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Triacetic acid lactone (TAL) is a platform chemical with a wide range of applications. Here, the authors report the discovery of a polyketoacyl-CoA thiolase from Burkholderia sp. RF2-non_BP3, termed as BktBbr, which has unusually high in vivo and in vitro activity for production of TAL.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

This study shows that high-molecular weight tau has enhanced seeding capacity, and seeding differences can define molecular subtypes of progressive supranuclear palsy, underpinning the disease’s heterogeneity.

Acute liver failure arises from rapid cell death and impaired liver regeneration. Here, the authors show that scalable, high-purity engineered extracellular vesicles derived from stem cells promote the clearance of dying hepatocytes and drive liver repair through in vivo macrophage reprogramming.

Spiking neural networks are generally used for sequential information and event data processing but still lack high performance. Through algorithm and hardware co-design, Zhang et al. report a State Space Model based approach to implement on compute-in memory hardware, enabling asynchronous and real-time processing capability with high energy efficiency for event sequences.

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.

Quantum simulations of the phase diagram of quantum chromodynamics faces hard challenges, such as having to prepare mixed states and enforcing the non-Abelian gauge symmetry constraints. Here, the authors show how to solve the two above problems in a trapped-ion device using motional ancillae and charge-singlet measurements.

We establish a spin nematic phase in the square-lattice iridate Sr₂IrO₄ and find a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state.

Lee and colleagues present AdaSlide, an AI-driven adaptive compression system for gigapixel pathology slides that preserves diagnostic quality while reducing storage by up to 90%, enabling scalable and cost-efficient digital pathology archiving.

Non-nutritive sensory components of high-fat diet, such as bacon flavour, are sufficient to impair metabolic health in offspring in mice.

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.

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.

Here, the authors identify the microbiota-derived corisin as a driver of diabetic kidney fibrosis via cellular aging and show that targeting corisin with a monoclonal antibody alleviates disease in mice, suggesting a potential therapeutic avenue.

Time-resolved serial femtosecond crystallography at X-ray free-electron lasers is a powerful approach for studying macromolecular dynamics, but its widespread use is limited by high sample consumption. Here, the authors introduce a segmented-droplet mix-and-inject strategy at the European XFEL that reduces sample consumption by up to 97% while preserving the data quality required for time-resolved structural studies of the enzyme NQO1.

There has been significant interest in using spin-waves or magnons for information processing, due to their low energy dissipation and short wavelength at terahertz frequencies, however, manipulating magnons can be challenging. Here, Kim et al show that magnons in Sr2IrO4 are extremely strain sensitive, with small applied strains leading to large variation in the magnon energy.

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.

In this multicenter phase 1 trial of patients with advanced solid tumors resistant to anti-PD-1 therapy, treatment with the anti-latent TGFβ1 antibody linavonkibart with or without pembrolizumab was safe, and encouraging clinical response rates were associated with T cell infiltration and immune activation.

Here, Cilleros-Portet et al. present a large placental methylation database as a tool to explore the genetic burden that acts in prenatal stages, giving insight into neuropsychiatric disorders, and with especial emphasis on schizophrenia.

A previously unsampled deep lineage in central Argentina was discovered that had distinctive genetic drift by 8,500 bp and persisted as the main Native American ancestry component in the region up to the present day.

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.

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.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Ionic liquid additives increase the power conversion efficiency of perovskite solar cells, but their effect on perovskite crystallization remains unclear. Xu et al. provide mechanistic insights and demonstrate improved operational stability under continous illumination and 90 °C thermal stress.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The authors identify pathogenic variants in the SMARCA1 gene as the cause of a variable neurodevelopmental disorder. Mouse studies suggest diverse genetic mechanisms related to NURF complex composition mediate the phenotype.

A flexible micro-electrocorticography brain–computer interface that integrates a 256 × 256 array of electrodes, signal processing, data telemetry and wireless powering on a single complementary metal–oxide–semiconductor substrate can provide stable, chronic in vivo recordings.

The kernel method in machine learning can be implemented on near-term quantum computers. A 27-qubit device has now been used to solve learning problems using kernels that have the potential to be practically useful.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Animal models of drug use require specialized technical expertise and often differ from how humans consume drugs. Here, the authors establish a robust method which allows mice to self-administer intranasal cocaine, greatly improving face validity and ease of use.

The link between gRNA sequence and Cas9 activity is well established but the mechanism underlying this relationship is not well understood. Here the authors show that gRNA sequence primarily influences activity by dictating the time it takes for Cas9 to find the target site in a species-specific manner.

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.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

Tokamak walls suffer erosion from steady and bursty heat loads. Here, the authors demonstrate that optimizing 3D magnetic field and cooling gas injection can tame destructive plasma bursts while enabling cooler, safer exhaust conditions.

Enhanced bone resorption induced by sRANKL or microgravity releases phosphate into the circulation and causes crystal-induced tubular injury in mice, identifying bone-derived phosphate as a driver of kidney damage.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

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.

Peritumoural pancreatitis and lobular injury are commonly seen in pancreatic cancer. Here, the authors reveal interactions between invading tumour cells and inflammation-related lobular cells, linked to switching from a basal to classical tumor cell phenotype.

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.

Biomolecular condensates are made of multiple components but current techniques cannot capture their complex composition quantitatively. Now it has been shown that the dense-phase binodal point defining the composition of multicomponent condensates can be inferred precisely from the intersection of a spectrometrically determined tie-line with an isorefractive line obtained from quantitative phase imaging.

A complementary metal–oxide–semiconductor (CMOS) imager that has a 512-pixel silicon image sensor post-processed into a 4.1-mm-long, 120-μm-wide shank with a collinear fibre for illumination can be used to record transient fluorescent signals in deep brain regions at 400 frames per second.

A protocol for cryogenic 3D correlative focused ion beam milling using an integrated fluorescence light microscope and montage cryo-ET for nonadherent and adherent mammalian cells, as well as primary Drosophila melanogaster neurons.

Acquiring subcellular-level three-dimensional (3D) tissue structures efficiently without damaging the tissue remains challenging in histopathology. Here, the authors integrate holotomography with deep learning to generate 3D virtual H&E staining images from label-free thick cancer tissues, and apply this approach to colon and gastric cancer samples.

Thin FeSe film on SrTiO₃ substrate becomes a superconductor with a transition temperature over 100 K, yet the origin remains controversial. Here, Seo et al. show superconductivity below 20 K on the electron-doped surface of an FeSe crystal, suggesting a decisive role of interfacial effects in the enhancement of superconductivity.