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BACKGROUND: Neonatal necrotizing enterocolitis (NEC) is one of the most prevalent and severe intestinal emergencies in newborns. The inflammatory activation of macrophages is associated with the intestinal injury of NEC. The neuroimmune regulation mediated by α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulating macrophage activation and inflammation progression, but in NEC remains unclear. This study aims to explore the effect of macrophage α7nAChR on NEC. METHODS: Mice NEC model were conducted with high-osmolarity formula feeding, hypoxia, and cold stimulation. The α7nAChR agonist PNU-282987 and mTOR inhibitor rapamycin were treated by intraperitoneal injections in mice. The expression and distribution of macrophages, α7nAChR, and phospho-mammalian target of rapamycin (p-mTOR) in the intestines of NEC patients and mice was assessed using immunohistochemistry, immunofluorescence, and flow cytometry. The expression of NLRP3, activated caspase-1 and IL-1ß in mice intestines was detected by flow cytometry, western blot or ELISA. In vitro, the mouse RAW264.7 macrophage cell line was also cultured followed by various treatments. Expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in macrophages was determined. RESULTS: Macrophages accumulated in the intestines and the expression of α7nAChR in the mucosal and submucosal layers of the intestines was increased in both the NEC patients and mice. The p-mTOR and CD68 were increased and co-localized in intestines of NEC patients. In vitro, α7nAChR agonist PNU-282987 significantly reduced the increase of NLRP3, activated caspase-1, and IL-1ß in macrophages. PNU-282987 also significantly reduced the increase of p-mTOR. The effect was blocked by AMPK inhibitor compound C. The expression of NLRP3, activated caspase-1, and IL-1ß was inhibited after mTOR inhibitor rapamycin treatment. In NEC model mice, PNU-282987 reduced the expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in the intestine. Meanwhile, rapamycin significantly attenuated NLRP3 activation and the release of IL-1ß. Moreover, the proportion of intestinal macrophages and intestinal injury decreased after PNU-282987 treatment. CONCLUSION: Macrophage α7nAChR activation mitigates NLRP3 inflammasome activation by modulating mTOR phosphorylation, and subsequently alleviates intestinal inflammation and injury in NEC.
Assuntos
Benzamidas , Compostos Bicíclicos com Pontes , Enterocolite Necrosante , Interleucina-1beta , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Serina-Treonina Quinases TOR , Receptor Nicotínico de Acetilcolina alfa7 , Animais , Feminino , Humanos , Recém-Nascido , Masculino , Camundongos , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Animais Recém-Nascidos , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Compostos Bicíclicos com Pontes/farmacologia , Compostos Bicíclicos com Pontes/uso terapêutico , Modelos Animais de Doenças , Enterocolite Necrosante/tratamento farmacológico , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Enterocolite Necrosante/imunologia , Interleucina-1beta/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVE: To explore the surgical risk variables in patients with necrotizing enterocolitis (NEC) and develop a nomogram model for predicting the surgical intervention timing of NEC. METHODS: Infants diagnosed with NEC were enrolled in our study. We gathered information from clinical data, laboratory examinations, and radiological manifestations. Using LASSO (least absolute shrinkage and selection operator) regression analysis and multivariate logistic regression analysis, a clinical prediction model based on the logistic nomogram was developed. The performance of the nomogram model was evaluated using the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). RESULTS: A surgical intervention risk nomogram based on hypothermia, absent bowel sounds, WBC > 20 × 109/L or < 5 × 109/L, CRP > 50 mg/L, pneumatosis intestinalis, and ascites was practical, had a moderate predictive value (AUC > 0.8), improved calibration, and enhanced clinical benefit. CONCLUSIONS: This simple and reliable clinical prediction nomogram model can help physicians evaluate children with NEC in a fast and effective manner, enabling the early identification and diagnosis of children at risk for surgery. It offers clinical revolutionary value for the development of medical or surgical treatment plans for children with NEC.
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Opal (SiO2·nH2O, amorphous silica), the by-product of alumina extraction from coal fly ash (CFA), has a strong adsorption capacity and is also an important component of clay minerals in soils. The combining of opal with sand to form artificial soils is an effective disposal strategy for large-scale CFA stockpiles and reduction of environmental risk. Nevertheless, its poor physical condition limits plant growth. Organic matter (OM) amendments have broad potential applications for water-holding and improving soil aggregation. Effects of OMs (vermicompost (VC), bagasse (BA), biochar (BC) and humic acid (HA)) on the formation, stability and pore characteristics of opal/sand aggregates were evaluated through 60-day laboratory incubation experiments. Results demonstrated that four OMs could reduce pH, with BC having the most significant effect, VC significantly increasing the electrical conductivity (EC) and TOC content of the aggregates. Except for HA, other OMs could improve the aggregates' water-holding capacity. The mean weight diameter (MWD) and percentage of >0.25 mm aggregates (R0.25) of BA-treated aggregates were the largest, and BA had the most noticeable contribution to macro-aggregate's formation. The best aggregate stability was obtained with HA treatment, meanwhile the percentage of aggregate destruction (PAD0.25) decreased with the addition of HA. After amendments, the proportion of organic functional groups increased, which favored aggregate's formation and stability; the surface pore characteristics were improved, with the porosity ranging from 70% to 75%, reaching the level of well-structured soil. Overall, the addition of VC and HA can effectively promote aggregates' formation and stabilization. This research may play a key role in converting CFA or opal into artificial soil. The combining of opal with sand to form artificial soil will not only solve the environmental problems caused by large-scale CFA stockpiles but will also enable the comprehensive utilization of siliceous materials in agriculture.
Assuntos
Areia , Dióxido de Silício , Solo/química , ÁguaRESUMO
Hydrogen can be used as an energy carrier for renewable energy to overcome the deficiency of its intrinsically intermittent supply. One of the most promising application of hydrogen energy is on-board hydrogen fuel cells. However, the lack of a safe, efficient, convenient, and low-cost storage and transportation method for hydrogen limits their application. The feasibility of mainstream hydrogen storage techniques for application in vehicles is briefly discussed in this Review. Formic acid (FA), which can reversibly be converted into hydrogen and carbon dioxide through catalysis, has significant potential for practical application. Historic developments and recent examples of homogeneous noble metal catalysts for FA dehydrogenation are covered, and the catalysts are classified based on their ligand types. The Review primarily focuses on the structure-function relationship between the ligands and their reactivity and aims to provide suggestions for designing new and efficient catalysts for H2 generation from FA.
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To prevent scaling and to recycle aqueous solutions in industrial processes, the thermodynamic properties of the CaSO4-H2SO4-H2O system are studied by thermodynamic modeling with the Pitzer model. The published solubility data of calcium sulfate hydrates in sulfuric acid solutions were collected and reviewed critically. Then, the CaSO4-H2SO4-H2O system was modeled using the Pitzer activity coefficient approach from critically selected experimental data to obtain optimized parameters. The model reproduces the solubility data with good accuracy up to 5 m sulfuric acid at temperatures of 283.15-368.15, 283.15-473.15, and 298.15-398.15 K for gypsum (CaSO4·2H2O), anhydrite (CaSO4), and hemihydrate (CaSO4·0.5H2O), respectively. However, at temperatures above 398.15 K and sulfuric acid concentration above 0.5 mol/kg, the solubility of anhydrite predicted by our model deviates significantly from the literature data. Our model predicts that the solubility of anhydrite would first increase but then decrease in more concentrated sulfuric acid solutions, which is in disagreement with the experimental data showing constantly increasing solubilities as a function of increasing sulfuric acid concentration. This discrepancy has been discussed. The transformations of gypsum to anhydrite and hemihydrate were predicted in sulfuric acid solutions. With increasing H2SO4 concentration, the transformation temperatures of gypsum to anhydrite and hemihydrate will decrease. Thus, gypsum is stable at low temperatures in solutions of low H2SO4 concentrations and transforms to anhydrite at high temperatures and in concentrated H2SO4 solutions, while hemihydrate is always a metastable phase. Furthermore, the predicted results were compared with previous experimental studies to verify the accuracy of the model.
RESUMO
Calcium sulfate is one of the most common inorganic salts with a high scaling potential. The solubility of calcium sulfate was modeled with the Pitzer equation at a temperature range from 273.15 to 473.15 K from published solubility data, which was critically evaluated. Only two Pitzer parameters, ß(1) and ß(2), with simple temperature dependency are required to model the solubility with excellent extrapolating capabilities up to 548.15 K. The stable temperature range for gypsum is 273.15-315.95 K, whereas above 315.95 K the stable phase is anhydrite. Hemihydrate is in the metastable phase in the whole temperature range, and the obtained metastable invariant temperature from gypsum to hemihydrate is 374.55 K. The obtained enthalpy and entropy changes at 298.15 K for the solubility reactions are in good agreement with literature values yielding solubility products of 2.40 × 10-05, 3.22 × 10-05, and 8.75 × 10-05 for gypsum, anhydrite, and hemihydrate, respectively. The obtained Pitzer model for the CaSO4-H2O system is capable of predicting the independent activity and osmotic coefficient data with experimental accuracy. The mean absolute average error of activity coefficient data at 298.15 K is less than 2.2%. Our model predicts the osmotic coefficient on the ice curve within 1.5% maximum error.