RESUMO
Sulfur disproportionation (S0DP) poses a challenge to the robust application of sulfur autotrophic denitrification due to unpredictable sulfide production, which risks the safety of downstream ecosystems. This study explored the S0DP occurrence boundaries with nitrate loading and temperature effects. The boundary values increased with the increase in temperature, exhibiting below 0.15 and 0.53 kg-N/m3/d of nitrate loading at 20 and 30 °C, respectively. A pilot-scale sulfur-siderite packed bioreactor (150 m3/d treatment capacity) was optimally designed with multiple subunits to dynamically distribute the loading of sulfur-heterologous electron acceptors. Operating two active and one standby subunit achieved an effective denitrification rate of 0.31 kg-N/m3/d at 20 °C. For the standby subunit, involving oxygen by aeration effectively transformed the facultative S0DP functional community from S0DP metabolism to aerobic respiration, but with enormous sulfur consumption resulting in ongoing sulfate production of over 3000 mg/L. Meanwhile, acidification by the sulfur oxidation process could reduce the pH to as low as 2.5, which evaluated the Gibbs free energy (ΔG) of the S0DP reaction to +2.56 kJ, thermodynamically suppressing the S0DP occurrence. Therefore, a multisubunit design along with S0DP inhibition strategies of short-term aeration and long-term acidification is suggested for managing S0DP in various practical sulfur-packed bioreactors.
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Carbonatos , Ecossistema , Compostos Férricos , Nitratos , Nitratos/metabolismo , Processos Autotróficos , Temperatura , Enxofre/metabolismo , Reatores Biológicos , Desnitrificação , NitrogênioRESUMO
Heteroblasty refers to a phenomenon that a plant produces morphologically or functionally different lateral organs in an age-dependent manner. In the model plant Arabidopsis thaliana, the production of trichomes (epidermal leaf hairs) on the abaxial (lower) side of leaves is a heteroblastic mark for the juvenile-to-adult transition. Here, we show that the heteroblastic development of abaxial trichomes is regulated by a spatiotemporally regulated complex comprising the leaf abaxial fate determinant (KAN1) and the developmental timer (miR172-targeted AP2-like proteins). We provide evidence that a short-distance chromatin loop brings the downstream enhancer element into close association with the promoter elements of GL1, which encodes a MYB transcription factor essential for trichome initiation. During juvenile phase, the KAN1-AP2 repressive complex binds to the downstream sequence of GL1 and represses its expression through chromatin looping. As plants age, the gradual reduction in AP2-like protein levels leads to decreased amount of the KAN1-AP2 complex, thereby licensing GL1 expression and the abaxial trichome initiation. Our results thus reveal a novel molecular mechanism by which a heteroblastic trait is governed by integrating age and leaf polarity cue in plants.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Folhas de Planta/crescimento & desenvolvimento , Regiões Promotoras Genéticas , Análise Espaço-Temporal , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , MicroRNAs/genética , Mutação , Fenótipo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação TranscricionalRESUMO
Sulfur-packed beds (SPBs) have been increasingly incorporated into constructed wetland systems to overcome limitations in achieving satisfactory nitrate removal efficiency. However, the underlying impact of hydraulic regimes on SPB performance remains understudied. This study investigated the performance of a pilot-scale SPB, encompassing sulfur autotrophic denitrification (SAD) and sulfur disproportionation (SDP) processes, under various horizontal flow (HF) and vertical flow (VF) regimes. The HF regime exhibited superior SAD efficiency, achieving 3.1-4.4 mg-N/L of nitrate removal compared to 0.9-2.8 mg-N/L under VF regimes. However, greater sulfide production of 3.8-5.6 mg/L was observed, in contrast to only 1.5-2.3 mg/L under VF regimes when SDP occurred. Employing current computational fluid dynamics simulations could predict general regimes but lacked precision in detailing sulfur layer dynamics. In contrast, determining the spatial distribution of SAD substrates and SDP products offered a viable solution, revealing stagnate, short-circuit, and back flows. Moreover, the feasibility of an aeration approach to reduce sulfide emissions below 0.5 mg/L in case of accidental SDP occurrence was confirmed. This study offers a method for assessing detailed hydraulic regimes within SPBs. Additionally, it provides guidance on optimizing the packing of sulfur-based materials when implementing SPBs in constructed wetland systems and presents a strategy for mitigating excessive sulfide emissions.
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Desnitrificação , Nitratos , Enxofre , Áreas Alagadas , Sulfetos , Reatores Biológicos , NitrogênioRESUMO
Dosing sulfide into the sulfur-packed-bed (S0PB) has great potential to enhance the denitrification efficiency by providing compensatory electron donors, however, the response of sulfur-metabolizing biofilm to various sulfide dosages has never been investigated. In this study, the S0PB reactor was carried out with increasing sulfide dosages by 3.6 kg/m3/d, presenting a decreasing effluent nitrate from 14.2 to 2.7 mg N/L with accelerated denitrification efficiency (k: 0.04 to 0.27). However, 6.5 mg N/L of nitrite accumulated when the sulfide dosage exceeded 0.9 kg/m3/d (optimum value). The increasing electron export contribution of sulfide a maximum of 85.5% illustrated its competition with the in-situ sulfur. Meanwhile, over-dosing sulfide caused serious biofilm expulsion with significant decreases in the total biomass, live cell population, and ATP by 90.2%, 86.7%, and 54.8%, respectively. This study verified the capacity of dosing sulfide to improve the denitrification efficiency in S0PB but alerted the negative effect of exceeded dosing.
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Reatores Biológicos , Desnitrificação , Sulfetos , Enxofre , BiofilmesRESUMO
This study was carried out to determine the inhibition of low temperature on the performance of S0-based autotrophic denitrification (S0-SAD) biofilter, and proposed to enhance the nitrate removal efficiency with thiosulfate as external electron donor. With the decline of temperature from 30 °C to 10 °C at 0.25 h of empty bed contact time (EBCT), the nitrate removal rate presented a logarithmical drop, and the effluent nitrate dramatically increased from 9.19 mg L-1 to 15.13 mg L-1. EBCT was prolonged until 0.33 h for 20 °C, 0.66 h for 15 °C and 1.5 h for 10 °C, respectively, to maintain the effluent nitrate below 10 mg L-1. Such excessive variation of EBCT for different temperature is undoubtedly incredible for practical engineering. Thiosulfate, as the external electron donor, was adopted to compensate the efficiency loss during temperature decrease, which significantly prompted nitrate removal rate to 0.59, 0.53 and 0.31 kg N m-3 d-1 at 20 °C, 15 °C and 10 °C conditions, respectively, even at a short EBCT of 0.25 h. It not only acted as compensatory electron donor for nitrate removal, but also promoted the contribution of elemental sulfur via accelerating the DO consumption and extended larger effective volume of S0-layer for denitrification. Meanwhile, the significant enrichment of Sulfurimonas and Ferritrophicum provided biological evidences to the enhancement process. However, the incomplete consumption of thiosulfate was observed especially at EBCT of 0.25 h and 10 °C, and the thiosulfate runoff needs to be concerned in case of contaminating the effluent. Herein, approximately extending EBCT to 0.66 h and decreasing thiosulfate dosage were conducted simultaneously, thereby achieving 100% thiosulfate utilization efficiency and expected nitrate removal. This study provided a fundamental guidance to design and operate S0-SAD biofilter in response to seasonal temperature variation for practical engineering.
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Desnitrificação , Tiossulfatos , Reatores Biológicos , Elétrons , Nitratos , Nitrogênio , TemperaturaRESUMO
This study was carried out to determine the effect of influent nitrate loading on nitrite accumulation during elemental-sulfur based denitrification process, and proposed to enhance the nitrogen removal efficiency by mitigating nitrite accumulation with thiosulfate as external electron donor. Along with increasing the nitrate influent loading (from 0.09 kg N/m3/d to 1.73 kg N/m3/d) by shortening the empty bed contact time (EBCT) (from 5 h to 0.25 h), the nitrate removal loading increased from 0.08 to 0.83 kg N/m3/d. Meanwhile, the raise of the nitrate influent loading obviously aggravated the nitrite accumulation. Herein, nitrite began to accumulate since the nitrate influent loading was over 0.86 kg N/m3/d, and a maximum nitrite accumulation of 2.39 mg/L was observed under the 0.25 h of EBCT and 15 mg/L of nitrate influent concentration condition. Thiosulfate was used as the external electron donor to accelerate the nitrite reduction rate in order to mitigate the nitrite accumulation. As a result, the nitrite accumulation significantly decreased from 2.39 mg/L to 0.17 mg/L with the thiosulfate dosage of 13.36 mg/L. However, the nitrite accumulation bounced with the on-going increase of the thiosulfate dosage, indicating that the nitrate reduction rate and nitrite reduction rate were accelerated alternatively. After dosing thiosulfate, the relative abundances of sulfurimonas and ferritrophicum grew up significantly.
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Nitritos , Tiossulfatos , Reatores Biológicos , Desnitrificação , Elétrons , Nitratos , NitrogênioRESUMO
BACKGROUND: The role of methylcrotonoyl-CoA carboxylase 2 (MCCC2) in the development of tumors is well-established, and the involvement of leucine in the liver is well-known. However, the role of MCCC2 and the correlation between MCCC2 and leucine in the progression of hepatocellular carcinoma (HCC) have not yet been reported. METHODS: In this study, the Gepia database was used to evaluate the prognostic value of MCCC2 in HCC. The expression and localization of MCCC2 in HCC cells were determined by western blot and immunofluorescence assays. Flow cytometry and CCK-8 and transwell assays were carried out to explore the effect of MCCC2 on cell proliferation, migration, and invasion. In addition, mass spectrometry analysis was used to predict the potential cell function of MCCC2 in HCC. RESULTS: We found that the expression of MCCC2 increased in HCC tissues and that high expression of MCCC2 could predict poor outcomes in HCC patients. Knockdown expression of MCCC2 in HCC cells could reduce cell proliferation, migration, and invasion ability in vitro and could inhibit HCC cell proliferation in vivo. Interestingly, we found that HCC cells transfected with MCCC2-sgRNA failed to respond to leucine deprivation. Meanwhile, leucine deprivation inhibited cell proliferation, migration, and invasion in HCC cells where MCCC2 was present rather than in cells where MCCC2 was absent. In addition, knockdown of MCCC2 significantly reduced the glycolysis markers, glucose consumption, lactate secretion, and acetyl-CoA level, which is a product of leucine metabolism. Furthermore, we found that MCCC2 promotes the activation of ERK. Profiling the MCCC2 binding proteins revealed that MCCC2-associated proteins are enriched in biological processes, such as protein metabolism, energy pathway, and metabolism in HCC cells. CONCLUSIONS: Our findings revealed that MCCC2 plays a critical role in the development of HCC, and the leucine metabolism pathway might be a novel target in HCC treatment.
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OBJECTIVE: To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen. METHODS: Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum. RESULTS: The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group (P < 0.05). The results of immunofluorescence assay for NeuN showed that the SDIT and 7DCT groups had a significantly higher number of NeuN+ cells in the cerebral cortex and the hippocampal CA1 region than the HIBD group, and the 7DCT group had a significantly higher number than the SDIT group (P < 0.05). MBP/NF200 double-label immunofluorescence showed that compared with the HIBD group, the SDIT group and the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus striatum, and the 7DCT group had significantly higher fluorescence intensities than the SDIT group (P < 0.05); the 7DCT group had significantly higher fluorescence intensities of MBP and NF200 in the corpus callosum than the SDIT and HIBD groups (P < 0.05). CONCLUSIONS: Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.
Assuntos
Hipóxia-Isquemia Encefálica , Melatonina , Substância Branca , Animais , Animais Recém-Nascidos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Melatonina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Current chemotherapy regimens on acute myeloid leukemia (AML) still have some drawbacks, such as intolerance and drug resistance, which calls need for the development of targeted therapy. Signal transducer and activator of transcription 5 (STAT5) is often overexpressed or abnormally activated in leukemia and involved in cell self-renewal, proliferation, and stress adaptation. Overexpressed Aurora A (AURKA) is associated with poor prognosis in tumors, and inhibitors against AURKA are already in clinical trials. However, it has rarely been reported whether AURKA inhibitors restrain STAT5-activated leukemia cells. In this study, we constructed STAT5 constitutively activated (cS5) cells and found that STAT5 promoted cell proliferation and colony formation. Moreover, cS5 cells showed elevated reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels, which indicated higher mitochondrial metabolism in cS5 cells. A novel AURKA inhibitor AKI604 was synthesized and showed significant inhibitory effects to the proliferation and colony formation in both STAT5 constitutively activated and nonactivated AML cells. AKI604 induced mitochondrial impairment, leading to the disruption of mitochondrial membrane potential and the elevation of ROS as well as cellular calcium (Ca2+ ) levels. AKI604 could also decline basal oxygen consumption rate and ATP biosynthesis, indicating the damage of oxidative phosphorylation. Furthermore, AKI604 exhibited significant antitumor effect in the HL-60 cS5 xenograft model of the BALB/c nude mice without an obvious influence on mice body weight and other healthy indicators. This study suggested that AKI604 was a potential strategy to overcome STAT5-induced leukemic proliferation in AML treatment by inducing mitochondrial impairment.
Assuntos
Antineoplásicos/farmacologia , Aurora Quinase A/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Transcrição STAT5/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To determine the presence and extent of preoperative biliary obstructions, using magnetic resonance cholangiopancreatography (MRCP), and to determine the clinicopathological consequences of these obstructions in a group of 83 patients with hilar cholangiocarcinoma (HC). METHODS: Fifty-five HC patients with biliary obstruction and 28 HC patients without biliary obstruction were included in the study. The associations between biliary obstruction (assessed using MRCP) and clinicopathological characteristics were analysed. RESULTS: Patients with biliary obstruction had a higher liver function and serum carbohydrate antigen than those without biliary obstruction. The Bismuth-Corlette classification, tumour stage and lymph node metastasis were identified as independent relative factors of biliary obstruction, while differentiation and biliary obstruction were identified as independent factors of overall survival. Furthermore, the size of the tumour, differentiation and biliary obstruction were independent prognostic indicators of disease-free survival for HC patients. CONCLUSIONS: The presence and extent of preoperative biliary obstruction, measured by MRCP, was associated with aggressive clinicopathological features and indicated poor prognosis in HC patients.
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Colangiopancreatografia por Ressonância Magnética/métodos , Tumor de Klatskin/patologia , Correlação de Dados , Humanos , Fígado/patologia , PrognósticoRESUMO
Background Patients with developmental dysplasia of the hip (DDH) may have decreased blood supply to the femoral heads. Finding a non-invasive method to evaluate whether the femoral heads in patients with DDH are ischemic is paramount for orthopedic surgeons. Purpose To identify whether parameters reflecting perfusion and diffusion in intravoxel incoherent motion (IVIM) sequences can be used to assess ischemia in femoral heads in patients with DDH after closed reduction. Material and Methods Twenty-eight patients with DDH who had undergone closed reduction were enrolled. IVIM data were acquired using a 3-T magnetic resonance scanner, regions of interest were placed on the epiphyses; ADCslow, ADCfast, f, and ADCfast×f were measured. A Mann-Whitney U test was performed to compare ADCslow, ADCfast, f, and ADCfast×f between the lesion and control sides. Receiver operating characteristic curves were generated with respective cut-off values. The lesion sides were classified based on the International Hip Dysplasia Institute (IHDI) classification. ADCslow, ADCfast, f, and ADCfast×f were compared among the groups. Results ADCslow was higher and ADCfast, f, and ADCfast×f were lower on the lesion sides ( P = 0.000-0.002). The optimal cut-off value for ADCfast×f, ADCfast, ADCslow, and f were 0.030, 0.626, 0.000251, and 0.636, respectively. Higher IHDI classification scores on the lesion side were associated with lower ADCfast, f, and ADCfast×f, and higher ADCslow values. Conclusion IVIM is a promising method to investigate the perfusion and diffusion of epiphyses of femoral heads.
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Epífises/irrigação sanguínea , Epífises/diagnóstico por imagem , Cabeça do Fêmur/irrigação sanguínea , Cabeça do Fêmur/diagnóstico por imagem , Luxação Congênita de Quadril/terapia , Imageamento por Ressonância Magnética/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lactente , MasculinoRESUMO
OBJECTIVE: To explore and compare the effects of propofol, ginsenoside Rg-1, protein phosphatae-2A, and lithium on the learning and memory and the concentration of glutamic acid in hippocampus after the electroconvulsive therapy (ECT) in the model of depressed rats induced after the removal of olfactory bulb. METHODS: The depressed rats were randomized into ECT intervention (two levels:no disposition and a course of electroconvulsive shock) and drug intervention (five levels:microinjection of saline injection, propofol, ginsenoside Rg-1, protein phosphatae-2A, and lithium, 20 g/L). Learning and memory were evaluated using the Morris water maze test within 24 h after the course of ECT. Glutamate contents in the hippocampus of rats were examined using high-performance liquid chromatography. RESULTS: Both propofol alone and ECT alone induced the impairment of learning and memory in depressed rats, but their combination alleviated the such impairment caused by ECT. Ginsenoside Rg-1, protein phosphatae-2A ,and lithium had no obvious effect on the leaning and improved the learning and memory when in combination with ECT. There was a synergic effect between ECT intervention and drug intervention. ECT remarkably increased the glutamate content in the hippocampus of depressed rats, which could be reduced by both propofol and ginsenoside Rg-1. Protein phosphatae-2A and lithium did not affect glutamate content in the hippocampus of depressed rats before and after ECT. CONCLUSIONS: ECT can increase the content of glutamate in hippocampus and thus cause the impairment of learning and memory in depressed rats. Propofol and ginsenoside Rg-1 can ameliorate the impairment by reducing the content of glutamate in hippocampus. Protein phosphatae-2A and lithium may also improve the learning and memory in depressed rats.
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Eletrochoque , Ginsenosídeos/farmacologia , Lítio/farmacologia , Propofol/farmacologia , Proteína Fosfatase 2/farmacologia , Animais , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The sulfur fluidizing bioreactor (S0FB) has significant superiorities in treating nitrate-rich wastewater. However, substantial self-acidification has been observed in engineering applications, resulting in frequent start-up failures. In this study, self-acidification was reproduced in a lab-scale S0FB. It was demonstrated that self-acidification was mainly induced by sulfur disproportionation process, accounting for 93.4 % of proton generation. Supplying sufficient alkalinity to both the influent (3000 mg/L) and the bulk (2000 mg/L) of S0FB was essential for achieving a successful start-up. Furthermore, the S0FB reached 10.3 kg-N/m3/d of nitrogen removal rate and 0.13 kg-PO43-/m3/d of phosphate removal rate, respectively, surpassing those of the documented sulfur packing bioreactors by 7-129 times and 26-65 times. This study offers a feasible and practical method to avoid self-acidification during restart of S0FB and highlights the considerable potential of S0FB in the treatment of nitrate-rich wastewater.
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Nitratos , Águas Residuárias , Processos Autotróficos , Desnitrificação , Enxofre , Reatores Biológicos , Concentração de Íons de Hidrogênio , NitrogênioRESUMO
AIM: To observe the effects of N-acetylserotonin (NAS) administration on retinal ischemia-reperfusion (RIR) injury in rats and explore the underlying mechanisms involving the high mobility group box 1 (HMGB1)/receptor for advanced glycation end-products (RAGE)/nuclear factor-kappa B (NF-κB) signaling pathway. METHODS: A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye. Eighty male Sprague Dawley were randomly divided into five groups: sham group (n=8), RIR group (n=28), RIR+NAS group (n=28), RIR+FPS-ZM1 group (n=8) and RIR+NAS+ FPS-ZM1 group (n=8). The therapeutic effects of NAS were examined by hematoxylin-eosin (H&E) staining, and retinal ganglion cells (RGCs) counting. The expression of interleukin 1 beta (IL-1ß), HMGB1, RAGE, and nod-like receptor 3 (NLRP3) proteins and the phosphorylation of nuclear factor-kappa B (p-NF-κB) were analyzed by immunohistochemistry staining and Western blot analysis. The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats. With NAS therapy, the HMGB1 and RAGE expression decreased significantly, and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression. Additionally, NAS exhibited an anti-inflammatory effect by reducing IL-1ß expression. The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression, so as to the IL-1ß expression and retinal edema, accompanied by an increase of RGCs in RIR rats. CONCLUSION: NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway, which may be a useful therapeutic target for retinal disease.
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Malus xiaojinensis is an important, iron-efficient rootstock germplasm. Iron uptake is an elaborately controlled process in plant roots, involving specialized transporters. MxIRT1, a Fe(II) transporter gene of M. xiaojinensis, is homologous to other iron transporters at the amino acid level. In the current study, the plasmid pYES2.0-MxIRT1, containing MxIRT1 cDNA, was constructed and transformed into yeast mutants. The results indicated that it could reverse the phenotype of yeast strain DEY1453, an iron uptake mutant. Complementation tests suggested that it might not be a specific transporter, as it was able to restore the phenotypes of other yeast mutant strains, including Mn, Cu and Zn uptake mutants. The functions of the critical histidine residues in the His-box of MxIRT1 were tested by transforming mutant yeast strain DEY1453 with different His residues altered by directed mutagenesis. The His-box of MxIRT1 was found to be necessary for iron transport, with different histidine residues (H(1-4)) playing different roles in the transport.
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Proteínas de Transporte de Cátions/genética , Malus/genética , Proteínas de Plantas/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Proteínas de Transporte de Cátions/biossíntese , Proteínas de Transporte de Cátions/fisiologia , Ferro/metabolismo , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Proteínas de Plantas/biossíntese , Proteínas de Plantas/fisiologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismoRESUMO
The effect of particle morphology on denitrification performance in element sulfur-based denitrification (ESDeN) packed-bed process is a gap. In this study, three different types of commercial sulfur particles were selected to build the ESDeN reactors. The results showed the reactors filled with rougher sulfur particles took shorter time to reach stable denitrification performance in the start-up stage. The reactors filled with cap-shape sulfur particles received the maximum nitrate removal rate of 849.49 ± 79.29 g N m-3 d-1 at empty bed contact time of 0.50 h, which was 2.34 times higher than that with ball-shape sulfur particles in the steady stage. The superior denitrification performance in the cap-shape particles set linked to its larger effective volumetric surface area (ωe, 1.67 times larger) and to the longer actual hydraulic retention time (AHRT, 1.80 times longer). This study extends the knowledge of the dependency of sulfur particle properties on denitrification performance in ESDeN packed-bed reactor.
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Reatores Biológicos , Desnitrificação , Enxofre , Nitratos , Processos Autotróficos , NitrogênioRESUMO
Elemental sulfur packed-bed (S0PB) bioreactors for autotrophic denitrification have gained more attention in wastewater treatment due to their organic carbon-free operation, low operating cost, and minimal carbon emissions. However, the rapid development of microbial S0-disproportionation (MS0D) in S0PB reactor during deep denitrification poses a significant drawback to this new technology. MS0D, the process in which sulfur is used as both an electron donor and acceptor by bacteria, plays a crucial role in the microbial-driven sulfur cycle but remains poorly understood in wastewater treatment setups. In this study, we induced MS0D in a pilot-scale S0PB reactor capable of denitrifying over 1000 m3/d nitrate-containing wastewater. Initially, the S0PB reactor stably removed 6.6 mg-NO3--N/L nitrate at an empty bed contact time (EBCT) of 20 mins, which was designated the S0-denitrification stage. To induce MS0D, we reduced the influent nitrate concentrations to allow deep nitrate removal, resulted in the production of large quantities of sulfate and sulfide (SO42-:S2- 3.2 w/w). Meanwhile, other sulfur-heterologous electron acceptors (SHEAs), e.g., nitrite and DO, were also kept at trace levels. The negative correlations between the SHEAs concentrations and the sulfide productions indicated that the absence of SHEAs was a primary inducing factor to MS0D. The microbial community drastically diverged in response to the depletion of SHEAs during the switch from S0-denitrification to S0-disproportionation. An evident enrichment of sulfur-disproportionating bacteria (SDBs) was found at the S0-disproportionation stage, accompanied by the decline of sulfur-oxidizing bacteria (SOBs). In the end, we discovered that shortening the EBCT and increasing the reflux ratio could inhibit sulfide production by reducing it from 43.9 mg/L to 3.2 mg/L or 25.5 mg/L. In conclusion, our study highlights the importance of considering MS0D when designing and optimizing S0PB reactors for sustainable autotrophic sulfur denitrification in real-life applications.
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Desnitrificação , Nitratos , Processos Autotróficos , Enxofre , Reatores Biológicos/microbiologia , Bactérias , Sulfetos , NitrogênioRESUMO
Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology, and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types, including hematopoietic malignancy. However, acute myeloid leukemia (AML) is a heterogeneous disease and there is still a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage. Thus, the identification of molecules that drive tumor immunosuppression and stratify patients according to the benefit from immune checkpoint inhibitors is urgently needed. Here, we reported that STAT5 was highly expressed in the AML cohort and activated the promoter of glycolytic genes to promote glycolysis in AML cells. As a result, the increased-lactate accumulation promoted E3BP nuclear translocation and facilitated histone lactylation, ultimately inducing PD-L1 transcription. Immune checkpoint inhibitor could block the interaction of PD-1/PD-L1 and reactive CD8+ T cells in the microenvironment when co-culture with STAT5 constitutively activated AML cells. Clinically, lactate accumulation in bone marrow was positively correlated with STAT5 as well as PD-L1 expression in newly diagnosed AML patients. Therefore, we have illustrated a STAT5-lactate-PD-L1 network in AML progression, which demonstrates that AML patients with STAT5 induced-exuberant glycolysis and lactate accumulation may be benefited from PD-1/PD-L-1-based immunotherapy.
Assuntos
Histonas , Leucemia Mieloide Aguda , Humanos , Linfócitos T CD8-Positivos , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Inibidores de Checkpoint Imunológico/uso terapêutico , Fator de Transcrição STAT5/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Terapia de Imunossupressão , Lactatos/uso terapêutico , Microambiente TumoralRESUMO
OBJECTIVE: To explore the effects of different liquid therapies on the intracranial pressure, brain water content, and expressions of aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue. METHODS: Two intervention factors including the colloids (two levels: 4% gelofusine; 6% hydroxyethyl starch and sodium chloride injection) and the crystal/gel ratios (two levels: 0:1; 1:1) were set based on the results of the analysis of variance of factorial design. Thirty-two patient who had undergone epilepsy surgery were equally and randomly divided into four groups: group A (4% gelofusine, crystal/gel ratio 0:1); group B (6% hydroxyethyl starch and sodium chloride injection, crystal/gel ratio 0:1); group C (4% gelofusine, crystal/gel ratio 1:1); and group D (6% hydroxyethyl starch and sodium chloride injection, crystal/gel ratio 1:1). The intracranial pressure during operation was recorded. After the operation, the intracranial pressure and brain water content were measured and the expressions of aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue were determined with Western blot. Glasgow coma scores were obtained 2 hours after operation. RESULTS: The intracranial pressure (F=55.714, P=0.000; F=142.432, P=0.000) and the brain water content (F=31.477, P=0.000; F=84.896, P=0.000) significantly increased after the application of the 6% hydroxyethyl starch and sodium chloride injection and crystal/gel ratio 1:1, and the expressions of aquaporin-4 (F=37.205, P=0.000; F=149.652, P=0.014) and N-methyl-D-aspartate-1(F=29.664, P=0.000; F=65.951, P=0.000) in the brain tissue significantly increased. There were additive effects between two of them (the intracranial pressure: F=11.056, P=0.002; the brain water content: F=8.007, P=0.008; the expression of aquaporin-4: F=9.845, P=0.004; and the expression of N-methyl-D-aspartate-1: F=5.020, P=0.033). However, the Glasgow coma score showed no significant difference after the administration (P>0.05). CONCLUSION: The liquid therapy with 4% gelofusine and crystal/gel ratio 0:1 can result in better control on the intracranial pressure, brain water content and expressions of aquaporin-4 and N-methyl-D-aspartate-1 in the brain tissue better than the liquid therapy with 6% hydroxyethyl starch and crystal/gel ratio 1:1 during neurosurgery, although it may not improve the coma status.
Assuntos
Aquaporina 4/metabolismo , Encéfalo/metabolismo , Hidratação/métodos , Pressão Intracraniana/efeitos dos fármacos , N-Metilaspartato/metabolismo , Adolescente , Adulto , Encéfalo/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Água/metabolismo , Adulto JovemRESUMO
OBJECTIVES: Mutant C/EBPα p30 (mp30), the product of C/EBPα double mutations (DM), lacks transactivation domain 1 and has C-terminal loss-of-function mutation. Acute myeloid leukaemia (AML) patients harbouring C/EBPα DM could be classified as a distinct subgroup with favourable prognosis. However, the underlying mechanism remains elusive. MATERIALS AND METHODS: Autophagy regulated by mp30 was detected by western blot and immunofluorescence. Immune infiltration analysis and GSEA were performed to investigate autophagic and inflammatory status of AML patients from the GSE14468 cohort. Flow cytometry was applied to analyse T cell activation. RESULTS: Mp30 inhibited autophagy by suppressing nucleus translocation of NF-κB. Autophagy-associated secretion of IL-1ß was decreased in mp30-overexpressed AML cells. Bioinformatic analysis revealed that inflammatory status was attenuated, while CD8+ T cell infiltration was upregulated in C/EBPα DM AML patients. Consistently, the proportion of CD8+ CD69+ T cells in peripheral blood mononuclear cells (PBMCs) was upregulated after co-culture with mp30 AML cell conditional culture medium. Knock-out of IL-1ß in AML cells also enhanced CD8+ T cell activation. Accordingly, IL-1ß expression was significantly reduced in the bone marrow (BM) cells of C/EBPα DM AML patients compared to the wildtype, while the CD8+ CD69+ T cell proportion was specifically elevated. CONCLUSIONS: C/EBPα DM alleviates immunosuppression of CD8+ T cells by inhibiting the autophagy-associated secretion of IL-1ß, which elucidated that repression of autophagy-related inflammatory response in AML patients might achieve a favourable clinical benefit.