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BACKGROUND: Egg yolk powder (EYP) with high immunoglobulin of yolk (IgY) content and good solubility is in great demand in the market of functional foods. In this article, the properties of spray-dried EYP with the addition of five protectants (maltodextrin, trehalose, mannitol, maltitol and sucrose) were investigated. RESULTS: All the protectants increased IgY activity and solubility of EYP. Among them, EYP with maltodextrin displayed the highest activity of IgY (27.11 mg/g), the highest solubility (66.39%) and the lowest surface hydrophobicity. Moreover, the average particle size of EYP with maltodextrin was the smallest (9.78 µm). The egg yolk particles obtained by adding the protectants are more uniformly distributed and have smaller particle size. Fourier-transform infrared spectroscopy confirmed the structural integrity of the proteins, indicating that the protectants addition enhanced the hydrogen bonding forces between the EYP protein molecules. CONCLUSION: The addition of protectants can significantly improve the IgY content, solubility and structural stability of EYP. © 2023 Society of Chemical Industry.
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Yema de Huevo , Inmunoglobulinas , Animales , Polvos , Inmunoglobulinas/química , Sacarosa , PollosRESUMEN
BACKGROUND: Cisplatin is a first-line drug for the treatment of human non-small cell lung cancer (NSCLC); however, the majority of patients will develop drug resistance after treatment. In order to overcome cisplatin resistance, it is important to understand the mechanisms underlying the resistance. METHODS: A gene microarray was used to screen for genes related to cisplatin resistance in NSCLC cell lines. Subsequently, the correlation between the HDAC, RXR and HtrA1 genes, in NSCLC, were verified using gene manipulation. Immunohistochemical staining was used to detect HDAC, RXR and HtrA1 expression in NSCLC specimens. Proliferation, migration and invasion assays were performed in vitro and in vivo to determine the role of the HDAC/RXR/HtrA1 signaling axis in cisplatin resistance, and luciferase reporter analysis and ChIP assays were performed to ascertain the mechanisms by which HDAC and RXR regulate the expression of HtrA1. Furthermore, in vitro and in vivo experiments were conducted in NSCLC cisplatin-resistant NSCLC to elucidate the effect of the low molecular weight compound, DW22, which targets the NSCLC cisplatin resistance HDAC/RXR/HtrA1 signaling pathway. RESULTS: HtrA1 was identified as a cisplatin resistance-related gene in NSCLC cells. The regulation of HtrA1 by HDAC and RXR significantly decreased the efficacy of cisplatin in NSCLC cells resistant to cisplatin. Immunohistochemistry results showed a negative relationship between HDAC1 and HtrA1, and a positive relationship between RXRα and HtrA1 in NSCLC patients' tissues. Notably, the expression of HDAC1 and HtrA1 can be considered as biomarkers for the efficacy of platinum-based drugs and prognosis in NSCLC patients. Mechanistically, the heterodimers of the nuclear receptor RXR, in combination with the enzyme, HDAC, regulate the transcription of HtrA1 in NSCLC cells. The rescue of HtrA1 expression by dual targeting of HDAC and RXR with the compound, DW22, significantly inhibited the proliferation, migration and invasion of NSCLC cells resistant to cisplatin, and induced NSCLC cell apoptosis. CONCLUSION: Our results indicate that HtrA1, a cisplatin resistance-related gene, is synergistically regulated by HDAC and RXR in NSCLC. Targeting the HDAC/RXR/HtrA1 signaling axis can rescue HtrA1 expression and reverse cisplatin resistance in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Histona Desacetilasa 1/genética , Receptores X Retinoide/genética , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/efectos adversos , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Many reports implied that the BRAF serine/threonine kinase was mutated in various types of human tumors, which were related with cell growth, survival and differentiation. To provide new therapeutic opportunities, a series of novel 4,5-dihydro-1H-pyrazole derivatives (6a-10d) containing thiazole moiety as potential V600E mutant BRAF kinase (BRAF(V600E)) inhibitors were designed and synthesized. All compounds were evaluated in vitro for anticancer activities against WM266.4 human melanoma cell line and breast cancer MCF-7 cell line. Compound 10d displayed the most potential antiproliferative activity with an IC50 value of 0.12µM against cell line WM266.4 and 0.16µM against MCF-7 with positive control Sorafenib. Results of the inhibitory activity against BRAF(V600E) revealed that compound 10d was bearing the best bioactivity with IC50 of 0.05µM as well. On the basis of the result of flow cytometry, with the dose of compound 10d increasing, more and more cancer cell gradually encountered apoptosis or died, which indicated the compound 10d could induce remarkable apoptosis of MCF-7 and WM266.4 cells in a dose dependent manner. Furthermore, docking simulation of inhibitor analogues and 3D-QSAR modeling provided potential binding model and further knowledge of pharmacophore.
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Inhibidores de Proteínas Quinasas/química , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Pirazoles/química , Pirazoles/farmacología , Tiazoles/química , Tiazoles/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Células MCF-7 , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/química , Proteínas Proto-Oncogénicas B-raf/genética , Pirazoles/síntesis química , Relación Estructura-Actividad Cuantitativa , Tiazoles/síntesis químicaRESUMEN
A series of novel 5-phenyl-1H-pyrazole derivatives (5 a-5 u) containing niacinamide moiety were synthesized and evaluated for biological activity as potential BRAF(V600E) inhibitors. Among them, compound 5h exhibited the most potent inhibitory activity with an IC50 value of 0.33 µM for BRAF(V600E). Antiproliferative assay results indicated that compound 5h has better antiproliferative activity against WM266.4 and A375 in vitro with IC50 value of 2.63 and 3.16 µM, respectively, being comparable with the positive control vemurafenib. Molecular docking of 5h into the BRAF(V600E) active site was performed to determine the probable binding mode. Furthermore, molecular docking and 3D QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.
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Antineoplásicos/química , Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Pirazoles/química , Pirazoles/farmacología , Antineoplásicos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología , Inhibidores de Proteínas Quinasas/síntesis química , Proteínas Proto-Oncogénicas B-raf/metabolismo , Pirazoles/síntesis química , Relación Estructura-Actividad Cuantitativa , Relación Estructura-ActividadRESUMEN
To enhance the value proposition of sweet potato and oat while broadening their applicability in further processing, this study systematically investigated the impact of oat flour incorporation ratios (5%-25% of sweet potato dry weight) on the quality attributes of sweet potato-oat composite dough and its resulting steamed cake products. The results showed that the addition of oat flour could promote the rheological, water retention, and thermomechanical properties of the composite dough and improve the internal microstructure, specific volume, texture, and other processing properties of the steamed cake products. The rheology, water retention, and protein stability of the dough were maximized when the proportion of oat flour was 25%. The textural properties of steamed cakes, hardness, elasticity, cohesion, adhesion, chewiness, and recovery significantly increased (p < 0.05) and viscosity significantly decreased (p < 0.05) with the addition of oat flour. It is noteworthy that thermodynamic properties, internal structure of the dough, and air holding capacity, which are critical for processing, showed the best results at 20% oat flour addition. Therefore, the addition of 20%-25% oats is recommended to produce composite doughs with optimal quality and processing characteristics. PRACTICAL APPLICATION: As living standards improve, traditional cereals may no longer able to meet people's health needs. Therefore, there is an urgent consumer demand for nutritious, tasty alternatives to staple foods. In this study, oat flour and sweet potato mash were mixed to make sweet potato-oat cake, and the effect of ingredient ratio on the performance and quality of composite dough containing sweet potato-oat flour was analyzed, thus proposing an innovative approach to the research, development, and industrial production of sweet potato and oat food products.
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Avena , Harina , Manipulación de Alimentos , Ipomoea batatas , Reología , Ipomoea batatas/química , Avena/química , Harina/análisis , Manipulación de Alimentos/métodos , Viscosidad , Agua , Vapor , Pan/análisis , Culinaria/métodosRESUMEN
The edible rose (Rosa Crimson Glory) petals were dried using infrared-assisted spouted bed drying technology. The effects of different drying temperature conditions (30, 35, 40, 45, and 50°C, as well as stepped heating drying [SHD] and stepped cooling drying) on the drying characteristics, physicochemical properties, antioxidant capacity, and changes in volatile flavor compounds of the rose petals were investigated. The results showed that the drying time was shortened with increasing drying temperature. Both variable temperature drying processes gave the shortest drying times. Optimal color retention of rose petals was achieved at a constant temperature of 40°C and SHD. Increased drying temperature resulted in higher water-soluble polysaccharide content in the dried rose petals, whereas lower temperatures facilitated anthocyanin preservation. The variable temperature drying processes favored the retention of water-soluble polysaccharides in rose petals, but not anthocyanins. Regarding antioxidant capacity, the samples dried at 40°C and those subjected to the two variable temperature drying processes performed better. This study also analyzed the differences in volatile flavor compounds of rose petals dried under different drying conditions. It was found that the majority of volatile flavor compounds in the rose petals dried by SHD exhibited higher content levels than the other drying conditions. Therefore, considering a thorough evaluation of all relevant factors, it was clear that utilizing the SHD process was the most efficient method for obtaining the best quality rose petals overall.
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Antioxidantes , Rosa , Temperatura , Antioxidantes/química , Rosa/química , Desecación/métodos , Antocianinas/química , AguaRESUMEN
The RAF-MEK-ERK cascade appears to be intimately involved in the regulation of cell cycle progression and apoptosis. The BRAF(V600E) mutant results in constitutive activation of the ERK pathway, which can lead to cellular growth dysregulation. A series of 5-phenyl-1H-pyrazol derivatives (3a-5e) have been designed and synthesized, and their biological activities were evaluated as potential BRAF(V600E) inhibitors. All the compounds were reported for the first time except 3e, and compound 1-(4-bromo-2-hydroxybenzyl)-3-phenyl-1-(5-phenyl-1H-pyrazol-3-yl)urea (5c) displayed the most potent inhibitory activity (BRAF(V600E) IC50 = 0.19 µM). Antiproliferative assay results indicated that compound 5c possessed high antiproliferative activity against cell lines WM266.4 and A375 in vitro, with IC50 values of 1.50 and 1.32 µM, respectively, which were comparable with the positive control vemurafenib. Docking simulations showed that compound 5c binds tightly to the BRAF(V600E) active site and acts as BRAF(V600E) inhibitor. A 3D-QSAR model was also built to provide more pharmacophore understanding towards designing new agents with more potent BRAF(V600E) inhibitory activity.
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Antineoplásicos , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Pirazoles/síntesis química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Humanos , Concentración 50 Inhibidora , Mutación , Proteínas Proto-Oncogénicas B-raf/química , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Pirazoles/química , Pirazoles/farmacología , Relación Estructura-Actividad CuantitativaRESUMEN
FabH, ß-ketoacyl-acyl carrier protein (ACP) synthase III, is critically important to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of novel secnidazole derivatives (1-20) were synthesized and fully characterized by spectroscopic methods and elemental analysis. Among these compounds, 6, 8, 11, 13, 14, 16-20 were reported for the first time. These compounds were tested for antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The compounds inhibitory assay and docking simulation indicated that compound 20 (E)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)-N'-(3,4,5-trimethylbenzylidene)acetohydrazide with MIC of 3.13-6.25 µg/mL against the tested bacterial strains was a potent inhibitor of Escherichia coli FabH.
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Acetiltransferasas/química , Antibacterianos/síntesis química , Inhibidores Enzimáticos/síntesis química , Proteínas de Escherichia coli/química , Metronidazol/análogos & derivados , Bases de Schiff/síntesis química , 3-Oxoacil-(Proteína Transportadora de Acil) Sintasa , Acetiltransferasas/antagonistas & inhibidores , Acetiltransferasas/metabolismo , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/enzimología , Bacillus subtilis/crecimiento & desarrollo , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Escherichia coli/crecimiento & desarrollo , Proteínas de Escherichia coli/antagonistas & inhibidores , Proteínas de Escherichia coli/metabolismo , Acido Graso Sintasa Tipo II/antagonistas & inhibidores , Acido Graso Sintasa Tipo II/química , Acido Graso Sintasa Tipo II/metabolismo , Metronidazol/síntesis química , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/crecimiento & desarrollo , Bases de Schiff/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/enzimología , Staphylococcus aureus/crecimiento & desarrollo , Relación Estructura-ActividadRESUMEN
To improve the stability and solubility of Cornus officinalis flavonoid (COF), spray drying (SD), freeze-drying (FD), and microwave freeze drying (MFD) were used to encapsulate COF using whey isolate protein (WPI) and gum arabic as wall materials. The characterization of COF microparticles was performed with encapsulation efficiency (EE), particle size, morphology, antioxidant activity, structure, thermal stability, color, stability during storage, and in vitro solubility. The results showed that COF was successfully encapsulated in the wall material with an EE between 78.86% and 91.11%. The freeze-dried microparticles had the highest EE (91.11%) and the lowest particle size (12.42 ± 16.73 µm). However, the particle size of COF microparticles of SD and MFD was relatively large. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity of the microparticles obtained from SD (89.36 mg Vc /g) was higher than that of MFD (85.67 mg Vc /g), but the drying time and energy consumption of microparticles dried by SD and MFD were lower than those of FD. Furthermore, the spray-dried COF microparticles had higher stability compared to FD and MFD when stored at 4°C for 30 days. In addition, the dissolution of COF microparticles prepared by SD and MFD was 55.64% and 57.35%, respectively, in simulated intestinal fluids, which was lower than that of FD (64.47%). Therefore, the application of microencapsulation technology showed significant advantages in improving the stability and solubility of COF, and the SD can be used for the preparation of microparticles considering energy cost and quality. PRACTICAL APPLICATION: COF is an important bioactive ingredient, but its poor stability and water solubility decreases its pharmacological value. COF microparticles can improve the stability of COF, enhance the slow-release effect, and expand its application in the food field. The drying method will affect the properties of COF microparticles. Thus, the structures and properties analysis of COF microparticles by different drying methods can provide a reference basis for the preparation and application of COF microparticles.
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Cornus , Flavonoides , Preparaciones de Acción Retardada , Antioxidantes/química , Desecación , Liofilización/métodos , Proteína de Suero de LecheRESUMEN
The preparation of egg yolk powder (EYP) with excellent solubility and high retention of active IgY is of great significance for increasing the added value and promoting the application of EYP. A new method of preparing EYP by microwave-assisted freeze-drying (MFD) was researched. Confocal laser scanning microscopy results demonstrated that the supplementation of excipients (sucrose, trehalose, and maltodextrin) could inhibit lipoproteins aggregation in egg yolk induced by freezing. Scanning electron microscopy indicated that drying further damaged the structure of lipoproteins in EYP, leading to lipid separation from it. FTIR and fluorescence spectra confirmed this finding, indicating that excipients enhance protein stability. Compared with conventional freeze-drying (FD), EYP prepared by MFD, particularly that containing excipients, had higher solubility (63 g/100 g), active antibody retention rate and shorter drying time. Therefore, excipients can significantly improve the solubility and stability of EYP and the retention rate of active IgY.
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Disacáridos , Yema de Huevo , Polvos , Microondas , ExcipientesRESUMEN
The flavonoids in Cornus officinalis (CO) have various pharmacological activities, however, the flavonoid instability limits its application in food and pharmaceutical industries. In this study, Cornus officinalis flavonoid (COF) microcapsules were prepared by using a combination of whey isolate protein (WPI), soy isolate protein (SPI), gelatin (GE), and maltodextrin (MD) as wall materials, respectively. Meanwhile, the encapsulation efficiency, solubility, color, particle size, thermal stability and microstructure as well as the antioxidant capacity of microcapsules were assessed. When the protein/MD ratio was 3:7, three kinds of combined wall materials realized high encapsulation efficiency (96.32-98.24%) and water solubility index (89.20-90.10%). Compared with other wall material combinations, the microcapsules with WPI-MD wall ratio at 3:7 had lower particle size (7.17 µm), lower moisture content (6.13%), higher encapsulation efficiency (98.24%), better water solubility index (90.1%), higher thermal stability (86.00°C), brightness L* (67.84) and higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging capacity (6.98 mgVc/g), and better flowability. Results suggested that WPI and MD could be better wall materials applied in encapsulating COF.
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[This corrects the article DOI: 10.3389/fmicb.2020.589268.].
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The recent discovery of complete ammonia oxidizers (comammox), which convert ammonia to nitrate in a single organism, revolutionized the conventional understanding that two types of nitrifying microorganisms have to be involved in the nitrification process for more than 100 years. However, how different types of nitrifiers in response to salinity change remains largely unclear. This study not only investigated nitrifier community (including ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), comammox and nitrite-oxidizing Nitrospira) in the Nanliu estuary to find the ecological relationship between salinity and functional communities and also studied the physiology of a typical comammox Nitrospira inopinata in response to a salinity gradient. Based on sequences retrieved with four sets of functional gene primes, comammox Nitrospira was in general, mainly composed of clade A, with a clear separation of clade A1 subgroup in all samples and clade A2 subgroup in low salinity ones. As expected, group I.1b and group I.1a AOA dominated the AOA community in low- and high-salinity samples, respectively. Nitrosomonas-AOB were detected in all samples while Nitrosospira-AOB were mainly found in relatively high-salinity samples. Regarding general Nitrospira, lineages II and IV were the major groups in most of the samples, while lineage I Nitrospira was only detected in low-salinity samples. Furthermore, the comammox pure culture of N. inopinata showed an optimal salinity at 0.5 and ceased to grow at 12.8 for ammonia oxidation, but remained active for nitrite oxidation. These results show new evidence regarding niche specificity of different nitrifying microorganisms modulated mainly by salinity, and also a clear response by comammox N. inopinata to a wide range of simulated salinity levels.
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Ríos , Microbiología del Suelo , Amoníaco , Archaea , Bacterias/genética , Estuarios , Nitrificación , Oxidación-Reducción , Filogenia , SalinidadRESUMEN
In this study, we evaluated the biotransformation mechanisms of lincomycin (LIN) and three fluoroquinolone antibiotics (FQs), ciprofloxacin (CFX), norfloxacin (NFX), and ofloxacin (OFX), which regularly enter aquatic environments through human activities, by different ammonia-oxidizing microorganisms (AOM). The organisms included a pure culture of the complete ammonia oxidizer (comammox) Nitrospira inopinata, an ammonia oxidizing archaeon (AOA) Nitrososphaera gargensis, and an ammonia-oxidizing bacterium (AOB) Nitrosomonas nitrosa Nm90. The removal of these antibiotics by the pure microbial cultures and the protein-normalized biotransformation rate constants indicated that LIN was significantly co-metabolically biotransformed by AOA and comammox, but not by AOB. CFX and NFX were significantly co-metabolized by AOA and AOB, but not by comammox. None of the tested cultures transformed OFX effectively. Generally, AOA showed the best biotransformation capability for LIN and FQs, followed by comammox and AOB. The transformation products and their related biotransformation mechanisms were also elucidated. i) The AOA performed hydroxylation, S-oxidation, and demethylation of LIN, as well as nitrosation and cleavage of the piperazine moiety of CFX and NFX; ii) the AOB utilized nitrosation to biotransform CFX and NFX; and iii) the comammox carried out hydroxylation, demethylation, and demethylthioation of LIN. Hydroxylamine, an intermediate of ammonia oxidation, chemically reacted with LIN and the selected FQs, with removals exceeding 90%. Collectively, these findings provide important fundamental insights into the roles of different ammonia oxidizers and their intermediates on LIN and FQ biotransformation in nitrifying environments including wastewater treatment systems.
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Amoníaco , Nitrificación , Antibacterianos , Archaea , Biotransformación , Fluoroquinolonas , Humanos , Lincomicina , Nitrosomonas , Oxidación-Reducción , Filogenia , Microbiología del SueloRESUMEN
Nitrous oxide (N2O) and NOy (nitrous acid (HONO) + nitric oxide (NO) + nitrogen dioxide (NO2)) are released as byproducts or obligate intermediates during aerobic ammonia oxidation, and further influence global warming and atmospheric chemistry. The ammonia oxidation process is catalyzed by groups of globally distributed ammonia-oxidizing microorganisms, which are playing a major role in atmospheric N2O and NOy emissions. Yet, little is known about HONO and NO2 production by the recently discovered, widely distributed complete ammonia oxidizers (comammox), able to individually perform the oxidation of ammonia to nitrate via nitrite. Here, we examined the N2O and NOy production patterns by comammox bacterium Nitrospira inopinata during aerobic ammonia oxidation, in comparison to its canonical ammonia-converting counterparts, representatives of the ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Our findings, i) show low yield NOy production by the comammox bacterium compared to AOB; ii) highlight the role of the NO reductase in the biological formation of N2O based on results from NH2OH inhibition assays and its stimulation during archaeal and bacterial ammonia oxidations; iii) postulate that the lack of hydroxylamine (NH2OH) and NO transformation enzymatic activities may lead to a buildup of NH2OH/NO which can abiotically react to N2O ; iv) collectively confirm restrained N2O and NOy emission by comammox bacteria, an unneglectable consortium of microbes in global atmospheric emission of reactive nitrogen gases.
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Amoníaco , Óxido Nítrico , Archaea , Bacterias , Nitrificación , Óxido Nitroso , Oxidación-Reducción , Microbiología del SueloRESUMEN
Complete ammonia oxidizers (comammox), able to individually oxidize ammonia to nitrate, are considered to play a Complete ammonia oxidizers (comammox), able to individually oxidize ammonia to nitrate, are considered to play a significant role in the global nitrogen cycle. However, the distribution of comammox Nitrospira in estuarine tidal flat wetland and the environmental drivers affecting their abundance and diversity remain unknown. Here, we present a large-scale investigation on the geographical distribution of comammox Nitrospira along the estuarine tidal flat wetlands of China, where comammox Nitrospira were successfully detected in 9 of the 16 sampling sites. The abundance of comammox Nitrospira ranged from 4.15 × 105 to 6.67 × 106 copies/g, 2.21- to 5.44-folds lower than canonical ammonia oxidizers: ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA). Phylogenetic analysis based on the alpha subunit of the ammonia monooxygenase encoding gene (amoA) revealed that comammox Nitrospira Clade A, mainly originating from upstream river inputs, accounts for more than 80% of the detected comammox Nitrospira, whereas comammox Nitrospira clade B were rarely detected. Comammox Nitrospira abundance and dominant comammox Nitrospira OTUs varied within the estuarine samples, showing a geographical pattern. Salinity and pH were the most important environmental drivers affecting the distribution of comammox Nitrospira in estuarine tidal flat wetlands. The abundance of comammox Nitrospira was further negatively correlated with high ammonia and nitrite concentrations. Altogether, this study revealed the existence, abundance and distribution of comammox Nitrospira and the driving environmental factors in estuarine ecosystems, thus providing insights into the ecological niches of this recently discovered nitrifying consortium and their contributions to nitrification in global estuarine environments.
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Energy savings via achieving the reduction of aeration and excess sludge is required to realize energy self-sufficiency in wastewater treatment plants. A novel partial nitritation + simultaneous anammox denitrification and sludge fermentation (PN + SADF) process was operated for nearly two years, during which simultaneous energy-efficient nitrogen removal and waste activated sludge (WAS) reduction was achieved, with a stable nitrogen removal efficiency of 80% and external WAS reduction of 40%-50%. In the PN reactor, presence of ammonia oxidizing bacteria and absence of nitrite oxidizing bacteria ensured the stable nitritation. In the SADF reactor, nitrogen was removed via denitrification and anammox by using nutrients and organics released from WAS solubilization. Comparable performance of the SADF reactor at ambient temperature (12-32 °C) to that at 30 °C indicated a practical application potential for the PN + SADF process. An initial estimation of a full-scale PN + SADF process serving a population of 100000 showed that it could save economy and energy in comparison with conventional nitrification-denitrification process. Despite some challenges in implementation, this paper highlights the potential implication for sustaining mainstream nitritation-anammox towards energy-efficient operation with excess sludge reutilization.
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Desnitrificación , Fermentación , Nitrificación , Nitrógeno/aislamiento & purificación , Aguas del Alcantarillado , Compuestos de Amonio/química , Bacterias , Reactores Biológicos/microbiología , Conservación de los Recursos Energéticos , Oxidación-Reducción , Aguas ResidualesRESUMEN
Cisplatin yields significant efficacy and is generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, acquired resistance strongly limits its application. Here, we identified that a novel histone deacetylase (HDAC) inhibitor S11, with P-glycoprotein inhibitory activity, could obviously suppress cell growth in cisplatin-resistant NSCLC cell lines. In addition, S11 could increase the expression of Ac-H4 and p21, which confirmed its HDAC inhibitory action, suppress colony formation, and block cell migration of cisplatin-resistant NSCLC cells. Notably, co-treatment with S11 and cisplatin exhibited synergistically inhibitory efficacy in cisplatin-resistant NSCLC cells. Gene microarray data showed that OAZ1 was downregulated in resistant cells but upregulated after S11 treatment. Further study indicated that knockdown of OAZ1 by siRNA resulted in the decrease of sensitivity of resistant cells to cisplatin treatment and contributed to the increase of resistant cell migration. Additionally, ChIP assay data demonstrated that HDAC inhibitor S11 could increase the accumulation of Ac-H4 in OAZ1 promoter region, suggesting the direct regulation of OAZ1 by HDAC. Importantly, the combination of S11 and cisplatin overcome resistance through inhibiting HDAC activity and subsequently increasing the OAZ1 expression in preclinical model. Moreover, we observed that positive expression of HDAC1 was associated with the downregulation of OAZ1 in NSCLC patients with platinum-based treatment, and predicted drug resistance and poor prognosis. In summary, we demonstrated a role of HDAC/OAZ1 axis in cisplatin-resistant NSCLC and identified a promising compound to overcome cisplatin resistance.
Asunto(s)
Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Proteínas/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Sitios de Unión , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/uso terapéutico , Histona Desacetilasas/química , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Simulación del Acoplamiento Molecular , Regiones Promotoras Genéticas , Proteínas/antagonistas & inhibidores , Proteínas/genética , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
This work demonstrates the feasibility of simultaneous nitrogen removal and external waste activated sludge (WAS) reutilization/reduction by using the synergy of sludge fermentation, denitrification and anammox processes in up-flow reactors (SFDA). Pre-treated domestic wastewater and synthetic wastewater (containing nitrite â¼20mg/L, ammonium â¼10mg/L in both) were fed to 1# and 2# SFDA, respectively. Long-term operation of 1# SFDA was investigated with achieving the peak ammonium removal rate of 0.021 and nitrite removal rate of 0.081kgN/(m(3)d) as nitrogen loading rate elevated from 0.075 to 0.106kgN/(m(3)d). Negative effect of dissolved oxygen on anammox or fermentation in the 2# SFDA was demonstrated negligible due to rapid depletion by microorganisms. Furthermore, a "net" sludge reduction of 38.8% was obtained due to sludge decay and organics consumption by denitrification. The SFDA process was expected to potentially be used for nitrogen removal and WAS reutilization/reduction in full-scale application.
Asunto(s)
Nitrógeno/aislamiento & purificación , Eliminación de Residuos Líquidos/métodos , Compuestos de Amonio/química , Compuestos de Amonio/metabolismo , Reactores Biológicos/microbiología , Desnitrificación , Fermentación , Procesos Heterotróficos , Nitritos/química , Nitritos/metabolismo , Nitrógeno/metabolismo , Oxígeno/química , Oxígeno/metabolismo , Aguas del Alcantarillado , Eliminación de Residuos Líquidos/instrumentación , Aguas Residuales/químicaRESUMEN
A combined process including a partial nitritation SBR (PN-SBR) followed by a simultaneous sludge fermentation, denitrification and anammox reactor (SFDA) was established to treat low C/N domestic wastewater in this study. An average nitrite accumulation rate of 97.8% and total nitrogen of 9.4mg/L in the effluent was achieved during 140days' operation. The underlying mechanisms were investigated by using Illumina MiSeq sequencing to analyze the microbial community structures in the PN-SBR and SFDA. Results showed that the predominant bacterial phylum was Proteobacteria in the external waste activated sludge (WAS, added to the SFDA) and SFDA while Bacteroidetes in the PN-SBR. Further study indicated that in the PN-SBR, the dominant nitrobacteria, Nitrosomonas genus, facilitated nitritation and little nitrate was generated in the PN-SBR effluent. In the SFDA, the co-existence of functional microorganisms Thauera, Candidatus Anammoximicrobium and Pseudomonas were found to contribute to simultaneous sludge fermentation, denitrification and anammox.