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The underlying regulatory mechanisms of of human cortical diversity remains poorly understood. Here, authors profiled human brain cells to study how they use different gene programs across cortical regions, revealing molecular rules and specific transcription factors that drive functional specialization of neurons in the brain

In a large-scale prospective study run across 12 sites in Germany and involving 463,094 women and 119 radiologists, AI-supported screening increased breast cancer detection rates by a significant margin without affecting the recall rate.

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.

A WHO-supported pre−post study shows that implementation of the Y-Check comprehensive health check program is feasible and acceptable for adolescents in Zimbabwe, offering screening for 25 health conditions and behaviors, health promotion, on-site care and referral.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Hepatocyte-specific GPR110 mediates metabolic dysfunction-associated steatohepatitis progression by regulating hepatic oestrogen sensitivity in a sex-specific manner, specifically in female mice.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

The enzyme PCMT1 was found to install a C-terminal cyclic imide modification on proteins that marks them for degradation by CRBN, uncovering a conserved protein turnover pathway with implications in metabolism and neurological function.

Unprotected β-fluoroamines are important motifs in synthetic chemistry, offering versatility for the development of β-fluorinated nitrogen-containing compounds. Here, the authors disclose an iron-catalyzed three-component aminofluorination of alkenes using a hydroxylamine reagent and Et3N · 3HF, offering a direct entry to unprotected β-fluoroamines.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Understanding the dual role of neuraminidase and hemagglutinin antibodies in influenza transmission is crucial for enhancing vaccine efficacy. Here, the authors use household transmission studies and mathematical models and find that neuraminidase immunity reduces infectivity, suggesting vaccines targeting both glycoproteins could lower community transmission and offer broader protection.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

This study establishes the pig as a complementary model for studying human pancreas development. It shows pigs mimic human developmental tempo, gene regulation, and endocrine cell emergence, offering a valuable large-animal model for developmental biology.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

In this study, the authors investigate the association between price inflation and mental health service uptake in the United Kingdom, demonstrating that increasing costs of living exacerbate mental health needs, particularly among adults and older populations.

Experiments under upper-tropospheric conditions map the chemical formation of isoprene oxygenated organic molecules (important molecules for new particle formation) and reveal that relative radical ratios control their composition

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.

Optineurin is linked to ALS and glaucoma, but the mechanism is unknown. Here, the authors show that optineurin mutation causes deficits in axonal mitochondria transport and neurodegeneration, enhancing of which achieves axon protection and regeneration.

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.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Understanding how biosilica forms is crucial to our knowledge of this important biomaterial. Now, the role of collagen as structuring agent for the metre-long spicules of a primitive glass sponge has been revealed and found to have an unusual peptide motif.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Experiments performed in the CERN CLOUD chamber show that, under upper-tropospheric conditions, new atmospheric particle formation may be initiated by the reaction of hydroxyl radicals with isoprene emitted by rainforests.

Saber et al. show that the lipase DDHD2 provides endogenous saturated fatty acids to support fatty acid oxidation and energy production, proteostasis and membrane trafficking balance.

Water plays an essential role in enzyme catalysis, but direct observations linking enzyme catalysis and active-site water pose a significant challenge due to experimental difficulties. Here, the authors employ an ultraviolet photolysis technique with temperature-controlled X-ray crystallography to track the catalytic pathway of carbonic anhydrase II at 1.2 Å resolution.

This study reveals how distal DNA ‘switches’ control gene activity in human astrocytes. Using CRISPRi screens and single-cell RNA-seq, we map enhancer–gene links, highlight Alzheimer’s disease-related targets and introduce a model that predicts additional regulatory interactions.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Recent barcoding technologies allow the reconstruction of a cell’s lineage tree while capturing paired transcriptomic data. Here, the authors present a statistical method to automatically detect gene expression patterns related to lineage progression.

Using RFdiffusion, a general method for targeting intrinsically disordered proteins and regions for protein design has been developed.

The ubiquitin ligase, RNF168, promotes DNA break repair but must be regulated to prevent run-away ubiquitin signaling. Here, the authors identify a three-step post-translational cascade regulating RNF168 chromatin removal, acting to suppress excessive signaling and radiosensitivity.

The authors show that anxiety-like behavior in mice varies based on striatal D1/D2 receptor ratios. Elevated D1/D2 ratios enhanced alcohol relief, risk-avoidance, and persistent drinking, suggesting anxiety may predispose individuals to alcohol use disorder (AUD).

A study describes an approach using designed building blocks that are far more regular in geometry than natural proteins to construct modular multicomponent protein assemblies.

Pharmacotyping analyses of large cohorts of pediatric acute lymphoblastic leukemia identify correlations between drug sensitivities and clinical outcomes across different genomic subtypes.

How changes in brain blood vessels lead to a chronic reduction in blood flow and, consequently, to vascular dementia is poorly understood. Here, the authors show that venous endothelial dysfunction driven by EPAS1 promotes abnormal vascular remodeling and contributes to cognitive decline.

There are technical barriers to studying early virus-cell interactions with high temporal resolution. Here, using super-resolution microscopy and immobilized influenza A virions enabling live imaging the authors show nanoscale receptor accumulation, endocytosis induction, and actin remodeling.

The authors demonstrate ultra-broadband microscale optical dispersion in LiNbO₃ crystals, enabling precise and robust on-demand dispersion engineering in free space, with strong potential for applications in informatics and spectroscopy.

Tools to simultaneously trace multiple neuronal projections and/or profile projection neurons for multi-modal investigations are lacking. Here authors introduce Projection-TAGs, a retrograde AAV platform to enable multiplexed spatial neuroanatomical studies, high-throughput multi-modal (transcriptional, and epigenetic) profiling of projection neurons using various commercial assays.

Blanc et al. uncover how chronic inflammation triggers an epigenetic switch in aged muscle stem cells, leading to iron accumulation and cell death by ferroptosis—offering insights into muscle aging and potential paths for regenerative therapies.

The heart relies on fatty acid oxidation as its main energy source. Here they show that impaired fatty acid metabolism disrupts mitophagy in the heart and that enhancing mitophagy via USP30 inhibition can restore heart function in models of fatty acid oxidation deficiency.