ABSTRACT
The CsPbBr3 microwires with unique isosceles right triangle cross-sections are commonly observed via chemical vapor deposition method. In this work, we study the correlations between measured multi-mode lasing behaviors and the simulation of the mode patterns inside the triangular-rod microcavity. We confirm that lasing action with higher-order transverse modes can well sustain, even when these modes experience large optical loss due to the isosceles triangle cross-section. By comparing the experimental and simulation results, the higher-order transverse modes tend to show up prior to the fundamental transverse modes for wider microwires. We attribute this behavior to the nonuniform field distribution caused by the high absorption efficiency of CsPbBr3. We also elaborate on the difficulties to sustain the whispering gallery mode in the CsPbBr3 triangular-rod microcavity, which implies that the lateral dimension and geometry of the cavity should be considered carefully for the future design of low threshold wire-based laser devices.
ABSTRACT
Colorectal cancer (CRC) is a major health problem due to its high mortality rate. The incidence of CRC is increasing in young individuals. Oxaliplatin (OXA) is an approved third-generation drug and is used for first-line chemotherapy in CRC. Although current standard chemotherapy improves the overall survival of CRC patients, an increasing number of reports of OXA resistance in CRC therapy indicates that resistance has become an urgent problem in clinical applications. Dicer is a critical enzyme involved in miRNA maturation. The expression of Dicer has been reported to be involved in the resistance to various drugs in cancer. In the present study, we aimed to investigate the role of Dicer in OXA resistance in CRC. We found that OXA treatment inhibited Dicer expression through decreasing the protein stability. OXA-induced Dicer protein degradation occurred through both proteasomal and lysosomal proteolysis, while the CHIP E3 ligase was involved in OXA-mediated Dicer ubiquitination and degradation. We established stable OXA-resistant clones from CRC cells, and observed that the CHIP E3 ligase was decreased, along with the increased Dicer expression in OXA-resistant cells. Knockdown of Dicer resensitized CRC cells to OXA treatment. In this study, we have revealed the role of miRNA biogenesis factors in OXA resistance in CRC cells.
Subject(s)
Antineoplastic Agents/pharmacology , DEAD-box RNA Helicases/genetics , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Oxaliplatin/pharmacology , Ribonuclease III/genetics , Ubiquitin-Protein Ligases/genetics , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , DEAD-box RNA Helicases/antagonists & inhibitors , DEAD-box RNA Helicases/metabolism , HCT116 Cells , Humans , Lysosomes/drug effects , Lysosomes/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Protein Stability , Proteolysis , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Ribonuclease III/antagonists & inhibitors , Ribonuclease III/metabolism , Signal Transduction , Ubiquitin-Protein Ligases/metabolismABSTRACT
WD repeat and HMG-box DNA binding protein 1 (Wdhd1) is the mouse ortholog of budding yeast Chromosome Transmission Fidelity 4 (CTF4), the protein product of which integrates the MCM2-7 helicase and DNA polymerase α/primase complex to initiate DNA replication. Previous work in fruit flies, Xenopus egg extracts, and human cell lines suggest that Wdhd1 is required for efficient DNA synthesis. However, rigorous in vivo functional studies on Wdhd1 in mammals are unavailable. In the present study, we have successfully generated a Wdhd1 null allele in mice through CRISPR/Cas9-mediated genome editing to investigate the role of Wdhd1 in embryogenesis in vivo. We characterized Wdhd1 expression using quantitative reverse-transcription polymerase chain reaction, and assessed embryonic cell proliferation by histology in both pre- and peri-implantation embryos. While Wdhd1 heterozygous mutant mice were grossly normal and fertile, we observed a reduction in cell proliferation by the gastrulation stage in Wdhd1 homozygous null mutant embryos which severely hampered their growth and viability. These results indicate that Wdhd1 plays a major role in cell proliferation during embryogenesis in mice.
Subject(s)
DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Embryonic Development , Animals , CRISPR-Cas Systems , Cell Culture Techniques , Cell Line , Cell Proliferation , Fertility , Gastrulation , Gene Editing , Loss of Function Mutation , MiceABSTRACT
Large-grained and well-oriented methylammonium lead tribromide (MAPbBr3) perovskite was formed from the conversion of amorphous lead bromide (PbBr2) doped with phenethylamine (PEA). The addition of PEA ions (with an optimized molar ratio of 0.008%) to the PbBr2 solution assisted the formation of a smooth PEA-doped PbBr2 layer by spin-coating. Then, the PEA-doped PbBr2 thin film would convert into large-grained and well-oriented MAPbBr3 with the help of a solid-vapor reaction under a vaporized methylammonium bromide (MABr) and choline chloride (CC) atmosphere. Furthermore, both PEA and CC would passivate the defects of perovskite to improve the crystal quality of perovskite. By applying this perovskite layer in perovskite light-emitting diodes (PeLEDs), the maximum luminance and current efficiency of PeLEDs could reach 20,869 cd/m2 and 3.99 cd/A, respectively; these values are approximately five and three times larger than those of PeLEDs without PEA. The perovskite converted from spin-coated PbBr2 with a PEA dopant remarkably improved the luminance and current efficiency of its PeLEDs.
ABSTRACT
Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been implicated in many post-transcriptional processes, including RNA metabolism and mRNA splicing and translation. However, the role of hnRNP Q1 in tumorigenesis remains unclear. We previously performed RNA immunoprecipitation (RIP)-seq analysis to identify hnRNP Q1-interacting mRNAs and found that hnRNP Q1 targets a group of genes that are involved in mitotic regulation, including Aurora-A. Here, we demonstrate that altering the hnRNP Q1 level influences the expression of the Aurora-A protein, but not its mRNA. Stimulation with epidermal growth factor (EGF) enhances both binding between hnRNP Q1 and Aurora-A mRNA as well as the efficacy of the hnRNP Q1-induced translation of Aurora-A mRNA. The EGF/hnRNP Q1-induced translation of Aurora-A mRNA is mediated by the mTOR and ERK pathways. In addition, we show that hnRNP Q1 up-regulates the translation of a group of spindle assembly checkpoint (SAC) genes. hnRNP Q1 overexpression is positively correlated with the levels of Aurora-A and the SAC genes in human colorectal cancer tissues. In summary, our data suggest that hnRNP Q1 plays an important role in regulating the expression of a group of cell cycle-related genes. Therefore, it may contribute to tumorigenesis by up-regulating the translation of these genes in colorectal cancer.