Nuclear wrinkling and chromatin state mediate stiffness-induced breast cancer

This issue highlights a non-invasive physical biomarker of the long-term prognosis of corneal restoration in patients, the serial functional assessment of leukocytes isolated from microlitre samples of peripheral blood from sepsis patients, T-cells engineered via the orthotopic replacement of the T-cell receptor chains, the enhanced expansion of keratinocytes from adult human skin, aberrant mechanosensing in injured intervertebral discs, and mechanopathology in mammary epithelium.

The cover illustrates that a stiff extracellular matrix induces a tumorigenic phenotype in mammary epithelial cells through nuclear wrinkling and broad changes in chromatin accessibility.

See Stowers et al.

Deep learning discriminates visual impairments in infants via the analysis of recorded behavioural patterns

This issue highlights deep learning for the analysis of behavioural patterns in visually impaired infants, for generating volumetric tomographic images of a patient from a single projection view, and for the real-time tracking of the movements of multiple mice. It also includes the use of computation for designing self-assembled antibody–drug conjugates, for guiding personalized targeted ablation in patients with atrial fibrillation, for determining proteomic heterogeneities in acute myelogenous leukaemia and for finding factors that predict brain-connectivity patterns in patients with epilepsy.

The cover illustrates the deep-learning-based classification of infants by ophthalmologic condition via a deep-learning algorithm trained on standardized video recordings of the behaviour of infants with varying degrees of visual impairment.

See Long et al.

Traceless isolation of killer T cells via DNA aptamers

This issue highlights an overview of immunotherapies leveraging engineering approaches, the traceless isolation of CD8+ T cells for CAR-T cell therapy, high-throughput immunomagnetic cell sorting implemented in a microfluidic chip, orthologous therapeutic proteins that elude the adaptive immune system, glycosylated peptides for preventing T-cell-mediated diabetes in mice, and a cell-culture system for assembling 3D tissue models by stacking layers containing pre-conditioned microenvironments.

The cover illustrates the isolation of CD8+ T cells by magnetic microbeads functionalized with DNA aptamers that specifically bind to the T-cell marker CD8 and that can be displaced by a complementary oligonucleotide.

See Kacherovsky et al.

Barcoded DNA structures for the subcellular profiling of proteins

This issue highlights tumour-cell-derived microparticles as efficient drug-delivery carriers, the boosting of chemotherapy in colonic tumours via the phage-guided modulation of gut microbiota, the delivery of a therapeutic monoclonal antibody to metastases in the central nervous system, the augmentation of canonical Wnt signalling to produce cell factories of therapeutically potent exosomes, integrated glass microelectrodes for in vivo brain electrophysiology, and barcoded DNA nanostructures for the profiling of subcellular protein distribution.

The cover illustrates tetrahedral DNA nanostructures that act as barcodes for the high-throughput multiplexed profiling of the subcellular expression and distribution of proteins in cells.

See Sundah et al.

A sprayed supramolecular film cuts down on pericardial adhesions

This issue highlights a thermogelling polymer endotamponade for retinal-detachment repair, a supramolecular gel as a post-operative pericardial adhesion barrier, a mechanical injector that targets tissue by sensing the loss-of-resistance on encountering softer tissue or a cavity, a viscoelastic adhesive epicardial patch for treating myocardial infarction, bioresorbable photonic devices for the spectroscopic characterization of tissues and biofluids, and wireless soft optofluidic probes with plug-like drug cartridges for chronic in vivo pharmacology and optogenetics.

The cover illustrates a sprayable supramolecular hydrogel that adheres to the pericardium to reduce the incidence and severity of post-surgical adhesions. The image is a composite of two photographs, one from a gel-coated sheep heart (left) and one from an uncoated sheep heart (right).

See Stapleton et al.

A microphysiological model for the study of bronchial spasms

This issue highlights microphysiological systems of the human bronchial airways, the human gut microbiome, a glioblastoma tumour and cartilage, as well as an in vitro model of the formation of bone-like nodules recapitulating the osteogenesis-imperfecta phenotype, and a comparison of three congruent patient-specific cell types for the modelling of an inherited neurological disorder.

The cover shows a sham device of a microphysiological system that recapitulates the mechanochemical environment of the human bronchial airways.

See Kilic et al.

Amplification-free nucleic-acid testing

This issue highlights a nanopatterned microfluidic chip for the detection of circulating exosomes in patient samples, a microfluidic assay for the quantification of the metastatic propensity of breast cancer cells, an amplification-free electrical biosensor for nucleic acids, virtual staining of unlabelled tissue sections via deep learning, and a quantitative microimmunohistochemistry assay for the grading of immunostains on tumour tissues.

The cover illustrates an electrical biosensor for nucleic acids that relies on the binding of target sequences to Cas9 immobilized on a graphene field-effect transistor.

See Hajian et al.

Whole-brain optoacoustic imaging of neuronal dynamics

This issue highlights dual positron-emission-tomography–near-infrared probes for the visualization of the trafficking dynamics of a model mRNA vaccine in non-human primates, photoacoustic imaging applied to single-cell intratumoral metabolic heterogeneity and to whole-brain snapshots of neuronal calcium activity in mice, the spectral tracing of glucose metabolism in mice, optoacoustic mesoscopy for biomedicine, and a roadmap for the clinical implementation of optical-imaging biomarkers.

The cover illustrates high-resolution snapshots of neuronal calcium activity across the brain acquired via the optoacoustic imaging of live mice expressing a genetically encoded calcium indicator.

See Gottschalk et al.

Urinary nanosensors of allograft rejection

This issue highlights nanosensors for the non-invasive early detection of acute transplant rejection, an immunotoxin that suppresses autoimmunity, the enhancement of T-cell antitumour responses via the inhibition of PD-L1 palmitoylation, enhanced antitumour activity by a nanomedicine encapsulating a docetaxel prodrug and conjugated to an ephrin-receptor-specific antibody, and the combination of high-throughput nanoparticle synthesis and machine learning to efficiently explore structure–activity relationships for nanomedicines.

The cover illustrates nanoparticle sensors of the activity of the protease granzyme B, for the detection of acute rejection of transplanted skin grafts.

See Mac et al.

Scaled-up epidermal electrodes

This issue highlights large-area electrode arrays for epidermal electrophysiology, deep learning for the detection of acute intracranial haemorrhage, an inexpensive assay for the classification of cancer patients, a computationally designed small molecule that ameliorates the symptoms of transmissible spongiform encephalopathy in animal models, intradermal microneedles for the weeks-long delivery of a contraceptive in rats, and the mechanopathology of compressive tumours.

The cover illustrates a scalp covered by fractal mesh electrodes for electroencephalography.

See Tian et al.

Jointly acting gene variants in cardiomyopathy

This issue highlights complex genetic heritability in cardiomyopathy, magnetic-field-activated CRISPR-mediated local genome editing, the use of CRISPR to generate skin epidermal stem cells that protect mice from cocaine overdose, interleukin-31-mediated photoablation of itch-sensing skin neurons in mice with atopic dermatitis, and the stiffness-mediated activation of the expression of a common genetic polymorphism associated with cardiac pathology.

The cover illustrates that two genetic variants found in patients with dilated cardiomyopathy jointly contribute to the complex genetic heritability of the disease.

See Deacon et al.

Hydrogel electrodes for interfacing with tissue

This issue highlights advances in the fabrication and applications of implantable bioelectronic devices, including wireless and resorbable pressure sensors, soft nerve stimulators, a wirelessly powered optoelectronic device for low-dose and long-term photodynamic therapy, inductively coupled resonant circuits for the remote sensing of bioluminescence, and a wireless closed-loop neuromodulation device.

The cover illustrates a hydrogel-based polymer-encapsulated microelectrode array pressed against soft jelly.

See Liu et al.