2-trans-hexadecenal cooperates with BIM to allosterically activate BAX prior to membrane insertion.

Paternal obesity impacts offspring health, though the underlying mechanisms remain poorly understood. Here, the authors show that male obesity drives adipose mitochondrial dysfunction in F₁ mouse progeny via a let-7-DICER axis, identifying a pathway for intergenerational metabolic inheritance

Here, the authors investigate the mechanism by which human aspartate/asparagine-β-hydroxylase (AspH), a 2OG-dependent oxygenase with an atypical Fe(II) coordination environment, catalyses hydroxylation of aspartate and asparagine residues in epidermal growth factor-like domains.

Ultrafast shaping of exciton-polariton condensates enables applications for classical and quantum logic devices and provides insights into the physics of nonequilibrium quantum condensates in solid-state. Here, the authors demonstrate ultrafast and reversible dynamic Stark modulation of a semiconductor exciton-polariton quantum condensate.

This study presents a process that upcycles mixed end-of-life vehicle scrap into aluminium alloys surpassing current automotive alloy performance. It operates without sorting or downcycling for circular, low-emission aluminium recovery.

Efficacy of transdermal testosterone gel in treatment for female infertility remained unknown. Authors conducted randomized clinical trial to show transdermal testosterone did not improve clinical pregnancy rates.

Cholera remains a significant public health burden in sub-Saharan Africa, but the mechanisms of continental and regional spread remain undefined. Here, the authors investigate recent patterns of spread using Vibrio cholerae genomic surveillance data collected by a consortium of seven African Union member states from 2019-2024.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

The Mouse Cancer Cell line Atlas (MCCA) provides major advances towards a mechanistic understanding of cancer genomes.

Symmetry-protected topological phases are conventionally considered to be protected by global symmetries. Here, the authors demonstrate that topological protections can persist even when symmetries are preserved only within a partial region of the system, which they term local support symmetries.

Neoantigen-based adoptive T cell therapies represent a personalized approach for cancer immunotherapy. Here the authors describe NEO-STIM, an ex vivo T cell induction platform to STIMulate peripheral blood T cells to generate responses against tumor NEOantigens.

This study shows that contrail avoidance can recover 9% of the global temperature budget by 2050. For every year of delay, the recoverable warming will diminish by 0.6%. This makes inaction (not fuel penalties) the most significant climate risk associated with avoidance.

Peroxidases have long been considered to use ferryl heme intermediates (Fe(IV) = O) to catalyze oxidative chemistries. Here, Williams et al. find that ferric-oxyl (Fe^III–O^•–) excited states exist along the catalytic reaction coordinate of a peroxidase.

A skeleton of the alvarezsauroid Alnashetri cerropoliciensis—representing a highly complete alvarezsauroid skeleton from South America—provides evidence on the evolution of the peculiar anatomy and miniaturization within this unusual theropod dinosaur clade.

Targeted ablation of prostaglandin E₂ (PGE₂) signalling in CAR T cells enhances their activity in PGE₂-rich solid tumours, with demonstrations of efficacy in vitro, in mouse xenografts and in patient-derived organotypic tumour spheroids.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Mouse models show that lymphoedema caused by impaired lymphatic drainage is ameliorated by removal of cholesterol deposits, which promotes the regeneration of lymphatic vessels.

The Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

The authors report a trial subset analysis of the immune responses induced by two inactivated quadrivalent influenza vaccines (QIVs): Sinovac QIV and Vaxigrip-Tetra™. Both vaccines elicit robust humoral responses and distinct T cell profiles.

Leonhard Schreiner and colleagues investigate how EEG electrode density shapes visual decoding performance, showing that denser arrays yield higher accuracy. Their findings delineate the practical limits of non-invasive EEG and offer guidance for selecting electrode count and spatial configuration

Care-oriented policies, which promote health while addressing its social determinants, are increasingly common in Latin America. Using ethnographic observation, interviews and focus groups, this study finds that Bogotá, Colombia’s, District Care System (SIDICU) provided women caregivers with access to public institutions as well as new social networks.

In a case series of five patients with treatment-refractory antisynthetase syndrome and five patients with treatment-refractory systemic sclerosis, bispecific T cell engagers blinatumomab and teclistamab improved disease activity and were well tolerated.

Lazarevic et al. reveal a shared loss of a TBX5-dependent atrial gene network in cardiomyocytes and a disease-specific network gain in activated fibroblasts across atrial fibrillation and heart failure models.

The study shows a micron-scale polariton structure where an artificial gauge field creates topological, non-reciprocal edge transport without strong magnetic fields, overcoming key limits for topological polariton lasers and devices.

Resistance noise in memristive devices is often described as a thermally activated process across simple energy barriers, but this can underestimate the role of entropy in a complex free energy landscape. Quantifying transition rates between discrete resistance states during resistance fluctuations in nanoscale GeTe shows that entropic contributions can strongly shape the free energy barriers.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

The study shows how ship traffic in the Baltic Sea modifies seafloor morphology and disrupts water layers, thereby increasing the mixing of oxygen, nutrients and greenhouse gases, suggesting broad impacts on Baltic marine ecosystems.

The complex seismicity at Campi Flegrei caldera can be reliably simulated and forecasted using a model that combines rate-and-state frictional response with epidemic-type aftershock sequence modeling.

The operational stability of perovskite solar cells remains a challenge. Zhang et al. incorporate photoswitchable isomers at grain boundaries to improve their resilience and the stability of the solar cells under light cycling and ultraviolet exposure.

Researchers used explainable AI to analyze pancreas tissue from living donors, revealing that changes in fat cell clusters, nerve structures, and islet proximity to fat cells distinguish people with type 2 diabetes from those without the condition.

Beneficial effects of fasting combined with endocrine therapy for oestrogen receptor-α-expressing breast cancers can be recapitulated using exogenous glucocorticoid receptor ligands instead of fasting to reduce harmful effects.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Our computational model shows that calcium diffusion between spines via dendrites drives heterosynaptic plasticity, providing new learning mechanisms based on timing and spine location.

An optical archival storage technology based on femtosecond laser direct writing in glass addresses the practical demands of archival storage.

Forests are essential for both climate change mitigation and biodiversity conservation, yet how to balance these goals in managed forests remains unclear. Here, using a Europe-wide dataset, the authors find that biodiversity increases with carbon stocks, but mostly when deadwood is included.

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.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

The contribution of ether lipid species in cancer cell fate has not been fully understood yet. Here the authors show that malignant cancer cells employ ether lipids to modulate membrane biophysical properties, enhancing iron endocytosis and ferroptosis susceptibility.

Experimental realizations of discrete time crystals have mainly involved 1D models with Ising-like couplings. Here, the authors realize a 2D discrete time crystal with anisotropic Heisenberg coupling on a quantum simulator based on superconducting qubits, uncovering a rich phase diagram.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Strong cadmium isotope fractionation in stromatolites from the Tumbiana Formation in Western Australia at ~2.72 represents the earliest evidence of carbonic anhydrase, according to cadmium isotope analysis to trace deep-time enzymatic activity and microbial metabolism.

Ovrlpy identifies overlapping cell signals in the vertical dimension of spatial transcriptomics data.

Quantum interference of sodium nanoparticles, which can each contain more than 7,000 atoms at masses greater than 170,000 Da, is demonstrated.

European regions with the highest life expectancy, located in central and northern Spain, northern Italy, and Switzerland, continue to push the boundaries of human longevity, suggesting that there is still room for further lifespan extension.

This study of magic-angle twisted trilayer graphene moiré superconductors using scanning tunnelling microscopy and spectroscopy identifies two energy gaps that develop from many-body resonance in this highly tunable class of materials.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.