Do Glucose and Caffeine Nasal Sprays Influence Exercise or Cognitive Performance?

INTRODUCTION: Nasal spray (NAS) containing caffeine (CAF) or glucose (GLUC) activates sensory(motor) cortices. PURPOSE: To investigate the influence of CAF or GLUC NAS on exercise and cognitive performance. METHODS: Eleven male subjects (age 22 ± 2 y) performed a maximal cycle test and 2 familiarization and 3 experimental trials. Each trial included a 30-s Wingate test and a 30-min time-trial (TT) performance test interspersed by 15 min of rest. Before and after each exercise test a Stroop task was conducted. Placebo NAS with or without CAF or GLUC was provided before each exercise session and at each completed 25% of the TT. Exercise-performance, physiological, and cognitive measures were obtained. Magnitude-based inferences determined the likelihood that NAS solutions would be beneficial, trivial, or negative to exercise-performance measures based on the smallest worthwhile effect. Physiological and cognitive measures were analyzed using (non)parametric tests (P < .05). RESULTS: GLUC NAS substantially increased the average power output during the TT (very likely beneficial: 98%). No further worthwhile exercise-performance enhancements were found for both substances. In addition, no significant differences in physiological and cognitive measures were observed. In line with mouth rinsing, GLUC was shown to substantially enhance endurance performance, probably due to the activation of the olfactory pathway and/or extra-oral sweet-taste receptors. CONCLUSION: GLUC NAS enhances endurance performance, which indicates a novel administration route. The higher activity in sensory brain cortices probably elicited the ergogenic effect. However, no further physiological and cognitive changes occurred, indicating that higher doses of substrates might be required.

Identification, mechanism of action, and antitumor activity of a small molecule inhibitor of hippo, TGF-ß, and Wnt signaling pathways.

Embryonic signaling pathways, in particular those mediated by Wnt and TGF-ß, are known to play key roles in tumor progression through the induction of epithelial-mesenchymal transition (EMT). Their simultaneous targeting could therefore represent a desirable anticancer strategy. On the basis of recent findings that both Wnt and TGF-ß-associated pathways are regulated by Hippo signaling in mammalian cells, we reasoned that targeting the latter would be more effective in inhibiting EMT. In a search for such inhibitors, we identified a small molecule (C19) with remarkable inhibitory activity not only against Hippo, but also against Wnt and TGF-ß pathways. C19 inhibited cancer cell migration, proliferation, and resistance to doxorubicin in vitro, and exerted strong antitumor activity in a mouse tumor model. Mechanistically, C19 induced GSK3-ß-mediated degradation of the Hippo transducer TAZ, through activation of the Hippo kinases Mst/Lats and the tumor suppressor kinase AMPK upstream of the degradation complex. Overall, this study identified C19 as a multi-EMT pathway inhibitor with a unique mechanism of action. The findings that both AMPK and Mst/Lats mediate the antitumor activity of C19 shed light on a potential cross-talk between metabolic and organ size control pathways in regulating cancer progression. By simultaneously targeting these two pathways, C19 may represent a new type of agents to suppress cancer progression and/or its recurrence.

Amide enolate additions to acylsilanes: in situ generation of unusual and stereoselective homoenolate equivalents.

The synthesis of beta-hydroxy carbonyl compounds is an important goal due to their prevalence in bioactive molecules. A novel approach to construct these structural motifs involves the multicomponent reaction of acylsilanes, amides, and electrophiles. The addition of amide enolates to acylsilanes generates beta-silyloxy homoenolate reactivity by undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ can then undergo addition to alkyl halides, aldehydes, ketones, and imines. The gamma-amino-beta-hydroxy amide products derived from the addition of these homoenolates to N-diphenylphosphinyl imines are generated with excellent diastereoselectivity (> or = 20:1) and can be efficiently converted to highly valuable gamma-lactams. Finally, the use of optically active amide enolates delivers beta-hydroxy amide products with high levels of diastereoselectivity (> or = 10:1).

A frequency domain existence proof of single-molecule surface-enhanced Raman spectroscopy.

The existence of single-molecule surface-enhanced Raman spectroscopy (SMSERS) is proven by employing a frequency-domain approach. This is demonstrated using two isotopologues of Rhodamine 6G that offer unique vibrational signatures. When an average of one molecule was adsorbed per silver nanoparticle, only one isotopologue was typically observed under dry N2 environment. Additionally, the distribution of vibrational frequencies hidden under the ensemble average is revealed by examining the single-molecule spectra. Correlation with transmission electron microscopy reveals that SMSERS active aggregates are composed of multiple randomly sized and shaped nanoparticles. At higher coverage and in a humid environment, adsorbate interchange was detected. Using 2D cross correlation, vibrational modes from different isotopologues were anti-correlated, indicating that the dynamic behavior was from multiple molecules competing for a single hot spot. This allows hot-spot diffusion to be directly observed without analyzing the peak intensity fluctuations.

Synthesis of tertiary beta-hydroxy amides by enolate additions to acylsilanes.

The synthesis of tertiary beta-hydroxy amides from acylsilanes, acetamides, and electrophiles is described. The addition of amide enolates to acylsilanes generates beta-silyloxy homoenolate reactivity by undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ can then undergo smooth addition to alkyl halides, aldehydes, and ketones. Enolates derived from amides are crucial for the success of this process since ketone enolates suffer from internal return of the beta-carbanion onto the carbonyl carbon. The use of optically active amide enolates delivers beta-hydroxy amide products with good levels of diastereoselectivity (>/=10:1).