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Curcumin, the primary bioactive component isolated from turmeric, has been found to possess a variety of biological functions, including anti-leukemia activity. However, the effect of curcumin in different leukemia cells vary. In this study, we demonstrated that curcumin induced the expression of AIM2, IFI16, and NLRC4 inflammasomes in leukemia cells U937 by increasing the expression levels of ISG3 transcription factor complex, which activated caspase 1, promoted cleavage of GSDMD, and induced pyroptosis. We also found that pyroptosis executor GSDMD was not expressed in two curcumin-insensitive cells HL60 and K562 cells. In addition, exogenous overexpression of GSDMD by lentiviral transduction in K562 cells increased the anti-cancer activity of curcumin, and inhibiting the expression of GSDMD by shRNA enhanced U937 cells to resist curcumin. The results showed that inducing pyroptosis is a novel mechanism underlying the anti-leukemia effects of curcumin.

The construction of roads along rivers plays a crucial role in the construction of economic belts and social and economic development along rivers. Roadbeds are the foundation of highway construction, while the soft soil foundation is widely distributed on both sides of rivers, resulting in some difficulties for roadbed construction and highway use. Despite diverse technical methods for the treatment of general roadbeds, the treatment of soft soil roadbeds should be further explored. In this paper, various advantages of applying CFG (Cement Fly-ash Gravels) pile treatment to the soft foundation in Bailinhe Road, Yichang are investigated. Specifically, the soft soil roadbed treated by CFG pile is numerically simulated, the changes in engineering index response before and after foundation treatment are analyzed, and then the dynamic analysis under vehicle dynamic load is performed. The results demonstrate that the reinforcement effect of the CFG pile significantly weakens the influence of vehicle dynamic load on roadbeds.

In recent years, China has established many large water conservancy projects in the western mountainous areas. However, dam foundation excavation produces a huge amount of waste rock mixture. A soil-rock mixture with unique structural characteristics can easily cause geological disasters, such as collapse, landslide, and debris flow following an earthquake, rainfall, and engineering disturbance. Therefore, research on the strength and shear characteristics of the soil-rock mixture is beneficial to avoiding soil-rock mixture disasters. In this study, the soil-rock mixture in the slag dump site of Jinping Hydropower station is taken as the research object. The influence of different fillers on the gravel soil shear characteristics is investigated through a large-scale triaxial test of coarse-grained soil. The slope stability of the slag dump site is analyzed using Midas GTS. Then, the most unfavorable sliding surface of the slag dump site is discovered and the slope stability coefficient under the most unfavorable conditions is calculated. The results lay a scientific foundation for the design and construction of a slag dump slope.

Developing earth-abundant and highly effective electrocatalysts for electrocatalytic water splitting is a prerequisite for the upcoming hydrogen energy society. Recently, manganese-based materials have been one of the most promising candidates to replace noble metal catalysts due to their natural abundance, low cost, adjustable electronic properties, and excellent chemical stability. Although some achievements have been made in the past decades, their performance is still far lower than that of Pt. Therefore, further research is needed to improve the performance of manganese-based catalytic materials. In this review, we summarize the research progress on the application of manganese-based materials as catalysts for electrolytic water splitting. We first introduce the mechanism of electrocatalytic water decomposition using a manganese-based electrocatalyst. We then thoroughly discuss the optimization strategy used to enhance the catalytic activity of manganese-based electrocatalysts, including doping and defect engineering, interface engineering, and phase engineering. Finally, we present several future design opportunities for highly efficient manganese-based electrocatalysts.

The transcriptional repressor cAMP response element modulator (CREM) has an important role in T-cell development. In this study, we used the integrated Bioinformatics Methods to explore the role of CREM in gastric adenocarcinoma (GAC). Our results showed that high CREM expression was closely related with poorer overall survival in GAC. By GSEA cluster analysis, we found that the high expression of CREM was associated with the cancer-associated pathway in GAC. Moreover, single-cell sequencing data showed that CREM is mainly localized in exhausted CD8+ T cells. Its prognostic value and the potential function lead to T-cell exhaustion in the tumor microenvironment (TME). Similar results were also obtained in glioma and lung cancer. High expression of CREM, correlated with clinical relevance of GAC, was associated with T-cell exhaustion and M2 polarization in GAC. These findings suggest that CREM can be used as a prognostic biomarker in GAC, which might provide a novel direction to explore the pathogenesis of GAC.

Biogas resources in the Sanhu area of the Qaidam Basin have great potential, but there are few studies on biogas from shale, especially on the accumulation conditions of shale biogas. The study of biogas accumulation conditions of quaternary shale in the Sanhu area is of great significance to the theory of biogas accumulation and the guidance of exploration and development. This paper takes Quaternary shale in the Sanhu area as the research object. It is analyzed from multiple perspectives of shale hydrocarbon generation conditions, reservoir conditions, as well as hydrodynamic and structural conditions. Through the experiments of soluble organic carbon analysis and porosity and permeability analysis, the accumulation conditions of shale biogas reservoirs are clarified. The results show that the quaternary shale has a high soluble organic carbon content and high salinity formation water, which is conducive to late methane biochemical generation. Quaternary shale has the characteristics of high porosity and low permeability, mainly developing intergranular pores and intragranular pores. The large pore volume and specific surface area provide a lot of storage space for free gas and adsorbed gas, and the reservoir conditions are good. Under the structural characteristics of high in the south and low in the north and the action of formation hydrodynamics, biogas migrated from the south and deep to the north of the basin. The north slope is the main biogas-rich zone. On the whole, the quaternary shale in the Sanhu area has the characteristics of continuous hydrocarbon generation and dynamic accumulation, which has huge resource potential and exploration and development value.

Adsorbed gas is an important component of shale gas. The methane adsorption capacity of shale determines the composition of shale gas. In this study, the methane adsorption capacity of marine, transitional, and lacustrine shales in the Sichuan Basin was analyzed through its isothermal adsorption, mineral composition, water content, etc. The results show that the methane adsorption capacity of marine (Qiongzhusi Formation and Longmaxi Formation), transitional (Longtan Formation), and lacustrine (Xujiahe Formation and Ziliujing Formation) shales is significantly different. The Longtan Formation has the strongest methane adsorption capacity. This is primarily related to its high organic matter and organic matter type III content. The methane adsorption capacity of the lacustrine shale was the weakest. This is primarily related to the low thermal evolution degree and the high content of water-bearing clay minerals. Smectite has the highest methane adsorption capacity of the clay minerals, due to its crystal structure. The water content has a significant effect on methane adsorption largely because water molecules occupy the adsorption site. Additionally, the temperature and pressure in a specific range significantly affect methane adsorption capacity.

Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3′UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo. Moreover, Western blot results demonstrated that miR542-3p may promote EMT in the NRK52e cell line. In addition, we confirmed that BMP7, which played a crucial role in anti-kidney fibrosis and suppressed the progression of EMT, was a target of miR542-3p through Dual-Luciferase reporter assay, as did Western blot analysis. The effects of miR542-3p on regulating EMT could also be suppressed by transiently overexpressing BMP7 in NRK52e cells. Taken together, miR542-3p may be a critical mediator of the induction of EMT via directly targeting BMP7.

MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes and explore the underlying mechanisms of miR-30a in the impaired podocytes. The results revealed that downregulation of miR-30a in podocyte injury animal models and patients, highly induced the mesenchymal markers of EMT including Collagen I, Fibronectin and Snail. Furthermore, overexpression of miR-30a enhances epithelial markers (E-cadherin) but diminished mesenchymal markers (Collagen I, Fibronectin and Snail) in podocytes. In addition, we established miR-30a target NFATc3, an important transcription factor of Non-canonical Wnt signaling pathway. More importantly, our findings demonstrated that the augmentation of miR-30a level in podocytes inhibits the nuclear translocation of NFATc3 to protect cytoskeleton disorder or rearrangement. In summary, we uncovered the protective function of miR30a targeting NFATc3 in the regulation of podocyte injury response to EMT.

The metanephric mesenchyme (MM) cells are a subset of kidney progenitor cells and play an essential role in mesenchymal-epithelial transition (MET), the key step of nephron generation. Six2, a biological marker related to Wnt signaling pathway, promotes the proliferation, inhibits the apoptosis and maintains the un-differentiation of MM cells. Besides, LiCl is an activator of Wnt signaling pathway. However, the role of LiCl in cellular regulation of MM cells remains unclear, and the relationship between LiCl and Six2 in this process is also little known. Here, we performed EdU assay and flow cytometry assay to, respectively, detect the proliferation and apoptosis of MM cells treated with LiCl of increasing dosages. In addition, reverse transcription-PCR (RT-PCR) and Western-blot were conducted to measure the expression of Six2 and some maker genes of Wnt and bone-morphogenetic-protein (BMP) signaling pathway. Furthermore, luciferase assay was also carried out to detect the transcriptional regulation of Six2. Then we found LiCl promoted MM cell proliferation at low-concentration (10, 20, 30, and 40 mM). The expression of Six2 was dose-dependently increased in low-concentration (10, 20, 30, and 40 mM) at both mRNA and protein level. In addition, both of cell proliferation and Six2 expression in MM cells declined when dosage reached high-concentration (50 mM). However, Six2 knock-down converted the proliferation reduction at 50 mM. Furthermore, Six2 deficiency increased the apoptosis of MM cells, compared with negative control cells at relative LiCl concentration. However, the abnormal rise of apoptosis at 30 mM of LiCl concentration implies that it might be the reduction of GSK3β that increased cell apoptosis. Together, these demonstrate that LiCl can induce the proliferation and apoptosis of MM cells coordinating with Six2.

Nephron progenitor cells surround around the ureteric bud tips (UB) and inductively interact with the UB to originate nephrons, the basic units of renal function. This process is determined by the internal balance between self-renewal and consumption of the nephron progenitor cells, which is depending on the complicated regulation networks. It has been reported that Zeb1 regulates the proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in nephrons generation is not clear, especially in metanephric mesenchyme (MM). Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU assay, flow cytometry assay and wound healing assay, respectively. Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney. Besides, the dual-luciferase assay was conducted to study the molecular relationship between Zeb1 and Six2. We found that knock-down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in MM cells and Zeb1 overexpression contributed to the opposite results. Similarly, Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However, double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells compared with control cells. Nevertheless, double silence of Zeb1 and Six2 repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had an identical pattern in distinct developing phases of embryonic kidney. These results indicated that there may exist a complicated regulation network between Six2 and Zeb1. Together, we demonstrate Zeb1 promotes proliferation and apoptosis and inhibits the migration of MM cells, in association with Six2.

Apobec-1 complementation factor (A1CF) is a member of the heterogeneous nuclear ribonucleoproteins (hnRNP) family, which participates in site-specific posttranscriptional RNA editing of apolipoprotein B (apoB) transcript. The posttranscriptional editing of apoB mRNA by A1CF in the small intestine is required for lipid absorption. Apart from the intestine, A1CF mRNA is also reported to be highly expressed in the kidneys. However, it is remained unknown about the functions of A1CF in the kidneys. The aim of this paper is to explore the potential functions of A1CF in the kidneys. Our results demonstrated that in C57BL/6 mice A1CF was weakly expressed in embryonic kidneys from E15.5dpc while strongly expressed in mature kidneys after birth, and it mainly existed in the tubules of inner cortex. More importantly, we identified A1CF negatively regulated the process of epithelial-mesenchymal transition (EMT) in kidney tubular epithelial cells. Our results found ectopic expression of A1CF up-regulated the epithelial markers E-cadherin, and down-regulated the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) in NRK52e cells. In addition, knockdown of A1CF enhanced EMT contrary to the overexpression effect. Notably, the two A1CF variants led to the similar trend in the EMT process. Taken together, these data suggest that A1CF may be an antagonistic factor to the EMT process of kidney tubular epithelial cells.

To seek out the potential microRNAs (miRNAs) that target Wilms' tumor suppressor 1 (WT1), a transcription factor required for progenitor proliferation as well as normal development of the kidney, and to clarify the effects of the miRNAs on WT1, the 3'-untranslated region (3'-UTR) of WT1 was initially analyzed and miR-743a, a seldom-reported miRNA, was identified. In the present paper, luciferase reporter assays were performed to confirm that miR-743a is able to directly target the 3'-UTR of WT1. Subsequently, reverse transcription-quantitative polymerase chain reaction, combined with western blotting analyses, were performed, and the results revealed a significant inhibition of WT1 at the mRNA and the protein levels. Furthermore, a 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay, coupled with a WT1 rescue strategy, demonstrated that miR-743a inhibited the proliferation of metanephric mesenchymal (MM) cells, in part by targeting WT1. In conclusion, by targeting WT1, miR-743a suppresses the proliferation of MM cells in vitro, and probably possesses vital functions in kidney development and kidney-associated diseases. [ABSTRACT FROM AUTHOR]