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.

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

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

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

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 .

Multiple sclerosis ( MS) is an autoimmune disease of the central nervous system ( CNS) characterized by demyelination and inflammation lesions.MS predominantly affects young adults with a high incidence of disability. However, the exact pathogenesis of MS is still not clear.Studies found that microglia polarization tending to pro-inflammatory M1-like state during the onset of MS, causing the M1/M2 ratio imbalance, forming pro-inflammatory microenvironment state, and which further leading to nervous tissue damage ultimately.Microglia polarization may be considered as the initiator of pathologic alterations by releasing pro-inflammatory cytokines and secondarily trigger the initial microglia response.Given the pivotal role of imbalanced microglia polarization in MS initiation, a critical review of microglia polarization is presented here, in order to elucidate the pathogenesis of MS and highlight the noteworthy candidate therapeutic targets for clinic treatment.

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.