Efficacious fluorescence turn-on probe for high-contrast imaging of human cells overexpressing quinone reductase activity.

We report a new turn-on substrate probe whose intense fluorescent reporter signature is selectively provided upon probe activation by the cancer-associated oxidoreductase, hNQO1. The extremely high fluorescence turn-on of the probe was utilized to generate fluorescence microscope images of hNQO1-expressing, tumor-derived colorectal and ovarian cancer cells with unprecedented positive signal-to-negative background ratios (PNRs), a key step toward probe application in guided surgical removal of diseased tissues.

Environmentally Robust Rhodamine Reporters for Probe-based Cellular Detection of the Cancer-linked Oxidoreductase hNQO1.

Unlabelled: We successfully synthesized a fluorescent probe capable of detecting the cancer-associated

Nad(p)h: quinoneoxidoreductase isozyme-1 within human cells, based on results from an investigation of the stability of various rhodamines and seminaphthorhodamines toward the biological reductant NADH, present at ∼100-200 μM within cells. While rhodamines are generally known for their chemical stability, we observe that NADH causes significant and sometimes rapid modification of numerous rhodamine analogues, including those oftentimes used in imaging applications. Results from mechanistic studies lead us to rule out a radical-based reduction pathway, suggesting rhodamine reduction by NADH proceeds by a hydride transfer process to yield the reduced leuco form of the rhodamine and oxidized NAD(+).

Effects of examiner strength on reliability of hip-strength testing using a handheld dynamometer.

Context: Hip-muscle impairments are associated with a variety of lower-extremity dysfunctions. Accurate assessment in the clinical setting can be challenging due to the strength of hip muscles relative to examiner strength.

Objective: To examine the influence of examiner strength and technique on manual hip-strength testing using a handheld dynamometer.