Synthesis and Anti-Inflammatory Activity of Ferulic Acid-Sesquiterpene Lactone Hybrids.

Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.

Effects of Adverse Events and 12-Week Group Step Aerobics on Sleep Quality in Chinese Adolescents.

BACKGROUND: In China, sleep disorders have become a public health concern. This study aimed to model the relationship between adverse events and sleep quality, as well as the effect of group step aerobics on sleep quality. METHODS: The modeling was built on surveying 2760 16-19-year-old adolescents. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and the Adolescent Self-rating Life Events Checklist (ASLEC) was used to evaluate adverse events. Adolescents with sleep disorders (PSQI ≥ 8) were randomized into the control (n = 26) and exercise (n = 26) groups. The exercise group participated in 12-week step aerobics, and the 300 min weekly volume is compliant with the WHO physical activity guidelines. RESULTS: The double Poisson distribution was chosen to fit the data. ASLEC had a nonlinear relationship with the PSQI. Participants in the exercise group slept better (p < 0.05) from the eighth week until the end of the study. A random adolescent, therefore, has a 92.5% probability of experiencing improved sleep quality after 12 weeks of step aerobics. CONCLUSIONS: Intervention should be implemented before adverse events accumulate. An active lifestyle should be a preparedness strategy for increasing the resilience of adolescent mental health in the face of adversity.

Effects of message framing, psychological distance, and risk perception on exercise attitude in Chinese adolescents.

Objectives: Health communication campaign that promotes physical activity may aid in reducing the prevalence of childhood and adolescent obesity in China. This study examined the effects of message framing and psychological distance on the exercise attitude of Chinese adolescents, along with the interactive role of risk perception. Methods: Participants in this study were between 10 and 19 years of age. Three experiments were conducted independently. In experiment 1, 76 participants were recruited to assess the effectiveness of message manipulation. In experiment 2, 40 participants were recruited to compare the effects of gain- and loss-framed messages on the exercise attitude. In experiment 3, 37 participants were recruited to explore the interaction between message framing (gain vs. loss), temporal distance (proximal vs. distal), and risk perception (low vs. high) on the exercise attitude. Exercise attitude and risk perception were assessed by Likert-type questionnaires. Results: There was a significant main effect of message framing (P < 0.05), with the gain-framed message inducing a stronger exercise attitude than the loss-framed message. There was a significant main effect of temporal distance (P < 0.05), with the proximal temporal distance condition inducing a stronger exercise attitude than the distal temporal distance condition. In addition, a significant interaction (P < 0.05) was observed, and the perception of obesity-related risk was a crucial moderator of the message framing and temporal distance. Regardless of whether they were exposed to a gain- or loss-framed message, the proximal temporal distance condition induced a stronger exercise attitude in participants with a high risk perception (P < 0.05). Conclusion: Messages promoting exercise that are framed as having a near-future gain effect and that emphasize disease risks are effective in motivating adolescents to engage in physical activity.

Effect of mass sports activity on prosocial behavior: A sequential mediation model of flow trait and subjective wellbeing.

Objectives: Participation in mass sports is one of the most efficient strategies for people to attain physical and mental health in China. Prosocial behavior has a positive effect on social development. This study developed a conceptual model with mass sports activity as the independent variable, prosocial behavior as the dependent variable, and flow trait and subjective wellbeing as the mediating variables. Methods: Participants (N = 351) completed an online survey. Mass sports activity, flow trait, subjective wellbeing, and prosocial behavior were measured using the physical activity rank scale-3 (PARS-3), short dispositional flow scale (SDFS), index of wellbeing (IWB), and prosocial tendencies measure (PTM), respectively. Descriptive statistics compared differences between sports population (PARS-3, ≥ 36) and non-sports population (PARS-3, <36). Mediation effect was analyzed using the PROCESS (Template, Model 6). Results: Sports population scored significantly higher (all P ≤ 0.05) on SDFS, IWB, and PTM than non-sports population. Participation in mass sports stimulated flow trait and thus improved prosocial behavior, with a mediation effect value of 0.061 (95% CI, 0.028-0.104), which accounted for 30.18% of the total effect. Participation in mass sports enhanced subjective wellbeing and thus improved prosocial behavior, with a mediation effect value of 0.044 (95% CI, 0.007-0.090), which accounted for 21.96% of the total effect. Flow trait and subjective wellbeing mediated the relationship between mass sports activity and prosocial behavior in a sequential manner, with a mediation effect value of 0.059 (95% CI, 0.035-0.090), which accounted for 29.23% of the total effect. Conclusion: The preliminary results of the mediation model validated the hypothesized sequential links between mass sports activity, flow trait, subjective wellbeing, and prosocial behavior. Greater participation in mass sports increases the likelihood of prosocial behavior.

Synthesis of Glycosyl Chlorides and Bromides by Chelation Assisted Activation of Picolinic Esters under Mild Neutral Conditions.

A general method has been developed for the formation of glycosyl chlorides and bromides from picolinic esters under mild and neutral conditions. Benchtop stable picolinic esters are activated by a copper(II) halide species to afford the corresponding products in high yields with a traceless leaving group. Rare ß glycosyl chlorides are accessible via this route through neighboring group participation. Additionally, glycosyl chlorides with labile protecting groups previously not easily accessible can be prepared.

Site-Selective and Stereoselective O-Alkylation of Glycosides by Rh(II)-Catalyzed Carbenoid Insertion.

Carbohydrates are synthetically challenging molecules with vital biological roles in all living systems. Selective synthesis and functionalization of carbohydrates provide tremendous opportunities to improve our understanding on the biological functions of this fundamentally important class of molecules. However, selective functionalization of seemingly identical hydroxyl groups in carbohydrates remains a long-standing challenge in chemical synthesis. We herein describe a practical and predictable method for the site-selective and stereoselective alkylation of carbohydrate hydroxyl groups via Rh(II)-catalyzed insertion of metal carbenoid intermediates. This represents one of the mildest alkylation methods for the systematic modification of carbohydrates. Density functional theory (DFT) calculations suggest that the site selectivity is determined in the Rh(II)-carbenoid insertion step, which prefers insertion into hydroxyl groups with an adjacent axial substituent. The subsequent intramolecular enolate protonation determines the unexpected high stereoselectivity. The most prevalent trans-1,2-diols in various pyranoses can be systematically and predictably differentiated based on the model derived from DFT calculations. We also demonstrated that the selective O-alkylation method could significantly improve the efficiency and stereoselectivity of glycosylation reactions. The alkyl groups introduced to carbohydrates by OH insertion reaction can serve as functional groups, protecting groups, and directing groups.

Solvent-Controlled Synthesis of Thiocyanated Enaminones and 2-Aminothiazoles from Enaminones, KSCN, and NBS.

An effective and simple solvent-controlled synthesis of thiocyanated enaminones and 2-aminothiazoles has been demonstrated from enaminones, potassium thiocyanate, and N-bromosuccinimide. This process features mild reaction conditions, simple and easy operation, short reaction time, and high yield and chemoselectivity and thereby provides an efficient protocol for the divergent synthesis of thiocyanated enaminones and substituted 2-aminothiazoles controlled by simply varying the solvent. All reaction components are commercially available or easily accessible at low cost. The potential utility of these methods in organic chemistry and medicinal chemistry applications is highlighted.

Isoquinoline-1-Carboxylate as a Traceless Leaving Group for Chelation-Assisted Glycosylation under Mild and Neutral Reaction Conditions.

Glycosyl isoquinoline-1-carboxylate was developed as a novel benchtop stable and readily available glycosyl donor. The glycosylation reaction was promoted by the inexpensive Cu(OTf)2 salt under mild reaction conditions. The copper isoquinoline-1-carboxylate salt was precipitated from the solution and thus rendered a traceless leaving group. Surprisingly, the proton from the acceptor was absorbed by the precipitated metal complex and the reaction mixture remained at neutral pH. The copper-promoted glycosylation was also proven to be completely orthogonal to the gold-promoted glycosylation, and an iterative synthesis of oligosaccharides from benchtop stable anomeric ester building blocks becomes possible under mild reaction conditions.

Base-Mediated Cascade Substitution-Cyclization of 2H-Azirines: Access to Highly Substituted Oxazoles.

A novel strategy to synthesize highly functionalized oxazoles has been successfully developed via a base-mediated intermolecular substitution between 2-acyloxy-2H-azirines and N-nucleophile or O-nucleophile with a subsequent ring expansion of a 2H-azirine intermediate. This method provides straightforward access to highly substituted oxazoles with high efficiency and excellent functional group compatibility under metal-free reaction conditions.

Epothilone D and its 9-Methyl analogues: combinatorial syntheses, conformation, and biological activities.

Epothilone D (Epo D) and its 9-Methyl conformational analogues were synthesized through a highly efficient combinatorial approach. The fragment E was synthesized in 11 total steps with 6 longest linear steps, and each aldehyde B was prepared via a 3-step sequence. Starting from the common precursor E and a suitable aldehydes B, each target molecule were obtained in only 4 steps. The 9-(S)-epo D and 9-(R)-epo D demonstrated significant difference in inhibition activities against cancer cell lines and in conformational analysis.

Effects of alkali metal ion cationization on fragmentation pathways of triazole-epothilone.

The collisionally activated dissociation mass spectra of the protonated and alkali metal cationized ions of a triazole-epothilone analogue were studied in a Fourier transform ion cyclotron resonance mass spectrometer. The fragmentation pathway of the protonated ion was characterized by the loss of the unit of C(3)H(4)O(3). However, another fragmentation pathway with the loss of C(3)H(2)O(2) was identified for the complex ions with Na(+), K(+), Rb(+), and Cs(+). The branching ratio of the second pathway increases with the increment of the size of alkali metal ions. Theoretical calculations based on density functional theory (DFT) method show the difference in the binding position of the proton and the metal ions. With the increase of the radii of the metal ions, progressive changes in the macrocycle of the compound are induced, which cause the corresponding change in their fragmentation pathways. It has also been found that the interaction energy between the compound and the metal ion decreases with increase in the size of the latter. This is consistent with the experimental results, which show that cesiated complexes readily eject Cs(+) when subject to collisions.