RESUMO
Colloidal semiconductor nanocrystals enable the realization and exploitation of quantum phenomena in a controlled manner, and can be scaled up for commercial uses. These materials have become important for a wide range of applications, from ultrahigh definition displays, to solar cells, quantum computing, bioimaging, optical communications, and many more. Over the last decade, lead-halide perovskite nanocrystals have rapidly gained prominence as efficient semiconductors. Although the majority of studies have focused on large nanocrystals in the weak- to intermediate-confinement regime, quantum dots (QDs) in the strongly-confined regime (with sizes smaller than the Bohr diameter, which ranges from 4-12 nm for lead-halide perovskites) offer unique opportunities, including polarized light emission and color-pure, stable luminescence in the region that is unattainable by perovskites with single-halide compositions. In this tutorial review, we bring together the latest insights into this emerging and rapidly growing area, focusing on the synthesis, steady-state optical properties (including exciton fine-structure splitting), and transient kinetics (including hot carrier cooling) of strongly-confined perovskite QDs. We also discuss recent advances in their applications, including single photon emission for quantum technologies, as well as light-emitting diodes. We finish with our perspectives on future challenges and opportunities for strongly-confined QDs, particularly around improving the control over monodispersity and stability, important fundamental questions on the photophysics, and paths forward to improve the performance of perovskite QDs in light-emitting diodes.
RESUMO
BACKGROUND: IGF2BP3 functions as an RNA-binding protein (RBP) and plays a role in the posttranscriptional control of mRNA localization, stability, and translation. Its dysregulation is frequently associated with tumorigenesis across various cancer types. Nonetheless, our understanding of how the expression of the IGF2BP3 gene is regulated remains limited. The specific functions and underlying mechanisms of IGF2BP3, as well as the potential benefits of targeting it for therapeutic purposes in bladder cancer, are not yet well comprehended. METHODS: The mRNA and protein expression were examined by RT-qPCR and western blotting, respectively. The methylation level of CpG sites was detected by Bisulfite sequencing PCR (BSP). The regulation of IGF2BP3 expression by miR-320a-3p was analyzed by luciferase reporter assay. The functional role of IGF2BP3 was determined through proliferation, colony formation, wound healing, invasion assays, and xenograft mouse model. The regulation of HMGB1 by IGF2BP3 was investigated by RNA immunoprecipitation (RIP) and mRNA stability assays. RESULTS: We observed a significant elevation in IGF2BP3 levels within bladder cancer samples, correlating with more advanced stages and grades, as well as an unfavorable prognosis. Subsequent investigations revealed that the upregulation of IGF2BP3 expression is triggered by copy number gain/amplification and promoter hypomethylation in various tumor types, including bladder cancer. Furthermore, miR-320a-3p was identified as another negative regulator in bladder cancer. Functionally, the upregulation of IGF2BP3 expression exacerbated bladder cancer progression, including the proliferation, migration, and invasion of bladder cancer. Conversely, IGF2BP3 silencing produced the opposite effects. Moreover, IGF2BP3 expression positively correlated with inflammation and immune infiltration in bladder cancer. Mechanistically, IGF2BP3 enhanced mRNA stability and promoted the expression of HMGB1 by binding to its mRNA, which is a factor that promotes inflammation and orchestrates tumorigenesis in many cancers. Importantly, pharmacological inhibition of HMGB1 with glycyrrhizin, a specific HMGB1 inhibitor, effectively reversed the cancer-promoting effects of IGF2BP3 overexpression in bladder cancer. Furthermore, the relationship between HMGB1 mRNA and IGF2PB3 is also observed in mammalian embryonic development, with the expression of both genes gradually decreasing as embryonic development progresses. CONCLUSIONS: Our present study sheds light on the genetic and epigenetic mechanisms governing IGF2BP3 expression, underscoring the critical involvement of the IGF2BP3-HMGB1 axis in driving bladder cancer progression. Additionally, it advocates for the investigation of inhibiting IGF2BP3-HMGB1 as a viable therapeutic approach for treating bladder cancer.
Assuntos
Proteína HMGB1 , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Animais , Camundongos , MicroRNAs/genética , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , Metilação de DNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estabilidade de RNA , Inflamação/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Mamíferos/genéticaRESUMO
Mesenchymal stem cells (MSCs) possess significant differentiation potential, making them highly promising in medicine and immunotherapy due to their regenerative capabilities and exosome secretion. However, challenges such as limited cell divisions and complex testing hinder large-scale MSC production. In this study, we successfully established an immortalized MSC line by transfecting the human telomerase reverse transcriptase (TERT) gene into MSCs isolated from pregnant sheep umbilical cords. This approach effectively inhibits cell senescence and promotes cell proliferation, enabling the generation of umbilical cord mesenchymal stem cells (UCMSCs) on a larger scale. Our findings demonstrate that these transfected TERT-UCMSCs exhibit enhanced proliferative capacity and a reduced aging rate compared to regular UCMSCs while maintaining their stemness without tumorigenicity concerns. Consequently, they hold great potential for medical applications requiring large quantities of functional MSCs.