Unveiling radiobiological traits and therapeutic responses of BRAF-mutant colorectal cancer via patient-derived organoids.

Background: Radiotherapy (RT) is an essential treatment for colorectal cancer (CRC), yet the factors influencing radiosensitivity remain unclear. In the quest to enhance the therapeutic efficacy in CRC, the interplay between genetic mutations and RT sensitivity has emerged as a pivotal yet enigmatic area.

Methods: We harness the fidelity of patient-derived organoids (PDOs) to dissect the molecular landscape of radiosensitivity, with a particular emphasis on BRAF mutations.

Targeting tumor monocyte-intrinsic PD-L1 by rewiring STING signaling and enhancing STING agonist therapy.

STING is an important DNA sensing machinery in initiating immune response, yet therapies targeting STING have shown poor outcomes in clinical trials. Here, we reveal that STING signaling induces PD-L1 tumor monocytes (Tu.Mons) that dominate the resistance against STING agonist therapy.

Integrating genome-wide association studies and transcriptomics prioritizes drug targets for meningioma.

Meningioma, a prevalent central nervous system tumour, presents a significant challenge in neuro-oncology. This study harnesses genome-wide association studies (GWAS) and transcriptomic analysis to illuminate the pathological underpinnings of meningioma and spearhead the discovery of novel drug targets. By employing summary-data-based Mendelian randomization (SMR), colocalization analyses and Mendelian randomization, we pinpointed four genes as pivotal therapeutic targets.

Lactate dehydrogenase B deficiency-dependent hyperlactatemia coordinates with necroptosis to worsen septic liver and kidney injuries.

Hyperlactatemia is intimately correlated with severity and poor prognosis of patients with sepsis. However, little experimental evidence on this process is known. We report here that lactate dehydrogenase B (LDHB), the glycolytic enzyme that catalyzes conversion of lactate to pyruvate, is transcriptionally downregulated in blood samples of hyperlactatemic patients, while mice receiving lactate injection have reduced LDHB activity in liver and kidney.

Exploring the Interaction Between HLA-B27 and Other Risk Factors of Valvular Heart Disease in Axial Spondyloarthritis.

Objectives: HLA-B27 plays a critical role in axial spondyloarthritis (axSpA). Valvular heart disease (VHD) is a life-threatening extra-articular manifestation of axSpA. The evidence for the association between HLA-B27 and VHD in axSpA is still scarce and controversial.