HSP90 acts as a senomorphic target in senescent retinal pigmental epithelial cells.

The senescence of retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD), a leading cause of blindness in the world. HSP90 is a predominant chaperone that regulates cellular homeostasis under divergent physio-pathological conditions including senescence. However, the role of HSP90 in senescent RPE cells still remains unclear. Here, we reported that HSP90 acts as a senomorphic target of senescent RPE cells in vitro. Using H2O2-induced senescent ARPE-19 cells and replicative senescent primary RPE cells from rhesus monkey, we found that HSP90 upregulates the expression of IKKα, and HIF1α in senescent ARPE-19 cells and subsequently controls the induction of distinct senescence-associated inflammatory factors. Senescent ARPE-19 cells are more resistant to the cytotoxic HSP90 inhibitor IPI504 (IC50 = 36.78 µM) when compared to normal ARPE-19 cells (IC50 = 6.16 µM). Administration of IPI504 at 0.5-5 µM can significantly inhibit the induction of IL-1ß, IL-6, IL-8, MCP-1 and VEGFA in senescent ARPE-19 and the senescence-mediated migration of retinal capillary endothelial cells in vitro. In addition, we found that inhibition of HSP90 by IPI504 reduces SA-ß-Gal's protein expression and enzyme activity in a dose-dependent manner. HSP90 interacts with and regulates SA-ß-Gal protein stabilization in senescent ARPE-19 cells. Taken together, these results suggest that HSP90 regulates the SASP and SA-ß-Gal activity in senescent RPE cells through associating with distinctive mechanism including NF-κB, HIF1α and lysosomal SA-ß-Gal. HSP90 inhibitors (e.g. IPI504) could be a promising senomorphic drug candidate for AMD intervention.

Molecular Engineering toward an Enlarged Optical Band Gap in a Bismuth Sulfate via Homovalent Cation Substitution.

Materials capable of generating coherent short-wave (<300 nm) light have attracted extensive scientific and technical interest due to their wide utilization in laser research. In this study, a the rare-earth-metal sulfate NaCe(SO4)2(H2O) (NCSO) was synthesized through a hydrothermal method, while NaBi(SO4)2(H2O) (NBSO) was successfully obtained via a homovalent cation substitution of the parent compound NCSO under hydrothermal conditions. The space groups of crystalline NCSO and NBSO are P3121 and P3221, respectively. Both compounds have similar connectivities which feature a three-dimensional channel structure formed by asymmetric [CeO9]15-/[BiO9]15- tricapped trigonal prisms and distorted [SO4]2- tetrahedra. The introduction of Bi3+ with larger ionic radii and stereochemically active lone-pair electrons simultaneously enhanced the SHG effect and band gap of NBSO in comparison to its parent compound NCSO. In contrast to NCSO, which possesses a narrow energy band gap (2.46 eV), NBSO displays the largest energy band gap (4.54 eV) among the reported bismuth sulfate NLO materials. Powder frequency-doubling-effect measurements exhibit that NCSO and NBSO possess phase-matchable SHG responses of 0.2 × KDP and 0.38 × KDP at 1064 nm, respectively. Theoretical studies have been implemented to further elucidate the structure-performance relationships of the two compounds. Experimental and theoretical studies both demonstrate that NBSO may be a promising nonlinear material applied in the short-wavelength region.

Terminal Groups-Dependent Near-Field Enhancement Effect of Ti3C2Tx Nanosheets.

Both multilayered (ML) and few-layered (FL) Ti3C2Tx nanosheets have been prepared through a typical etching and delaminating procedure. Various characterizations confirm that the dominant terminal groups on ML-Ti3C2Tx and FL-Ti3C2Tx are different, which have been assigned to O-related and hydroxyl groups, respectively. Such deviation of the dominant terminals results in the different physical and chemical performance and eventually makes the nanosheets have different potential applications. In particular, before coupling to Ag nanoparticles, ML-Ti3C2Tx can present stronger near-field enhancement effect; however, Ag/FL-Ti3C2Tx hybrid structure can confine stronger near-field due to the electron injection, which can be offered by the terminated hydroxyl groups.

The Antimicrobial Peptide Melectin Shows Both Antimicrobial and Antitumor Activity via Membrane Interference and DNA Binding.

PURPOSE: Increasingly complex diseases require novel drugs for their treatment. Antimicrobial peptides (AMPs) are promising candidate treatments due to their broad existence and special characteristics. However, the current understanding of AMPs is not sufficient to allow them to be produced commercially for clinical use. MATERIALS AND METHODS: Melectin, from the venom of the cleptoparasitic bee Melecta albifrons, does not exhibit sequence homology with other wasp venom peptides. To investigate this more deeply, we explored the antibacterial and antitumor activities of Melectin and related mechanisms. RESULTS: Our results demonstrate that Melectin possesses antimicrobial properties against standard sensitive/clinical drug-resistant bacteria strains as well as antitumor activity. It has an α-helix form and exhibits moderate cytotoxicity. Its action mechanisms are involved with membrane interfering and DNA binding. The membrane interfering effect was distinct between different phospholipid compositions. CONCLUSION: We found that Melectin may serve as a new potential template in the battle against multidrug resistance, and our study indicated that there are promising prospects for medically applicable drugs based on AMPs.

Pd/MXene(Ti3C2Tx)/reduced graphene oxide hybrid catalyst for methanol electrooxidation.

A key challenge in developing direct methanol fuel cells is the fabrication of electrocatalysts with high activity and long durability. Herein, we report a performance enhanced electrocatalyst of nanoscale Pd on MXene (Ti3C2Tx) and reduced graphene oxide (rGO). The mass activity of Pd/Ti3C2Tx-rGO (1: 1) hybrid toward methanol oxidation reaction is 753 mA mg-1, which is 1.7 times than that of Pd/C (446 mA mg-1). Additionally, the current density of Pd/Ti3C2Tx-rGO (1:1) catalyst contains 212 mAmg-1 which is nine times higher than that of Pd/C (23 mA mg-1) after 7200 s. The Pd/Ti3C2Tx-rGO (1:1) catalyst exhibits excellent cycling stability and long-term life. These remarkable catalytic performances are attributed to the role of Ti3C2Tx and rGO in enhancing the catalytic activity surface area and rapid mass/charge transfer due to the synergistic effect between Pd and Ti3C2Tx/rGO.

In situ growth of hierarchical Al2O3 nanostructures onto TiO2 nanofibers surface: super-hydrophilicity, efficient oil/water separation and dye-removal.

Developing a facile strategy to synthesize template-free TiO2 membrane with stable super-hydrophilic surface is still a daunting challenge. In this work, super-hydrophilicity (close to 0°) and underwater super-oleophobicity (165°) have been successfully demonstrated on a hierarchical Al2O3/TiO2 membrane, which is prepared via a facile electrospinning method followed by simple calcination in air. The precisely-tuned Al2O3 heterojunctions grew in situ and dispersed uniformly on the TiO2 surface, resulting in an 'island in the sea' configuration. Such a unique feature allows not only achieving super-hydrophilicity by maximizing the surface roughness and enhancing the hydrogen bonding, but also improving the adsorption capacity toward different toxic dyes utilizing the abundant adsorption sites protected by the hierarchical nanostructure during sintering. The new Al2O3/TiO2 nanofibrous membrane can serve as a novel filter for gravity driven oil/water separation along with dye removal, achieving 97.7% of oil/water separation efficiency and 98% of dye capture, thanks to their superb wettability and the sophisticated adsorptive performance. Our presented fabrication strategy can be extended to a wide range of ceramic materials and inspires their advanced applications in water purification under harsh liquid-phase environments.

Fabrication of CsxFA1-xPbI3 Mixed-Cation Perovskites via Gas-Phase-Assisted Compositional Modulation for Efficient and Stable Photovoltaic Devices.

Over the past few years, significant attention has been focused on HC(NH2)2PbI3 (FAPbI3) perovskite due to its reduced band gap and enhanced thermal stability compared with the most studied CH3NH3PbI3 (MAPbI3). However, FAPbI3 is sensitive to moisture and also encounters a serious structural phase-transition from photoactive α-phase to photoinactive δ-phase. Herein, we first develop a novel FAI gas-phase-assisted mixed-cation compositional modulation method to fabricate CsxFA1-xPbI3 perovskite solar cells (PSCs), and realize the structural stabilization of α-phase FAPbI3 with the incorporation of smaller inorganic Cs+ ions. Through the setting of different Cs+ contents (x = 0, 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.50) along with a moderate FAI vapor deposition process, a series of CsxFA1-xPbI3 films with consistent compositions are fabricated, which perfectly resolves the main blocking problems of the conventional solution approach, such as difficulty in compositional control and rough film morphology. Meanwhile, we find that the Cs+ amount is crucial for generating phase-pure CsxFA1-xPbI3 (0 < x < 0.30) while higher contents result in phase segregation. Consequently, the optimum amount of Cs+ (x = 0.15) is verified, and Cs0.15FA0.85PbI3 shows the smallest unit cell volume and good moisture-resistant feature. Correspondingly, the highest power conversion efficiency (PCE) of 14.45% based on Cs0.15FA0.85PbI3 PSCs is successfully achieved in this work.

Exploring the expression bar code of SAA variants for gastric cancer detection.

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.

Solvent Engineering for Ambient-Air-Processed, Phase-Stable CsPbI3 in Perovskite Solar Cells.

Inorganic CsPbI3 perovskite solar cells (PSCs) owning comparable photovoltaic performance and enhanced thermal stability compared to organic-inorganic hybrid perovskites have attracted enormous interest in the past year. However, it is still a challenge to stabilize the desired black α-CsPbI3 perovskites in ambient air for photovoltaic applications. Herein, sequential solvent engineering including the addition of hydroiodic acid (HI) and subsequent isopropanol (IPA) treatment for fabricating stable and working CsPbI3 PSCs is developed, and a novel low-temperature phase-transition route from new intermediate Cs4PbI6 to stable α-CsPbI3 is also released for the first time. As such, the as-prepared PSCs give a relatively high power conversion efficiency (PCE) of 4.13% (reverse scan), and the steady-state power output of 1.88% is confirmed for the selected cell with an initial PCE of 3.13%. To the best of our knowledge, this is the first demonstration of fabricating CsPbI3 inorganic PSCs under fully open-air conditions.

A novel transformation route from PbS to CH3NH3PbI3 for fabricating curved and large-area perovskite films.

We present a new transformation route from PbS to CH3NH3PbI3 for the facile preparation of perovskites with all kinds of shapes via vapor-assisted chemical bath deposition (VACBD). As such, curved and large-area CH3NH3PbI3 films with high quality are successfully achieved, which are suitable for the manufacturing scale-up of perovskite solar cells.

Uniform, stable, and efficient planar-heterojunction perovskite solar cells by facile low-pressure chemical vapor deposition under fully open-air conditions.

Recently, hybrid perovskite solar cells (PSCs) have attracted extensive attention due to their high efficiency and simple preparing process. Herein, a facile low-pressure chemical vapor deposition (LPCVD) technology is first developed to fabricate PSCs, which can effectively reduce the over-rapid intercalating reaction rate and easily overcome this blocking issue during the solution process. As a result, the prepared uniform perovskite films exhibit good crystallization, strong absorption, and long carrier diffusion length. More strikingly, CH3NH3PbI3 absorbers by LPCVD demonstrate excellent moisture-resistant feature even under laser illumination and high-temperature conditions, which indicates that our proprietary method is very suitable for the future low-cost, nonvacuum production of the new generation photovoltaic devices. Finally, high efficiency of 12.73% is successfully achieved under fully open-air conditions. To the best of our knowledge, this is the first report of efficient PSCs with such a high humidity above 60%.

Coupling of single quantum emitters to plasmons propagating on mechanically etched wires.

We demonstrate the coupling of a single nitrogen vacancy center in a nanodiamond to propagating plasmonic modes of mechanically etched silver nanowires. The mechanical etch is performed on single crystalline silver nanoplates by the tip of an atomic force microscope cantilever to produce wires with pre-designed lengths. We show that single plasmon propagation can be obtained in these wires, thus making these structures a platform for quantum information processing.

BAD-lectins: boronic acid-decorated lectins with enhanced binding affinity for the selective enrichment of glycoproteins.

The weak and variable binding affinities exhibited by lectin-carbohydrate interactions have often compromised the practical utility of lectin in capturing glycoproteins for glycoproteomic applications. We report here the development and applications of a new type of hybrid biomaterial, namely a boronic acid-decorated lectin (BAD-lectin), for efficient bifunctional glycoprotein labeling and enrichment. Our binding studies showed an enhanced affinity by BAD-lectin, likely to be mediated via the formation of boronate ester linkages between the lectin and glycan subsequent to the initial recognition process and thus preserving its glycan-specificity. Moreover, when attached to magnetic nanoparticles (BAD-lectin@MNPs), 2 to 60-fold improvement on detection sensitivity and enrichment efficiency for specific glycoproteins was observed over the independent use of either lectin or BA. Tested at the level of whole cell lysates for glycoproteomic applications, three different types of BAD-lectin@MNPs exhibited excellent specificities with only 6% overlapping among the 295 N-linked glycopeptides identified. As many as 236 N-linked glycopeptides (80%) were uniquely identified by one of the BAD-lectin@MNPs. These results indicated that the enhanced glycan-selective recognition and binding affinity of BAD-lectin@MNPs will facilitate a complementary identification of the under-explored glycoproteome.

A chemically functionalized magnetic nanoplatform for rapid and specific biomolecular recognition and separation.

We have developed a target-molecule-functionalized magnetic nanoparticle (MNP)-based method to facilitate the study of biomolecular recognition and separation. The superparamagnetic property of MNPs allows the corresponding biomolecules to be rapidly separated from crude biofluids with a significant improvement in recovery yield and specificity. Various MNPs functionalized with tag molecules (chitin, heparin, and amylose) were synthesized for recombinant protein purification, and several probe-functionalized MNPs, such as nitrilotriacetic acid (NTA)@MNP and P(k)@MNP, exhibited excellent extraction efficiency for proteins. In a cell recognition study, mannose-functionalized MNPs allowed specific purification of Escherichia coli with FimH adhesin on the surface. In an immunoprecipitation assay, the antibody-conjugated MNPs reduced the incubation time from 12 to 1 h while maintaining a comparable efficiency. The functionalized MNPs were also used in a membrane proteomic study that utilized the interaction between streptavidin-functionalized MNPs and biotinylated cell membrane proteins. Overall, the functionalized MNPs were demonstrated to be promising probes for the specific separation of targets from proteins to cells and proteomics.

Propagation of plasmons in designed single crystalline silver nanostructures.

We demonstrate propagation of plasmons in single crystalline silver nanostructures fabricated using a combination of a bottom-up and a top-down approach. Silver nanoplates of thickness around 65 nm and a surface area of about 100 µm(2) are made using a wet chemical method. Silver nanotips and nanowires are then sculptured by focused ion beam milling. The plasmons are excited by using the fluorescence from the redeposited silver clusters during the milling process. Propagation of plasmons in the nanowires is observed in the visible spectral region. We also observe a cavity effect by measuring the emission spectrum from the distal wire end.

Iron oxide nanomatrix facilitating metal ionization in matrix-assisted laser desorption/ionization mass spectrometry.

The significance and epidemiological effects of metals to life necessitate the development of direct, efficient, and rapid method of analysis. Taking advantage of its simple, fast, and high-throughput features, we present a novel approach to metal ion detection by matrix-functionalized magnetic nanoparticle (matrix@MNP)-assisted MALDI-MS. Utilizing 21 biologically and environmentally relevant metal ion solutions, the performance of core and matrix@MNP against conventional matrixes in MALDI-MS and laser desorption ionization (LDI) MS were systemically tested to evaluate the versatility of matrix@MNP as ionization element. The matrix@MNPs provided 20- to >100-fold enhancement on detection sensitivity of metal ions and unambiguous identification through characteristic isotope patterns and accurate mass (<5 ppm), which may be attributed to its multifunctional role as metal chelator, preconcentrator, absorber, and reservoir of energy. Together with the comparison on the ionization behaviors of various metals having different ionization potentials (IP), we formulated a metal ionization mechanism model, alluding to the role of exciton pooling in matrix@MNP-assisted MALDI-MS. Moreover, the detection of Cu in spiked tap water demonstrated the practicability of this new approach as an efficient and direct alternative tool for fast, sensitive, and accurate determination of trace metal ions in real samples.

Nanoparticle-assisted MALDI-TOF MS combined with seed-layer surface preparation for quantification of small molecules.

Despite the advantages of simplicity and high-throughput detection that matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has over other methods, quantitative analysis of low-molecular-weight analyte is hampered by interference from matrix-derived background noise and signal fluctuation due to the inhomogeneous MALDI sample surface. Taking advantage of improved sample homogeneity through matrix-conjugated magnetic nanoparticles (matrix@MNP) and the seed-layer method, we report a new strategy for the rapid identification and quantification of drugs in urine samples, using morphine and 7-aminoflunitrazepam (7-aminoFM2) as model compounds. To our knowledge, this is the first attempt using the seed-layer method for small molecule analysis. By applying the proposed seed-layer method, which was specifically optimized for the 2,5-dihydroxybenzoic acid@MNP (DHB@MNP) matrix, homogeneous sample crystallization examined by microscopy analysis was obtained that generated reproducible MALDI signals (RSD<10.0%). For urine sample analysis, simple liquid-liquid extraction as a sample pretreatment step effectively reduced the ion suppression effect caused by the endogenous components in urine; good recoveries (82-90%) were obtained with a small ion suppression effect (<14% of signal decrease). This newly developed method demonstrated good quantitation linearity over a range of 50-2000 ng mL(-1) (R(2)>0.996) with reduced signal variation (RSD<10.0%). The detection limit is 30 ng mL(-1) with good precision (intra-day, 2.0-9.3%; inter-day, 5.0-10.0%) and accuracy (intra-day, 95.0-106.0%; inter-day, 103.0-115.5%). The nanoparticle-assisted MALDI-TOF MS combined with seed-layer surface preparation provides a rapid, efficient and accurate platform for the quantification of small molecules in urine samples.

Dihydrobenzoic acid modified nanoparticle as a MALDI-TOF MS matrix for soft ionization and structure determination of small molecules with diverse structures.

Efficient structural characterization is important for quality control when developing novel materials. In this study, we demonstrated the soft ionization capability of the hybrid of immobilized silica and 2,5-dihydrobenzoic acid (DHB) on iron oxide magnetic nanoparticles in MALDI-TOF MS with a clean background. The ratio between SiO(2) and DHB was examined and was found to affect the surface immobilization of DHB on the nanoparticle, critically controlling the ionization efficiency and interference background. Compared with commercial DHB, the functionalized nanoparticle-assisted MALDI-TOF MS provided superior soft ionization with production of strong molecular ions within 5 ppm mass accuracy on a variety of new types of synthetic materials used for solar cells, light emitting devices, dendrimers, and glycolipids, including analytes with either thermally labile structures or poor protonation tendencies. In addition, the enhancements of the molecular ion signal also provided high-quality product-ion spectra allowing structural characterization and unambiguous small molecule identification. Using this technique, the structural differences among the isomers were distinguished through their characteristic fragment ions and comprehensive fragmentation patterns. With the advantages of long-term stability and simple sample preparation by deposition on a regular sample plate, the use of DHB-functionalized nanoparticles combined with high-resolution MALDI-TOF MS provides a generic platform for rapid and unambiguous structure determination of small molecules.

Endomorphins and morphine limit anoxia-reoxygenation-induced brain mitochondrial dysfunction in the mouse.

The protection of brain mitochondria from oxidative stress is an important therapeutic strategy against ischemia-reperfusion injury and neurodegenerative disorders. Isolated brain mitochondria subjected to a 5 min period of anoxia followed by 5 min reoxygenation mirrored the effect of oxidative stress in the brain. The present study attempts to evaluate the protective effects of endomorphin 1 (EM1), endomorphin 2 (EM2), and morphine (Mor) in an in vitro mouse brain mitochondria anoxia-reoxygenation model. Endomorphins (EM1/2) and Mor were added to mitochondria prior to anoxia or reoxygenation. EM1/2 and Mor markedly improved mitochondrial respiratory activity with a decrease in state 4 and increases in state 3, respiratory control ratio (RCR) and the oxidative phosphorylation efficiency (ADP/O ratio), suggesting that they may play a protective role in mitochondria. These drugs inhibited alterations in mitochondrial membrane fluidity, lipoperoxidation, and cardiolipin (CL) release, which indicates protection of the mitochondrial membranes from oxidative damage. The protective effects of these drugs were concentration-dependent. Furthermore, these drugs blocked the enhanced release of cytochrome c (Cyt c), and consequently inhibited the cell apoptosis induced by the release of Cyt c. Our results suggest that EM1/2 and Mor effectively protect brain mitochondria against oxidative stresses induced by in vitro anoxia-reoxygenation and may play an important role in the prevention of deleterious effects during brain ischemia-reperfusion and neurodegenerative diseases.

Caffeic acid phenethyl ester and its related compounds limit the functional alterations of the isolated mouse brain and liver mitochondria submitted to in vitro anoxia-reoxygenation: relationship to their antioxidant activities.

It is an important therapeutic strategy to protect mitochondria from oxidative stress, especially during ischemia-reperfusion. In the present study, an attempt has been made to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and its related phenolic compounds on mouse brain and liver mitochondria injury induced by in vitro anoxia-reoxygenation. Added before anoxia or reoxygenation, CAPE markedly protected coupled respiration with the decrease in state 4 and the increases in state 3, respiratory control ratio (RCR) and ADP/O ratio in a concentration-dependent manner. CAPE effectively protected mitochondria by inhibiting the mitochondrial membranes fluidity decrease, the lipoperoxidation and the protein carbonylation increase, which indicated its protective action against the mitochondrial oxidative damage. Meanwhile, CAPE blocked the enhanced release of cardiolipin (CL) and cytochrome c (Cyt c). The related phenolic compounds like caffeic acid (CA), ferulic acid (FA) and ethyl ferulate (EF) also had different-degree protective effects. CAPE and CA were more potent than FA and EF. Their structural differences played the key role in their activity levels. These results suggest that CAPE and its related phenolic compounds protect mitochondria mainly correlated to their antioxidative activities and may be of interest for the prevention and therapy of ischemia-reperfusion injuries.