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.

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

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.

To explore the utility of apparent diffusion coefficient(ADC)histogram analysis for differentiating genetic subtypes of diffuse lower-grade gliomas. A total of 55 patients with WHO grade Ⅱ/Ⅲ diffuse lower-grade gliomas who underwent preoperative routine brain magnetic resonance imaging and diffusion weighted imaging in our center were retrospectively evaluated.Among whom there were 14 patients with isocitrate dehydrogenase(IDH)wild-type gliomas(IDH group),19 patients with IDH-mutant 1p19q intact gliomas(IDH 1p19q group),and 22 patients with IDH-mutant 1p19q co-deleted gliomas(IDH 1p19q group).The whole-lesion ADC values derived from histogram analysis(including ADC,ADC,ADC5%,ADC10%,ADC25%,ADC50%,ADC75%,ADC90%,ADC95%,ADC,mode,range,skewness,kurtosis,standard deviation,inhomogeneity,and entrophy)were measured for each patient.All parameters between the different genetic subtypes were compared by using the Student's test or Mann-Whitney test.Receiver operating curve(ROC)analysis was used to assess the diagnostic performance of ADC histogram in distinguishing the different genetic subtypes. Compared with IDH group,the ADC75%(=0.021),ADC90%(=0.015),ADC95%(=0.014),ADC (=0.035),range(=0.009),standard deviation(=0.001)and inhomogeneity(=0.001)were significantly lower in IDH group;in contrast,the ADC (=0.031)and kurtosis(=0.020)of IDH group were significantly higher than those in IDH group.The ADC(=0.010),ADC5%(=0.016),ADC10%(=0.012),ADC25%(=0.007),ADC50%(=0.005),ADC75%(=0.015),and mode(=0.002)were significantly higher in IDH 1p19q group than in IDH 1p19q group.Inhomogeneity achieved the highest area under ROC(AUC)(0.811)in differentiating IDH gliomas and IDH gliomas,with a cutoff value of 0.229;the sensitivity and specificity were 85.7% and 73.2%.The mode achieved the highest AUC(0.744)in differentiating IDH 1p19q gliomas and IDH 1p19q gliomas,with a cutoff value was 1448.75×10 mm /s;the sensitivity and specificity were 57.9% and 90.9%. ADC histograms analysis may be helpful to differentiate genetic subtypes in lower-grade gliomas.
Brain Neoplasms ; Diffusion Magnetic Resonance Imaging ; Glioma ; Humans ; ROC Curve ; Retrospective Studies

Objective To explore the changs of serum brain type creatine kinase isoenzyme(CK-BB),cystatin C of newborns with hypoxic-ischemic encephalopathy(HIE) and assess their applications.Methods The serum concentrations of CK-BB and cystatin C were measured by turbidimertric immunoassay in 56 HIE newborns and 42 normal neonates.Results 1.Compared with controls,the concentration of serum CK-BB in moderate HIE newborns had significant differences(P

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.

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