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.

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.

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.

Objective To observe the expression of bone morphogenetic protein 7 (BMP-7) in different stages of diabetic rats and investigate the potential role of BMP-7 in diabetic nephropathy (DN). Methods Wistar rats were divided into diabetes mellitus(DM) group induced by intravenous injection of streptozotocin (65 mg/kg) , and normal control group injected with citrate buffer. The rats were sacrificed at day 30,60,90,120,150 and 180 following injection, respectively. The blood glucose,Scr, urinary albumin and urinary creatinine were measured in each rat before sacrifice. The renal pathological changes were examined with hematoxylin and eosin (HE),periodic acid-silver-methenamine staining (PASM) and protein expression of collagenⅣ(ColⅣ). The mRNA and protein expression of BMP-7 and TGF-?1 in kidney were detected by reverse transcription-polymerase chain reaction (RT-RCR) and immunohistochemical staining respectively, and were quantified by computer image analysis system. Results The levels of blood glucose and urinary albumin in diabetic group were remarkably higher than those in control group (P

Adult ; Burns ; etiology ; mortality ; China ; epidemiology ; Coal Mining ; Explosions ; Female ; Gases ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Adult ; Child ; Endoscopy ; Fibrous Dysplasia of Bone ; pathology ; surgery ; Humans ; Male ; Nose ; surgery ; Orbit ; pathology

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.