Design and synthesis of fluorescence-labeled nucleotide with a cleavable aryl-triazene linker for DNA sequencing by synthesis.

A novel acid-cleavable triazene linker was synthesized and then reacted with modified 2'-deoxyuridine triphosphate (dUTP), followed by Cy3 NHS ester, the final product serves as an excellent reversible terminator for DNA sequencing by synthesis (DNA SBS). The synthesized dye-labeled terminator incorporated into DNA strand faithfully in a DNA-elongation, and the fluorophore incorporated into DNA strands was cleaved completely under weak acidic conditions within short time. Further the first cleaved product can be incorporated with 100% efficiency for the second time.

RGD peptide-decorated micelles assembled from polymer-paclitaxel conjugates towards gastric cancer therapy.

Development of polymer-drug conjugate capable of controlled drug release is urgently needed for gastric cancer therapy. Herein, arginine-glycine-aspartic acid (RGD)-decorated polyethylene glycol (PEG)-paclitaxel (PTX) conjugates containing disulfide linkage were synthesized. The amphiphilic PEG-PTX conjugates were found to assemble into micelles (RGD@Micelles), which would be decomposed under the reduction of glutathione (GSH) and finally release PTX in weakly acidic conditions characteristic of intracellular environment.

Expression of Synthetic Phytoene Synthase Gene to Enhance β-Carotene Production in Scenedesmus sp. CPC2.

β-carotene is a valuable pigment abundant in some microalgal species but the low β-carotene productivity of microalgae has become the major obstacles against its commercialization. This work aims to improve the productivity of algae-based β-carotene via genetic engineering approaches. First, a synthetic psy gene construct (891 bp) encoding 297 amino acids is expressed in Scenedesmus sp.

Dynamic covalent linked triblock copolymer micelles for glutathione-mediated intracellular drug delivery.

Redox-responsive linkages dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their niche. In the present work, triblock copolymer PEG-PLA-PEG synthesized and characterized by H -NMR and SEC can self-assemble into redox-responsive micelles in aqueous media with nanosized 33nm and 47nm. And the copolymers PEG-PLA-PEG and PEG-PLA-PEG present lower CMC with 0.

Controllable release of nitric oxide and doxorubicin from engineered nanospheres for synergistic tumor therapy.

Unlabelled: NaYF:Yb,Er upconversion nanoparticles (UCNPs) capped with long-chain carboxylic acid were synthesized and then conjugated with chitosan (CS) in the aid of N-hydroxysuccinimide. The resultant nanocompound was integrated with doxorubicin (DOX) and Roussin's black salt (RBS), a photosensitive nitric oxide (NO) donor to produce stimuli-responsive UCNPs(DOX)@CS-RBS nanospheres as nanocarriers for controllable drug delivery. On the one hand, the encapsulated UCNPs can efficiently absorb NIR photons and convert them into visible photons to trigger NO release.

Chitosan-based core-shell nanomaterials for pH-triggered release of anticancer drug and near-infrared bioimaging.

As a naturally-abundant biopolymer, chitosan (CS) exhibit pH-sensitive structural transformation within a narrow pH range. Integrating hydrophobic groups to CS molecules gives modified CS polymers with more adjustable pH responsiveness. In this paper, near-infrared (NIR) photoluminescent AgS QDs capped by long-chain carboxylic acid were synthesized and then conjugated with CS via esterification reaction.

Synthesis and evaluations of an acid-cleavable, fluorescently labeled nucleotide as a reversible terminator for DNA sequencing.

An acid-cleavable linker based on a dimethylketal moiety was synthesized and used to connect a nucleotide with a fluorophore to produce a 3'-OH unblocked nucleotide analogue as an excellent reversible terminator for DNA sequencing by synthesis.

Design and synthesis of fluorescence-labeled nucleotide with a cleavable azo linker for DNA sequencing.

A cleavable azo linker was synthesized and reacted with 5-(6)-carboxytetramethyl rhodamine succinimidyl ester, followed by further reactions with di(N-succinimidyl) carbonate and 5-(3-amino-1-propynyl)-2'-deoxyuridine 5'-triphosphate [dUTP(AP3)] to obtain the terminal product dUTP-azo linker-TAMRA as a potential reversible terminator for DNA sequencing by synthesis with no need for 3'-OH blocking.

Redox-responsive micelles self-assembled from dynamic covalent block copolymers for intracellular drug delivery.

Redox-responsive micelles self-assembled from dynamic covalent block copolymers with double disulfide linkage in the backbone have been developed successfully. The amphiphilic block copolymers PEG-PLA associated with complementary H-bonding sequences can self-assemble into spherical micelles in aqueous media with sizes from 34 nm to 107 nm with different molar mass of PEG and PLA. Moreover, in vitro drug release analyses indicate that reductive environment can result in triggered drug release profiles.

Design and synthesis of new acid cleavable linkers for DNA sequencing by synthesis.

A new kind of acid sensitive tetrahydrofuranyl (THF) linker was synthesized and then reacted with 5-(6)-carboxytetramethylrhodaminesuccinimidyl ester (5(6)-TAMRA, SE), followed by di(N-succinimidyl) carbonate (DSC) and modified 2'-deoxyuridine triphosphate (dUTP); the final product, as a reversible terminator for DNA sequencing by synthesis (DNA SBS), was given obtained and confirmed by 1H-NMR, 31P-NMR, and HRMS with purity of up to 99%. The synthesized dye-labeled terminator incorporated into DNA strand successfully, and the fluorophore was cleaved completely under acidic conditions. The preliminary results encourage us to explore more acid-sensitive linkers for DNA SBS to increase the cleavage efficiency under weakly acidic conditions.

Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis.

Objective: Fat-soluble vitamin (FSV) deficiencies are common complications in pediatric patients with chronic cholestasis. The aim of the present study was to evaluate the status of FSV deficiencies in patients under present practice and to test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV) in these patients.

Methods: We recruited a total of 23 pediatric patients receiving conventional FSV supplementation in a single medical center, with diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis (9), Alagille syndrome (2), and other conditions (2).

Synthesis and 188Re radiolabelling of dendrimer polyamide amine (PAMAM) folic acid conjugate.

Folic acid receptors (FR) are usually over expressed in many cancer cells and are considered as potential targeted therapy agent. Generation of five polyamido amine (PAMAM) dendrimer folic acid conjugate was synthesised and radiolabelled with (188)Re, furthermore the in vitro/in vivo stability was evaluated accordingly. The labelling yield of the conjugate G5-FA-DTPA-(188)Re was 67.

Characteristics and incidences of pediatric Crohn's disease in the decades before and after 2000.

Objective: The increasing incidence of pediatric Crohn's disease (CD) is well known in Western countries in the last two decades. This study was conducted to delineate the trends of incidence during this period and clinical patterns of pediatric CD in Taiwan.

Methods: All children admitted to National Taiwan University Hospital between 1990 and 2009 who met the Porto Criteria for CD were included.

Radiosynthesis, biodistribution and micro-SPECT imaging study of dendrimer-avidin conjugate.

Partially acetylated generation five polyamidoamine (PAMAM) dendrimer (G5-Ac) was reacted with biotin and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetria minepentaacetic acid (1B4M-DTPA), respectively to form the complex Bt-G5-Ac-1B4M which was further conjugated with avidin to give the conjugate Av-G5-Ac-1B4M. Then both of the conjugates were radiolabeled with technetium-99m ((99m)Tc), respectively. Their in vitro cellular uptake study shows that the conjugate of Av-G5-Ac-1B4M-(99m)Tc exhibits much higher cellular uptake in HeLa cells than that of Bt-G5-Ac-1B4M-(99m)Tc.

[Tragus cartilage tympanoplasty for treatment of adhesive otitis media].

Objective: To evaluate the efficacy of cartilage tympanoplasty in the treatment of adhesive otitis media.

Methods: From June to October, 2008, 18 patients with adhesive otitis media (18 ears) were treated with tragus cartilage tympanoplasty. The air-bone gap changes and the self-perceived symptomatic improvement were evaluated at 1 month and 1 year after the operation.

Synthesis and binding affinities of Re(I) and (99m)Tc(I)-containing 16alpha-substituted estradiol complexes: Models for potential breast cancer imaging agents.

To develop technetium and rhenium-labeled imaging agents for estrogen receptor (ER) positive breast tumors, we have synthesized tridentate metal tricarbonyl chelates substituted at the 16alpha-position of estradiol. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or elemental analysis. The rhenium complex 7b showed the highest ER binding affinity (RBA=25.

Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates.

Three conjugates based on dendrimer PAMAM generation five were synthesized and radiolabeled successfully. To investigate their tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and micro-SPECT imaging were evaluated, respectively. The conjugate of (99m)Tc labeled PEGylated dendrimer PAMAM folic acid conjugate ((99m)Tc-G5-Ac-pegFA-DTPA) shows much higher uptake in KB cancer cells and accumulated more in the tumor area than that of the other two conjugates.

Design, synthesis, and evaluation of cyclofenil derivatives for potential SPECT imaging agents.

To develop technetium- and rhenium-labeled nonsteroidal estrogen imaging agents for estrogen receptor (ER) positive breast tumors, two groups of rhenium and technetium cyclofenil derivatives were synthesized and characterized. The binding affinities of the rhenium complexes for ERs were determined. The tricarbonyl rhenium complex showed the highest binding affinity for ERs (81.

Radiosynthesis and micro-SPECT imaging of 99mTc-dendrimer poly(amido)-amine folic acid conjugate.

Acetylated (Ac) dendrimer poly(amido)-amine (PAMAM) generation 5 (G5) reacted with folic acid (FA), followed by reacting with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetria minepentaacetic acid (1B4M DTPA) to form the conjugate of Ac-G5-FA-1B4M DTPA which was further radiolabeled with (99m)Tc. The radiochemical yield is up to 98.9% with excellent in vitro/in vivo stability, rapid blood clearance and certain tumor accumulation which was further confirmed by micro-SPECT imaging study.

Early development of acute myeloid leukemia following treatment of osteosarcoma: a case report and review of the literature.

We report a case of treatment-related acute myeloid leukemia (t-AML) in a 16-year-old male following treatment for osteosarcoma (OS). He had been treated with a protocol comprising neoadjuvant chemotherapy, definitive surgery with wide excision and adjuvant chemotherapy for OS. Four months after completion of the treatment, a routine hemogram showed hyperleukocytosis with 90% blasts.

Synthesis and antimicrobial evaluation of bile acid tridentate conjugates.

Two series of novel bile acid tridentate conjugates with different linkers were synthesized and characterized, and their biological activities in vitro were evaluated. The procedure was straightforward and efficient to be carried out with high overall yield. The antimicrobial activity of the synthesized compounds against Saccharomyces cerevisiae, Aspergillus niger, Escherichia coli and Staphylococcus aureus was investigated in vitro.

Radioactive synthesis and biodistribution study of beta-elemene-99mTc(CO)3 conjugates.

Beta-elemene, (5S,7R,10S)-(-)-(1-methyl-1-vinyl-2,4-diisopropenylcyclohexane), is an anticancer agent from traditional Chinese herbal medicine. Three novel (99m)Tc(CO)(3)-beta-elemene conjugates were synthesized successfully, and compared with beta-elemene exhibited improved water solubility. A biodistribution and micro single photon emission computed tomography image study showed there is a visible accumulation in Lewis lung cancer tumors.

Synthesis and in vitro anti-proliferative activity of beta-elemene monosubstituted derivatives in HeLa cells mediated through arrest of cell cycle at the G1 phase.

Beta-elemene monosubstituted amine, ether and rhenium coordinated complex were synthesized. Their structures were characterized by IR, (1)H NMR, (13)C NMR, HRMS or EA. Their IC(50) on HeLa cell lines, cell cycle and protein expression of G(1) phase (Cyclin D(1), Rb, P-Rb) were detected respectively by the method of WST-1, Flow Cytometry and Western Blot.

Enantioselective synthesis of gamma-aryl-gamma-butyrolactones by sequential asymmetric epoxidation, ring expansion, and Baeyer-Villiger oxidation.

This paper describes an enantioselective synthesis of gamma-butyrolactones, using the N-tolyl-substituted oxazolidinone-containing ketone as catalyst and Oxone as oxidant via a sequential asymmetric epoxidation of benzylidenecyclopropanes, ring expansion, and Baeyer-Villiger oxidation. Up to 91% ee was obtained. Optically active cyclobutanones can also be obtained by suppressing the Baeyer-Villiger oxidation with use of more ketone catalyst and less Oxone.