Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

Objective To investigate the effects of high-flux hemodialysis (HFD) on fibroblast growth factor-23 (FGF-23) levels in maintenance hemodialysis (MHD) patients and its clinical significance.Methods Sixty uremia patients were divided into HFD group and hemodialysis (HD)group and observed for 12 months.Flow mediated dilation (FMD),cardiac ultrasonography,levels of FGF-23,serum phosphorus,serum calcium,25-(OH)D3,parathyroid hormone (PTH),homocysteine (Hcy) and interleukin-6 (IL-6) were tested in all patients before and after treatment.The correlation of above indexes were analyzed.Results No statistical difference were found in primary disease,age and duration of dialysis in two groups.The levels of FGF-23 [(56.07±26.63) vs (85.53±40.54) ng/L,P ＜0.01],IL-6 [(3.37±2.48) vs (5.59±2.53) ng/L,P ＜ 0.05] and Hcy [(21.13±6.95) vs (29.40±11.66) μmol/L,P ＜ 0.05] decreased and FMD,25-(OH)D3 [(27.3± 10.26) vs (23.15± 10.73) μg/L,P ＜ 0.05] increased significantly after the treatment of HFD.There were no significant changes in the HD group.The baseline FMD was negatively correlated with FGF-23 (r =-0.413,P ＜ 0.05) and Hcy (r =-0.301,P ＜0.05).The baseline LVMI was correlated with FGF-23 (r =0.464 P ＜ 0.05).After one year's trearmeat of HFD,the changes of FMD(/△ FMD) was negatively correlated with the changes of FGF-23 (/△ FGF-23)(r =-0.347,P ＜ 0.05).Conclusions HFD can improve FMD and decrease FGF-23 levels.The improvement of FMD may be related to the decreased level of FGF-23.The effect of FGF-23 on FMD should be independent of serum phosphate.

OBJECTIVE:To study the solubilization effect of different surfactant on amphotericin B.METHODS:Surfaceactive solution with series of concentrations were prepared by several agents including span-20,tween-40,tween-60,tween-80 and poloxamer 188 as non-ionic surfactant,hexadecyltrimethylammonium chloride (HTMAC) as cationic surfaceactive agent,sodium dodecyl benzene sulfonate (SDBS) and sodium deoxycholate as anionic surfaceactive agent,lecithin as bi-ionactiveagent.The solubilization effect of surfactant on amphotericin B was determined by UV spectrophotometry with maximum solubilization percentage as index.RESULTS:Maximum solubilization ratio in the range of 0.2～4.0 mg?mL-1 were as follows:1 365.44% for span-20 (4 mg?mL-1),353.46% for tween-40 (0.8 mg?mL-1),1 165.30% for tween-60 (4 mg?mL-1),973.46% for tween-80 (0.4 mg?mL-1),1 527.95% for poloxamer 188 (4 mg?mL-1),1 199.16% for sodium dodecyl benzene sulfonat (4 mg?mL-1),1 671.68% for hexadecyltrimethylammonium chloride (4 mg?mL-1),88.62% for sodium deoxycholate (4 mg?mL-1) and 314.36% for lecithin (4 mg?mL-1).CONCLUSIONS:Surfactant span-20,tween-60,tween-80,poloxamer 188,sodium dodecyl benzene sulfonat and hexadecyltrimethylammonium chloride have remarkable solubilization effect on amphotericin B.But tween-40,sodium deoxycholate and lecithin have unapparent solubilization effect on amphotericin B.

Animals ; Antigens, CD ; metabolism ; Cell Movement ; Cell Proliferation ; Endoglin ; Genetic Therapy ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Neoplasms ; pathology ; therapy ; Receptors, Cell Surface ; metabolism ; Thy-1 Antigens ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

Chromatography, Gas ; methods ; Chromatography, High Pressure Liquid ; methods ; Humans ; Hypnotics and Sedatives ; blood ; Pentobarbital ; blood ; Pharmaceutical Preparations ; blood ; Sensitivity and Specificity

Acupuncture Therapy ; Chest Pain ; therapy ; Female ; Humans ; Middle Aged ; Stroke ; therapy

Adolescent ; Adult ; Burns, Inhalation ; etiology ; therapy ; Explosions ; Female ; Gases ; Humans ; Male ; Retrospective Studies ; Young Adult

Objective To investigate the characteristics of pathogenic bacteria/the drug resistance/the correlated risk fators/the prophylaxis control strategy of the severe craniocerebral injury patients combined with intracranial infection .Methods The clinical data of 35 craniocerebral injury patients with intracranial infection were retrospectively analyzed .Results 35 patients′cerebrospinal fluid were separated and 54 pathogenic bacterium had been cultured ,including G+ bacterium(61 .11% ) ,the G - bacteria(33 .33% ) , fungi(5 .56% ) .The pathogenic bacteria showed a higher resistance .The single factor analysis found that the wound itself exists in-fection factors ,the postoperative drainage of incision ,liquorrhoea ,with other basic diseases ,surgery lasted for a long time (>4 h) reoperative ,surgery is placed foreign body is severe craniocerebral trauma combined with intracranial infection were the main rele-vant factors .The total effective rate was 62 .86% ,and the mortality was 11 .43% by the positive therapy .Conclusion G+ bacteria were the main pathogenic bacterium in the severe craniocerebral injury patients combined with intracranial infection .The iatrogenic factors leaded to the increase of the proportion of intracranial infection and the resistance increased year after year .The clinical in-travenous antibiotics combined intrathecal injections were beneficial to control intracranial infection ,shorten the course of treatment and enhance the curative effect .

The correlated proteome of Penicillium marneffei resistant to fluconazole was investigated in the present study, in which 11 strains of P. marneffei of both the mycelial and yeast forms sensitive to fluconazole were cultivated in Sabouraud's liquid medium containing 8 g fluconazole and the MICs of fluoconazile to P.marneffei before and after inducing cultures were tested by E-test method. The strains of the mycelial and yeast forms showing the most significant increase in MIC value were selected and the protein clip CM10 was used to detect the proteome differences before and after inducing cultures. It was found that 11 strains of the mycelial forms and 2 strains of the yeast forms could tolerate the action of fluconazole and could grow at a drug concentration of 8 μg/mL. Furthermore, the MICs of fluoconazole to the mycelial forms were significantly increased after 7 days of inducing culture and the geometric means of MICs were increased from 1.22 μg /mL to 55.56 μg/mL. After the mycelial forms had been induced to be resistant, 16 proteins were highly expressed with specific expression of the 4581.1 Da and 6109.7 Da proteins; whereas 22 resistant yeast form were highly expressed with specific expression of the 3575.2 Da, 8507.0 Da and 8563.3 Da proteins. These results suggest that the mycelial form of P.narneffei seems to be more tolerant to the action of fluconazole than the yeast form. The resistance of these organisms to fluconazole may be associated to some specific proteins.

AIM: To investigate the efficacy of N-acetylcysteine (NAC) and taurine (Tau) in preventing hyperoxia-induced the lens opacification and the changes of biochemical parameters on organ cultured rabbit lenses.METHODS: Twenty-four lenses from adult rabbits were divided into the control group, the hyperoxia-exposed group, the hyperoxia-exposed group containing 20mmol/L of NAC, the hyperoxia-exposed group containing 80mmol/L of Tau, respectively. The treated groups incubated with hyperoxia ( pO2>80%) for 4 hours per day throughout a 7-day period. Lens transparency, histology and enzymatic activities measurements were determined after this incubation.RESULTS: Gross morphological examination of these lenses revealed some severe cortical opacification in the hyperoxia-exposed group, moderate cortical opacification in the control group and the Tau treated group. There was minimal cortical opacification in the NAC treated group. The glutathione (GSH) content and the activity of Na, K-ATPase were significantly decreased in the hyperoxia-exposed group than that of the control group, by 37.8% (P<0.05) and 53.5% (P<0.05), respectively. However, they were increased in the two treated groups, especially in the NAC treated group. There were no significant differences in the water-soluble protein content and the catalase and GSH reductase activities in all group lenses.CONCLUSION: Hyperoxia can induce the cortical opaci-fication in the lens. The role of NAC in the prevention of hyperoxia-induced cataract is superior to Tau.