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CAR-T cells engineered with αPD-L1–IL-12 fusion proteins show antitumour activity in mouse models of prostate and ovarian cancer.

Scanning tunnelling microscopy shows that electrons in twisted bilayer graphene are strongly correlated for a wide range of density. In particular, a correlated regime appears near charge neutrality and theory suggests nematic ordering.

Additions to alkenes and alkynes are useful routes for generating highly functionalized products. Here the authors report the 1,1-difunctionalization of alkynes through a CuH-catalysed asymmetric hydroboration/hydroamination cascade.

Amyloid fibrils can adopt a range of distinct conformations, yet it is challenging to rapidly discriminate between these polymorphs. Now methods have been developed to screen large, diverse libraries of turn-on fluorescent dyes to rapidly identify probes that recognize fibril subsets.

The feasibility of satellite-assisted quantum communication is demonstrated by a field test on the ground. To supress noise due to sunlight the wavelength of 1,550 nm is chosen, and spectrum and spatial filtering technology developed.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Bacterial enzymes synthesize androgens that could promote cancer cell progression interfering with the efficacy of steroid-targeted prostate cancer therapies.

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.

Wearable sensors typically require innovative methods of energy harvesting for low-power electronics. Here, the authors present an adaptive power management system with a trimodal energy harvesting approach.

Previous work has realized a superconducting switch in heterostructures of superconductors and ferromagnetic insulators, but the effect has been smaller than originally predicted. Here, the authors report an absolute superconducting switch by inserting a heavy metal layer in the EuS/Nb/EuS heterostructure.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Single-cell data analysis is challenging due to inherent noise and sparsity. Here, authors introduce scMINER, a mutual information-based integrative tool to enhance clustering and reveal regulatory networks and hidden biological drivers by transforming scRNA-seq expression into activity profiles.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

The efficient separation of chiral molecules is a fundamental challenge in the manufacture of pharmaceuticals and light-polarising materials. Here, the authors develop an approach that combines machine learning with a physics-based representation to predict resolving agents for chiral molecules, using a transformer-based neural network.

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

Directed evolution is a powerful method to optimize protein fitness. Here, authors develop an active learning workflow using machine learning to more efficiently explore the design space of proteins.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The bactericidal action of some antibiotics is associated with increased ATP consumption, cellular respiration, and reactive oxygen species formation. Here, Li et al. show that constitutive hydrolysis of ATP and NADH (or ‘bioenergetic stress’) potentiates the evolution of antibiotic resistance and persistence in E. coli.

Using large-scale multimodal retinal and brain imaging data, the authors map eye-brain connections and uncover underlying genetic factors, suggesting the retina as a window into brain structure, function, and disorders.

The crystal structure of V1/V2, the only unresolved portion of the HIV-1 gp120 envelope glycoprotein, is reported in complex with human antibody PG9 and reveals a paradigm of antibody recognition with implications for vaccine development.

Yang et al. show that transcription–replication collisions lead to large tandem duplications, which are frequent in female-enriched, upper gastrointestinal tract and prostate cancers and are associated with poor survival and mutations in specific genes, such as CDK12.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Based on numerical models and the comparison with natural settings, this study reveals that divergent mantle flow induced by lower-mantle upwelling can cause anomalous subsidence. Interaction between the upwelling and remnant blocks can extend the duration of the upwelling and focus the subsidence into a narrow region.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

Water has a role to play in the future of cooling but is currently limited by the lack of meaningful control methods. Here, authors demonstrate the ability of electrostatic fields to act as a catalyst for water-based evaporative cooling, paving the way for widescale adoption of evaporative cooling.

A new Cretaceous arachnid fossil encased in Burmese amber sheds light on the evolution of spiders, as it preserves both primitive and derived features, suggestive of a basal Araneae position.

Using RFdiffusion, a general method for targeting intrinsically disordered proteins and regions for protein design has been developed.

An example of hybrid incompatibility between maize and teosinte reveals a selfish toxin–antidote system mediated by small RNAs that may have contributed to the origin of maize.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Multidrug-resistant (MDR) tuberculosis threatens global control of tuberculosis disease. Here, the authors investigate mechanisms underlying the collateral sensitivity of MDR Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline.

The sensitivity of mesothelioma to the treatment of immune checkpoint blockade remains elusive. Here this group reports a double blind, placebo-controlled, randomized phase III trial of PD1 inhibitor (Nivolumab) on 332 patients with relapsed mesothelioma, and to uncover determinants of efficacy.

Comprehensive genomic and transcriptomics analyses of more than 1,300 cases of childhood T-lineage acute lymphoblastic leukaemia identify 15 distinct subtypes that are associated with specific outcomes.

Alkynes found in natural products are typically assembled by metal-dependent enzymes. The enzyme BesB instead forms a terminal alkyne-containing amino acid using pyridoxal phosphate as a cofactor. Here, the authors use structural and mechanistic investigations to identify the key features of BesB that allow it to carry out its fascinating chemistry.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Protocol for fabricating synthetic viscoelastic antigen-presenting cells and their application in T cell engineering. These synthetic cells support robust T cell activation and expansion and improve chimeric antigen receptor transduction efficiency.

Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

In a prespecified interim analysis of the phase 3 trial GEMSTONE-304, anti-PD-L1 with chemotherapy versus chemotherapy alone led to significantly prolonged progression-free survival and overall survival of patients with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

The causative agent of sea star wasting disease has been elusive. This study used genetic datasets and experimental exposures to demonstrate that a strain of the bacterium Vibrio pectenicida caused disease and mortality in sea stars.