Investigating the L-Glu-NMDA receptor-H2S-NMDA receptor pathway that regulates gastric function in rats' nucleus ambiguus.

Background: In previous investigations, we explored the regulation of gastric function by hydrogen sulfide (H2S) and L-glutamate (L-Glu) injections in the nucleus ambiguus (NA). We also determined that both H2S and L-Glu have roles to play in the physiological activities of the body, and that NA is an important nucleus for receiving visceral sensations. The purpose of this study was to explore the potential pathway link between L-Glu and H2S, resulting in the regulation of gastric function. Methods: Physiological saline (PS), L-glutamate (L-Glu, 2 nmol), NaHS (2 nmol), D-2-amino-5-phopho-novalerate (D-AP5, 2 nmol) + L-Glu (2 nmol), aminooxyacetic acid (AOAA, 2 nmol) + L-Glu (2 nmol), D-AP5 (2 nmol) + NaHS (2 nmol) were injected into the NA. A balloon was inserted into the stomach to observe gastric pressure and for recording the changes of gastric smooth muscle contraction curve. The gastric fluid was collected by esophageal perfusion and for recording the change of gastric pH value. Results: Injecting L-Glu in NA was found to significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01). On the other hand, injecting the PS, pre-injection N-methyl-D-aspartate (NMDA) receptor blocker D-AP5, cystathionine beta-synthase (CBS) inhibitor AOAA and re-injection L-Glu did not result in significant changes (p > 0.05). The same injection NaHS significantly inhibit gastric motility and promote gastric acid secretion in rats (p < 0.01), but is eliminated by injection D-AP5 (p > 0.05). Conclusion: The results indicate that both exogenous L-Glu and H2S injected in NA regulate gastric motility and gastric acid secretion through NMDA receptors. This suggests that NA has an L-Glu-NMDA receptor-CBS-H2S pathway that regulates gastric function.

Effects of solution chemistry on dielectric barrier atmospheric non-thermal plasma for operative degradation of antiretroviral drug nevirapine.

The global prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has been an environmental menace. Tons of drug wastes from antiretroviral therapy are released into the environment annually. We, for the first time, employed the novel dielectric barrier atmospheric non-thermal plasma (DBANP) discharge, to mitigate the inadvertent pollution arising from the antiretroviral therapy. A 40-min treatment of nevirapine achieved >94 % (0.075 min-1) removal efficiency at discharge power of 63.5 W and plasma working gas of atmospheric air. Chemical probes confirmed •OH, ONOO- and eaq- as the dominant reactive species whilst further revealing the reaction acceleration role of NaNO3 and CCl4 which are known reaction terminators. The commonly coexisting inorganic anions potentiated nevirapine removal with over 98 % efficiency, achieving the highest rate constant of 0.148 min-1 in this study. Moreover, the initial solution pH (1.5-11.1) was no limiting factor either. The insensitivity of the DBANP discharge to actual water matrices was an eminent inference of its potential applicability in practical conditions. With reference to data obtained from the liquid chromatography-mass spectrometer analysis, nevirapine degradation pathway was proposed. A nucleophilic attack by ONOO- at the cyclopropyl group and •OH attack at the carbonyl carbon of the amide group, respectively, initiated nevirapine degradation process. It is anticipated that the findings herein, will provide new insights into antiretroviral drug waste management in environmental waters using the innovative and green non-thermal plasma process.

Potential and mechanism of disinfection by-products removal in drinking water by bubbling corona discharge.

Disinfection by-products (DBPs) with significant teratogenic and carcinogenic properties have become a growing concern among the public. As an efficient and environmentally friendly technology, non-thermal plasma offers potential for removing emerging micro-pollutants. In this study, the degradation performance of bubbling corona discharge was evaluated on 24 halogenated alicyclic and aliphatic DBPs present in drinking water at concentrations ranging from ng/L to µg/L. The degradation of DBPs followed pseudo-first-order kinetics with rate constants (kobs) in the descending order of halonitromethanes (HNMs), halogenated benzoquinones (HBQs), haloacetonitriles, trihalomethanes (THMs), haloketones, halogenated aldehydes, and haloacetic acids (HAAs). THMs, HNMs, and HBQs were effectively removed within 5 min under a discharge power of 28 W. Degradation rates achieved by plasma treatment surpass those of other conventional treatment technologies. The required energy consumption was in the range of 5-30 kW·h/m3/order. Furthermore, the study investigated the effects of discharge power, initial concentration, and economic analysis on the degradation of four selected DBPs as representatives of mono-, di- and multi-carbon-containing DBPs, namely chloroform (TCM) and bromoform (TBM), tribromoacetic acid (TBAA), and 2,3,5,6-tetrachloro-1,4-benzoquinone (TetraC-BQ). Reactive radicals in the plasma system were investigated using electron paramagnetic resonance, optical emission spectroscopy, fluorimetry, and radical scavengers. Hydrated electrons and hydroxyl radicals played an important role in the removal of DBPs. The intermediates generated during the degradation of TCM, TBM, TBAA, and TetraC-BQ were identified, and the possible degradation pathways for mono- and binary C-DBPs and HBQs were deduced. The breakdown of HBQs did not produce secondary contamination with aliphatic DBPs. The carbon in DBPs was primarily converted to formic acid, acetic acid, and oxalic acid, and the halogens were mainly converted to halogen ions. Additionally, luminescent bacteria toxicity testing confirmed that plasma treatment could reduce the acute toxicity of water samples. These findings demonstrate the potential of plasma treatment as a post-treatment device at the household level.

Simultaneous degradation of glucocorticoids and sterilization using bubbling corona discharge plasma based systems: A promising terminal water treatment facility for hospital wastewater.

Glucocorticoids (GCs) have drawn great concern due to their widespread contamination in the environment and application in treating patients with COVID-19. Due to the lack of data about GC removal using advanced treatment processes, a novel Paralleling and bubbling corona discharge reactor (PBCD) combined with iron-loaded activated-carbon fibre (Fe-ACF) was addressed in this study to degrade GCs represented by Hydrocortisone (HC) and Betamethasone (BT). The results showed that the PBCD-based system can degrade GCs effectively and can achieve effective sterilization. The removal rates of GCs were ranked as PBCD/Fe-ACF > PBCD/ACF > PBCD. The concentration of E. coli was reduced from 109 to 102 CFU/mL after 60 min of PBCD-based system treatment. The abundance of bacteria in actual Hospital wastewater (HWW) was significantly reduced. Plasma changed the physical and chemical properties of ACF and Fe-ACF by etching axial grooves and enhancing stretching vibrations of surface functional groups, thus promoting adsorption and catalytic degradation. For GC degradation, the functional reactive species were identified as •OH, 1O2, and •O2 radicals. Possible degradation pathways for HC and BT were proposed, which mainly included defluorination, keto acid decarboxylation, demethylation, intramolecular cyclization, cleavage and ester hydrolysis, indicating a reduction in GC toxicity. Since GCs are widely used in patients with COVID-19 and their wastewater needs to be sterilized simultaneously, the intensive and electrically driven PBCD-based system is promising in GC pollution control and sterilization in terminal water treatment facilities.

Maintenance of multipotency of bone marrow mesenchymal stem cells on poly(ε-caprolactone) nanoneedle arrays through the enhancement of cell-cell interaction.

Mesenchymal stem cells (MSCs), with high self-renewal ability and multipotency, are commonly used as the seed cells for tissue engineering. However, the reduction and loss of multipotential ability after necessary expansion in vitro set up a heavy obstacle to the clinical application of MSCs. Here in this study, we exploit the autologous crystallization ability of biocompatible poly (ε-caprolactone) (PCL) to obtain uniformly distributed nanoneedle arrays. By controlling the molecular weight of PCL, nanoneedle with a width of 2 µm and height of 50 nm, 80 nm, and 100 nm can be successfully fabricated. After surface chemical modification with polydopamine (PDA), the water contact angle of the fabricated PCL nanoneedle arrays are reduced from 84° to almost 60° with no significant change of the nanostructure. All the fabricated substrates are cultured with bone marrow MSCs (BMMSCs), and the adhesion, spreading, proliferation ability and multipotency of cells on different substrates are investigated. Compared with the BMMSCs cultured on pure PCL nanoneedle arrays, the decoration of PDA can improve the adhesion and spreading of cells and further change them from aggregated distribution to laminar distribution. Nevertheless, the laminar distribution of cultured cells leads to a weak cell-cell interaction, and hence the multipotency of BMMSCs cultured on the PCL-PDA substrates is decimated. On the contrary, the pure PCL nanoneedle arrays can be used to maintain the multipotency of BMMSCs via clustered growth, and the PCL1 nanoneedle array with a height of 50 nm is more promising than the other 2 with regard to the highest proliferation rate and best multipotential differentiation ability of cultured cells. Interestingly, there is a positive correlation between the strength of cell-cell interaction and the multipotency of stem cells in vitro. In conclusion, we have successfully maintained the multipotency of BMMSCs by using the PCL nanoneedle arrays, especially the PCL1 nanoneedle array with a height of 50 nm, as the substrates for in vitro extension, and further revealed the importance of cell-cell interaction on the multipotency of MSCs. The study provides a theoretical basis for the behavioral regulation of MSCs, and is instructive to the design of tissue engineering scaffolds.

Effectiveness of chelating agent-assisted Fenton-like processes on remediation of glucocorticoid-contaminated soil using chemical and biological assessment: performance comparison of CaO2 and H2O2.

Glucocorticoids (GCs) have drawn great concern due to widespread contamination in the environment and application in treating COVID-19. Most studies on GC removal mainly focused on aquatic environment, while GC behaviors in soil were less mentioned. In this study, degradation of three selected GCs in soil has been investigated using citric acid (CA)-modified Fenton-like processes (H2O2/Fe(III)/CA and CaO2/Fe(III)/CA treatments). The results showed that GCs in soil can be removed by modified Fenton-like processes (removal efficiency gt; 70% for 24 h). CaO2/Fe(III)/CA was more efficient than H2O2/Fe(III)/CA at low oxidant dosage (< 0.28-0.69 mmol/g) for long treatment time (> 4 h). Besides the chemical assessment with GC removal, effects of Fenton-like processes were also evaluated by biological assessments with bacteria and plants. CaO2/Fe(III)/CA was less harmful to the richness and diversity of microorganisms in soil compared to H2O2/Fe(III)/CA. Weaker phytotoxic effects were observed on GC-contaminated soil treated by CaO2/Fe(III)/CA than H2O2/Fe(III)/CA. This study, therefore, recommends CaO2-based treatments to remediate GC-contaminated soils.

Highly photostable croconium dye-anchored cell membrane vesicle for tumor pH-responsive duplex imaging-guided photothermal therapy.

The development of tumor acidic microenvironment-responsive theranostic agents is a research hotspot. Herein, we developed highly photostable amphiphilic croconium dye-anchored red blood cell membrane vesicle (denoted as LET-5) for tumor pH-responsive near-infrared fluorescence (NIRF) and photoacoustic (PA) duplex imaging-guided photothermal therapy. In tumor acidic microenvironment, both NIRF and PA signals of LET-5 were significantly enhanced and the photothermal effect of LET-5 was activated. Notably, cell membrane-based vesicle with enhanced stability and long blood circulation significantly improved the tumor accumulation of croconium dye, thus achieving better therapeutic effect than free croconium dye. These findings provide a promising approach to construct amphiphilic dye-anchored cell membrane vesicle for cancer theranostics.

Depletion of lncRNA MALAT1 inhibited sunitinib resistance through regulating miR-362-3p-mediated G3BP1 in renal cell carcinoma.

Long non-coding RNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) contributes to chemotherapy resistance in some cancers, but the role of MALAT1 in sunitinib (SU) chemoresistance of carcinoma (RCC) is still unknown. In this study, MALAT1 expression in SU-resistance tumor tissues and cells was tested by qRT-PCR. Then, CCK-8, Annexin V-FITC/PI, transwell, and Western blotting assays were used to evaluate cell viability and IC50, apoptosis, cell invasion, and resistance of SU-resistance RCC cells after transfected with small interfering RNA against MALAT1. Further, RNA pull-down and luciferase reporter assay were applied to investigate the underlying mechanism of MALAT1 in SU resistance. The results showed that MALAT1 expression was dramatically upregulated in SU-resistance RCC tissues and cell lines. Knockdown of MALAT1 inhibited proliferation, invasion, and SU chemoresistance, but induced apoptosis in RCC cells. The results of RNA pull-down and luciferase reporter assay indicated that MALAT1 could interact with miR-362-3p and miR-362-3p interact with RasGAP SH3-domain-Binding Protein 1 (G3BP1). Moreover, G3BP1 also played a role in SU chemoresistance of RCC cells, and MALAT1 could perform as a miR-362-3p sponge to modulate G3BP1 expression. Rescue experiments suggested that downregulation of miR-362-3p and overexpression of G3BP1 can reverse the SU chemosensitivity of MALAT1 knockdown in RCC cells. In conclusion, depletion of LncRNA MALAT1 inhibited SU chemoresistance through modulating G3BP1 via sponging miR-362-3p in RCC cells, suggesting that targeting MALAT1 may be a potential therapeutic strategy for SU-resistance RCC.

pH-Responsive Nanoprobe for In Vivo Photoacoustic Imaging of Gastric Acid.

In vivo real-time monitoring gastric acid is of great importance for diagnosis and treatment of gastrointestinal diseases. Herein, we synthesized a pH-responsive photoacoustic (PA) nanoprobe (denoted as LET-4) based on near-infrared (NIR) dye (IR1061) for in vivo photoacoustic imaging (PAI) of gastric acid in living subjects. In the acidic condition, the protonated LET-4 nanoprobe has a strong absorbance peak at 808 nm, followed by a strong PA signal output at 808 nm. The PA808 signal at pH 3 is 3.45-fold higher than the signal at pH 7. More importantly, the LET-4 nanoprobe could monitor in vivo gastric acid secretion assessment in animal model using PAI. This organic small molecule NIR dye-based probe with simple components, facile preparation, good biocompatibility, and rapid excretion has great potential for gastrointestinal disease diagnosis.

Effect of Dielectric Barrier Discharge Cold Plasma on Pea Seed Growth.

Traditional seed pretreatment methods cause secondary pollution for the application of various chemicals. This study investigated the effect of dielectric barrier discharge (DBD) cold plasma on seedling growth. Effects of plasma-activated tap water (PATW) and plasma-activated seeds (PAS) were compared for germination rates, seedling height, dry weight, and chlorophyll content. Results show that compared with controls these growth parameters were all increased by more than 50%. The yields and contributions of hydrogen peroxide, nitrate, nitrite, and ammonium were quantified. Hydrogen peroxide and nitrate have an important role in seedling growth. By etching, the seed epidermis free radicals can reduce the apparent contact angle and increase the water absorption of the seeds. In addition to the low cost of PATW and PAS compared with commercial fertilizers, DBD does not involve any chemical addition. Thus, both PATW and PAS can be an alternative for improvement of agricultural production.

In Vivo Near-Infrared Fluorescence and Photoacoustic Dual-Modal Imaging of Endogenous Alkaline Phosphatase.

Alkaline phosphatase (ALP) is distributed widely in living organisms and is an important biomarker closely related to many physiological and pathological processes. However, in vivo real-time detection of ALP remains a significant challenge. Herein, we developed a turn-on molecular probe (denoted as LET-3) to visualize ALP activity in tumor tissues through near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging. LET-3, composed of NIR hemicyanine dye (LET-CyOH) and a phosphate moiety, showed a 23-fold NIRF enhancement at 730 nm and 27-fold PA enhancement at 710 nm upon activation by ALP. More importantly, both in vitro and in vivo diagnostic experiments indicated that LET-3 has a high sensitivity and good selectivity for ALP. These findings provide a promising strategy for in vivo ALP detection using NIRF and PA dual-channel turn-on probes.

In Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects.

The detection of Cu2+ in living plants and animals is of great importance for environment monitoring and disease diagnosis. Here, a near-infrared (NIR) turn-on photoacoustic (PA) probe (denoted as LET-2) is developed for Cu2+ detection in living subjects, such as soybean sprouts and mice. The absorbance band of LET-2 shifts from 625 to 715 nm after the interaction with Cu2+ , thus producing strong PA signal output at 715 nm (PA715 ) as an indicator. The PA715 value is increased as a function of the concentration of Cu2+ (0 × 10-6 -20 × 10-6 m), with a calculated limit of detection of 10.8 × 10-9 m. More importantly, both in vitro and in vivo studies in soybean sprouts and mice indicate that the as-prepared LET-2 PA probe is highly sensitive and selective for Cu2+ detection. These findings provide a solution for in vivo detection of metal ions by using chemoselective PA probes.

Copper-catalyzed synthesis of primary arylamines via cascade reactions of aryl halides with amidine hydrochlorides.

We have developed an efficient method for the synthesis of primary arylamines from aryl halides using amidine hydrochlorides as the ammonia surrogates. The protocol uses 10 mol % CuI as the catalyst, 20 mol % L-proline as the ligand, Cs2CO3 as the base, and DMF as the solvent and proceeds the sequential coupling of aryl halides with amidine hydrochlorides and hydrolysis of intermediates to give the target products. This is a convenient, inexpensive, and practical approach to primary arylamines.