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An updated analysis of the DYNAMIC biomarker-driven trial, including mature survival data at 5 years, supports a ctDNA-guided approach to adjuvant chemotherapy for stage II colon cancer.

The authors show that LARP4 drives T cell dysfunction in tumors by promoting hypertranslation of oxidative phosphorylation-related mRNAs, resulting in mitochondrial dysfunction. They also target LARP4 to enhance T cell persistence and anti-tumor activity and provide a CAR T cell strategy for treating solid and liquid tumors.

Illness signals from the gut reactivate and strengthen flavour representations in the amygdala to support learning from delayed postingestive feedback.

Boiko et al. enhance expressiveness and interpretability of molecular representation in graph neural networks by including quantum-chemical-rich information into molecular graphs.

The metabolically driven maturation of geometrically aligned human cardiac microtissues on a microfabricated chip reduces cell-phenotype-dependent variabilities in the action-potential morphology and calcium handling of the cardiomyocytes.

The dynamic behavior of supramolecular polymers in aqueous environments remains poorly understood due to the assembly pathway complexity. Here, the authors present a combinatorial titration methodology to probe in situ a binary assembly mechanism between spheroidal micelles and β-sheet polymers of peptide amphiphiles, which collectively govern supramolecular dynamics.

Shabanzadeh et al. identify and validate a pathway whereby RGMa cleavage by SKI-1 modifies gene expression related to blood–brain barrier (BBB) integrity after stroke. SKI-1 inhibition restores BBB integrity and neuronal function in mouse and rabbit stroke models.

TASL is an adaptor molecule bridging Toll-like receptor signalling and transcription activation by IRF5. Here the authors show that TASL deficiency impacts TLR7/9 responses, and that a TASL paralogue, Gm6377/TASL2, also contributes to IRF5 activation, as dual TASL/TASL2 deficiency dampens both protective and pathogenic inflammatory responses in mice.

Dissolution-dynamic nuclear polarization is able to enhance nuclear magnetic resonance signals, but requires complex procedures to generate hyperpolarized nuclear spins. Here the authors establish a fast and facile method to transfer hyperpolarized samples into the liquid solution where the measurement is performed.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

SLEAP is a versatile deep learning-based multi-animal pose-tracking tool designed to work on videos of diverse animals, including during social behavior.

Incorporating functional information has shown promise for improving polygenic risk prediction of complex traits. Here, the authors describe polygenic prediction method LDpred-funct, and demonstrate its utility across 21 heritable traits in the UK Biobank.

The PI(3,4)P₂ 4-phosphatase, INPP4B, functions as a tumour suppressor in triple negative breast cancer. Here, the authors show that INPP4B enhances proliferation and growth of PIK3CA-mutant ER⁺ breast cancers by promoting PI3Kα-dependent late endosome formation and trafficking that leads to the activation of Wnt/β-catenin signalling.

Our basic understanding of neuromodulation in the claustrum remains limited. Here Madden et al., identify a key mechanism by which serotonin and the psychedelic psilocybin modulate cortical signalling through the claustrum, a brain region involved in regulating cognition and brain network states.

A nanomesh sensor that is directly printed on a person’s hand and is coupled with an unsupervised meta-learning framework can provide user-independent and data-efficient recognition of different hand tasks.

In the worm, netrin and the TGFβ-related molecule UNC-129 form opposing dorsoventral gradients. Motor axons are repelled by netrin and attracted to UNC-129, but no TGFβ receptors appear to be involved in the attraction. This study shows that UNC-129 enhances repulsive signaling from the netrin receptor complex UNC-5/UNC-40, via a direct interaction with UNC-5.

Trach and McDougle show that motor responses can form part of structured, graph-like memory representations.

Experimental models of breast cancer reveal the phosphoinositide-phosphatases PIPP and PTEN play non-redundant roles in suppressing mouse mammary epithelial cell transformation, and disease progression in a subset of human breast cancers.

A wearable sweat sensor powered by a flexible solar cell can continuously collect multimodal physicochemical data—glucose, pH, sodium ion, sweat rate and skin temperature—across indoor and outdoor physical activities for over 12 h.

The adenine analogue 2-aminopurine has been considered as intrinsically fluorescent and is widely used in biochemical assays to probe DNA and RNA structure. It is now shown that the molecule alone is nearly non-fluorescent, however, its fluorescence is increased by up to 95 times through hydrogen bonding to a single water molecule.

An end-to-end continuous-variable quantum key distribution system with an untrusted node is proposed. A proof-of-principle experiment shows that 10⁻¹ secret key bits per relay use are distributed at 4 dB loss, corresponding to 20 km in optical fibre.

A comprehensive single-cell RNA sequencing study delineates cell-type-specific transcriptomic changes in the brain associated with normal ageing that will inform the investigation into functional changes and the interaction of ageing and disease.

Xenium spatial transcriptomic profiling of pulmonary fibrosis characterizes cell composition dynamics and histopathological features associated with the disease.

Rhesus macaques are susceptible to oral challenge of human noroviruses and can be used as a model to recapitulate infection and adaptive immune responses in humans.

A device for generating precise spatial and temporal patterns of airborne odorants is reported. In combination with machine vision tracking software, the authors use the device to monitor navigation of freely moving Drosophila melanogaster larvae.

The structure of a neutralizing human monoclonal antibody isolated from an individual immunized in a Plasmodium vivax Duffy binding protein vaccine clinical trial, in complex with its target, elucidates the mechanism by which parasite invasion of immature red blood cells is inhibited.

Complex structural variations and rearrangements in cancer are identified using long-read sequencing.

Implant infection is the most common mode of joint replacement failure with serious complications. Here, the authors report on the in vivo application of a prophylactic coating technology that can incorporate a range of antibiotics and be applied in the operating room prior to implantation.

The pathogenic bacterium Pseudomonas aeruginosa can be found in vacuoles and cytoplasm within infected cells. Here, Schator et al. show that extracellular bacteria use a type-III secretion system to induce Ca²⁺ influx into host cells and promote vacuole escape of intracellular bacteria and in vivo dissemination.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

Here the authors develop a probabilistic model for single-cell DNA sequencing of aneuploid tumors that infers clone-specific replication timing and S-phase fractions, unveiling their relationships with copy number evolution and clonal fitness.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Arya et al. report that migrating neutrophils resolve acute inflammation by releasing exosomes associated with nuclear DNA. This process is distinct from the release of neutrophil extracellular traps, and relies on the lamin B receptor.

DeepRETStroke is a deep learning system using retinal photographs to detect silent brain infarction and predict future stroke events.

Due to the limited efficacy of vaccines against SARS-CoV-2 and resistance to current therapies additional anti-viral therapeutics with pan-coronavirus activity are of high interest. Here, the authors screened 2.8 billion compounds from a DNA-encoded chemical library and identified small molecules that are non-covalent inhibitors targeting the conserved 3CL protease of SARS-CoV-2 and other coronaviruses.

Data from questionnaires distributed to hunters and wild meat vendors in Nigeria suggest that most captured pangolins are not specifically targeted and that the animals are primarily captured for their meat, which is mostly consumed by hunters’ households, rather than for their scales.

Sensorimotor inputs are first compressed before being routed to the cerebellum and similar brain structures. The authors develop a theory to understand the computational role of this compression, leading to anatomical and functional predictions.

Real-time lab analysis is key to support clinical research during space missions. Here, the authors show scant test samples can be measured in microgravity using a miniature cytometery-based analyzer, the rHEALTH ONE with specific spaceflight modifications.

CD4⁺ T cells promote immunity to tuberculosis infection via macrophages. Here the authors show upregulation of SLAMF1/CD150 on infected macrophages after interaction with CD4⁺ T cells and that the presence of SLAMF1 promotes ROS production by macrophages and the absence of Slamf1 in macrophages results in higher mycobacterial loads in infected mice.

Pancreatic ductal carcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) enriched in stromal cells. Here the authors show that TSG-6-positive cancer associated fibroblasts modulate myeloid cell responses and that TSG-6 targeting improves response to immune checkpoint inhibitors in preclinical PDAC models.

[¹⁸F]OXD-2314 is a brain penetrant positron emission tomography radiotracer with high affinity for tau aggregates in Alzheimer’s disease (AD) and non-AD tauopathies based on in vitro and in vivo studies, and is suitable for first-in-human use.

Activity-dependent gene expression is thought to involve translocation of Ca²⁺/calmodulin (CaM) to the nucleus. Here, the authors examine a translocation-deficient mutant of γCaMKII, a Ca²⁺/CaM shuttle protein, to show that translocation of Ca²⁺/CaM is required for memory and synaptic plasticity.

Small molecule drugs promise to remain a valuable tool in controlling the ongoing COVID-19 pandemic. Here the authors describe optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for potential treatment of COVID-19.