This paper studies mechanical properties and energy damage evolution of fiber-reinforced cemented sulfur tailings (CSTB) backfill. The effects of fiber length and fiber content on the stress, ...toughness and failure properties of the CSTB were systematically revealed. In addition, the energy index evolution law was studied, and the energy damage evolution mechanism of CSTB was revealed. The results show that the deformation failure of fiber-reinforced CSTB mainly goes through four stages: initial crack compaction, linear elastic deformation, yield failure and post-peak failure. The peak stress and residual stress of the CSTB firstly increase and then decrease with the increase of fiber content and the addition of fiber can promote the change from brittle failure to ductile failure of the CSTB. Adding appropriate amount of fiber can improve the toughness of CSTB, and the influence degree of fiber length on the toughness index of CSTB is 6mm>12mm>3mm. The total strain energy increases linearly along the variation of fiber content, while the elastic strain energy and dissipated energy increase exponentially at the peak stress point. In the process of CSTB deformation and failure, "gentle-linear growth-slow growth-rapid decline" is for elastic strain energy, while "gentle-slow growth-rapid growth-linear growth" is for dissipation energy. The damage and failure of CSTB mainly experienced four stages: initial damage, slow growth of damage, accelerated damage and damage failure, and the damage evolution curve also showed the changing characteristics of "gentle-slow growth-rapid growth-linear growth". The CSTB without added fiber showed obvious "Y-type" and "linear-type" shear failure characteristics and the phenomenon of shear cracks penetrating the backfill appeared. No big shear crack occur when it is damaged, showing that the fiber addition restrain the crack growth and improve the overall crack resistance of the CSTB. Hydration products are obviously distributed on the surface of the fiber, which indicates that the fiber will be evenly dispersed in the CSTB and form a certain bonding force with the cement-tailings matrix, thus improving the overall mechanical properties of the CSTB.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In order to study the static and dynamic flocculation settlement characteristics of fine total tailings and the influence law of flocculant on the mechanical properties of fine tailings backfill, the ...experimental research on the flocculation settlement and mechanical properties of fine total tailings was carried out in the laboratory. The static flocculation settlement test of fine total tailings was carried out by orthogonal test scheme, and the influence law of the full-tail mortar concentration (FTMC), flocculant unit consumption (FUC) and flocculant solution concentration (FSC) on the concentration of underflow and sedimentation rate was analyzed, and the best static flocculation settlement parameters were obtained. Secondly, the dynamic flocculation test was carried out on the basis of static flocculation settlement parameters to reveal the influence law of dynamic flocculation settlement on underflow concentration. Finally, the compressive strength of fine tailings backfill under different flocculant unit consumption were tested, and the microscopic evolution of backfill was investigated by scanning electron microscopy. The results show that: Anionic flocculant has better flocculation effect than non-ionic flocculant, so anionic flocculant can be preferred as flocculant for flocculation settlement of fine full tailings. The flocculation settlement process of fine tailings slurry can be divided into four regions: clarification region, settlement region, transition region and compression region. The influence degree of the three factors on settling velocity and underflow concentration is full-tail mortar concentration > flocculant unit consumption > flocculant solution concentration, and full-tail mortar concentration and flocculant unit consumption are significant influencing factors on settling velocity and underflow concentration. The flocculation settlement parameters of fine full tailings slurry are not only affected by single factor, but also by the interaction between factors. The optimal static flocculation sedimentation parameters are as follows: the full tailings slurry concentration is 20 %, the flocculant unit consumption is 10 g/t and the flocculant solution concentration is 0.3 %. The dynamic flocculation settlement can greatly increase the underflow concentration, and the underflow concentration increases with the residence time, but there is no significant change in the underflow concentration when the residence time exceeds 5 h. The compressive strength of fine tailings backfill decreases with the increase of flocculant unit consumption, and the microscopic test results show that the increase of flocculant unit consumption will weaken the compactness of the microstructure of the backfill, which leads to the decrease of the compressive strength of the backfill.
Although clinically associated with severe developmental defects, the biological function of FOXK2 remains poorly explored. Here we report that FOXK2 interacts with transcription corepressor ...complexes NCoR/SMRT, SIN3A, NuRD, and REST/CoREST to repress a cohort of genes including HIF1β and EZH2 and to regulate several signaling pathways including the hypoxic response. We show that FOXK2 inhibits the proliferation and invasion of breast cancer cells and suppresses the growth and metastasis of breast cancer. Interestingly, FOXK2 is transactivated by ERα and transrepressed via reciprocal successive feedback by HIF1β/EZH2. Significantly, the expression of FOXK2 is progressively lost during breast cancer progression, and low FOXK2 expression is strongly correlated with higher histologic grades, positive lymph nodes, and ERα−/PR−/HER2- status, all indicators of poor prognosis.
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•FOXK2 is a transcription repressor•FOXK2 is physically associated with multiple corepressor complexes•FOXK2 and its associated corepressor complexes target the hypoxia pathway•FOXK2 suppresses the growth and metastasis of breast cancer
Shan et al. show that FOXK2 interacts with multiple corepressor complexes to repress the expression of a cohort of genes including HIF1β and EZH2. They show that an ERα-FOXK2-HIF1β/EZH2 axis is critically involved in breast cancer progression and that low FOXK2 expression correlates with poor prognosis.
Previous studies have confirmed that for cemented tailings backfill, mechanical properties are improved through the addition of fiber. However, for fiber-reinforced cemented sulfur tailings backfill ...(FRCSTB), physical and flow properties are still unknown. In this paper, the changes in fluidity, splitting tensile strength (STS) and uniaxial compressive strength (UCS) of cemented sulfur tailings backfill (CSTB) are analyzed in detail. Secondly, regarding the addition of glass fiber and polypropylene fiber, the changes in the fluidity, STS and UCS of the CSTB, resulting from the fiber length, fiber content and method of fiber addition used, were analyzed. Moreover, the relationship between the UCS and fiber content is established. Finally, the mechanism behind the influence of fiber and sulfur content on the mechanical properties of CSTB is revealed. The results indicate that with the increase in sulfur content, the fluidity of the tailings slurry exhibits exponential growth. During the process of increasing sulfur content, the UCS and STS of CSTB initially increase and then decrease, reaching maximum values at 12% sulfur content. Similarly, at a fiber content of 0.6%, the UCS and 28d STS of CSTB reach their maximum values. In terms of enhancing the mechanical properties of CSTB, the effectiveness of glass fibers surpasses that of polypropylene fibers. In addition, regarding the improvement of the UCS of CSTB, the mixed addition of fibers is obviously worse than that of fiber alone. However, in terms of enhancing the STS of CSTB, the mixed addition of fibers outperforms the single addition of polypropylene fiber. From a microscopic perspective, polypropylene and glass fiber are able to form strong cohesion with the cement–tailings matrix and effectively prevent the formation and expansion of pores and cracks.
The histone methyl transferase enhancer of zeste homolog 2 (EZH2) is a master transcriptional regulator involved in histone H3 lysine 27 trimethylation. We aimed to elucidate the precise ...post-translational regulations of EZH2 and their role in cancer pathogenesis. Here, we show that SET and MYND domain containing 2 (SMYD2) directly methylates EZH2 at lysine 307 (K307) and enhances its stability, which can be relieved by the histone H3K4 demethylase lysine-specific demethylase 1 (LSD1). SMYD2 is critical for EZH2 function in repressing a cohort of genes governing several cancer-associated pathways. In addition, SMYD2 promotes breast cancer cell proliferation, epithelial-mesenchymal transition, and invasion through EZH2 K307 methylation, and it is markedly upregulated in various human cancers. Our data suggest that dynamic crosstalk between SMYD2-mediated EZH2 methylation plays an important role in fine-tuning EZH2 functions in chromatin recruitment and transcriptional repression.
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•EZH2 is methylated by SMYD2 and is demethylated by LSD1 on lysine (K) 307•EZH2 K307 methylation enhances the protein stability of EZH2•SMYD2 and EZH2 collaboratively participate in transcriptional repression•SMYD2 coordinates EZH2 to promote breast cancer tumorigenesis and metastasis
Post-translational modification of proteins is involved in protein stability regulation. Zeng et al. demonstrate that EZH2 K307 is methylated by SMYD2 and demethylated by LSD1. This modification protects EZH2 from degradation. The dynamic crosstalk between SMYD2-mediated EZH2 methylation plays an important role in the transcriptional repression of EZH2.
A series of experiments was conducted to study the performance and mechanisms of Cemented Ultrafine Tailings Backfill (CUTB). Firstly, the optimum fiber type was selected by single factor multilevel ...test. Secondly, the effects of cement content, rice husk ash content, fiber content and fiber length on backfill properties were analyzed by orthogonal test and microstructure test, and the influence mechanism of fiber and rice husk ash content was revealed. Finally, fuzzy mathematics theory is used to optimize the ratio parameters. The results show, compared to glass and basalt fiber, polypropylene fiber yields the most substantial enhancement in backfill strength. The increase of cement content, polypropylene fiber content and length can reduce slump, but the change of rice husk ash content has no obvious effect. Increased cement or fiber content effectively restrained the formation of primary fractures in CUTB, thus enhancing its integrity. Adding an optimal dosage range of 0–4 % of rice husk ash boosted the early compressive strength, albeiting at the expense of later compressive strength. Fiber addition with the optimum content range between 0.1 and 0.4 % enhanced the strengthening effect of cement content on compressive strength. Fiber primarily enhances the macroscopic strength of backfill through the dispersion and co-loading of forces, whereas rice husk ash enhances strength by optimizing void structure distribution. The optimal ratio parameters of a cement content of 310 kg/m³, rice husk ash content of 8.0 %, fiber content of 0.4 %, and fiber length of 9 mm were proposed finally.
2,5-Dimethyl-celecoxib (DMC) is a close structural analog of the selective COX-2 inhibitor celecoxib that lacks COX-2-inhibitory function. Thus, DMC is a promising drug for anti-tumor. In this study, ...we evaluated the efficacy and the molecular basis of DMC in the treatment of human glioblastoma multiforme (GBM). DMC inhibited the growth and proliferation of GBM cell lines (LN229, A172, U251, and U87MG) in a dose-dependent manner (
P
< 0.001). In GBM cells treated with DMC, detection by flow cytometry showed cell cycle arrest, and proteins involved in cell cycle such as P21 were increased. Compared with control group, Annexin-V/PI-staining in DMC-treatment group was increased, indicating that DMC could induce apoptosis in GBM cells. Also, associated proteins including cleaved caspase 3 and cleaved PARP-1 were increased. It was further explored whether DMC blocked cell cycle and induced apoptosis in GBM cells through CIP2A/PP2A/AKT signaling pathway. After treatment of DMC, the phosphorylation of Akt was reduced while the total Akt level was not affected. DMC suppressed the expression of CIP2A in a time-dependent manner, while the CIP2A overexpression group reversed cell cycle and apoptotic protein expression led by DMC. Finally, in a xenograft model in nude mice using LN229 cells, DMC suppressed tumor growth. These findings proved that DMC could block cell cycle and induce apoptosis in GBM cells by suppressing CIP2A/PP2A/Akt signaling axis, which indicated that DMC could be an effective option for GBM treatment.
In order to improve the mechanical properties of backfill, steel slag and straw fiber were used as materials to prepare backfill. The law of sand-cement ratio, mass concentration, steel slag content ...and straw fiber on strength and rheological parameters of backfill was analyzed by orthogonal test method, and the influence mechanism of steel slag content and straw fiber on physical properties of backfill was revealed. The results show that mass concentration exerts the most substantial impact on rheological parameters, emerging as a significant determinant. Moreover, the yield stress diminishes with escalating tailings-cement ratio, while it escalates with higher mass concentration, steel slag content and straw fiber content. Augmenting the tailings-cement ratio and steel slag content serves to impede the amplification effect of mass concentration on yield stress. Notably, the tailings-cement ratio emerges as the most influential factor affecting the uniaxial compressive strength (UCS) of the backfill, albeit the UCS diminishes with rising tailings-cement ratio. Elevating the mass concentration and steel slag content can counteract the debilitation caused by an increase in the tailings-cement ratio on the UCS of the backfill. Furthermore, heightened mass concentration can bolster the reinforcing impact of steel slag content on early UCS. The increase of tailings-cement ratio increases the size and range of the void inside the backfill, subsequently leading to the degradation of its macroscopic compressive strength. The adhesion between straw fiber and mortar matrix constitutes a pivotal factor in improving the integration of backfill, whereas steel slag contributes to improving the mechanical properties by enhancing the distribution of void structures within the backfill. This research not only offer data support and scientific guidance for the design of backfill ratio parameters but also facilitate the broader application of straw fiber and steel slag in mine backfilling operations.
•The variation characteristics of compressive strength and rheological parameters of the backfill are revealed.•The influence of the interaction of various factors on the strength and rheological parameters of the backfill is revealed.•The influence mechanism of steel slag content and straw fiber on mechanical properties of backfill was investigated.
The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. ...However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin a chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and MST2 (MST1/2). WW45 interaction with MST1/2 was thereby enhanced, resulting in the activation of Hippo signaling to block YAP activity for cell contact inhibition. Importantly, low cell density led to SPTAN1 dephosphorylation and NUMB cytoplasmic location, along with MST1/2 inhibition and, consequently, YAP activation. Moreover, double KO of NUMB and WW45 in the liver led to appreciable organ enlargement and rapid tumorigenesis. Interestingly, NUMB isoforms 3 and 4, which have a truncated phosphotyrosine-binding (PTB) domain and are thus unable to interact with phosphorylated SPTAN1 and activate MST1/2, were selectively upregulated in liver cancer, which correlated with YAP activation. We have thus revealed a SPTAN1/ NUMB1/2 axis that acts as a cell density sensor to restrain cell growth and oncogenesis by coupling external cell-cell contact signals to intracellular Hippo signaling.
Mixing coarse aggregates into cemented paste backfill can significantly affect its mechanical properties. Many mixed aggregates cemented backfill samples were carried out uniaxial compression tests ...to see how the coarse aggregate replacement rate affects its uniaxial compressive strength, and analyze the influence on the damage energy consumption characteristics of the backfill before peak stress based on damage mechanics theory. Then taking Jinchuan No. 2 Mine as an example, study the stability and mechanical behaviour of the backfill in the stope by means of numerical simulation. The results show as following: The uniaxial compressive strength of the backfill at different curing ages has a quadratic function curve relationship with an increasing coarse aggregates replacement rate. This indicates that there exists an optimal replacement rate of 60%. When the content of coarse aggregate exceeds the optimal value, the strain value of the backfill sample corresponding to the peak stress damage value decreases, which means that the more the content of coarse aggregate, the more the backfill sample is prone to brittle failure. The peak stress specific energy increases first and then decreases with increasing coarse aggregate replacement rate, shows a similar change with its uniaxial compressive strength, so the backfill with the higher uniaxial compressive strength have stronger energy storage mechanism. The numerical simulation results show that the backfill with the optimal coarse aggregate replacement rate can effectively relieve the stress concentration of the rock mass in the stope, however the filling body has obvious tensile damage due to the mining activities.
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