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Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dramatically reduced ALK and c-MET kinase-inhibitory potential. Furthermore, the prodrugs showed high stability in serum and release of crizotinib in an enzymatic nitroreductase-based cleavage assay was observed for prodrug A. The in vitro activity of both prodrugs was investigated against ALK- and c-MET-dependent or -overexpressing cells, revealing a distinct hypoxia-dependent activation for prodrug A. Finally, inhibition of c-MET phosphorylation and cell proliferation could also be proven in vivo. In summary of the theoretical, chemical and biological studies, prodrug derivatization of the 2-aminopyridine position can be considered as a promising strategy to reduce the side effects and improve the anticancer activity of crizotinib. Four new 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, aqulisinone A (1), (5S, 6R,7S,8S)-8-chloro-5,6,7-trihydroxy-2-[2-(4'-methoxyphenylethyl)]-5,6,7,8-tetrahydrochromone (2), (5S,6R,7S,8S)-8-chloro-5,6,7-trihydroxy-2-(2-phenylethyl)-5,6,7,8-tetrahydrochromone (3), (5S*,6R*,7R*,8S*)-8-chloro-5-ethoxy-6,7-dihydroxy-2-[2-(3'-hydroxy-4'-methoxy-phenylethyl)-5,6,7,8-tetrahydrochromone (4), and seven known analogues (5-11) were isolated from agarwood produced of Aquilaria sinensis. Among the new compounds, 4 is an artifact. The structures were elucidated using spectroscopic methods and by comparison with published NMR spectroscopic data. click here The absolute configurations of 1-3 were defined based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) data. Compound 1 features a (5,5)-carbon-carbon bond linkage connecting two 2-(2-phenylethyl)chromone monomeric units. All the new compounds were evaluated for their anti-inflammatory activities by inhibiting the lipopolysaccharide (LPS)-induced nitric oxide (NO) release in RAW264.7 cells, 2 with an IC50 value of 3.46 μM. Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F. INTRODUCTION This study firstly aimed to identify different profiles of narcissism and self-esteem in adolescents using latent profile analysis (LPA). A secondary aim was to examine associations between the identified profiles and subsequent measures of comprehensive mental health. METHODS Chinese adolescents (N = 1009, 50.8%girls, Mage = 12.99, SD = 0.66) completed a packet of measures on two occasions at 6-month intervals. Narcissism and self-esteem were assessed at Time 1. Positive and negative indicators of mental health were assessed at Time 2. RESULTS Latent profile analysis of narcissism and self-esteem identified six profiles (1) high narcissism and high self-esteem; (2) high-moderate self-regard; (3) moderate self-regard; (4) low-moderate self-regard; (5) high narcissism but low self-esteem; (6) low self-regard. Adolescents in the high narcissism and high self-esteem and high-moderate self-regard profiles displayed positive mental health outcomes whereas adolescents in the high narcissism but low self-esteem and low self-regard profiles reported problematic mental health outcomes. CONCLUSION Differing profiles of narcissism and self-esteem in adolescents were identified; these profiles provide new insight into the structure of self-concept for adolescents. Further, the identified profiles of narcissism and self-esteem were differentially related to subsequent comprehensive mental health outcomes. When compared to younger adults, older adults tend to favor positive over negative information in attention and memory. This is known as the positivity effect. Although this is a robust phenomenon, there is still debate about how it relates to individual differences in cognitive capabilities and future time perspective (FTP). To address this, we investigated how measures of fluid cognitive capabilities and FTP related to positivity effects within the domains of episodic memory, visual attention, and autobiographical memory. Cognitive capabilities were assessed using the National Institute of Health Toolbox Cognition battery, and included assessments of executive function, working memory, episodic memory, and processing speed. FTP was assessed via the Carstensen and Lang (1996) scale. Within our final sample (N = 196), we replicated positivity effects in all three task domains, which were all driven by age differences in how people responded to negative (but not positive) information. However, there was limited evidence that the magnitude of these age-related reductions in negativity varied as a function of individual differences in older adults' cognitive capabilities or FTP. Furthermore, when FTP did emerge as a predictor, the pattern was not in line with expectations based upon socioemotional selectivity theory. Thus, the positivity effect may be less reliant on cognitive capabilities and self-reported FTP than is often assumed. Given that there was also very little consistency in the extent to which participants displayed positivity effects across the task domains, these results also raise the possibility that there may be multiple mechanisms underlying positivity effects.