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Glioblastoma (GBM) is an aggressive tumor characterized by an immunosuppressive microenvironment. Here, the authors present a therapeutic approach based on the implantation of a biodegradable scaffold for the sustained, local release of a TLR7/8 agonist at the time of tumor resection, to achieve anti-tumor immunity and protection from future tumor challenge.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.

The Zika viral protease NS2B-NS3 is a crucial target for antiviral drug development due to its role in processing viral polyproteins. Here, the authors utilize crystallographic fragment screening and deep mutational scanning to identify binding sites for resistance-resilient inhibitors.

Current photoproximity labelling methods often require metal-based catalysts to map protein interactomes but, owing to their toxicity, they have limited intracellular applicability. A deazaflavin cofactor has now been developed as a biocompatible alternative for diazirine activation inside living cells, offering accurate mapping of protein interactors and dynamics with excellent spatio-temporal control.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

The placenta plays vital roles in supporting fetal development. Here, Richards et al. develop a high-throughput bioprinted trophoblast organoid model to recapitulate the microenvironment of the early placenta, enabling investigation of placenta development and evaluation of therapeutics for placenta dysfunction disorders.

Bennu comprises components of intra- and extra-Solar System origins. The parent bodies of Bennu, Ryugu and CI chondrites likely formed from a shared but heterogeneous reservoir in the outer parts of the solar protoplanetary disk.

The use of antimicrobial agents can exacerbate the proliferation of antimicrobial resistance genes, which can put public health at risk; evaluating this risk requires proper monitoring. An extensive investigation of Australian wastewater reveals a distinct correlation between the type of antimicrobial used and the socioeconomic status of the population.

The authors introduce the Neurolipid Atlas, a dynamic resource for the community to gain insight into lipid alterations in neurodegenerative disease, and they leverage the platform to show how cholesterol alterations in astrocytes can dysregulate neuroinflammatory pathways in Alzheimer disease.

Shigella sonnei is divided into five lineages and most infections are caused by Lineage 3. Here, the authors investigate factors contributing to the epidemiological success of Lineage 3 through comparative genomics and virulence analyses in a zebrafish infection model.

Structural and functional characterization of the β-barrel assembly machinery complex in Bacteroidota reveals a distinct, seven-component complex with a large extracellular domain that may enable β-barrel–surface lipoprotein complex assembly.

The antibiotic polymyxin B requires bacterial metabolic activity to cause sufficient damage to the outer membrane to access the inner membrane, which it permeabilizes via an energy-independent mechanism to kill the cell.

Aerosol deposition onto the surface of the ocean has been underestimated, suggesting that aerosol lifetimes over the ocean are longer than previously appreciated, according to a global compilation of cosmogenic beryllium isotope data.

Massively parallel reporter assays (MPRAs) are powerful technologies for measuring the impact of non-coding sequences on gene expression. Here, the authors demonstrate that MPRA reporters often undergo cryptic splicing that is activated by U-rich sequences, which can convolute MPRA measurements.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

In a randomized, placebo-controlled, stepwise dose-escalation phase 1 trial evaluating a conjugate vaccine against both typhoid and invasive non-typhoidal Salmonella infections, the vaccine was found to be safe and immunogenic in healthy adults.

Using simultaneous electrophysiological and optical imaging, this study finds that it is the linear summation of stimulus-independent trial-related and stimulus-dependent components that yield the signal seen in neuroimaging studies. However, the trial-related component, which does not correlate with neural spiking or LFPs, can account for over half of the neuroimaging signal, suggesting that it is crucial to take this component into account when interpreting neuroimaging studies.

Here, the authors report that combining Army Liposome Formulation with QS21 saponin (ALFQ) and Alum to formulate the ΔV1gp120 boost decreases the risk of simian immunodeficiency virus (SIV) mac251 acquisition in female macaques.

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

This work reveals how a regulatory domain in O-GlcNAc hydrolase (OGA) shapes enzyme flexibility and activity, uncovering mechanisms that help maintain O-GlcNAc balance in cells.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

Dual cyclin A/B RxL inhibitors selectively kill small cell lung cancer cells and other cancer cells with high E2F activity.

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.

CaMKII is a key enzyme in brain, heart, and egg cells, regulated by calcium signals. Here, authors show that charged residues in the variable linker tune CaMKII activity, a mechanism that may underlie cell type–specific responses.

The treatment potential of psilocybin for postpartum depression was investigated in a preclinical mouse model. Here the authors show both acute and long-term effects of psilocybin in mothers and their offspring who were exposed via lactation.

In the randomized phase 1b/2 Morpheus-Melanoma trial evaluating various neoadjuvant immune checkpoint inhibitor regimens in patients with resectable stage III melanoma, tobemstomig, an anti-PD-1/anti-LAG-3 bispecific antibody, showed the highest pathologic response rate with a better safety profile than the standard treatment approach of ipilimumab plus nivolumab.

A luminescence cascade system achieves 500-fold higher intensity and 8-fold longer signal persistence than conventional bioluminescence assays, enabling reliable and effective use of bioluminescence for point-of-care diagnostics.

The authors identify a single main-chain hydrogen bond required to keep GABA_A receptors closed in the absence of neurotransmitter. Electrophysiology and molecular dynamics simulations suggest disruption of this bond is a key component of channel opening during inhibitory synaptic signaling in the brain.

Using visible-light-induced crosslinking, a local stiffening approach is developed for ex vivo mouse and human lung tissue as an early lung injury model, directing epithelial cell mechanosensing, differentiation and nascent protein deposition.

Results from the randomized, noncomparative, phase 2 MATISSE trial show that ultra-short neoadjuvant therapy with ipilimumab and nivolumab can prevent surgery and radiotherapy in patients with resectable cutaneous squamous cell carcinoma, with an early decrease in total lesion glycolysis by [¹⁸F]FDG-PET/CT associated with response.

An optical sieve—an array of optically resonant voids in gallium arsenide—enables sorting, detecting and counting nanoplastics as small as a few hundreds of nanometres at concentrations as low as 150 μg ml⁻¹ in lake water samples.

Using in silico neuroscience, Gifford et al. developed a neural control algorithm to modulate the representational relationships between visual cortical areas, revealing how these areas jointly represent the world as an interconnected network.

Despite the efficacy of artemisinin against Plasmodium falciparum, young intraerythrocytic ring stage parasites may survive and persist in a dormant state. In this study, Yu et al elucidate the epigenetic regulatory mechanism of artemisinin resistance in P. falciparum ring-stage survival.

The Perseverance rover detected polycyclic aromatic hydrocarbons preserved within sulfates in the fan and floor of Jezero crater on Mars, offering new insights into past habitability and the preservation of organic matter on Mars.

Lithium has an essential role in the brain and is deficient early in Alzheimer’s disease, which can be recapitulated in mice and treated with a novel lithium salt that restores the physiological level.

Psychophysical studies predict that retinal cone-opponent mechanisms interact in specific combinations to generate color perception. Here, the authors show that the predicted interactions are implemented by organized circuits in primary visual cortex.

The very low water contents of minerals in achondrite meteorites from the early Solar System show that substantial amounts of water could only have been delivered to Earth by means of unmelted material.

Egan et al. examine multisensory evidence accumulation and show that auditory and visual evidence is accumulated in distinct processes during multisensory detection, and cumulative evidence in the two modalities sub-additively co-activates a single, thresholded motor process.

Hematoxylin and eosin (H&E) staining is a widely used method in histopathology, but it cannot directly inform about specific molecular markers. Here, the authors present ROSIE, a deep-learning framework that computationally imputes the expression and localisation of dozens of proteins from H&E images.