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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.

Whether dopaminergic modulation of synaptic transmission can vary by the anatomical location of striatopallidal synapses in the GPe (external globus pallidus) is not fully understood. Here authors demonstrate that dopamine fine-tunes striatopallidal synaptic transmission by acting on presynaptic D2 and postsynaptic D4 receptors across subregions of the GPe. In addition, dopamine depletion reshapes this modulation in the opposite direction.

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.

Germ cell tumours are a complex and heterogenous type of tumour which are difficult to classify using biomarkers. Here, the authors use PhIP-seq to develop an immunosignature panel for classification.

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.

This study identifies an FDA-approved leukemia drug, Homoharringtonine, that can eliminate aged fat cells, improve metabolic health, reduce inflammation and extend lifespan in mice, revealing a potential approach to treat age- and obesity-related metabolic disease.

Divergent white matter metabolic patterns reveal a mechanistic basis for cognitive resilience and enhance prediction of future cognitive decline beyond established aging and dementia biomarkers.

N-desethyl-fluornitrazene is a µ-opioid receptor agonist derived from nitazenes that has supramaximal intrinsic efficacy that produces analgesia with minimal adverse effects in rodent models.

A study of reproducibility in a stratified random sample of 600 papers published from 2009 to 2018 in 62 journals spanning the social and behavioural sciences finds higher reproducibility among more recent papers and papers from journals that require data sharing.

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

Cryo-electron microscopy structures of three large ornate natural bacterial RNA molecules reveal their quaternary structures and intra- and intermolecular interactions that stabilize them.

Elucidating the dynamics of non-equilibrium orders remains a challenge. Here, the authors show that time-varying electrostatic interactions drive confined alginate hydrogels to self-organize into tunable, hexagonally ordered lattices.

Melanocytic nevi are small, pigmented benign skin tumours. This large-scale genome-wide association study for nevus count identifies novel genomic regions, highlighting pathways beyond pigmentation and offers new insights into melanoma risk and biology.

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.

Acute-on-chronic liver failure is a complex condition with varied definitions. Using unbiased clustering, the study identifies two distinct subtypes with markedly different 30-day mortality risks and highlights key determinants.

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.

An improved strategy for siting food and energy production is needed to avoid further habitat loss. This paper presents a multi-sector framework that can empower land use planners to find synergies across conservation and development sectors.

In the nonpivotal stage 1 of the randomized phase 3 PRESERVE-003 trial, patients with immunochemotherapy-resistant metastatic squamous non-small cell lung cancer without actionable genomic alterations treated with the next-generation, pH-sensitive anti-CTLA-4 agent gotistobart had encouraging overall survival outcomes compared to docetaxel.

Linker histone proteins (H1) play a key role in chromatin regulation, but their behavior in crowded nucleosome environments is poorly understood. Here, the authors show that different H1 variants bind and connect multiple nucleosomes in diverse ways, supporting dynamic chromatin organization.

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.

3D seismic image reveals inward dipping volcano stratigraphy down to magma reservoir at Axial volcano, SE Pacific, caused by emptying of magma reservoir. It also shows injected melt sills within the stratigraphy, indicating that the upper crust is formed by melt sill lava flow interaction.

Over five years, implementation of the NHS England Lung Cancer Screening Programme achieved high early-stage detection rates and demonstrated that the programme is both feasible and scalable for reaching high-risk and underserved populations.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

Genome-wide analysis coupled with long-read sequencing identifies a repeat expansion in GOLGA8A associated with high risk for atypical frontotemporal lobar degeneration with ubiquitin-positive inclusions.

Precision oncology requires access to high quality data, as well as the application of current technologies. Here, the authors use federated learning to predict clinical outcomes in anal cancer patients across 16 centres as part of the atomCAT consortium.

It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

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.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Age-related microbiome changes increase medium-chain fatty acid-producing bacteria, driving GPR84-mediated myeloid inflammation, impaired vagal signalling and hippocampal dysfunction; targeting this gut–brain pathway restores memory in aged mice.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

The authors from the ALICE collaboration identify multiple species of mesons and baryons and measure the anisotropic flow with non-flow removal techniques in pp and p-Pb collisions at the LHC, identifying the hallmark of quark flow associated with an expanding quark-gluon plasma.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

Nickel-rich layered oxide cathodes suffer from chemomechanical degradation, and current mitigation methods require complex syntheses. Here the researchers show that simple control of LiOH melting produces uniform microstructures that stabilize the cathodes without doping or coatings.

A national classification system of wetland hydrologic connectivity to streams, which could be applied globally, demonstrates and advances current understanding of how wetland connectivity affects surface water quality.

INSTALL overcomes fundamental challenges for DNA delivery and integration methods by synergizing immune-stealth nucleic acids with recombinases to enable kilobase-scale integration strategies without viral vectors.

Natural Killer cells are key mediators of anti-tumour immunosurveillance and anti-viral immunity. Here, the authors map regulatory genetic variation in primary Natural Killer cells, providing new insights into their role in human health and disease.

The rapid evolution of SARS-CoV-2 challenges antibody therapeutics, but glycan-masked antigens enable isolation of class 3 monoclonal antibodies that potently neutralize diverse Omicron variants and reveal cross-reactive epitopes.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Germline and somatic interactions define actionable genomic patterns driving acquired therapy resistance in breast cancer.

This study shows that the Cantor alloy (CoCrFeNiMn), inert to hydrogen at room temperature, forms a stoichiometric hydride under high-pressure, high-temperature conditions, supported by X-ray, neutron diffraction, and ab initio calculations.

A monolithic cryptographic sensor, which integrates a sensor device with a hashing unit and a cryptographic signature unit, can be used to create a recording system that provides a cryptographic link between a physical process and an immutable digital entity.

Traditional quiz scores provide limited insight into what students know. Here, the authors show that text embedding models combined with short multiple-choice quizzes yield detailed maps of conceptual knowledge and learning.

Critical life-history traits, like growth and body size, can influence species’ survival. Using more than 7500 observations, this study suggests that the growth performance of marine fish has declined by 9% over the past century as a result of commercial size-based harvesting.

Here the authors report that intestinal interleukin-22 promotes GLP-1 production through STAT3 signaling in male mice. This mechanism improves glucose regulation in diet-induced obesity and provides insight into the role of IL-22–GLP-1 signaling in metabolic regulation.