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Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Metabolite signatures were identified for subtypes of dietary carbohydrate, including added sugar, whole grain and refined grain, and showed different associations with type 2 diabetes, providing an objective measure of dietary risk.

B cell receptor sequencing with ligand blocking speeds up neutralizing antibody discovery.

PPARγ regulates glucose and lipid metabolism, yet safer PPARγ-targeted insulin sensitizers are needed to treat metabolic disorders. Here, Kuang-Ting et al. elucidate structure–function relationships of non-covalent inverse agonists that enhance receptor binding and improve insulin sensitivity, providing a framework for next-generation drug design.

The interplay between neuronal activity and tumor progression is well-established. Here, the authors demonstrate that blockade of β-adrenergic signaling via administration of propranolol suppresses lung metastasis in multiple mouse tumor models by enhancing the accumulation of cytotoxic CD4 T cells while reducing CCR2+ monocytes, highlighting the re-purposing of β-blockers as a valid therapeutic approach for cancer treatment.

The evolution of cutaneous squamous cell carcinoma (cSCC) remains poorly understood. Here, the authors employ multi-omics and multi-scale analyses to explore the genetic evolution of keratinocytes to cSCC, finding key pathogenic mutations that break the resistance to ultraviolet radiation as well as spatial heterogeneity patterns.

An individualized, heterologous chimpanzee adenovirus (ChAd68) and self-amplifying mRNA-based neoantigen vaccine is safe and well tolerated in patients, warranting further studies to test its potential to rescue response to checkpoint blockade in tumors of low immune reactivity.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Estrogen receptor α is a primary driver of ER+ breast cancer and reproductive development. Here, the structure of the apo state is reported, providing a revised model for ligand-dependent and -independent regulation of receptor function.

Seronegative healthcare workers with an innate signature of infection preferentially expand pre-existing T cells targeting the conserved replication transcription complex of SARS-CoV-2 in abortive infection.

Engineering of a high-affinity Delta-like variant, named Delta^MAX, potently activates Notch signaling when provided in a bead-bound or cellular format, while administration as a soluble decoy inhibits signaling.

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

Methane emissions from oil and gas systems are underestimated in official inventories. Here the authors synthesize thousands of field measurements and develop an inventory-based model for a better understanding of why this underestimation exists and how it can be fixed.

There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the import of PTS2-containing proteins.

High-content protein arrays were used to identify cysteine dioxygenase (CDO1) as a small-molecule glue target for the von Hippel–Lindau (VHL) E3 ubiquitin ligase and induces VHL-dependent proteasomal degradation of CDO1 in cells.

In this work, Beyer and colleagues have utilized display screening technologies to comprehensively chart RAS proteins “druggability” and in doing so unravel a targetable ligand-induced pocket in RAS opening unprecedented anti-RAS targeted opportunities.

A mix-and-go system enables the rapid prototyping of antibody formulations, allowing control of their orientation on the surface of LNPs for specific cell targeting, significantly improving the ex vivo and in vivo deliveries of mRNA.

Four distinct tuft cell states are identified by combining analysis of primary human intestinal resection material and organoids, and studying tuft cell development shows that they represent a damage-induced reserve intestinal stem cell pool in humans.

Engineered carbon nanotube sensors enable the detection of intracranial tumours in blood, identify low-abundance biomarkers and amplify cancer detection by capturing secreted factors from the entire tumour ecosystem for early-stage disease diagnosis.

Trends in global H₂ sources and sinks are analysed from 1990 to 2020, and a comprehensive budget for the decade 2010–2020 is presented.

Nitric oxide has been shown to target mitochondrial aconitase 2 and pyruvate dehydrogenase to reprogramme macrophage metabolism. Here, the authors extend these findings to show that lipoate is used to generate nitroxyl in this process.

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

Understanding the heterogeneity of HIV infection, such as in persons with non-suppressible HIV-1 viremia despite adherence to antiretroviral treatment, is crucial to better tailor therapeutic interventions to abrogate HIV-1 persistence.

Pseudomonas aeruginosa biofilms are composed of exopolysaccharides, exogenous DNA, and proteins. Here, da Silva et al show that protein LecB binds to matrix exopolysaccharide Psl, thus contributing to increased retention of bacterial cells and exopolysaccharide in growing biofilms.

Genetically encoded sensors are generally optimized to function during exponential growth rather than stationary phase, which limits their potential value for metabolic engineering and bioproduction. Here, authors engineer a stationary phase green light sensor and use pulsatile light to optimize production of industrially relevant small molecules.

Personalized treatment for cancer patients relies on the deep characterization of tumor cells from patient biopsies. In this study, functional multi-omics profiling of a pan-cancer cohort of malignant serous effusions (MSE) finds strong coherence between MSE and matched solid tumors, underlining the feasibility and utility of multi-modal MSE-based precision oncology.

Gunawan et al. propose an Extensible Immunofluorescence (ExIF) strategy that integrates distinct 4-plex image panels from routine fluorescence microscopy into multiplexed datasets enabling quantitative interrogation of complex, multimolecular single-cell processes.

The multidomain scaffold protein SH3 and multiple ankyrin repeat domain 3 (SHANK3) can bind GTP-bound Ras and Rap small GTPases. Here the authors show that, by binding active KRAS, SHANK3 maintains oncogenic KRAS/MAPK/ERK signaling at an optimal level while its depletion in KRAS-mutant cancer cell lines results in ERK signalling overdose and impaired cell proliferation.

Mountains are hotspots of climate change, with melting glaciers, changing water flows and moving ecosystems. Here the authors discuss how these different changes in mountain regions affect downstream regions.

Despite their essentiality, human ANP32A and ANP32B are redundant host factors for influenza virus genome replication. In this work, authors show that an influenza virus grown in cells lacking ANP32A and ANP32B evolved to use ANP32E. They explore the polymerase mutations that enable this, and demonstrate increased virulence in mice.

Here the authors present results from a randomized, double-blinded Phase 1 clinical trial, testing a thermostable presentation of a clinical-stage adjuvanted subunit tuberculosis vaccine candidate. The vaccine candidate is safe and well tolerated, and elicits comparable or improved immune responses compared to the non-thermostable presentation.

CRISPR-mediated gene knockout and activation are used to identify molecules in cancer cells and macrophages that regulate antibody-dependent cancer cell phagocytosis.

Toxoplasma gondii secretion systems can be engineered to deliver multiple large therapeutic proteins to neurons in vitro and in vivo.

Tissue-resident marcophages have both generic and tissue-specific functions, but how the latter functions are imbued is still unclear. Here the authors show that peritoneal macrophages express a specialised genetic programme to utilise the locally enriched glutamate for a metabolic setting that facilitates protective in situ immunity.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Heart failure can be caused by cardiac fibroblasts replacing myocytes. Here, the authors use functional genomic data from fibroblasts, genetic signals enriched in people with heart disease, and gene perturbation analyses to link disease-associated regulatory elements to protein-coding genes.

Liccione et al. report the isolation and characterization of neutralizing antibodies targeting the spike protein of the endemic Alphacoronavirus HCoV-229E.

By coupling robotic cell culture systems with artificial intelligence–powered image analysis, Schiff et al. identify previously unseen characteristics of Parkinson’s disease in patient skin cells that distinguish them from healthy controls.

How lymphoid and myeloid specification occurs in human haematopoietic progenitors is not fully understood. Here the authors perform a proteomic screen on human bone marrow progenitors and suggest TdT⁺ and CD84^- progenitors as lymphoid-primed progenitors with residual myeloid potentials.

Chemical reactions on femtolitre scales are necessary to study confined biological processes. Here, the authors use a microfluidic pen lithography technique to perform a series of discrete femtoscale acid-base and synthetic reactions, and crystallizations on a surface with high registration accuracy.

Mutations in mtDNA contribute to mitochondrial disease and aging only if they rise in abundance. Here, the authors show that deleterious mutations reach high abundance by hitchhiking on genomes that have a replicative advantage.

Employing pharmacology, genetics and all-optical approaches in zebrafish, Braaker et al. find that neuronal activity influences the growth of myelin sheaths along axons by signaling through metabotropic glutamate receptor 5 on oligodendrocytes.

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT₈₀ biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition.

Determinants of WEE1 inhibitor sensitivity in cancer cells are largely undefined. Here, the authors show that WEE1 inhibitors beyond their cell cycle perturbing effects also lead to paradoxical activation of the integrated stress response kinase GCN2.

A large-scale livestock prevalence study in Cameroon identified Brucella abortus as the sole endemic species, primarily affecting cattle, and revealed its genetic link to African strains, underscoring the need for regional surveillance and control.

Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity and identified potential therapeutic targets.

The 2022 global mpox outbreak underscored the challenge of distinguishing between monkeypox virus infection and vaccination-induced immunity due to cross-reactive antibodies. Here, the authors develop a machine learning-assisted serological assay that differentiates MPXV infection from vaccination, achieving 88% specificity and 92% sensitivity, paving the way for seroepidemiological studies with improved resolution.