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Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.

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.

Human immunodeficiency virus (HIV)-associated gut microbiome dysbiosis correlates with systemic immunodeficiency and opportunistic gut infections. Faecal microbiome transplantation from people living with HIV with high peripheral CD4⁺ T cell counts improved intestinal immunity and protection against Cryptosporidium parvum in mice.

Pancreatic ductal carcinoma is often diagnosed at a late stage due to challenges in detection. Here, the authors develop a serum metabolomics-based algorithm, which outperforms existing detection methods.

When used as intended, an AI stethoscope enhanced the detection of cardiovascular disease — but low uptake and workflow challenges hampered effectiveness in a large pragmatic trial.

Bacteria use diverse defence systems against phages, including a 164-residue prophage-encoded protein, Rip1, which senses conserved phage assembly rings to form membrane pores that block virion maturation and trigger premature host cell death.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Sheep producers face growing expectations to produce more food, conserve biodiversity, stay profitable and cut emissions. The authors find that interventions work best when addressing underperforming environmental, economic, or psychological areas.

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).

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Mislocalized and aggregated TDP-43 drives neurodegeneration in several diseases. The current work shows that RAD23A contributes to TDP-43 toxicity by driving pathological re-distribution of key proteins into an insoluble fraction of cells and thereby leading to loss of function phenotypes.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

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.

This study finds that plastic mulch substantially increases crop yields but also contaminates soils and pollutes the environment. The authors propose biodegradable films, AI-driven farming, and policy reforms to address the productivity–sustainability trade-offs.

Baird et al. present the phase 2 PIONEER trial findings on the antitumor activity of combining aromatase inhibitor letrozole with megestrol in postmenopausal women with operable estrogen-receptor-positive human epidermal-growth-factor-receptor-2-negative breast cancer.

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.

The therapeutic relevance of telomere maintenance mechanisms in cancer, remains to be explored. Here, the authors integrate multi-omic data and functional readouts, generate a resource of telomere biology metrics and identify potential molecular vulnerabilities.

Inconsistent diagnostic criteria and treatment approaches may hinder medical care and research for lipedema. Here the authors report a multi-phase Delphi study proposing consensus-based definition and management of lipedema.

Aneuploidy impacts differentiation and threatens the safety of stem cell therapies. Here, the authors show that mosaic aneuploidies are eliminated during RPE differentiation, except 1q gain, which is rescued by co-culture through paracrine signals.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

Using operando synchrotron X-ray imaging, the study reveals 3D morphological and chemical changes of thermochemical particles during redox cycles, uncovering degradation mechanisms and insights for improved thermal energy materials.

Early results from the phase 2b VIBRANT-HD trial of the oral splicing modulator branaplam in Huntington’s disease suggested reduced cerebrospinal fluid huntingtin levels, but safety monitoring revealed signs of peripheral neurotoxicity, prompting early termination of the study.

The textile industry’s reliance on synthetic dyes is an important source of greenhouse gas emissions. Here the authors describe a process involving sustainable solvents that allows the extraction, purification, and reuse of dyes, as well as the recycling of dye-free fabrics.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

Here, the authors perform metagenomic analysis of Ecuadorian mothers and children showing that improved WASH and reduced animal exposure can lower antimicrobial resistance in the gut but may reduce gut microbial diversity, with the strongest effects observed in mothers.

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.

In a year that has dealt many blows to biomedical research, many breakthroughs nevertheless continued to inspire us. From regenerative medicine to reproductive technologies and everything in between — here is our selection of critical developments that moved medicine forward in 2025.

A single ultrashort pulse from X-ray free-electron laser is shown to produce a submicron, with >1,000 length-to-diameter aspect ratio long channel in solid material. The results open a new avenue for development of artificial nanofluidic devices with confinement down to the molecular level.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Liquid biopsy methods have mainly been focused on the use of peripheral blood, and comparison between body fluids has been limited. Here, the authors utilize samples from a rapid tissue donation program to compare body fluid sites in their representativeness of the metastatic disease in patients with breast cancer.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Antibody drug conjugate (ADC) target expression beyond the traditional targets is poorly studied in metastatic cancer. Here, the authors analyse the expression of known and potential new ADC targets in normal and multi-organ metastatic samples of a post-mortem tissue donation program from patients with metastatic breast cancer.

The origin and dispersal of Homo erectus, a long-lived and geographically widespread human ancestor, are unclear despite a rich fossil record. Here, the authors reconstruct the face from a Homo erectus cranium from Gona, Ethiopia, dated to 1.5-1.6 million years ago, providing insights into the evolutionary transition from early Homo to H. erectus.

Young individuals with a history of self-harm exhibit heightened electrodermal activity in response to neutral and stress-related stimuli, extending our understanding of the biophysiological factors for self-harm vulnerability.

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.