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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.

Selective C–H amination of electronically diverse (hetero)arene substrates is reported using an electrochemical strategy. Two convergent mechanistic pathways enable the tolerance of both electron-rich and electron-deficient (hetero)arenes. When electron-deficient substrates are used the process proceeds through electrophilic N-radical dicationic intermediates, following amine oxidation, whereas electron-rich substrates undergo arene oxidation.

Here the authors develop a novel statistical method for quantifying mutation burden from whole genome sequencing data and use it to discover the genetic, genomic, and phenotypic correlates of clonal hematopoiesis without known driver genetic lesions.

An Fe^III/V redox mechanism in Li₄FeSbO₆ on delithiation without Fe^IV or oxygen formation with resistance to aging, high operating potential and low voltage hysteresis is demonstrated, with implications for Fe-based high-voltage applications.

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.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Resistance mutations in BCL-2 reduce the clinical efficacy of venetoclax. DeAngelo et al. show stapled BAD BH3 peptides can retain and even enhance binding to these mutants, offering a structurally informed strategy to overcome this mechanism of cancer drug resistance.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

A combination of whole-genome NanoSeq with deep whole-exome and targeted NanoSeq is used to accurately characterize mutation rates and genes under positive selection in sperm cells.

Thermal lepton pairs are ideal probes for the temperature of quark-gluon plasma. Here, the STAR Collaboration uses thermal electron-positron pair production to measure quark-gluon plasma average temperature at different stages of the evolution.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Sun et al. reveal that root-knot nematode attack activates a phyB-HY5 cascade that integrates light and GLR3.5-CaM2 signals to boost JA synthesis in tomato, with HY5 moving from leaves to roots to sustain signaling and trigger JA-mediated defense.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Tree cover gains in the moist tropics (1982–2015) were 56% naturally regenerated forests and 27% managed tree systems, with forest type influencing carbon recovery. Effective forest restoration requires robust tracking of forest types established by restoration efforts.

Plant roots elongate under mild nitrogen deficiency as part of a foraging response that facilitates nutrient uptake. Here the authors show that natural variation in this response among Arabidopsis accessions depends on the brassinosteroid (BR) signaling kinase BSK3, which can enhance BR sensitivity and root growth.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Distinguishing glioblastoma and primary central nervous system lymphoma (PCNSL) remains challenging due to their overlapping pathology features. Here, the authors develop a computational tool, PICTURE, for differentiating similar pathological features enabling improved diagnosis of CNS tumours.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Green roofs enhance urban ecosystem services, but the long-term vegetation health and design’s impact is underexplored. This study shows a temporal increase in vegetation health and identifies key factors and thresholds that support sustained vegetation health, offering guidance for effective green roof planning and design.

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.

A population genomic analysis of 1,854 Listeria soil isolates collected across the contiguous United States identifies geographically prevalent phylogroups with increased pangenome openness and recombination, as a result of adaptation to variable environments.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Results from the randomized, noncomparative, phase 2 MATISSE trial show that ultra-short neoadjuvant therapy with ipilimumab and nivolumab can prevent surgery and radiotherapy in patients with resectable cutaneous squamous cell carcinoma, with an early decrease in total lesion glycolysis by [¹⁸F]FDG-PET/CT associated with response.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

A general stereospecific glycosylation is developed that is applicable across a range of monosaccharides. A directing-group-on-leaving-group strategy allows mild donor activation and enables the complete inversion of anomeric configuration with excellent yields. This method can be applied in multistep oligosaccharide syntheses and automated glycan assembly.

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.

The study of isotopes away from the beta stability valley is crucial for the understanding of nuclear structure, especially for neutron-deficient heavy nuclei. Here, the authors report the observation of the alpha-decay isotope 210-protactinium (Pa), extending the alpha-decay systematics of underexplored regions of the nuclides chart.

High-density multimodal soft bioelectronic fibres provide a platform for minimally invasive implantable electronics, where diverse sensing and stimulation functionalities can be effectively integrated.

The regulatory landscape controlling Hoxd gene expression in tetrapod digit development was probably co-opted from a pre-existing cloacal regulatory mechanism, as evidenced by the effects of genetic deletion experiments in zebrafish fin, cloaca and mouse urogenital development.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Designer box H/ACA RNA-guided pseudouridylation can target both mRNA and tRNA. Modifying the first U of a stop codon and U36 of the matching anticodon forms one Ψ–Ψ and two Watson–Crick pairs, enabling efficient and specific stop codon readthrough.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

The authors combine tracking and body mass data from five migratory waterfowl species to understand their capacity to accelerate migration in response to earlier spring. They show considerable scope for faster migration by reducing the fuelling time before departure and subsequently on stopovers

A natural circular RNA termed ciRS-7 is shown to function as a negative regulator of microRNA; ciRS-7 acts as an efficient sponge for the microRNA miR-7, and is resistant to the usual microRNA-mediated degradation pathway of exonucleolytic RNA decay.

Stable and robust topological edge modes are observed at finite temperatures in an array of 100 programmable superconducting qubits because of emergent symmetries present in the prethermal regime of this system.

Tamnes et al. explore the complex relationship between ill-being—including mental and behavioural disorders—and mental well-being.

Glucocorticoid (GC) induced osteoporosis (GIOP) remains a significant clinical problem. Here, the authors find that GCs disrupt skeletal stem cell–endothelial crosstalk via Basigin that can be targeted as a potential therapy for GIOP.

Sex differences are well established in the prevalence and symptoms of depression. Here, the authors identify a novel X chromosome variant, greater genetic risk, and stronger links to metabolic traits in females, highlighting the importance of sex-aware approaches.

Weak transitions have a prominent role in optical clock devices and fundamental physics tests but are challenging to resolve due to the unfavourable scaling of the cross section with transition strengths. Here, the authors demonstrate enhanced cross sections due to beyond single-photon excitations in He atoms, facilitating applications in precision spectroscopy.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Genetic factors affecting Aedes aegypti susceptibility to dengue virus infection aren’t well studied. Here the authors show that a cytochrome P450 gene, typically linked to cuticle structure and insecticide resistance, influences dengue infection in Aedes aegypti.