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Experimental and computational studies establish the operation of Fe(iii)-based metalloradical catalysis for the asymmetric cyclopropanation of alkenes with different classes of diazo compounds. The reaction proceeds through a stepwise radical mechanism involving α-Fe(iv)-alkyl and γ-Fe(iv)-alkyl radical intermediates. This work provides a future direction for the development of metalloradical catalysis.

Migration can increase regional differences in both DNA variants and environmental factors that are associated with socio-economic status. Without controlling for geography, associations between genes and complex traits will therefore include effects of environmental differences between high-income and low-income regions.

Phenotypic plasticity of cancer cells is increasingly recognized as a mechanism of tumor escape from targeted therapies. Yet, the phenotypic heterogeneity of colorectal cancer remains poorly explored. Our study identifies oncofetal reprogramming of neoplastic stem cells, driven by the transcription factors YAP and AP-1, as a critical driver of phenotypic heterogeneity, lineage plasticity and therapy resistance. Targeting the oncofetal program enhances the efficacy and durability of current treatments.

NKX3.1-expressing intermediate Basal-B cells represent a transient basal stem cell state during prostate regeneration, inflammation and cancer initiation. Remarkably, activation of JAK/STAT signaling is essential in regulating expansion and differentiation of Basal-B-like cells during prostate inflammation, identifying this signaling pathway as a potential therapeutic target in prostatitis associated with increased Basal-B signature.

Existing functional genomics datasets are European-centric. The Asian Immune Diversity Atlas incorporated single-cell RNA-sequencing data from approximately 1 million peripheral blood mononuclear cells from around 500 donors of diverse Asian ancestries. Mapping of splicing quantitative trait loci revealed context-specific regulation of alternative splicing, as well as cell-type and ancestry-specific genetic effects on complex diseases.

PopV is an ensemble method for cell type labeling in single-cell genomics. A Cell Ontology-inspired voting procedure across different algorithms highlights low confidence annotations, thereby guiding human-in-the loop components of the annotation process.

DNA variants arising in the genome of cancer cells are a major cause of therapy failure, but for most variants, their effects on drug response are unknown. Base-editing screens provide a systematic approach to uncover the functions of cancer variants at scale, which might help to inform the use of precision cancer therapies.

This study presents a spatial transcriptomic analysis of matched primary tumors, liver metastases and lymph node metastases from patients with pancreatic ductal adenocarcinoma. Using a tumor ecosystem approach, we uncovered notable tumor microenvironmental heterogeneity and marked differences between primary and metastatic samples, providing key insights into metastatic pancreatic cancer.

The identification of KRAS G12C inhibitors has reignited interest in targeting RAS proteins. This work describes the discovery of the KRAS G12D -specific inhibitor MRTX1133 and demonstrates the feasibility of potently and selectively targeting this oncogenic variant. MRTX1133 treatment markedly inhibited KRAS-dependent signaling and induced tumor regression in xenograft models harboring the KRAS G12D mutation.

The Irf8 +32-kb enhancer controls transcriptional autoactivation to generate ‘IRF8 on’ and ‘IRF8 off’ states that define type 1 conventional dendritic cell (cDC1) and cDC2 lineages, respectively. Weak affinity of this enhancer for BATF3–JUNB–IRF8 complexes allows specified cDC2 progenitors to successfully turn off Irf8 transcription. If this enhancer is made stronger, cDC2 commitment and cDC1–cDC2 lineage segregation are compromised.