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The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHP plus , which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa . Furthermore, dHTSN1@pHP plus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHP plus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa -infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHP plus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa .

By using a nonadiabatic molecular dynamics method combined with the hierarchical equations of motion, we have investigated the nonequilibrium transient transport through a conjugated polymer chain. The polymer chain is described by the Su-Schrieffer-Heeger model, and its two ends are coupled with metal electrodes of different chemical potentials. In order to present the evolutions of the electronic injection and transport in the real-time domain, we have mainly discussed the dynamic relaxation processes of the excited states and transient transport currents. It is found that due to the existence of electron-phonon couplings in the conjugated polymers, creation of solitons not only affects the time of the system achieving the steady state but also leads to periodical oscillations of the steady-state transport currents with time in our simulations. Furthermore, with increasing applied bias voltage, the steady-state transport electronic current increases, which proved that the creation of the solitons can assist the electronic transport. These results have shown that the creation of the excited states is important in understanding the transport properties in organic nanostructures.

Optogenetics is a novel biotechnology widely used to precisely manipulate a specific peripheral sensory neuron or neural circuit. However, the use of optogenetics to assess the therapeutic efficacy of analgesics is elusive. In this study, we generated a transgenic mouse stain in which all primary somatosensory neurons can be optogenetically activated to mimic neuronal hyperactivation in the neuropathic pain state for the assessment of analgesic effects of drugs. A transgenic mouse was generated using the advillin-Cre line mated with the Ai32 strain, in which channelrhodopsin-2 fused to enhanced yellow fluorescence protein (ChR2-EYFP) was conditionally expressed in all types of primary somatosensory neurons (advillin cre /ChR2 +/+ ). Immunofluorescence and transdermal photostimulation on the hindpaws were used to verify the transgenic mice. Optical stimulation to evoke pain-like paw withdrawal latency was used to assess the analgesic effects of a series of drugs. Injury- and pain-related molecular biomarkers were investigated with immunohistofluorescence. We found that the expression of ChR2-EYFP was observed in many primary afferents of paw skin and sciatic nerves and in primary sensory neurons and laminae I and II of the spinal dorsal horns in advillin cre /ChR2 +/+ mice. Transdermal blue light stimulation of the transgenic mouse hindpaw evoked nocifensive paw withdrawal behavior. Treatment with gabapentin, some channel blockers, and local anesthetics, but not opioids or COX-1/2 inhibitors, prolonged the paw withdrawal latency in the transgenic mice. The analgesic effect of gabapentin was also verified by the decreased expression of injury- and pain-related molecular biomarkers. These optogenetic mice provide a promising model for assessing the therapeutic efficacy of analgesics in neuropathic pain., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Resonant Auger scattering (RAS) provides information on the core-valence electronic transition and impresses a rich fingerprint of the electronic structure and nuclear configuration at the time-initiating RAS process. Here, we suggest using a femtosecond X-ray pulse to trigger RAS in a distorted molecule, which is generated from the nuclear evolution on a valence excited state pumped by a femtosecond ultraviolet pulse. With the time delay varied, the amount of molecular distortion can be controlled and the RAS measurements imprint both their electronic structures and changing geometries. This strategy is showcased in H 2 O prepared in an O-H dissociative valence state, where molecular and fragment lines appear in RAS spectra as signatures of ultrafast dissociation. Given the generality of this approach for a broad class of molecules, this work opens a new alternative pump-probe technique for mapping the core and valence dynamics with ultrashort X-ray probe pulses.

On-chip light sources are an essential component of scalable photonic integrated circuits (PICs), and coupling between light sources and waveguides has attracted a great deal of attention. Photonic waveguides based on bound states in the continuum (BICs) allow optical confinement in a low-refractive-index waveguide on a high-refractive-index substrate and thus can be employed for constructing PICs. In this work, we experimentally demonstrated that the photoluminescence (PL) from a monolayer of tungsten sulfide (WS 2 ) could be coupled into a BIC waveguide on a lithium-niobate-on-insulator (LNOI) substrate. Using finite-difference time-domain simulations, we numerically obtained a coupling efficiency of ∼2.3% for an in-plane-oriented dipole and a near-zero loss at a wavelength of 620 nm. By breaking through the limits of 2D-material integration with conventional photonic architectures, our work offers a new perspective for light-matter coupling in monolithic PICs.

Mustard gas [sulfur mustard (SM)] and phosgene are the most frequently used chemical warfare agents (CWAs), which pose a serious threat to human health and national security, and their rapid and accurate detection is essential to respond to terrorist attacks and industrial accidents. Herein, we developed a fluorescent probe with o -hydroxythioketone as two sensing sites, AQso, which can detect and distinguish mustard gas and phosgene. The dual-sensing-site probe AQso reacts with mustard gas to form a cyclic product with high sensitivity [limit of detection (LOD) = 70 nM] and is highly selective to SM over phosgene, SM analogues, active alkylhalides, acylhalides, and nerve agent mimics, in ethanol solutions. When encountering phosgene, AQso rapidly converts to cyclic carbonate, which is sensitive (LOD = 14 nM) and highly selective. Their sensing mechanisms of AQso to mustard gas and phosgene were well demonstrated by separation and characterization of the sensing products. Furthermore, a facile test strip with the probe was prepared to distinguish 2-chloroethyl ethyl sulfide (CEES) and phosgene in the gas phase by different fluorescence colors and response rates. Not using the complicated instrument, the qualitative and quantitative detection of CEES or phosgene can be achieved only by measuring the red-green-blue (RGB) channel intensity of the test strip after being exposed to CEES or phosgene gas by the smartphone with an RGB color application.

The great development potential of polymer dielectric capacitors in harsh environments urgently requires enhancing capacitive performance at high temperatures. However, the exponentially increased conduction loss at high temperature and high field results in a drastic drop in energy density and charge-discharge efficiency. Here, a bilayer-structured polyimide (PI) composite film containing a wide-band gap inorganic layer as a charge blocking layer is designed. The inorganic layer improves the charge trapping ability and regulates the charge mobility at the electrode/dielectric interface. The charge injection mechanism in the interface-optimized PI/boron nitride nanosheet (BNNS) composite films is investigated by finite element simulation, and the effect of the BNNS layer on high temperature conduction is further understood. An appropriate thickness of the charge blocking layer establishes an effective energy barrier. Therefore, the composite films exhibit significantly suppressed conduction loss and excellent capacitive performance at a high temperature. A high energy density of 4.37 J cm -3 with efficiency of 92% is obtained at 200 °C and 500 MV m -1 , which is superior to reported high-temperature dielectric polymers and their composite films. This work provides a promising approach to improve the energy storage performance of polymer materials at high temperatures.

Single photon emitters (SPEs) are critical components of photon-based quantum technology. Recently, the interaction between surface plasmons and emitters has attracted increasing attention because of its potential to improve the quality of single-photon sources through stronger light-matter interactions. In this work, we use a hybrid plasmonic probe composed of a fiber taper and silver nanowire to controllably modulate the radiation properties of SPEs with differently oriented polarization. For out-of-plane oriented SPEs such as single CdSe quantum dots, the radiation lifetime could be reduced by a factor as large as seven; for in-plane oriented SPEs such as hBN defect SPEs, the average modulation amplitude varied from 0.69 to 1.23, depending on the position of the probe. The experimental results were highly consistent with the simulations and theory. This work provides an efficient approach for optimizing the properties of SPEs for quantum photonic integration.

A simple and efficient protocol was developed for the preparation of challenging α-aryl primary amides. This metal-free coupling process was triggered by TfOH-promoted electrophilic activation of α-silyl nitrile to generate keteniminium ion species, followed by reaction with aryl sulfoxide through [3,3]-sigmatrophic rearrangement to provide the target product. To the best of our knowledge, α-silyl nitrile has been rarely used as a pro-electrophilic reagent. Computational investigations confirmed the transient existence of a highly electrophilic keteniminium intermediate.

A practical and eco-friendly strategy for the radical-mediated decarboxylative [3 + 2] and [4 + 2] annulation of enynals and γ,σ-unsaturated N -(acyloxy)phthalimides through the photoactivation of an electron donor-acceptor (EDA) complex has been developed. A wide range of primary, secondary, and tertiary alkyl N -hydroxyphthalimide (NHP) esters can be used as suitable substrates for the synthesis of fused ketones without any transition-metal catalysts or oxidants. This protocol features a broad substrate scope, excellent selectivity, and clean reaction conditions.

Methionine sulfoxide reductases (Msrs) play essential roles in maintaining mitochondrial function and are recognized as potential therapeutic targets. However, current probes for Msrs fail to target mitochondria and exhibit a relatively slow response and limited sensitivity. Here we develop a novel turn-on fluorescence probe that facilitates imaging of mitochondrial Msrs in living cells. The probe is constructed by conjugating a methyl phenyl sulfoxide, a mimic Msrs substrate, to an electron-withdrawing hydrophobic cation, methylpyridinium. The probe of acceptor-acceptor structure is initially nonemissive. Msrs catalyzed reduction of sulfoxide to sulfide generated a fluorophore of distinct donor-acceptor structure. The probe is demonstrated to exhibit high sensitivity, fast response, and high selectivity toward MsrA in vitro. Furthermore, the probe is successfully introduced to detect and image Msrs in living cells with excellent mitochondrial-targeting capability. Moreover, the probe also reveals decreased Msrs activity in a cellular Parkinson's disease model. Our probe affords a powerful tool for detecting and visualizing mitochondrial Msrs in living cells.

Food contamination by toxic mycotoxins not only causes a considerable loss in economy, but importantly poses a huge threat to human health through accidental ingestion. Hence, it is an ongoing and imperative need to develop a convenient, cost-effective method for the detection of the mycotoxin-infected agricultural commodities. To this end, we herein fabricated a novel metal-organic framework-derived composite material that displays a strong solid-state emission in the visible region, by attaching a frequently used fluorescent label, fluorescein isothiocyanate (FITC), via guest adsorption. Significantly, owing to the inherent pH-responsive conformational changes of FITC, the resulting composite material provides, to the best of our knowledge, the first example of the sensitive and selective fluorescence sensing toward 3-nitropropionic acid, which, as a major naturally occurring mycotoxin in moldy sugarcane, has been closely linked to poisoning episodes in human beings and animals.

Mitochondrial vicinal dithiol-containing proteins (VDPs) are key regulators in cellular redox homeostasis and useful markers for diagnostics of redox-dependent diseases. Current probes fail to target mitochondrial VDPs and show limited sensitivity and response rate. We develop a novel fluorescent probe using an engineered benzoxadiazole fluorophore that allows selective targeting of mitochondria and exhibits highly sensitive environment responsiveness. This probe is almost nonfluorescent in aqueous media, while delivering intense fluorescence upon binding to VDPs via a cyclic dithiaarsane ligand. The fluorescence probe is shown to have rapid response within 30 s and high sensitivity for detecting reduced bovine serum albumin (rBSA) in the concentration range from 0 to 0.1 μM with a detection limit of 2 nM. To our knowledge, this is the first fluorescence probe for VDPs which exhibits deep red emission, instantaneous response, high turn-on fluorescence ratio, and specific mitochondrial localization. It may provide a new tool for in situ monitoring mitochondrial VDPs.

Water instability is a crucial limiting factor in the practical application of most fluorescent metal-organic frameworks (MOFs). Here, by introducing a fascinating double-helical structure generated through dense stacking of organic ligands, a water-stable fluorescence MOF has been synthesized, namely, [Cd2(tib)2(bda)2]·(solvent)n (1) [tib =1,3,5-tris(1-imidazolyl) benzene; H2bda = 2,2'-biphenyl dicarboxylic acid]. This helical structure helps to enhance the stability of 1 against common organic solvents and water, even acid/base aqueous solutions with a pH value ranging from 3 to 11. Furthermore, this material can be a potential fluorescent sensor for ketones.

Despite numerous applications, the cellular-clearance mechanism of multiwalled carbon nanotubes (MWCNTs) has not been clearly established yet. Previous in vitro studies showed the ability of oxidative enzymes to induce nanotube degradation. Interestingly, these enzymes have the common capacity to produce reactive oxygen species (ROS). Here, we combined material and life science approaches for revealing an intracellular way taken by macrophages to degrade carbon nanotubes. We report the in situ monitoring of ROS-mediated MWCNT degradation by liquid-cell transmission electron microscopy. Two degradation mechanisms induced by hydroxyl radicals were extracted from these unseen dynamic nanoscale investigations: a non-site-specific thinning process of the walls and a site-specific transversal drilling process on pre-existing defects of nanotubes. Remarkably, similar ROS-induced structural injuries were observed on MWCNTs after aging into macrophages from 1 to 7 days. Beside unraveling oxidative transformations of MWCNT structure, we elucidated an important, albeit not exclusive, biological pathway for MWCNT degradation in macrophages, involving NOX2 complex activation, superoxide production, and hydroxyl radical attack, which highlights the critical role of oxidative stress in cellular processing of MWCNTs.

Biofouling is of great concern in numerous applications ranging from ophthalmological implants to catheters, and from bioseparation to biosensors. In this report, a general and facile strategy to combat surface fouling is developed by grafting of amino acids onto polymer substrates to form zwitterionic structure through amino groups induced epoxy ring opening click reaction. First of all, a library of poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) hydrogels with zwitterionic surfaces were prepared, resulting in the formation of pairs of carboxyl anions and protonated secondary amino cations. The analysis of attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the successful immobilization of amino acids on the hydrogel surfaces. After that, the contact angle and equilibrium water content of the modified hydrogels showed that the hydrogels exhibited improved hydrophilicity compared with the parent hydrogel. Furthermore, the protein deposition was evaluated by bicinchoninic acid assay using bovine serum albumin (BSA) and lysozyme as models. The results indicated that the performance of the hydrogels was determined by the nature of incorporated amino acid: the hydrogels incorporated with neutral amino acids had nonspecific antiadsorption capability to both BSA and lysozyme; the hydrogels incorporated with charged amino acids showed antiadsorption behaviors against protein with same charge and enhanced adsorption to the protein with opposite charge; the optimal antiadsorption performance was observed on the hydrogels incorporated with polar amino acids with a hydroxyl residual. The improvement of antiprotein fouling of the neutral amino acids grafted hydrogels can be ascribed to the formation of zwitterionic surfaces. Finally, a couple of soft contact lenses grafted with amino acids were fabricated having improved antifouling property and hydrophilicity. The result demonstrated the success of amino acids based zwitterionic antifouling strategy in ophthalmology. This strategy is also applicable to substrates including filtration membranes, microspheres and nanofibers as well. It is a versatile method for amino acids grafting onto polymer substrates to construct zwitterionic surfaces and achieve antifouling properties.

In recent years, free-electron lasers operating in the true X-ray regime have opened up access to the femtosecond-scale dynamics induced by deep inner-shell ionization. We have investigated charge creation and transfer dynamics in the context of molecular Coulomb explosion of a single molecule, exposed to sequential deep inner-shell ionization within an ultrashort (10 fs) X-ray pulse. The target molecule was CH3I, methane sensitized to X-rays by halogenization with a heavy element, iodine. Time-of-flight ion spectroscopy and coincident ion analysis was employed to investigate, via the properties of the atomic fragments, single-molecule charge states of up to +22. Experimental findings have been compared with a parametric model of simultaneous Coulomb explosion and charge transfer in the molecule. The study demonstrates that including realistic charge dynamics is imperative when molecular Coulomb explosion experiments using short-pulse facilities are performed.

This article reports a novel scalable method to prepare ultrathin and uniform Pd@Pt nanowires (NWs) with controllable composition and shell thickness, high aspect ratio, and smooth surface, triggered by bromide ions via a galvanic replacement reaction between PtCl6(2-) and Pd NWs. It was found that bromide ions played a vital role in initiating and promoting the galvanic reaction. The bromide ions served as capping and oxidized etching agents, counterbalancing the Pt deposition and Pd etching on the surface to give final Pd@Pt core-shell nanostructures. Such a counterbalance and the formation PtBr6(2-) with lower redox potential could lower the reaction rate and be responsible for full coverage of a smooth Pt shell. The full coverage of Pt deposited on Pd NWs is important for the enhancement of the activity and stability, which depend strongly on the Pt content and Pt shell thickness. Significantly, the Pd@Pt NWs with Pt content of 21.2% (atomic ratio) exhibited the highest mass activity (810 mA mg(-1)(Pt)) and specific activity (0.4 mA cm(-2)). Interestingly, the mass activity (1560 mA mg(-1)(Pt)) and specific activity (0.98 mA cm(-2)) of Pd@Pt (21.2%) NWs increased to 2.45 and 1.95 times the initial values after 60k cycles tests, 8.5 and 9.0 times greater than those of Pt/C catalysts. In addition, these ultrathin NW electrocatalysts with large aspect ratio are easy to form into a freestanding film, which improves the mass transport, electrical conductivity, and structure stability.

Due to strong electron correlation effects and electron coupling with nuclear motion, the molecular inner-valence photoionization is still a challenge in electron spectroscopy, resulting in several interesting phenomena such as drastic changes of angular dependencies, spin-orbit induced predissociation, and complex interplay between adiabatic and nonadiabatic transitions. We investigated the excited electronic states of HCl(+) in the binding energy range 27.5-30.5 eV using synchrotron radiation based high-resolution inner-valence photoelectron spectroscopy with angular resolution and interpreted the observations with the help of ab initio calculations. Overlapping electronic states in this region were disentangled through the analysis of photoelectron emission anisotropies. For instance, a puzzling transition, which does not seem to obey either an adiabatic or a nonadiabatic picture, has been identified at ∼28.6 eV binding energy. By this study, we show that ultrahigh-resolution photoelectron spectroscopy with angular selectivity represents a powerful tool to probe the highly excited ionic molecular electronic states and their intricate couplings.

An ionic liquid (IL)-based one-step micellar extraction procedure was developed for the extraction of multiclass polar analytes (protocatechuic acid, chlorogenic acid, epicatechin, hyperoside, isoquercitrin, quercetin) from hawthorn fruits and their determination using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Compared to conventional organic solvent extractions, this newly proposed method was much easier, more sensitive, environmentally friendly, and effective as well. Several important parameters influencing the micellar extraction efficiency are discussed, such as selection of ILs, surfactant concentration, and extraction time. Under the optimal conditions, good linearity was achieved for each analyte with correlation coefficients (r(2)) ranging from 0.9934 to 0.9999, and the recovery values ranged from 89.3 to 106% with relative standard deviations lower than 5.5%. Results suggest that the IL-based one-step micellar extraction could be an alternative and promising means in future food analysis.

We report a solution-based synthesis of monodispersed Cu(2)CdSnSe(4) nanocrystals and a study on the thermoelectric properties of these wide-band-gap dense materials compacted from nanocrystals for the first time. With the help of copper dopants and selenium vacancies generated during wet-chemistry synthesis, a large increment in the power factor is observed, and the dimensionless figure-of-merit ZT reaches a peak value of 0.65 at 450 °C.

Combining the one-dimensional tight-binding Su-Schrieffer-Heeger (SSH) model and the extended Hubbard model (EHM), the scattering and combination of oppositely charged bipolarons in conjugated polymers are investigated using a nonadiabatic evolution method. On the basis of this physical picture, bipolarons can scatter into a singlet biexcitonic state, in which two electrons and two holes are trapped together by a lattice distortion. This biexcitonic state can emit one photon to an exciton state, which can subsequently decay to the ground state. The results indicate that the scattering and combination of oppositely charged bipolarons may provide guidance for improving the internal quantum efficiency for electroluminescence to as high as 75% in polymer light-emitting diodes.

8-Prenylnaringenin (8PN), which presents in hop, enjoys fame as the most potential phytoestrogen. Although a number of health effects are attributed to 8PN, few reports are available about the production of it. In this work, screening of fungi to efficiently transform isoxanthohumol (IXN) into 8PN was designed. The biotransformation of IXN was significantly observed in Eupenicillium javanicum, Cunninghamella blakesleana, and Ceriporiopsis subvermispora under five kinds of transformation conditions. As a comparative result of IXN transformation, E. javanicum was the optimal biocatalyst to produce 8PN. Transformation caused by growing precultured fungal mycelia, a process designated as G2, was a favorable condition for IXN transformation in view of the yield of 8PN. The possible transformation pathway of 8PN bioproduction is postulated in this work. The construction of fungus and transformation mode derived from the current work is viable and an alternative procedure for 8PN formation.

Combining the one-dimensional tight-binding Su-Schrieffer-Heeger (SSH) model and the extended Hubbard model (EHM), we analyze the scattering and combination in conjugated polymers of two polarons with the same charges and parallel or antiparallel spins using a nonadiabatic evolution method. Results show that collisions between the two same charge polarons with parallel spin are essentially elastic due to strong Pauli repulsion, whereas the two same charge polarons with antiparallel spins can combine into a singlet bipolaronic state. The dynamics of bipolarons on two coupled polymer chains and at the interface of a polymer/polymer heterojunction are discussed in detail. This knowledge will serve to understand the dynamics of the system when many polarons are created in the system, e.g., by electroluminescence.

The origin of the rare and highly strong phosphorescent (PL) and electroluminescent (EL) Ir(III) complexes with C--N=N ligand, tris[3,6-bis(phenyl)pyridazinato-N(1),C(2)]iridium (Ir(BPPya)(3)) (1), tris[1,4-bis(phenyl)phthalazine]iridium (Ir(BPPa)(3)) (2), and tris[1-(2,6-dimethylphenoxy)-4-(4-chlorophenyl)phthalazine]iridium ((Ir(MPCPPZ)(3)) (3) are investigated theoretically. By changing the conjugation length of the C--N=N ligand from BPPya to BPPa, one can tune the emission color from green in 1 to saturated red in 2. The addition of sterically bulky phenolic substituents in 3 exhibits the highest external quantum efficiency of 20.2% ph el(-1) and luminescence efficiency of 18.4 cd A(-1). Density functional theory (DFT) and time-dependent DFT (TDDFT) methods are used to rationalize these properties. The more promising PL and EL properties of 3 result from the bulky phenolic group, which acts as a pendant at the periphery of the emitting core and protects the emitting core from the hazardous intermolecular interaction of emitters and reduces luminescence quenching.

An analytical form connecting the energy shift of Raman modes directly to the bonding identities (order, nature, length, energy) of a specimen and the response of the bonding identities to the applied stimuli of temperature and pressure was presented for a deeper understanding of the atomistic origin of the ZnO Raman shift. Theoretical reproduction based on the BOLS correlation theory [Sun, C. Q. Prog. Solid State Chem. 2007, 35, 1] and the local bond average (LBA) approach [Sun, C. Q. Prog. Mater. Sci. 2009, 54, 179] of the measurements revealed that the thermally softened ZnO Raman modes arise from bond expansion and bond weakening due to vibration and that the pressure-stiffened Raman modes result from bond compression and bond strengthening due to mechanical work hardening. The developed approach could be useful in generalizing the lattice dynamics directly to the process of vibration and relaxation of a representative bond of the specimen under external stimuli.

Nanoporous thin films fabricated by both a core-shell-shaped organic-inorganic hybrid sphere (octa(2,4-dinitrophenyl)silsesquioxane, ODNPSQ) and a four-leg-numbered surfactant (polyoxyethylene sorbitan monolaurate, Tween-20) for porogens in a higher molecular weight precursor (polyphenylsilsesquioxane, PPSQ) were characterized, respectively, by grazing incidence small-angle X-ray scattering (GISAXS), and the measured 2D GISAXS profiles were analyzed quantitatively by using a GISAXS formula based on the distorted wave Born approximation (DWBA). The fitted 2D GISAXS data show that the PPSQ porous thin films imprinted with ODNPSQ porogen exhibit sphere-shaped closed pores with the average pore size within a range of 1.18-3.12 nm and pore size distribution widths about 3.0 nm when the porogen loadings increase from 10 to 40 wt % and those imprinted with Tween-20 porogen give out an average pore size of 1.07-1.29 nm and pore size distribution widths about 2.0 nm with the porogen loading varying from 5 to 30 wt %. The nanoporous dielectric thin films imprinted with ODNPSQ porogen show a reducing to the molecular aggregation of porogens and significant antiphase separation behavior in the cross-linked matrix.

Quantum-chemistry methods were explored to investigate the electronic structures, injection and transport properties, absorption and phosphorescence mechanism of a series of blue-emitting Ir(III) complexes {[(F(2)-ppy)(2)Ir(pta -X/pyN4)], where F(2)-ppy = (2,4-difluoro)phenylpyridine; pta = pyridine-1,2,4-triazole; X = phenyl(1); p-tolyl (2); 2,6-difluororophenyl (3); -CF(3) (4), and pyN4 = pyridine-1,2,4-tetrazolate (5)}, which are used as emitters in organic light-emitting diodes (OLEDs). The mobility of hole and electron were studied computationally based on the Marcus theory. Calculations of Ionization potentials (IPs) and electron affinities (EAs) were used to evaluate the injection abilities of holes and electrons into these complexes. The reasons for the lower EL efficiency and phosphorescence quantum yields in 3-5 than in 1and 2 have been investigated. These new structure-property relationships can guide an improved design and optimization of OLED devices based on blue-emitting phosphorescent Ir(III) complexes.

The pyridyl-lead complexes [Pb(m)-C5H4N](-) (m = 1-4), which are produced from the reactions between lead clusters formed by laser ablation and the pyridine molecules seeded in argon carrier gas, are studied by photoelectron (PE) spectra and density functional theory. The adiabatic electron affinity (EA) of [Pb(m)C5H4N](-) is obtained from PE spectra at photon energies of 308 and 193 nm. Theoretical calculation is carried out to elucidate their structures and bonding modes. A variety of geometries for the isomers are optimized to search for the lowest-energy geometry. By comparing the theoretical results, including the EA and simulated density of state spectra, with the experimental determination, the lowest-energy structures for each species are obtained. The following analysis of the molecular orbital composition provides the evidence that the pyridyl binds on lead clusters through the Pb-C sigma bond. Moreover, there is an apparent spin-state transition from triplet state toward singlet state for the ground-state structure of [Pb(m)C5H4N](-) with an increase of lead cluster.

The electronic and magnetic properties of CaCu3Cr4O12 and CaCu3Cr2Sb2O12 are investigated by the use of the full-potential linearized augumented plane wave (FPLAPW) method. The calculated results indicate that CaCu3Cr4O12 is a ferrimagnetic and half-metallic compound, in good agreement with previous theoretical studies. CaCu3Cr2Sb2O12 is a ferrimagnetic semiconductor with a small gap of 0.136 eV. In both compounds, because Cr4+ 3d (d2) and Cr3+ 3d (d3) orbitals are less than half filled, the coupling between Cr-Cu is antiferromagnetic, whereas that between Cu-Cu and Cr-Cr is ferromagnetic. The total net spin moment is 5.0 and 3.0 microB for CaCu3Cr4O12 and CaCu3Cr2Sb2O12, respectively. In CaCu3Cr4O12, the 3d electrons of Cr4+ are delocalized, which strengthens the Cr-Cr ferromagnetic coupling. For CaCu3Cr2Sb2O12, the doping of nonmagnetic ion Sb5+ reduces the Cr-Cr ferromagnetic coupling, and the half-filled Cr3+ t2g (t2g3) makes the chromium 3d electrons localized. In addition, the ordering arrangement of the octahedral chromium and antimony ions also prevents the delocalization of electrons. Hence, CaCu3Cr2Sb2O12 shows insulating behavior, in agreement with the experimental observation.

The important intermediate phenyl-copper metal complexes [C(6)H(5)Cu(m)]- (m = 1-3), which are produced from the reactions between copper metal clusters formed by laser ablation and the benzene molecules seeded in argon carrier gas, are studied by photoelectron spectroscopy(PES) and density functional theory (DFT). Their structures and bonding patterns are investigated, which results in the conclusion that C(6)H(5) groups bond perpendicularly on copper clusters through Cu-C sigma bond. The formation mechanism of these complexes has been studied at B3LYP//6-311G(d, p)/Lanl2dz level. Direct insertion reaction between [Cu(m)]- and C(6)H(6) yields intermediate complex [C(6)H(5)Cu(m)H]-, and then eliminates the H atom, or releases the H atom to other neutral Cu atoms or anionic Cu ions via H abstraction reaction. The first step is the rate-limiting step with C-H activation and cleavage, and H abstraction by neutral Cu atom is the most energetically favorable pathway for the final step. Moreover, the complex [C(6)H(5)Cu(2)]- is ascertained to be easier to be generated than [C(6)H(5)Cu(3)]- and [C(6)H(5)Cu]-, which are in excellent agreement with the experimental results.

The influence of the Mn-O-Mn bond angle on the magnetic and electronic properties of YBaMn(2)O(5) was studied by density functional theory, which was implemented in the CASTEP code. In practical calculation, both G- and A-type antiferromagnetic (AFM) orderings were considered. The calculated results indicated that G-type is more stable than A-type, in agreement with both experiment and previous theoretical study. It is also interesting to note that a transition from G-type to A-type at an Mn-O-Mn angle of ca. 170 degrees was found upon increasing Mn-O-Mn angle. Therefore, the calculation suggested that what is essential to stabilize the G-type AFM state is the reduction of the Mn-O-Mn bond angle. For both magnetic orderings, the compound changes from semiconductor to metal with the increase of Mn-O-Mn angle.

Further structure-activity relationship studies of a series of substituted uracils at the 1, 3, and 5 positions resulted in the discovery of several potent antagonists of the human gonadotropin-releasing hormone receptor. Uracils bearing a side chain derived from phenylglycinol at the 3-position were shown to be orally bioavailable in monkeys. 3-[(2R)-Amino-2-phenylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)-6-methylpyrimidin-2,4-dione (R-13b, NBI 42902) displayed subnanomolar binding affinity (K(i) = 0.56 nM) and was a potent functional antagonist (IC(50) = 3.0 nM in Ca(2+) flux assay) at the human GnRH receptor. It also bound to the monkey GnRH receptor with high affinity (K(i) = 3.9 nM). In addition, R-13bhad good plasma exposure in cynomolgus monkeys after oral administration, with a C(max) of 737 ng/mL and an AUC of 2392 ng/mL.h at a 10 mg/kg dose. Moreover, oral administration of R-13b to castrated male cynomolgus monkeys resulted in a significant decrease in serum levels of luteinizing hormone. These results demonstrate that compounds from this series of uracils are potent GnRH antagonists with good oral bioavailability and efficacy in nonhuman primates.

We have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF(1) receptor. Moreover, the hydrophilic and weakly basic pyridine moiety increased the water solubility of some analogues. Compound 26 h exhibited good binding affinity at the human CRF(1) receptor with a K(i) value of 3.5 nM. As a functional antagonist, it dose-dependently inhibited CRF-stimulated cAMP production in cells expressing the CRF(1) receptor (IC(50) = 50 nM), and CRF-stimulated ACTH release from cultured rat pituitary cells (IC(50) = 20 nM). 26 h had a log P value of 4.9 and water solubility of greater than 10 mg/mL. Pharmacokinetic studies in rats showed that 26 h was orally bioavailable and able to penetrate into the brain. 26 h has been demonstrated in vivo efficacy in animal behavioral models that measure anxiolytic activity. These results suggest that analogues from this series were potent CRF(1) receptor antagonists with proper physicochemical properties and good pharmacokinetic profiles. 26 h was developed into a clinical compound and exhibited efficacy in patients with major depression.

Maternal fish consumption brings both risks and benefits to the fetus from the standpoint of methylmercury (MeHg) and n-3 PUFA (polyunsaturated fatty acids). MeHg is one of the most risky substances to come through fish consumption, and mercury concentrations in red blood cells (RBC-Hg) are the best biomarker of MeHg exposure. Docosahexaenoic acid (DHA, C22:6n-3), which is one of the most important fatty acids for normal brain development and function, is also derived from fish consumption. Our objective in this study was to examine the relationships between RBC-Hg and plasma fatty acid composition in mother and fetus at parturition. Venous blood samples were collected from 63 pairs of mothers and fetuses (umbilical cord blood) at delivery. In all cases, fetal RBC-Hg levels were higher than maternal RBC-Hg levels. The geometric mean of fetal RBC-Hg was 13.4 ng/g, which was significantly (p < 0.01) higher than that of maternal RBC-Hg (8.41 ng/g). While the average fetal/maternal RBC-Hg ratio was 1.6, the individual ratios varied from 1.08 to 2.19, suggesting considerable individual differences in MeHg concentrations between maternal and fetal circulations at delivery. A significant correlation was observed between maternal and fetal DHA concentrations (r = 0.37, p < 0.01). Further, a significant correlation was observed between RBC-Hg and plasma DHA in fetus (r = 0.35, p < 0.01). These results confirm that both MeHg and DHA which originated from fish consumption transferred from maternal to fetal circulation and existed in the fetal circulation with a positive correlation. Pregnant women in particular need not give up eating fish to obtain such benefits. However, they would do well to at least consume smaller fish, which contain less MeHg, thereby balancing the risks and benefits from fish comsumption.

CC chemokine receptor 7 (CCR-7) is expressed on mature dendritic cells and T-cells. Its ligands, CCL-19 (MIP-3beta) and CCL-21 (SLC), play an important role in the migration of these cells to secondary lymphoid organs where they are predominantly expressed. For most chemokines, the N-terminal domain preceding the first two conserved cysteines is involved in stabilizing the active conformation of its cognate receptors. We have chemically synthesized N-terminal analogues of CCL-19 with the aid of a native chemical ligation method to investigate structure function requirements of this ligand domain by performing ligand binding, GTP-gammaS binding, and chemotaxis assays. Successive truncations of the N-terminus of CCL-19 reduced the affinity of the receptor for the ligand in a size-dependent manner. Furthermore, Ala substitutions of Asn(3), Asp(4), and Asp(7) show that the side chains of these residues are important for high-affinity binding of CCL-19 to CCR-7. The effects observed were mirrored in both GTP-gammaS binding and chemotaxis assays, highlighting the functional importance of this ligand domain. We also describe two partial agonists of CCR-7 ([Nle(72)]CCL-19(6-77) and Ac-[Nle(72)]CCL-19(7-77)), and identify the first analogue of CCL-19 (Ac-[Nle(72)]CCL-19(8-77)) that acts as a functional antagonist in vitro (K(B) approximately 350 nM for GTP-gammaS binding assays). As mutations of both Glu(6) and Asp(7) to Ala did not dissociate effects on ligand binding from receptor activation, it is likely that the backbone of these two residues is crucial for agonist activity.

Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (>100 nM), this large pool of IGF is biologically inactive because of its association with six distinct binding proteins, which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants, which bind to IGFBPs but not the IGF-I receptor, have been shown to be potent IGF/IGFBP inhibitors, small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by 1 and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.