Nitric oxide (NO) is an essential endogenous signaling molecule regulating multifaceted physiological functions in the (cardio)vascular, neuronal, and immune systems. Due to the short half-life and ...location-/concentration-dependent physiological function of NO, translational application of NO as a novel therapeutic approach, however, awaits a strategy for spatiotemporal control on the delivery of NO. Inspired by the magnetic hyperthermia and magneto-triggered drug release featured by Fe3O4 conjugates, in this study, we aim to develop a magnetic responsive NO-release material (MagNORM) featuring dual NO-release phases, namely, burst and steady release, for the selective activation of NO-related physiology and treatment of bacteria-infected cutaneous wound. After conjugation of NO-delivery Fe(μ-S-thioglycerol)(NO)22 with a metal–organic framework (MOF)-derived porous Fe3O4@C, encapsulation of obtained conjugates within the thermo-responsive poly(lactic-co-glycolic acid) (PLGA) microsphere completes the assembly of MagNORM. Through continuous/pulsatile/no application of the alternating magnetic field (AMF) to MagNORM, moreover, burst/intermittent/slow release of NO from MagNORM demonstrates the AMF as an ON/OFF switch for temporal control on the delivery of NO. Under continuous application of the AMF, in particular, burst release of NO from MagNORM triggers an effective anti-bacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). In addition to the magneto-triggered bactericidal effect of MagNORM against E. coli-infected cutaneous wound in mice, of importance, steady release of NO from MagNORM without the AMF promotes the subsequent collagen formation and wound healing in mice.
To ensure clean drinking water, viable pathogens in water must be rapidly and efficiently screened. The traditional culture or spread-plate process-the conventional standard for bacterial ...detection-is laborious, time-consuming, and unsuitable for rapid detection. Therefore, we developed a colorimetric assay for rapid microorganism detection using a metabolism-based approach. The reaction between a viable microorganism and the combination of 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt (WST-8) and 1-methoxy-5-methylphenazinium methyl sulfate (mPMS) results in a color change. In combination with a microplate reader, WST-8-mPMS reactivity was leveraged to develop a colorimetric assay for the rapid detection of various bacteria. The detection limit of the WST-8-mPMS assay for both gram-negative and gram-positive bacteria was evaluated. This WST-8-mPMS assay can be used to perform colorimetrical semi-quantitative detection of various bacterial strains in buffers or culture media within 1 h without incubation before the reaction. The easy-to-use, robust, rapid, and sensitive nature of this novel assay demonstrates its potential for practical and medical use for microorganism detection.
Nanoscale zerovalent iron (NZVI) features potential application to biomedicine, (electro-/photo)catalysis, and environmental remediation. However, multiple-synthetic steps and limited ZVI content ...prompt the development of a novel strategy for efficient preparation of NZVI composites. Herein, a dinitrosyl iron complex (N3MDA)Fe(NO)2 (1-N 3 MDA) was explored as a molecular precursor for one-pot photosynthesis of a cubic Fe@Fe3O4 core–shell nanoparticle (ZVI% = 60%) well-dispersed in an N-doping carbonaceous polymer (NZVI@NC). Upon photolysis of 1-N 3 MDA, photosensitizer Eosin Y, and sacrificial reductant TEA, the α-diimine N3MDA and noninnocent NO ligands (1) enable the slow reduction of 1-N 3 MDA into an unstable (N3MDA)Fe(NO)2− species, (2) serve as a capping reagent for controlled nucleation of zerovalent Fe atom into Fe nanoparticle, and (3) promote the polymerization of degraded Eosin Y with N3MDA yielding an N-doping carbonaceous matrix in NZVI@NC. This discovery of a one-pot photosynthetic process for NZVI@NC inspires continued efforts on its application to photolytic water splitting and ferroptotic chemotherapy in the near future.
Through nitrosylation of Fe–S proteins, or the chelatable iron pool, a dinitrosyl iron unit (DNIU) Fe(NO)2 embedded in the form of low-molecular-weight/protein-bound dinitrosyl iron complexes ...(DNICs) was discovered as a metallocofactor assembled under inflammatory conditions with elevated levels of nitric oxide (NO) and superoxide (O2 –). In an attempt to gain biomimetic insights into the unexplored transformations of the DNIU under inflammation, we investigated the reactivity toward O2 – by a series of DNICs (NO)2Fe(μ-MePyr)2Fe(NO)2 (1) and (NO)2Fe(μ-SEt)2Fe(NO)2 (3). During the superoxide-induced conversion of DNIC 1 into DNIC (K-18-crown-6-ether)2(NO2)Fe(μ-MePyr)4(μ-O)2(Fe(NO)2)4 (2-K-crown) and a Fe3+(MePyr) x (NO2) y (O) z n adduct, stoichiometric NO monooxygenation yielding NO2 – occurs without the transient formation of peroxynitrite-derived •OH/•NO2 species. To study the isoelectronic reaction of O2(g) and one-electron-reduced DNIC 1, a DNIC featuring an electronically localized {Fe(NO)2}9-{Fe(NO)2}10 electronic structure, K-18-crown-6-ether(NO)2Fe(μ-MePyr)2Fe(NO)2 (1-red), was successfully synthesized and characterized. Oxygenation of DNIC 1-red leads to the similar assembly of DNIC 2-K-crown, of which the electronic structure is best described as paramagnetic with weak antiferromagnetic coupling among the four S = 1/2 {FeIII(NO – )2}9 units and S = 5/2 Fe3+ center. In contrast to DNICs 1 and 1-red, DNICs 3 and K-18-crown-6-ether(NO)2Fe(μ-SEt)2Fe(NO)2 (3-red) display a reversible equilibrium of “3 + O2 – ⇋ 3-red + O2(g)”, which is ascribed to the covalent Fe(μ-SEt)2Fe core and redox-active Fe(NO)2 unit. Based on this study, the supporting/bridging ligands in dinuclear DNIC 1/3 (or 1-red/3-red) control the selective monooxygenation of NO and redox interconversion between O2 – and O2 during reaction with O2 – (or O2).
The oxidation rate of SiC can be greatly enhanced by pre-amorphization ion-implantation (PAI), and the PAI process has been employed to form the LOCal Oxidation of SiC (LOCOSiC) structure for device ...isolation in SiC integrated circuits (ICs). This work presents the study on the defect layer below the thermally grown SiO 2 and the impact of the defect layer on devices. The deep-level transient spectroscopy (DLTS) analysis reveals that the defect layer consists lots of C vacancies and Si vacancies. The leakage current of the edge-intensive N + /P-junction exhibits stronger temperature dependence than that of the P + /N-junction. This result confirms that C vacancy is an effective lifetime killer in n-type SiC, but not in p-type SiC. Although these defects increase the leakage current of the edge-intensive SiC N + /P-junction by 42 times at 150 °C compared with the junction with conventional chemical vapor deposited (CVD) field oxide (FOX), the leakage current is still much lower than the required OFF-state current of ICs. The defect layer has high resistance, and it is hard to let the SiC surface into inversion state so that the threshold voltage of the field MOSFET is higher than ±24 V.
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•A 2-stage method is proposed to predict the 1-month ahead price for 13 U.S. indices.•Ensembles of macroeconomic factors alone are more predictive than time-series models.•Errors in ...time-series models are explained by the ensembles of macroeconomic factors.•A decision support system for predicting the monthly stock price is presented.•The code is freely available for investors and researchers.
This paper proposes a two-stage approach that can be used to investigate whether the information hidden in macroeconomic variables (alone) can be used to accurately predict the one-month ahead price for major U.S stock and sector indices. Stage 1 is constructed to evaluate the hypothesis that the price for different indices is driven by different economic indicators. It consists of three phases. In phase I, the data is automatically acquired using freely available APIs (application programming interfaces) and prepared for analysis. Phase II reduces the set of potential predictors without the loss of information through several variable selection methods. The third phase employs four ensemble models and three time-series models for prediction. The prediction performance of the seven models are compared using the Mean Absolute Percent Error (and two additional metrics). If the hypothesis were to be true, one expects that the performance of the ensemble models to outperform the time-series models since the information in the economy is more important than the information in previous prices. In Stage 2, a hybrid approach of the recurring neural network used for time-series prediction (i.e., the LSTM) and the ensemble models is constructed to examine the secondary hypothesis that the residuals from the time-series models are not random and can be explained by the macroeconomic indicators. To test the two hypotheses, the monthly closing prices for 13 U.S. stock and sector indices and the corresponding values for 23 macroeconomic indicators were collected from 01/1992–10/2016. Based on the case study, the four ensembles prediction performance were superior to that of the three time-series models. The MAPE of the best model for a given index was < 1.87%. The Stage 2 results also show that the three evaluation metrics (RMSE, MAPE and MAE) can be typically improved by 25–50% by incorporating the information hidden in the macroeconomic indicators (through the ensemble approach). Thus, this paper shows that, for the analysis period and the indices studied, the macro-economic indicators are leading predictors of the price of 13 U.S. sector indices.
Nanoscale zerovalent iron (NZVI) features potential application to biomedicine, (electro-/photo)catalysis, and environmental remediation. However, multiple-synthetic steps and limited ZVI content ...prompt the development of a novel strategy for efficient preparation of NZVI composites. Herein, a dinitrosyl iron complex (N
MDA)Fe(NO)
(
) was explored as a molecular precursor for one-pot photosynthesis of a cubic Fe@Fe
O
core-shell nanoparticle (ZVI% = 60%) well-dispersed in an N-doping carbonaceous polymer (NZVI@NC). Upon photolysis of
, photosensitizer Eosin Y, and sacrificial reductant TEA, the α-diimine N
MDA and noninnocent NO ligands (1) enable the slow reduction of
into an unstable (N
MDA)Fe(NO)
species, (2) serve as a capping reagent for controlled nucleation of zerovalent Fe atom into Fe nanoparticle, and (3) promote the polymerization of degraded Eosin Y with N
MDA yielding an N-doping carbonaceous matrix in NZVI@NC. This discovery of a one-pot photosynthetic process for NZVI@NC inspires continued efforts on its application to photolytic water splitting and ferroptotic chemotherapy in the near future.
Endogenous signals, such as nitric oxide (NO) and electrons, induce multifaceted physiological functions in the regulation of cell fate as well as vascular and neuronal systems. However, clinical ...difficulties exist due to the short half-life of NO and the lack of tools to spatiotemporally drive gas release and electrical stimulation. Here, we propose a "magnetoelectric massager" strategy based on alternating magnetic field (AMF)-triggered on-demand NO release and electrical stimulation to restore brain function in traumatic brain injury. The NO and electron transport system was constructed as a metal-organic framework (MOF)-derived molybdenum carbide octahedron (MoCx-Cu) and an NO donor (S-nitrosoglutathione, GSNO), which was embedded in an implantable silk in a microneedle. Under AMF irradiation, eddy currents on conductive MoCx-Cu induced NO release from GSNO through electrical stimulation, thereby significantly promoting the differentiation and growth of neural stem cell (NSC) synapses. A combined strategy of in vivo traumatic brain injury allows NO and electrical stimulation-mediated inhibition of inflammation, angiogenesis, and neuronal interrogation.
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●A "magnetoelectric massager" strategy triggered on-demand NO release and electrical stimulation to restore brain function.
Reaction of compounds (NO)2Fe(TMEDA) and BH4− affords the first hydride-containing dinitrosyl iron complex (DNIC) (NO)2Fe(η2-BH4)− (2). Hydride-insertion reactivity of DNIC 2 promotes the reductive ...transformation of CS2 into DNIC (NO)2Fe(η3-HCS2)−, the first DNIC featuring both linear/bent NO ligands and Fe 3dz2-to-HCS2 π* backbonding interaction.
The pumping function of corneal endothelial cells (CECs) plays a pivotal role in the maintenance of corneal water homeostasis. Corneal endothelial dysfunction (CED) leads to corneal edema and ...opacity, but with the exception of keratoplasty, no optimal therapeutic strategies have been established for CED. In this study, we aimed to investigate the ameliorative effect of ascorbic acid (AA) on CED and the underlying mechanism of action in the corneal endothelium.
Rabbit corneal endothelial damage was induced by anterior chamber injection of benzalkonium chloride (BAK). AA was topically administered to the corneal surface, and the transparency and thickness of the cornea were assessed by external eye photography, slit-lamp photography, and ultrasonic pachymetry. To further analyze the mechanism, rabbit CECs and immortalized human CECs (B4G12 cells) were cultured. A ferric reducing/antioxidant and AA (FRASC) assay was performed to measure the AA concentration. Cell proliferation was evaluated by cell counting and bromodeoxyuridine (BrdU) labeling assays, and protein expression was examined by liquid chromatography–mass spectrometry (LC/MS) and immunoblotting. The involvement of glucose transporter 1 (GLUT1) and phospho-ERK was evaluated via GLUT1-siRNA and phospho-ERK inhibitor (PD98059) treatment.
We observed that topical AA ameliorates BAK-induced rabbit corneal endothelial damage. Furthermore, we demonstrated that AA is transported into B4G12 cells via GLUT1, and afterward, AA increases ERK phosphorylation and promotes cell proliferation. Our findings indicate that CEC proliferation stimulated via the noncanonical AA-GLUT1-ERK axis contributes to AA-enhanced healing of CED.
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