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Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung.
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Hidrolases de Éster Carboxílico , Macrófagos Alveolares , Animais , Camundongos , Lipopolissacarídeos/toxicidade , Pulmão , Macrófagos Alveolares/imunologia , Receptor 4 Toll-Like , Hidrolases de Éster Carboxílico/metabolismoRESUMO
Metallic carbohydrazide perchlorates (M[(N2H3)2C = O](ClO4)2, M2+ = Mn2+, Fe2+, Co2+, Ni2+, Zn2+ and Cd2+, simplified as MCPs) are a series of energetic primary explosives, among which ZnCP and CdCP are already applied in civilian/military fields. The six MCPs possess similar structures but demonstrate different energetic performances in their decomposition, which are obviously determined by their different central metals. Here, we apply DFT and Car-Parrinello molecular dynamics (CPMD) to understand the electronic structures and decomposition pathways of the MCPs. Based on the results, the crystal MCPs with larger electronic band gaps show lower impact sensitivity. However, the friction sensitivity of MCPs is dominated by the strength of their intermolecular Oâ¯H interactions. In the CPMD simulations, we obtained a different conclusion from the traditional viewpoint, where the decomposition is spontaneous from the cleavage of M-N bonds. Indeed, there are two stages in the decomposition of the MCPs, based on our calculations: (I) nonspontaneous 3-step departure of the CHZ groups and (II) spontaneous exoergic decomposition pathways of the CHZ groups triggered by the transfer of O/H radicals. Our study provides a systematic study of the MCP family, which also affords a new route for understanding the relationship between the energetic properties and electronic structures of energetic metal complexes.
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Copper (Cu) is an essential trace element, playing an important role in lipid metabolism, and its transporters ATP7A and ATP7B, as Cu-transporting P-type ATPases, are involved in maintaining the Cu homeostasis in cells. Numerous studies in mammals have shown that Cu homeostasis and lipid metabolism are closely related, but studies on the link between the effects of excess Cu, ATP7A, and ATP7B on lipid metabolism during vertebrate embryogenesis are scarce. In this study, zebrafish disease models with Cu overload and ATP7A and ATP7B inactivation, respectively, were used to study the lipid metabolism-related differentially expressed genes (DEGs) which were enriched in the models. The dynamic and spatiotemporal expressions of the DEGs in WTs, atp7a-/-, and atp7b-/- mutants with or without Cu stress were unveiled in this study and they mostly distributed in brain at 24 hpf then in liver and intestine at 96 hpf, suggesting their potential roles in lipid and glycogen metabolism to apply energy for normal development in zebrafish. Meanwhile, the correlation analysis for the DEGs among the three groups unveiled that most of the DEGs were involved in the glyceride metabolism pathway. This is the first report to establish the relationship between atp7a and atp7b with Cu-stimulated intestinal and liver lipid metabolism during fish embryogenesis, and this study will provide a theoretical basis for fish embryonic development and lipid metabolism disorders under unbalanced copper homeostasis.
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Cobre , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Cobre/metabolismo , Homeostase , Metabolismo dos Lipídeos , Lipídeos , Mamíferos/metabolismoRESUMO
An effective approach has been used to synthesize N-doped HTiNbO5 (denoted as N-HTiNbO5) with a better intercalation property. The synthesis of polyaniline (PANI) with N-HTiNbO5 to form PANI-N-HTiNbO5 lamellar nanocomposites by in situ polymerization using the aniline (ANI) intercalation compound ANI/N-HTiNbO5 as the intermediate has been investigated. The resulting PANI-N-HTiNbO5 nanocomposite showed a better crystallinity with a monolayer of PANI within the interlayers of N-HTiNbO5, because nitrogen doping can affect the surface charge distribution of [TiNbO5](-) layers. The cyclic voltammetry (CV) results indicated that the PANI-N-HTiNbO5 nanocomposite had good redox activity and electrochemical-cycling stability in acidic solution. The visible-light response of the PANI-N-HTiNbO5 nanocomposite was enhanced through N-doping, acid exchange, and the intercalation of PANI. The PANI-N-HTiNbO5 nanocomposite showed the highest activity with 97.8% methylene blue (MB) photodegraded in 170 min under visible light irradiation. The significant enhancement of photocatalytic performance can be attributed to the high efficiency of charge separation, induced by the synergistic effect between PANI and N-HTiNbO5. In addition, the PANI-N-HTiNbO5 nanocomposite had a high thermal and photodegradation stability due to the intercalation reaction at the molecular level.
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Introduction: Arid and semi-arid regions are climate-sensitive areas, which account for about 40% of the world's land surface area. Future environment change will impact the environment of these area, resulting in a sharp expansion of arid and semi-arid regions. Cotoneaster multiflorus is a multi-functional tree species with extreme cold, drought and barren resistance, as well as ornamental and medicinal functions. It was found to be one of the most important tree species for ecological restoration in arid and semi-arid areas. However, bioclimatic factors play an important role in the growth, development and distribution of plants. Therefore, exploring the response pattern and ecological adaptability of C. multiflorus to future climate change is important for the long-term ecological restoration of C. multiflorus in arid and semi-arid areas. Methods: In this study, we predicted the potential distribution of C. multiflorus in China under different climate scenarios based on the MaxEnt 2.0 model, and discussed its adaptability and the major factors affecting its geographical distribution. Results: The major factors that explained the geographical distribution of C. multiflorus were Annual precipitation (Bio12), Min air temperature of the coldest month (Bio6), and Mean air temperature of the coldest quarter (Bio11). However, C. multiflorus could thrive in environments where Annual precipitation (Bio12) >150 mm, Min air temperature of the coldest month (Bio6) > -42.5°C, and Mean air temperature of the coldest quarter (Bio11) > -20°C, showcasing its characteristics of cold and drought tolerance. Under different future climate scenarios, the total suitable area for C. multiflorus ranged from 411.199×104 km² to 470.191×104 km², which was 0.8~6.14 percentage points higher than the current total suitable area. Additionally, it would further shift towards higher latitude. Discussion: The MaxEnt 2.0 model predicted the potential distribution pattern of C. multiflorus in the context of future climate change, and identified its ecological adaptability and the main climatic factors affecting its distribution. This study provides an important theoretical basis for natural vegetation restoration in arid and semi-arid areas.
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Collagen type IV α1 chain (COL4A1) is a collagen protein that acts as a tumor-promoting factor in several types of cancer. However, the role and the potential mechanisms involving COL4A1 in oral squamous cell carcinoma (OSCC) remain unclear. Using reverse transcription-quantitative PCR and western blotting, the expression levels of COL4A1 and (nidogen-1) NID1 in OSCC cells were assessed. Cell Counting Kit-8, EdU staining and colony formation assays were used to evaluate cell proliferation. Cell migration and invasion were assessed using wound healing and Transwell invasion assays, respectively. The expression levels of proteins involved in epithelial-mesenchymal transition (EMT) were assessed using western blotting. In addition, the association between COL4A1 and NID1 was analyzed using TNMplot and the STRING database and verified by co-immunoprecipitation analysis. COL4A1 expression was found to be significantly increased in OSCC cells. Knockdown of COL4A1 expression decreased SCC-4 cell proliferation, migration and invasion, as well as the progression of EMT. In addition, COL4A1 was shown to be significantly positively associated with NID1 in OSCC and to bind to NID1. NID1 overexpression reversed the inhibitory effects of COL4A1 knockdown on cell proliferation, migration and invasion as well as on the progression of EMT in OSCC cells. In summary, the present findings demonstrated that COL4A1 promoted cell proliferation and migration as well as the progression of EMT in OSCC cells by binding to NID1, highlighting a potential avenue for therapeutic management of OSCC.
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It has been reported that protein arginine methyltransferase 5 (PRMT5) serves a significant role in osteogenic differentiation and inflammatory response. Nevertheless, its role in periodontitis as well as its underlying mechanism remain to be elucidated. The aim of the present study was to explore the role of PRMT5 in periodontitis and whether PRMT5 could reduce liposaccharide (LPS)-induced inflammation of human periodontal ligament stem cells (hPDLSCs) and promote osteogenic differentiation through STAT3/NF-κB signaling. In the current study, the expression levels of PRMT5 were determined in LPS-induced hPDLSCs by reverse transcription-quantitative PCR and western blot analysis. ELISA and western blot analysis were employed to assess the secretion and expression levels of inflammatory factors, respectively. The osteogenic differentiation and mineralization potential of hPDLSCs were evaluated using alkaline phosphatase (ALP) activity assay, Alizarin red staining and western blot analysis. Additionally, western blot analysis was applied to determine the expression levels of the STAT3/NF-κB signaling pathway-related proteins. The results showed that the expression levels of PRMT5 were significantly enhanced in LPS-induced hPDLSCs. Additionally, PRMT5 knockdown reduced the contents of IL-1ß, IL-6, TNF-α, inducible nitric oxide synthase and cyclooxygenase-2. PRMT5 depletion also enhanced ALP activity, improved the mineralization ability and upregulated bone morphogenetic protein 2, osteocalcin and runt-related transcription factor 2 in LPS-induced hPDLSCs. Furthermore, PRMT5 knockdown inhibited inflammation and promoted the osteogenic differentiation of hPDLSCs via blocking the activation of the STAT3/NF-κB signaling pathway. In conclusion, PRMT5 inhibition suppressed LPS-induced inflammation and accelerated osteogenic differentiation in hPDLSCs via regulating STAT3/NF-κB signaling, thus providing a potential targeted therapy for the improvement of periodontitis.
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AIM: The objective of this research was to analyse the correlation between intracapsular pressure and shrinkage rate of cystic lesion volume at different time points after decompression and to evaluate the relationship between the concentration of interleukin-1α (IL-1α) in cystic fluid and intracapsular pressure. METHODS: Fifty patients with jaw cystic lesions who underwent decompression were included. We measured the intracapsular pressure and IL-1α concentration in the cyst fluid. Moreover, we calculated the rate of shrinkage (RS) of cystic cavity volume at different time points. In addition, data on age, sex, preoperative cystic cavity volume, and lesion location were collected. Linear correlation analysis and variance analysis were used for statistical analysis. RESULTS: Fastest volume decline was observed between 0 and 3 months after surgery; the average RS0-3 was 45.71%. RS3-6 presented the second-fastest volume decline, with an average of 17.46%, and RS6-12 presented the slowest volume decline, with an average of 3.933%. A statistically significant difference in RS was observed amongst the 3 time points (P < .0001). RS0-3 was negatively correlated with intracapsular pressure (r = -0.6326, n = 50, P < .0001). A negative correlation between the preoperative cystic cavity volume and intracapsular pressure (r = -0.6384, n = 50, P < .001) was also observed. A significant positive correlation was observed between preoperative cystic cavity volume and RS0-3 (r = 0.611, n = 50, P < .0001). Moreover, a significant positive correlation was observed between the intracapsular pressure and IL-1α concentration in the cystic fluid (r = 0.03477, n = 50, P < .0001). CONCLUSIONS: Intracapsular pressure and the preoperative volume were the factors that affected the RS during the first 3 months after surgery. Therefore, the effectiveness of decompression can be evaluated by the intracapsular pressure and preoperative volume.
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Descompressão Cirúrgica , Cistos Maxilomandibulares , Humanos , Resultado do Tratamento , Cistos Maxilomandibulares/cirurgiaRESUMO
The concentration of negative air ions (NAIs) is an important indicator of air quality. Here, we analyzed the distribution patterns of negative air ion (NAI) concentrations at different time scales using statistical methods; then described the contribution of meteorological factors of the different season to the concentration of NAIs using correlation analysis and regression analysis; and finally made the outlook for the trends of NAI concentrations in the prospective using the auto regressive integrated moving average (ARIMA) models. The dataset of NAI concentrations and meteorological factors measured at the fixed stations in the Mountain Wuyi National Park were obtained from the Fujian Provincial Meteorological Bureau. The study showed that NAI concentrations were correlated with relative humidity spanning all seasons. Water was an important factor affecting the distribution of NAI concentrations in different time series. Compared with other ARIMA models, the outlook value of the ARIMA (0,1, 1) model was closer to the original data and the errors were smaller. This article provided a unique perspective on the study of the distribution of negative air oxygen ions over time series.
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Poluentes Atmosféricos , Poluição do Ar , Ar/análise , Poluentes Atmosféricos/análise , Íons , Parques Recreativos , Estudos Prospectivos , Estações do AnoRESUMO
A series of pyrrole/polycyclic aromatic unit hybrid fluorophores was developed by a two-stage synthetic strategy. Their central aryl-substituted pyrrole cores were constructed by a Paal-Knorr pyrrole synthesis reaction. The reaction conditions and mechanism are also discussed in detail. End-capping triflate onto the central pyrrole core enables the core to incorporate various polycyclic aromatic units. The Buchwald-Hartwig amination reaction and the Suzuki-Miyaura cross-coupling reaction were adopted to incorporate the triflate end-capping pyrrole with N-phenylnaphthalen-1-amine and various polycyclic aromatic units to form the hybrid fluorophores. The photophysical properties and thermal properties of the fluorophores were characterized. Most of the pyrrole fluorophores emitted blue light and exhibited high quantum efficiency. The fluorescence properties of these pyrrole fluorophores were induced by manipulating the surrounding polycyclic aromatic units. When the central pyrrole core was incorporated with amino or naphthalene moieties, the fluorescence efficiency and thermal stability of fluorophores 1 and 2 were low (phi(f) < 0.35, T(g) <140 degrees C). Rigid and highly fluorescent moieties (such as pyrenyl, 9,9-dimethylfluorenyl, 9,9-diphenylfluorenyl, and spirofluorenyl groups) were grafted onto the pyrrole. Fluorophores 3-6 had high fluorescence efficiency (phi(f) > 0.99) and stable glassy morphology (the T(g) value of the fluorophore 6 was as high as 220 degrees C). Results of this study demonstrate that the sterically induced fluorescence of crowded pyrrole and the fluorescent polycyclic aromatic units significantly affect the emission properties of the hybrid fluorophores.
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Fe-Ni bimetallic nanoparticles supported on CNTs (Fe-Ni/CNTs) were synthesized, characterized, and applied for removal of 2,4-dichlorophenol (2,4-DCP) in aqueous solution. The removal performance was enhanced drastically on Fe-Ni/CNTs with respect to monometallic Fe/CNTs. The synergistic effect between Fe-Ni nanoparticles and CNTs has been studied in detail. The research results indicated that the doping of Ni played an important role in promoting the catalytic degradation of 2,4-DCP. And the presence of CNTs not only could effectively reduce the aggregation of nanoparticles but also facilitate the mass transfer of 2,4-DCP and the formation of active atomic hydrogen during the catalytic process. In addition, the removal kinetics of 2,4-DCP by Fe-Ni/CNTs were in agreement with a pseudo-first-order model, and the rate constants were dependent on a number of factors including the initial concentration of 2,4-DCP, the dosage of Fe-Ni/CNTs, pH value of the solution, and doping amount of Ni. The degradation mechanism involved the adsorption by CNTs and catalytic reduction by Fe under the stimulating of Ni, and the preferred dechlorination followed the order of para-Cl > ortho-Cl. The study confirmed that Fe-Ni/CNTs had a potential to be a promising catalytic material for removal of chlorophenol and had a great prospect for practical application.
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Clorofenóis/química , Ferro/química , Nanotubos de Carbono , Níquel/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Catálise , CinéticaRESUMO
OBJECTIVE: To explore the effect of regional synergistic treatment system on the treatment time and short-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A retrospective analysis of the clinical data of STEMI patients who admitted to emergency center of Suzhou Kowloon Hospital Affiliated to Shanghai Jiaotong University School of Medicine and underwent primary percutaneous coronary intervention (PPCI) from January 2013 to January 2017 were conducted. All patients were divided into two groups, group A was the patients who underwent the PPCI before the establishment of the acute chest pain area co-treatment system (from January 2013 to December 2014), and group B was the patients who received the treatment after the establishment of the area co-treatment system (from January 2015 to January 2017). The length of time from onset of symptoms to the balloon dilatation (S2B), the length of time from the first medical contact to the balloon dilatation (FMC2B), the length of time from entering the gate of hospital to the balloon dilatation (D2B), and the incidence of 90-day end point events (including heart failure, all-cause death, and other related adverse events) were collected. The relations of the establishment of the acute chest pain area co-treatment system and the incidence of 90-day end point events were analyzed by multivariable Logistic regression analysis. RESULTS: Among the 221 enrolled patients with STEMI, 83 patients were in group A and 138 patients were in group B respectively. Compared with group A, S2B time [minutes: 180 (140, 210) vs. 201 (154, 225)], FMC2B time [minutes: 89 (78, 100) vs. 94 (83, 107)] and D2B time [minutes: 66 (62, 70) vs. 85 (72, 99)] were significantly shortened in group B (all P < 0.05), the incidence of 90-day end point events were significantly decreased (heart failure: 20.3% vs. 32.5%, all-cause death: 1.4% vs. 7.2%, other related adverse events: 23.2% vs. 36.1%, all P < 0.05). It was shown by multivariable Logistic regression analysis that the establishment of the acute chest pain area co-treatment system could lower the incidence of 90-day end point events [heart failure: odds ratio (OR) = 1.904, 95% confidence interval (95%CI) = 0.968-1.004, P = 0.048; all-cause death: OR = 11.724, 95%CI = 0.955-1.048, P = 0.013; other related adverse events: OR = 1.925, 95%CI = 1.049-3.530, P = 0.034]. CONCLUSIONS: The construction of regional synergistic treatment system can shorten the emergency treatment time of STEMI patients and reduce the incidence of 90-day end point events including heart failure and death.
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Serviços Médicos de Emergência , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Tempo para o Tratamento/estatística & dados numéricos , China , Humanos , Intervenção Coronária Percutânea , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Sinomenine (SIN) is a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum. Results of studies have shown that the anti-inflammatory, immunosuppressive and anti-arthritic effects of SIN are partially attributed to the inhibition of cyclooxygenase-2 (COX-2) expression. COX-2 overexpression is associated with enhanced proliferation and angiogenesis of gastric cancer (GC). SGC-7901 cells were treated with different concentrations of SIN in order to observe its effect on the proliferation of human gastric adenocarcinoma cells and to explore the potential underlying molecular mechanism via the detection of COX-2 expression. Celecoxib was used as the positive control. Morphological alterations of the cells were observed microscopically. Cell proliferation was evaluated using MTT assay. COX-2 expression was detected using semi-quantitative RT-PCR and Western blotting. The results showed that SIN inhibited the proliferation of SGC-7901 cells in a time- and dose-dependent manner. In the presence of SIN or celecoxib, SGC-7901 cells became round and detached morphologically, indicating cell apoptosis. The expression of COX-2 was inhibited by SIN in a dose-dependent manner at both the mRNA and protein levels. Our findings indicate that the protective effects of SIN are mediated through the inhibition of COX-2 expression. These findings suggest a novel therapy to treat inflammation-mediated gastric adenocarcinomata.
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ZrO(2)-doped TiO(2) hollow nanospheres with anatase phase are efficiently fabricated via functionalized negatively charged polystyrene (PS) spheres without any surfactant or polyelectrolyte. The resulting Ti(1-)(x)Zr(x)O(2) (hereafter denoted as TZ) hollow nanospheres are characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (XRD), Laser Raman spectroscopy (LRS), X-ray photoelectron spectroscopy (XPS), X-ray fluorescence spectroscopy (XRF), nitrogen sorption, and UV-vis diffuse reflectance spectroscopy (UV-vis). The Zr(4+) incorporation decreases the anatase crystallite size, increases the specific surface area, and changes the pore size distribution. Furthermore, it induces enrichment of electron charge density around Ti(4+) ions and blueshift of absorption edges. The TZ hollow nanospheres doped with moderate ZrO(2) (molar ratio, Ti:Zr=10:1) exhibit better photocatalytic activity than the other samples for the degradation of rhodamine B in aqueous solution, which is correlated with the effect of Zr(4+) doping on the physicochemical properties in terms of surface structures, phase structures, and the electronic structures.