RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury.

Acute lung injury (ALI) is characterised by severe pulmonary inflammation, alveolar-capillary barrier disruption, and pulmonary oedema. Therefore, establishing effective therapeutic targets for ALI prevention is crucial. The present study reports a novel function of RNF128 in regulating LPS-induced ALI. Severe lung damage and increased immune cell infiltration were detected in RNF128-deficient mice. In vitro experiments revealed that RNF128 inhibits neutrophil activation by binding to myeloperoxidase (MPO) and reducing its levels and activity. Moreover, RNF128 regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-κB activation, hence decreasing pro-inflammatory cytokines. Our results demonstrate for the first time that RNF128 is a negative regulator of MPO and TLR4 in neutrophils and alveolar macrophages, respectively. However, AAV9-mediated RNF128 overexpression alleviated lung tissue damage and reduced inflammatory cell infiltration. Thus, RNF128 is a promising therapeutic candidate for pharmacological interventions in ALI.

Surface modifications of eight-electron palladium silver superatomic alloys.

Atomically precise thiolate-protected coinage metal nanoclusters and their alloys are far more numerous than their selenium congeners, the synthesis of which remains extremely challenging. Herein, we report the synthesis of a series of atomically defined dithiophosph(in)ate protected eight-electron superatomic palladium silver nanoalloys [PdAg20{S2PR2}12], 2a-c (where R = OiPr, a; OiBu, b; Ph, c) via ligand exchange and/or co-reduction methods. The ligand exchange reaction on [PdAg20{S2P(OnPr)2}12], 1, with [NH4{Se2PR2}12] (where R = OiPr, or OnPr) leads to the formation of [PdAg20{Se2P(OiPr)2}12] (3) and [PdAg20{Se2P(OnPr)2}12] (4), respectively. Solid state structures of 2a, 2b, 3 and 4 unravel different PdAg20 metal frameworks from their parent cluster, originating from the different distributions of the eight-capping silver(I) atoms around a Pd@Ag12 centered icosahedron with C2, D3, Th and Th symmetries, respectively. Surprisingly ambient temperature crystallization of the reaction product 3 obtained by the ligand exchange reaction on 1 has resulted in the co-crystallization of two isomers in the unit cell with overall T (3a) and C3 (3b) symmetries, respectively. To our knowledge, this is the first ever characterized isomeric pair among the selenolate-protected NCs. Density functional theory (DFT) studies further rationalize the preferred geometrical isomerism of the PdAg20 core.

Electron work function: an indicative parameter towards a novel material design methodology.

Electron work function (EWF) has demonstrated its great promise in materials analysis and design, particularly for single-phase materials, e.g., solute selection for optimal solid-solution strengthening. Such promise is attributed to the correlation of EWF with the atomic bonding and stability, which largely determines material properties. However, engineering materials generally consist of multiple phases. Whether or not the overall EWF of a complex multi-phase material can reflect its properties is unclear. Through investigation on the relationships among EWF, microstructure, mechanical and electrochemical properties of low-carbon steel samples with two-level microstructural inhomogeneity, we demonstrate that the overall EWF does carry the information on integrated electron behavior and overall properties of multiphase alloys. This study makes it achievable to develop "electronic metallurgy"-an electronic based novel alternative methodology for materials design.

Forecasting Air Quality in Taiwan by Using Machine Learning.

This study proposes a gradient-boosting-based machine learning approach for predicting the PM2.5 concentration in Taiwan. The proposed mechanism is evaluated on a large-scale database built by the Environmental Protection Administration, and Central Weather Bureau, Taiwan, which includes data from 77 air monitoring stations and 580 weather stations performing hourly measurements over 1 year. By learning from past records of PM2.5 and neighboring weather stations' climatic information, the forecasting model works well for 24-h prediction at most air stations. This study also investigates the geographical and meteorological divergence for the forecasting results of seven regional monitoring areas. We also compare the prediction performance between Taiwan, Taipei, and London; analyze the impact of industrial pollution; and propose an enhanced version of the prediction model to improve the prediction accuracy. The results indicate that Taipei and London have similar prediction results because these two cities have similar topography (basin) and are financial centers without domestic pollution sources. The results also suggest that after considering industrial impacts by incorporating additional features from the Taichung and Thong-Siau power plants, the proposed method achieves significant improvement in the coefficient of determination (R2) from 0.58 to 0.71. Moreover, for Taichung City the root-mean-square error decreases from 8.56 for the conventional approach to 7.06 for the proposed method.

Spherical Composite Powder by Coupling Polymethyl Methacrylate and Boron Nitride via Spray Drying for Cosmetic Application.

In the present study, spherical composite powder was successfully prepared via spray drying process using polymethyl methacrylate (PMMA) and hexagonal boron nitride (h-BN) powders. The pristine and as-prepared composite powders were examined using scanning electron microscopy, a particle size analyzer, oil absorption, and specific surface area analyses. These powders were then mixed with linseed oil to prepare samples for UV-Visible-Near Infrared spectroscopy investigation to determine their light absorption ability. Blank and powder-added blemish balm creams were examined using a sun protection factor tester and a thermal conductivity tester. In addition, transmittances of these creams were also evaluated. The experimental results show that spray-dried spherical composite powder exhibited good oil absorption ability. The blemish balm cream with 10 wt.% spray-dried composite powder not only exhibited superior sunscreen protection ability, but also good thermal conductivity.

RTN and Annealing Related to Stress and Temperature in FIND RRAM Array.

In this work, an observation on random telegraph noise (RTN) signal in the read current of a FinFET dielectric RRAM (FIND RRAM) device is presented. The RTN signal of a FIND RRAM cell is found to change after the device being subjected to cycling stress. After undergoing cycling stress, RRAM cells have a stronger tendency to show more frequent and intense RTN signals. The increase of noise levels in FIND RRAM cells can be alleviated generally by high temperature anneal, and with this concept, an on chip annealing scheme is proposed and demonstrated.

The application of convergent beam electron diffraction (CBED) analysis on transformation-induced plasticity (TRIP) steels.

Convergent beam electron diffraction (CBED) in transmission electron microscopy (TEM) was applied to determine local carbon concentrations in low-carbon transformation-induced plasticity (TRIP) steels. High-order Laue-zone (HOLZ) lines were experimentally obtained for comparison with simulation results. A new procedure for calculating carbon content is thus proposed. Retained austenite (RA) is classified into three types by morphology; the relationship between the carbon content and the corresponding RA morphology is discussed based on CBED results. Furthermore, results of X-Ray diffractometry measurements are also used for comparison.

Incomplete inhibition of HIV infection results in more HIV infected lymph node cells by reducing cell death.

HIV has been reported to be cytotoxic in vitro and in lymph node infection models. Using a computational approach, we found that partial inhibition of transmissions of multiple virions per cell could lead to increased numbers of live infected cells. If the number of viral DNA copies remains above one after inhibition, then eliminating the surplus viral copies reduces cell death. Using a cell line, we observed increased numbers of live infected cells when infection was partially inhibited with the antiretroviral efavirenz or neutralizing antibody. We then used efavirenz at concentrations reported in lymph nodes to inhibit lymph node infection by partially resistant HIV mutants. We observed more live infected lymph node cells, but with fewer HIV DNA copies per cell, relative to no drug. Hence, counterintuitively, limited attenuation of HIV transmission per cell may increase live infected cell numbers in environments where the force of infection is high.

Chlorophyll-Inspired Red-Region Fluorophores: Building Block Synthesis and Studies in Aqueous Media.

Fluorophores that absorb and emit in the red spectral region (600-700 nm) are of great interest in photochemistry and photomedicine. Eight new target chlorins (and 19 new chlorins altogether)-analogues of chlorophyll-of different polarities have been designed and synthesized for various applications; seven of the chlorins are equipped with a bioconjugatable tether. Hydrophobic or amphiphilic chlorins in a non-polar organic solvent (toluene), polar organic solvent (DMF), and aqueous or aqueous micellar media show a sharp emission band in the red region and modest fluorescence quantum yield (Φf = 0.2-0.3). A Poisson analysis implies most micelles are empty and few contain >1 chlorin. Water-soluble chlorins each bearing three PEG (oligoethyleneglycol) groups exhibit narrow emission bands (full-width-at-half maximum <25 nm). The lifetime of the lowest singlet excited state and the corresponding yields and rate constants for depopulation pathways (fluorescence, intersystem crossing, internal conversion) are generally little affected by the PEG groups or dissolution in aqueous or organic media. A set of chlorin-avidin conjugates revealed a 2-fold increase in Φf with increased average chlorin/avidin ratio (2.3-12). In summary, the chlorins of various polarities described herein are well suited as red-emitting fluorophores for applications in aqueous or organic media.

A virus-like particle vaccination strategy expands its tolerance to H3N2 antigenic drift by enhancing neutralizing antibodies against hemagglutinin stalk.

Seasonal influenza viruses impact public health annually due to their continual evolution. However, the current inactivated seasonal vaccines provide poor protection against antigenically drifted viruses and require periodical reformulation through hit-and-miss predictions about which strains will circulate during the next season. To reduce the impact caused by vaccine mismatch, we investigated the drift-tolerance of virus-like particles (VLP) as an improved vaccine candidate. The cross-protective humoral immunity elicited by the H3N2-VLP vaccine constructed for the 2011-2012 season was examined against viruses isolated from 2010 to 2015 in Taiwan evolving chronologically through clades 1, 4, 5, 3B and 3C, as well as viruses that were circulating globally in 2005, 2007 and 2009. Mouse immunization results demonstrated that H3N2-VLP vaccine elicited superior immunological breadth in comparison with the cognate conventional whole-inactivated virus (WIV) vaccine. Titers of neutralizing antibodies against heterologous strains representing each epidemic period in the VLP group were significantly higher than in the WIV group, indicating the antibody repertoire induced by the H3N2-VLPs was insensitive to viral antigenic drift over a span of at least 10 years. Noticeably, H3N2-VLP elicited higher levels of anti-stalk antibodies than H3N2-WIV, which offset the ineffectiveness caused by antigenic drift. This advantageous effect was attributed to the uncleaved precursor of their HA proteins. These results suggest a mechanism through which VLP-induced humoral immunity may better tolerate the evolutionary dynamics of influenza viruses and point to the possible use of a VLP vaccine as a method by which the requirement for annual updates of seasonal influenza vaccines may be diminished.

Calcinated gold nanoparticle arrays for on-chip, multiplexed and matrix-free mass spectrometric analysis of peptides and small molecules.

A patterned gold nanoparticle microarray, functionalized with a nanoscale silicate coating, has been developed for on-chip, high-throughput mass spectrometric analyses of biomolecules with minimal sample preparation and reagent costs. Fabrication was realized by the combination of layer-by-layer functionalization of the nanoparticles with suitable polyelectrolytes, followed by fluidic patterning of the glass microarray support and calcination for permanent fixation of the nano-coating. Performance of the microarray was evaluated for surface-assisted laser-desorption/ionization mass spectrometry (SALDI-MS), where the nano-silicate coating was found to enhance SALDI efficiency, resulting in comparable performance to some common organic matrices for small and medium sized molecules. Performance contributing factors of this material have been discussed; heat confinement and interband transition/plasmonic resonance may play important roles. Taking the accessibility of fabrication, performance, and reusability of this substrate together, the material developed here provides a new tool for multiplexed and chip-based mass spectrometric analysis.

Bioconjugatable, PEGylated Hydroporphyrins for Photochemistry and Photomedicine. Narrow-Band, Red-Emitting Chlorins.

Chromophores that absorb and emit in the red spectral region (600-700 nm), are water soluble, and bear a bioconjugatable tether are relatively rare yet would fulfill many applications in photochemistry and photomedicine. Here, three molecular designs have been developed wherein stable synthetic chlorins - analogues of chlorophylls - have been tailored with PEG groups for use in aqueous solution. The designs differ with regard to order of the installation (pre/post-formation of the chlorin macrocycle) and position of the PEG groups. Six PEGylated synthetic chlorins (three free bases, three zinc chelates) have been prepared, of which four are equipped with a bioconjugatable (carboxylic acid) tether. The most effective design for aqueous solubilization entails facial encumbrance where PEG groups project above and below the plane of the hydrophobic disk-like chlorin macrocycle. The chlorins possess strong absorption at ~400 nm (B band) and in the red region (Qy band); regardless of wavelength of excitation, emission occurs in the red region. Excitation in the ~400 nm region thus provides an effective Stokes shift of >200 nm. The four bioconjugatable water-soluble chlorins exhibit Qy absorption/emission in water at 613/614, 636/638, 698/700 and 706/710 nm. The spectral properties are essentially unchanged in DMF and water for the facially encumbered chlorins, which also exhibit narrow Qy absorption and emission bands (full-width-at-half maximum of each <25 nm). The water-solubility was assessed by absorption spectroscopy over the concentration range ~0.4 µM - 0.4 mM. One chlorin was conjugated to a mouse polyclonal IgG antibody for use in flow cytometry with compensation beads for proof-of-principle. The conjugate displayed a sharp signal when excited by a violet laser (405 nm) with emission in the 620-660 nm range. Taken together, the designs described herein augur well for development of a set of spectrally distinct chlorins with relatively sharp bands in the red region.

A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.

Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development.

Nanoglassified, optically-active monolayer films of gold nanoparticles for in situ orthogonal detection by localized surface plasmon resonance and surface-assisted laser desorption/ionization-MS.

Localized surface plasmon resonance (LSPR) represents a sensitive and versatile method for detection of biomolecules in a label-free fashion, but identification of bound analytes can be challenging with LSPR alone, especially for samples in a complex medium. We report the fabrication of an optically active, plasmonic film of gold nanoparticles by using a self-assembly and calcination process, which offers orthogonal measurements enabling multifaceted characterization on the same surface with LSPR and surface-assisted laser desorption/ionization mass spectrometry. This proof-of-concept study involves plasmonic characterization of the fabricated nanofilm, real-time monitoring of vesicle-surface interactions toward formation of fluid lipid bilayer, and mass spectrometric analysis of peptides and cytochrome c digest. This multifunction-enabling surface material can yield complementary analytical information, providing new tools for comprehensive analysis of biomolecular samples.

Dual-mode optical sensing of organic vapors and proteins with polydiacetylene (PDA)-embedded electrospun nanofibers.

Optical sensors capable of colorimetric visualization and/or fluorescence detection have shown tremendous potential for field technicians and emergency responders, owing to the portability and low cost of such devices. Polydiacetylene (PDA)-enhanced nanofibers are particularly promising due to high surface area, facile functionalization, simple construction, and the versatility to empower either colorimetric or fluorescence signaling. We demonstrate here a dual-mode optical sensing with electrospun nanofibers embedded with various PDAs. The solvent-dependent fluorescent transition of nanofibers generated a pattern that successfully distinguished four common organic solvents. The colorimetric and fluorescent sensing of biotin-avidin interactions by embedding biotinylated-PCDA monomers into silica-reinforced nanofiber mats were realized for detection of biomolecules. Finally, a PDA-based nanofiber sensor array consisting of three monomers has been fabricated for the determination and identification of organic amine vapors using colorimetry and principal component analysis (PCA). The combination of PCA and the strategy of probing analytes in two different concentration ranges (ppm and ppth) led to successful analysis of all eight amines.

Vibronic Characteristics and Spin-Density Distributions in Bacteriochlorins as Revealed by Spectroscopic Studies of 16 Isotopologues. Implications for Energy- and Electron-Transfer in Natural Photosynthesis and Artificial Solar-Energy Conversion.

Vibronic characteristics and spin-density distributions in the core bacteriochlorin macrocycle were revealed by spectroscopic and theoretical studies of 16 isotopologues. The vibrational modes in copper bacteriochlorin isotopologues were examined via resonance Raman and Fourier-transform infrared spectroscopy. The resonance Raman spectra exhibit an exceptional sparcity of vibronically active modes of the core macrocycle, in contrast with the rich spectra of the natural bacteriochlorophylls. The Qy-excitation resonance Raman spectrum is dominated by a single mode at 727 cm-1, which calculations suggest is due to a symmetrical accordion-like deformation of the five-atom Cm(CaNCa)pyrroleCm portion of the ring core. This deformation also dominates the vibronic features in the absorption and fluorescence spectra. The spin-density distributions in the π-cation radical of the zinc bacteriochlorin isotopologues were studied by electron paramagnetic resonance spectroscopy. The spectra indicate a significant electron/spin density (ρ ∼ 0.1) on each meso-carbon atom. This observation contradicts the predictions of early calculations that have been assumed to be correct for nearly four decades. Collectively, these findings have implications for how the structural features that characterize natural bacteriochlorophylls might influence energy- and electron-transfer processes in photosynthesis and alter the thinking on the design of synthetic, bacteriochlorin-based arrays for solar-energy conversion.

Synthesis of 24 bacteriochlorin isotopologues, each containing a symmetrical pair of 13C or 15N atoms in the inner core of the macrocycle.

Synthetic bacteriochlorins containing site-specific isotopic substitution enable spectroscopic interrogation to delineate physicochemical features relevant to bacteriochlorophylls in photosynthesis but have been little explored. A de novo synthesis has been employed to prepare bacteriochlorins wherein each macrocycle contains a pair of (13)C or (15)N atoms yet lacks substituents other than a geminal dimethyl group in each pyrroline ring. Preparation of a dihydrodipyrrin­acetal with single-isotopic substitution gives rise to a bacteriochlorin that contains two isotopic substitutions symmetrically disposed by a 180° rotation about the normal to the plane of the macrocycle. Eight such isotopically substituted bacteriochlorins were prepared from commercially available reactants (bacteriochlorin sites): ((13)C)paraformaldehyde (1, 11); ((13)C)formamide (4, 14); triethyl ((13)C)orthoformate (5, 15); K(13)CN (6, 16); (13)CH3NO2 (9, 19); N,N-dimethyl((13)C)formamide (10, 20); ((15)N)pyrrole (21, 23); CH3(15)NO2 (22, 24). Some loss of (15)N upon TiCl3-mediated McMurry-type ring closure of a nitro((15)N)hexanone is attributed to a parallel sequence of three reactions (Nef, exchange with natural-abundance NH4OAc buffer, and Paal­Knorr ring closure) leading to the dihydrodipyrrin­acetal. Zinc and copper chelates of each bacteriochlorin also were prepared. Together, the 24 bacteriochlorin isotopologues should provide valuable benchmarks for understanding ground- and excited-state molecular physics of the macrocycles related to photosynthetic function of bacteriochlorophylls.

Unichromophoric platinum-acetylides that contain pentiptycene scaffolds: torsion-induced dual emission and steric shielding of dynamic quenching.

The effect of the rigid bulky pentiptycene scaffolds on the photoluminescence, redox properties, and oxygen sensing behavior of unichromophoric Pt-acetylides is reported. When the pentiptycene groups are near the Pt(PBu3)2 center, the Pt-acetylides display both blue fluorescence and green phosphorescence with long phosphorescence lifetimes (90-202 µs) in THF. Their phosphorescence intensity is highly sensitive to molecular oxygen, and the emission color depends on the concentration of not only oxygen but also the complexes, which allows a feasible determination of oxygen in the range of 1-5% air volume. The dynamic quenching rate constants decrease linearly with increasing the number of pentiptycene groups, revealing the steric shielding effect of the peripheral rings of pentiptycene. A dependence of oxidation potential on the number of pentiptycene groups also revealed the steric shielding effect on the electron transfer between the complexes and the electrode. In a PMMA matrix, the dual emissive properties are diminished due to increased phosphorescence and decreased fluorescence intensity, and the phosphorescence lifetimes are significantly increased (up to ∼700 µs), leading to an "on-off" optical response to oxygen concentration. Both the dual emissive properties and long-lived triplet excitons are attributed to diminished spin-orbit couplings caused by twisting and steric shielding of the π-conjugated backbone around the Pt center.

Enhancement of the immune response against Salmonella infection of mice by heat-killed multispecies combinations of lactic acid bacteria.

Heat-killed lactic acid bacteria (LAB) has advantages over live LAB in that it has a long shelf-life and is therefore easy to store and transport. From four LAB strains selected by immunomodulatory activity and adherent properties, we prepared the heat-killed multispecies combination of LAB (MLAB) and the cell walls from MLAB under two conditions (100 °C for 30 min and 121 °C for 15 min). Different effects on the adherent properties of these four LAB strains were observed, depending on the heating conditions. With mouse macrophage cells, the two heat-killed MLABs (HMLABs) showed significantly higher induction activities on the production of interleukin 12 (IL-12) than their individual strains did. Heat-killed MLABs and cell-wall preparations were able to reduce the Salmonella invasion of Caco-2 and mouse macrophage cells. Feeding mice with HMLAB could inhibit the Salmonella invasion of mice significantly. For these mice, the expression level of pro-inflammatory cytokines, such as TNF-α and IL-6, in mouse serum was reduced while that of the anti-inflammatory cytokine, i.e. IL-10, was enhanced. The HMLABs developed in this study showed higher protective effect against Salmonella invasion either of Caco-2 cells or of mice, relative to the heat-killed lactobacilli, which consisted of Lactobacillus acidophilus strains selected at random. In conclusion, the HMLABs were potentially useful for the protection of mice against Salmonella infection and the induced inflammation.

A low-power bio-potential acquisition system with flexible PDMS dry electrodes for portable ubiquitous healthcare applications.

This work describes a bio-potential acquisition system for portable ubiquitous healthcare applications using flexible polydimethylsiloxane dry electrodes (FPDEs) and a low-power recording circuit. This novel FPDE used Au as the skin contact layer, which was made using a CO2 laser and replica method technology. The FPDE was revised from a commercial bio-potential electrode with a conductive snap using dry electrodes rather than wet electrodes that proposed reliable and robust attachment for the purpose of measurement, and attaching velcro made it wearable on the forearm for bio-potential applications. Furthermore, this study proposes a recording device to store bio-potential signal data and provides portability and low-power consumption for the proposed acquisition system. To acquire differential bio-potentials, such as electrocardiogram (ECG) signals, the proposed recording device includes a low-power front-end acquisition chip fabricated using a complementary metal-oxide-semiconductor (CMOS) process, a commercial microcontroller (MSP430F149), and a secure digital (SD) card for portable healthcare applications. The proposed system can obtain ECG signals efficiently and are comfortable to the skin. The power consumption of the system is about 85 mW for continuous working over a 3 day period with two AA batteries. It can also be used as a compact Holter ECG system.