Drug resistance largely limits the efficacy and efficiency of chemotherapeutics, which is a first-line treatment for liver cancer, consequently triggering a complete failure in clinical application. There are numerous attempts in exploring potential strategies for avoiding drug resistance, but none of them has effectively addressed this problem. Therefore, novel molecular targets and agents proposed for addressing drug resistance are needed. This study established 5-fluorouracil (5-Fu)-resistant HepG2 cells (HepG2/R) and showed that a FOXM1-targeted peptide, P201, reactivated 5-Fu to attenuate HepG2/R cell viability, proliferation, migration and promote apoptosis. Moreover, both pharmacological studies and RNA genomic sequencing results uncovered that combination of P201 and 5-Fu notably decreased expressions of FOXM1, MDR1 and ABCG2 compared to 5-Fu alone, indicating P201 overcame 5-Fu resistance mainly through inhibiting FOXM1 and ABC transporters. Therefore, P201 could inhibit ABC transporters by targeting FOXM1 in HepG-2/R cells, overcoming 5-Fu resistance and enhancing anti-cancer drug sensitivity. FOXM1 may be a new target for overcoming 5-Fu resistance in HepG2 cell while the combination treatment of P201 and 5-Fu may serve as a potential strategy for treating liver cancer.
Rechargeable aqueous Zn/MnO2 batteries are very attractive large‐scale energy storage technologies, but still suffer from limited cycle life and low capacity. Here the novel adoption of a near‐neutral acetate‐based electrolyte (pH ≈ 6) is presented to promote the two‐electron Mn4+/Mn2+ redox reaction and simultaneously enable a stable Zn anode. The acetate anion triggers a highly reversible MnO2/Mn2+ reaction, which ensures high capacity and avoids the issue of structural collapse of MnO2. Meanwhile, the anode‐friendly electrolyte enables a dendrite‐free Zn anode with outstanding stability and high plating/stripping Coulombic efficiency (99.8%). Hence, a high capacity of 556 mA h g?1, a lifetime of 4000 cycles without decay, and excellent rate capability up to 70 mA cm?2 are demonstated in this new near‐neutral aqueous Zn/MnO2 battery by simply manipulating the salt anion in the electrolyte. The acetate anion not only modifies the surface properties of MnO2 cathode but also creates a highly compatible environment for the Zn anode. This work provides a new opportunity for developing high‐performance Zn/MnO2 and other aqueous batteries based on the salt anion chemistry. 相似文献
A new type of biosorbent was developed for binding anionic precious metals through cross-linking waste biomass Corynebacterium glutamicum with polyethylenimine (PEI). This biomass was evaluated for the removal and recovery of palladium and compared to commercial adsorbents, such as Amberjet 4200 Cl, Lewatit Monoplus TP 214, SPC-100, and SPS-200. The kinetic experiments revealed that the sorption equilibrium was reached with 30 min for the PEI-modified biomass. The maximum uptake of the biosorbent was 176.8 mg/g, which was calculated using the Langmuir model. The Pd(II) maximum uptake exhibited the following order: Amberjet 4200 Cl > Lewatit Monoplus TP 214 > PEI-modified biomass > SPC-100 > SPS-200. Acidified thiourea in 1.0 M HCl was used to desorb Pd(II) from all of the sorbents examined. 相似文献
RNA (guanine-7-)-methyltransferase is the enzyme responsible for methylating the 5' cap structure of eukaryotic mRNA. The Saccharomyces cerevisiae enzyme is a 436-amino-acid protein encoded by the essential ABD1 gene. In this study, deletion and point mutations in ABD1 were tested for the ability to support growth of an abd1 null strain. Elimination of 109 amino acids from the N terminus had no effect on cell viability, whereas a more extensive N-terminal deletion of 155 residues was lethal, as was a C-terminal deletion of 55 amino acids. Alanine substitution mutations were introduced at eight conserved residues within a 206-amino-acid region of similarity between ABD1 and the methyltransferase domain of the vaccinia virus capping enzyme. ABD1 alleles H253A (encoding a substitution of alanine for histidine at position 253), T282A, E287A, E361A, and Y362A were viable, whereas G174A, D178A, and Y254A were either lethal or severely defective for growth. Alanine-substituted and amino-truncated ABD1 proteins were expressed in bacteria, purified, and tested for cap methyltransferase activity in vitro. Mutations that were viable in yeast cells had either no effect or only a moderate effect on the specific methyltransferase activity of the mutated ABD1 protein, whereas mutations that were deleterious in vivo yielded proteins that were catalytically defective in vitro. These findings substantiate for the first time the long-held presumption that cap methylation is an essential function in eukaryotic cells. 相似文献
Genetic linkage maps are indispensable tools in genetic, genomic and breeding studies. As one of genotyping-by-sequencing methods, RAD-Seq (restriction-site associated DNA sequencing) has gained particular popularity for construction of high-density linkage maps. Current RAD analytical tools are being predominantly used for typing codominant markers. However, no genotyping algorithm has been developed for dominant markers (resulting from recognition site disruption). Given their abundance in eukaryotic genomes, utilization of dominant markers would greatly diminish the extensive sequencing effort required for large-scale marker development. In this study, we established, for the first time, a novel statistical framework for de novo dominant genotyping in mapping populations. An integrated package called RADtyping was developed by incorporating both de novo codominant and dominant genotyping algorithms. We demonstrated the superb performance of RADtyping in achieving remarkably high genotyping accuracy based on simulated and real mapping datasets. The RADtyping package is freely available at http://www2.ouc.edu.cn/mollusk/ detailen.asp?id=727. 相似文献
abstractThe objective of this study was to investigate whether human placental multipotent mesenchymal stromal cell (hPMSC)-derived Slit2 and endothelial cell Roundabout (Robo) receptors are involved in placental angiogenesis. The hPMSC-conditioned medium and human umbilical vein endothelial cells were studied for Slit2 and Robo receptor expression by immunoassay and RT-PCR. The effect of the conditioned medium of hPMSCs with or without Slit2 depletion on endothelial cells was investigated by in vitro angiogenesis using growth factor-reduced Matrigel. hPMSCs express Slit2 and both Robo1 and Robo4 are present in human umbilical vein endothelial cells. Human umbilical vein endothelial cells do not express Robo2 and Robo3. The hPMSC-conditioned medium and Slit2 recombinant protein significantly inhibit the endothelial cell migration, but not by the hPMSC-conditioned medium with Slit2 depletion. The hPMSC-conditioned medium and Slit2 significantly enhance endothelial tube formation with increased cumulated tube length, polygonal network number and vessel branching point number compared to endothelial cells alone. The tube formation is inhibited by the depletion of Slit2 from the conditioned medium, or following the expression of Robo1, Robo4, and both receptor knockdown using small interfering RNA. Furthermore, co-immunoprecipitation reveals Slit2 binds to Robo1 and Robo4. Robo1 interacts and forms a heterodimeric complex with Robo4. These results suggest the implication of both Robo receptors with Slit2 signaling, which is involved in endothelial cell angiogenesis. Slit2 in the conditioned medium of hPMSCs has functional effect on endothelial cells and may play a role in placental angiogenesis. 相似文献
The effect of N′-nitrosonornicotine (NNN), one of the tobacco-specific nitrosamines, on the catalytic activity of glutamate dehydrogenase (GLDH) in the α-ketoglutarate amination, using reduced nicotinamide adenine dinucleotide as coenzyme, was studied by a chronoamperometric method. The maximum reaction rate of the enzyme-catalyzed reaction and the Michaelis-Menten constant, or the apparent Michaelis-Menten constant, were determined in the absence and presence of NNN. NNN remarkably inhibited the bio-catalysis activity of GLDH, and was a reversible competitive inhibitior with Ki, estimated as 199?μmol?l?1 at 25°C and pH 8.0. 相似文献