The cannabinoid type 2 receptors (CB2Rs) play crucial roles in inflammatory diseases. There has been considerable interest in developing potent and selective ligands for CB2R. In this study, quinoline-2,4(1H,3H)-dione analogs have been designed, synthesized, and evaluated for their potencies and binding properties toward the cannabinoid type 1 receptor (CB1R) and CB2R. C5- or C8-substituted quinoline-2,4(1H,3H)-diones demonstrate CB2R agonist activity, while the C6- or C7-substituted analogs are antagonists of CB2R. In addition, oral administration of 21 dose-dependently alleviates the clinical symptoms of experimental autoimmune encephalomyelitis in a mouse model of multiple sclerosis and protects the central nervous system from immune damage. Furthermore, the interaction modes predicted by docking simulations and the 3D-QSAR model generated with CoMFA may offer guidance for further design and modification of CB2R modulators.

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The aim of the study was to investigate the efficacy of combined application of lactulose oral solution and polyethylene glycol electrolyte powder compared with conventional method in preparing for colonoscopy bowel cleanliness in patients with constipation. Ninety patients, who had constipation and needed to have colonoscopy, were divided into study group and control group with 45 cases in each group, respectively. One day before the colonoscopy, patients in the experimental group were given lactulose oral solution and polyethylene glycol electrolyte powder, whereas the patients in the control group were given oral polyethylene glycol electrolyte powder only. The following parameters were then obtained: time of the first defecation (duration of the time from taking the drugs to the first bowel movement), defecation frequency, completion of bowel cleaning (duration from the first bowel movement to the stool becoming clear), and adverse reaction. Cleansing effect in the study group bowel preparation was significantly better than that in the control group (P < 0.05). Specifically, time of the first defecation and completion of bowel cleaning were statistically shorter in the study group than those in the control group (P < 0.05), and defecation frequency was significantly higher in the study group than that in the control group (P < 0.05). Incidence of adverse reaction, however, was not significantly different between the 2 groups (P > 0.05). Combined application of lactulose oral solution and polyethylene glycol electrolyte powder is superior to the conventional method of polyethylene glycol electrolyte powder alone for colonoscopy bowel preparation in patients with constipation. Therefore, combined clinical application of the 2 compounds is strongly recommended for colonoscopy bowel preparation in patients with constipation.

Isoneochamaejasmin A (INCA), a biflavonoid, is one of main active ingredients in the dried root of Stellera chamaejasme L., a widely used traditional Chinese medicine. In the present study, we identified the glucuronidation metabolite of INCA and characterized the UDP glucuronosyltransferases (UGTs) responsible for INCA glucuronidation. 7-O-glucuronide (M1) and 49-O-glucuronide (M2) were identified by incubation of INCA with human liver microsomes (HLMs) in the presence of UDP glucuronic acid, and their structures were confirmed by high-resolution mass spectrometry and nuclear magnetic resonance analyses. Although INCA is a single enantiomer molecule, its M1 metabolite showed two equal-size peaks on a pNAP stationary phase but only one peak on a C 18 stationary phase, indicating that the 7-/799-and 49-/4999-hydroxyl groups of INCA were in different spatial configurations relative to each other.Among the recombinant human UGT isoform test and correlation analysis, UGT1A1, UGT1A3, and UGT1A9 were found to mediate M1 formation, whereas only UGT1A3 mediated M2 formation. Kinetic studies showed obvious species differences between human, mouse, rat, dog, and pig liver microsomes. UGT1A1, HLMs, and human intestinal microsomes, but not human kidney microsomes, exhibited substrate inhibition for the formation of M1. UGT1A1-mediated formation of M1 showed a 6-and 11-fold higher V max than did UGT1A3-and UGT1A9-mediated formation of M1, respectively. The results of the relative activity factor assay showed that UGT1A1 contributed approximately 75% in the formation of M1. These findings collectively indicate that UGT1A1 is the major enzyme in the formation of M1, whereas UGT1A3 is the major enzyme in the formation of M2.

A suite of the fossil-rich marine-land interbedded strata (Nanshuangyashan Formation) is distributed at the eastern margin of the Jiamusi massif in the eastern Heilongjiang Province, NE China. The authors had recently discovered a suite of arkose beneath the marine-land interbedded strata, which overlays unconformably on the Permain granite in the eastern margin of the Jiamusi massif. The LA-ICP-MS zircon U-Pb dating indicate that all detrital zircons from the analysed four arkose samples show the four population ages of ＞800 Ma, 538-481 Ma, 269-250 Ma and 223-215 Ma. The former three population ages are widely recorded in the Jiamusi-Khanka massif and the Songnen massif. The later group is the minimal age population in the analyzed samples, limiting the sedimentation time of the arkoses occurred after the Late Triassic. At present, the minimal age population is not recorded in the Jiamusi massif, but the granites with the ages of 228-210 Ma are widely distributed in the Songnen-Zhangguangcai Range massif and the Khanka massif. The predominantly Permian zircons are characterized by oscillatory zoning and euhedral shapes, with variable zircon ε Hf (t) values (−5.5 to +11.2), indicating that they were derived from mixture sources, possibly mixed with components of the Songnen-Zhangguangcai Range massif and the Jiamusi-Khanka massif. These results, combined with regional analyses, indicate that the closing of Mudanjiang ocean and Panthalassa ocean possibly existed from Early Permian to Late Triassic.