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Soft auditory brainstem implant in the cochlear nucleus of macaque evokes auditory-like perceptions with high resolution and tonotopic specificity.

Spinal cord injury leads to lasting motor and sensory loss, with limited treatment options. Here, the authors show that subdural electric field stimulation delivered across the injury via an ultra-thin implant improves functional recovery in rats.

By unifying data from engineered β-barrel nanopores and supported by modelling, it is demonstrated that the lumen charge in a β-barrel nanopore governs rectification and voltage-driven gating, with applications in computing using nanofluidic synapses.

Using extended-gate capacitive coupling and diode connection, stretchable biosensors with a built-in differential circuit design can be created that can offer low signal distortion under bias stress instability, uniaxial strain, compression and temperature variations.

An integrated smart capsule that encapsulates an array of electrochemical sensors can provide real-time, continuous and multiplexed monitoring of the gastrointestinal tract.

Intravenous delivery of an adenine base editor and a single-guide RNA for the Fah gene can correct an A>G splice-site mutation in an adult mouse model of tyrosinaemia.

Nease and colleagues demonstrate that the methyltransferase FTSJ1 mediates selenocysteine-specific tRNA methylation of selenoproteins, which protects melanoma cells against oxidative stress and promotes metastasis.

Directed evolution typically requires extensive screening. This work presents an ultrahigh-throughput microfluidic assay, based on a coupled reaction and fluorescence-activated droplet sorting, enabling a 960-fold activity improvement of an amine oxidase for a non-natural substrate in a single round.

Intradermal microneedles for the co-delivery of mRNA and near-infrared fluorescent microparticles are used in combination with deep learning-based image analysis for the simultaneous administration of therapeutics and registry of patient information records into the skin.

Existing patterning methods for thin metal films rely on prefabricated rigid masks incompatible with soft substrates. Here, the authors report printable and stretchable metal-vapor-desorption layers that facilitate high-fidelity patterning, enabling circuits and devices on 3D curvilinear and stretchable substrates.

A high-fructose diet in mice improves the survival of intestinal epithelial cells, which leads to an increase in gut surface area, enhanced absorption of lipids and the promotion of tumour growth and obesity.

Injury repair is characterized by the generation of transient cell states important for tissue recovery. Here, the authors present a single cell RNA-seq map of recovery from bleomycin lung injury in mice and uncover a Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis.

The transient reactivation of ETV2 in adult human endothelial cells reprograms these cells to become adaptable vasculogenic endothelia that in three-dimensional matrices self-assemble into vascular networks that can transport blood and physiologically arborize organoids and decellularized tissues.

A wearable sweat sensor powered by a flexible solar cell can continuously collect multimodal physicochemical data—glucose, pH, sodium ion, sweat rate and skin temperature—across indoor and outdoor physical activities for over 12 h.

A surface functionalization approach allows for preparing a nanostructured molecular protection layer, enabling stretchable polymer electronics that stably operate in physiological environments over 80 days.

Miniaturization of optical components could give way to dense photonic-integrated circuits. Here, the authors demonstrate the control of evanescent waves using all-dielectric metamaterials and show that they can reduce cross-talk and bending loss, which limit the integration density in photonic circuits.

A model that predicts the force behaviour for solid/liquid-dielectric multilayer stacks independent of actuator design, and solely based on the material properties, can be used to develop actuators that provide a steady force output under constant-voltage operation.

Endothelial cells at the inner surface of blood vessels are exposed to mechanical forces as a result of blood flow. Here the authors show that the interaction of extracellular matrix proteins with adhesion molecules on the endothelial cell surface determines cellular stiffness and sensitivity to mechanical forces.

Pannexins are oligomeric plasma membrane channels that allow permeation of ions and large molecules. Here the authors show that human Pannexin 1 activation is a multistep event, where modification of each monomer opens the channel to a unique conductance state and fine tunes its activity.

The function of single-nucleotide variants can now be tested in a base editor mouse model.

Recent evidence suggests thatEIF3E–RSPO2 and PTPRK–RSPO3gene fusions promote colorectal cancer. Here, using CRISPR-mediated genome editing, the authors show that endogenous Rspo2 or Rspo3 chromosome rearrangements result in intestinal tumours extremely sensitive to Wnt ligand inhibition.

Alterations in oncogenes and tumor suppressor genes are a hallmark of cancer, yet how they interact remains poorly understood. Here, the authors describe a quantitative functional cancer genomics platform in genetically engineered mice, and uncover complex interactions between tumor suppressors and KRAS, BRAF, and EGFR oncogenes across more than 100 different lung tumor genotypes.

Improved base editing libraries enable high-throughput functional analysis of single-nucleotide variants in cancer.

Mouse lines with an inducible Cas9 gene enable in vivo disease modeling.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

A microfluidic chip is used to construct a microarray of proteins, each labeled with a dockerin tag, for high-throughput single-molecule force spectroscopy experiments using a single cohesin-modified cantilever.

CRISPR base editors can induce single-base-pair changes in the genome, although they are often inefficient. A study now shows that fusion of the DNA-binding domain of RAD51 to base editors enhances both the efficiency and the targeting range of optimized enzymes. These ‘hyper-editors’ offer effective tools for disease modeling and gene therapy.

Genetically engineered colon organoids form tumors that undergo a stepwise progression toward metastatic disease after orthotopic transplantation.

Rectal cancer organoids retain the pathological features of matched patient tumors and recapitulate clinical responses to chemoradiation.

The efficiency of base editing is substantially increased by optimizing expression and nuclear localization of the editing enzymes.

Targeting the adipokine adipsin and its downstream pathway may provide an approach for preservation of beta cell loss in type 2 diabetes.

BET bromodomain inhibitors are being explored as potential therapeutics in cancer; here, AML cells are shown to evade sensitivity to BET inhibition through rewiring the transcriptional regulation of BRD4 target genes such as MYC in a process that is facilitated by suppression of PRC2 and WNT signalling activation.

The use of shRNA in vivo to investigate genes involved in proliferation and survival is confounded by the competitive advantage of cells with insufficient shRNA expression. Zuber et al. address this issue with a system that combines Tet-regulated shRNA expression, two fluorescent reporters and robust transactivator production.

Innate lymphoid cells increase the growth of mouse intestinal organoids via IL-22 production; recombinant IL-22 promotes growth of both mouse and human organoids, and promotes mouse intestinal stem cell (ISC) expansion and ISC-driven organoid growth via a STAT3-dependent pathway and independently of Paneth cells; IL-22 treatment in vivo enhances the recovery of ISCs from intestinal injury.

The advent of CRISPR technologies has enabled programmable nucleic acid editing in mammalian cells. In this Review, Katti et al. outline the enormous progress that has been made in the application of CRISPR tools to the study of cancer and also describe the potential use of CRISPR systems in clinical cancer management including diagnosis and treatment.