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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 CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

The ATR inhibitor ceralasertib has shown clinical activity in combination with immune-checkpoint inhibitors in several cancer types. Here the authors report the anti-tumor activity and the immunomodulatory changes, dependent on up-regulation of type I interferon pathway, following intermittent ATR inhibition in preclinical cancer models.

Invariant natural killer T (iNKT) cells rapidly enhance cytokine secretion and effector function following activation, but the underlying mechanism is still unclear. Here the authors show that an endoplasmic reticulum stress sensor, inositol-requiring enzyme 1α, activates the p38 kinase to stabilize cytokine mRNA for enhanced iNKT functions.

PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.

Schlafen 11 serves as an antiviral restriction factor and a predictive biomarker in cancer. Here, the authors use cryoelectron microscopy and biochemical assays to understand tRNA endoribonuclease and DNA binding functions of human Schlafen 11.

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism, which is currently treated with life-long low-protein diet that can be challenging to maintain. Here the authors develop an AAV8-directed gene therapy providing sustainable disease rescue in a mouse model of MSUD.

Fusion with the cell membrane is the earliest event in viral infection. Paludan and colleagues show that 'unscheduled' membrane-fusion events elicit an innate immune response dependent on the adaptor STING.

Methods for stabilizing enzymatic activity in the gastrointestinal tract are rarely investigated because of the difficulty in protecting proteins from an environment that promotes their digestion. Now, functionally diverse polymers have been conjugated to therapeutic enzymes, which lead to a substantial enhancement of their in vivo activity in the gastrointestinal tract.

DNA methylation in the brain is a dynamic process, but gene-specific regulation of this process is poorly understood. Here, Day and colleagues show that extra-coding RNAs interact with DNA methyltransferases and regulate neuronal DNA methylation to control gene expression in locus-specific manner in neurons.

Current approaches for volumetric super-resolution microscopy can yield large and complex PSF spatial footprints. Here, the authors show a super-resolution microscopy approach using a hexagonal microlens array, which offers speed improvements in volumetric imaging compared to other single-molecule methods.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

The nature of the active species over Cu/ZnO catalysts for methanol synthesis remains elusive. Here, the authors shed light on the evolution of the nanoparticle/support interface and correlate its structural and chemical transformations with changes in the catalytic performance.

I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single stranded, cytosine-rich genomic region, but the specific contributions of several factors involved in their formation are unknown. Using in-cell NMR, the authors examined DNA i-motif formation in human cells at body temperature, suggesting i-M occur in a small portion (<1%) of genomic sites predisposed to its formation.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

Transferrin receptor (TfR) and CD98hc are increasingly used to enable more effective drug delivery to the central nervous system. Here, the authors reveal comprehensive and distinct brain cellular and whole body biodistribution patterns of TfR- and CD98hc-binding molecules.

A bio-inspired supramolecular material combines tiny amino acid sequences present in proteins with equally small segments of the plastic poly(vinylidene fluoride), yielding high-performance sustainable ferroelectric nanostructures with potential for future resorbable bioelectronics, ultra-low power devices, and large-scale information storage.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

Population-scale whole-genome sequencing across four remote Indigenous Australian communities reveals a large fraction of structural variants that are unique to these populations, emphasizing the genetic distinctiveness of and diversity among Indigenous Australians.

Ferumoxytol (Fer) is an FDA-approved iron oxide formulation that disrupts caries-causing biofilms with high specificity but cannot interfere with enamel acid demineralization. Here, Fer is combined with stannous fluoride (SnF2), resulting in enhanced stability of SnF2 and inhibition of both biofilm accumulation and enamel damage more effectively than either alone.

Intrinsic mechanical properties of sub-100 nm thin films are markedly difficult to obtain, yet an ever-growing necessity for emerging fields such as soft organic electronics. Here, the authors present a shear motion assisted transfer technique for fabricating free-standing sub-100 nm thin films and measuring their inherent structural–mechanical properties.

Greatly enhanced light absorption is reported in large perovskite quantum dots by realizing a transition with a giant oscillator strength at the optical bandgap.

AfCycDesign: Cyclic offset to the relative positional encoding in AlphaFold2 enables accurate structure prediction, sequence redesign, and de novo hallucination of cyclic peptide monomers and binders.

Here the authors characterize a single-domain antibody that broadly neutralizes SARS-CoV-2 variants with high potency by targeting the heptad repeat 2 (HR2) coiled coil, conserved in sarbecoviruses. Binding to its quaternary epitope blocks membrane fusion, by locking HR2 in its prefusion conformation.

The mechanisms that regulate the initiation of DNA replication in archaea are poorly understood. Here, Dhanaraju et al. identify a sequence element and its interacting protein required for DNA replication initiation in the model archaeon Sulfolobus islandicus.

Covalent functionalization of single-walled carbon nanotubes with luminescent sp³-defects generally produces a variety of binding configurations and emission wavelengths. The authors propose a base-mediated nucleophilic functionalization approach to selectively achieve configurations for E₁₁* and E₁₁*^- or purely E₁₁*^- defect emission.

Apicomplexan parasites share complex cell pellicular structures that isolates the cytosol from most of the plasma membrane. Koreny et al show that, as an early adaptation to this barrier, dedicated stable endocytic structures occur at select sites in these cells. In Toxoplasma, plasma membrane homeostasis is particularly dependent on endocytosis.

Phospholipids enhance the structural and colloidal integrity of hybrid organic–inorganic lead halide perovskites and lead-free metal halide nanocrystals, which then exhibit enhanced robustness and optical properties.

Genomic analysis of 118 cervical tumors from Ugandan individuals identifies HPV-clade-specific differences in tumor DNA methylation, regulatory-region-associated histone marks, gene expression and pathway dysregulation.

Neutralizing antibodies to oligomannose glycans on HIV Env are difficult to elicit, possibly due to B cell tolerance. Here, Pantophlet et al. synthesize mimetics based on a bacterial oligosaccharide and show that they evoke HIV-neutralizing antibody responses in animals with a human Ig repertoire.

Here, the authors have generated a metacapase type II depletion model providing evidence for their paramount role in seed longevity. They also show that this is accomplished by regulating the ERAD, the proteostatic pathway crucial for seeds.

Oestrogen negative breast cancer is associated with a poor prognosis. In this study, the authors perform a meta-analysis of 11 breast cancer genome-wide association studies and identify four new loci associated with oestrogen negative breast cancer risk. These findings may aid in stratifying patients in the clinic.

Combining localization and polarization microscopy can yield detailed insights into subcellular structures. POLCAM uses a polarization camera and wide-field microscopy for rapid measurement of super-resolution orientation imaging in live cells.

Dysfunctions of the mitochondrial OXPHOS system lead to severe human disorders. Here, the authors analyzed a mouse mutant that mimics a mitochondrial disorder patient and find that reactive oxygen species trigger RNA release and inflammatory pathway in liver.

Ska1 is a kinetochore-localised protein that couples kinetochore movement to microtubule (MT) depolymerisation. Here Thomas et al. show that the MT +TIP binding protein EB1 recruits Ska1 to the MT-kinetochore interface and stabilises the interaction between Ska1 and MTs.

Antibody pre-adsorption on the nanocarrier surface is a mild modification strategy that preserves antibody functionality and targeting ability.

In S. pombe, small non-coding RNA mediates heterochromatin formation by recruiting the nucleosome remodeling and histone deacetylase complex. Here, the authors show that fly nucleosome remodeler Mi-2 and histone deacetylase Rpd3 are involved in piRNA-dependent transcriptional silencing of transposable elements.

The architecture of functional TNTs is still under debate. Here, the authors combine correlative FIB-SEM, light- and cryo-electron microscopy approaches to elucidate the structure of TNTs in neuronal cells, showing that they form structures that are distinct form other membrane protrusions.

Inhibiting POLR2A expression upon siRNA delivery represents a promising therapeutic strategy for triple negative breast cancers characterized by p53 inactivation.

Splicing factors such as BUD31 are identified in a synthetic-lethal screen with cells overexpressing the transcription factor MYC; oncogenic MYC leads to an increase in pre-mRNA synthesis, and spliceosome inhibition impairs the growth and tumorigenicity of MYC-dependent breast cancers, suggesting that spliceosome components may be potential therapeutic targets for MYC-driven cancers.

Eumelanin’s potential in electrochemical applications is hindered by its poor solubility in polar solvents. Here, the authors explore functional group modifications, revealing that nitro groups enhance water solubility and electrochemical performance, highlighting the critical role of electron-withdrawing effects in optimizing eumelanin-based devices.

It remains critical to identify colorectal cancers (CRC) that will disseminate as early as possible. Here, the authors identify CRC tumours that are aggressive and prone to early dissemination, characterised by epithelial TGFβ and growth-factor signalling - which could be targeted with MEK/EGFR inhibitors.

Characterization of the myotis bat morbillivirus shows that infection in human cells is restricted by innate immune responses in vitro and cross-neutralization by sera from measles, mumps and rubella vaccinees.

Pseudocapacitors based on redox-active materials have relatively high energy density but suffer from low power capability. Here the authors report that two-dimensional transition metal carbides exhibit high gravimetric, volumetric and areal capacitance values at high charge/discharge rates.

Lipid droplets (LDs) are cellular organelles dedicated to triacylglycerol storage that can undergo fusion and dissociation events. Here the authors show that formin-like 1-dependent acto-myosin assembly on LDs facilitates their dissociation and, as a consequence, affects hydrolysis and storage of triacylglycerols.

Myosin VI (MVI) is known to interact with RNA Polymerase II and to play non-cytoplasmic roles in cells. Here, the authors provide evidence that the transcription co-activator NDP52 regulates MVI binding to DNA and that MVI interacts with nuclear receptors to drive gene expression.