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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.

Transcription factor COUP-TFII is elevated in the hearts of non-ischaemic cardiomyopathy patients, but the nature of this correlation is unknown. Here the authors show that forced cardiac expression of COUP-TFII in mice causes dilated cardiomyopathy because of altered mitochondrial function and impaired metabolic remodelling.

Cryo-electron microscopy structure of heterodimeric GABA_B receptor in complex with G_i1 protein reveals that the mode of G-protein binding in this class-C G-protein-coupled receptor differs from that of other classes.

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

Here, a long noncoding RNA, termed Mhrt, is identified in the loci of myosin heavy chain (Myh) genes in mice and shown to be capable of suppressing cardiomyopathy in the animals, as well as being repressed in diseased human hearts.

Zeroth-order optimization is used on problems where no explicit gradient function is accessible, but single points can be queried. Hoffman et al. present here a molecular design method that uses zeroth-order optimization to deal with the discreteness of molecule sequences and to incorporate external guidance from property evaluations and design constraints.

The metastatic tumour microenvironment in pancreatic ductal adenocarcinoma (PDAC) remains to be explored. Here, the authors perform single cell RNA sequencing analysis for synchronously resected PDAC primary tumours and matched liver metastases and find differences in cellular composition.

Nitric oxide delivered and released by a nanoscale carrier improves the therapeutic effectiveness of chemotherapeutics and immunotherapy by normalizing tumour vasculature.

Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

Cells in large heterogeneous cell populations can be selectively photolabelled according to specific functional dynamics via an optical microscope with an ultrawide field of view, fast image analysis and a photoactivatable dye.

Metasurfaces suffer from large chromatic aberration due to the high phase dispersion of their building blocks, limiting their applications. Here, Wang et al. design achromatic metasurface devices which eliminate the chromatic aberration over a continuous region from 1200 to 1680 nm in a reflection schleme.

Marine cyanobacteria contribute to global carbon balance by fixing CO₂ and the shift between CO₂ fixation and ATP production requires fine-tuning its metabolic fluxes to light–dark cycles. These cycles can be very short in marine environments due to sea currents and fast adaptation is key to avoid futile cycles. In this study, Lu et al. provide a mechanistic insight into how this process is tightly regulated.

A synthetic control approach to model avoided forest loss shows that a protected-areas programme in India aimed at tiger conservation is associated with significant reductions in carbon emissions.

Characterisation of the human antibody response to SARS-CoV-2 can help the design of serological tests and vaccines. Here, the authors identify two linear epitopes in SARS-CoV-2 spike protein that elicit neutralising antibodies in several patients and could thus be useful for serology and vaccine development.

The proteogenomic landscape of diffuse gliomas remains to be explored. Here, the authors perform proteogenomic characterisation of diffuse gliomas, investigate the functional role of genomic alterations and suggest three proteomic subgroups.

Mutations in PHF8 gene are genetically associated with X-linked mental retardation. Here, Chen et al. show that Phf8 KO mouse have cognitive and synaptic plasticity impairment, and pharmacological inhibition of mTOR signaling can partially alleviate such defects.

The molecular mechanisms controlling injury-dependent neuronal regeneration are largely unknown. Here, the authors use integrated multiomic analysis to characterize gene regulatory networks controlling injury-induced neurogenesis in zebrafish retina

The adaptor protein zyxin is known for its mechanosensing function in the maintenance of actin network. Here the authors show that zyxin is key to blood homeostasis and thrombosis by controlling the endothelial release of von Willebrand factor and the formation of actin scaffolds on exocytic granules.

Energy band alignment theory is used to understand interface charge transfer in semiconductor/semiconductor junctions but many abnormal results cannot be well explained. Here, the authors demonstrate a Faradaic junction theory with isoenergetic charge transfer at semiconductor/semiconductor interfaces to explain these abnormal results.

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.

Chen et al. demonstrate that transient Scute activation induces asymmetric division in Drosophila intestinal stem cells, which generates enteroendocrine progenitor cells that divide once before differentiation to yield a pair of enteroendocrine cells.

The authors describe stem cell-derived bone marrow organoids that accurately model the structural and functional properties of the human bone marrow niche.

Huang et al. analyze matched adults with obesity receiving Tirzepatide, Semaglutide, Phentermine/Topiramate, Naltrexone/Bupropion, or Phentermine monotherapy. Iirzepatide mirrors semaglutide for ocular safety, while both drugs link to fewer cataracts, oculomotor dysfunction, and visual issues than phentermine or naltrexone/bupropion.

Fuel cells are promising for converting fuel into electricity, but rely on development of high-performance catalysts for oxygen reduction. Here the authors report a highly durable platinum-trimer decorated cobalt-palladium catalyst with low platinum loading for electrocatalysis of oxygen reduction.

In a phase 2a clinical trial in patients with nonalcoholic steatohepatitis, dual inhibition of sodium–glucose cotransporters 1 and 2 with 150 mg of licogliflozin led to reductions in serum alanine aminotranferase levels.

The molecular mechanisms that direct the development of intestinal intraepithelial lymphocytes (IELs) remain unclear. Chen and co-workers demonstrate a role for TGF-β in the development of TCRαβ⁺CD8αα⁺ IELs.

LKB1 is frequently mutated in lung squamous cell carcinomas. Here, the authors show that sole LKB1 depletion is sufficient to drive the development of this cancer, where downstream defective MKK7-JNK1/2 signalling activates the ∆Np63/p63 pathway to induce subsequent epithelial cells transformation and tumour progression.

Interferons are critical soluble components of the inflammatory process and are composed of three types with associated receptor complexes. Here the authors identify and characterise the type IV interferon, IFN-υ, and identify its associated receptors, denote functionality during in vivo infection and ascertain its genomic localisation.

Early cancer detection by cell-free DNA (cfDNA) is challenged by the low amount of tumour DNA in cfDNA, tumour heterogeneity and the small patient cohorts. Here, the authors develop a method, cfMethyl-Seq, for cost-effective methylome profiling of cfDNA and for detecting and locating cancer.

Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

TOM complex is a bidirectional channel in the mitochondrial outer membrane that mediates import of proteins into mitochondria and retrotranslocation of damaged proteins out of the organelle in the Mitochondria-Associated Degradation pathway.

Extracellular vesicles (EVs) are present in circulation at relatively early stages of disease, providing potential opportunities for early cancer diagnosis. Here, the authors report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific EV purification system for early detection of HCC by performing digital scoring on the purified EVs.

A mild electrochemical exfoliation method has been developed to obtain large-size two-dimensional superconductor monolayers with high crystallinity and production yield, which enables the easy fabrication of twisted van der Waals heterostructures and printed films.

In metastatic lymph nodes, solid stress generated by metastatic growth prevents the infiltration of lymphocytes into the lesions.

A computational method leveraging deep learning and molecular dynamics simulations enables the rapid discovery of antimicrobial peptides with low toxicity and with high potency against diverse Gram-positive and Gram-negative pathogens.

Single-atom catalysts are very attractive due to their ability to maintain high activities at the lowest possible precious metal loading. Here, a double transition metal MXene that effectively anchors single Pt atoms is reported, and exhibits superior performance and stability towards the hydrogen evolution reaction.

TGF-β and Foxp3 are required for the development of regulatory T cells. Chen and colleagues show that the helix-loop-helix proteins E2A and Id3 enhance Foxp3 expression and relieve it from inhibition by other transcription factors.

Aging is associated with immune attrition that may impact the effectiveness of the immune system to protect the host from pathogens. Here the authors show that immune aging is associated with alterations in the Wnt/β-catenin signaling and reduced stem cell memory T lymphocytes, hinting the Wnt/β-catenin pathway as a potential therapy target.

Mitochondria of alveolar type 2 epithelial cells (AEC2) in the lung have been suggested to play a role in the development of idiopathic pulmonary fibrosis (IPF). Here the authors show that loss of mitofusin1 and mitofusin2 in murine AEC2 cells leads to the development of lung fibrosis through the regulation of surfactant lipids.