Hydrogen Peroxide-Mediated Oxygen Enrichment Eradicates Helicobacter pylori In Vitro and In Vivo.

Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo During oral administration and after drug withdrawal, H. pylori counts were evaluated by Giemsa staining in animal cohorts. An oxygen-enriched environment in which H. pylori could not survive was successfully established by adding hydrogen peroxide into several solutions and rabbit gastric juice. Hydrogen peroxide effectively killed H. pylori in Columbia blood agar and special peptone broth. Minimum inhibition concentrations and minimum bactericidal concentrations of hydrogen peroxide were both relatively stable after promotion of resistance for 30 generations, indicating that hydrogen peroxide did not easily promote resistance in H. pylori In models of Mongolian gerbils and Kunming mice, hydrogen peroxide has been shown to significantly eradicate and effectively prevent the recurrence of H. pylori without toxicity and damage to the gastric mucosa. The mechanism of hydrogen peroxide causing H. pylori death was related to the disruption of bacterial cell membranes. The oxygen-enriched environment achieved by hydrogen peroxide eradicates and prevents the recurrence of H. pylori by damaging bacterial cell membranes. Hydrogen peroxide thus provides an attractive candidate for anti-H. pylori treatment.

Establishing a rat model for the study of vitamin K deficiency.

The main vitamin K-deficient model, minidose warfarin, is different from the pathological mechanism of vitamin K deficiency, which is a shortage of vitamin K. The objective of this study was to establish a new method of vitamin K-deficient model combining a vitamin K-deficient diet with the intragastrical administration of gentamicin in rats. The clotting was assayed by an automated coagulation analyser. The plasma PIVKA-II was assayed by ELISA. The vitamin K status was detected by an HPLC-fluorescence system. In the diet- and gentamicin-induced vitamin K-deficient 14-day group, the rats had undetected vitamin K1 and vitamin K2 in the liver and a prolonged APTT. In the 21-day group, there was also a prolonged PT and a decrease of the FIX activities. In the 28-day group, the undetected vitamin K1 and vitamin K2, the prolonged PT and APTT, and the decrease of the FII, FVII, FIX, and FX activities prompted the suggestion that there were serious deficiencies of vitamin K and vitamin K-dependent coagulation in rats. It is suggested that the diet- and gentamicin-induced vitamin K-deficient 14-day or 21-day model can be used for studies related to the status of vitamin K. The vitamin K-deficient 28-day model can be applied to research involving both the status of vitamin K and of vitamin K-dependent coagulation. In conclusion, the combination of a vitamin K-deficient diet with the administration of gentamicin results in a useful model of vitamin K-deficieny.

Construction of S-Scheme heterojunction Ni11(HPO3)8(OH)6/CdS photocatalysts with open framework surface for enhanced H2 evolution activity.

The emerging S-scheme heterojunction shows a particular superiority in enhancing the efficiency of charge separation in photocatalyst. Herein, a Ni11(HPO3)8(OH)6/CdS heterojunctions (NiPO/CdS) are constructed for the first time by loading open framework structure NiPO on the surface of CdS nanoparticles (CdS NPs). The built-in electric field generated at the interface promotes the directional migration of photogenerated electrons from NiPO to CdS. This S-scheme pathway achieves a strong redox capacity and efficient carrier separation. More importantly, the unique triangular and hexagonal channels of NiPO facilitate the exposure of CdS active sites for proton adsorption, H2 production and escape. The hydrogen evolution rate of NiPO/CdS is 39 mmol g-1 h-1 under visible light irradiation, which is 6.5 times higher than that of pure CdS. The NiPO/CdS heterojunction also exhibits remarkable long-term stability. This study provides a new strategy for the ingenious design of S-scheme photocatalysts with excellent photocatalytic performance.

In-situ synthesis of NixCo4-xN/N-doped carbon ultrathin nanosheet arrays by supramolecular pyrolysis for boosting electrocatalytic hydrogen evolution in universal pH range water and natural seawater.

Nanostructured electrocatalysts with unique surfaces and interfaces for hydrogen evolution reaction (HER) are crucial for achieving high performance in universal pH water and natural seawater. Herein, a supramolecular liquid precursor was designed and applied to grow NixCo4-xN/N-doped carbon (NC) ultrathin nanosheet arrays (NixCo4-xN/NC) on carbon cloth through one-step pyrolysis. According to the X-ray absorption spectra, Ni was successfully alloyed into Co4N to form NixCo4-xN/NC, which regulates the intrinsic electronic structure and optimizes the adsorption/desorption energy of the catalyst. The unique structure of NixCo4-xN anchored on NC can increase the electron transport efficiency and protect the catalyst from corrosion in the extreme corrosive electrolytes. As a result, the NixCo4-xN/NC catalyst exhibits excellent electrocatalytic HER activity over a wide pH range requiring only 46, 75, and 55 mV at 10 mA/cm2 in the acidic, neutral, and alkaline electrolytes, respectively. Interestingly, the catalyst also shows outstanding HER performance in the natural seawater. This work provides an alternative option for the rational design of efficient electrocatalysts for universal pH water/seawater splitting.

Surface engineering of carbon-coated cobalt-doped nickel phosphides bifunctional electrocatalyst for boosting 5-hydroxymethylfurfural oxidation coupled with hydrogen evolution.

Multiple surface/interface engineering is an effective approach to develop efficient electrocatalysts for promoting the practical application of electrocatalysis and achieving carbon neutrality. Herein, a deep eutectic liquid precursor containing phosphorus was designed. The self-supported three-dimensional (3D) cobalt-doped Ni12P5/Ni3P nanowire networks coated with a thin layer of carbon (Co-NixP@C) were prepared by using an in-situ one-step pyrolysis method. The as-obtained Co-NixP@C hybrid possesses a superaerophobic/superhydrophilic surface, which could promote electrolyte diffusion and enhance bubble release. Density functional theory (DFT) calculations reveal that Co-doping in NixP@C can promote the adsorption and activation of 5-hydroxymethylfurfural (HMF) molecules, and optimize the energy barrier of H* absorption. The self-supported Co-NixP@C was used as an efficient bifunctional electrocatalyst for HMF oxidation coupled with hydrogen evolution reaction (HER) in a 1.0 M KOH solution. A nearly 100 % yield of 2,5-furandicarboxylic acid (FDCA) was achieved. The self-supported Co-NixP@C displayed high activity and stability for both HER and HMF conversion. The HMF oxidation coupled with HER can be efficiently driven by a 1.5 V commercial photovoltaic panel under sunlight. This study lays the foundation for large-scale industrialization in sustainable fine-chemical and energy engineering.

Ultrasmall RuM (Mo, W, Cr) Decorated on Nitrogen-doped Carbon Nanosheet with Strong Metal-support Interactions for Electrocatalytic Hydrogen Generation in Wide pH Range.

Developing efficient electrocatalysts for hydrogen evolution reaction (HER) in full pH range can promote the practical applications of hydrogen energy. In this work, nitrogen doped carbon nanosheets supported RuM (Mo, W, Cr) (RuM/NCN) are prepared through an ultrafast microwave approach. The carbon nanosheet structure coupled with the ultrasmall RuM nanoparticles can expose rich active sites to optimize the catalytic activity. Moreover, the strong metal-support interactions also favor to accelerate the reactions kinetics and improve stability. Thus, the developed RuMo/NCN (RuW/NCN) show excellent HER catalytic activities with overpotentials of 72 (75) mV, 82 (82) mV and 124 (119) mV to reach current density of 10 mA cm -2 in 1 M KOH, 0.5 M H2SO4 and alkaline seawater, respectively, and also achieve excellent performance in 1 M PBS. This work provides a valid and novel avenue to design efficient electrocatalysts in renewable energy-related fields.

Graphene oxide coupled high-index facets CdZnS with rich sulfur vacancies for synergistic boosting visible-light-catalytic hydrogen evolution in natural seawater: Experimental and DFT study.

Constructing photocatalysts with high activity and anti-photocorrosion is a key to harvesting hydrogen energy from seawater efficiently. Herein, graphene oxide closely coupled high-index facets CdZnS with rich sulfur vacancies (Vs-CZS@GO) has been successfully synthesized via one-pot sulfidation accompanied pyrolysis. DFT calculation confirmed the delicate surface/interface/defect engineering endowed high-index facets Vs-CZS@GO with a lower ΔGH* value and significant charge transfer behavior for efficient H2-generation. The synergistic effect of sulfur vacancy, high-index facets, and tightly coupling interface not only enhanced intrinsic active sites and carrier separation efficiencies, but also greatly promoted H2 evolution rate and stability. Consequently, Vs-CZS@GO displayed a significantly high H2-generation rate of 23.2 mmol∙g-1∙h-1 in natural seawater under visible-light irradiation, which is up to 82% of that in pure water. This work provides deeply insight into the synergistic regulation of electronic structure for exposed high-index facets photocatalysts via defect engineering and interface engineering for synergistic boosting visible-light-to-H2 evolution.

Quantitative analysis and pharmacokinetic study of a novel diarylurea EGFR inhibitor (ZCJ14) in rat plasma using a validated LC-MS/MS method.

1-(4-(Pyrrolidin-1-yl-methyl)phenyl)-3-(4-((3-(trifluoromethyl) phenyl)amino)quinazolin-6-yl)urea (ZCJ14), a novel epidermal growth factor receptor (EGFR) inhibitor, with diarylurea moiety, displays anticancer effect. In the present study, an LCMS/MS method was established to determine the concentration of ZCJ14 in rat plasma. Furthermore, the method was applied to investigate the pharmacokinetic characteristics of ZCJ14. Chromatographic separation of ZCJ14 and internal standard (IS) [1-phenyl-3-(4-((3-(trifluoromethyl)phenyl)amino) quinazolin-6-yl)urea] was accomplished by gradient elution using the Kromasil C18 column. The selected reaction monitoring transitions were performed at m/z 507.24→436.18 and 424.13→330.96 for ZCJ14 and IS, resp. The established method was linear over the concentration range of 10-1000 ng mL-1. The intra- and inter-day precisions were < 11.0 % (except for LLOQ which was up to 14.3 %) and the respective accuracies were within the range of 87.5-99.0 %. The extraction recovery and matrix effect were within the range of 88.4-104.5 % and 87.3-109.9 %, resp. ZCJ14 was stable under all storage conditions. The validated method was successfully applied to the pharmacokinetic study of ZCJ14 in rats, and the pharmacokinetic parameters have been determined. The oral bioavailability of ZCJ14 was found to be 46.1 %. Overall, this accurate and reliable quantification method might be useful for other diarylurea moiety-containing drugs.

Label-Free Quantitative Proteomic Profiling of LAD2 Mast Cell Releasates Reveals the Mechanism of Tween-80-Induced Anaphylactoid Reaction.

PURPOSE: Tween-80 is one of the most important causes resulting in anaphylactoid reaction. However, its mechanism remains unclear. Proteomic characterizations of mast cells' excreta in response to Tween-80 are assayed to investigate the mechanism of anaphylactoid reaction. EXPERIMENTAL DESIGN: A label-free LCMS/MS-based proteomics is used to analyze Tween-80-stimulated Laboratory of Allergic Diseases 2 (LAD2) mast cells releasates. The results of proteomic are analyzed by bioinformatics analysis. Western blotting is used to verify the expression of proteins. RESULTS: Overall, endocytosis, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and calcium signaling pathways play important roles in Tween-80-induced LAD2 cells activation by bioinformatics analysis. The expressions of relative proteins including actin-related protein 2/3 complexes, vacuolar protein sorting-associated protein, phosphorylation of transcription factor of P105 and P65, phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3 R), phosphoinositide phospholipase Cγ (PLCγ), and protein kinase C (PKC), are significantly increased in Tween-80 group compared to control. Tween-80 might be internalized via endocytosis, which induces degranulation by PLCγ/PKC pathways mediated calcium influx, and promotes the generation of inflammatory mediators via NF-κB pathway resulting in anaphylactoid reaction.

H2S Prevents Cyclosporine A-Induced Vasomotor Alteration in Rats.

Cyclosporine A (CsA) induces hypertension after transplantation. Hydrogen sulfide (H2S) was found to have hypotensive/vasoprotective effects in the cardiovascular system. The present study aims to investigate the role of H2S on CsA-induced vascular function disorder in rats. Rats were subcutaneously injected with CsA 25 mg/kg for 21 days. Blood pressure was measured by the tail-cuff method. Vasomotion was determined using a sensitive myograph. Western blotting and immunohistochemistry were used to quantify the protein expression of endothelin type A (ETA) receptor and essential MAPK pathway molecules. Vascular superoxide anion production and serum contents of malondialdehyde were determined. The results showed that sodium hydrosulfide (NaHS), a H2S donor, significantly attenuated the increase of blood pressure and contractile responses, and the upregulation of ETA receptor induced by CsA. In addition, NaHS could restore the CsA decreased acetylcholine-induced vasodilatation. Furthermore, NaHS blocked the CsA-induced elevation of reactive oxygen species level, extracellular signal-regulated kinase and p38 MAPK activities. In conclusion, H2S prevents CsA-induced vasomotor dysfunction. H2S attenuates CsA-induced ETA receptor upregulation, which may be associated with MAPK signal pathways. H2S ameliorates endothelial-dependent relaxation, which may be through antioxidant activity.

Formononetin upregulates nitric oxide synthase in arterial endothelium through estrogen receptors and MAPK pathways.

OBJECTIVES: Formononetin, a phytoestrogen, can improve arterial endothelial cell function by upregulating endothelial nitric oxide synthase (eNOS). The estrogen receptor plays an important role in the regulation of eNOS. This study investigated the hypothesis that formononetin upregulates eNOS through estrogen receptors and MAPK pathways. METHODS: The rat superior mesenteric arteries were cultured with formononetin or formononetin plus inhibitors for 24 h. The isometric tension of the arteries was measured using a myograph system. The mRNA and protein expression levels of eNOS were determined by real-time PCR and immunohistochemistry, respectively. KEY FINDINGS: Acetylcholine (ACh) relaxed the mesenteric arteries precontracted with 5-hydroxytryptamine. This relaxation could be enhanced by formononetin. The removal of endothelium or incubation with l-NAME (a NOS inhibitor) completely abolished the formononetin-enhanced relaxation induced by ACh, suggesting that the formononetin-enhanced vasodilatation is dependent on endothelium and NO pathway. The estrogen receptor inhibitor ICI 182780 attenuated the formononetin-enhanced vasodilatation induced by ACh, suggesting that the formononetin-enhanced arterial relaxation is mediated by the estrogen receptor. Formononetin increased the mRNA and protein expression levels of eNOS. ICI 182780, U0126 (an ERK1/2 inhibitor) and SP600125 (a JNK inhibitor) prevented the increases in arterial relaxation and eNOS levels. CONCLUSIONS: Formononetin upregulates eNOS expression in mesenteric arteries via estrogen receptors, ERK1/2 and JNK pathways.

Vasodilation and hypotension of a novel 3-benzylquinazolin- 4(3H)-one derivative via the inhibition of calcium flux.

A novel 3-benzylquinazolin-4(3H)-one derivative Z32, namely 6,7-dimethoxy-3-(3-chloro-4-(4-fluorobenzyloxy)benzyl)quinazolin-4(3H)-one was synthesized. The vasorelaxant and antihypertensive effects of Z32 and its underlying mechanisms were investigated. The following methods were used. The isometric tension of artery ring segments was recorded using an in vitro myography system. Changes in the calcium influx in mesenteric arteries were surveyed using a real-time confocal microscopy. The arterial pressure of spontaneously hypertensive rats was measured in vivo using a non-invasive tail cuff blood pressure system. The results showed that Z32 can relax rat mesenteric arteries pre-constricted by KCl or phenylephrine in a concentration-dependent manner. The vasorelaxant effects were not affected by the removal of the endothelium, blockade of potassium channels by tetraethylammonium chloride, or inhibition of either guanylate cyclase by ODQ, nitric oxide synthase by l-NAME, or cyclooxygenase by indomethacin. In Ca2+-free conditions, Z32 did not affect the constriction evoked by caffeine, however, significantly reduced the constrictions induced (1) by phenylephrine, (2) by CaCl2 in either phenylephrine (in the presence of verapamil) or KCl stimulated arteries, (3) by extracellular Ca2+ restoration in thapsigargin-treated mesenteric arteries, and (4) by the activator of protein kinase C phorbol-12, 13-dibutyrate, and the inhibitor of protein tyrosine phosphatase sodium orthovanadate. Further, Z32 decreased the systolic and diastolic arterial pressure of spontaneously hypertensive rats in a dose-dependent manner. In conclusion, Z32 lowers the arterial pressure and induces vasorelaxation through the inhibition of calcium flux, probably via a protein tyrosine phosphorylation-dependent way.