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Lu and colleagues show that signaling through the lactate receptor HCAR1 in colorectal tumor cells promotes the recruitment of immunosuppressive CCR2⁺ PMN-MDSCs and that inhibition of HCAR1 by reserpine augments the CD8⁺ T cell-mediated antitumor immune response.

Through rational engineering of A3A deaminase, Yang and colleagues have designed CBEs termed haA3A-CBEs, which feature a condensed editing window and minimal off-target effects that are independent of defined sequence contexts and methylation status.

Yuan et al. present S2-omics, an end-to-end workflow that automatically identifies regions of interest in histology images to maximize molecular information capture in spatial omics experiments.

The proton-sensing GPCRs detect extracellular low pH and regulate diverse physiological responses. Here, the authors report cryo-EM structures of GPR4, which provide insight into the structural features of proton sensing mechanism.

A light-inducible RNA base editor fine-tunes gene expression for therapeutics.

The authors of this manuscript identify that Gpr54 activation by its natural ligand Kisspeptin-10 can abrogate bone resorption. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase, which causes Dusp18 to dephosphorylate Src at Tyr 416.

Based on an immunogenicity screen of monkeypox virus (MPXV) surface proteins, the authors develop an mRNA vaccine with 12 antigens, which they combine with T cell epitope-rich regions to achieve protection through coordinated activation of humoral and cellular immune responses.

Efficient adenine base editors for mitochondrial DNA are achieved with evolved TadA deaminases.

Preliminary results from a phase 1/2 trial with 18-month follow-up show that transplantation of CRISPR–Cas9 BCL11A-edited autologous hematopoietic cells in two children with β-thalassemia was safe and achieved transfusion independence.

MISO (MultI-modal Spatial Omics) integrates two or more spatial omics modalities, despite differences in data quality and spatial resolution for improved feature extraction and clustering to reveal biologically meaningful tissue organization.

The severe fever with thrombocytopenia syndrome virus (SFTSV, officially named Dabie bandavirus) is a tick-borne human-infecting bunyavirus. Here, the authors report the cryo-EM structure of SFTSV virion, and discuss the mechanisms of viral assembly, membrane fusion and antibody neutralization.

Radiotherapy is an important part of glioblastoma (GBM) treatment, but patient outcomes are often limited by resistance. Here, the authors identify a role for IFI16 in the promotion of a cellular senescence-like phenotype, inhibiting ferroptosis and driving radioresistance which can be overcome with Glyburide in preclinical GBM models.

Despite being an established oncogenic driver of non-small cell lung cancer (NSCLC), therapies targeting NRF2 hyperactivation are lacking. Here, the authors identify peptidylprolyl isomerase A (PPIA) as a mediator of NRF2 stability and demonstrate the efficacy of targeting this interaction with cyclosporin A in preclinical models of NSCLC.

Spatially resolved transcriptomic profiling of primary tumours and metastases from patients with pancreatic cancer provides insight into the evolutionary progression to metastasis, and the variation in clonal architecture within and between individuals.

There is a low efficiency of A-to-G base conversion in at specific positions using base editors. Here the authors fuse ABE8e with the Rad51 DNA-binding domain to generate a hyperactive ABE allowing improved A-to-G editing efficiency at the region proximal to the PAM and improved simultaneous A/C conversion efficiency.

Pathologic α-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologic α-synuclein.

Analyses of single epithelial cells from early-stage lung adenocarcinoma and normal lung identifies a population of intermediate cells that may have an increased likelihood of transforming to tumour cells after injury such as tobacco exposure.

A precise adenine base editor variant, ABE9, was developed to generate single adenine transition at pathogenic homopolymeric adenine sites with minimal DNA/RNA off-target effects, suggesting promising potential for gene therapeutics.

The authors use lipid nanoparticles (LNPs) that predominantly accumulate in the lung to deliver mRNA encoding for the broadly neutralizing antibody 8-9D, and achieve superior inhibition of SARS-CoV-2 infection in mice compared to control LNPs.

In this study, the authors isolate and characterize BBIBPCorV inactivated vaccine-elicited human antibodies. They show that these can broadly neutralize a range of SARS-CoV-2 variants and protect mice from Delta and Omicron infection. The neutralization mechanism of bispecific antibodies were solved structurally.

Chen et al. perform single-cell analysis and identify transcriptomic remodelling in epithelial cells, macrophages, T cells, fibroblasts and endothelial cells, which together regulate prostate cancer progression.

The role of PHD finger protein 8 (PHF8) in anti-tumour immunity remains to be investigated. Here, the authors suggest PHF8 as an epigenetic checkpoint and show that targeting PHF8 induces a viral mimicry response enhancing anti-tumour immunity in colorectal cancer.

A base editor for precise adenine transversions is demonstrated in mouse embryos.

A spatial transcriptomic analysis of healthy kidneys and those from individuals with chronic kidney disease characterizes the fibrotic microenvironment and highlights features that could be used to predict prognosis.

Ex vivo perfusion is a unique platform to study isolated human lungs. Here, authors show that a machine learning model, InsighTx, derived from data generated during ex vivo lung perfusion can accurately predict transplant outcomes and increase organ utilization rates.

The role of translationally controlled tumour protein (TCTP) in Drosophila development using genetics is examined. An interesting connection between TCTP and another signalling pathway, called tuberous sclerosis complex, which controls organ size by modulating cell proliferation and cell size is found. Genetic and biochemical evidence that TCTP is a direct regulator of Rheb, a component of the TSC pathway, and may be a guanine nucleotide exchange factor for Rheb is also provided.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Dorsal root ganglia (DRGs) contain a plethora of neuron types. The authors show that the existence of human-specific DRG neuronal types and microneurography recordings reveal distinct temperature-sensing properties across human sensory afferent types.

Improved cytosine base editors are created by repurposing an adenine deaminase.

The growth of colorectal cancer is reduced by ketogenic diet consumption, the properties of which are mediated by the ketone body β-hydroxybutyrate.

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

KRas is frequently mutated in multiple cancer types; identifying drugs to treat such cancers is a good therapeutic strategy. Here, the authors perform a synthetic lethal screen in mice and show that inhibiting Plk1 and ROCK results in the inhibition of tumour growth by increasing expression of the tumour suppressor p21.

Epigenetic and transcriptional dynamics are critical for both tissue homeostasis and injury response in the kidney. Leveraging a single cell multiomics atlas of the developing mouse kidney, the authors reveal key events in chromatin regulation and gene expression dynamics during postnatal development.

Organs from donors with transmissible viral infections, such as hepatitis C virus (HCV), are not offered for transplantation due to a high risk of transmission. Here, Galasso et al. develop a method for treatment of HCV-infected human donor lungs that is safe and prevents HCV transmission in the pig model.

Obesity results from accumulation of white adipose tissue, whereas brown adipose tissue can counteract these effects through thermogenesis. Ning and colleagues have found that the GPCR family member Lgr4 controls the balance between brown and white adipose tissue. In its absence, mice have reduced adiposity and obesity symptoms, and exhibit an increase in brown-like adipocytes, possibly the result of a decrease in Rb expression.

Li and colleagues report base editor variants with improved targeting efficiencies and broader editing windows by fusing the original base editors with the single-stranded DNA-binding domain of Rad51.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Non-viral CAR-T cells with gene-specific targeted integration are safe and effective in patients with lymphoma.