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Here, the authors functionally characterize a complex genetic variant relevant in prostate cancer that regulates IRX4 expression through epigenetic activation. This work highlights the significance of non-single nucleotide polymorphism causal variants in explaining disease risk.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

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.

Smale and colleagues explore evolutionary divergence in the NF-κB family. They show that intrinsic DNA-binding affinity rather than specificity led to neofunctionalization in mammals within this transcription factor family, supporting immunoregulatory rewiring in mammalian species.

Beta-relaxation in glasses is commonly attributed to the confined motions of constituent atoms in nanosized domains, but there is no direct evidence so far. Here, Zhu et al. show the correlation between the evolution of spatial heterogeneity at nanoscale and beta-relaxation below glass transition point.

A precise structure measurement of liquid carbon at pressures of around 1 million atmospheres obtained by in situ X-ray diffraction at an X-ray free-electron laser shows a complex fluid with transient bonding and approximately four nearest neighbours on average.

Electrochromic materials reversibly change their colour upon application of an electric field. Seidelet al. measure the optical properties of doped bismuth ferrite and report the largest electrochromic response for an inorganic material, which they attribute to the melting of oxygen-vacancy ordering.

Cyborg insects combine living insects with miniature electronic controllers, offering several advantages over conventional robots. Here, the authors propose an algorithm that can navigate a swarm of cyborgs from the start to a predetermined goal in an unknown sandy terrain in the presence of obstacles and hills.

The role of metabolism in acute myeloid leukaemia (AML) onset remains to be explored. Here, the authors explore the metabolic landscape of AML cells and the signature of extracellular vesicles (EVs) in peripheral blood and show that circulating EVs regulate leukaemia (stem) cell metabolic reprogramming.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

Epichaperomes are chaperone assemblies that reorganize protein networks under stress. Here, authors reveal how HSP90 phosphorylation drives epichaperome formation, linking this process to cancer cell behaviors and pluripotent stem cell functions.

This paper highlights the far-red chemigenetic H₂O₂ reporter oROS-HT₆₃₅, which enables detailed insights into intricate intracellular and intercellular H₂O₂ dynamics, along with their environmental interactants, through spatially resolved, multiplexed real-time H₂O₂ imaging.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

The poor bench stability of phosphoramidites is a drawback for fast automised chemical oligonucleotide synthesis. Here, the authors report a method for on-demand flow synthesis of phosphoramidites within short reaction times, in near-quantitative yields and sufficient purity for integration with DNA synthesizers.

The authors demonstrate a biosensing platform based on whispering gallery mode microtoroid resonators, which enables sensing at zeptomolar concentrations and real-time monitoring of molecular binding events

Ark⁺, a fully open artificial intelligence foundation model, demonstrates exceptional capabilities in diagnosing common, rare and novel thoracic diseases.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

Household water, sanitation, and handwashing (WASH) interventions can reduce diarrhoea-related morbidity in young children. Here, the authors report findings from a pre-specified secondary analysis of a cluster-randomised trial assessing how WASH impacts vary by socioeconomic position and season.

Nano et al. introduce a pipeline to generate meta-atlases of the human brain from existing single-cell datasets and extract gene modules linked to cell fate specification. Perturbing these programs in human cortical chimeroids validated their roles in cell type specification.

Endovascular thrombectomy (EVT) achieves high recanalization rates in acute stroke, but many patients still experience poor outcomes. Here, the authors show that intravenous edaravone dexborneol (ED) is safe and reduces early hemorrhage but does not significantly improve 90-day functional outcomes in stroke patients after EVT.

By implementing random circuit sampling, experimental and theoretical results establish the existence of transitions to a stable, computationally complex phase that is reachable with current quantum processors.

A magnetic-spectrometer-free method for electron–proton scattering data reveals a proton charge radius 2.7 standard deviations smaller than the currently accepted value from electron–proton scattering, yet consistent with other recent experiments.

Combined hepatocellular-cholangiocarcinomas (cHCC-CCA) are challenging to diagnose, as they exhibit features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). Here, the authors use deep learning to re-classify cHCC-CCA tumours into HCC or ICCA based on histopathology images.

In the original Maxwell’s demon thought experiment, a potential gradient of particles between two neighbouring compartments is created without the apparent use of work. Now a functional example of this experiment where material is pumped over centimetres has been reported—o-fluoroazobenzene is transported unidirectionally under light stimulation between two arms of a U-tube across an aqueous layer containing coordination cages.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Ahmed, Nguyen et al. show that two FDA-approved antibiotics, paromomycin and neomycin, promote cardiomyocyte proliferation and improve cardiac function after myocardial infarction in mice and pigs by interfering with the cell division inhibiting function of transcription factors Meis1 and Hoxb13.

Analysis of 4,041 single-nucleotide variants (SNVs) linked to 13 cancers performed in primary human cell types identifies 380 potentially regulatory SNVs and their putative target genes. Editing one SNV, rs10411210, revealed that the risk allele increases RHPN2 expression and stimulus-responsive RhoA activation.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Transcriptomic and proteomic analyses show that high levels of the extracellular-matrix protein osteopontin are associated with the attenuated foreign-body response elicited by breast silicone implants wrapped with acellular dermal matrix.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

This Analysis estimates the health benefits and economic value of enhancing social determinants of mental health in Brisbane South, Australia, home to 1.2 million people. Crosland et al. analyze the impact of a 5% improvement in social cohesion, childhood difficulties, substance misuse, unemployment, underemployment, homelessness and staying engaged with education over 11 years.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

Shen et al. report a method for multiplexing isogenic iPSCs for single-cell RNA-seq. With it, they created an atlas of in vitro differentiation and identified TMEM88 as a regulator of cardiovascular development, impacting blood pressure in adult mice.

The authors demonstrate integration of a single-slit diffraction method into linear-array transducers for advancing 3D photoacoustic and ultrasound imaging in biological tissues. The method enhances spatial resolution and signal-to-noise ratio while maintaining low-cost and practicality.

An evidence-based approach for dealing with insufficient, conflicting and biased materials data is proposed for recommending high-entropy alloys, showing good capabilities for extrapolating the number of components.

The APC/C ubiquitylates histones to regulate gene expression in pluripotent cells. Here, the authors pair cryo-EM and biochemical and biophysical assays to show that instead of modifying nucleosome-incorporated histones, the APC/C ubiquitylates extranucleosomal histone complexes through a mechanism that bypasses canonical substrate degrons.