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.

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

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

Humans ; Myocardium ; Stem Cell Transplantation ; Stem Cells ; Tissue Engineering

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

Objective To study mathematical model and to perform computer simulation for an important subsystem in the bioregenerative life support system(BLSS),i.e.,light-algae bioreactor(LABR)forcontinuously cultivating green microalgae andsignificantly maintaining life support function of BLSS.MethodsBased on the theories of system dynamics and stoichiometry,the mathematical model and simulation model of LABR were respectively established with experimental data,and then computer experiments were conducted to simulate dynamic responses of LABR under different parameters as well as their combinations.Results It was shown that the kinetic model of LABR was valid for its real-life counterpart by a series of verification tests.It could reliably and beneficially provede technical and methodologcal helps for further investigations of LABR,such as theoretical analysis,design,control and optimization,and so on.Conclusion With computer experiments based on mathematical model and simulation model,it decreases much more in time and money consumption for investigations than with real experiment.This method can also be extended to use in other subsystems studies of BLSS.

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

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.