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Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

The replication stress response ensures genomic stability throughout DNA duplication. Here, the authors show that VCP/p97 extracts the DNA polymerase α/Primase complex from chromatin, preventing excessive priming in the lagging strand and reducing the activation of the replication stress response.

Genomic analyses of DNA from modern individuals show that, about 800 years ago, pre-European contact occurred between Polynesian individuals and Native American individuals from near present-day Colombia, while remote Pacific islands were still being settled.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

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.

Down syndrome causes extensive Alzheimer’s disease pathology in all individuals and has been instrumental in development of the amyloid hypothesis in AD. Here, the authors use proteomics on Down syndrome spinal fluid and brain tissues to illustrate the common and unique changes in DSAD compared to other genetic forms of AD and the more common late-onset form of the disease.

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).

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Single-cell analysis of patient brains and cortical organoids links disrupted developmental metabolic reprogramming to postnatal synaptic dysfunction in dup15q syndrome, revealing shared neuronal changes with idiopathic autism.

During tuberculosis infection there is formation of a TB containing lesion within the lungs. Here the authors characterise the cellular and molecular features of human TB lesions and demonstrate associations with clinical severity and treatment efficacy.

A Homo aff. erectus individual dated to 1.4 million to 1.1 million years ago found at Sima del Elefante (Sierra de Atapuerca, Spain) does not display the modern-human-like aspect of Homo antecessor found at the neighbouring Gran Dolina site (900,000–800,000 years ago).

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.

As presented at the 2025 ASCO Annual Meeting: in cohort 3 of the phase 2 TUXEDO-3 trial, patients with leptomeningeal metastatic disease from any solid tumor were treated with the HER3-targeting antibody–drug conjugate patritumab deruxtecan and showed encouraging 3-month overall survival rates.

Analysis of 20 chemical and morphological plant traits at diverse sites across 6 continents shows that the transition from semi-arid to arid zones is associated with an unexpected 88% increase in trait diversity.

Basidiomycete fungi typically have two mating-type loci located on different chromosomes. Here, Lucotte et al. report the convergent loss-of-function of mating-type genes across several species of phytopathogenic fungi of the genus Microbotryum.

JWST and Keck II spectral observations of Saturn’s moon Titan reveal methyl (CH₃) as well as non-local thermodynamic equilibrium emission bands of CO and CO₂. Imaging shows clouds in Titan’s northern hemisphere at several epochs, with some appearing to evolve in altitude.

A single-arm phase 2 trial in patients with mostly PD-L1-negative advanced triple-negative breast cancer shows that treatment with the anti-PD-L1 agent atezolizumab, paclitaxel and the anti-VEGF agent bevacizumab prolongs progression-free survival.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Public untargeted metabolomics data hold great promise for discovery but are difficult to access across repositories. Here, the authors develop universal identifiers and harmonized metadata to integrate major databases, enabling streamlined analysis and expanded research possibilities.

In vivo gene delivery to haematopoietic stem and progenitor cells in newborn mice using engineered lentiviral vectors shows promise as an effective treatment for genetic diseases.

The endoplasmic reticulum (ER) has a central role in mounting effective and durable antitumour immunity. In this Review, Hwang et al. outline how tumour-induced ER stress responses alter the function of intratumoural immune cells and the efficacy of immunotherapy, highlighting the potential of unfolded protein response-targeted interventions to improve cancer outcomes.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Genetic and Structural analysis of COVID patients cohort reveals a correlation between mitochondrial haplogroup and SARS-CoV-2 severity.

The IL-1β pathway is upregulated in patients with myelodysplastic syndromes (MDS). Here the authors report the results of a phase 2 clinical trial of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS.

Protection afforded by inorganic minerals is assumed to make mineral-associated organic carbon less susceptible to loss under climate change than particulate organic carbon. However, a global study of soil organic carbon from drylands suggests that this is not the case.