Psychometric investigation of the Chinese version of the Habit, Reward and Fear Scale (HRFS).

BACKGROUND: Tobacco use is one of the most important risk factors for health, and China is the largest producer and consumer of tobacco in the world. Monitoring and controlling the tobacco epidemic is an important issue. However, the motivation underlying smoking behavior is complex and specific to the individual. The Habit, Reward and Fear Scale (HRFS) is a feasible tool to evaluate this complex motivation. OBJECTIVES: To validate the psychometric properties of the HRFS Chinese version (HRFS-C) and to assess the relationship between motivation and smoking behavior. METHOD: We recruited 967 participants through social media and assessed their smoking behavior with three instruments: the Fagerstrom Test for Nicotine Dependence-Chinese version (FTND-C), the Questionnaire on Smoking Urges-Brief Scale-Chinese version (QSU-brief-C), and the HRFS-C. Ultimately, we retained 700 valid data points. Cronbach's α and split-half tests were used to evaluate the reliability. Confirmatory factor analysis, Pearson's r and an analysis of variance (ANOVA) were used to evaluate the validity. In addition, linear regression was used to explore the relationship among the three instruments. The HRFS-C showed good homogeneity (α = 0.965), concurrent validity, and discriminant validity. A significant linear relationship was observed among the FTND-C, QSU-brief-C, and HRFS-C (p < .001). CONCLUSION: The motivation measured by the HRFS-C can significantly predict nicotine dependence and craving in the smoking population. The HRFS-C can be used to carry out targeted interventions for addicted patients (e.g., motivational enhancement therapy).

[Toosendanin induces apoptosis of human gastric cancer MGC-803 cells and its mechanism].

Objective: To explore the apoptosis of human gastric cancer MGC-803 cells induced by toosendanin(TSN) and its mechanism. Methods: The human gastric cancer MGC-803 cells were divided into 5 groups, each group was set with 3 replicate. Fluorouracil (5-FU) and 0 nmol/L toosendanin (TSN) were used as positive control and negative control, respectively. The other three groups were treated with toosendanin at the final concentrations of 30, 50, and 70 nmol/L, respectively. After 48 h of treatment with toosendanin, the morphology of the cells were observed under laser confocal microscopy. Flow cytometry was used to detect the mitochondrial membrane potential, and enzyme-labeled assays were used to detect the activities of Caspase-3 and Caspase-9. The mRNA and protein levels of Bcl-2, Bax, Cyt c and APAF-1 were measured by qRT-PCR and Western blot. Results: Compared with the 0 nmol/L TSN group, after the human gastric cancer MGC-803 cells were treated with toosendanin at the concentrations of 30, 50, and 70 nmol/L for 48 h, the cell volume shrinkage, nucleus cleavage and chromatin morphological changes were observed under the microscope. The activities of Caspase-3 and Caspase-9 were increased significantly (P＜0.05), while the mitochondrial membrane potential was decreased significantly (P＜0.05). In addition, the mRNA and protein expression levels of Bax, Cyt c and APAF-1 were increased significantly (P＜0.05), while the mRNA and protein expression levels of Bcl-2 were decreased significantly (P＜0.05). Conclusion: Toosendanin up-regulates the expressions of Bax, Cyt c and APAF-1, down-regulates the expression of Bcl-2 gene, enhances the activities of caspase-3 and caspase-9, and induces the apoptosis of human gastric cancer MGC-803 cells.

Cajaninstilbene acid analogues as novel quorum sensing and biofilm inhibitors of Pseudomonas aeruginosa.

Biofilm formation and virulence factor secretion in opportunistic pathogen Pseudomonas aeruginosa are essential for establishment of chronic and recurrent infection, which are regulated by quorum sensing (QS) system. In this study, a set of cajaninstilbene acid analogues were designed and synthesized, and their abilities to inhibit QS and biofilm formation were investigated. Among all the compounds, compounds 3g, 3m and 3o showed potent anti-biofilm activity, especially 3o exhibited promising biofilm inhibitory activity with biofilm inhibition ratio of 49.50 ± 1.35% at 50 µM. Three lacZ reporter strains were constructed to identify the effects of compound 3o on different QS systems. Compound 3o showed the suppression on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors. Therefore, compound 3o is expected to be generated as a lead compound with inhibition of biofilm formation and QS of Pseudomonas aeruginosa.

Synthesis and Biological Evaluation of Cajaninstilbene Acid and Amorfrutins A and B as Inhibitors of the Pseudomonas aeruginosa Quorum Sensing System.

The quorum sensing (QS) system inhibitors of Pseudomonas aeruginosa are thought to attenuate bacterial pathogenicity and drug resistance by inhibiting biofilm formation and the production of virulence factors. In this study, a synthetic approach to the natural products cajaninstilbene acid (1) and amorfrutins A (2) and B (3) has been developed and was characterized by the Heck reaction, which was used to obtain the stilbene core and a Pinick oxidation to give the O-hydroxybenzoic acid. The biological activities of these compounds against the P. aeruginosa quorum sensing systems were evaluated. Amorfrutin B (3) showed promising antibiofilm activity against P. aeruginosa PAO1 with a biofilm inhibition ratio of 50.3 ± 2.7. Three lacZ reporter strains were constructed to identify the effects of compound 3 on different QS systems. Suppression efficacy of compound 3 on the expression of lasB-lacZ and pqsA-lacZ as well as on the production of their corresponding virulence factors elastase and pyocyanin was observed.

4-arylamidobenzyl substituted 5-bromomethylene-2(5H)-furanones for chronic bacterial infection.

Bacterial quorum-sensing (QS) can cause bacterial biofilm formation, thus induce antibiotic resistance and inflammation in chronic bacterial infections. A series of novel 4-arylamidobenzyl substituted 5-bromomethylene-2(5H)-furanones were designed by introducing of brominated furanones into rosiglitazone skeleton, and their potential application in the treatment of chronic bacterial infection was evaluated with regard to their disruption of quorum sensing and anti-inflammatory activities in vitro as well as in animal infection model. Compound 2e displayed both potent QS inhibitory activity and anti-inflammatory activity. Further mechanism studies revealed that the biological effects of 2e and 2k could be attributed, at least in part, to their interaction with PPARγ, and consequent suppression of the activation of NF-κB and MAPK cascades. Importantly, pretreatment with 2e significantly protects mice from lethal-dose LPS challenge. Thus, these data suggest that the dual effective derivative 2e may serve as a valuable candidate for the treatment of chronic bacterial infection.

Novel 4-(4-substituted amidobenzyl)furan-2(5H)-one derivatives as topoisomerase I inhibitors.

In this study, two series of novel 4-(4-substituted amidobenzyl)furan-2(5H)-one derivatives containing an α,ß-unsaturated lactone fragment were synthesized and screened for Topo I inhibition and antitumor activity. The topoisomerase I inhibitory activities and cytotoxicities against three human cancer cell lines (MCF-7,Hela,A549) were evaluated. The results revealed that series 2, compounds bearing an exocyclic double bond on the furanone ring, generally showed more potent activity than series 1, compounds lacking an exocyclic double bond. Several compounds of series 2 possess significant Topo I inhibitory activity and potent antiproliferative activity against cancer cell lines. Further mechanism studies of the most active compound of series 2 (B-15) indicated that synthetic compounds can not only stabilize the drug-enzyme-DNA covalent ternary complex as well as camptothecin, but also interfere with the binding between Topo I and DNA. The binding patterns of these compounds with Topo I and structure-activity relationships are discussed.

Synthesis and antibacterial activities of acylide derivatives bearing an aryl-tetrazolyl chain.

Seventeen acylides bearing an aryl-tetrazolyl alkyl-substituted side chain were synthesized, starting from clarithromycin, via several reactions including hydrolysis, acetylating, esterification, carbamylation, and Michael addition. The structures of all new compounds were confirmed by (1)H nuclear magnetic resonance spectroscopy, (13)C nuclear magnetic resonance spectroscopy, and mass spectrometry. All these synthesized acylides were evaluated for in vitro antimicrobial activities against gram-positive pathogens (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative pathogens (Pseudomonas aeruginosa, Escherichia coli), using the broth microdilution method. Results showed that compounds 10 e, 10 f, 10 g, 10 h, 10 o have good antibacterial activities.

Seasonal variation of metabolic thermogenesis in Eurasian tree sparrows (Passer montanus) over a latitudinal gradient.

Phenotypic flexibility of various morphological and physiological characters is widespread in animals. Resident endothermic animals of temperate climates provide a natural experiment in phenotypic flexibility. In this study, we took an integrative approach to assess seasonal and geographic influences on metabolism in Eurasian tree sparrows (Passer montanus). We measured resting metabolic rate (RMR), masses of internal organs, mitochondrial respiration capacities in liver and muscle, cytochrome C oxidase (COX) activities in liver and muscle, and circulating levels of plasma triiodothyronine (T3) and thyroxine (T4) in summer and winter sparrows at two sites from southeastern (Wenzhou) and northeastern (Qiqihar) China that differ in climate. Body masses of tree sparrows were significantly higher in winter than in summer at both sites but did not differ with latitude. RMRs of tree sparrows varied significantly with both latitude and season, with RMRs of Qiqihar birds being higher than those of Wenzhou birds and with RMRs being higher in winter than in summer. Consistently, dry masses of brain, lung, liver, gizzard, small intestine, rectum, and total digestive tract varied significantly with either latitude or season. State 4 respiration and COX activity in liver and muscle were remarkably higher in Qiqihar and increased significantly in winter. Circulating levels of plasma T3 also showed significant seasonal and latitudinal variation and was higher in Qiqihar in winter than in other groups. These data suggest that tree sparrows mainly coped with cold by enhancing thermogenic capacities through heightened activity of respiratory enzymes and higher levels of plasma thyroid hormones (T3). These results are consistent with a pronounced seasonal and latitudinal phenotypic flexibility mediated through physiological and biochemical adjustments in Eurasian tree sparrows.

3D-QSAR and molecular docking for the discovery of ketolide derivatives.

INTRODUCTION: There is an urgent need to discover novel antibiotics to overcome the growing problem of antibiotic resistance, which has become a serious concern in current medicine. Ketolides, the third generation of macrolide antibiotics, have shown promising effect against macrolide-resistant pathogens in respiratory diseases. Currently, a number of ketolide derivatives with excellent antibacterial activities have been reported, while their structure-activity relationships (SARs) were rarely explored systematically. Computer-aided drug design (CADD) such as 3D-QSAR and molecular docking are useful tools to study drug SARs in medicinal chemistry. Using these technologies, ketolide derivatives were systemically analyzed revealing important useful information about their SARs, providing useful information which can guide new drug design and optimization. AREAS COVERED: The authors provide an overview of the currently reported 3D-QSAR models of ketolide derivatives. The authors present a comprehensive SAR model obtained from in-depth 3D-QSAR and molecular docking analysis for all kinds of ketolide derivatives. EXPERT OPINION: 3D-QSAR has been shown to be a reliable tool that had successfully assisted the design of several new antibiotics with improved activity and reduced toxicity. By applying 3D-QSAR and molecular docking, a comprehensive and systematic SAR model for ketolide derivative discovery was formed, which is important to guide future drug design for the discovery of better ketolides with lower toxicity.

Geographic variation in basal thermogenesis in little buntings: relationship to cellular thermogenesis and thyroid hormone concentrations.

Acclimatization to different ambient conditions is an essential prerequisite for survival of small passerine birds. Long-distance migration and winter acclimatization induce similar physiological and biochemical adjustments in passerines. To understand metabolic adaptations, the resting metabolic rate (RMR), the thermogenic properties of mitochondria in liver and muscle, and the activity of thyroid hormones were examined in field-captured little buntings (Emberiza pusilla) between Southeastern (Wenzhou) and Northeastern (Qiqihar) China from March to May in 2008 during their migration. Twelve birds were trapped from March to April in Wenzhou region, Zhejiang Province (27°29'N, 120°51'E) and eleven birds originated from April to May in Qiqihar region, Heilongjiang Province (47°29'N, 124°02'E). We found that RMRs of little buntings were significantly higher in Qiqihar than in Wenzhou. Consistently, mitochondrial state-4 respiration capacities and cytochrome c oxidase activities (COX) in liver and muscle, and circulating levels of plasma triiodothyronine (T(3)) of little buntings were also significantly higher in Qiqihar than in Wenzhou. Variation in metabolic biochemical markers of liver and muscle, such as state-4 respiration and COX, and variation in thyroid hormone levels were correlated with variation in RMR. There was also a positive relationship between T(3) and metabolic biochemical markers. Little buntings mainly coped with a cold environment by enhancing thermogenic capacities through enhanced respiratory enzyme activities and plasma T(3). These results support the view that the primary means by which small birds meet energetic challenges of cold conditions is through metabolic adjustments.

Co-transfection and tandem transfection of HEK293A cells for overexpression and RNAi experiments.

pIRES2-EGFP was employed and a non-target shRNA expressing plasmid was constructed to simulate overexpression and RNAi (RNA interference) experiments. Transfection of pIRES2-EGFP into HEK293A cells by cationic lipids VigoFect demonstrated that transfection efficiency increased in a dose-dependent manner with amount of DNA plasmid used, and optimal transfection time and cell density should be identified to reach a compromise of higher transfection efficiency and lower toxicity. Co-transfection experiments indicated that the two co-transfected plasmids were equivalently delivered into the same cells, and the co-transfection efficiency was rarely affected by cell density and proportion of the two plasmids. However, plasmid-receipted cells seemed indisposed to accept plasmid again during the second transfection, and very low co-transfection efficiency was observed in tandem transfection.

[Genetic polymorphism of blood protein of six Passeriformes species in Zhalong National Nature Reserve].

The polymorphism of hemoglobin (Hb), serum albumin (Alb), trandferring (Tf) and adenosin deaminase (Ada) in the blood of Emberiza elegans, Phylloscopus inornatus, E. aureola, Lanius tigrinus, Passer montanus, and E. spodocephala in Zhalong National Nature Reserve were studied by SDS-polyacrylamide-gel electrophoresis. All the protein loci of the six Passeriformes species exhibited polymorphism, and Ada locus had a relatively high heterozygosity. The analysis of average heterozygosity demonstrated that P. inornatus had a higher population genetic variance, while E. spodocephala was relatively stable. The six species could be classified into two clusters. E. elegans, E. aureola, E. spodocephala and P. inornatus were clustered into one group, while P. montanus and L. tigrinus were clustered into another group. This clustering was consistent with the actual taxonomic status of the six species. The higher thermoregulation index and predation pressure of the study area did not lead to the substantial variation of hereditary constitution of the six species, possibly due to the gene intercommunion between the six species and the outside of the study area, which decreased the variance and differentiation of the population genetics of the six species.