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An efficient synthesis of bisbenzopyrones by a N-heterocyclic carbene (NHC)-catalyzed intramolecular hydroacylation-Stetter reaction cascade has been developed. A series of symmetrical and unsymmetrical bisbenzopyrones were obtained with good to excellent yields. Bisbenzopyran-4-ol was synthesized efficiently. [ABSTRACT FROM AUTHOR]

An efficient N-heterocyclic carbene catalyzed glycosylation of 2-nitrogalactals with alcohols and phenol has been developed for the first time. A wide variety of 1,2-cis-2-nitroglycosides can be obtained with good to excellent yields and high to excellent α-selectivities. [ABSTRACT FROM AUTHOR]

Dimethylzirconocene reacts with 2 molar equiv of the persistent radical TEMPO to give the Cp2Zr(Me)OTMP complex 12 with formation of TEMPOMe. Methyl anion abstraction from 12 with B(C6F5)3 generates the [Cp2ZrOTMP+] cation 13 (with the [MeB(C6F5)3]- anion) that undergoes a typical intramolecular frustrated Zr+/N Lewis pair (FLP) reaction with phenylacetylene. With PtBu3 it reacts as an intermolecular Zr+/P FLP trapping carbon dioxide. Complex 12 reacts with HB(C6F5)2 also by methyl anion abstraction to form the μ-H bridged tight ion pair Cp2ZrOTMP(μ-H)BMe(C6F5)2 (19). It serves as a Cp2Zr(H)OTMP zirconocene hydride source in the reaction with CO2, giving the respective [Zr](μ-formate)[B] complex 23. With carbon monoxide it forms the Zr-(η²-acetaldehyde)[B] complex 30 by transfer of both the hydride and the methyl anion from the Zr/B pair to the carbon atom of the CO molecule. [ABSTRACT FROM AUTHOR]

The first catalytic enantioselective isomerization of secondary allylic alcohols to access ketones with a α-tertiary stereocenter is presented. The racemic allylic alcohol substrates can be converted to the enantioenriched ketone products in a stereoconvergent fashion. The use of commercially available catalysts and mild reaction conditions makes this an attractive method in stereoselective synthesis. [ABSTRACT FROM AUTHOR]

What are the physical laws of the diffusive search of proteins for their specific binding sites on DNA in the presence of the macromolecular crowding in cells? We performed extensive computer simulations to elucidate the protein target search on DNA. The novel feature is the viscoelastic non-Brownian protein bulk diffusion recently observed experimentally. We examine the influence of the protein-DNA binding affinity and the anomalous diffusion exponent on the target search time. In all cases an optimal search time is found. The relative contribution of intermittent three-dimensional bulk diffusion and one-dimensional sliding of proteins along the DNA is quantified. Our results are discussed in the light of recent single molecule tracking experiments, aiming at a better understanding of the influence of anomalous kinetics of proteins on the facilitated diffusion mechanism. [ABSTRACT FROM AUTHOR]

An In-based metal-organic framework, with 1D nanotubular open channels, In2(OH)(btc)(Hbtc)0.4(L)0.6·3H2O (1), has been synthesized via an in situ ligand reaction, in which 1,2,4-H3btc is partially transformed into the L ligand. Compound 1 exhibits exceptional thermal and chemical stability, especially in water or acidic media. The activated 1 presents highly selective sorption of carbon dioxide (CO2) over dinitrogen. Interestingly, diffuse-reflectance infrared Fourier transform spectroscopy with a carbon monoxide probe molecule demonstrates that both Lewis and Brønsted acid sites are involved in compound 1. As a result, as a heterogeneous Lewis and Brønsted acid bifunctional catalyst, 1 possesses excellent activity and recyclability for chemical fixation of CO2 coupling with epoxides into cyclic carbonates under mild conditions. In addition, the mechanism for the CO2 cycloaddition reaction has also been discussed. [ABSTRACT FROM AUTHOR]

Polyethyleneglycol borate (PEG-BAE) toughening agents were preparedfrom the esterification reaction between boric acid and PEG and characterizedby FTIR and NMR. The effect of reaction conditions such as reactiontemperatures, reaction times, and entrainer amounts on the esterificationreaction rate was studied. Incorporation of PEG-BAE into phenolic(PF) foams leads to an improvement in the flexural and compressionstrengths, and a reduced pulverization ratio compared with pure andPEG-toughened foams. The LOI results illustrate the flame-retardingeffect of PEG-BAE is better than that of pure PEG, with LOI in therange 35.5–39.0%, and all PF foams pass UL 94 V-0 rating. Conecalorimeter results indicate that the incorporation of PEG400 increasesthe peak heat-release rate (PHRR) of PF foam by 38%, whereas PEG400-BAEresults in a slightly decreased PHRR. Moreover, thermal decompositionof pure and toughened PF foams was investigated. [ABSTRACT FROM AUTHOR]

The effects of medicine on the biomolecular interaction have been given increasing attention in biochemistry and affinity-based analytics since the environment in vivo is complex especially for the patients. Herein, myoglobin, a biomarker of acute myocardial infarction, was used as a model, and the medicine effects on the interactions of myoglobin/aptamer and myoglobin/antibody were systematically investigated using atomic force microscopy (AFM) for the first time. The results showed that the average binding force and the binding probability of myoglobin/aptamer almost remained unchanged after myoglobin-modified gold substrate was incubated with promazine, amoxicillin, aspirin, and sodium penicillin, respectively. These parameters were changed for myoglobin/antibody after the myoglobin-modified gold substrate was treated with these medicines. For promazine and amoxicillin, they resulted in the change of binding force distribution of myoglobin/antibody (i.e., from unimodal distribution to bimodal distribution) and the increase of binding probability; for aspirin, it only resulted in the change of the binding force distribution, and for sodium penicillin, it resulted in the increase of the average binding force and the binding probability. These results may be attributed to the different interaction modes and binding sites between myoglobin/aptamer and myoglobin/antibody, the different structures between aptamer and antibody, and the effects of medicines on the conformations of myoglobin. These findings could enrich our understanding of medicine effects on the interactions of aptamer and antibody to their target proteins. Moreover, this work will lay a good foundation for better research and extensive applications of biomolecular interaction, especially in the design of biosensors in complex systems. [ABSTRACT FROM AUTHOR]

Understanding the microtubule-dependent behaviors of viruses in live cells is very meaningful for revealing the mechanisms of virus infection and endocytosis. Herein, we used a quantum dots-based single-particle tracking technique to dynamically and globally visualize the microtubule-dependent transport behaviors of influenza virus in live cells. We found that the intersection configuration of microtubules can interfere with the transport behaviors of the virus in live cells, which lead to the changing and long-time pausing of the transport behavior of viruses. Our results revealed that most of the viruses moved along straight microtubules rapidly and unidirectionally from the cell periphery to the microtubule organizing center (MTOC) near the bottom of the cell, and the viruses were confined in the grid of microtubules near the top of the cell and at the MTOC near the bottom of the cell. These results provided deep insights into the influence of entire microtubule geometry on the virus infection. [ABSTRACT FROM AUTHOR]

In this work, we reported a simple rapid and point-of-care magnetic immunofluorescence assay for avian influenza virus (AIV) and developed a portable experimental setup equipped with an optical fiber spectrometer and a microfluidic device. We achieved the integration of immunomagnetic target capture, concentration, and fluorescence detection in the microfluidic chip. By optimizing flow rate and incubation time, we could get a limit of detection low up to 3.7 × 104 copy/μL with a sample consumption of 2 μL and a total assay time of less than 55 min. This approach had proved to possess high portability, fast analysis, high specificity, high precision, and reproducibility with an intra-assay variability of 2.87% and an interassay variability of 4.36%. As a whole, this microfluidic system may provide a powerful platform for the rapid detection of AIV and may be extended for detection of other viral pathogens; in addition, this portable experimental setup enables the development of point-of-care diagnostic systems while retaining adequate sensitivity. [ABSTRACT FROM AUTHOR]

Recent studies have shown that NP (nucleoprotein), which possesses multiple functions in the viral life cycle, is a new potential anti-influenza drug target. NP inhibitors reliably induce conformational changes in NPs, and these changes may confer inhibition of the influenza virus. The six conserved tryptophan residues in NP can be used as an intrinsic probe to monitor the change in fluorescence of the tryptophan residues in the protein upon binding to an NP inhibitor. In the present study, we found that the fluorescence of recombinant NP proteins was quenched following the binding of available NP inhibitors (such as nucleozin) in a concentration- and time-dependent manner, which suggests that the inhibitor induced conformational changes in the NPs. The minimal fluorescence-quenching effect and weak binding constant of nucleozin to the swine-origin influenza virus H1N1pdm09 (SOIV) NP revealed that the SOIV is resistant to nucleozin. We have used the fluorescence-quenching property of tryptophans in NPs that were bound to ligands in a 96-well-plate-based drug screen to assess the ability of promising small molecules to interact with NPs and have identified one new anti-influenza drug, CSV0C001018, with a high SI value. This convenient method for drug screening may facilitate the development of antiviral drugs that target viruses other than the influenza virus, such as HIV and HBV. [ABSTRACT FROM AUTHOR]

Domain swapping creates protein oligomers by exchange of structural units between identical monomers. At present, no unifying molecular mechanism of domain swapping has emerged. Here we used the protein Cyanovirin-N (CV-N) and 19F-NMR to investigate the process of domain swapping. CV-N is an HIV inactivating protein that can exist as a monomer or a domain-swapped dimer. We measured thermodynamic and kinetic parameters of the conversion process and determined the size of the energy barrier between the two species. The barrier is very large and of similar magnitude to that for equilibrium unfolding of the protein. Therefore, for CV-N, overall unfolding of the polypeptide is required for domain swapping. [ABSTRACT FROM AUTHOR]

Herein we report that isobutyl-β-C-galactoside (IBCG) is also a promising inducer of gene expression in mammalian cells and report a new synthetic route to the compound that should make obtaining the multigram quantities of material required for animal studies more feasible. A convenient synthesis of IBCG, an inducer of genes controlled by the lac operon system in bacterial cells, was achieved in 5 steps from galactose in 81% overall yield without any chromatographic separation steps. An optimized microwave-assisted reaction at high concentration was key to making the C-glycosidic linkage. A Wittig reaction on a per-O-silylated rather than per-O-acetylated or -benzylated substrate proved most effective in installing the final carbon atom. [ABSTRACT FROM AUTHOR]

The prion protein (PrP) takes up 4-6 equiv of copper in its extended N-terminal domain, composed of the octarepeat (OR) segment (human sequence residues 60-91) and two mononuclear binding sites (at His96 and His111; also referred to as the non-OR region). The OR segment responds to specific copper concentrations by transitioning from a multi-His mode at low copper levels to a single-His, amide nitrogen mode at high levels (Chattopadhyay et al. J. Am. Chem. Soc.2005, 127, 12647-12656). The specific function of PrP in healthy tissue is unclear, but numerous reports link copper uptake to a neuroprotective role that regulates cellular stress (Stevens, et al. PLoS Pathog.2009, 5 (4), e1000390). A current working hypothesis is that the high occupancy binding mode quenches copper's inherent redox cycling, thus, protecting against the production of reactive oxygen species from unregulated Fenton type reactions. Here, we directly test this hypothesis by performing detailed pH-dependent electrochemical measurements on both low and high occupancy copper binding modes. In contrast to the current belief, we find that the low occupancy mode completely quenches redox cycling, but high occupancy leads to the gentle production of hydrogen peroxide through a catalytic reduction of oxygen facilitated by the complex. These electrochemical findings are supported by independent kinetic measurements that probe for ascorbate usage and also peroxide production. Hydrogen peroxide production is also observed from a segment corresponding to the non-OR region. Collectively, these results overturn the current working hypothesis and suggest, instead, that the redox cycling of copper bound to PrP in the high occupancy mode is not quenched, but is regulated. The observed production of hydrogen peroxide suggests a mechanism that could explain PrP's putative role in cellular signaling. [ABSTRACT FROM AUTHOR]

The first fluorous protecting group for phosphate is reported. This group can be used as a facile tag for purification and be removed under mild reducing conditions using zinc and ammonium formate. Synthesis of a disaccharide from Leishmaniausing this fluorous protecting group demonstrated the group’s stability to the acidic conditions necessary for glycosylation as well as its orthogonality to several other common protecting groups. [ABSTRACT FROM AUTHOR]

A major constituent in the deposit of the brain in a patient with Alzheimer's disease (AD) is the aggregates/fibrils of amyloid-β (Aβ) peptides containing 39-43 amino acids. The total Aβ levels and the concentration ratio between the most abundant Aβ(1-40) peptide and the more aggregation-prone Aβ(1-42) in body fluids (e.g., cerebrospinal fluid or CSF) have been suggested as possible criteria for early diagnosis of AD. By immobilizing capture antibodies specific to the two peptides in separate fluidic channels, surface plasmon resonance (SPR) has been used to quantify Aβ(1-40) and Aβ(1-42) present in CSF samples collected from AD patients and healthy donors. With signal amplification by streptavidin conjugated to an antibody that is selective to the common N-terminus of the Aβ peptides, concentrations as low as 20 pM can be readily measured. The range of Aβ peptide concentrations measurable by this method spans 4 orders of magnitude. The ability of regenerating the sensor surface for repeated measurements not only improves the reproducibility but also enhances the sample throughput. Our data reveal that the ratio of Aβ(1-40) concentration versus Aβ(1-42) concentration in CSF samples from AD patients is almost twice as high as that from healthy persons. In contrast to the commonly used enzyme-linked immunosorbent assay (ELISA), SPR obviates the need of a more expensive and less stable enzyme conjugate and the use of carcinogenic substrate for the signal detection and allows the binding events to be monitored in real time. [ABSTRACT FROM AUTHOR]

α-Synuclein (α-syn), a presynaptic protein believed to play an important role in neuropathology in Parkinson's disease (PD), is known to bind Cu2+. Cu2+ has been shown to accelerate the aggregation of α-syn to form various toxic aggregates in vitro. Copper is also a redox-active metal whose complexes with amyloidogenic proteins/peptides have been linked to oxidative stress in major neurodegenerative diseases. In this work, the formation of the Cu2+ complex with α-syn or with an N-terminal peptide, α-syn(1-19), was confirmed with electrospray-mass spectrometry (ES-MS). The redox potentials of the Cu2+ complex with α-syn (α-syn-Cu2+) and α-syn(1-19) were determined to be 0.018 and 0.053 V, respectively. Furthermore, the Cu2+ center(s) can be readily reduced to Cu+, and possible reactions of α-syn-Cu2+ with cellular species (e.g., O2, ascorbic acid, and dopamine) were investigated. The occurrence of a redox reaction can be rationalized by comparing the redox potential of the α-syn-Cu2+ complex to that of the specific cellular species. For example, ascorbic acid can directly reduce α-syn-Cu2+ to α-syn-Cu+, setting up a redox cycle in which O2 is reduced to H2O2 and cellular redox species is continuously exhausted. In addition, the H2O2 generated was demonstrated to reduce viability of the neuroblastoma SY-HY5Y cells. Although our results ruled out the direct oxidation of dopamine by α-syn-Cu2+, the H2O2 generated in the presence of α-syn-Cu2+ can oxidize dopamine. Our results suggest that oxidative stress is at least partially responsible for the loss of dopaminergic cells in PD brain and reveal the multifaceted role of the α-syn-Cu2+ complex in oxidative stress associated with PD symptoms. [ABSTRACT FROM AUTHOR]

A mild method for selective synthesis of o-acylbenzylphosphonates has been developed by the reactions of arynes with β-ketophosphonates. In the presence of CsF and THF, the carbon-carbon σ-bonds of 2-oxopropylphosphonates were selectively cleaved and added to arynes providing the corresponding 2-acylbenzylphosphonates in moderate to good yields. [ABSTRACT FROM AUTHOR]

Palladium-catalyzed cocyclotrimerization of allenes with arynes has been developed for selectively synthesizing phenanthrenes. In the presence of [(allyl)PdCl]2 and P(o-tol)3, a variety of allenes, including internal and terminal allenes, underwent the cocyclotrimerization with arynes to afford the corresponding phenanthrenes in moderate to good yields. The results showed the selectivity of the reaction based on allenes. [ABSTRACT FROM AUTHOR]

The COMPASS (condensed-phase optimized molecular potentials for atomistic simulation studies) force field with two sets of partial atomic charges of water was used to simulate adsorption and diffusion behavior of water/methanol and water/ethanol mixtures in zeolite 4A at 298 K. The adsorption of alcohol first increased and then decreased with increasing pressure, whereas the adsorption of water increased progressively until an adsorption equilibrium was reached. Both the adsorbed molecules and the zeolite framework were treated as a fully flexible model in MD simulations. The simulation results show that the effects of the size and steric hindrance of the diffusing molecules on diffusivity are significant. The diffusivity of water, methanol, and ethanol molecules decreases by 1 order of magnitude in the order of water > methanol > ethanol. The diffusivity of water molecules depends on the mass fraction and the partial charges of water in zeolite 4A. The ethanol and methanol molecules have restricted motion through the α-cages, whereas the water molecules can easily pass through the α-cages window at low feed alcohol concentrations. And the extent of hydrogen bonding increased with increasing water concentration. [ABSTRACT FROM AUTHOR]

The relaxation dynamics of excited electronic states of [(1,1′-biphenyl)-4,4′-diyldi-2,1-ethenediyl]bis(dimethylsilane) dissolved in various solvents with varied polarity and viscosity have been investigated. Upon excitation at wavelength 266 nm, we measured the fluorescence curves that exhibit a rise time constant ∼100 fs, and two decay time constants, 7−65 ps and ∼1 ns. We attribute the former decay to upper excited states to the S1state, and the latter decay to geometric relaxation and the lifetime of the S1state. Only the tens of picosecond decay shows a dependence on the solvent viscosity, indicating that the torsional motion dominates the relaxation. Theoretical calculations were performed to obtain the optimized structures of the free [(1,1′-biphenyl)-4,4′-diyldi-2,1-ethenediyl]bis(dimethylsilane) molecule in its ground and first excited states with methods B3LYP/6-311G(d) and CIS/6-311G(d), respectively. The results of these calculations show that the dihedral angle between the two phenyl rings is ∼34° for transand ∼38° for cisconformers in the ground state and that the first excited state has a planar structure, in agreement with the experimental results that indicate that the torsional motion of two phenyl groups elevates the relaxation of the S1state. Enhanced vibrational relaxation of S1in alcoholic solvents is observed. Rapid relaxation in methanol-OH compared with that in methanol-OD is explained by the excess energy dissipated efficiently through high-frequency vibrational mode (>500 cm−1). [ABSTRACT FROM AUTHOR]

A new uranyl silicate, K2Ca4[(UO2)(Si2O7)2], with a 1D chain structure has been synthesized from a solution of mixed alkali- and alkaline-earth-metal cations under hydrothermal conditions at 550 °C and 1400 bar and characterized by single-crystal X-ray diffraction and photoluminescence spectroscopy. It crystallizes in the triclinic space group P1̅ (No. 2) with a = 6.6354(2) Å, b = 6.6791(2) Å, c = 9.6987(3) Å, α = 98.324(2)°, β = 93.624(2)°, γ = 112.310(2)°, and Z = 1. Its crystal structure consists of a 1D chain of uranyl disilicate formed of corner-sharing UO6 tetragonal bipyramids and Si2O7 double groups. The adjacent chains are separated by K+ and Ca2+ cations. It is the first example of uranyl silicate with a 1D chain structure. [ABSTRACT FROM AUTHOR]

Typical sulfur-containing amino acids, cysteine and methionine, were employed as stabilizers in place of lead(II) acetate in the electroless nickel plating (ENP) system. Each of these compounds presents a critical stabilizing concentration of ca. 10 −5mol/L, below which the ENP rate is slightly promoted with increasing concentration but above which it is significantly suppressed. Their role in stabilizing the ENP bath was found to involve inhibition of the anodic reaction of hypophosphite. The chemical adsorption of these two amino acids on active nickel sites at the Ni plating surface was studied via their adsorption on an in situ generated Ni powder. In addition, the stabilization mechanism was investigated by using potentiometry, X-ray photoelectron spectroscopy (XPS), and UV−vis/infrared spectroscopy. Finally, the bath stabilizing capabilities of these two amino acids and the change in ENP properties with time were assessed through a continuous operation comprising four metal-turnover (MTO) runs. [ABSTRACT FROM AUTHOR]

A mild and general cycloaddition of arynes with iodonium ylides protocol has been developed for the synthesis of benzofurans. In the presence of CsF, ortho-silyl aryltriflates were reacted with iodonium ylides smoothly at room temperature in moderate to good yields. [ABSTRACT FROM AUTHOR]

A simplified activity model was developed based on the nonrandom version of statistical thermodynamics. The partition function consists of two parts:  one is a random distribution of the empty sites, which corresponds to the ideal solution part, and the other is a correction factor for the actual nonrandom distribution of the empty sites, which corresponds to the excess part. Model parameters are not difficult to obtain in comparison with other model equations. The applicability of this model was demonstrated by calculating the solvent activities in 12 polymer solutions. It is found that the calculated results are consistent with the experimental data. The present model was also applied to describe the phase diagram of polystyrene−cyclohexane and polystyrene−ethyl acetate. It is proved that the method was able to correlate both low critical solution temperature and upper critical solution temperature. Furthermore, extension of this model equation to multicomponent systems is straightforward, so the present model can be taken as an alternative for the description of the phase behaviors in polymer solutions. [ABSTRACT FROM AUTHOR]

Novel organic−inorganic hybrid membranes were prepared through sol−gel reaction of poly(vinyl alcohol) (PVA) with -aminopropyl-triethoxysilane (APTEOS). The membranes were characterized by FT−IR, solid-state NMR, WXRD, SEM, and contact angle meter. The swelling degree of the hybrid membranes in an aqueous isopropanol (IPA) solution has been controlled owing to the formation of hydrogen and covalent bonds in the membrane matrix. The effect of APTEOS content in the membrane, feed flow, feed concentration, and temperature on pervaporation (PV) performance was investigated. The water permselectivity increased, and permeation flux increased quickly with increasing APTEOS content when it was less than 5 wt %. The membrane containing 5 wt % of APTEOS has the highest separation factor of 1580 with a permeation flux of 26.5 × 10-3kg·m-2·h-1at 30 °C in PV separation of 90 wt % IPA in water. The temperature dependence of permeation flux can be described by an Arrhenius-type relationship. [ABSTRACT FROM AUTHOR]

Deposition of β-amyloid (Aβ) fibrils is an early event in the neurodegenerative processes associated with Alzheimer's disease. According to the ‘amyloid cascade’ hypothesis, Aβ aggregation, and its subsequent deposition as fibrils, is the underlying cause of disease. Aβ is a proteolytic product of amyloid precursor protein (APP); several mutations in APP have been identified that are associated with early onset of disease. Transgenic mice overexpressing APP with the Swedish mutation develop numerous plaques but, surprisingly, lack the neurofibrillary tangles and neuronal loss characteristic of Alzheimer's disease, in apparent contradiction of the amyloid cascade hypothesis. However, recent studies suggest that coproduction of sAPPα, an alternative proteolytic product of APP, increases synthesis of transthyretin that, in turn, interacts directly with Aβ to inhibit its toxicity. Here we report results from biophysical analysis of Aβ aggregation kinetics in the presence of transthryetin. At substoichiometric ratios, transthyretin drastically decreased the rate of aggregation without affecting the fraction of Aβ in the aggregate pool. Detailed analysis of the data using a mathematical model demonstrated that the decrease in aggregation rate was due to both a decrease in the rate of elongation relative to the rate of initiation of filaments and a decrease in lateral association of filaments to fibrils. Tryptophan quenching data indicated that transthyretin binds weakly to Aβ, with an estimated apparent Ks of 2300 M-1. Taken together, the data support a hypothesis wherein transthyretin preferentially binds to aggregated rather than monomeric Aβ and arrests further growth of the aggregates. [ABSTRACT FROM AUTHOR]

As the population ages, the need to develop methods to understand and intercept the processes responsible for protein aggregation diseases is becoming more urgent. The aggregation of the protein β-amyloid (Aβ) has been implicated in Alzheimer's Disease (AD); however, whether the toxic species is a large, insoluble aggregate or some lower order form is not yet known. Agents that can modulate the aggregation state of Aβ could resolve this controversy by facilitating our understanding of the consequences of aggregation and its underlying mechanism. To date, however, ligands that bind to specific forms of Aβ have not been identified. To address this deficiency, we tested whether phage display could yield such ligands by screening libraries against Aβ in two different states: monomeric or highly aggregated. Intriguingly, the peptides selected had different effects on Aβ aggregation. Peptides selected for binding to monomeric Aβ did not perturb aggregation, but those selected using highly aggregated Aβ increase the rate of aggregation drastically. The latter also alter the morphology of the resulting aggregate. The ability of a peptide to promote aggregation correlated with its affinity for the N-terminal 10 residues of Aβ. This result indicates that the mechanism by which the peptides influence aggregation is related to their affinity for the Aβ N-terminus. Thus, the identification of compounds that bind to this Aβ section can afford agents that affect aggregation. Moreover, the data suggest that endogenous ligands that interact with the N-terminal region can influence the propensity of Aβ to form aggregates and the morphology of those that form. Our data highlight the utility of phage display for identifying ligands that bind to target proteins in different states, and they indicate that such agents can be used to perturb protein aggregation. [ABSTRACT FROM AUTHOR]

Molecular dynamics (MD) simulations have been used to study the transport properties of oxygen and nitrogen in the para-substituted polystyrenes which possess one to four Si atoms in each substituent. The Condensed-phase Optimized Molecular Potentials for Atomistic Simulation Studies (COMPASS) force field was used to construct the polymers. Diffusion coefficients were obtained from molecular dynamics (NVT ensemble) with up to 3 ns simulation times. After molecular dynamic simulation, the trajectories of the small molecules in the polymer matrix were obtained. Then diffusion coefficients have been calculated from the Einstein relationship revealing a considerable agreement between the simulated and the experimental data. And solubility coefficients have been calculated by the Grand Canonical Monte Carlo (GCMC) method. The solubility of oxygen increased with increasing Si content in the polymer membrane. The para-substituted polystyrenes with a branched substituent at the -position showed higher permeability than those of the nonbranched ones. The higher the glass transition temperature (Tg) of the membrane, the larger the diffusion coefficients of oxygen and nitrogen obtained. [ABSTRACT FROM AUTHOR]

Herein, two stable lead(II) molecular-bowl-based metal-organic frameworks and their micro- and nanosized forms with open metal sites were presented. These materials could act as Lewis acid catalysts to cyanosilylation reaction. Moreover, the catalytic performances are size-dependent, with the catalyst with nanosized form being 1 order of magnitude more efficient than those with micro- and millisized forms. [ABSTRACT FROM AUTHOR]

We report a highly enantioselective Morita-Baylis-Hillman (MBH) reaction of isatins and acrolein to provide enantiomerically enriched 3-substituted 3-hydroxyoxindoles, which could serve as valuable synthetic building blocks. This is also the first time that a ketone has been used as the electrophile and acrolein as the nucleophile in a highly enantioselective catalytic asymmetric MBH reaction. Hatakeyama's catalyst, β-isocupreidine (1), turned out to be a powerful catalyst for this transformation. [ABSTRACT FROM AUTHOR]

Brønstedacid p-TsOH·H2O-catalyzedhydrovinylation of styrenes with internal olefins α-oxo ketenedithioacetals was efficiently achieved in the presence of N-phenylselenophthalimide (N-PSP), regioselectivelyaffording Markovnikov phenylselenative hydrovinylation products throughPhSe transfer of the phenylseleno ketene dithioacetal intermediates.Radical reduction of the resultant PhSe-alkyl-substituted ketene dithioacetalswith AIBN/n-Bu3SnH gave the corresponding anti-Markovnikov hydrovinylation products formally fromthe linear codimerization of styrenes and the internal olefins. [ABSTRACT FROM AUTHOR]

The methodology based on target-responsive structural switching is powerful in bioanalysis with the controllability and sensitivity. In this paper, an aptamer-functionalized DNA hydrogel was designed as a specifically target-responsive switchable material for protein detection. This pure DNA hydrogel was constructed by using a Y-shaped DNA and an aptamer linker through a DNA self-assembly without synthetic polymer backbone. With use of thrombin as the model analyte, the DNA hydrogel was first applied to visual detection with the entrapped Au nanoparticles (AuNPs) as indicating agent. Furthermore, the positively charged quantum dots (QDs) as the fluorophore were synthesized by using polyethyleneimine (PEI) as wrapper and characterized with spectroscopy, transmission electron micrograph, ζ potential, and dynamic laser scattering techniques. Along with a gel-to-sol transition in the presence of the target, the released negatively charged AuNPs from the hydrogel could approach the positively charged QDs. Due to the electrostatic interaction, fluorescence resonance energy transfer between PEI-QDs and AuNPs therefore occurred and quenched the fluorescence signal for the sensitive detection of thrombin. This assay for the detection of thrombin showed a good linear relationship in a range of 0.075 to 12.5 μM with a detection limit of 67 nM at 3σ, and demonstrated excellent feasibility in complex serum matrixes. The biocompatible DNA hydrogel provides a universal switchable material for signal transduction and significantly demonstrates proof-of-concept for the detection of proteins. [ABSTRACT FROM AUTHOR]

Rapid characterization of thermally stable chemical compounds in solid or liquid states is achieved through thermal desorption electrospray ionization mass spectrometry (TD-ESI/MS). A feature of this technique is that sampling, desorption, ionization, and mass spectrometric detection are four separate events with respect to time and location. A metal probe was used to sample analytes in their solid or liquid states. The probe was then inserted in a preheated oven to thermally desorb the analytes on the probe. The desorbed analytes were carried by a nitrogen gas stream into an ESI plume, where analyte ions were formed via interactions with charged solvent species generated in the ESI plume. The analyte ions were subsequently detected by a mass analyzer attached to the TD-ESI source. Quantification of acetaminophen in aqueous solutions using TD-ESI/MS was also performed in which a linear response for acetaminophen was obtained between 25 and 500 ppb (R2 = 0.9978). The standard deviation for a reproducibility test for ten liquid samples was 9.6%. Since sample preparation for TD-ESI/MS is unnecessary, a typical analysis can be completed in less than 10 s. Analytes such as the active ingredients in over-the-counter drugs were rapidly characterized regardless of the different physical properties of said drugs, which included liquid eye drops, viscous cold syrup solution, ointment cream, and a drug tablet. This approach was also used to detect trace chemical compounds in illicit drugs and explosives, in which samples were obtained from the surfaces of a cell phone, piece of luggage made from hard plastic, business card, and wooden desk. [ABSTRACT FROM AUTHOR]

Spectrophotometric-dual-enzyme-simultaneous assay in one reaction solution (SDESA) is proposed. SDESA requires the following: (a) Enzyme A acts on Substrate A to release Product A bearing the longest difference absorbance peak (λA) much larger than that of Product B (λB) formed by Enzyme B action on Substrate B; λB is close to the longest isoabsorbance wavelength of Product A and Substrate A (λ0); (b) absorbance at λA and λ0 is quantified via swift alternation of detection wavelengths and corrected on the basic of absorbance additivity; (c) inhibition/activation on either enzyme by any substance is eliminated; (d) Enzyme A is quantified via an integration strategy if levels of Substrate A are lower than the Michaelis constant Chemosneliics of SDESA was tested with γ-glutamyltransfersse and lactate-dehydrogenase of complicated kinetics. γ-Glutansyltransferase releases p-nitroaniline from γ-glutamyl-p-nitroaniline with λ0 at 344 run and λA close to 405 nm, lactate-dehydrogenase consumes reduced nicotinamide dinucleotide bearing λB at 340 nm. Kinetic analysis of reaction curve yielded lactate-dehydrogenase activity free from inhibition by p-nitroaniline; the linear range of initial rates of γ-glutamyltransferase via the integration strategy, and that of lactate-dehydrogenase after interference elimination, was comparable to those by separate assays, respectively; the quantification limit of either enzyme by SDESA at 25-fold higher activity of the other enzyme remained comparable to that by a separate assay. To test potential application, SDESA of alkaline phosphatase (ALP) and β-D-galactosidase as enzyme-linked-immunoabsorbent assay (ELISA) labels were examined. ALP releases 4-intro-1-naphthol from 4-nitronaphthyl-1-phosphate with λ0, at 405 nm and λA at 458 nm, β-D-galactosidase releases 4-nitrophenol from β-D-(4-nitrophenyl)-galactoside with λB at 405 nm. No interference from substrates/products made SDESA of β-galactosidase and ALP simple for ELISA of penicillin G and denhuterol in one well, and the quantification limit of either hapten was comparable to that via a separate assay. Hence, SDESA is promising. [ABSTRACT FROM AUTHOR]

Phosphine (R3P) compounds being a typical type of coordination ligand used in homogeneous catalysis are known to possess a tunable affinity with the nickel atom. As such, it deserves to be studied whether a water-soluble phosphine ligand could also be used as a plating stabilizer in the electroless nickel plating (ENP) system in place of hazardous Pb(II) salt and what will be the unique effects generated due to this replacement. Triphenylphosphine-3,3′,3′′-trisulfonic acid trisodium salt (TPPTS) was then chosen as a model phosphine stabilizer to perform the study. TPPTS could indeed work to prevent the ENP process from running out of control. In addition, unlike the existing ENP stabilizers, TPPTS does not reveal a percolation concentration for a sharp ceasing of plating. Also according to the voltammetry investigation, TPPTS can be classified as a cathodic stabilizer. A Ni−P plating layer with high phosphorus content (>15%) has been achieved using10−4mol/L TPPTS in the plating bath. Furthermore, this work investigated the relation between P weight percent and corrosion resistance of either the as-plated or the annealed Ni−P plating layer by electrochemical impedance spectroscopy (EIS). The annealing was found, according to the depth profile analysis, to drive diffusion of both Ni and P toward the bulk phase, which strongly revamps corrosion resistance of the plating layer. Finally, the stability of the ENP bath was evaluated using the metal-turnover (MTO) test. [ABSTRACT FROM AUTHOR]

A tubular condenser column was designed and constructed to evaluate the performances of the condensation process with a high fractional noncondensable gas in the dewvaporation desalination process. An experimental investigation has been conducted to determine the local condensation heat transfer coefficient, which is related to steam−air mixed gas condensation in an annulus around a vertical copper tube. The results show that the local heat transfer coefficient decreases with increase of the distance from the mixed gas inlet, and varies from 200 to 1900 W/m2·°C, which is high enough for steam condensation in the presence of a high fractional noncondensable gas. The correlation of steam condensing local heat transfer coefficient in the presence of a high fractional noncondensable gas was developed in terms of the local mixture Reynolds number, Jakob number, and ratio of noncondensable gas mass fraction. It is found that the correlation has a good agreement with the experimental data. [ABSTRACT FROM AUTHOR]

Studies the nitration of annexin II tetramer (AII(sub t)), a member of the calcium(sup 2+)- and phospholipid-binding protein family. Effects of peroxynitrite (ONOO(sup -)) on AII(sub t); Dose-dependent nitration of tyrosine residues in AII(sub t) treated with ONOO(sup -); Effect of the conformational change of AII(sub t) on the inhibition.

Two series of OAc–-dependent unique homoleptic nonanuclear [Ln9(L1)3(HL1)2(μ3-OH)4(OAc)10] (1–7) and hexanuclear {[Ln6(L2)4(HL2)(μ3-OH)(OAc)2(H2O)2]·(OAc)} (8–14) are obtained from the self-assembly of the partially deprotonated OH-H2Salen ligand H3L1 (N,N′-bis(salicylidene)(propylene-2-ol)-1,3-diamine) or OH-MeO-H2Salen ligand H3L2 (N,N′-bis(3-methoxysalicylidene)(propylene-2-ol)-1,3-diamine) with Ln(OAc)3 (Ln = La, Eu, Tb, Gd, Nd, Yb, or Er), respectively. The result of their photophysical properties shows that the sensitization for single-component near-white-light of complex 2, efficient Eu3+-centered red-light (ΦLEu = 13.4%) of complex 9, or or Tb3+-centered yellowish-green-light (ΦLTb = 8.1% and 21.3%) of complexes 3 and 10, and Nd3+- or Yb3+-centered NIR luminescence (η = ΦLLn/ΦLnLn = 67–75% and 76–85%) for complexes 5–6 and 12–13, arose from the ligands’ 3π–π* excited state, due to effective intramolecular energy transfer and multiple Ln3+-to-Ln3+ electron-communications. [ABSTRACT FROM AUTHOR]

Black phosphorene (BP)/carbon nanotube (CNT) heterostructures can be classified as either type I or II, depending on the size of the CNTs. An external electric field (Eext) can modulate the interfacial electronic structures and separate the electron and hole carriers of the BP/CNT heterostructures. The giant Stark effect is observed, and the band gap of the semiconducting heterostructures can vary several-fold. The intercalation of 3d transition metals can strongly bond BP and CNTs together. Furthermore, strong ferromagnetism with Curie temperature (TC) above room temperature is predicted. It is expected that these BP/CNT heterostructures will provide new opportunities and applications in the fields of optoelectronics and electronics as well as spintronics. [ABSTRACT FROM AUTHOR]

Knowledge of lectin and glycosidase specificities is fundamental to the study of glycobiology. The primary specificities of such molecules can be uncovered using well-established tools, but the complex details of their specificities are difficult to determine and describe. Here we present a language and algorithm for the analysis and description of glycan motifs with high complexity. The language uses human-readable notation and wildcards, modifiers, and logical operators to define motifs of nearly any complexity. By applying the syntax to the analysis of glycan-array data, we found that the lectin AAL had higher binding where fucose groups are displayed on separate branches. The lectin SNA showed gradations in binding based on the length of the extension displaying sialic acid and on characteristics of the opposing branches. A new algorithm to evaluate changes in lectin binding upon treatment with exoglycosidases identified the primary specificities and potential fine specificities of an α1- 2-fucosidase and an α2-3,6,8-neuraminidase. The fucosidase had significantly lower action where sialic acid neighbors the fucose, and the neuraminidase showed statistically lower action where α1-2 fucose neighbors the sialic acid or is on the opposing branch. The complex features identified here would have been inaccessible to analysis using previous methods. The new language and algorithms promise to facilitate the precise determination and description of lectin and glycosidase specificities. [ABSTRACT FROM AUTHOR]

Development of underwater superoleophobic surfaces has captured the imagination of researchers because of their applications; especially, oil manipulation based on such surfaces has attracted much attention. Here, we show a simple and effective way to fabricate an underwater transparent miniature "mechanical hand" based on controllable oil-adhesive patterned glass using a femtosecond laser. The underwater oil-adhesive force of the patterned glasses that compose the "mechanical hand" device can be controlled from ultralow to ultrahigh by adjusting the ratio of the untreated flat glass area to the laser-ablated rough area. These surfaces also showed favorable transparency in water. Various oils such as chloroform, hexadecane, n-dodecane, decane, liquid paraffin, and petroleum ether were tested, and their repellency against the as-prepared surfaces in water medium was confirmed. Moreover, the "mechanical hand" was used to implement oil transportation, fusion, and rapid capture, which can be applied in the construction of microfluidic devices, in situ detectors, and bioreactors. [ABSTRACT FROM AUTHOR]

Metal nanoclusters (NCs) as a new type of fluorescent material have been extensively explored because of their attractive set of features such as their ultrafine size, low toxicity, and excellent photostability. However, little progress has been made in producing water-soluble, homogeneous, and ultrabright metal NCs. In this study, gold NCs (AuNCs) with a photoluminescence quantum yield (QY) as high as 65% are synthesized in water through a simple blending route. Weak emission is observed from the 6-aza-2-thiothymine-protected AuNCs (ATT-AuNCs); however, the fluorescence intensity can be prominently enhanced by introducing l-arginine (Arg) into the capping layer. The fluorescence enhancement mechanism is systematically investigated by the measurements of ultraviolet-visible absorption spectroscopy, photoluminescence spectroscopy, fluorescence lifetime spectroscopy, transmission electron microscopy, dynamic light scattering, X-ray photoelectron spectroscopy, ¹H nuclear magnetic resonance, and calculations from density functional theory, with results isolating the vital role of the ligand shell and ruling out the effect of the gold core. The supramolecular host-guest assemblies formed between ATT capped on the gold core and the guanidine group of Arg make the capping ligands of ATT rigid. Subsequently, the intramolecular vibration and rotation of ATT are greatly suppressed, which reduce the nonradiative relaxation of excited states and, as a result, predominantly increase the luminescence QY of ATT-AuNCs. Further experiments demonstrate that a small change in guanidine substituents can arouse obvious changes in the photoluminescence features of NCs. We envision that this work will substantively contribute to the process of developing efficient synthetic routes to high-quality metal NCs. [ABSTRACT FROM AUTHOR]

Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity. Herein we report a nanoparticle-based photoimmunotherapy (nano-PIT) approach that addresses the need. Specifically, we exploit ferritin, a compact nanoparticle protein cage, as a photosensitizer carrier, and we conjugate to the surface of ferritin a FAP-specific single chain variable fragment (scFv). With photoirradiation, the enabled nano-PIT efficiently eliminates CAFs in tumors but causes little damage to healthy tissues due to the localized nature of the treatment. Interestingly, while not directly killing cancer cells, the nano-PIT caused efficient tumor suppression in tumor-bearing immunocompetent mice. Further investigations found that the nano-PIT led to suppressed C-X-C motif chemokine ligand 12 (CXCL12) secretion and extracellular matrix (ECM) deposition, both of which are regulated by CAFs in untreated tumors and mediate T cell exclusion that prevents physical contact between T cells and cancer cells. By selective killing of CAFs, the nano-PIT reversed the effect, leading to significantly enhanced T cell infiltration, followed by efficient tumor suppression. Our study suggests a new and safe CAF-targeted therapy and a novel strategy to modulate tumor microenvironment (TME) for enhanced immunity against cancer. [ABSTRACT FROM AUTHOR]

Capecitabine, an oral prodrug of 5-fluorouracil, inhibits DNA synthesis and has received FDA approval for treatment of metastatic colorectal and breast cancers. Hand-foot syndrome (HFS) is a serious dose-limiting toxicity and the most frequently reported side effect of capecitabine. Because of the lack of knowledge about the causative mechanism of HFS, scarce information is available for effective treatment or prevention. Data are based on published literatures and reports available from the HFS development program database. The purpose of this Review is to provide information regarding definition, clinical manifestation, and the possible mechanisms of HFS induced by capecitabine. Ethnic variations in the clinical presentation of HFS warrant further attention. Several physiological and pharmacological mechanisms have been investigated, such as cyclooxygenase (COX) inflammatory-type reaction, accumulation of capecitabine metabolites, and enzymes and transporters involved in the metabolism and absorption. Although current studies describe the possible mechanisms of HFS induced by capecitabine, much remains to be determined. It appears from this scientific evidence that additional study is needed to determine the effect of skin-mediated metabolism in the possible mechanism of HFS induced by capecitabine. [ABSTRACT FROM AUTHOR]

The first Pd-catalyzed multisite-selective acetoxylation reactions are disclosed at an unactivated alkene sp² C-H bond versus secondary allylic sp³ C-H bond in cyclic olefins via the modulation of directing groups. The different directing groups overcome the key challenge in differentiating C-H bonds and provide a new controlling approach for site-specific C-H activation. A wide variety of substrates are readily acetoxylated under operationally simple conditions. Mechanistic studies suggest that different Pd (IV) intermediates were involved in the multisite-selective acetoxylation reactions. [ABSTRACT FROM AUTHOR]

A visible-light-promoted, mild, and direct difunctionalization of alkynoates has been accomplished. This procedure provides a new strategy toward synthesis of the coumarin core structure by photoredox-mediated oxidation to generate the α-oxo radical, which supervenes a domino radical addition/cyclization reaction in moderate to good yields with high regioselectivity at ambient temperature. [ABSTRACT FROM AUTHOR]

Vanadium dioxide (VO2) is a compelling candidate for next-generation electronics beyond conventional silicon-based devices due to the exhibition of a sharp metal-insulator transition. In this study, in order to realize functional VO2 film for flexible electronics, the growth of VO2 film directly on a transparent and flexible muscovite via van der Waals epitaxy is established. The heteroepitaxy and structural transition of VO2 films on muscovite are examined by a combination of high-resolution X-ray diffraction, transmission electron microscopy, and Raman spectroscopy. The unique metal-insulator transition of VO2 is further revealed with a change in electrical resistance over 10³ and a more than 50% variation of optical transmittance. Furthermore, due to the nature of muscovite, the VO2/muscovite heterostructure possesses superior flexibility and optical transparence. The approach developed in this study paves an intriguing way to fabricate functional VO2 film for the applications in flexible electronics. [ABSTRACT FROM AUTHOR]