The histone demethylase lysine‐specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of ...H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48‐linked deubiquitin and stability. Interestingly, we found c‐Myc was a key downstream effector of the USP1‐KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.
This study identifies USP1 as a critical deubiquitinase for stabilizing KDM4A, thereby promoting prostate cancer growth and tumorigenesis. Targeting KDM4A stabilization through pharmacological inhibition of USP1 by ML323 could thus open an avenue for therapeutic intervention in prostate cancer patients.
Game-Theoretic Control of Active Loads in DC Microgrids Ling-Ling Fan; Nasirian, Vahidreza; Modares, Hamidreza ...
IEEE transactions on energy conversion,
2016-Sept., 2016-9-00, 20160901, Volume:
31, Issue:
3
Journal Article
Peer reviewed
Open access
Low-inertia dc microgrids often rely on storage devices to buffer energy and handle abrupt load changes. An alternative approach involves the concept of power buffers, power electronics converters ...with bulky storage components that precede the final point-of-load converters, and decouple the grid and load dynamics. Proper adjustment of the input impedances of power buffers helps to shape the trajectory of the transient imposed on a dc microgrid. A communication network facilitates information exchange among active loads (loads augmented with power buffers). Such group information helps to collectively respond to any load change; an optimal response with the least energy extract from individual buffers. A game-theoretic performance function is defined for active loads. Then, a distributed control policy simultaneously minimizes all performance functions. A low-voltage dc microgrid, simulated in MATLAB/Simulink environment, is used to study the effectiveness of the proposed methodology.
A low cost nonaqueous potassium‐based battery–supercapacitor hybrid device (BSH) is successfully established for the first time with soft carbon as the anode, commercialized activated carbon as the ...cathode, and potassium bis(fluoro‐slufonyl)imide in dimethyl ether as the electrolyte. This BSH reconciles the advantages of potassium ion batteries and supercapacitors, achieving a high energy density of 120 W h kg−1, a high power density of 599 W kg−1, a long cycle life of 1500 cycles, and an ultrafast charge/slow discharge performance (energy density and power density are calculated based on the total mass of active materials in the anode and cathode). This work demonstrates a great potential of applying the nonaqueous BSH for low cost electric energy storage systems.
A low cost nonaqueous potassium‐based battery–supercapacitor hybrid device (BSH) is successfully established with soft carbon as the anode, commercialized activated carbon as the cathode, and potassium bis(fluoro‐slufonyl)imide in dimethyl ether as the electrolyte. This BSH reconciles the advantages of potassium‐ion batteries and supercapacitors, achieving a high energy density, a long cycle life, and an ultrafast charge/slow discharge performance.
Carbonaceous materials as anodes usually exhibit low capacity for lithium ion batteries (LIBs) and sodium ion batteries (SIBs). Oxygen‐doped carbonaceous materials have the potential of high capacity ...and super rate performance. However, up to now, the reported oxygen‐doped carbonaceous materials usually exhibit inferior electrochemical performance. To overcome this problem, a high reactive oxygen‐doped 3D interdigital porous carbonaceous material is designed and synthesized through epitaxial growth method and used as anodes for LIBs and SIBs. It delivers high reversible capacity, super rate performance, and long cycling stability (473 mA h g−1after 500 cycles for LIBs and 223 mA h g−1 after 1200 cycles for SIBs, respectively, at the current density of 1000 mA g−1), with a capacity decay of 0.0214% per cycle for LIBs and 0.0155% per cycle for SIBs. The results demonstrate that constructing 3D interdigital porous structure with reactive oxygen functional groups can significantly enhance the electrochemical performance of oxygen‐doped carbonaceous material.
3D interdigital organic carbonaceous material with reactive oxygen functional groups exhibits excellent performance for both lithium ion batteries (LIBs) and sodium ion batteries (SIBs). It delivers a high reversible capacity, excellent rate capacity, and superior cycling stability (500 cycles for LIBs and 1200 cycles for SIBs, with a capacity decay of 0.0214% per cycle for LIBs and 0.0155% per cycle for SIBs).
At least some cancer stem cells (CSCs) display intrinsic drug resistance that may thwart eradication of a malignancy by chemotherapy. We explored the genesis of such resistance by studying mouse ...models of liver cancer driven by either MYC or the combination of oncogenic forms of activation of v‐akt murine thymoma viral oncogene homolog (AKT) and NRAS. A common manifestation of chemoresistance in CSCs is efflux of the DNA‐binding dye Hoechst 33342. We found that only the MYC‐driven tumors contained a subset of cells that efflux Hoechst 33342. This “side population” (SP) was enriched for CSCs when compared to non‐SP tumor cells and exhibited markers of hepatic progenitor cells. The SP cells could differentiate into non‐SP tumor cells, with coordinate loss of chemoresistance, progenitor markers, and the enrichment for CSCs. In contrast, non‐SP cells did not give rise to SP cells. Exclusion of Hoechst 33342 is mediated by ATP binding cassette drug transporter proteins that also contribute to chemoresistance in cancer. We found that the multidrug resistance gene 1 (MDR1) transporter was responsible for the efflux of Hoechst from SP cells in our MYC‐driven model. Accordingly, SP cells and their tumor‐initiating subset were more resistant than non‐SP cells to chemotherapeutics that are effluxed by MDR1. Conclusion: The oncogenotype of a tumor can promote a specific mechanism of chemoresistance that can contribute to the survival of hepatic CSCs. Under circumstances that promote differentiation of CSCs into more mature tumor cells, the chemoresistance can be quickly lost. Elucidation of the mechanisms that govern chemoresistance in these mouse models may illuminate the genesis of chemoresistance in human liver cancer. (HEPATOLOGY 2012)
AbstractMost previous studies have made great progress in the size effect of concrete materials and several classic size effect laws (SELs) have been proposed. However, there is a lack of size effect ...laws for RC components including beams, columns, and beam-column joints. The focus of this study is the size effect in RC columns confined by stirrups under axial compression. A three-dimensional mesoscale numerical method for the simulation of the failure of RC columns was established. The numerical results were found in good accordance with the available experimental ones, demonstrating the rationality of the simulation method. The simulation method was then extended to model the size effect of circular RC columns having larger sizes. The main parameter, stirrups ratio, which evaluates the size and interaction effects between the concrete and reinforcement, was examined and analyzed. Furthermore, the influence mechanisms of confinement effect generated by stirrups on the nominal compressive strength were explored. Finally, based on the available classic SEL for concrete materials, a predictive formula was built that can describe the quantitative influence of constraint generated by stirrups on size effect of RC columns under axial compression. For comparison, the validation of the predictive theorical formula with the available test data is presented.
Conventional ether‐based electrolytes exhibited a low polarization voltage in potassium‐ion batteries, yet suffered from ion–solvent co‐intercalation phenomena in a graphite anode, inferior ...potassium‐metal performance, and limited oxidation stability. Here, we reveal that weakening the cation–solvent interactions could suppress the co‐intercalation behaviour, enhance the potassium‐metal performance, and improve the oxidation stability. Consequently, the graphite anode exhibits K+ intercalation behaviour (K||graphite cell operates 200 cycles with 86.6 % capacity retention), the potassium metal shows highly stable plating/stripping (K||Cu cell delivers 550 cycles with average Coulombic efficiency of 98.9 %) and dendrite‐free (symmetric K||K cell operates over 1400 hours) properties, and the electrolyte exhibits high oxidation stability up to 4.4 V. The ion–solvent interaction tuning strategy provides a promising method to develop high‐performance electrolytes and beyond.
In low‐concentrated ether‐based electrolytes, the weak K+–solvent interactions are conducive to enhancing the potassium metal performance, the oxidation stability of the electrolyte, and enabling the graphite anode to undergo K+ intercalation rather than K+‐solvent co‐intercalation behaviour.
We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending ...the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high‐fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high‐fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n‐6/n‐3 ratio but significantly increased the n‐3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF‐κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
This study investigates the effects and mechanisms of a high dose of epigallocatechin gallate (EGCG) in extending the lifespan of obese rats. We find that EGCG improved serum glucose, lipids, inflammation, oxidative stress associated with ageing in obese rats induced by a high‐fat diet, total free fatty acids (FFAs), transcriptome, and proteome. The results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
Mitochondria and cell membrane play important roles in maintaining cellular activity and stability. Here, a single-agent self-delivery chimeric peptide based nanoparticle (designated as M-ChiP) was ...developed for mitochondria and plasma membrane dual-targeted photodynamic tumor therapy. Without additional carrier, M-ChiP possessed high drug loading efficacy as well as the excellent ability of producing reactive oxygen species (ROS). Moreover, the dual-targeting property facilitated the effective subcellular localization of photosensitizer protoporphyrin IX (PpIX) to generate ROS in situ for enhanced photodynamic therapy (PDT). Notably, plasma membrane-targeted PDT would enhance the membrane permeability to improve the cellular delivery of M-ChiP, and even directly disrupt the cell membrane to induce cell necrosis. Additionally, mitochondria-targeted PDT would decrease mitochondrial membrane potential and significantly promote the cell apoptosis. Both in vitro and in vivo investigations indicated that this combinatorial PDT in mitochondria and plasma membrane could achieve the therapeutic effect maximization with reduced side effects. The single-agent self-delivery system with dual-targeting strategy was demonstrated to be a promising nanoplatform for synergistic tumor therapy.
A series of novel indole1,2-c-1,2,4-benzotriazine derivatives were obtained by a modified Sandmeyer reaction in the presence of tert-butylnitrite (t-BuONO). As compared with hymexazol, a commercially ...available agricultural fungicide, at the concentration of 50 μg/mL, two indole1,2-c-1,2,4-benzotriazines, 5h and 5k, exhibited the more promising and pronounced antifungal activities in vitro against five phytopathogenic fungi. It clearly demonstrated that introduction of appropriate substituents on the indolyl ring of indole1,2-c-1,2,4-benzotriazine (5a) would lead to the more potent derivatives.
Two indole1,2-c-1,2,4-benzotriazine derivatives have been identified as potent antifungal agents and might be considered as novel promising lead candidates for further design and synthesis of agricultural fungicides. Display omitted
► Indole1,2-c-1,2,4-benzotriazine derivatives were synthesized by a modified Sandmeyer reaction. ► Their antifungal activities were tested against phytopathogenic fungi. ► Two compounds exhibited the promising and pronounced antifungal activities.
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