Measurement of nitric oxide spectral parameters: Considering the effects of CO2 and H2O.

A continuous-wave quantum cascade laser (CW-QCL) based spectrometer is developed to investigate the high-resolution spectral parameters of nitric oxide (NO). Line strengths and nitrogen (N2)-, carbon dioxide (CO2)-, water vapor (H2O)-, broadening coefficients for NO R(6.5) are measured. The spectral region ranging from 1989 cm-1 to 1901 cm-1, which is suitable for the in situ laser sensing of trace NO, is investigated. Spectral parameters are determined by fitting absorption spectra with multi-peak Voigt profiles. The measured intensities are compared to the HITRAN2020 database to assess the performance of the system and a good agreement within ±5% is obtained for the established lines. The measurement results are useful for the design of a spectroscopic sensor for monitoring exhaled breath NO, vehicle exhaust, and industrial emissions.

Synthesis and Biological Evaluation of Spirocyclic Chromane Derivatives as a Potential Treatment of Prostate Cancer.

As a significant co-activator involved in cell cycle and cell growth, differentiation and development, p300/CBP has shown extraordinary potential target in cancer therapy. Herein we designed new compounds from the lead compound A-485 based on molecular dynamic simulations. A series of new spirocyclic chroman derivatives was prepared, characterized and proven to be a potential treatment of prostate cancer. The most potent compound B16 inhibited the proliferation of enzalutamide-resistant 22Rv1 cells with an IC50 value of 96 nM. Furthermore, compounds B16-P2 displayed favorable overall pharmacokinetic profiles, and better tumor growth inhibition than A-485 in an in vivo xenograft model.

Highly visible-light-responsive Cu2O/rGO decorated with Fe3O4@SiO2 nanoparticles as a magnetically recyclable photocatalyst.

The rhombic dodecahedral cuprous oxide-reduced graphene oxide/core-shell Fe3O4@SiO2 composites (denoted as rCu2O-rGO/Fe3O4@SiO2) are successfully synthesized facilely via a wet-chemical route. The resulting rCu2O-rGO/Fe3O4@SiO2 combines the unique structure of Cu2O, electronic characteristics of reduced graphene oxide (rGO) and magnetic property of Fe3O4@SiO2 to be an effective and recoverable photocatalyst for the degradation of methyl orange (MO). The obtained results show that rCu2O-rGO/Fe3O4@SiO2 is capable of completely degrading MO in the presence of a very low catalyst concentration (0.125 g l-1) within a short time (60 min) under visible light compared to the reported catalysts. The observations may be due to the distinctive interfacial structures of rhombic dodecahedral Cu2O nanoparticles connected to rGO sheets that can enhance the separation of photogenerated electron-hole pairs, stabilize the Cu2O and increase MO adsorption, as evidenced by a variety of spectroscopic analyses (transmission electron microscopy, x-ray photoelectron spectroscopy and photoluminescence). More importantly, these efficient photocatalysts can easily be recovered under a magnetic field and remain highly photoactive towards the degradation of MO after cyclic tests, and may be promising photocatalysts for practical applications in the solar-energy purification of wastewater.

Effects of Glycosylation on Biodistribution and Imaging Quality of Necrotic Myocardium of Iodine-131-Labeled Sennidins.

PURPOSE: Sennidins are necrosis-avid agents for noninvasive assessment of myocardial viability which is important for patients with myocardial infarction (MI). However, high accumulation of radioactivity in the liver interferes with the assessment of myocardial viability. In this study, we compared sennidins with sennosides to investigate the effects of glycosylation on biodistribution and imaging quality of sennidins. PROCEDURES: Sennidin A (SA), sennidin B (SB), sennoside A (SSA), and sennoside B (SSB) were labeled with I-131. In vitro binding to necrotic cells and hepatic cells and in vivo biodistribution in rats with muscular necrosis were evaluated by gamma counting, autoradiography, and histopathology. Single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired in rats with acute MI. RESULTS: The uptake of [131I]SA, [131I]SSA, [131I]SB, and [131I]SSB in necrotic cells was significantly higher than that in viable cells (p < 0.05). Hepatic cells uptake of [131I]SSA and [131I]SSB were 7-fold and 10-fold lower than that of corresponding [131I]SA and [131I]SB, respectively. The biodistribution data showed that the radioactivities in the liver and feces were significantly lower with [131I]sennosides than those with [131I]sennidins (p < 0.01). Autoradiography showed preferential accumulation of these four radiotracers in necrotic areas of muscle, confirmed by histopathology. SPECT/CT imaging studies showed better image quality with [131I]SSB than with [131I]SB due to less liver interference. CONCLUSIONS: Glycosylation significantly decreased the liver uptake and improved the quality of cardiac imaging. [131I]SSB may serve as a promising necrosis-avid agent for noninvasive assessment of myocardial viability.

Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium.

Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I-anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I-rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis.

Guanine nucleotide induced conformational change of Cdc42 revealed by hydrogen/deuterium exchange mass spectrometry.

Cdc42 regulates pathways related to cell division. Dysregulation of Cdc42 can lead to cancer, cardiovascular diseases and neurodegenerative diseases. GTP induced activation mechanism plays an important role in the activity and biological functions of Cdc42. P-loop, Switch I and Switch II are critical regions modulating the enzymatic activity of Cdc42. We applied amide hydrogen/deuterium exchange coupled with liquid chromatography mass spectrometry (HDXMS) to investigate the dynamic changes of apo-Cdc42 after GDP, GTP and GMP-PCP binding. The natural substrate GTP induced significant decreases of deuteration in P-loop and Switch II, moderate changes of deuteration in Switch I and significant changes of deuteration in the α7 helix, a region far away from the active site. GTP binding induced similar effects on H/D exchange to its non-hydrolysable analog, GMP-PCP. HDXMS results indicate that GTP binding blocked the solvent accessibility in the active site leading to the decrease of H/D exchange rate surrounding the active site, and further triggered a conformational change resulting in the drastic decrease of H/D exchange rate at the remote α7 helix. Comparing the deuteration levels in three activation states of apo-Cdc42, Cdc42-GDP and Cdc42-GMP-PCP, the apo-Cdc42 has the most flexible structure, which can be stabilized by guanine nucleotide binding. The rates of H/D exchange of Cdc42-GDP are between the GMP-PCP-bound and the apo form, but more closely to the GMP-PCP-bound form. Our results show that the activation of Cdc42 is a process of conformational changes involved with P-loop, Switch II and α7 helix for structural stabilization.

Synthesis and Preclinical Evaluation of Radioiodinated Hypericin Dicarboxylic Acid as a Necrosis Avid Agent in Rat Models of Induced Hepatic, Muscular, and Myocardial Necroses.

Myocardial infarction (MI) leads to substantial morbidity and mortality around the world. Accurate assessment of myocardial viability is essential to assist therapies and improve patient outcomes. (131)I-hypericin dicarboxylic acid ((131)I-HDA) was synthesized and evaluated as a potential diagnostic agent for earlier assessment of myocardium viability compared to its preceding counterpart (131)I-hypericin ((131)I-Hyp) with strong hydrophobic property, long plasma half-life, and high uptake in mononuclear phagocyte system (MPS). Herein, HDA was synthesized and characterized, and self-aggregation constant Kα was analyzed by spectrophotometry. Plasma half-life was determined in healthy rats by γ-counting. (131)I-HDA and (131)I-Hyp were prepared with iodogen as oxidant. In vitro necrosis avidity of (131)I-HDA and (131)I-Hyp was evaluated in necrotic cells induced by hyperthermia. Biodistribution was determined in rat models of induced necrosis using γ-counting, autoradiography, and histopathology. Earlier imaging of necrotic myocardium to assess myocardial viability was performed in rat models of reperfused myocardium infarction using single photon emission computed tomography/computed tomography (SPECT/CT). As a result, the self-aggregation constant Kα of HDA was lower than that of Hyp (105602 vs 194644, p < 0.01). (131)I-HDA displayed a shorter blood half-life compared with (131)I-Hyp (9.21 vs 31.20 h, p < 0.01). The necrotic-viable ratio in cells was higher with (131)I-HDA relative to that with (131)I-Hyp (5.48 vs 4.63, p < 0.05). (131)I-HDA showed a higher necrotic-viable myocardium ratio (7.32 vs 3.20, p < 0.01), necrotic myocardium-blood ratio (3.34 vs 1.74, p < 0.05), and necrotic myocardium-lung ratio (3.09 vs 0.61, p < 0.01) compared with (131)I-Hyp. (131)I-HDA achieved imaging of necrotic myocardium at 6 h postinjection (p.i.) with SPECT/CT, earlier than what (131)I-Hyp did. Therefore, (131)I-HDA may serve as a promising necrosis-avid diagnostic agent for earlier imaging of necrotic myocardium compared with (131)I-Hyp. This may support further development of radiopharmaceuticals ((123)I and (99m)Tc) based on HDA for SPECT/CT of necrotic myocardium.

Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.

Synthesis and Evaluation of 131I-Skyrin as a Necrosis Avid Agent for Potential Targeted Radionuclide Therapy of Solid Tumors.

An innovative anticancer approach targeted to necrotic tissues, which serves as a noncancerous and generic anchor, may present a breakthrough. Necrosis avid agents with a flat conjugate aromatic structure selectively accumulate in necrotic tissues, but they easily form aggregates that undesirably distribute to normal tissues. In this study, skyrin, a dianthraquinone compound with smaller and distorted π-cores and thus decreased aggregates as compared with hypericin (Hyp), was designed to target necrosis for tumor therapy. Aggregation studies of skyrin by UV/vis spectroscopy showed a smaller self-association constant with skyrin than with Hyp. Skyrin was labeled by iodine-131 with a radiochemical purity of 98% and exhibited good stability in rat serum for 72 h. In vitro cell uptake studies showed significant difference in the uptake of 131I-skyrin by necrotic cells compared to normal cells (P < 0.05). Compared in rats with liver and muscle necrosis, radiobiodistribution, whole-body autoradiography, and SPECT/CT studies revealed higher accumulation of 131I-skyrin in necrotic liver and muscle (p < 0.05), but lower uptake in normal organs, relative to that of 131I-Hyp. In mice bearing H22 tumor xenografts treated with combretastatin A4 disodium phosphate, the highest uptake of 131I-skyrin was found in necrotic tumor. In conclusion, 131I-skyrin appears a promising agent with reduced accumulation in nontarget organs for targeted radionuclide therapy of solid tumors.

Effects of Interface Layers and Domain Walls on the Ferroelectric-Resistive Switching Behavior of Au/BiFeO3/La0.6Sr0.4MnO3 Heterostructures.

The electric field effects on the electric and magnetic properties in multiferroic heterostructures are important for not only understanding the mechanisms of certain novel physical phenomena occurring at heterointerfaces but also offering a route for promising spintronic applications. Using the Au/BiFeO3/La0.6Sr0.4MnO3 (Au/BFO/LSMO) multiferroic heterostructure as a model system, we investigated the ferroelectric-resistive switching (RS) behaviors of the heterostructure. Via the manipulation of the BFO ferroelectric polarizations, the nonvolatile tristate of RS is observed, which is closely related to the Au/BFO and BFO/LSMO interface layers and the highly conducting BFO domain walls (DWs). More interestingly, according to the magnetic field dependence of the RS behavior, the negative magnetoresistance effect of the third resistance state, corresponding to the abnormal current peak in current-pulse voltage hysteresis near the electric coercive field, is also observed at room temperature, which mainly arises from the possible oxygen vacancy accumulation and Fe ion valence variation in the DWs.

Research on characteristic spectrum extracting and matching for high-fidelity reproduction.

Reconstructing the spectrum rapidly and accurately is the key to the research on high-fidelity reproduction. A characteristic spectrum extracting and matching method for high-fidelity printing is proposed aiming at the problem of complex conversion between spectrum and ink combination caused by multi-color. The method filters and extracts feature bands of primary ink through derivative spectrum, and a characteristic spectrum multi-threshold coding method is proposed. Considering the problem of subarea judgment in hi-fi printing, an average derivative spectrum is taken as characteristic spectrum of each subarea and a spectrum matching method between target spectrum and average derivative spectrum of sub-spaces is proposed. The results show that the feature bands extracted can represent spectral characteristic of primary color significantly and the precision of color conversion model based on feature bands is higher than the model based on full bands. The spectrum matching method can achieve a high accuracy in sub-space judgments and greatly improve the efficiency of color convention. The spectrum extracting and matching method has the high practicability.

Structural evolution from Bi4.2K0.8Fe2O9+δ nanobelts to BiFeO3 nanochains in vacuum and their multiferroic properties.

In this paper, we report the structural evolution of Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts to BiFeO3 nanochains and the related variations in multiferroic properties. By using in situ transmission electron microscopy with comprehensive characterization, it was found that the layered perovskite multiferroic Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts were very unstable in a vacuum environment, with Bi being easily removed. Based on this finding, a simple vacuum annealing method was designed which successfully transformed the Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts into one-dimensional BiFeO(3) nanochains. Both the Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts and the BiFeO3 nanochains showed multiferroic behavior, with their ferroelectric and ferromagnetic properties clearly established by piezoresponse and magnetic measurements, respectively. Interestingly, the BiFeO(3) nanochains had a larger magnetization than the Bi(4.2)K(0.8)Fe(2)O(9+δ) nanobelts. Moreover, the BiFeO(3) nanochains exhibited a surprisingly large exchange bias with small training effects. This one-dimensional BiFeO(3) multiferroic nanostructure characterized by a relatively stable exchange bias offers important functionalities that may be attractive for device applications.

Non-volatile 180° magnetization reversal by an electric field in multiferroic heterostructures.

The deterministic rotation of magnetization by electric fields is a challenging issue for future low-power spintronics. In a Co/0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 multiferroic heterostructure, piezostrain-mediated, macroscopically maneuverable, and non-volatile magnetization reversal without an applied magnetic field is demonstrated. This, combined with the presented phase-field simulations, is of practical relevance for designing prototype devices.

Fluoroketone inhibition of Ca(2+)-independent phospholipase A2 through binding pocket association defined by hydrogen/deuterium exchange and molecular dynamics.

The mechanism of inhibition of group VIA Ca(2+)-independent phospholipase A(2) (iPLA(2)) by fluoroketone (FK) ligands is examined by a combination of deuterium exchange mass spectrometry (DXMS) and molecular dynamics (MD). Models for iPLA(2) were built by homology with the known structure of patatin and equilibrated by extensive MD simulations. Empty pockets were identified during the simulations and studied for their ability to accommodate FK inhibitors. Ligand docking techniques showed that the potent inhibitor 1,1,1,3-tetrafluoro-7-phenylheptan-2-one (PHFK) forms favorable interactions inside an active-site pocket, where it blocks the entrance of phospholipid substrates. The polar fluoroketone headgroup is stabilized by hydrogen bonds with residues Gly486, Gly487, and Ser519. The nonpolar aliphatic chain and aromatic group are stabilized by hydrophobic contacts with Met544, Val548, Phe549, Leu560, and Ala640. The binding mode is supported by DXMS experiments showing an important decrease of deuteration in the contact regions in the presence of the inhibitor. The discovery of the precise binding mode of FK ligands to the iPLA(2) should greatly improve our ability to design new inhibitors with higher potency and selectivity.