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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.

A study of dependencies associated with cancer-causing mutations has identified a small molecule that binds to SHOC2 and inhibits RAS signalling in cells carrying NRAS Q61 mutations, a common oncogenic driver in melanoma.

Fine-tuning the RoseTTAFold structure prediction network on protein structure denoising tasks yields a generative model for protein design that achieves outstanding performance on a wide range of protein structure and function design challenges.

In this work, the authors develop mirror-image monobodies (Mb) made of D-amino acids against the BCR::ABL1 SH2 ___domain with high binding affinities. The heterochiral Mb-SH2 structures reveal an unusual binding mode. The D-Mbs are protease-resistant, inhibit BCR::ABL1 kinase activity and bind BCR::ABL1 in cell lysates.

This article reports a method based on a bifunctional chemical probe called TME and a workflow named RUBICON to capture, enrich and profile endogenous disordered proteins in cells. The method enables a proteome-wide analysis of protein disorder via high-throughput fluorescence and mass spectrometry-based proteomics.

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

The functional role of intestinal secretory IgA for host–microbiota interactions is investigated, showing that intestinal bacterial exposure leads to selection of diverse plasma cells that secrete antigen-specific IgA, which predominantly targets bacterial membranes.

Gut microbiota contribute to the pathogenesis of ulcerative colitis (UC), but the molecular mechanisms are still unclear. Here the authors show that colonic fluid from patients with UC is enriched for bacteria extracellular vesicles (BEV) coated with host IgA, and that these IgA-coated BEV may activate CD89⁺ immune cells to aggravate inflammation and colitis in mouse models.

Proteomics is often used to map protein-drug interactions but identifying a drug’s protein targets along with the binding interfaces has not been achieved yet. Here, the authors integrate limited proteolysis and machine learning for the proteome-wide mapping of drug protein targets and binding sites.

Here, the authors constructed a deep-learning approach to design closed repeat proteins with central binding pockets—a step towards designing proteins to specifically bind small molecules.

This study describes the development and characterization of peptidomimetic inhibitors of TMPRSS2, which primes the Spike protein of SARS-CoV-2. The inhibitors are shown to prevent SARS-CoV-2 infection in cells as efficiently as camostat mesylate.

Henneberg et al. developed conformation-specific antibodies enabling probing NEDD8-activated cullin–RING ubiquitin E3 ligase networks in response to extracellular stimuli, metabolic signals and degrader drugs.

Enhanced light–molecule interactions in high-finesse fibre-based Fabry–Pérot microcavities are used to detect and profile individual unlabelled solution-phase biomolecules, leading to potential applications in the life and chemical sciences.

The WNT/b-catenin pathway is essential for bloodbrain barrier (BBB) and blood-retina barrier (BRB) function. A bioengineered FZD4-selective WNT surrogate demonstrated systemic efficacy during BRB and ischemic stroke BBB dysfunction in mice.

Wong et al. demonstrate the efficacy of super-amphiphobic surfaces for in situ defoaming and inhibition of foam growth while handling aqueous solutions. Without the use of chemical additives, their passive approach suggests a facile alternative route to froth management in industrial processes.

The structure of a human exosome–ribosome supercomplex reveals the mechanisms behind the formation of active cytoplasmic exosomes and their role in co-translational RNA decay.

We combined human intestinal immuno-organoids and single-cell transcriptomics to investigate intestinal inflammation triggered by cancer-targeting biologics, which was associated with an activated population of CD8⁺ T cells that progressively acquired intraepithelial and cytotoxic features.

The subset of chronic lymphocytic leukemia (CLL) expressing the IGLV3- 21R110 BCR light chain often shows an aggressive clinical course. Here the authors report the development and characterization of IGLV3-21R110- targeted CAR T cells, showing selective targeting and eradication of IGLV3- 21R110 expressing CLL cells.

Dishevelled (DVL) is the key component of Wnt signaling pathway that acts as a signaling hub. Here, authors study the conformational dynamics of DVL3 in vivo using their engineered FlAsH-based FRET biosensors and describe how Wnt activation opens DVL and facilitates Frizzled recruitment.

A phase 1 clinical trial provides evidence that a vaccine against mutant IDH1 is safe and produces a T helper immune response in patients with glioma.

The immune system monitors the health status of cells by surveilling fragments of foreign molecules from invaders presented on MHC I complexes at the cell surface. Here, the authors investigate the sequence of events of MHC I assembly and quality control cycle.

This study identifies protein structural changes in cerebrospinal fluid of people with Parkinson’s disease relative to healthy individuals and proposes the concept of structural disease biomarkers. It also analyzes proteome structural variability in healthy people.

Battery production cost models are critical for evaluating cost competitiveness but frequently lack transparency and standardization. A bottom-up approach for calculating the full cost, marginal cost, and levelized cost of various battery production methods is proposed, enriched by a browser-based modular user tool.

Cyclic five-membered disulfides (1,2-dithiolanes) have been reported either as nonspecific redox motifs, or as highly specific cellular probes for thioredoxin reductase (TrxR). Here the authors show that 1,2-dithiolane probes are nonspecifically reduced by a range of thiol reductants and are not sensitive to TrxR modulation, thus they are unsuitable as cellular probes for TrxR.

Effects from electrolytes on supercapacitor electrodes, especially pseudocapacitive materials, are important but often overlooked. Gogotsi and colleagues demonstrate strong influences from electrolyte solvents on charge-storage processes in a titanium carbide and identify a best-performing electrode/electrolyte couple for supercapacitors.

Anticancer drugs such as Taxol can affect microtubule dynamics and organization in cells. Direct visualization of the action of such drugs has shown that they can trigger local and cooperative changes in microtubule lattice and induce formation of stable microtubule regions that promote rescues.

The TGF-β signalling pathway promotes cancer progression in late stage breast cancer, but how the pathway is activated is not always clear. In this study, Zhou et al.identify that the expression of nuclear receptor NR4A1 is induced by inflammation and is an activator of TGF-β-induced metastasis.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

Correlating the morphology of lithium-ion cathode particles with battery performance is difficult due to length-scale differences between grain architecture and particle size. Here, a generative adversarial network-based model can generate 3D cathode particles using 2D data for virtual characterization and materials testing.

Alloy systems like Si/FeSi₂ nano composites have great potential as stable anode materials in Li-ion batteries, but their characterization at different scales and throughout their ageing remains challenging. Here the authors use scattering and 2D/3D imaging techniques combined with modeling to elucidate morphology changes upon cycling of the anode.

The authors employ Quantum Monte Carlo simulations to study the scaling behavior of the magnetic structure factor and other observables in a 2D quantum critical magnet coupled to a single cavity mode. They find that while the quantum critical point remains unchanged, critical fluctuations are significantly enhanced and a fractional scaling exponent deviates from expectations based on perturbation theory.

Variability of summertime Arctic sea-ice reduction is closely linked to transient Arctic anticyclones, which result from air mass injections into the Arctic upper troposphere  associated with extratropical cyclones.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.