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The mechanisms underlying differential chemotherapeutic response to 5-fluorouracil are not fully known. Here, the authors show that ABDH5 regulates sensitivity to 5-fluorouracil in colorectal cancer by regulating lysosome function.

Trade risks associated with fossil fuels and critical materials matter for energy security, and will evolve with the low-carbon transition. Here the researchers find that overall trade risks decrease for most countries in net-zero scenarios, although risks to electricity or transportation sectors may increase.

Legionella effector LnaB, a recently identified actin-activated AMPylase, mediates phosphoryl-AMPylation in a yet-unknown manner. Here the authors unveil a two-step catalytic process involving dual ATPase–AMPylase activity based on structural studies, providing a biochemical basis for AMPylation.

Here the authors show that viral infections facilitate accumulation of cellular iron by degradation of iron exporter ferroportin (FPN1), and that high intracellular iron suppresses type I IFN responses and autophagy by promoting TBK1 hydroxylation and STING carbonylation.

Chronic visceral pain is frequently accompanied by changes in food preference and the underlying neural circuitry mechanisms remain unclear. Here, the authors elucidate a circuit from cholecystokinin neurons in the paraventricular hypothalamus (PVH^CCK) projecting to glutamatergic neurons in the anterior cingulate cortex (ACC^Glu) to regulate food preference accompany with chronic visceral pain.

Leukaemia inhibitory factor (LIF) is a p53 target but its role in cancer is unclear. Here Hu et al.show that LIF confers chemoresistance in colorectal cancer cells by Stat3-mediated upregulation of inhibitor of DNA-binding 1, leading to MDM2 E3 ubiquitin ligase upregulation and p53 degradation.

Currently, most miRNA profiling study of complex tissues are based on bulk sample sequencing, among which the cellular heterogeneity may become an important potential confounding factor. Here, the authors developed a deconvolution method to systematically decode cellular components of complex tissues from miRNA profiling data.

Endothelial cells (ECs) and bone marrow stromal cells (BMSCs) support hematopoiesis and hematopoietic regeneration. Whether ECs are a source of BMSCs remains unclear. Here, using lineage tracing models the authors show that ECs are not a source of BMSCs during homeostasis and regeneration.

Standard mass spectrometry analyses often miss key targets required for phospho-signalling reconstruction. Here, authors present an intelligent data acquisition strategy that combines discovery and targeted analysis in one run and apply it to maximize the information from single spheroids drug screenings.

Tao et al. study the role of TRMT6 in colorectal cancer, where it is upregulated and show that TRMT6 supports histone biosynthesis by stabilizing tRNA-Lys-TTT-1-1. Targeting TRMT6 reduced histone mRNA translation in a codon-biased manner.

Predicting drug responses in cancer patients requires robust computational frameworks. Here, the authors develop an integral genomic signature —iGenSig— approach to predict drug responses using multi-omics data from tumour samples, and validate this approach using genomic datasets from multiple clinical studies.

The red fluorescent protein mScarlet3-H is bright, photostable and very robust to high temperature, chaotropic conditions and oxidative environments. mScarlet3-H works well in correlative light and electron microscopy, tissue clearing and time-lapse super-resolution microscopy.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

The authors introduce DD2D, a physics-guided deep learning method that predicts 2D structures directly from diffraction patterns using a twin-tower framework. The method demonstrates high anti-interference, robust recognition, and up to 99.0% prediction accuracy, showing promise for future 2D materials discoveries.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

The reaction between Criegee intermediates and water vapour greatly impacts atmospheric chemistry and climate, yet its dynamics remain poorly understood. Now it has been shown that syn-CH₃CHOO reacts with water vapour at rates much higher than previously estimated, through a roaming mechanism that enhances reactivity and challenges conventional understanding of atmospheric OH radical production.

The clinical outcomes of esophageal squamous cell carcinoma (ESCC) remain poor, and thus it remains critical to find prognostic molecular markers. Here, the authors identify prognostic ESCC subtypes based on bulk and single-cell RNA-seq combined with histology AI in samples from patients with more than four years of follow-up, and find markers associated with immune evasion.

Tang, Yue, Xu and colleagues map the proteome of several thousand individuals over a 9-year period to identify potential biomarkers of ageing and of age-associated diseases.

Long-term stability is a key challenge for ruthenium-based oxygen evolution reaction (OER) catalysts. Here, the authors present a RuO2/LiCoO2 catalyst with dynamic Li dissolution, which weakens the covalency of the Ru-O bond to prevent the lattice oxygen mechanism, thereby ensuring stable acidic OER.

CBF transcription factors facilitate the formation of SKIP nuclear condensates to increase the splicing efficiency of cold-responsive transcripts, bridging transcriptional and post-transcriptional regulation during cold acclimation.

Dick and colleagues identify human LT-HSC subsets with distinct quiescent states. They link these differences to INKA1-mediated downregulation of the transmembrane protein CD112 and its interaction with the protein deacetylase SIRT1. INKA1 is inversely correlated with the histone H4K16Ac mark, which then distinguishes ‘latent’ CD112^lo LT-HSCs from CD112^hi LT-HSCs that are more readily activated in response to hematopoietic stress.

The study reveals that PLETHORA 5, a transcription factor activated by auxin signalling in the vascular cambium, regulates cell expansion and cell wall thickening of fibres by directly repressing SND1 genes during wood formation in Populus tomentosa.

The search for lunar polycyclic aromatics is challenging. Here abundance, aromatic structures and carbon isotope composition of polycyclic aromatics in Chang’E 5 lunar soils are reported, shedding light on the fate of polycyclic aromatics and accretion of organic carbon on the Moon.

In a phase 1 trial, pediatric or adult patients with T-ALL who received CD5-targeted CAR-T cell therapy using cells from previous or newly matched donors showed an encouraging clinical response rate, with some severe adverse events that required attention and effective management.

The tumour microenvironment features influencing response to neoadjuvant immunochemotherapy (nICT) in esophageal squamous cell carcinoma (ESCC) remain to be explored. Here, single cell and TCR sequencing on pre- and post- nICT treatment ESCC tissues identifies the presence of CXCL13⁺CD8⁺ T cells as a predictor of improved response and the enrichment of TNFRSF4⁺CD4⁺ Tregs as a marker of treatment resistance.

Worldwide, the number of only-child families is increasing. This research examines how growing up without siblings affects adult brain structure, function and connectivity, cognition, personality and mental health.

It is challenging to regulate the interfacial motifs of Cu⁰-Cu⁺ sites to understand roles of Cu⁰ and Cu⁺ for nitrate electrochemical reduction reaction. Here, the authors report a tunable construction of Cu⁰-Cu⁺ interfacial structure by modulating the size-effect of Cu₂O electrocatalysts.

The health of brain cells is known to depend on functional autophagy, but the details are unclear. Here, the authors perform systematic proteomic profiling of human and mouse neurons, delineating the landscape of autophagy degradation in brain.

Catalytic asymmetric radical dearomatization has remained a daunting task due to the challenges in exerting stereocontrol over highly reactive radical intermediates. Now, using metalloredox biocatalysis, new-to-nature radical dearomatases P450_rad1–P450_rad5 have been engineered to facilitate asymmetric dearomatization of a broad spectrum of aromatic substrates, including indoles, pyrroles and phenols.

Pesticides affect a diverse range of non-target species and the magnitude of this hazard remains only partially understood. Wan et al. found that insecticides, fungicides and herbicides have negative effects on non-target plants, animals and microorganisms within terrestrial and aquatic systems.

The authors showcase a method to design negative lumped elements by engineering the effective permittivity within the waveguide, which enables realizations of wideband waveguide metatronics and promises performance enhancement in various fields.

Zhou et al. demonstrate that bone marrow adipocytes, but not intraperitoneal adipocytes, express high levels of stem cell factor (SCF), which is essential for the regeneration of haematopoietic stem cells and haematopoiesis after irradiation.