摘要：A new conformationally restricted cyclic analogue of muramyl dipeptide was designed and manually synthesized by our 揗eshed-Bag Gathered-Bunch?method with a combination of Fmoc, allyl and N-1-(4,4-dimethyl2,6-dioxocyclo-hexylidene)ethyl chemical protection strategy.

摘要：As a non-specific modulator of macrophage, multiplied muramyl dipeptide (MMD) is solid-phase synthesized by application of standard Fmoc chemistry strategy. Tarn's multiple antigen system (MAS) is used as our four branched-linker on Lysine.

摘要：By choosing neuroimmunophilin FKBP12 as a therapeutical target, we have attempted to discover a new structural drug for treating neurodegenerative disease. This drug should possess neurotrophic activity and not affect the immune system. Based on the crystal structure of FKBP12, FK506 and Calcineurin complex, a series of small organic molecules were designed. These molecules were to have the ability of binding to FKBP12 in a virtual screening. By using a solution parallel synthetic method, these compounds were synthesized. The neuroprotective and neuroregenerative activities of these compounds were evaluated by binding assays, PC12 cells survival and neurite outgrowth model, chick dorsal root ganglion cultures (DRG) and 6-OHDA lesioned mice sympathetic nerve endings model. The evaluation results of these compounds showed that compound N308 has great promise as a candidate for a neuroprotective and neuroregenerative agent.

摘要：Antibody-based fusion proteins are the next generation of antibody therapies for cancer and other ***20 antigen,which is overexpressed on cell membranes in nearly 95% of cases of B-cell Non-Hodgkin's Lymphoma,is an attractive target for the therapy of B-lymphoid *** (LDM) is a potent enediyne-containing antitumor antibiotic that now has entered phase II clinical *** this study,we prepared an engineered fusion protein,scFv-LDP,consisting of an anti-CD20 scFv fragment and the apoprotein LDP of LDM using DNA *** purification and refolding,scFv-LDP was found to bind specifically to CD20-positive lymphoma cells using ELISA and indirect immunofluorescent cytochemical staining *** energized fusion protein scFv-LDP-AE was obtained using molecular reconstitution of the active chromophore AE of LDM and *** assay revealed potent cytotoxicity of scFv-LDP-AE to CD20-positive Raji and Daudi cells,with IC 50 values of 1.21×10-11 and 6.24×10-11 mol L-1,*** in vivo subcutaneous xenograft model of CD20-positive B cell lymphoma in BALB/c (nu/nu) mice was also *** were given intravenously on day 14 and 21 after tumor *** terms of maximal tolerated doses,scFv-LDP-AE at 0.3 mg kg-1 suppressed tumor growth by 79.3%,and LDM at 0.05 mg kg-1 by 68.6% (P<0.05).Results suggested scFv-LDP-AE could be a potential candidate for tumor-targeting therapy.

摘要：The construction of engineered neural tissue using cell-derived extracellular matrix(ECM)-modified scaffolds is a promising *** fibroin(SF)sponge is an advantageous scaffold for the construction of engineered neural tissues,but it can still be modified to enhance its *** mouse embryonic fibroblasts(MEFs)are proven that they can secrete amounts of ECM and soluble factors including neurotrophic ***-derived ECM is expected to improve the activity of the *** we aimed to construct 3D functional neural tissues based on MEFs-derived ECM modified SF *** were cultured on porous SF sponges and decellularized with Triton X-100 and *** decellularized ECM deposited scaffolds were characterized through scanning electron microscopy and confocal *** efficiency of decellularization was evaluated by quantifying remaining ***,we investigated the primary cortical neuronal growth and 3D neural network formation effect on MEFs-derived ECM modified SF *** to bare SF sponges,ECM-SF sponges showed improved neuronal growth and axon extension indicated by immunofluorescence staining and ***,ECM-SF sponges showed increased 3D neural network formation with functional ***,this study demonstrated that functionalization of SF scaffolds using cell-derived ECM could improve the bioactivity of SF materials and provide an ideal microenvironment for functional neural tissue formation.

摘要：Contamination of soil and water by arsenic is a global problem. In Australia, the dipping of cattle in arsenic-containing solution to control cattle ticks in last centenary has left many sites heavily contaminated with arsenic and other toxicants. We had previously isolated five soil bacterial strains （CDB 1-5） highly resistant to arsenic. To understand the resistance mechanism, molecular studies have been carried out. Two chromosome-encoded arsenic resistance （ars） gene clusters have been cloned from CDB3 （Bacillus sp.）. They both function in Escherichia coli and cluster i exerts a much higher resistance to the toxic metalloid. Cluster 2 is smaller possessing four open reading frames （ORFs） arsRorf2BC, similar to that identified in Bacillus subtilis Skin element. Among the eight ORFs in cluster 1 five are analogs of common ars genes found in other bacteria, however, organized in a unique order arsRBCDA instead of arsRDABC. Three other putative genes are located directly downstream and designated as arsTIP based on the homologies of their theoretical translation sequences respectively to thioredoxin reductases, iron-sulphur cluster proteins and protein phosphatases. The latter two are novel of any known ars operons. The arsD gene from Bacillus species was cloned for the first time and the predict protein differs from the well studied E. coli ArsD by lacking two pairs of C-terminal cysteine residues. Its functional involvement in arsenic resistance has been confirmed by a deletion experiment. There exists also an inverted repeat in the intergenic region between arsC and arsD implying some unknown transcription regulation.

摘要：A novel series of diaryl urea derivatives bearing sulfonamide moiety have been designed and synthesized. Their in vitro antitumor effect against human cancer cell lines MX-1, A375, HepG2, Ketr3 and HT-29 was screened and evaluated by the standard MTT assay with sorafenib as the positive control. Some of the compounds showed significant inhibitory activity against multiple cell lines compared to sorafenib. In particular, 2,6-dimethyl-4-{6-[3-（4-chloro-3-（trifluoromethyl）phenyl）urealnaphthalen- 2-yllsulfonyl morpholine （10d） was found to be the most potent against A375, HepG2 and Ketr3 with ICs0 values of 0.65-0.97 μmol/L, which were 5-20-fold more potent than sorafenib. Compound 10d emerged as a valuable lead for further optimization.

摘要：Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease(AD). We analyzed by an inverse docking procedure(INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE,PSEN, IDE, CASP, calpain and TNF-a, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aβ deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

摘要：Laccases, multicopper oxidoreductases, are mainly produced in white-rot fungi and are considered as ideal green catalysts in industrial and biotechnological applications. However, the development of laccases is limited due to the slow growth of natural laccase producing strains and the low expression levels of laccases. In this study, we designed three regulation strategies for laccase gene expression in the model fungus Aspergillus nidulans. By introducing various promoters in front of the laccase gene pslcc from the white-rot fungus Pycnoporus sanguineus, we found that the laccase gene with the original promoter had effective expression in A. nidulans. Using the previously identified transcription factor RsmA regulatory mechanism, the aflR promoter was inserted into the pslcc expression vectors, and the laccase production was 15-fold higher in the strain overexpressing of RsmA compared to the control strain. To improve the laccase yield, the dipeptidyl-peptidase DppV, aspartic protease PepA and mannosyltransferase Mnn9 were successfully deleted in the A. nidulans host. The laccase activities were increased approximately 8-fold and 13-fold in the double deletions strains of Δmnn9ΔpepA and ΔdppVΔpepA over the control strains, *** together, these results not only demonstrate an efficient system for heterologous protein production in the model fungus *** but also provide a general approach to applying regulatory methods to control gene expression.

摘要：The ^1 H nuclear magnetic resonance （^1 H NMR） fingerprints of fractionated non-polar extracts （control substance for a plant drug （CSPD） A） from Rhizoma chuanxiong, the rhizomes of Ligusticum chuanxiong Hort., of seven specimens from different sources were measured on Fourier Transform （FT）-NMR spectrometer and assigned by comparing them with the ^1 H NMR spectra of the isolated pure compounds. The ^1 H NMR fingerprints showed exclusively characteristic resonance signals of the major special constituents of the plant. Although the differences in the relative intensity of the ^1H NMR signals due to a discrepancy in the ratio of the major constituents among these samples could be confirmed by high performance liquid chromatography analysis, the general features of the ^1H NMR fingerprint established for an authentic sample of the rhizomes of L. chuanxiong e. hibited exclusive data from those special compounds and can be used for authenticating L. Chuanxiong species.