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Background Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. Methods shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. Results We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. Conclusion In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

Background Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis. Methods ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Results We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells. Conclusions In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.

Background Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB. Results In this study, we found that nanomolar concentrations of GNE987 markedly diminished NB cell proliferation and survival via degrading BRD4. Meanwhile, GNE987 significantly induced NB cell apoptosis and cell cycle arrest. Consistent with in vitro results, GNE987 administration (0.25 mg/kg) markedly decreased the tumor size in the xenograft model, with less toxicity, and induced similar BRD4 protein degradation to that observed in vitro. Mechanically, GNE987 led to significant downregulation of hallmark genes associated with MYC and the global disruption of the SEs landscape in NB cells. Moreover, a novel candidate oncogenic transcript, FAM163A, was identified through analysis of the RNA-seq and ChIP-seq data. FAM163A is abnormally transcribed by SEs, playing an important role in NB occurrence and development. Conclusion GNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

The mixer settler is widely employed in the extraction and recycling of battery materials. The improvement of the separation efficiency is one of the most important issues. In order to investigate the effect of agitating speed on the flow characteristics and settling performance, both computational fluid dynamics coupled population balance model simulations and experiments with particle image velocimetry measurement have been performed in this work to investigate the flow field at different agitating speeds. The predicted data were in good agreement with the experimental data. The results demonstrated that an appropriate agitating speed could effectively promote the collision efficiency of organic phase droplets and accelerate the separation process. When the agitating speed was too large, the shear stress of the fluid would promote the breakage of the organic phase droplets and decrease the separation efficiency. This work will contribute to optimizing and designing large-scale stirring settlers.

Bayer red mud accounts for the largest proportion of solid waste produced in the non-ferrous metallurgy industry and is usually handled by stockpiling because of its high alkalinity. The calcification–carbonation method (CCM) was proposed to extract alumina and sodium oxide from red mud using a fully hydrometallurgical process in order to scale the valuable utilization of Bayer red mud. In this study, a modified CCM was applied, using calcium aluminate hydrate as the calcium source to recover alumina from a low-NaOH-concentration digested solution. Thermodynamic analysis revealed that the stable product of the calcification process was hydrogarnet with a high silicon saturation coefficient (x, 3CaO·Al2O3·xSiO2·6-2xH2O), and a higher reaction temperature was beneficial for the formation of hydrogarnet with a high silicon saturation coefficient. Experimental results indicated that: (1) the calcification temperature was the most important determinant of the coefficient x of the hydrogarnet, which varied from 0.35 to 0.98 over a temperature range of 60–280 °C; (2) the x value and Na mass content in the calcified slag were 0.98 and 0.35%, respectively, under calcification conditions with an NaOH concentration of 200 g/L, a temperature of 260 °C, and a C/S of 2.5:1; (3) the Na mass content and A/S decreased to 0.03% and 0.52, respectively, in the new red mud structure due to the carbonation and digestion process. The Na mass content in the new red mud structure satisfies the raw material requirements for the cement industry, and approximately 74% of the alumina in the Bayer red mud was recovered by the CCM treatment. The primary phase in the new red mud structure was CaCO3, which can be used for preparing cement or other building materials.

The relationship between the silicon saturation coefficient of hydrogarnets and Bayer reaction parameters was studied. The peak position, crystal plane spacing, and cell edge length of typical hydrogarnet patterns were calculated to find the key factors influencing the relationship. The results showed that the crystal face (420) is the optimal garnet growth direction during hydration and crystal growth along the faces (521) and (611) were not affected significantly by the varying experimental conditions. The reaction temperature significantly influenced the silicon saturation coefficient of hydrogarnets. The silicon saturation coefficient of hydrogarnets increased from 0.2 to about 1.0 in the temperature range of 30–270 °C and a rapid expansion process was observed in the temperature range of 120–150 °C. Moreover, the reaction time, alumina concentration, and C/S were shown to be less important factors. Averaging the results obtained by the 3 methods was shown suitable for calculating the SiO2 saturation coefficient of hydrogarnets. The calculated results of the Al2O3 and SiO2 contents matched the actual ones. However, the actual SiO2 content was about 10 % less than the calculated one for SiO2 saturation coefficients higher than 1.

In terms of secondary resource recovery and environmental impact, fly ash is attracting a great deal of attention in China. This study aimed to investigate the carbochlorination process of titanium oxide to recover titanium. The extraction kinetics mechanism of titanium oxide from fly ash was investigated at temperatures ranging from 850°C to 1050°C. The effect of various experimental parameters was studied. The reactants and reaction residues were analyzed by scanning electronic microscopy and chemical analysis. The results show that the best extraction efficiency of 91.66% was obtained at a temperature of 1050°C, a coking coal content of 34.64 wt.%, a pellet diameter of 8 mm, an average gas flow of 0.35 L/min, and a time of 120 min. The carbochlorination reaction of titanium oxide is controlled by the chemical reaction. The apparent activation energy is approximately 44.45 kJ/mol between 800°C and 1050°C.

In the metal extraction process, recovery of valuable elements from fly ash can have economic benefits and maximize its utilization. Extraction of Mg and Ca from fly ash by the carbochlorination method was studied as a function of carbochlorination temperature, time, carbon content, pellet diameter, and chlorine gas flow rate. The kinetic regime of the carbochlorination of Mg- and Ca-bearing compounds in the fly ash was identified. The carbochlorination residues were analyzed by chemical analysis and scanning electron microscopy. The results showed that chemical reaction control was dominant in carbochlorination of Mg in the temperature range of 800°C to 1050°C. However, for carbochlorination of Ca, the carbochlorination reaction was controlled by the diffusion process. Morphological changes such as the breakage and disappearance of spherical particles showed that the original spherical structure of fly ash was destroyed in the carbochlorination process.

Mixer-settlers have been widely employed in the rare earth element separation industry. Presently, reducing the loss of reagents and occupied areas and achieving a highly efficient separation in the settler are challenging issues. In this work, we report numerical simulations of the liquid–liquid flow in a stirring settler and thereafter describe the experimental validation. A computational fluid dynamics coupled population balance model (CFD-PBM) was developed to investigate the liquid–liquid flow characteristics and settling performance. The dispersion band thickness predicted by the turbulent aggregation model was in good agreement with the experimental measurements. The effects of the total liquid flow rate and initial average droplet diameter on the settling characteristics were further investigated. It was found that the dispersion band thickness increased significantly as the droplet diameter decreased. Moreover, this research shows that the CFD-PBM coupled model is promising for designing large-scale stirring settlers.

Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL. Methods Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP). Results BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo. Conclusions BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.

The synthetic rutile was prepared by aeration leaching process in a novel gas–liquid–solid reactor and compared with traditional reactor. The effects of aeration leaching on the phase transformation of reduced ilmenite were studied at a liquid-to-solid ratio of 4:1 by XRD, while the microstructure and composition of the reduced ilmenite were characterized by SEM and chemical analysis. The vigorous stirring helped break bubbles and was favorable to the reaction. There exists an optimum value of gas flow rate. Using this process, synthetic rutile containing 0.6% metallic iron and 82.11% titanium dioxide was obtained at 2% ammonium chloride with 1.5% hydrochloric acid and reaction time 1 h.

Objective To explore the clinical factors that can be used to predict the early weight loss after laparoscopic sleeve gastrectomy(LSG).Methods The clinical data of 64 obese patients undergoing LSG in Peking Union Medical College Hospital from August 2015 to January 2018 were retrospectively analyzed.We analyzed the relationship between different clinical factors and early weight loss,determined the independent predictors based on

Large quantities of indium-bearing zinc-leached residue (ZLR) are produced constantly in the hydrometallurgical production of zinc, including zinc, indium, iron and other valuable metals. In order to recover valuable metals from the residue, a new reductive leaching process using galena as reductant has been developed, in which the extensive leaching of zinc and indium is achieved. A shrinking core model under the control of surface chemical reaction best fitted the leaching of indium from the residue. The apparent activation energy of indium leaching was calculated to be 64 kJ/mol, and the reaction orders were determined as −0.34 and 1.47 with respect to particle size and initial H2SO4 concentration, respectively. The extent of leaching was 87% for zinc, 91% for iron and 88% for indium after 90 min at 85 °C, using an initial H2SO4 concentration of 140 g/L and a molar ratio of lead sulfide to zinc ferrite of 1:1. The reductive leaching process of the residue achieved high dissolution of zinc and indium, and iron existed as Fe2+ in solution would prove beneficial for the subsequent iron removal stage.

With the outbreak of the Internet celebrity economy, coupled with the rapid expansion of the live broadcast industry and technology, the new Internet economy has shown a diversified development pattern. This article has conducted an in-depth study of the impact of webcast on consumer purchasing decisions. The author believes that the goods brought by celebrities is a relatively new industry with potential for development. Especially in the post-epidemic era, the goods brought by celebrities on the Internet will be promoted by more and more brands and capital; but as an industry with only about ten years of development history. In the industry, the industry norms and guidelines are largely missing, and we can only find a few legal provisions to restrict it. As a sales model that is directly related to consumers, consumers, sellers and Internet celebrities should all be protected by corresponding laws. Despite the existence of irregular management, the intervention of the platform can make the three parties reach a certain degree of balance.

Rare earth oxide was prepared via direct pyrolysis of rare earth chloride solution. Based on this technique, a new-type jet-flow pyrolysis reactor was designed, and then the fluid dynamics (pressure and velocity) inside the reactor was numerically simulated using a computational fluid dynamics method. The self-produced pressure ( p ) and the fuel inlet velocity ( v ) satisfied a quadratic function, p =0.06 v 2 +0.23 v −4.49. To fully utilize the combustion-generated heat in pyrolysis of rare earth chloride, an appropriate external pressure p = v 2 +3 v −4.27 should be imposed at the feed inlet. The 1.25- and 1.5-fold increase of feed inlet diameter resulted in decline of adsorption dynamic pressure, but the intake of rare earth chloride increased by more than 30% and 60%, respectively. The fluid flow in the reactor was affected by the feeding rate; the fluid flow peaked near the throat of venturi and gradually smoothed down at the jet-flow reactor's terminal along with the sharp decline of feeding rate.

Roughing disorder (RD) is a significant quality barrier in citrus fruit, prevalent on easy-peeling mandarins. As RD is not yet well-understood, this study aimed to examine the changes and synergic molecular processes involved in peel RD. Peel with RD was induced by severely defruiting Satsuma mandarin trees. Morphology observations, RNA-sequencing, and targeted and untargeted metabolic analyses were conducted. The results showed that the primary metabolites of sugars, organic acids and amino acids are dramatically changed in RD peel. The RD peel was always characterized by higher magnesium content during development. Comparative transcriptome profiling was performed for CK and RD peels at 30, 80, and 170 days after full bloom (DAFB) which represented fruit at cell division stage, cell enlargement stage and fruit maturity stage, respectively. Physiological and molecular biological evidence suggested that the month after full bloom is a crucial stage for RD initiation. A total of 4,855 differentially expressed genes (DEGs) in RD peel, relative to CK peel were detected at cell division stage, about 2 to 4-fold more than other stages had. Among the differentially expressed transcription factors, the bHLH family were affected most by RD, and six bHLH transcription factors functionally involved in GA metabolism were assessed to associate with RD occurrence. Gene set enrichment analysis suggested that RD significantly altered starch and GA metabolism in peel. Higher starch content and hydrolysed chain status were found in RD peel at cell division stage. RD occurrence on the peel was influenced significantly by GA, especially abundant GA before July. These changes may mean a significant alteration in sink strength of RD peel. The findings of this study provide insights into the emergence, development and molecular mechanisms of RD.

The improved Intermig impeller has been used in the seed precipitation tank in China, which could enhance the mixing and suspension of Al(OH)3 particles and the power consumption declined largely. The flow field, solids hold-up, cloud height, just off-bottom speed and power consumptions were investigated in solid–liquid mixing system with this new type of impeller by CFD and water experiment methods. Compared with the standard Intermig impeller, the improved one coupled with specially sloped baffles could promote the fluid circulation, create better solids suspension and consume less power. Besides lower impeller off-bottom clearance is good for solid suspension and distribution. The just-off-bottom speed was also determined by a power number criterion. Meanwhile, the predicted results were in good agreement with the experimental data.

In this paper, we propose a kernel canonical correlation analysis (KCCA) based idle-state detection method for asynchronous steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) systems. KCCA method can offer a flexible nonlinear solution to adequately extract nonlinear features of multi-electrode electroencephalogram signals. Based on this method, an ensemble KCCA coefficients feature model is proposed by weighting effectively multi-harmonic information and afterwards a threshold classification strategy for idle-state detection is presented. The weights of the model and optimal threshold are trained by the presented parameters learning scheme. Using our method, offline analysis was performed on 10 subjects with 8 fixed common electrodes. The results showed that the idle state could be detected with 95.9% average accuracy when SSVEP could be determined with 93.8% average accuracy. Further, the analysis verified the effectiveness and significant superiority of our method over other widely used ones.

Numerical simulations of solid-liquid mixing in a stirred tank with an improved Intermig impeller were performed by adopting standard κ-e turbulence model coupled with Eulerian granular multiphase model. An unsteady sliding mesh approach was used to simulate the impeller rotation. The flow field, solids hold-up and power consumptions were investigated in the solid-liquid mixing system. Compared to the standard Intermig impeller, the improved Intermig impeller coupled with the special sloped baffle could promote the fluid circulation, creating better solid suspension and consuming lesser power.