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The meningeal compartment communicates with the brain to modulate homeostatic functions. Here, the authors demonstrate that natural killer (NK) cells and innate lymphoid cells (ILC) 1 shape synaptic neuronal transmission and affect mouse behavior.

Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential in C. elegans and mouse models.

Neuroimmune interactions are important in amyotrophic lateral sclerosis (ALS). Here the authors characterize the role of NK cells in mouse models of ALS, and in patient tissue.

Engineering a mutant-specific customized base editor precisely corrects a mutation while minimizing bystander edits, leading to substantial phenotypic recovery in mouse models of multisystemic smooth muscle dysfunction syndrome.

Sandhoff disease (SD) is a lysosomal storage disorder caused by deficiency in the β subunit of the β-hexosaminidase enzyme. Here, the authors show via bone marrow-based microglial replacement in a SD mouse model that myeloid-derived β-hexosaminidase is necessary for maintaining neuronal health.

Flores et al. show that brain-penetrant eIF2B agonists suppress ISR activation in cellular and mouse models of ALS and reduce ISR biomarkers in humans, enabling further clinical studies of ISR inhibition in individuals with neurological diseases

Particle therapy is subject to uncertainties in the range of the beam. In this study, tumours in the necks of mice were treated with radioactive ion beams, which enabled real-time verification of the beam range.

Despite advances in GPCR structures and peptide design, creating high-affinity ligands remains a challenge. Here the authors develop a computational method, successfully identifying peptide-based molecules for KOR: their platform shows promise for streamlined GPCR ligand discovery.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

The authors show the endocytotic adaptor subunit called AP2A2 is differentially expressed in CGRP⁺ nociceptors. Locally inhibiting nociceptor endocytosis with a lipidated AP2 inhibitor peptide reduces acute and chronic pain-like behaviour in mice and rats, indicating prolonged analgesia.

Amado et al. develop a gene therapy for sporadic ALS using motor neuron-targeting AAVs to deliver RNAi targeting ataxin-2. In a mouse model, survival, strength, and disease-related pathology are improved; and human motor neurons are strongly transduced.

Astrocytic glycogen dynamics is necessary to support neuronal transmission of long-term inflammatory pain signals in the spinal cord.

Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.

POLG mutations impair mitochondrial DNA replication and cause diverse mitochondrial diseases. Here, the authors show that structural differences in the POLγB subunit between humans and mice modulate mutation severity.

Phage-assisted noncontinuous selection of protein binders (PANCS-Binders) allows multiple high-diversity protein libraries to each be screened against a panel of dozens of targets for high-throughput protein binder discovery.

Research on pain often relies on animals, and there is always a need for more precise and more ethical tools. Here, authors present a light-activatable molecule that induces pain in freely moving animal models in a reversible, non-invasive, and spatiotemporally defined way.

Fluoxetine is a serotonin reuptake inhibitor antidepressant. Here, the authors demonstrate the that fluoxetine can trigger muscle regeneration in male mice by acting on muscle stem cells, vascularization, and inflammation, resulting in faster muscle healing.

The caudal ventrolateral medulla was thought to be involved in pain control, but its pathway was unknown. Here, Gu et al. identify the molecular components of a caudal ventrolateral medulla–locus coeruleus–spinal cord pathway and show it has a role in counter-stimulus pain control.

THOC2 is an essential subunit of Transcription mRNA Export complex of eukaryotic cells and its compromise causes adverse (neuro)development. Using mouse model and patient cells the authors unravel molecular pathology of the syndrome, from R-loops dysregulation, to altered transcriptome and DNA damage triggered cell death.

Gehrlach et al. show how the posterior insular cortex processes and modulates diverse internally and externally generated aversive states, and they dissect the functional contribution of segregated projections mediating inhibition of ongoing behaviors.

Mice lacking the mechanically activated ion channel Piezo2 in both sensory neurons and Merkel cells are almost totally incapable of light-touch sensation while other somatosensory functions, such as mechanical nociception, remain intact, implying that other mechanically activated ion channels must now be identified to account for painful touch sensation.

Stress shielding, a common cause of orthopedic implant failure, reduces the activity of intracellular mechanotransduction molecules, which are also regulated by nociceptors. Here, Wang et al. develop a small, implantable, wirelessly rechargeable device for optogenetic regulation of mechanosensitive nociceptors to investigate and improve implant osseointegration.

Home haemodialysis offers increased flexibility over in-centre haemodialysis for adopting different dialysis regimes aimed at improving solute removal. In this Review, Vanholder et al. discuss strategies that can improve haemodialysis adequacy in the home setting. The authors examine vascular access, reaching dialysis adequacy targets, increasing dialyser pore size, increasing dialysis frequency, and increasing dialysis duration, and also discuss the idea of the wearable artificial kidney.

Microglial states are dynamically regulated during development and disease. Here, the authors show that these changes are mediated by cell autonomous TGF-β signaling in microglia, which is developmentally regulated by ITGB8 in radial glia.

A study in a mouse model of obesity and prediabetes demonstrates that recruitment of macrophages to nerves has a protective role in diet-induced peripheral neuropathy.

Hallmarks of post-acute consequences of SARS-CoV-2 infection are still insufficiently understood. Here, the authors identify alveolar bronchiolization, interstitial fibrosis, and exercise-induced lung function impairment as features of respiratory long COVID in aged hamsters.

Lymphatic vessels are vital in the musculoskeletal system, but their role in bone repair is unclear. Here the authors found early lymphatic drainage insufficiency in fractures impacts osteoblast survival and stem cell proliferation by modulating the hematoma niche via DAMP transport.

The vascular stem cell niche regulates the proliferation and differentiation of neural stem cells (NSCs) in the adult subventricular zone. Here the authors identify EGFL7 as a neurovascular regulator of NSCsin vivo; EGFL7-knockout mice show reduced neurogenesis, and exhibit impaired olfactory perception and behaviour.

Pyruvic acid and its conjugate base, the pyruvate anion, are largely present in the atmosphere. Here the authors, using photoelectron imaging and quantum chemistry calculations, investigate the photochemistry of isolated pyruvate anions initiated by UVA radiation and report the formation of CO₂, CO, and CH₃⁻ further decomposing into CH₃ and a free electron.

Antila et al. show that brain amyloid-β load is not significantly affected by sustained dural lymphatic vessel atrophy or hyperplasia induced by lymphangiogenic growth factor manipulation in two mouse models of Alzheimer’s disease.

Ge, Zhou, Fu et al. find caspase-2 accumulates in biomolecular condensates with ubiquitin and proteasomal components and functions as a deubiquitinase following stress. Caspase-2-deficient mice accumulate poly-ubiquitinated TDP-43 and show motor defects.

Ibogaine is a natural substance that interrupts opioid addiction but has cardiac risks. This article introduces novel ibogaine analogs that show reduced cardiac risk and enhanced neuroplasticity and therapeutic-like effects in models of opioid use disorder.

Lateral heterojunctions between two-dimensional semiconductor crystals are essential building blocks for electronic devices. Here, the authors utilize electron-beam lithography and selective conversion to simultaneously fabricate arrays of molybdenum diselenide–molybdenum disulfide heterojunctions.

During senescence, minority mitochondrial outer membrane permeabilization leads to the release of mtDNA into the cytosol through BAX and BAK macropores, in turn activating the cGAS–STING pathway, a major regulator of the senescence-associated secretory phenotype.

Intermediate-length repeat expansions in ATXN-2 are the strongest genetic risk factor for ALS. Here, the authors combine patient-derived motor neurons and organoids with mouse models to dissect the pathogenic effects of ATXN2 intermediate expansions.

The authors describe cortical projections mediating the modulation of social behavior. Neural projections from the medial prefrontal cortex to the dorsal periaqueductal gray play a critical role in the behavioral adaptation to social defeat in mice.

Health effects of dietary restriction are uncoupled from longevity.

The authors uncover the relevance of Piezo1 mechanosensors expressed in the stomach for sensing gastric distention and regulating feeding behaviour.

The molecular diversity of microglia has been described. Here the authors show that ARG1-expressing microglia are enriched in phagocytic inclusions and are involved in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also modulate cognition in a sex-dependent manner.