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Emmett and colleagues evaluate the frequency, magnitude and clinical significance of early prostate-specific membrane antigen (PSMA) upregulation in patients with metastatic castrate-resistant prostate cancer treated with enzalutamide with or without ¹⁷⁷Lu-PSMA-617.

Kancharla, Kelly et al. identify an acridone antimalarial potent across all major parasite life stages. Lead candidate T111 shows oral efficacy, low toxicity, and synergy with tafenoquine, providing a unique mechanism to overcome resistance.

This study develops a platform that enables simultaneous, multiplexed tracing of 30 nitrogen isotope-labelled metabolites, uncovering differences in pyrimidine synthesis pathway choice between primitive and differentiated cells.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

This work provides a mechanistic understanding of how certain prefrontal circuits in the rodent brain permit flexibility to selectively stop learned behaviours through interactions with core subcortical reward systems.

This long-term, large-scale intervention and follow-up MRI study suggests that sustained visceral fat loss, rather than weight loss, is linked to better cognition and attenuation of brain atrophy years later, mainly via improved glycaemic control.

In this Perspective, the authors evaluate the current status of prostate-specific membrane antigen (PSMA) ligand-enabled imaging, summarizing novel developments, therapeutic advances and combinatorial approaches. The potential future role of PSMA-based strategies in the future management of prostate cancer is also discussed.

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.

Mapping DNA variants that modulate mortality using a starting population of 6,438 young mice defined 29 distinct loci that influence lifespan and mortality with divergent age- and sex-specific effects, as well as 30 loci that specifically couple body mass with longevity.

This study from Wei-Guang Li, Tian-Le Xu and colleagues shows that neuropeptide Y released by specific hippocampal inhibitory neurons can switch fear memories into extinction memories by acting on two distinct receptor-defined neuron populations.

The Human Development Multiomic Atlas catalogues single-cell accessibility and gene expression data from human fetal cells across 12 organs, enabling the inference of syntactic rules for motifs that govern cell-type-specific transcription factor binding and chromatin accessibility during human development.

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.

New research introduces a global, high-resolution power system model to show that achieving a net-zero electricity sector while ensuring equitable access to decent living standards is both technically feasible and economically viable by mid-century.

Metamorphic soles beneath ophiolites record rapid subduction initiation, with high-temperature metamorphism that may be driven by relative motion across the plate interface, according to diffusion speedometry of garnets combined with isotopic data.

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.

Decade-long warming increased soil antibiotic-resistance genes by about 24%, enriching resistant microbes and gene transfer, driven by selection for thermal tolerance and linked traits, with implications for public health.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Store-operated Ca²⁺ entry is essential for cellular signalling, yet excessive calcium influx drives disease. Here, authors develop genetically encoded CRAC channel inhibitory binders (CRABs) to precisely modulate Ca²⁺ signalling, with therapeutic potential in channelopathies and cancer immunotherapy.

The environmental impacts of food consumption in the European Union are global. This study estimates the environmental footprints of EU27 household food consumption, simulating the mitigation potential of tax policies and assessing consumption-related welfare costs.

In a phase 1 trial enrolling six patients with heterozygous familial hypercholesterolemia, treatment with lipid nanoparticles designed for base editing and inactivation of PCSK9 in hepatocytes showed preliminary evidence of reduced low-density lipoprotein levels without the occurrence of serious adverse events or evidence of off-target editing.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

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.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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

Wu et al. investigated the efficacy and safety of fruquintinib plus sintilimab in 34 Chinese patients with advanced cervical cancer. The study finds that 32% of patients responded to the combination treatment and disease was controlled in 97%; side effects were manageable.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Radiometric dating and oxygen isotopes of Pilbara Craton zircons reveal early continent formation via seafloor hydrothermal alteration and subsequent shallow depth partial melting of mafic protcrust some 3565 million years ago.

Gene correction in the lung is achieved with inhalable mRNA lipid nanoparticles containing an amino acid-derived ionizable lipid identified from screening and structure–function optimization studies.

Electrification is a promising way to decarbonize the chemical industry but could also have important effects on power systems. Here the authors assess the impact of electrifying the production of methanol and ammonia on the Chinese power system in terms of emissions and potential security risks.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The physics of resonant electro-optic microcomb generation is underexplored, limiting their potential applications. Now several technological advances are realized by studying the state space of a thin-film lithium niobate photonic frequency comb.

Assessing thymic function and health has highlighted the lifelong importance of the thymus as an organ that could be targeted to improve health outcomes, protect against disease and promote healthy ageing.

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.

The impact of cooling through the Eocene-Oligocene transition on the marine biosphere is not well constrained. Here the authors construct a high-resolution record of foraminiferal species richness history spanning this transition that reveals differential diversity trends depending on foraminiferal habitat and life mode.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Evo 2 is an artificial intelligence-based biological foundation model trained on 9 trillion DNA base pairs spanning all domains of life that predicts functional properties from genomic sequences and provides a rich generative model for researchers in biology.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Here the authors demonstate that counter to expectation provided by the relevant standard reduction potentials, a chloroberyllate, [{SiNDipp}BeClLi]2, reacts with the group 1 elements (M = Na, K, Rb, Cs) to provide the respective heavier alkali metal analogues, [{SiNDipp}BeClM]2.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.