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Anti-CTLA4-based immunotherapy enhances anti-tumor responses, but severe immune-related adverse events limit its therapeutic application. Here, the authors develop ProCTLA-4, an anti-CTLA4 prodrug sensitive to matrix metalloproteinase activity, that achieves promising control over tumor growth across several preclinical mouse models while limiting systemic toxicity.

Liquid films are essential in semiconductor lithography but microscopic behaviors of photoresist within these films remain unclear. This study uses cryo-electron tomography to reconstruct photoresist structures, achieving 99% defect reduction.

Solitary fibrous tumors (SFTs) of the central nervous system (CNS) are uncommon mesenchymal neoplasms with limited treatment options. Here, the authors perform a multi-omics analysis of 189 cases of CNS SFTs to identify potential clinical biomarkers and therapeutic targets.

In a small trial of patients with severe systemic lupus erythematosus and nephritis, treatment with allogeneic T cells with a CD19 chimeric antigen receptor inserted into the T cell receptor locus and deletion of the PD-1 (PDCD1) gene were safe and associated with reduced disease activity.

On-target, off-tumour toxicity is a major concern in immunotherapy. Here, aided by computer docking analysis, the authors introduce a single oxygen atom into the TLR7/8 agonist R848, generating a radiotherapy-activatable prodrug agonist that in mice helps mitigate systemic toxicity while triggering effective anti-tumor immunity responses upon radiation.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Radiopharmaceuticals engineered with click chemistry to selectively bind to tumour-specific proteins can be used to successfully target tumour cells, boosting the pharmacokinetics of radionuclide therapy and improving tumour regression.

It has been 25 years since the first 3D coherent Raman microscope was reported. Owing to the contributions of many researchers worldwide, coherent Raman microscopy has blossomed as a field of its own and found wide applications in chemical, material, environmental, biological and medical applications. Here I highlight the emergence of nonlinear optical spectroscopy and microscopy and their key technical milestones that led to the rapid expansion and wide use of this imaging modality for biomedicine.

Diverse plant species synthesize salicylic acid from phenylalanine through a pathway that includes a conserved triple-enzyme module that converts benzoyl-CoA to salicylic acid.

The photochemical properties of Electron Donor-Acceptor (EDA) complexes present exciting opportunities, but often require an inert atmosphere to maintain high efficiency. Here, the authors develop a photocatalytic system through rational design, which overcomes the oxygen-sensitive limitation of traditional EDA photocatalytic systems.

Blockade of alternative T cell checkpoint molecules, such as Tim3, is a promising alternative to inhibition of PD-1-PD-L1 interaction in cancers. Here authors show that anti-Tim3 therapy is working only in the presence of Il-2 co-stimulation, and the 2 necessary signals can be provided in the form of an anti-Tim3-Pro-Il2 construct, harboring modifications to the cytokine to resist the acidic tumour microenvironment.

Broad and potent neutralizing antibodies to SARS-CoV-2 variants can be efficiently identified via accurate deep-mutational-scanning-based prediction of viral evolution and delivered to mice using mRNA–lipid nanoparticles.

A prime editor screen systematically identifies deleterious synonymous variants in human cells.

Systemic administration of TRL7/8 agonists enhances anti-tumor immunity by enhancing dendritic cell (DC) activation, but also causes systemic toxicity. Here, the authors show that, in tumor mouse models, a radiotherapy-activated, N-oxide imidazoquinoline prodrug promotes controlled, local activation of intratumoral DC-T cell dynamics, while promoting systemic anti-tumor responses.

Convergent mutations in hotspots of the SARS-CoV-2 Omicron receptor-binding domain can cause immune evasion and maintain sufficient ACE2-binding capability.

The role of vascular plasticity in brain function remains poorly understood. Here, the authors demonstrate that a significant portion of blood vessels in the adult brain periodically occlude and regress, a process that is associated with a reduction in neuronal activity.

Exposure to early variants of SARS-CoV-2 results in immune imprinting in mouse models and in humans, reducing neutralizing antibody titres against Omicron variants, which could be mitigated with multiple updated boosters.

CDK4/6 inhibition is often effective for those with breast cancer but success is limited by adverse reactions. Here, the authors report a phase III randomised trial comparing fulvestrant (oestrogen receptor antagonist) with or without lerociclib (CDK4/6 inhibitor) for the treatment of hormone receptor-positive HER2-negative, endocrine-resistant advanced breast cancer.

An anti-4-1BB antibody fused to interleukin-15 via a peptide sensitive to tumour proteases augments tumour inhibition without increasing systemic toxicity by concurrently depleting regulatory T cells and expanding cytotoxic T cells in the tumours.

A deep mutational scanning approach identifies mutations that allow subvariants of the prevalent JN.1 SARS-CoV-2 strain to evade Omicron-induced neutralizing antibodies, indicating a need for careful monitoring of this lineage in vaccine development.

Spatial omics technologies reveal the organisation of cells in various biological systems. Here, authors propose SLAT, a graph-based algorithm for aligning heterogenous data across technologies, modalities and timepoints, enabling spatiotemporal reconstruction of complex developmental processes.

Glycosphingolipids (GSLs) are abnormally expressed in cancer cells. Here, in addition to showing that inhibition of the synthesis of GSLs with eliglustat promotes anti-tumor immune responses in preclinical models, the authors report the results of a phase I trial of eliglustat and anti-PD-1 antibodies for the treatment of advanced cancers.

H5N1 avian influenza viruses can be highly pathogenic. Here, the authors show that H5N1 infection leads to increased serum levels of angiotensin II in patients and mice, and that administration of angiotensin-converting enzyme 2 ameliorates lung injury in infected mice.

High-resolution cryo-EM study of human muscle phosphorylase kinase reveals its complex structure and how calcium ions activate it, offering insights into glycogen metabolism and kinase regulation.

A fast chemical reprogramming system to generate human pluripotent stem cells was developed, revealing epigenetic enzymes as key barriers and providing an innovative and promising strategy for stem cell manufacturing.

Ye and colleagues show that an oncolytic virus that delivers tumor-irrelevant bystander T cell epitopes to tumor cells can exploit the abundant population of bystander T cells in the tumor for anti-tumor immunity and potentiate cancer immunotherapy.

The crystal structure of the full-length human glucagon receptor reveals the essential role of the 12-residue ‘stalk’ segment and an extracellular loop in the regulation of ligand binding and receptor activation.

A mitochondrial disease is modeled using engineered base editors in rats.

Lipopolysaccharide-induced breakdown of the blood–brain barrier requires activation of GSDMD-mediated plasma membrane permeabilization and pyroptosis in brain endothelial cells.

Boron neutron capture therapy (BNCT) is a type of radiotherapy that induces cell damage through a localized nuclear reaction. Here the authors describe the design of a carborane-based covalent organic framework as a boron capsule loaded with immune adjuvants for concurrent BNCT and immunotherapy, promoting anti-tumour immune responses in preclinical cancer models.

Drg1 is a cytoplasmic AAA + ATPase responsible for releasing Rlp24 during ribosome assembly. Here, the authors show that Drg1 structurally and functionally shares many regulatory features with that of Cdc48/p97, suggesting a unfoldase role for Drg1.

The cryo-EM structure of the GSDMB pore reveals mechanisms by which GSDMB pore-forming activity is regulated by pathogenic bacteria and mRNA splicing.

Biochemical and structural studies of the interactions between antibodies and spike proteins from SARS-CoV-2 Omicron subvariants indicate how these variants have evolved to escape antibody-mediated neutralization.

Bioactive peptides regulate many physiological functions but progress in discovering them has been slow. Here, the authors use a machine learning framework to predict mammalian peptide candidates from the global and local structure of large-scale tissue-specific mass spectrometry data.

The environmental and socio-economic implications of the growth in welfare and trade in Asia-Pacific (APAC) remain unclear. Here the authors show that over the past two decades (1995–2015), owing to intraregional trade, the APAC economies have grown increasingly interdependent in natural resource use, air emissions, and labor and economic productivity.

Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.

Alien species invasions are thought to be important to zoonotic diseases through the introduction of both existing and novel pathogens to invaded ranges. Using data from 795 established alien animals and 10,473 zoonosis events worldwide, this study examines the role of alien zoonotic hosts on zoonosis emergences after accounting for climate, propagule pressure, global change and sampling bias.

Magnesium alloys usually have poor corrosion resistance, which inhibits their use in the automotive and biomedical industries. Here, the authors use an environmental TEM to carbonate the natural corrosion products at the surface of magnesium alloys and form a compact and protective surface layer.