A novel magnetic AgVO3/rGO/CuFe2O4 hybrid catalyst for efficient hydrogen evolution and photocatalytic degradation.

A superior semiconductor material with efficient charge separation and easy reuse could be a promising route for efficient photocatalytic hydrogen evolution and pollutant degradation. AgVO3 is one of the best visible light active materials which has attracted much attention for several biological and environmental applications. In the aim of enhancing its stability and recyclability a novel AgVO3/rGO/CuFe2O4 heterojunction was prepared by hydrothermal method for hydrogen generation (H2) and 4-nitrophenol (4-NP) degradation as well. The composite was well characterized by XRD, SEM, HR-TEM, XPS and VSM. The morphological images suggested the rod shaped AgVO3 and irregular shaped CuFe2O4 are unevenly distributed on reduced graphene oxide (rGO) layers. The hydrogen evolution results indicated that the composite showed around 8.937 mmol g-1h-1 of H2 generation which was ∼2.3 times and ∼9.2 times higher than pure AgVO3 (3.895 mmol g-1h-1) and CuFe2O4 (0.96 mmol g-1h-1) respectively. The 4-NP degradation efficiency of the prepared composite was observed as 94.7% (k = 0.01841 min-1) which is much higher than the AgVO3 (66.3%) and CuFe2O4 (38.2%) after 4 h of irradiation. The higher efficiency could be attributed to the heterojunction formation and faster charge separation. The radical trapping results indicated that the •OH, O2•- and photogenerated h+ are the main species responsible for efficient activity. The AgVO3/rGO/CuFe2O4 heterojunction showed 49.6 emu/g of saturation magnetization and confirms that it could be easily separated with an external magnet, and showed 85.3% of degradation efficiency even after 6 recycles which indicated its higher stability and recyclability. Thus, our study provides new insight into hydrogen generation and phenol degradation using AgVO3 based recyclable composites.

ANP promotes HTR-8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition.

Preeclampsia is a gestational disease characterized by two major pathological changes-shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified. Here, we performed isobaric tags for relative and absolute quantification (iTRAQ) in ANP-treated HTR-8/SVneo cells and identified Protein Kinase 3 (PKN3) as the downstream factor of ANP, which was downregulated in preeclamptic placenta. Chromatin immunoprecipitation analysis and luciferase assays showed that NFYA was one of the transcription factors for the PKN3 promoter, which was also regulated by ANP treatment in HTR-8/SVneo cells. Transmission electron microscopy and Western Blotting in HTR-8/SVneo cells indicated that ANP inhibited autophagy via AMPK-mTORC1 signaling, while excess autophagy was observed in preeclamptic placenta. The increased expression of PKN3 and enhanced cell invasion ability in HTR-8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR-A shRNA via regulating the invasion-related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling-dependent manner.

Observation of a transient intermediate in the ultrafast relaxation dynamics of the excess electron in strong-field-ionized liquid water.

A unified picture of the electronic relaxation dynamics of ionized liquid water has remained elusive despite decades of study. Here, we employ sub-two-cycle visible to short-wave infrared pump-probe spectroscopy and ab initio nonadiabatic molecular dynamics simulations to reveal that the excess electron injected into the conduction band (CB) of ionized liquid water undergoes sequential relaxation to the hydrated electron s ground state via an intermediate state, identified as the elusive p excited state. The measured CB and p-electron lifetimes are 0.26 ± 0.02 ps and 62 ± 10 fs, respectively. Ab initio quantum dynamics yield similar lifetimes and furthermore reveal vibrational modes that participate in the different stages of electronic relaxation, with initial relaxation within the dense CB manifold coupled to hindered translational motions whereas subsequent p-to-s relaxation facilitated by librational and even intramolecular bending modes of water. Finally, energetic considerations suggest that a hitherto unobserved trap state resides ~0.3-eV below the CB edge of liquid water. Our results provide a detailed atomistic picture of the electronic relaxation dynamics of ionized liquid water with unprecedented time resolution.

ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication.

53BP1 activates nonhomologous end joining (NHEJ) and inhibits homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Dissociation of 53BP1 from DSBs and consequent activation of HR, a less error-prone pathway than NHEJ, helps maintain genome integrity during DNA replication; however, the underlying mechanisms are not fully understood. Here, we demonstrate that E3 ubiquitin ligase SPOP promotes HR during S phase of the cell cycle by excluding 53BP1 from DSBs. In response to DNA damage, ATM kinase-catalyzed phosphorylation of SPOP causes a conformational change in SPOP, revealed by x-ray crystal structures, that stabilizes its interaction with 53BP1. 53BP1-bound SPOP induces polyubiquitination of 53BP1, eliciting 53BP1 extraction from chromatin by a valosin-containing protein/p97 segregase complex. Our work shows that SPOP facilitates HR repair over NHEJ during DNA replication by contributing to 53BP1 removal from chromatin. Cancer-derived SPOP mutations block SPOP interaction with 53BP1, inducing HR defects and chromosomal instability.

Solar-Blind Photodetector with Lower Dark Current and Higher Ilight/Idark Ratio Based on Mg0.38Zn0.62O Film Deposited by Pulsed Laser Deposition Method.

In this study, pulsed laser deposition method (PLD) was employed to grow MgxZn1-xO films on quartz substrates. The optimal deposition temperature of 300 °C for MgxZn1-xO film was decided and Mg0.38Zn0.62O, Mg0.56Zn0.44O and Mg0.69Zn0.31O films were grown respectively using MgxZn1-xO targets with different Mg contents (x = 0.3, 0.5 and 0.7). As-deposited Mg0.38Zn0.62O film possessed the mixed-phase (hexagonal and cubic phase) structure, appropriate band gap of 4.68 eV and smaller surface roughness of 1.72 nm, and the solar-blind photodetector (PD) based on it was fabricated. The key features of our PD are the cutoff wavelength of 265 nm lying in solar-blind band, lower dark current (Idark) of 88 pA, higher peak responsivity of 0.10 A/W and bigger Ilight/Idark ratio of 1688, which provide the new idea for the application of solar-blind PDs based on MgxZn1-xO films.

Multimodal Loading Environment Predicts Bioresorbable Vascular Scaffolds' Durability.

Bioresorbable vascular scaffolds were considered the fourth generation of endovascular implants deemed to revolutionize cardiovascular interventions. Yet, unexpected high risk of scaffold thrombosis and post-procedural myocardial infractions quenched the early enthusiasm and highlighted the gap between benchtop predictions and clinical observations. To better understand scaffold behavior in the mechanical environment of vessels, animal, and benchtop tests with multimodal loading environment were conducted using industrial standard scaffolds. Finite element analysis was also performed to study the relationship among structural failure, scaffold design, and load types. We identified that applying the combination of bending, axial compression, and torsion better reflects incidence observed in-vivo, far more than tranditional single mode loads. Predication of fracture locations is also more accurate when at least bending and axial compression are applied during benchtop tests (>60% fractures at connected peak). These structural failures may be initiated by implantation-induced microstructural damages and worsened by cyclic loads from the beating heart. Ignoring the multi-modal loading environment in benchtop fatigue tests and computational platforms can lead to undetected potential design defects, calling for redefining consensus evaluation strategies for scaffold performance. With the robust evaluation strategy presented herein, which exploits the results of in-vivo, in-vitro and in-silico investigations, we may be able to compare alternative designs of prototypes at the early stages of device development and optimize the performance of endovascular implants according to patients-specific vessel dynamics and lesion configurations in the future.

Nickel-Titanium peripheral stents: Which is the best criterion for the multi-axial fatigue strength assessment?

Ni-Ti stents fatigue strength assessment requires a multi-factorial complex integration of applied loads, material and design and is of increasing interest. In this work, a coupled experimental-numerical method for the multi-axial fatigue strength assessment is proposed and verified for two different stent geometries that resemble commercial products. Particular attention was paid to the identification of the material fatigue limit curve. The common approach for the Ni-Ti stents fatigue assessment based on the von Mises yield criterion was proven unsuitable for a realistic fatigue strength assessment. On the other hand, critical plane-based criteria were more representative of the experimental outcomes regardless of stent design.

Flat-Type Gas Sensors Based on ZnO Nanorod Arrays.

ZnO seed layers were deposited on silicon and sapphire substrates by the pulsed laser deposition (PLD) method, and ZnO nanorod arrays with different orientation degrees were grown using the chemical vapor deposition (CVD) method. Flat-type gas sensors based on the ZnO nanorod arrays were fabricated, and their gas sensitivity properties were studied. The ZnO seed layer with a thickness of approximately 450 nm exhibits high c-axis orientation and possesses few defects. The ZnO nanorods fabricated on both of the substrates grow along the [0001] direction and contain a large number of oxygen vacancy defects. These nanorods have lengths of 8~10 µm and diameters of 200~500 nm. The ZnO nanorods grown on the silicon substrate are perpendicular to the surface of the substrate, and their areal density is approximately 3.0×108/cm², while those grown on the sapphire substrate exhibit a lower orientation degree, and their areal density is approximately 0.9×108/cm². The largest response of the gas sensor for gaseous alcohol reaches 48.2, and the optimal operating temperature for all of the sensors is approximately 280 °C. The gas sensitivity property of the silicon-based sensor is superior to that of the sapphire-based sensor, and the corresponding sensing mechanism is discussed.

Solar-Blind Photodetector with Lower Dark Current and Higher Ilight/Idark Ratio Based on Mg0.38Zn0.62O Film Deposited by Pulsed Laser Deposition Method.

In this study, pulsed laser deposition method (PLD) was employed to grow MgxZn1-xO films on quartz substrates. The optimal deposition temperature of 300 °C for MgxZn1-xO film was decided and Mg0.38Zn0.62O, Mg0.56Zn0.44O and Mg0.69Zn0.31O films were grown respectively using MgxZn1-xO targets with different Mg contents (x = 0.3, 0.5 and 0.7). As-deposited Mg0.38Zn0.62O film possessed the mixed-phase (hexagonal and cubic phase) structure, appropriate band gap of 4.68 eV and smaller surface roughness of 1.72 nm, and the solar-blind photodetector (PD) based on it was fabricated. The key features of our PD are the cutoff wavelength of 265 nm lying in solar-blind band, lower dark current (Idark) of 88 pA, higher peak responsivity of 0.10 A/W and bigger Ilight/Idark ratio of 1688, which provide the new idea for the application of solar-blind PDs based on MgxZn1-xO films.

High Sensitivity NO2 Gas Sensor Based on 3D WO3 Microflowers Assembled by Numerous Nanoplates.

Tungsten oxide microflowers (WO3 MFs) were fabricated by a simple hydrothermal process through adjusting the pH of the solution by HCl. These MFs possess the outer diameters of about 2 µm and are composed of numerous nanoplates with the average pore size of 10.9 nm. Chemiresistive activity of as-fabricated WO3 MFs sensor was attempted towards oxidizing and reducing target gases, revealing a superior selectivity to NO2 with a maximum response of 22.95 (2 ppm NO2) @105 °C compared to other target gases. One of the key features of as-fabricatedWO3 MFs sensor is the lower detection limit of 125 ppb and operating temperature of 105 °C to NO2 with better reproducibility, signifying commercial prospective of the developed sensor materials. Finally, the gas sensing mechanism of WO3 MFs sensor has been proposed.

Ultrafast structural rearrangement dynamics induced by the photodetachment of phenoxide in aqueous solution.

The elementary processes that accompany the interaction of ionizing radiation with biologically relevant molecules are of fundamental importance. However, the ultrafast structural rearrangement dynamics induced by the ionization of biomolecules in aqueous solution remain hitherto unknown. Here, we employ femtosecond optical pump-probe spectroscopy to elucidate the vibrational wave packet dynamics that follow the photodetachment of phenoxide, a structural mimic of tyrosine, in aqueous solution. Photodetachment of phenoxide leads to wave packet dynamics of the phenoxyl radical along 12 different vibrational modes. Eight of the modes are totally symmetric and support structural rearrangement upon electron ejection. Comparison to a previous photodetachment study of phenoxide in the gas phase reveals the important role played by the solvent environment in driving ultrafast structural reorganization induced by ionizing radiation. This work provides insight into the ultrafast molecular dynamics that follow the interaction of ionizing radiation with molecules in aqueous solution.

Field Emission Properties of Molybdenum Nanoparticles Decorated ZnO Nanorod Arrays.

Precisely controlled dimensions of heterostructured ZnO nanorod arrays were grown on micropatterned Au films supported by Si substrate using chemical vapor deposition (CVD). The field emission properties were attributed to pointed nanorods, thickness of catalyst, preferential growth, density, morphology of ZnO and Molybdenum (Mo) decorated ZnO nanorod arrays (Mo/ZnO). The selective restrained heterostructure approach resulted in excellent control over periodicity, location and density of ZnO nanorod arrays. Overall, field emission properties of bare ZnO nanorod arrays showed a low turn-on field of ~4.7 V/µm and a high field enhancement factor (ß) ~1686 to 7.3 V/µm and (ß) ~807 for Mo/ZnO. It was also found that the field emission properties were significantly influenced by densely decorated Mo nanoparticles on as-grown ZnO nanorod arrays.

Effect of working environment and procedural strategies on mechanical performance of bioresorbable vascular scaffolds.

Polymeric bioresorbable scaffolds (BRS), at their early stages of invention, were considered as a promising revolution in interventional cardiology. However, they failed dramatically compared to metal stents showing substantially higher incidence of device failure and clinical events, especially thrombosis. One problem is that use of paradigms inherited from metal stents ignores dependency of polymer material properties on working environment and manufacturing/deployment steps. Unlike metals, polymeric material characterization experiments cannot be considered identical under dry and submerged conditions at varying rates of operation. We demonstrated different material behaviors associated with variable testing environment and parameters. We, then, have employed extracted material models, which are verified by computational methods, to assess the performance of a full-scale BRS in different working condition and under varying procedural strategies. Our results confirm the accepted notion that slower rate of crimping and inflation can potentially reduce stress concentrations and thus reduce localized damages. However, we reveal that using a universal set of material properties derived from a benchtop experiment conducted regardless of working environment and procedural variability may lead to a significant error in estimation of stress-induced damages and overestimation of benefits procedural updates might offer. We conclude that, for polymeric devices, microstructural damages and localized loss of structural integrity should complement former macroscopic performance-assessment measures (fracture and recoil). Though, to precisely capture localized stress concentration and microstructural damages, context-related testing environment and clinically-relevant procedural scenarios should be devised in preliminary experiments of polymeric resorbable devices to enhance their efficacy and avoid unpredicted clinical events. STATEMENT OF SIGNIFICANCE: Bioresorbable scaffolds (BRS) with the hope to become the next cardiovascular interventional revolution failed in comparison to metal stents. When BRS were characterized using methods for metal stents, designers were misled to seek problem sources at erroneous timeframe and use inefficient indicators, and thus no signal of concern emerged. We demonstrated fundamental flaws associated with applying a universal set of material properties to study device performances in different phases of manufacturing/implantation, and these may be responsible for failure in predicting performance in first-generation BRS. We introduced new criterion for the assessment of structural integrity and device efficacy in next-generation BRS, and indeed all devices using polymeric materials which evolve with the environment they reside in.

Strain-induced accelerated asymmetric spatial degradation of polymeric vascular scaffolds.

Polymer-based bioresorbable scaffolds (BRS) seek to eliminate long-term complications of metal stents. However, current BRS designs bear substantially higher incidence of clinical failures, especially thrombosis, compared with metal stents. Research strategies inherited from metal stents fail to consider polymer microstructures and dynamics--issues critical to BRS. Using Raman spectroscopy, we demonstrate microstructural heterogeneities within polymeric scaffolds arising from integrated strain during fabrication and implantation. Stress generated from crimping and inflation causes loss of structural integrity even before chemical degradation, and the induced differences in crystallinity and polymer alignment across scaffolds lead to faster degradation in scaffold cores than on the surface, which further enlarge localized deformation. We postulate that these structural irregularities and asymmetric material degradation present a response to strain and thereby clinical performance different from metal stents. Unlike metal stents which stay patent and intact until catastrophic fracture, BRS exhibit loss of structural integrity almost immediately upon crimping and expansion. Irregularities in microstructure amplify these effects and can have profound clinical implications. Therefore, polymer microstructure should be considered in earliest design stages of resorbable devices, and fabrication processes must be well-designed with microscopic perspective.

The ventromedial hypothalamic nucleus plays an important role in anxiolytic-like effect of neuropeptide S.

Neuropeptide S (NPS), the endogenous neuropeptide ligand of NPSR, has been reported to regulate anxiety-related behavior involved in multiple brain regions, including amygdale, locus coeruleus and Barrington's nucleus. However, little research has been conducted on the anxiolytic-like behaviors of NPS on the hypothalamus, which was an important area in defensive behavior. Here, we investigated a role of hypothalamus in anxiolytic-like behaviors of NPS. We found that NPSR protein of mouse distributed mainly in the ventromedial hypothalamus (VMH). And in the single prolonged stress model (SPS), the results showed that NPS mRNA of the mice exposed to SPS was significantly higher than control, while NPSR mRNA was remarkable lower than control in hypothalamus. Further studies found that NPS intra-VMH infusion dose-dependently (1, 10 and 100pmol) induced anxiolytic effects, using elevated plus maze and open field tests. These anxiolytic effects could be blocked by NPSR antagonist (SHA68), but not by picrotoxin (a GABAA receptor antagonist) and sacolfen (a GABAB receptor antagonist). Meanwhile, our data showed that the expression of c-Fos was significantly increased in VMH after NPS delivered into the lateral ventricles. These results cast a new light on the hypothalamic nucleus in the anxiolytic-like effect of NPS system.

Development and validation of a UPLC-MS/MS method for quantitation of droxidopa in human plasma: Application to a pharmacokinetic study.

In this study, a simple and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for quantitation of droxidopa in human plasma for the first time. A simple plasma protein precipitation method using methanol containing 3% formic acid was selected, and the separation was achieved by an Acquity UPLC™ BEH Amide column (2.1mm×50mm, 1.7µm) with a gradient elution using acetonitrile, ammonium formate buffer and formic acid as mobile phase. The detection of droxidopa and benserazide (internal standard, IS) was performed using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The precursor-to-product ion transitions m/z 214.2→m/z 152.0 for droxidopa, and m/z 258.1→m/z 139.1 for IS were used for quantification. A lower limit of quantification of 5.00ng/mL was achieved and the linear curve range was 5.00-4000ng/mL using a weighted (1/x(2)) linear regression model. Intra-assay and inter-assay precision was less than 10.2%, and the accuracy ranged from 0.1% to 2.1%. Stability, recovery and matrix effects were within the acceptance criteria recommended by the regulatory bioanalytical guidelines. The method was successfully applied to a pharmacokinetic study of droxidopa in healthy Chinese volunteers.

[Anticancer drugs targeting glutathione S-transferase π].

Glutathione S-transferase(GSTπ), one of the phase II detoxification enzymes, is usually over- expressed in many human tumors. It displays a key role in protecting cells through catalyzing the conjugation of glutathione(GSH) with a broad range of electrophilic substrates including chemotherapeutic agents. As the above conjugates can be effluxed from cells easily, the efficacy of various chemotherapeutic agents is reduced. Recent studies suggest that GSTπ also plays an important role in inhibiting apoptosis through blocking the JNK signaling pathway. In this way, GSTπ protects cells from apoptosis. Therefore, GSTπ has become an attractive target against cancers, especially for drug-resistant tumors. A great deal of effort has been devoted to the discovery of GSTπ inhibitors and prodrugs over the last decade. In connection with authors' current research, we provide a review on studies on progress of GSTπ inhibitors and prodrugs along with the future strategies.

Synthesis of phosphaisocoumarin amidates via DIBAL-H-mediated selective amidation of phosphaisocoumarin esters.

A series of phosphaisocoumarin amidates were synthesized for the first time via DIBAL-H-mediated direct amidation of phosphaisocoumarin esters under mild conditions in good to excellent yields. The present reaction showed high selectivity. In each case, the phostone ring was intact and only the exocyclic ethoxy group was amidated. A plausible mechanism of the reaction was provided.