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Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Confocal microscopy enables high-resolution, high-plex 3D cyclic immunofluorescence of 30- to 50-µm-thick tissue sections. The approach allows for rich phenotypic assessments of intact cells and intercellular interactions with subcellular resolution.

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.

Some 3 million years ago, during the mid-Pliocene Warm Period, which was characterised by an atmospheric carbon dioxide content similar to modern levels, Greenland experienced ice growth intervals paced by a 41,000-year astronomical cycle.

Four researchers — Nicolas Bonne, Cheryl Fogle-Hatch, Garry Foran and Enrique Perez Montero — discuss the accessibility challenges in astronomy research, education and outreach for persons who are blind or visually impaired. Solutions to these challenges create innovative data analysis methods for all astronomers.

Rainbow trout with depleted secretory IgM reveal interesting insights into the elusive role of this immunoglobulin in maintaining gut microbiota.

A multicenter randomized controlled trial found that incorporating time-restricted eating, regardless of the timing of the eating window, into usual care—combining a Mediterranean diet with a nutritional education program—did not reduce visceral adipose tissue compared with usual care alone in adults with overweight or obesity.

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).

A CasRx-based screening platform for genome-scale long noncoding RNA transcriptome perturbation is described.

ACVR1 and H3.1K27M mutations co-occur in diffuse intrinsic pontine glioma. Here, the authors generate a mouse model that recapitulates these genetic lesions and show, using genetic and pharmacological approaches, that the bone morphogenetic protein pathway may be a therapeutic target in these tumours.

Analysing >1,700 inventory plots from the Amazon Tree Diversity Network, the authors show that the majority of Amazon tree species can occupy floodplains and that patterns of species turnover are closely linked to regional flood patterns.

Pulsed laser deposition is used for the heteroepitaxial growth of methylammonium lead iodide (CH₃NH₃PbI₃) thin films on a KCl substrate at room temperature. Experimental and computational results confirm cubic phase stabilization by tensile epitaxial strain in the CH₃NH₃PbI₃ thin films.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Most tumours are characterized by increased aerobic glycolytic activity. Here the authors show that elevated  aerobic glycolysis is not essential for cancer initiation by testing the effect of lactate dehydrogenase depletion on the ability of hair follicle stem cells (HFSCs) to form squamous cell carcinoma (SCC) in mouse genetic models.

Wilkerson et al. interrogate transcriptomic and proteomic peripheral immune signatures that associate with response to immune checkpoint inhibition in triple negative breast cancer. Divergent CD33+ phenotypes result in functional differences in lymphocytes.

There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Knockout studies using CRISPR–Cas9 identify PCDH10 as a selective host cellular receptor for western equine encephalitis virus.

Bhattacharjee and Schaeffer et al. map exclusive breastfeeding (EBF) in 94 low- and middle-income countries (LMICs), finding increased EBF practice and reduced subnational variation across the majority of LMICs from 2000 to 2018. However, only six LMICs will meet WHO’s target of ≥70% EBF by 2030 nationally, and only three will achieve this in all districts.

FRESH, a multi-lab collaboration, reveals how data quality, analysis pipelines, and researcher expertise influence reproducibility in fNIRS neuroimaging, highlighting key factors driving variability in hypothesis outcomes.

MAPK-targeted therapies fail to achieve complete remission. Here, the authors show that anti-apoptosis resistance is acquired in these targeted therapies through the mRNA destabilization of NOXA which leads to dependence on MCL-1, and that sequential combination of MCL-1 inhibition with targeted therapies overcomes this resistance.

Data on marine litter are scattered. Harmonizing worldwide aquatic litter inventories, this study finds global litter dominated by plastics from take-out food, followed by fishing, with litter being trapped in nearshore areas and land-sourced plastic reaching the open ocean mostly as small fragments.

Shlien and colleagues report on 300 patients from the SickKids Cancer Sequencing program and identify clinically actionable variants in 56% of the patients by profiling somatic and germline data at multiple clinical time points.

Chemical abundances derived from infrared nebular lines reveal strongly depressed metallicities in interacting galaxies, suggesting that in luminous infrared galaxies chemical enrichment and stellar-mass growth take place through mergers, which drive these galaxies out of equilibrium.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

The mechanisms underlying adaptive response to the stress elicited by radiotherapy in glioma cells remains unclear. Here, the authors show that therapeutic ionizing radiation induces rapid genome-wide chromatin reorganization to facilitate P-TEFb-mediated nascent transcriptional induction, which could be targeted to sensitize radiotherapy response in glioma.

The molecular mechanisms underlying metastasis in pheochromocytoma/paraganglioma (mPPGL) remain to be explored. Here, the authors perform genomic and immunogenomic profiling of mPPGL tumors and suggest potential biomarkers for risk of metastasis and immunotherapy response.

Saur and colleagues perform a high-throughput combinatorial drug screen and identify a synergistic combination between nintedanib and trametinib that sensitizes mesenchymal PDAC to immune checkpoint blockade.

Na⁺ controls the function of the mitochondrial oxidative phosphorylation system and hypoxic redox signalling through an unexpected interaction with phospholipids.

Plasmodium malariae can cause chronic asymptomatic infections. Here, Ibrahim and colleagues provide WGS data for > 200 P. malariae isolates. Describing mutations in genes associated with drug resistance, and using ortholog replacement in P. knowlesi, they identify dhfr genotypes with reduced susceptibility to pyrimethamine.

Goel and colleagues show that CDK4/6 inhibition induces global chromatin changes mediated by AP-1 factors, which mediate key biological and clinical effects in breast cancer.

Climate change threatens to alter the carbon balance of tropical forests. Increases in the age of carbon in soil CO₂ emissions with experimental warming or drying suggest that climate change will exacerbate soil carbon losses in tropical forests.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.