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A preclinical covalent compound, CMX410, contains a aryl fluorosulfate warhead that targets the acyltransferase domain of Mtb Pks13, an essential enzyme in cell-wall biosynthesis, making it a promising candidate for tuberculosis treatment regimens.

Using data from the UK Biobank, the authors develop a comprehensive human metabolome–phenome atlas, including a browsable web tool, to uncover unique metabolite–trait and metabolite–disease associations with time, and discuss potential causal relationships.

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.

Generalizable Pathology Foundation Model (GPFM) consolidates expertise from a variety of existing models for use in a broad spectrum of computational pathology tasks.

In the multicenter phase 2 OptiTROP-Lung01 trial in patients with treatment-naive advanced non-small-cell lung cancers, the antibody–drug conjugate sacituzumab tirumotecan with anti-PD-L1 tagitanlimab was safe and showed encouraging clinical efficacy.

Feng, Luo and colleagues show that the combination of glucose and fructose, as found in sugar-sweetened beverages, promotes colorectal cancer metastasis through a mechanism involving sorbitol dehydrogenase (SORD).

The authors analyze rare coding variants in 1990 individuals with congenital kidney anomalies, finding diagnostic variants in 14.1% of cases. They identify two new causal genes, ARID3A and NR6A1, along with 38 candidate genes, providing evidence for shared genetics with other developmental disorders.

RNF214 ubiquitin ligase is understudied. Here the authors show RNF214 promotes hepatocellular carcinoma progression by inducing non-proteolytic ubiquitylation of TEADs and activating YAP signaling pathway.

This study reveals that CYBDOM proteins promote drought tolerance by regenerating apoplastic ascorbic acid (AsA) and activating autophagy through interaction with RbohD, and link AsA redox, ROS and selective autophagy in plant stress responses

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 use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

The authors report an ultra-broadband ptychography method, suitable for dispersive samples, by exploiting structured illumination and a novel joint deconvolution algorithm.

This work presents a strategy for synthesizing and assembling megabase-scale DNA, along with a delivery method for introducing the synthetic DNA into mouse embryos, offering a valuable tool for investigating de novo epigenetic regulation.

Intrinsically soft electronics marry high-conductivity metallic nanomaterials and liquid metals with elastomeric/hydrogel matrices to deliver stretchable, durable, and biocompatible devices. This review synthesizes design principles from percolation-guided nanocomposites (0D/1D/2D fillers), liquid-metal patterning, and unconventional fabrication (printing, soft/photolithography, laser) to overcome fatigue and resolution limits of geometry-engineered rigid systems. We highlight applications spanning low-impedance electrodes and sensors, strain-invariant interconnects and circuits, optoelectronics, wireless components, energy storage/harvesting, and stretchable memory. Remaining challenges—long-term stability, scalable manufacturing, and safe biointegration—are outlined with prospects for closed-loop, AI-enabled systems and fully integrated soft platforms.

Complex environments with varying temperatures remain a major challenge for batteries. Here, authors develop a polymer composite binder with dynamic active sites and phase change properties, enabling lithium sulfur batteries to operate stably over a wide temperature range of −40 °C to 60 °C.

The promise of X-ray tabletop broadband light sources by high-order harmonics generated in a gas medium has been limited by low conversion efficiencies. Here, Jin et al.show a method to enhance the high harmonic generation by optimizing the waveform of synthesized two and three colour laser fields.

The discovery of 2023 KQ₁₄, a Sedna-like object with a perihelion of 66 au, fills a gap in the known population. Its orbit does not align with other Sedna-like objects, shedding light on the diversity and dynamical history of the outer Solar System.

The molecular mechanisms underlying the transformation of Chronic Myeloid Leukaemia (CML) from chronic phase (CP) to blast crisis (BC) are not completely elucidated. Here, the authors show that acquired miR-142 deficiency drives CML BC by regulating mitochondrial metabolism and is a potential therapeutic target to prevent BC in CML murine models.

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.

Adoro and colleagues report the involvement of the IRE1α–XBP1 signaling axis in protecting hematopoietic stem and progenitor cells from proteomic stress and as a safeguard against leukemic transformation.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Amino acids are required for cell survival and growth. However, the different requirements of amino acid metabolic pathways in normal haematopoiesis and leukaemogenesis have not been explored. Here the authors focus on the transporter of neutral amino acids and show that malignant blood cells rely more on ASCT2-mediated amino acid metabolism than normal cells.

Cerebellar ataxia, a hallmark of cerebellar degeneration (CBND), is driven by mitochondrial dysfunction in Purkinje cells. In this study, transplanting mitochondria into CBND mice improve mitochondrial function, reduce mitophagy, and reduce ataxia.

CRISPR screens identify hepatic ABCC4 as a modulator of LDLR. Inhibiting ABCC4 increases hepatic LDLR, lowers plasma LDLC and acts via the cAMP-Epac2/Rap1a signaling pathway to suppress PCSK9, preventing LDLR degradation.

USP17L, encoded by a gene family expressed in mouse 2-cell embryos and 2-cell-like cells, is shown to promote the 2-cell program in mESCs at both transcriptional and post-translational levels, in part through deubiquitinating H2AK119ub1 and ZSCAN4.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Wu et al. show that glucosamine acts as a P-glycoprotein activator, rapidly enhancing intestinal drug efflux and reducing drug absorption. The authors propose this as a detox strategy to improve survival outcomes following paraquat exposure.

Xiang et al. use patient samples and mouse models of osteoarthritis to examine the link with muscle atrophy. They identify that, in osteoarthritis, senescent macrophages promote ferroptosis in skeletal muscle cells, and they show the therapeutic value of targeting this pathological mechanism.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

Mobilization of hematopoietic stem and progenitor cells (HSPCs) into the circulation is essential for maintaining homeostasis. Here, the authors show that Phc2 in bone marrow stromal cells represses the cell adhesion molecule Vcam1 and facilitates mobilization of HSPCs through regulation of epigenetic marks.

Insulinomas develop from pancreatic β-cells and secrete insulin, but the underlying genetic defects are largely unknown. In this study, Cao et al. identify recurrent T372R mutations in the transcription factor YY1, and validate this hotspot mutation in 30% of insulinomas.

Teixobactin is a recently identified antibiotic that shows activity against drug resistant strains of bacteria. Here, the authors report a highly convergent total synthesis of this natural product, with sufficient flexibility to also allow the synthesis of a number of analogues.

How changes in brain blood vessels lead to a chronic reduction in blood flow and, consequently, to vascular dementia is poorly understood. Here, the authors show that venous endothelial dysfunction driven by EPAS1 promotes abnormal vascular remodeling and contributes to cognitive decline.

Covalent organic frameworks have emerged as a robust platform for enzyme immobilization, but mimicking biofilm structures for in-situ enzyme immobilization is challenging. Here, the authors immobilized enzymes using vesicular covalent organic frameworks synthesized with Gemini surfactants providing enzyme stability and activity.

Cao et al. report an A-site co-doping strategy by substituting Cs+ cation by alkali metals for perovskite quantum wires embedded in nanoporous alumina template, stabilising the crystal structure and enabling high-colour purity LEDs spanning from blue to green spectral region.

A high-peak-power low-duty-cycle pulsed fibre laser enables stimulated Brillouin scattering microscopy with pixel dwell times as low as 0.2 ms and spatial resolution as low as 500 nm and 2 μm in the lateral and axial directions, respectively.

Pancreatic cancer detection can be challenging, and is often diagnosed at a late stage. Here, the authors present a cfDNA-based liquid biopsy model that enables early detection and prognosis prediction of pancreatic cancer.