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Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Topological phases with knotted configurations in momentum space have been challenging to realize. Here, Lee et al. provide a systematic design and measurement of a three-dimensional knotted nodal structure, and resolve its momentum space drumhead states via a topolectrical RLC-type circuit.

Chen et al. provide an m⁵C landscape in bladder cancer and show m⁵C enrichment at oncogene mRNAs that promotes tumour progression. They identify YBX1 as the m⁵C ‘reader’ that recruits ELAVL1 to stabilize mRNAs.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

The defense-associated sirtuin 2 (DSR2) system protects bacteria from phages by depleting NAD⁺. Here, authors elucidate the molecular mechanisms underlying DSR2 assembly, activation, and inhibition, providing important insights into bacterial anti-phage defense.

The ferroelectric polarization generally reduces at the domain walls. Here, the authors demonstrate that a huge enhancement (43%) of ferroelectric polarization in ε-Fe₂O₃ in the domain wall with a low bound charge density.

A HfNbTiVAl₁₀ alloy shows tensile ductility and ultrahigh yield strength from the addition of aluminium to a HfNbTiV alloy, resulting in a negative mixing enthalpy solid solution, which promotes strength and favours formation of hierarchical chemical fluctuations.

Epigenomic profiling and massively parallel reporter assays identify 892 functional differentially-active single-nucleotide variants (daSNVs) linked to ten neuropsychiatric diseases. CRISPRi and gene editing approaches show magnesium transport dysfunction as a common genetic pathomechanism.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

Carbapenemase-producing Enterobacterales cause healthcare-associated infections but modes of transmission are not well understood. Here, the authors find evidence of transmission without direct patient contact, indicating presence of undetected environmental reservoirs, whilst half of the transmission events are likely due to plasmid-mediated transmission.

A ketogenic diet and the ketone body β-hydroxybutyrate are shown to confer resistance to malaria in mice by inducing metabolic reprogramming in Plasmodium parasites, suggesting a dietary strategy for malaria prevention.

To mark the occasion of Nature Chemistry turning 10 years old, we asked scientists working in different areas of chemistry to tell us what they thought the most exciting, interesting or challenging aspects related to the development of their main field of research will be — here is what they said.

The quantitative relationship between the fluctuation of specific extrinsic and intrinsic factors, and stochastic fluctuations in gene expression - or noise - has not been clearly established. Here, Yang et al.demonstrate that intrinsic noise is independent of - while extrinsic noise scales linearly with - variation in RNA polymerase abundance.

SpatialGlue is a graph neural network-based approach for integrating multimodal spatial omics data. Combining complementary data modalities improves the discovery of spatial domains as well as the identification of cell subpopulations across tissues.

Increasing the metal loading of single-atom catalysts (SACs) typically results in aggregation, which can have a detrimental effect on catalytic performance. Now, a nitrogen-doping-assisted atomization approach is reported that transforms metal-sulfide nanoparticles into ultrahigh-density metal–nitrogen–carbon SACs.

Favoured cathodes for batteries should include abundant and redox-active elements, such as manganese. Here the authors report a Na_0.6Li_0.2Mn_0.8O₂ cathode design featuring a unique layer stacking sequence that provides topological protection to oxygen redox to overcome the performance fading.

Cancer cells often develop resistance to radiotherapy but the molecular mechanisms responsible remain unclear. Here the authors show that miR-205 promotes radiosensitivity and is downregulated in radioresistant subpopulations of breast cancer cells, and that its loss is associated with poor distant relapse-free survival in breast cancer patients.

Here the authors identify silicon as an optimal element for anchoring oxygen on copper, nickel or iron surfaces to prevent oxidation. An atomically thin layer of SiMOx (M = Cu, Ni, or Fe) renders the metal surface impermeable to oxygen up to 400 °C while preserving the electrical properties.

Methods for transition-metal-catalysed enantioselective C(sp³)–S bond construction are underdeveloped. Now, by taking advantage of the biomimetic radical homolytic substitution manifold, the copper-catalysed enantioconvergent C(sp³)–S cross-coupling of racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles has been realized. This reaction provides access to an array of α-chiral alkyl organosulfur compounds.

Niacin is used to treat cardiovascular disease through its activation of the GPCR HCAR2. Here, the authors present cryo-EM structures of HCAR2 bound to niacin and other drug-like small molecules, which explain the basis of HCAR2 ligand recognition.

Intrinsic resistance to tyrosine kinase inhibitor (TKI) drugs is limiting the progress of targeted cancer therapies. The efficacy of TKIs relies on their inhibition of oncogenic signaling but also on the induction of apoptosis in cancer cells, driven by activation of pro-apoptotic BIM proteins. The authors identify a germline BIM polymorphism common in East Asian individuals that switches BIM splicing, eliminating the BH3 domain responsible for apoptosis induction. The polymorphism provides resistance to TKIs, such as BCR-ABL inhibitors in chronic myeloid leukemia and EGFR inhibitors in non–small-cell lung cancer samples, and drug sensitivity can be reinstated by addition of BH3-mimetic drugs. The polymorphism predicts treatment responses and outcome in East Asian patients with leukemia and lung cancer and could provide useful guidance for therapeutic implementation.

Chemical vapor deposition enables the scalable production of 2D semiconductors, but the grown materials are usually affected by high defect densities. Here, the authors report a hydroxide vapour phase deposition method to synthesize wafer-scale monolayer WS₂ with reduced defect density and electrical properties comparable to those of exfoliated flakes.

Riboswitches recognize and respond to specific metabolites by altering gene expression. Here, the authors developed a high-throughput method (PARCEL) to experimentally identify RNA aptamers across transcriptomes.

A synthesis of global change experiments that manipulated temperature, precipitation, carbon dioxide or nitrogen identifies a need to consider site-specific factors and interactions in Earth system models.

The bacterium Helicobacter pylori, often found in the human stomach, can be classified into distinct subpopulations associated with the geographic origin of the host. Here, the authors provide insights into H. pylori population structure by collecting over 1,000 clinical strains from 50 countries and generating and analyzing high-quality bacterial genome sequences.

Multicomponent colloidal nanostructures have topologically dependent chemical and physical properties, but are difficult to synthesise with high order complexity. Here, Nie and co-workers show a general and scalable route to synthesise such structures with unique coaxial-like construction.

Microtubule-stabilizing agents (MSAs) promote the polymerization of tubulin and are of great interest as anticancer drugs. Here the authors present the crystal structure of the MSA taccalonolide AJ bound to tubulin and give insights into its mode of action, which might help in the design of novel MSAs.

The development of highly ordered intermetallic catalyst for oxygen reduction reactions suffers from large diffusion barrier for atom ordering. Here, the authors use a low melting-point metal doping strategy to synthesize a series of highly ordered metal-doped platinum–cobalt alloy fuel cell catalysts.

A novel synthetic approach makes it possible to grow MoS₂ monolayers where S is fully replaced with Se atoms only in the top layer.

The tumour suppressor p53 inhibits cancer cell proliferation and induces apoptosis. A new tumour-suppressive effect of p53 is to induce MDM2-dependent degradation of the tumour invasion factor Slug, resulting in reduced metastasis.

A magnetic spin Hall effect is reported in the collinear antiferromagnet Mn₂Au.

Electrically switching perpendicular magnetized ferromagnets using spin-orbit torques without assisting magnetic fields is a major goal for spintronics. Recently, several works have proposed using out-of-plane spin polarized currents to achieve this, but these rely on antiferromagnetic metals with low Neel temperatures. Here, Wang et al show that such out-of-plane spin polarization driven switching can be achieved using the interface of an antiferromagnetic insulator and a heavy metal.

Binning is an essential step in genome-resolved metagenomic analysis in which assembled contigs originating from the same source population are clustered. However it is challenging, especially for low abundance microbial species. Here the authors introduce a toolkit that integrates multiple prominent binning tools and AI for efficient and high-resolution recovery of non-redundant bins from short- and long-read metagenomic sequencing datasets.

Invasion of the gut by oral bacteria in liver cirrhosis.

Achieving stable production by co-culturing multiple microorganisms is often challenging due to difficulties in controlling its population. Here, the authors develop a “population guider” that can acclimate a population to higher production.

The magnetic exchange interaction of MnBi₂Te₄—an intrinsic magnetic topological insulator—can be tuned by intercalating ferromagnetic layers of MnTe.

A chemoproteomic strategy called RNA-mediated activity-based protein profiling (RNABPP) was developed to profile RNA-modifying enzymes in live cells and uncover the RNA substrates of the human dihydrouridine synthase DUS3L.

Rubio-Navarro et al. identify a subset of pancreatic beta cells marked by high CD63 levels with enhanced glucose-stimulated insulin secretion. CD63-high beta cells are diminished in mouse models of and in humans with type 2 diabetes.

Potential synergism between BTK inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab in patients with aggressive Relapsed/Refractory aggressive B-cell non-Hodgkin lymphoma.

Engineering the coordination environment of single atom catalysts offers to opportunity to optimize electrocatalytic activity. In this work, the authors prepare an unsymmetrical Cu-S₁N₃ single atom site on porous carbon with high performance in the oxygen reduction reaction.

Metal-organic framework glasses are gaining interest, but large samples are difficult to fabricate and mechanical properties are not well understood. Here, the authors use experiments and simulations to assess fracture toughness and flexural strength of a zeolitic imidazolate framework glass.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype with limited effective therapeutic options. Here, the authors identify the RNA-binding protein ELAVL3 as a driver of differentiation into NEPC via a positive feedback loop with MYCN and demonstrate the use of the repurposed drug pyrvinium pamoate to target this axis using preclinical models of NEPC.

Copper is unique among CO₂ electrocatalysts owing to its ability to produce multicarbon products at high rates; however, achieving selectivity for specific products remains challenging. Here, Cu surfaces decorated with alkaline earth metal oxides are found to strongly favour alcohols over hydrocarbons.

A unified framework to understand gene expression noise is still lacking. Here the authors derive a universal theorem relating the biological noise with dynamics of birth and death processes and present a model of transcription dynamics, allowing analytical prediction of the dependence of mRNA noise on mRNA lifetime variability.

Non-viral CAR-T cells with gene-specific targeted integration are safe and effective in patients with lymphoma.