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Assessing the hepatotoxicity of a drug is critical in drug development. Here, the authors develop human multi-lineage liver organoids and identify imipramine as an inducer of indirect hepatotoxicity from a drug screen. The study offers insight into indirect hepatotoxicity and an in vitro platform for drug safety testing.

Grignard reagents face challenges in synthesizing complex architectures, and quaternary carbon centres remain difficult targets. Now it has been shown that a nickel-catalysed alkene carbomagnesiation strategy, employing a rare contra-electronegativity transmetallation, efficiently synthesizes β-quaternary Grignard reagents with high regio- and enantiocontrol, offering new possibilities for cross-coupling chemistry.

Fractional Chern insulators have been observed in moiré MoTe₂ at zero magnetic field, but the expected zero longitudinal resistance has not been demonstrated. Now it is shown that improving device quality allows this effect to appear.

PAK4 promotes Mdm2-mediated NLRP1 ubiquitination and degradation by phosphorylating Mdm2 at Ser186, thereby suppressing GEM-induced pyroptosis via the NLRP1/caspase-9/caspase-3/GSDME axis in pancreatic cancer cells

A new artificial intelligence model, DeepSeek-R1, is introduced, demonstrating that the reasoning abilities of large language models can be incentivized through pure reinforcement learning, removing the need for human-annotated demonstrations.

Lithium metal batteries are restricted by their low safety and poor electrochemical performance. Here, authors present a flame-retardant electrolyte with weakly coordinating dichloroalkane diluents, demonstrating application potential in safer lithium metal batteries in the −60 to +60 °C temperature range.

Leaf rust threatens wheat production worldwide. Here, the authors report a high-quality genome assembly of the leaf rust resistant durum wheat landrace PI 192051 and the cloning of the leaf rust resistance gene Lr.ace-4A/Lr30.

Vaccines for SARS-CoV-2 are needed to fight the pandemic. Here the authors show immunogenicity of an adjuvanted subunit vaccine, SARS-CoV-2 spike protein trimerized with trimer-tag technology, in small animal models and protection from SARS-CoV-2 challenge in non-human primates.

This study shows that keto-enol tautomerism in 2,4,6-trihydroxybenzaldehyde (Tp) imine COFs acts as variable electron/hole traps, boosting exciton dissociation and charge transfer. Tp COF (TpBpy) achieves an photocatalytic H₂O₂ generation rate of 8350 μmol h^-1 g^-1 under simulated light, and a solar-to-chemical conversion efficiency of 0.038% in a flow reactor under natural sunlight.

This study employs time-lapse single-nucleus RNA sequencing in Arabidopsis seedlings, revealing distinct circadian rhythms in specific cell types and identifying ABF1 as a regulator that shortens the circadian period.

Powdery mildew is a devasting disease for both common wheat and durum wheat. Here, the authors report the powdery mildew resistance locus derived from wild emmer wheat is conferred by the combined effect of two complementary nucleotide-binding and leucine-rich repeat genes.

The gut microbiome is closely connected to health. Pang et al. explored the gut microbiome and aging in a large cohort of 297 centenarians. The study shows that the gut microbiome in centenarians has a Bacteroides-enriched enterotype and youth-associated features.

Despite delivering gene-specific silencing, the use of deoxyribozymes (DNAzymes) for cancer therapy is limited by toxicity due to off-target effects. Here, the authors develop a multi-component DNAzyme, targeting both miRNA21 and HSP70, to induce tumour-specific sensitisation to photothermal therapy in preclinical models of pancreatic cancer.

A method is reported that produces highly strong, tough and elastic 2D COF films, using a sacrificial go-between, which endows them with new properties, enhances their current applications and paves the way for new applications.

High-throughput immunoassay is crucial for scientific and clinical applications. Here, the authors introduce a multiplex immunoassay platform engineered by modifying a pipette tip with a self-assembled barcoded protein array. It outperforms the gold standard in sensitivity, speed, and sample volume.

Polyester waste is increasingly accumulating in the environment, and alcoholysis recycling offers a sustainable management solution. This study demonstrates the use of an oxygen vacancy-rich catalyst to transform waste blended polyester/textiles into high-value monomers.

Hepatocellular carcinomas (HCC) present spatial intratumour heterogeneity (sITH). Here, the authors perform a genomic and phylogenetic analysis of spatially-sampled HCC tumour sections, observe block-shaped sITH, and find ongoing natural selection where ancestral and derived clones spatially compete in the same tumor.

Here, authors design and test synthetic nano-kirigami structures with Archimedean spirals to achieve large-range, bi-directional deformations. These results in high-performance optical modulation and high-resolution dynamic information displays, addressing limitations in existing nano-kirigami deformability.

Currently, there is limited understanding of the molecular subtypes of fumarate hydratase (FH)-deficient renal cell carcinoma (RCC). Here, the authors employ integrated genomics and transcriptomics to develop a CpG site-specific methylation signature for the identification of FH-deficient RCC, and to identify three distinct molecular subtypes for this rare but highly lethal kidney cancer.

The evolutionary genetics of a keystone savannah species the blue wildebeest, and the related black wildebeest, remain largely unexplored. This study finds evidence for archaic introgression of black wildebeest to blue wildebeest and detrimental effects of human activities on migratory populations.

There is substantial research underway into the development of efficient and stable electrocatalysts as alternatives to platinum for the oxygen reduction reaction. Here, the authors optimize both porosity and surface functionalization of a nitrogen doped carbon material to achieve notable performance.

The authors propose a targeted doping strategy that enables copper atoms to occupy specific positions within the material’s crystal structure, avoiding the unwanted defects typically introduced by conventional methods.

Min Deng, Kai Wang and colleagues report genome-wide association analyses of amyotrophic lateral sclerosis in the Han Chinese population. They identify two new risk loci at 1q32 and 22p11.

Hyperactivation of Akt promotes tumorigenesis. Here, the authors show that SAV1, a member of Hippo signalling, interacts with Akt to suppress Akt activity and MERTK-mediated Akt phosphorylation relieves this suppression to facilitate Akt oncogenic activity in clear cell renal carcinomas.

Radiofrequency ablation is used to treat metastatic colorectal cancer. In this study, the authors show that incomplete ablation of tumours results in metastases and show in mouse models that the chemokine CCL2 recruits myeloid cells to the partially ablated tumours, which can block T cell function.

In analogy with quantum Hall systems, it may be possible to find non-abelian anyons in the higher bands of Chern insulators. Now, the phase diagram of the second moiré band of twisted MoTe₂ is explored, laying the groundwork for such investigations.

Mitochondria dysfunction contributes to acute liver injuries. Zhang et al. find that Zhx2 deletion enhances mitochondrial function by promoting electron transport chain gene expression via PGC-1α dependent and independent manner.

Well-dispersed nanoparticles are critical for catalysis but face challenges of easy agglomeration. Here the authors report synthesis of ultrasmall nanoparticles anchored on two-dimensional porous carbon via coordinated carbothermal shock and the application of resulted nanoparticles as catalysts for oxygen electrocatalysis.

A nanoscale printing method is developed to fabricate three-dimensional high-refractive index photonic crystals whose bandgap spans in the entire visible range.

The authors report a wet-chemical selenization-based anisotropy optimization to control the orientation of the Ag₂Se thin film, achieving a power factor of 30.8 μW cm⁻¹ K⁻² in the thin film and a normalized power density of 1.8 μW cm⁻² K⁻² in the device.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, the authors report human papillomavirus features and genomic landscape in SCCC via high-throughput sequencing methods and identify MYC, SOX, NR4A, ANKRD and CEA family genes as HPV-integrated hotspots.

Cepharanthine is a secondary metabolite isolated from Stephania with a variety of medicinal properties. Here, the authors assembled three Stephania genomes, propose cepharanthine biosynthetic pathway, and assess the antiviral potential of cepharanthine-related metabolites.

This work reports on a new concept of time-resolved photon counting Fourier-transform micro-spectroscopy, allowing continuous scanning by converting photon arrival times to interferometer position.

Using the unique valley properties of a twisted MoTe₂ bilayer, measurements of the degree of circular polarization of trion photoluminescence reveal optical signatures of a zero-field composite Fermi liquid.

A deep learning algorithm shows promising performance in predicting progression to diabetic retinopathy in patients, up to 5 years in advance, potentially providing support for medical treatment decisions and indications for personalized screening frequency in a real-world cohort.

The histone-acetylation-reader protein ENL is mutated in a paediatric kidney cancer in such a way that it clusters at target genes, increasing the recruitment of the transcriptional machinery, enhancing transcription and deregulating cell fate during development.