Biased Bowl-Direction of Monofluorosumanene in the Solid State.

A new curved π-conjugated molecule 1-fluorosumanene (1) was designed and synthesized that possesses one fluorine atom on the benzylic carbon of sumanene. This compound can exhibit bowl inversion in solution, leading to the formation of two diastereomers, 1endo and 1exo, with different dipole moments. Experimental and theoretical investigation revealed an energetical relationship among 1exo, 1endo, and solvent to realize the various endo:exo ratios in the single crystals of 1 depending on the crystallization solvent. Significantly, the molecular dynamics (MD) simulations revealed that 1exo positively worked for the elongation of the stacking structure and the final endo:exo ratio was affected by the relative stability difference between 1endo and 1exo derived by solvation. Such an arrangeable endo:exo ratio of 1 realized the preparation of unique materials showing a different dielectric response from the same molecule 1 just by changing the crystallization solvent.

Investigating the Combined Effects of Mechanical Stress and Nutrition on Muscle Hypertrophic Signals Using Contractile 3D-Engineered Muscle (3D-EM).

Since 3D-EM closely resembles in vivo muscles, the aim of this study was to investigate the effects of exercise (electrical pulse stimulation (EPS)) and nutrition (maca), which contains triterpenes, on muscle hypertrophy by using 3D-EM for the first time. The 3D-EM was composed of C2C12 cells and type 1 collagen gel, was differentiated for 14 days, and was divided into four groups: control, maca, EPS, and maca + EPS. The medium was replaced every two days before each EPS intervention, and the concentration of maca in the culture solution was 1 mg/mL. The intervention conditions of the EPS were 30 V, 1 Hz, and 2 ms (24 h on, 24 h off, for one week). The expression levels of proteins were examined by Western blotting. The intervention of maca and EPS upregulated the expression of MHC-fast/slow (both p < 0.05) compared with the control group, and the addition of maca had no effect on the phosphorylation of mTOR (p = 0.287) but increased the AMPK phosphorylation (p = 0.001). These findings suggest that intervention with maca and EPS has a positive effect on muscle hypertrophy, which has a positive impact on sarcopenia. However, the underlying mechanisms remain to be further explored.

Ergogenic Effects of Very Low to Moderate Doses of Caffeine on Vertical Jump Performance.

Although the ergogenic effects of 3-6 mg/kg caffeine are widely accepted, the efficacy of low doses of caffeine has been discussed. However, it is unclear whether the ergogenic effects of caffeine on jump performance are dose responsive in a wide range of doses. This study aimed to examine the effect of very low (1 mg/kg) to moderate doses of caffeine, including commonly utilized ergogenic doses (i.e., 3 and 6 mg/kg), on vertical jump performance. A total of 32 well-trained collegiate sprinters and jumpers performed countermovement jumps and squat jumps three times each in a double-blind, counterbalanced, randomized, crossover design. Participants ingested a placebo or 1, 3, or 6 mg/kg caffeine 60 min before jumping. Compared with the placebo, 6 mg/kg caffeine significantly enhanced countermovement jump (p < .001) and squat jump (p = .012) heights; furthermore, 1 and 3 mg/kg of caffeine also significantly increased countermovement jump height (1 mg/kg: p = .002, 3 mg/kg: p < .001) but not squat jump height (1 mg/kg: p = .436, 3 mg/kg: p = .054). There were no significant differences among all caffeine doses in both jumps (all p > .05). In conclusion, even at a dose as low as 1 mg/kg, caffeine improved vertical jump performance in a dose-independent manner. This study provides new insight into the applicability and feasibility of 1 mg/kg caffeine as a safe and effective ergogenic strategy for jump performance.

Acute Effect of Caffeine Supplementation on 100-m Sprint Running Performance: A Field Test.

PURPOSE: No study has assessed the acute effect of caffeine supplementation on 100-m sprint running in athletics and caffeine's net ergogenicity on 100-m sprint running remains unclear. We investigated the acute effects of caffeine supplementation on 100-m sprint running performance in a field test. METHODS: Thirteen male collegiate sprinters were subjected to 100-m sprint running time trials (TT) after the ingestion of 6 mg·kg -1 body weight caffeine or placebo supplementation in a double-blind, counterbalanced, randomized, and crossover design. Sprint velocity was measured with a laser system, and sprint time was calculated from the data in which the effects of environmental factors that would act as confounding factors on sprint time during TT were eliminated. RESULTS: The corrected 100-m sprint time was significantly shortened by 0.14 s with caffeine supplementation compared with placebo (placebo: 11.40 ± 0.39 s, caffeine: 11.26 ± 0.33 s; P = 0.007, g = -0.33). The corrected sprint time up to 60 m during TT was also significantly shorter with caffeine supplementation than with placebo ( P = 0.002). Furthermore, the mean sprint velocity for splits of 0-10 and 10-20 m was significantly increased by caffeine supplementation (all P < 0.05). CONCLUSIONS: Acute caffeine supplementation enhanced the corrected 100-m sprint time by improving the sprint performance in the first 60 m after more explosive acceleration in the early stage of the acceleration phase. Thus, for the first time, we directly demonstrated caffeine's ergogenicity on 100-m sprint performance in athletics.

Inflammation and hyperglycemia mediate Deaf1 splicing in the pancreatic lymph nodes via distinct pathways during type 1 diabetes.

Peripheral tolerance is partially controlled by the expression of peripheral tissue antigens (PTAs) in lymph node stromal cells (LNSCs). We previously identified a transcriptional regulator, deformed epidermal autoregulatory factor 1 (Deaf1), that can regulate PTA expression in LNSCs of the pancreatic lymph nodes (PLNs). During the pathogenesis of type 1 diabetes (T1D), Deaf1 is spliced to form the dominant-negative isoform Deaf1-Var1. Here we show that Deaf1-Var1 expression correlates with the severity of disease in NOD mice and is reduced in the PLNs of mice that do not develop hyperglycemia. Inflammation and hyperglycemia independently drive Deaf1 splicing through activation of the splicing factors Srsf10 and Ptbp2, respectively. Inflammation induced by injection of activated splenocytes increased Deaf1-Var1 and Srsf10, but not Ptbp2, in the PLNs of NOD.SCID mice. Hyperglycemia induced by treatment with the insulin receptor agonist S961 increased Deaf1-Var1 and Ptbp2, but not Srsf10, in the PLNs of NOD.B10 and NOD mice. Overexpression of PTBP2 and/or SRSF10 also increased human DEAF1-VAR1 and reduced PTA expression in HEK293T cells. These data suggest that during the progression of T1D, inflammation and hyperglycemia mediate the splicing of DEAF1 and loss of PTA expression in LNSCs by regulating the expression of SRSF10 and PTBP2.

Prediction and experimental validation of a putative non-consensus binding site for transcription factor STAT3 in serum amyloid A gene promoter.

We previously demonstrated that though the human SAA1 gene shows no typical STAT3 response element (STAT3-RE) in its promoter region, STAT3 and the nuclear factor (NF-κB) p65 first form a complex following interleukin IL-1 and IL-6 (IL-1+6) stimulation, after which STAT3 interacts with a region downstream of the NF-κB RE in the SAA1 promoter. In this study, we employed a computational approach based on indirect read outs of protein-DNA contacts to identify a set of candidates for non-consensus STAT3 transcription factor binding sites (TFBSs). The binding of STAT3 to one of the predicted non-consensus TFBSs was experimentally confirmed through a dual luciferase assay and DNA affinity chromatography. The present study defines a novel STAT3 non-consensus TFBS at nt -75/-66 downstream of the NF-κB RE in the SAA1 promoter region that is required for NF-κB p65 and STAT3 to activate SAA1 transcription in human HepG2 liver cells. Our analysis builds upon the current understanding of STAT3 function, suggesting a wider array of mechanisms of STAT3 function in inflammatory response, and provides a useful framework for investigating novel TF-target associations with potential therapeutic implications.