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This article focuses on a study related to the detection of prostate-specific antigen. Nanostructured devices, fabricated using single-walled carbon nanotubes, silicon nanowires, or metal oxide nanowires, are good candidates to manufacture future generations of biosensors. Researchers have previously demonstrated that phosphonic acids strongly bind to indium oxide surfaces and are stable under a variety of conditions. First step after anchoring PSA-AB to the NW and SWNT devices was to investigate the chemical gating effect of PSA on the devices.

Protein degradation is a tightly regulated biological process that maintains bacterial proteostasis. ClpPs are a highly conserved family of serine proteases that associate with the AAA + ATPase (an ATPase associated with diverse cellular activities) to degrade protein substrates. Identification and biochemical characterization of protein substrates for the AAA + ATPase-dependent ClpP degradation systems are considered essential for gaining an understanding of the molecular operation of the complex ClpP degradation machinery. Consequently, expanding the repertoire of protein substrates that can be degraded in vitro and within bacterial cells is necessary. Here, we report that AAA + ATPase-ClpP proteolytic complexes promote degradation of the secondary metabolite surfactin synthetases SrfAA, SrfAB, and SrfAC in Bacillus subtilis . On the basis of in vitro and in-cell studies coupled with activity-based protein profiling of nonribosomal peptide synthetases, we showed that SrfAC is targeted to the ClpC-ClpP proteolytic complex, whereas SrfAA is hydrolyzed not only by the ClpC-ClpP proteolytic complex but also by different ClpP proteolytic complexes. Furthermore, SrfAB does not appear to be a substrate for the ClpC-ClpP proteolytic complex, thereby implying that other ClpP proteolytic complexes are involved in the degradation of this surfactin synthetase. Natural product biosynthesis is regulated by the AAA + ATPase-ClpP degradation system, indicating that protein degradation plays a role in the regulatory stages of biosynthesis. However, few studies have examined the regulation of protein degradation levels. Furthermore, SrfAA, SrfAB, and SrfAC were identified as protein substrates for AAA + ATPase-ClpP degradation systems, thereby contributing to a better understanding of the complex ClpP degradation machinery.

In this study, we report a significant enhancement in the performance of GaNAs-based single nanowire lasers through optimization of growth conditions, leading to a lower lasing threshold and higher operation temperatures. Our analysis reveals that these improvements in the laser performance can be attributed to a decrease in the density of localized states within the material. Furthermore, we demonstrate that owing to their excellent nonlinear optical properties, these nanowires support self-frequency conversion of the stimulated emission through second harmonic generation (SHG) and sum-frequency generation (SFG), providing coherent light emission in the cyan-green range. Mode-specific differences in the self-conversion efficiency are revealed and explained by differences in the light extraction efficiency of the converted light caused by the electric field distribution of the fundamental modes. Our work, therefore, facilitates the design and development of multiwavelength coherent light generation and higher-temperature operation of GaNAs nanowire lasers, which will be useful in the fields of optical communications, sensing, and nanophotonics.

Energy upconversion via optical processes in semiconductor nanowires (NWs) is attractive for a variety of applications in nano-optoelectronics and nanophotonics. One of the main challenges is to achieve a high upconversion efficiency and, thus, a wide dynamic range of device performance, allowing efficient upconversion even under low excitation power. Here, we demonstrate that the efficiency of energy upconversion via two-photon absorption (TPA) can be drastically enhanced in core/shell NW heterostructures designed to provide a real intermediate TPA step via the band states of the narrow-bandgap region with a long carrier lifetime, fulfilling all the necessary requirements for high-efficiency two-step TPA. We show that, in radial GaAs(P)/GaNAs(P) core/shell NW heterostructures, the upconversion efficiency increases by 500 times as compared with that of the constituent materials, even under an excitation power as low as 100 mW/cm 2 that is comparable to the 1 sun illumination. The upconversion efficiency can be further improved by 8 times through engineering the electric-field distribution of the excitation light inside the NWs so that light absorption is maximized within the desired region of the heterostructure. This work demonstrates the effectiveness of our approach in providing efficient photon upconversion by exploring core/shell NW heterostructures, yielding an upconversion efficiency being among the highest reported in semiconductor nanostructures. Furthermore, our work provides design guidelines for enhancing efficiency of energy upconversion in NW heterostructures.

Hitachimycin is a macrolactam antibiotic with an ( S )-β-phenylalanine (β-Phe) at the starter position of its polyketide skeleton. ( S )-β-Phe is formed from l-α-phenylalanine by the phenylananine-2,3-aminomutase HitA in the hitachimycin biosynthetic pathway. In this study, we produced new hitachimycin analogs via mutasynthesis by feeding various ( S )-β-Phe analogs to a Δ hitA strain. We obtained six hitachimycin analogs with F at the ortho , meta , or para position and Cl, Br, or a CH 3 group at the meta position of the phenyl moiety, as well as two hitachimycin analogs with thienyl substitutions. Furthermore, we carried out a biochemical and structural analysis of HitB, a β-amino acid-selective adenylation enzyme that introduces ( S )-β-Phe into the hitachimycin biosynthetic pathway. The K M values of the incorporated ( S )-β-Phe analogs and natural ( S )-β-Phe were similar. However, the K M values of unincorporated ( S )-β-Phe analogs with Br and a CH 3 group at the ortho or para position of the phenyl moiety were high, indicating that HitB functions as a gatekeeper to select macrolactam starter units during mutasynthesis. The crystal structure of HitB in complex with ( S )-β-3-Br-phenylalanine sulfamoyladenosine (β- m -Br-Phe-SA) revealed that the bulky meta- Br group is accommodated by the conformational flexibility around Phe328, whose side chain is close to the meta position. The aromatic group of β- m -Br-Phe-SA is surrounded by hydrophobic and aromatic residues, which appears to confer the conformational flexibility that enables HitB to accommodate the meta -substituted ( S )-β-Phe. The new hitachimycin analogs exhibited different levels of biological activity in HeLa cells and multidrug-sensitive budding yeast, suggesting that they may target different molecules.

Aryl acids are most commonly found in iron-scavenging siderophores but are not limited to them. The nonribosomal peptide synthetase (NRPS) codes of aryl acids remain poorly elucidated relative to those of amino acids. Here, we defined more precisely the role of active-site residues in aryl acid adenylation domains (A-domains) by gradually grafting the NRPS codes used for salicylic acid (Sal) into an archetypal aryl acid A-domain, EntE [specific for the substrate 2,3-dihydroxybenzoic acid (DHB)]. Enzyme kinetics and modeling studies of these EntE variants demonstrated that the NRPS code residues at positions 236, 240, and 339 collectively regulate the substrate specificity toward DHB and Sal. Furthermore, the EntE variants exhibited the ability to activate the non-native aryl acids 3-hydroxybenzoic acid, 3-aminobenzoic acid, 3-fluorobenzoic acid, and 3-chlorobenzoic acid. These studies enhance our knowledge of the NRPS codes of aryl acids and could be exploited to reprogram aryl acid A-domains for non-native aryl acids.

We control the formation of Bi-induced nanostructures on the growth of GaAs/GaAsBi core-shell nanowires (NWs). Bi serves as not only a constituent but also a surfactant and nanowire growth catalyst. Thus, we paved a way to achieve unexplored III-V nanostructures employing the characteristic supersaturation of catalyst droplets, structural modifications induced by strain, and incorporation into the host GaAs matrix correlated with crystalline defects and orientations. When Ga is deficient during growth, Bi accumulates on the vertex of core GaAs NWs and serves as a nanowire growth catalyst for the branched structures to azimuthal <112>. We find a strong correlation between Bi accumulation and stacking faults. Furthermore, Bi is preferentially incorporated on the GaAs (112)B surface, leading to spatially selective Bi incorporation into a confined area that has a Bi concentration of over 7%. The obtained GaAs/GaAsBi/GaAs heterostructure with an interface defined by the crystalline twin defects in a zinc-blende structure can be potentially applied to a quantum confined structure. Our finding provides a rational design concept for the creation of GaAsBi based nanostructures and the control of Bi incorporation beyond the fundamental limit.

A coherent photon source emitting at near-infrared (NIR) wavelengths is at the heart of a wide variety of applications ranging from telecommunications and optical gas sensing to biological imaging and metrology. NIR-emitting semiconductor nanowires (NWs), acting both as a miniaturized optical resonator and as a photonic gain medium, are among the best-suited nanomaterials to achieve such goals. In this study, we demonstrate the NIR lasing at 1 μm from GaAs/GaNAs/GaAs core/shell/cap dilute nitride nanowires with only 2.5% nitrogen. The achieved lasing is characterized by an S-shape pump-power dependence and narrowing of the emission line width. Through examining the lasing performance from a set of different single NWs, a threshold gain, g th , of 4100-4800 cm -1 , was derived with a spontaneous emission coupling factor, β, up to 0.8, which demonstrates the great potential of such nanophotonic material. The lasing mode was found to arise from the fundamental HE 11a mode of the Fabry-Perot cavity from a single NW, exhibiting optical polarization along the NW axis. Based on temperature dependence of the lasing emission, a high characteristic temperature, T 0 , of 160 (±10) K is estimated. Our results, therefore, demonstrate a promising alternative route to achieve room-temperature NIR NW lasers thanks to the excellent alloy tunability and superior optical performance of such dilute nitride materials.

A hitherto unreported member of γ-alkylidenebutenolides in Melodorum fruticosum (Annonaceae), (4 E)-6-benzoyloxy-7-hydroxy-2,4-heptadiene-4-olide, named as isofruticosinol (4) was isolated from the methanol extract of flowers, along with the known related butenolides, namely, the (4 Z)-isomer (3) of 4, melodrinol (1), and its (4 E)-isomer (2). To unambiguously determine the absolute configuration at the C-6 position in these butenolides, the first total syntheses of both enantiomers of 2-4 were achieved over 6-7 steps from commercially available D- or L-ribose (D- and L-5). Using the same protocol, both enantiomers of 1 were also synthesized. Based on chiral HPLC analysis of all synthetic compounds ( S- and R-1-4), all naturally occurring butenolides were assigned as partial racemic mixtures with respect to the chiral center at C-6 (enantiomeric ratio, 6 S/6 R = ∼83/17). Furthermore, the melanogenesis inhibitory activities of S- and R-1-4 were evaluated, with all shown to be potent inhibitors with IC 50 values in the range 0.29-2.9 μM, regardless of differences in the stereochemistry at C-6. In particular, S-4 (IC 50 = 0.29 μM) and R-4 (0.39 μM) showed potent inhibitory activities compared with that of reference standard arbutin (174 μM).

Acyltransferases (ATs) are responsible for the selection and incorporation of acyl building blocks in the biosynthesis of various polyketide natural products. The trans-AT modular polyketide synthases have a discrete trans-acting AT for the loading of an acyl unit onto the acyl carrier protein (ACP) located within each module. Despite the importance of protein-protein interactions between ATs and ACPs in trans-AT assembly lines, the dynamic actions of ACPs and trans-acting ATs remain largely uncharacterized because of the inherently transient nature of ACP-enzyme interactions. Herein, we report the crystal structure of the AT-ACP complex of disorazole trans-AT polyketide synthase. We used a bromoacetamide pantetheine cross-linking probe in combination with a Cys mutation to trap the transient AT-ACP complex, allowing the determination of the crystal structure of the disorazole AT-ACP complex at 2.03 Å resolution. On the basis of the cross-linked AT-ACP complex structure, ACP residues recognized by trans-acting AT were identified and validated by mutational studies, which demonstrated that the disorazole AT recognizes the loop 1 and helix III' residues of disorazole ACP. The disorazole AT-ACP complex structure presents a foundation for defining the dynamic processes associated with trans-acting ATs and provides detailed mechanistic insights into their ability to recognize ACPs.

A facile and highly diastereoselective approach toward the synthesis of potent salacinol-type α-glucosidase inhibitors, originally isolated from plants of the genus "Salacia", was developed using the S-alkylation of thiosugars with epoxides in HFIP (∼90%, dr, α/β = ∼ 26/1). The dr ratio of the product was significantly improved by the protocol as compared to that of the conventional S-alkylation of thiosugars (dr, α/β = ∼ 8/1). The protocol could be used for gram scale synthesis of the desired compounds. The 3'-O-benzylated salacinol analogs, which are the most potent in vitro inhibitors to date, were synthesized and evaluated in vivo; all analogs suppressed blood glucose levels in maltose-loaded mice, at levels comparable to those of the antidiabetic agent, voglibose.

Among imaging techniques, fluorescence microscopy is a unique method to noninvasively image individual molecules in whole cells. If the three-dimensional spatial precision is improved to the angstrom level, various molecular arrangements in the cell can be visualized on an individual basis. We have developed a cryogenic reflecting microscope with a numerical aperture of 0.99 and an imaging stability of 0.05 nm in standard deviation at a temperature of 1.8 K. The key optics to realize the cryogenic performances is the reflecting objective developed by our laboratory. With this cryogenic microscope, an individual fluorescent molecule (ATTO647N) at 1.8 K was localized with standard errors of 0.53 nm (x), 0.31 nm (y), and 0.90 nm (z) when 10 6 fluorescence photons from the molecule were accumulated in 5 min.

Nanowire (NW) lasers operating in the near-infrared spectral range are of significant technological importance for applications in telecommunications, sensing, and medical diagnostics. So far, lasing within this spectral range has been achieved using GaAs/AlGaAs, GaAs/GaAsP, and InGaAs/GaAs core/shell NWs. Another promising III-V material, not yet explored in its lasing capacity, is the dilute nitride GaNAs. In this work, we demonstrate, for the first time, optically pumped lasing from the GaNAs shell of a single GaAs/GaNAs core/shell NW. The characteristic "S"-shaped pump power dependence of the lasing intensity, with the concomitant line width narrowing, is observed, which yields a threshold gain, g th , of 3300 cm -1 and a spontaneous emission coupling factor, β, of 0.045. The dominant lasing peak is identified to arise from the HE 21b cavity mode, as determined from its pronounced emission polarization along the NW axis combined with theoretical calculations of lasing threshold for guided modes inside the nanowire. Even without intentional passivation of the NW surface, the lasing emission can be sustained up to 150 K. This is facilitated by the improved surface quality due to nitrogen incorporation, which partly suppresses the surface-related nonradiative recombination centers via nitridation. Our work therefore represents the first step toward development of room-temperature infrared NW lasers based on dilute nitrides with extended tunability in the lasing wavelength.

Taking advantage of antibody molecules to generate tailor-made binding sites, we propose a new class of protein modifications, termed as "site-directed chemical mutation." In this modification, chemically synthesized catalytic components with a variety of steric and electronic properties can be noncovalently and nongenetically incorporated into specific sites in antibody molecules to induce enzymatic activity. Two catalytic antibodies, 25E2 and 27C1, possess antigen-combining sites which bind catalytic components and act as apoproteins in catalytic reactions. By simply exchanging these components, antibodies 25E2 and 27C1 can catalyze a wide range of chemical transformations including acyl-transfer, β-elimination, aldol, and decarboxylation reactions. Although both antibodies were generated with the same hapten, phosphonate diester 1, they showed different catalytic activity. When phenylacetic acid 4 was used as the catalytic component, 25E2 efficiently catalyzed the elimination reaction of β-haloketone 2, whereas 27C1 showed no catalytic activity. In this work, we focused on the β-elimination reaction and examined the site-directed chemical mutation of 27C1 to induce activity and elucidate the catalytic mechanism. Molecular models showed that the cationic guanidyl group of Arg H52 in 27C1 makes a hydrogen bond with the P═O oxygen in the hapten. This suggested that during β-elimination, Arg H52 of 27C1 would form a salt bridge with the carboxylate of 4, thus destroying reactivity. Therefore, we utilized site-directed chemical mutation to change the charge properties of the catalytic components. When amine components 7-10 were used, 27C1 efficiently catalyzed the β-elimination reaction. It is noteworthy that chemical mutation with secondary amine 8 provided extremely high activity, with a rate acceleration [(k cat /K m 2)/k uncat ] of 1 000 000. This catalytic activity likely arises from the proximity effect, plus general-base catalysis associated the electrostatic interactions. In 27C1, the cationic guanidyl group of Arg H52 is spatially close to the nitrogen of the amine components. In this microenvironment, the intrinsic pK a of the amine is perturbed and shifts to a lower pK a , which efficiently abstracts the α-proton during the reaction. This mechanism is consistent with the observed kinetic isotope effect (E2 or E1cB mechanism). Thus, site-directed chemical mutation provides a better understanding of enzyme functions and opens new avenues in biocatalyst research.

A significant gap exists between protein engineering and enzymes used for the biosynthesis of natural products, largely because there is a paucity of strategies that rapidly detect active-site phenotypes of the enzymes with desired activities. Herein, we describe a proof-of-concept study of an enzyme-linked immunosorbent assay (ELISA) system for the adenylation (A) domains in nonribosomal peptide synthetases (NRPSs) using a combination of active site-directed probes coupled to a 5'-O-N-(aminoacyl)sulfamoyladenosine scaffold with a biotin functionality that immobilizes probe molecules onto a streptavidin-coated solid support. The recombinant NRPSs have a C-terminal His-tag motif that is targeted by an anti-6×His mouse antibody as the primary antibody and a horseradish peroxidase-linked goat antimouse antibody as the secondary antibody. These probes can selectively capture the cognate A domains by ligand-directed targeting. In addition, the ELISA technique detected A domains in the crude cell-free homogenates from the Escherichia coli expression systems. When coupled with a chromogenic substrate, the antibody-based ELISA technique can visualize probe-protein binding interactions, which provides accurate readouts of the A-domain functions in NRPS enzymes. To assess the ELISA-based engineering of the A domains of NRPSs, we reprogramed 2,3-dihydroxybenzoic acid (DHB)-activating enzyme EntE toward salicylic acid (Sal)-activating enzymes and investigated a correlation between binding properties for probe molecules and enzyme catalysts. We generated a mutant of EntE that displayed negligible loss in the kcat/Km value with the noncognate substrate Sal and a corresponding 48-fold decrease in the kcat/Km value with the cognate substrate DHB. The resulting 26-fold switch in substrate specificity was achieved by the replacement of a Ser residue in the active site of EntE with a Cys toward the nonribosomal codes of Sal-activating enzymes. Bringing a laboratory ELISA technique and adenylating enzymes together using a combination of active site-directed probes for the A domains in NRPSs should accelerate both the functional characterization and manipulation of the A domains in NRPSs.

GaAs/GaAsBi coaxial multishell nanowires were grown by molecular beam epitaxy. Introducing Bi results in a characteristic nanowire surface morphology with strong roughening. Elemental mappings clearly show the formation of the GaAsBi shell with inhomogeneous Bi distributions within the layer surrounded by the outermost GaAs, having a strong structural disorder at the wire surface. The nanowire exhibits a predominantly ZB structure from the bottom to the middle part. The polytipic WZ structure creates denser twin defects in the upper part than in the bottom and middle parts of the nanowire. We observe room temperature cathodoluminescence from the GaAsBi nanowires with a broad spectral line shape between 1.1 and 1.5 eV, accompanied by multiple peaks. A distinct energy peak at 1.24 eV agrees well with the energy of the reduced GaAsBi alloy band gap by the introduction of 2% Bi. The existence of localized states energetically and spatially dispersed throughout the NW are indicated from the low temperature cathodoluminescence spectra and images, resulting in the observed luminescence spectra characterized by large line widths at low temperatures as well as by the appearance of multiple peaks at high temperatures and for high excitation powers.

Nonribosomal peptide synthetases (NRPSs) and polyketide synthases are large diverse families of biosynthetic enzymes that catalyze the synthesis of natural products that display biologically important activities. Genetic investigations have greatly contributed to our understanding of these biosynthetic enzymes; however, proteomic studies are limited. Here we describe the application of active site-directed proteomic probes for adenylation (A) domains to profile the activity of NRPSs directly in native proteomic environments. Derivatization of a 5'-O-N-(aminoacyl)sulfamoyladenosine appended clickable benzophenone functionality enabled activity-based protein profiling of the A-domains in NRPSs in proteomic extracts. These probes were used to identify natural product producing microorganisms, optimize culture conditions, and profile the activity dynamics of NRPSs. Our proteomic approach offers a simple and versatile method to monitor NRPS expression at the protein level and will facilitate the identification of orphan enzymatic pathways involved in secondary metabolite production.

Semiconductor/oxide composite nanowires (NWs) were synthesized by molecular beam epitaxial growth and subsequent wet oxidation. Nonselective and selective oxidation conditions applied to the GaAs/AlGaAs core-shell NWs grown on silicon substrates produced GaOx/AlGaOx and GaAs/AlGaOx NWs, respectively. The oxidized amorphous AlGaOx shell produced cathodoluminescence over a wide spectral range encompassing ultraviolet and visible wavelengths, possibly sourced from molecular species related to oxygen. The wire core was buried in the oxides when the diameter of the oxide shell increased, forming a planar structure. These composites are expected to pave the way to future electrical and optical functions for NWs.

Acyl carrier proteins (ACPs) play a central role in acetate biosynthetic pathways, serving as tethers for substrates and growing intermediates. Activity and structural studies have highlighted the complexities of this role, and the protein-protein interactions of ACPs have recently come under scrutiny as a regulator of catalysis. As existing methods to interrogate these interactions have fallen short, we have sought to develop new tools to aid their study. Here we describe the design, synthesis, and application of pantetheinamides that can cross-link ACPs with catalytic β-hydroxy-ACP dehydratase (DH) domains by means of a 3-alkynyl sulfone warhead. We demonstrate this process by application to the Escherichia coli fatty acid synthase and apply it to probe protein-protein interactions with noncognate carrier proteins. Finally, we use solution-phase protein NMR spectroscopy to demonstrate that sulfonyl 3-alkynyl pantetheinamide is fully sequestered by the ACP, indicating that the crypto-ACP closely mimics the natural DH substrate. This cross-linking technology offers immediate potential to lock these biosynthetic enzymes in their native binding states by providing access to mechanistically cross-linked enzyme complexes, presenting a solution to ongoing structural challenges.

1,5-Anhydro-D-glucitol (1,5-AG) is fairly widespread in food products. It is also one of the major polyols in the human body, and its concentration is homeostatically regulated. We report here on the beneficial effects of 1,5-AG in preventing hyperglycemia and its role in improving metabolic syndrome. The findings revealed that it does not affect blood glucose levels itself under normal conditions but clearly has a suppressive effect on the levels of dietary sugars, such as glucose, maltose, and sucrose. A long-term administration study revealed that feeding db/db diabetic mice 3% 1,5-AG for 8 weeks significantly decreased blood glucose levels compared to untreated mice (339 ± 30 versus 438 ± 34 mg/dL; p < 0.05). Furthermore, this treatment also significantly suppressed serum cholesterol levels (110.2 ± 18.0 versus 168.4 ± 9.8 mg/dL; p < 0.01). 1,5-AG did not inhibit intestinal α-glucosidase activities but regulated liver glucose levels via affecting both the glycogenolysis and gluconeogenesis pathways. Furthermore, the oral administration of 1,5-AG significantly increased urinary glucose excretion in hyperglycemic conditions. These results clearly suggest that dietary 1,5-AG acts as a modulator of glucose levels in hyperglycemia. 1,5-AG therefore represents a new class of promising functional sweeteners, where the daily consumption of 1,5-AG with meals could inhibit the progress of hyperglycemia and metabolic syndrome.

We targeted the development of a dehydratase (DH)-specific reactive probe that can facilitate detection, enrichment, and identification of DH enzymes in fatty acid synthases (FASs) and polyketide synthases (PKSs). The first reported mechanism-based inactivator, 3-decynoyl-N-acetylcysteamine (3-decynoyl-NAC), while active against the Escherichia coli β-hydroxydecanoyl thiol ester DH FabA, translates poorly to an activity-based probe because of nonspecific reactivity of the thioester moiety. Here we describe the design, synthesis, and utility of a DH-specific probe that contains a sulfonyl 3-alkyne reactive warhead engineered to avoid hydrolysis or nonenzymatic inactivation. When coupled with a fluorescent tag, this probe targets DH enzymes from recombinant type I and type II FAS and PKS enzyme systems and in whole proteomes. Activity studies, including FabA inactivation and antibiotic susceptibility, suggest that this sulfonyl 3-alkyne scaffold selectively targets a common DH mechanism. These studies indicate that the DH-specific mechanism-based probe can greatly accelerate both the functional characterization and molecular identification of virtually any type of FAS and PKS in complex proteomes., (© 2011 American Chemical Society)

A single antibody catalyzes multiple chemical transformations upon replacement of the funcctionalized small nonportein components.

We evaluated the protective potential of anthocyanins from purple sweet potato Ipomoea batatas cultivar Ayamurasaki (APSP) against low-density lipoprotein (LDL) oxidation in vitro and atherosclerotic lesion development in apolipoprotein E-deficient mice given a cholesterol- and fat-enriched diet with or without 1% APSP for 4 weeks. APSP protected LDL against oxidation more potently than other anthocyanins and l-ascorbic acid in vitro. In mice, APSP significantly lowered the atherosclerotic plaque area to about half of the control, the liver level of thiobarbituric acid-reactive substances as an oxidative stress marker, and the plasma level of soluble vascular cell adhesion molecule-1 (sVCAM-1). However, APSP showed no effects on body weight and cholesterol and lipid levels in the plasma. The results suggest that APSP can suppress the development of atherosclerotic lesions and both enhancements of oxidative stress and sVCAM-1 independently of the changes in cholesterol and lipid levels in mice.

Optically transparent, mechanically flexible displays are attractive for next-generation visual technologies and portable electronics. In principle, organic light-emitting diodes (OLEDs) satisfy key requirements for this application-transparency, lightweight, flexibility, and low-temperature fabrication. However, to realize transparent, flexible active-matrix OLED (AMOLED) displays requires suitable thin-film transistor (TFT) drive electronics. Nanowire transistors (NWTs) are ideal candidates for this role due to their outstanding electrical characteristics, potential for compact size, fast switching, low-temperature fabrication, and transparency. Here we report the first demonstration of AMOLED displays driven exclusively by NW electronics and show that such displays can be optically transparent. The displays use pixel dimensions suitable for hand-held applications, exhibit 300 cd/m2 brightness, and are fabricated at temperatures suitable for integration on plastic substrates.

We report complementary detection of prostate-specific antigen (PSA) using n-type In2O3 nanowires and p-type carbon nanotubes. Our innovation involves developing an approach to covalently attach antibodies to In2O3 NW surfaces via the onsite surface synthesis of phosphonic acid-succinylimide ester. Electronic measurements under dry conditions revealed complementary response for In2O3 NW and SWNT devices after the binding of PSA. Real-time detection in solution has also been demonstrated for PSA down to 5 ng/mL, a benchmark concentration significant for clinical diagnosis of prostate cancer, which is the most frequently diagnosed cancer.

A concise enantiospecific synthesis of nemorensic acid 3, a necic acid component of the macropyrrolizidine alkaloid nemorensine 2, isolated from Senecio nemorensis L., is described. Reaction of an epsilon-halo-alpha,beta-unsaturated ester (8), readily accessible from a monoterpene (-)-carvone, with samarium iodide gave a fragmentation product (9), where a carbon-carbon bond cleavage reaction occurred between the gamma and delta positions of the carbonyl group, regioselectively. Deprotection of the silyl group of 9 brought about an intramolecular cyclization to provide tetrahydrofuran derivatives (10), which, upon chemical modification of the side chain, gave nemorensic acid.

A series of 1-imidazolylalkyl-substituted or 5-thiazolylalkyl-substituted tetrahydronaphthalenecarboxylic acid and indancarboxylic acid derivatives were prepared and tested for the inhibitory activities of thromboxane A2 (TXA2) production in vitro and ex vivo. Most of the compounds showed potent TXA2 synthetase inhibitory activities in vitro and had long duration of inhibition of TXA2 production in rats when orally or intravenously administrated. The imidazole analogues had slightly less potency in vitro than the thiazole analogues, but the activities of the imidazole analogues in ex vivo models were equal or superior to the activities of the thiazole analogues. 6-(1-Imidazolyl-methyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride hemihydrate (47a, DP-1904) was chosen for clinical studies.

A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, -[3,2,-d]-, and -[3,4-d]pyrimidin-2-one derivatives has been prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. These compounds were synthesized through the following reactions: sodium borohydride reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood and platelet aggregation. Structure-activity relationships have indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro-[1]benzothieno[2,3-d]imidazo[1,2-a]pyrimidin-2-one (9m) exhibited the most favorable activity.

A series of novel 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one derivatives substituted with a secondary amino group has been prepared and tested for the activities of inhibiting platelet aggregation in rats in vitro and ex vivo. Most of the compounds were found to be the potent inhibitors of platelet aggregation. Some of the active compounds were soluble in water and effective via iv infusion in rats. Structure-activity relationships have indicated that a lipophilic secondary amino group located at position 6 or 7 contributed to retention of potent activity. Among the compounds studied, 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2- one (13 g,DN-9693) was the most favorable compound.