Transcription factor AP-2α activates RNA polymerase III-directed transcription and tumor cell proliferation by controlling expression of c-MYC and p53.

Deregulation of transcription factor AP2 alpha (TFAP2A) and RNA polymerase III (Pol III) products is associated with tumorigenesis. However, the mechanism underlying this event is not fully understood and the connection between TFAP2A and Pol III-directed transcription has not been investigated. Here, we report that TFAP2A functions as a positive factor in the regulation of Pol III-directed transcription and cell proliferation. We found TFAP2A is also required for the activation of Pol III transcription induced by the silencing of filamin A, a well-known cytoskeletal protein and an inhibitor in Pol III-dependent transcription identified previously. Using a chromatin immunoprecipitation technique, we showed TFAP2A positively modulates the assembly of Pol III transcription machinery factors at Pol III-transcribed gene loci. We found TFAP2A can activate the expression of Pol III transcription-related factors, including BRF1, GTF3C2, and c-MYC. Furthermore, we demonstrate TFAP2A enhances expression of MDM2, a negative regulator of tumor suppressor p53, and also inhibits p53 expression. Finally, we found MDM2 overexpression can rescue the inhibition of Pol III-directed transcription and cell proliferation caused by TFAP2A silencing. In summary, we identified that TFAP2A can activate Pol III-directed transcription by controlling multiple pathways, including general transcription factors, c-MYC and MDM2/p53. The findings from this study provide novel insights into the regulatory mechanisms of Pol III-dependent transcription and cancer cell proliferation.

Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway.

RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription.

LncRNA Pnky Positively Regulates Neural Stem Cell Migration by Modulating mRNA Splicing and Export of Target Genes.

Directed migration of neural stem cells (NSCs) is critical for embryonic neurogenesis and the healing of neurological injuries. The long noncoding RNA (lncRNA) Pnky has been reported to regulate neuronal differentiation of NSCs by interacting with PTBP1. However, its regulatory effect on NSC migration remains to be determined. Herein, we identified that Pnky is also a key regulator of NSC migration in mice, as underscored by the finding that Pnky silencing suppressed but Pnky overexpression promoted the in vitro migration of both C17.2 and NE4C murine NSCs. Additionally, in vivo cell tracking demonstrated that Pnky depletion attenuated but Pnky overexpression facilitated the migration of NE4C cells in the spinal canal after transplantation via injection into the spinal canal. Mechanistically, Pnky regulated the expression of a core set of critical regulators that direct NSC migration, including MMP2, MMP9, Connexin43, Paxillin, AKT, ERK, and P38MAPK. Using catRAPID, a web server for large-scale prediction of protein-RNA interactions, the splicing factors U2AF1 and U2AF1L4, as well as the mRNA export adaptors SARNP, Aly/Ref, and THOC7, were predicted to interact strongly with Pnky. Further investigations using colocalization and RNA immunoprecipitation (RIP) assays confirmed the direct binding of Pnky to U2AF1, SARNP, Aly/Ref, and THOC7. Transcriptomic profiling revealed that as many as 5319 differential splicing events of 3848 genes, which were highly enriched in focal adhesion, PI3K-Akt and MAPK signaling pathways, were affected by Pnky depletion. The predominant subtype of differential splicing by Pnky depletion is intron retention, followed by alternative 5' and 3' splice sites and mutually exclusive exons. Moreover, Pnky knockdown substantially blocked but Pnky overexpression facilitated the export of MMP2, Paxillin, AKT, p38MAPK, and other mRNAs to the cytosol. Collectively, our data showed that through interacting with U2AF1, SARNP, Aly/Ref, and THOC7, Pnky couples and modulates the splicing and export of target mRNAs, which consequently controlling NSC migration. These findings provide a possible theoretical basis of NSC migration regulation.

Early Growth Response 1 Strengthens Pol-III-Directed Transcription and Transformed Cell Proliferation by Controlling PTEN/AKT Signalling Activity.

RNA polymerase III (Pol III) products play essential roles in ribosome assembly, protein synthesis, and cell survival. Deregulation of Pol-III-directed transcription is closely associated with tumorigenesis. However, the regulatory pathways or factors controlling Pol-III-directed transcription remain to be investigated. In this study, we identified a novel role of EGR1 in Pol-III-directed transcription. We found that Filamin A (FLNA) silencing stimulated EGR1 expression at both RNA and protein levels. EGR1 expression positively correlated with Pol III product levels and cell proliferation activity. Mechanistically, EGR1 downregulation dampened the occupancies of Pol III transcription machinery factors at the loci of Pol III target genes. Alteration of EGR1 expression did not affect the expression of p53, c-MYC, and Pol III general transcription factors. Instead, EGR1 activated RhoA expression and inhibited PTEN expression in several transformed cell lines. We found that PTEN silencing, rather than RhoA overexpression, could reverse the inhibition of Pol-III-dependent transcription and cell proliferation caused by EGR1 downregulation. EGR1 could positively regulate AKT phosphorylation levels and is required for the inhibition of Pol-III-directed transcription mediated by FLNA. The findings from this study indicate that EGR1 can promote Pol-III-directed transcription and cell proliferation by controlling the PTEN/AKT signalling pathway.

RNA polymerase I subunit 12 plays opposite roles in cell proliferation and migration.

RNA polymerase I (Pol I) is responsible for the synthesis of the majority of ribosomal RNA molecules in eukaryotes. Pol I subunit 12 (RPA12) is involved in the transcriptional termination and lipid metabolism in yeast. However, its role in human cells hasn't been investigated so far. Here, we show that RPA12 is present in the nucleolus and nucleoplasm of HeLa cells. RPA12 can act as a positive factor to regulate Pol I-mediated transcription and the proliferation of 293T and HeLa cells. Unexpectedly, RPA12 can repress HeLa cell migration, indicating that RPA12 plays opposite roles in cell proliferation and migration. This study provides a novel insight into the role of RPA12 in human cells.

CoIn dual-atom catalyst for hydrogen peroxide production via oxygen reduction reaction in acid.

The two-electron oxygen reduction reaction in acid is highly attractive to produce H2O2, a commodity chemical vital in various industry and household scenarios, which is still hindered by the sluggish reaction kinetics. Herein, both density function theory calculation and in-situ characterization demonstrate that in dual-atom CoIn catalyst, O-affinitive In atom triggers the favorable and stable adsorption of hydroxyl, which effectively optimizes the adsorption of OOH on neighboring Co. As a result, the oxygen reduction on Co atoms shifts to two-electron pathway for efficient H2O2 production in acid. The H2O2 partial current density reaches 1.92 mA cm-2 at 0.65 V in the rotating ring-disk electrode test, while the H2O2 production rate is as high as 9.68 mol g-1 h-1 in the three-phase flow cell. Additionally, the CoIn-N-C presents excellent stability during the long-term operation, verifying the practicability of the CoIn-N-C catalyst. This work provides inspiring insights into the rational design of active catalysts for H2O2 production and other catalytic systems.

Long-sequence voltage series forecasting for internal short circuit early detection of lithium-ion batteries.

Accurate early detection of internal short circuits (ISCs) is indispensable for safe and reliable application of lithium-ion batteries (LiBs). However, the major challenge is finding a reliable standard to judge whether the battery suffers from ISCs. In this work, a deep learning approach with multi-head attention and a multi-scale hierarchical learning mechanism based on encoder-decoder architecture is developed to accurately forecast voltage and power series. By using the predicted voltage without ISCs as the standard and detecting the consistency of the collected and predicted voltage series, we develop a method to detect ISCs quickly and accurately. In this way, we achieve an average percentage accuracy of 86% on the dataset, including different batteries and the equivalent ISC resistance from 1,000 Ω to 10 Ω, indicating successful application of the ISC detection method.

In Situ Crystallization of Active NiOOH/CoOOH Heterostructures with Hydroxide Ion Adsorption Sites on Velutipes-like CoSe/NiSe Nanorods as Catalysts for Oxygen Evolution and Cocatalysts for Methanol Oxidation.

Hydroxide ion (OH-) adsorption process is critical for accelerating the half-reactions of both metal-air batteries and direct methanol fuel cells in alkaline media. This study designs a rational catalyst/cocatalyst by constructing the readily available OH-adsorption sites to boost oxygen evolution reaction (OER) and methanol oxidation reaction (MOR). Cobalt selenide-coated nickel selenide nanorods are in situ grown on nickel foam to obtain CoSe/NiSe-nrs/NF via a one-pot solvothermal synthesis route. CoSe-0.2/NiSe-nrs/NF (Co/Ni molar ratio of 0.26) exhibits an excellent OER activity(an overpotential of 310 mV at 100 mA cm-2 and a Tafel slope of 58.3 mV dec-1). The differently oriented CoSe/NiSe-nrs with a velutipes-like structure and metallic property provide a promising electrical conductivity for charge transfer. In situ X-ray diffraction tests verify the crystallization of active ß-NiOOH during OER, and the crystallized NiOOH/CoOOH contributes to the excellent OER cycling stability in alkaline media. Synergistic effects between CoSe and NiSe-nrs/NF can balance the formation of NiOOH/CoOOH heterostructures to govern the exposure of available active sites. NiOOH/CoOOH as a highly active component can energetically adsorb OH- to promote OER. CoSe/NiSe-nrs/NFs as a low Pt-loading (0.5 wt%) support offer the mutually beneficial interactions for promoting cocatalytic and COads (poisonous intermediate) co-oxidation activities toward MOR. The electrochemically active surface area and mass activity of Pt/CoSe-0.2/NiSe-nrs/NF are 85 m2 gpt-1 and 1437.1 mA mgpt-1, respectively, which are much higher than those of commercial Pt/C (10.0 wt%). OH- absorbed on the NiOOH/CoOOH structure eliminates COads on the Pt surface via bifunctional mechanisms to improve the MOR activity. This study provides a promising reference for designing the versatile catalysts for energy conversion.

Co8FeS8 wrapped in Auricularia-derived N-doped carbon with a micron-size spherical structure as an efficient cathode catalyst for strengthening charge transfer and bioelectricity generation.

The main issues regarding the practical application of microbial fuel cells (MFCs) are the poor activity and tolerance of oxygen reduction reaction (ORR) catalysts in wastewater. In this study, Auricularia chelated with Co, Fe and S ions is used as a nitrogen (N)-enriched carbon source to prepare N-doped bimetallic sulfide (Co8FeS8)-embedded carbon spheres (Co8FeS8/NSC) using a hydrothermal method. The effects of various temperatures (800-950 °C) on the structure and catalytic activity of Co8FeS8/NSC catalysts are investigated. The MFC with a Co8FeS8/NSC (900 °C) cathode obtained the maximum power density of 1.002 W m-2, which is higher than that of Pt/C (0.88 W m-2). After 1440 h of operation, the power density of the Co8FeS8/NSC (900 °C) cathode only declined by 5.49%, indicating that the Co8FeS8 activity, charge transfer and O2 transport were slightly influenced by the attached microbes and poisonous substances in the wastewater. The electrochemical results indicate that Co8FeS8/NSC (900 °C) mainly proceeds by a 4e- ORR pathway, indicating that Co8FeS8 (Co2+ and Fe2+) wrapped in NSCs (carbon spheres) can trigger synergistic effects to provide more active sites and high electrical conductivity to achieve the rapid kinetics required for the ORR. Moreover, the porous structures of the NSCs (220.97 m2 g-1) with incorporated pyridinic N, pyrrolic N and graphitic N can provide abundant available channels for O2 and OH- transport to ensure the preferential accessibility of the reactant molecules to active sites. This indicates that Auricularia-derived Co8FeS8/NSC catalysts have great potential as alternatives for precious metal-based catalysts in neutral electrolyte MFCs.

Enhanced generation of hydroxyl radicals on well-crystallized molybdenum trioxide/nano-graphite anode with sesame cake-like structure for degradation of bio-refractory antibiotic.

Anodic electro-catalysis oxidation is a highly effective way to solve the pollution problem of antibiotics in wastewater and receiving water bodies. In this study, for the first time, molybdenum trioxide/Nano-graphite (MoO3/Nano-G) composites are synthesized as anodic catalysts by a surfactant-assisted solvothermal method followed by low-temperature calcination. The effects of the proportion of MoO3 to Nano-G (10, 30 and 50%) on the properties of composites are investigated through structural characterizations and electrochemical measurements. Results indicate that MoO3(30)/Nano-G electrode displays the electro-catalysis degradation efficiency of 99.9% towards ceftazidime, which is much higher than those of Nano-G (46.7%) and dimensionally stable anode (69.2%). The degradation mechanism for ceftazidime is studied by investigating the yields and kinds of active species. Results show that all of the OH, O2- and H2O2 are responsible for the electro-catalytic degradation process, and the produced OH radicals are the major active species for ceftazidime degradation. The synergistic effects between MoO3 and Nano-G greatly contribute to the activation of H2O molecules to produce OH, meanwhile the special sesame cake-like structure facilitates to the exposure of contaminants to OH on active sites to enhance the degradation efficiency. These results suggest that MoO3/Nano-G electrodes can be considered as the promising catalysts for treating bio-refractory organic wastewater.