ABSTRACT
Radiation therapy is one of the most common treatments for cancer. However, enhancing tumors' radiation sensitivity and overcoming tolerance remain a challenge. Previous studies have shown that the Ras signaling pathway directly influences tumor radiation sensitivity. Herein, we designed a series of Ras-targeting stabilized peptides, with satisfactory binding affinity (KD = 0.13 µM with HRas) and good cellular uptake. Peptide H5 inhibited downstream phosphorylation of ERK and increased radio-sensitivity in HeLa cells, resulting in significantly reduced clonogenic survival. The stabilized peptides, designed with an N-terminal nucleation strategy, acted as potential radio-sensitizers and broadened the applications of this kind of molecule. This is the first report of using stabilized peptides as radio-sensitizers, broadening the applications of this kind of molecule.
ABSTRACT
In vivo imaging has been widely used for investigating the structure and function of neurons typically located within ~ 800 µm below the cortical surface. Due to light scattering and absorption, it has been difficult to perform in-vivo imaging of neurons in deep cortical and subcortical regions of large animals with two-photon microscopy. Here, we combined a thin-wall quartz capillary with a GRIN lens attached to a prism for large-volume structural and calcium imaging of neurons located 2 mm below the surface of rabbit and monkey brains. The field of view was greatly expanded by rotating and changing the depth of the imaging probe inside a quartz capillary. Calcium imaging of layer 5/6 neurons in the rabbit motor cortex revealed differential activity of these neurons between quiet wakefulness and slow wave sleep. The method described here provides an important tool for studying the structure and function of neurons located deep in the brains of large animals.
