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Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Topological insulators offer lossless surface transport because of the suppression of conduction-electron backscattering from defect sites. Here, the authors show that the nanoscale voltage drops caused by such scattering can be directly measured using scanning tunnelling potentiometry.

Ferrimagnets possess multiple spin sub-lattices resulting in a complex magnon band structure and subtle spin transport across interfaces. Here, the authors show how the spin Seebeck effect, the thermal generation of pure spin current, may be an effective tool to study these magnetic excitations.

In gastrointestinal stromal tumours early mutations in known genes are frequently followed by chromosome 14q deletion. Here the authors find mutations resulting in loss of MAX protein expression conserved between primary tumours and metastases in the same patients, suggesting thatMAXmutation is an early event.

The molecular genetic landscape of leiomyosarcoma (LMS) is largely unknown. Here, the authors identify frequent DNA copy number alterations, whole-genome duplication, TP53 and RB1 inactivation, alternative telomere lengthening, and genomic imprints of defective DNA repair via homologous recombination as a potential therapeutic target in LMS patients.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

RNA variants derived from cancer-associated RNA editing events can be a source of neoantigens. Here, based on a proteogenomic pipeline combining DNA and RNA sequencing with MS-based immunopeptidomics, the authors identity and validate potential neoantigen candidates in patients with different tumor entities, highlighting RNA as important neoantigen source.

Using RFdiffusion, a general method for targeting intrinsically disordered proteins and regions for protein design has been developed.

Antimicrobial resistance is a major global health threat and its development is promoted by antibiotic misuse. Here, the authors present an offline smartphone application for automated and standardized antibiotic susceptibility testing, to be deployed in resource-limited settings.

Exploratory ctDNA analyses from the phase 3 INTRIGUE trial indicate that ripretinib may provide benefits in patients with advanced gastrointestinal stromal tumors with KIT exon 11 + 17/18 mutations

Cryopreservation is standard protocol prior to using NK cells in immunotherapy. Here the authors show that cryopreservation substantially reduces the clinical utility of these cells owing to a defect in their motility, an effect that might account for failure to treat some cancers with NK cell immunotherapy.

Adding short, complementary oligonucleotides to single-stranded DNA condensates creates a concentrated, linearly propagating, sharp diffusion front that contradicts the fuzzy concentration gradients and nonlinear kinetics typical of Fickian diffusion.

Reducing thermal conductivity of thermoelectric materials usually results in a tradeoff of electrical conductivity. Here, the authors demonstrate a strategy, which allows for a decoupling of charge and heat transport by incorporating topological-insulating Bi-Sb alloys at the grain boundaries of Fe₂VAl-based Heusler compounds.

Metagenomics and Hi-C proximity-ligation sequencing show that viruses in dense microbial communities can interact with multiple, distantly related microbial hosts.

The spin-dependent Peltier effect has been demonstrated in a nanostructure consisting of a non-magnetic metal sandwiched between two ferromagnetic layers.

Chordomas are rare bone tumors with limited therapeutic options. Here, the authors identify molecular alterations associated with defective homologous recombination DNA repair in advanced chordomas and report prolonged response in a patient treated with a PARP inhibitor, which later acquired resistance due to a newly gained PARP1 mutation.

Histological slides often contain artifacts that affect the performance of downstream image analysis. Here, the authors present GrandQC, a tool that enables high-precision tissue and artifact segmentation in histological slides. This tool can be used to monitor sample preparation and scanning quality across pathology departments.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

This study employs a citizen science approach to identify and classify over 230,000 light sources in German city centers, suburbs and villages. The results underscore the pivotal role of citizen science in expanding knowledge of artificial light emissions and bolstering policymaking efforts to mitigate urban light pollution.

Non-line-of-sight imaging can recover the 3D geometry of hidden objects, but is limited by weak multibounce signals. Here, the authors introduce a multipixel time-of-flight NLOS imaging approach, combining array detectors and a fast algorithm, for live reconstruction of natural nonretroreflective objects.

Steroid-refractory acute graft-versus-host disease (aGVHD) is associated with a low one-year survival rate. Here, the authors show that ROCK1 is upregulated in leukocytes from patients with steroid-refractory aGVHD and that ROCK1/2 inhibition reduces the severity of aGVHD in mice by interfering with activation of multiple immune cell types.

The authors discuss the dysregulated host response in sepsis and the use of biomarkers to gauge the immunological status of patients and potentially guide precision medicine. They also highlight potential immunomodulatory therapies for sepsis and discuss the future of sepsis clinical trials.

Susac syndrome is an inflammatory pathology of the brain endothelium. Here the authors show that the pathology is driven by CD8 T cells attacking the endothelium, and that blocking T cell-endothelial adhesion ameliorates the disease in a mouse model, and associates with improved clinical score in 4 patients.

High-energy interlayer excitons in van der Waals semiconducting transition metal dichalcogenides lie far above the bandgap and emit in the ultraviolet range.

Wang et al. report on an inhibitor of the lysine methyltransferase KMT9 with cellular activity. The inhibitor blocks proliferation of androgen-resistant prostate cancer cells, opening therapeutics avenues to treat this type of cancer.

Peter Robinson and colleagues performed exome sequencing on three siblings to identify mutations in PIGV in Hyperphosphatasia-Mental Retardation (HPMR) syndrome.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Here, Heitmann et al. report results from a Phase I/II trial evaluating CoVac-1, a peptide-based T-cell activator, in patients with B-cell deficiency, demonstrating potent induction of SARS-CoV-2-specific T-cell responses along with a favorable safety profile.

Researchers show that resonant coupling of light pulses with excitonic transitions affects the optimal time difference between pulses for sum-frequency generation and four-wave mixing in monolayer WSe₂.

Probing spin pumping in the terahertz regime allows one to reveal its initial elementary steps. Here, the authors show that the formation of the spin Seebeck current in YIG/Pt critically relies on hot thermalized metal electrons because they impinge on the metal-insulator interface with maximum noise.

The mechanisms driving B cell differentiation into resident bone marrow plasma cells (BMPC) remain unclear. Here the authors use single cell sequencing and BMPC phenotyping to infer developmental pathways and regulation by IL-21 in germinal centres to promote maintenance of BMPC after vaccination in humans.

During viral infections high levels of antibodies can form soluble immune complexes (sICs) with antigen and trigger Fcγ receptors (FcγR) leading to increased immunopathology. Here the authors measure FcγRs activation by sICs and consider how these may lead to excessive immunopathology during severe SARS-CoV-2 infection.

Using JWST, more than 40 individual stars have been detected in a distant galaxy, dating back to when the Universe was only half of its current age. The stars appear to be red (super)giants that are magnified by factors of hundreds.

A phase I open-label trial evaluating the immunogencity, reactogenicity and safety of a peptide-based SARS-CoV-2 vaccine candidate to induce SARS-CoV-2-specific T cell responses.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

SARS-CoV-2-specific CD4⁺ and CD8⁺ T cell epitopes are found in both convalescent patients and virus-naive volunteers and are indicative of heterologous recognition shared with seasonal cold viruses.

Although ageing is the most important risk factor for chronic ailments, effective interventions remain rare. Here, the authors identify the flavonoid 4,4’-dimethoxychalcone and demonstrate that it extends lifespan and promotes health in multiple organisms by inducing autophagy.

Expression profiles of several hundred microRNAs in the blood of individuals with disease, including autoimmune disease, cancers, cardiovascular disease and chronic inflammatory disease are reported.

Heralded entanglement between two independently trapped single rubidium atoms is generated over long telecom fibre links using quantum frequency conversion in an important step towards the realization of large-scale quantum network links.

Here, the authors report on the large twist-angle susceptibility of excitons involving upper conduction bands in transition metal dichalcogenide bilayers. These high-lying excitons couple with band-edge excitons, and give rise to nonlinear quantum-optical processes that become tuneable by twisting.