ABSTRACT
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.
Subject(s)
Pre-Eclampsia , Female , Humans , Pregnancy , AMP-Activated Protein Kinases/metabolism , Autophagy , Cell Line , Cell Movement , Mechanistic Target of Rapamycin Complex 1/metabolism , Placenta/metabolism , Pre-Eclampsia/metabolism , RNA, Small Interfering/metabolism , Trophoblasts/metabolism , Atrial Natriuretic FactorABSTRACT
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 â¼2.3 times and â¼9.2 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 â¢OH, O2â¢- 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.
Subject(s)
Graphite , Hydrogen , Light , CatalysisABSTRACT
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.
Subject(s)
Polymers/chemistry , Tissue Scaffolds/chemistry , Absorbable Implants , Animals , Biocompatible Materials/chemistry , Blood Vessels/growth & development , Humans , Polyesters/chemistry , Spectrum Analysis, RamanABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Glutathione S-Transferase pi/antagonists & inhibitors , Neoplasms/drug therapy , Apoptosis , Glutathione , Humans , ProdrugsABSTRACT
Lower global cognitive function scores are a common symptom of autism spectrum disorders (ASDs). This study investigates the effects of melatonin on hippocampal serine/threonine kinase signaling in an experimental ASD model. We found that chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued valproic acid (VPA, 600 mg/kg)-induced decreases in CaMKII (Thr286), NMDAR1 (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting total protein levels. Compared with control rats, the immunostaining of pyramidal neurons in the hippocampus revealed a decrease in immunolabeling intensity for phospho-CaMKII (Thr286) in the hippocampus of VPA-treated rats, which was ameliorated by chronic melatonin treatment. Consistent with the elevation of CaMKII/PKA/PKC phosphorylation observed in melatonin-treated rat, long-term potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as reflected by extracellular field potential slopes that increased from 56 to 60 min (133.4 ± 3.9% of the baseline, P < 0.01 versus VPA-treated rats) following high-frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin treatment also significantly improved social behavioral deficits at postnatal day 50 in VPA-treated rats. Taken together, the increased phosphorylation of CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin on autism symptoms.
Subject(s)
Autistic Disorder , Behavior, Animal/drug effects , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Hippocampus/drug effects , Hippocampus/enzymology , Melatonin/pharmacology , Analysis of Variance , Animals , Antioxidants/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2/analysis , Calcium-Calmodulin-Dependent Protein Kinase Type 2/chemistry , Disease Models, Animal , Female , Hippocampus/chemistry , Immunohistochemistry , Male , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley , Valproic Acid/pharmacologyABSTRACT
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.
Subject(s)
Amides/chemistry , Esters/chemistry , Isocoumarins/chemical synthesis , Organometallic Compounds/chemistry , Organophosphonates/chemical synthesis , Amines/chemistry , Magnetic Resonance Spectroscopy , Organophosphonates/chemistryABSTRACT
Quasi core shell alloyed CdSeS quantum dots (QDs) have been prepared through a facile aqueous-phase route employing microwave irradiation technique. The optical spectroscopy and structure characterization evidenced the quasi core shell alloyed structures of CdSeS QDs. The X-ray diffraction patterns of the obtained CdSeS QDs displayed peak positions very close to those of bulk cubic CdS crystal structures and the result of X-ray photoelectron spectroscopy data re-confirmed the thick CdS shell on the CdSe core. The TEM images and HRTEM images of the CdSeS QDs ascertained the well-defined spherical particles and a relatively narrow size distribution. On the basis, the stability of the obtained QDs in an oxidative environment was also discussed using etching reaction by H2O2. The experiments result showed the as-prepared QDs present high tolerance towards H2O2, obviously superior to the commonly used CdTe QDs and core-shell CdTe/CdS QDs, which was attributed to the unique quasi core-shell CdSeS crystal structure and the small lattice mismatch between CdSe and CdS semiconductor materials. This assay provided insight to obtain high stable crystal structured semiconductor nanocrystals in the design and synthesis process.
Subject(s)
Cadmium Compounds/chemistry , Microwaves , Quantum Dots , Selenium Compounds/chemistry , Sulfides/chemistry , Cadmium Compounds/chemical synthesis , Hydrogen Peroxide/chemistry , Oxidation-Reduction , Selenium Compounds/chemical synthesis , Sulfides/chemical synthesis , Water/chemistryABSTRACT
In the title mol-ecule, C(9)H(10)N(4)S, the dihedral angle between the benzene and triazole rings is 81.05â (5)°. In the crystal, N-Hâ¯N hydrogen bonds link the mol-ecules into infinite zigzag chains along [010].
ABSTRACT
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.
ABSTRACT
In the title compound, C(8)H(8)ClNO, the acetamide group is twisted out the benzene plane with a dihedral angle of 83.08â (1)°. In the crystal, mol-ecules are linked by N-Hâ¯O hydrogen bonds, forming layers parallel to the ab plane.
ABSTRACT
In the title compound, C(8)H(7)ClN(4), the phenyl and tetra-zole rings are inclined at a dihedral angle of 67.52â (6)°. In the crystal, mol-ecules are linked by an N-Hâ¯N hydrogen bond into a chain structure along [010]. π-π inter-actions with centroid-centroid distances of 3.526â (1)â Å between adjacent tetra-zole rings further link the chains, forming a ribbon structure.
ABSTRACT
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.
Subject(s)
Absorbable Implants , Coronary Vessels/physiology , Tissue Scaffolds , Animals , Female , Finite Element Analysis , Male , Polyesters , Stress, Mechanical , SwineABSTRACT
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.
Subject(s)
Nickel , Titanium , Fatigue , Humans , StentsABSTRACT
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.
Subject(s)
Chromatin , DNA Breaks, Double-Stranded , Chromatin/genetics , DNA End-Joining Repair , DNA Replication , Nuclear Proteins , Recombinational DNA Repair , Repressor Proteins , Tumor Suppressor p53-Binding Protein 1ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.