Detecting Zn(II) Ions in Live Cells with Near-Infrared Fluorescent Probes.

Two near-infrared fluorescent probes (A and B) containing hemicyanine structures appended to dipicolylamine (DPA), and a dipicolylamine derivative where one pyridine was substituted with pyrazine, respectively, were synthesized and tested for the identification of Zn(II) ions in live cells. In both probes, an acetyl group is attached to the phenolic oxygen atom of the hemicyanine platform to decrease the probe fluorescence background. Probe A displays sensitive fluorescence responses and binds preferentially to Zn(II) ions over other metal ions such as Cd2+ ions with a low detection limit of 0.45 nM. In contrast, the emission spectra of probe B is not significantly affected if Zn(II) ions are added. Probe A possesses excellent membrane permeability and low cytotoxicity, allowing for sensitive imaging of both exogenously supplemented Zn(II) ions in live cells, and endogenously releases Zn(II) ions in cells after treatment of 2,2-dithiodipyridine.

Ketogenic-Mimicking Diet as a Therapeutic Modality for Bipolar Disorder: Biomechanistic Rationale and Protocol for a Pilot Clinical Trial.

There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a 'ketogenic-mimicking diet' (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.

A cyanine-based fluorescent cassette with aggregation-induced emission for sensitive detection of pH changes in live cells.

An aggregation-induced emission (AIE) cyanine-based fluorescent cassette with a large pseudo-Stokes shift was designed and prepared to sensitively image pH changes in live cells via through-bond energy transfer (TBET) from a tetraphenylethene (TPE) donor to a cyanine acceptor.