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The restriction of appropriate tumour-specific antigens is a current limitation for T cell-engaging immunotherapy. Here, the authors have designed a new system constituted by two halve antibodies, which engage T cells once binding to two different antigens, to specifically eliminate double positive cells in preclinical leukemia and breast cancer mouse models.

Loss of communication between the brain and the body severely impacts the sensorimotor abilities of disabled individuals. Here, the authors design and test a neuroscience-driven framework for advancing bionic devices that leverages biomimetic stimulation to induce physiologically plausible information flow in animals and enhances patient performance with neuroprostheses.

The authors show that haploinsufficiency of TBK1 causes familial forms of the neurodegenerative diseases ALS and FTD. Loss of binding of a TBK1 protein interaction domain to optineurin, a protein previously linked to ALS, is sufficient to cause the disease. Both proteins regulate autophagy and inflammation.

Retinal prostheses hold potential for artificial vision in blind people. Here, authors show that POLYRETINA, a large and high-density photovoltaic epiretinal device, restores light-evoked cortical responses in blind Göttingen minipigs at safe irradiance levels.

Synapse loss is prominent in the cortex in multiple sclerosis (MS). In a cortical MS model, Jafari et al. show that phagocytes remove synapses by engulfment, which is triggered by local calcium accumulations and prevented by blocking colony-stimulating factor 1 signaling.

Progressive respiratory failure is the primary cause of death in patients with COVID-19, but pathologies in other tissues may also occur. Here the authors report that adrenal tropism of SARS-CoV-2 is associated with adrenalitis, reduced adrenal cortisol levels and severe adrenal damage in a post-mortem case series of patients with severe fatal COVID-19.

Targeted protein degradation (TPD) is a key modality for drug discovery. Here the authors present the discovery and analysis of reversible DCAF1-PROTACs, which show efficacy in cellular environments resistant to VHL-PROTACs or with acquired resistance to CRBN-PROTACs.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Chemotherapy-induced peripheral neuropathy (CIPN) represents a major reason for discontinuation of treatment. Here, the authors show that LEI-515, a peripherally restricted monoacylglycerol lipase inhibitor, suppresses CIPN without inducing central nervous system side effects or physical dependence.

Geis et al. investigate the potential application of hemibodies, a pair of complementary antibody fragments that redirect T cells against cancer-defining antigen combinations, such as CD38 and SLAMF7, to target multiple myeloma. Their study provides evidence that hemibodies can be developed for effective immunotherapy against multiple myeloma.

The maxilloturbinal, an area of the mammalian nasal cavity, has been proposed to play a pivotal role in body temperature maintenance. Here, the authors use computed tomographic data to show that neither corrected basal metabolic rate nor body temperature significantly correlate with the relative surface area of the maxilloturbinal.

Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU). Existing anti-tubercular drugs have been used to treat the condition with varying success. Here, the authors show that a clinical-stage drug candidate for tuberculosis, Q203, is effective at killing M. ulcerans and is a promising therapeutic candidate for BU.

Here, the authors reveal using single-cell RNA sequencing that Parkinson’s disease (PD) patient-derived neuronal cells show altered primary cilia morphology and signaling suggesting cilia dysfunction may underlie PD pathogenesis.

The origin of the genus Homo is debated. Here, the authors investigate the morphology of the H. habilis enamel-dentine junction using a sample of 911 hominin and extant ape teeth, finding that H. habilis has more in common with Australopithecus than later members of the genus Homo.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Ices are sources of organic matter in various astrophysical environments, but the impact of their composition on the formation of volatile organic compounds (VOCs) remains underexplored. Here, the authors use gas chromatography coupled to high-resolution mass spectrometry (GC-Orbitrap-MS) to show that ice photo-processing and thermal evolution are directly correlated to VOC formation during the warming of different H₂O:CH₃OH:NH₃ ices and highlight the role of NH₃ in driving the formation of nitrogen refractory compounds.

Oligodendrocyte damage is a key component of demyelinating diseases. Here, the authors use in vivolight and correlated electron microscopy in EAE mouse models, and find early damage occurs at the myelin sheath before spreading to the oligodendrocyte cell body.

Thymic epithelial tumors are associated with increased risk of immune checkpoint inhibitor (ICI)-induced myotoxicities, and the presence of anti-acetylcholine-receptor antibodies has the potential to serve as a biomarker for ICI-induced myocarditis in patients with cancer.

Zhang et al. use single-cell RNA sequencing and functional analyses to describe the hyaluronic acid–GPRC5C signalling axis as an essential component controlling the state of dormancy for human and mouse haematopoietic stem cells.

The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.

The accurate determination of quark mixing parameters is essential for the understanding of the Standard Model. The LHCb collaboration now reports the coupling strength of the b quark to the u quark through the measurement of a baryonic decay mode.

The LHCb collaboration reports an improved measurement of the oscillation frequency of mesons consisting of a bottom quark and strange quark, which is then combined with previous results.

The Large Hadron Collider beauty collaboration reports a test of lepton flavour universality in decays of bottom mesons into strange mesons and a charged lepton pair, finding evidence of a violation of this principle postulated in the standard model.

Various fatty acids and aldehydes can be synthesized from acetylene and carbon monoxide by nickel sulfide catalysts under volcanic hydrothermal conditions compatible with aqueous early earth conditions, however, their chemical complexity remains underexplored. Here, the authors use ¹³C-labelling together with untargeted ultrahigh-resolution mass spectrometry to categorize carboxylic acid functional groups, revealing C2-addition driven compound diversity as well as new sulfur containing classes.

Combined analysis of proton-proton collision data from the Large Hadron Collider at CERN by the CMS and LHCb collaborations leads to the observation of the extremely rare decay of the strange B meson into muons; the result is compatible with the standard model of particle physics, and does not show any signs of new physics, such as supersymmetry.

The authors report that the presynaptic protein bassoon forms toxic aggregates in neuronal somata in multiple sclerosis. Stimulation of proteasomal activity reduces bassoon aggregates, neuroaxonal loss and disability during CNS inflammation.

CP violation has deep implications for particle physics and cosmology. Previously observed only in meson decays, signs of CP violation have now been spotted in baryon decays by analysing the proton–proton collision data from the LHCb detector.

Colonization of germ-free mice with microbiota promotes vascular growth in the small intestine through a mechanism involving tissue factor, PAR1 and Ang1.

Holger Lerche, Camila Esguerra and colleagues report the identification of inactivating mutations in STX1B in individuals with various seizure-related disorders, including febrile seizures and epilepsy. Functional studies indicate that STX1B acts in the presynaptic release machinery.