Non-coding RNA in tumor-infiltrating regulatory T cells formation and associated immunotherapy

Cancer immunotherapy has exhibited promising antitumor effects in various tumors. Infiltrated regulatory T cells (Tregs) in the tumor microenvironment (TME) restrict protective immune surveillance, impede effective antitumor immune responses, and contribute to the formation of an immunosuppressive microenvironment. Selective depletion or functional attenuation of tumor-infiltrating Tregs, while eliciting effective T-cell responses, represents a potential approach for anti-tumor immunity. Furthermore, it does not disrupt the Treg-dependent immune homeostasis in healthy organs and does not induce autoimmunity. Yet, the shared cell surface molecules and signaling pathways between Tregs and multiple immune cell types pose challenges in this process. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate both cancer and immune cells and thus can potentially improve antitumor responses. Here, we review recent advances in research of tumor-infiltrating Tregs, with a focus on the functional roles of immune checkpoint and inhibitory Tregs receptors and the regulatory mechanisms of ncRNAs in Treg plasticity and functionality

Molecular characterization of sub-frontal recurrent medulloblastomas reveals potential clinical relevance

BackgroundSingle recurrence in the sub-frontal region after cerebellar medulloblastoma (MB) resection is rare and the underlying molecular characteristics have not been specifically addressed.MethodsWe summarized two such cases in our center. All five samples were molecularly profiled for their genome and transcriptome signatures.ResultsThe recurrent tumors displayed genomic and transcriptomic divergence. Pathway analysis of recurrent tumors showed functional convergence in metabolism, cancer, neuroactive ligand–receptor interaction, and PI3K-AKT signaling pathways. Notably, the sub-frontal recurrent tumors had a much higher proportion (50–86%) of acquired driver mutations than that reported in other recurrent locations. The acquired putative driver genes in the sub-frontal recurrent tumors functionally enriched for chromatin remodeler-associated genes, such as KDM6B, SPEN, CHD4, and CHD7. Furthermore, the germline mutations of our cases showed a significant functional convergence in focal adhesion, cell adhesion molecules, and ECM–receptor interaction. Evolutionary analysis showed that the recurrence could be derived from a single primary tumor lineage or had an intermediate phylogenetic similarity to the matched primary one.ConclusionRare single sub-frontal recurrent MBs presented specific mutation signatures that might be related to the under-dose radiation. Particular attention should be paid to optimally covering the sub-frontal cribriform plate during postoperative radiotherapy targeting

Expression of neurotrophin receptors and its role in the compartmentalization of the cerebellum in the rodent

published_or_final_versionMedicineDoctoralDoctor of Philosoph

Preparation and Photocatalytic Activities of TiO₂-Based Composite Catalysts

While modern industry has contributed to the prosperity of an increasingly urbanized society, it has also led to serious pollution problems, with discharged wastewater and exhaust gases causing significant environmental harm. Titanium dioxide (TiO2), which is an excellent photocatalyst, has received extensive attention because it is inexpensive and able to photocatalytically degrade pollutants in an environmentally friendly manner. TiO2 has many advantages, including high chemical stability, low toxicity, low operating costs, and environmental friendliness. TiO2 is an N-order semiconductor material with a bandgap of 3.2 eV. Only when the wavelength of ultraviolet light is less than or equal to 387.5 nm, the valence band electrons can obtain the energy of the photon and pass through the conduction band to form photoelectrons, meanwhile the valence band forms a photogenerated hole. And light in other wavelength regions does not excite this photogenerated electrons. The most common methods used to improve the photocatalytic efficiency of TiO2 involve increasing its photoresponse range and reducing photogenerated-carrier coupling. The morphology, size, and structure of a heterojunction can be altered through element doping, leading to improved photocatalytic efficiency. Mainstream methods for preparing TiO2 are reviewed in this paper, with several excellent preparation schemes for improving the photocatalytic efficiency of TiO2 introduced. TiO2 is mainly prepared using sol-gel, solvothermal, hydrothermal, anodic oxidation, microwave-assisted, CVD and PVD methods, and TiO2 nanoparticles with excellent photocatalytic properties can also be prepared. Ti-containing materials are widely used to purify harmful gases, as well as contaminants from building materials, coatings, and daily necessities. Therefore, the preparation and applications of titanium materials have become globally popular research topics

The miR-1224-5p/ELF3 Axis Regulates Malignant Behaviors of Pancreatic Cancer via PI3K/AKT/Notch Signaling Pathways

Purpose: Aberrant expression of microRNAs contributes to the progression of pancreatic cancer by targeting downstream genes. A novel regulatory axis, miR-1224-5p/ELF3, was identified by bioinformatic analysis and experimental verification. Studies of the underlying molecular mechanisms behind this axis lead to a better understanding of the development of pancreatic cancer. Materials and Methods: The differential expression of miR-1224-5p and ELF3 was verified based on Gene Expression Omnibus (GEO) datasets and clinical samples. The relationship between miR-1224-5p and ELF3 was demonstrated by luciferase assay and Western blot. The related signaling pathways of the miR-1224-5p/ELF3 axis in pancreatic cancer were investigated by gene set enrichment analysis (GSEA) and verified by Western blot. An analysis between ELF3 expression and immune infiltration was performed. Cellular and animal experiments were utilized to explore the effects of miR-1224-5p and ELF3 in pancreatic cancer. Results: Suppressed expression of miR-1224-5p in pancreatic tumor tissues and cancer cells was identified first. Furthermore, miR-1224-5p is correlated with clinicopathological features, and decreased expression of miR-1224-5p indicates poor prognosis. miR-1224-5p serves as a tumor suppressor and inhibits malignant behaviors of pancreatic cancer based on in vivo and in vitro assays. The putative target gene ELF3 was predicted by bioinformatic analysis and confirmed by dual-luciferase reporter assay. Overexpression of ELF3 can improve the malignant behaviors of pancreatic cancer and demonstrates poor prognosis and advanced clinical stage. The inhibitory role of miR-1224-5p in pancreatic cancer is manifested by its direct targeting of ELF3. A negative correlation between ELF3 expression and immune cell infiltration was identified, suggesting an immunosuppressive state resulting from ELF3 overexpression. The PI3K/AKT/Notch signaling pathways and epithelial-to-mesenchymal transition (EMT) are important underlying mechanisms. Conclusion: The miR-1224-5p/ELF3 axis may serve as a new diagnostic, therapeutic, and prognostic biomarker in pancreatic cancer. The related PI3K/AKT/Notch/EMT signaling pathways greatly promote the elucidation of the progression of pancreatic cancer

The Impact of Different Ventilation Conditions on Electric Bus Fires

Once a fire breaks out in an electric bus, it can easily lead to mass casualties and severe injuries, resulting in significant property damage and social impact. The high-temperature smoke and toxic gases in an electric bus fire are key factors that cause a large number of casualties, both of which are closely related to ventilation conditions. In view of this, this study utilized the Fire Dynamics Simulator (FDS 6) software to establish a three-dimensional experimental model of an electric bus. Numerical simulations of the fire combustion process in the electric bus under different ventilation conditions were conducted. Multiple fire scenes were established based on varying ventilation areas, different wind speeds, and diverse window opening positions. This study specifically analyzed the temperature and CO concentration variations under different fire scenes. By comparing the simulation results under different ventilation conditions, it can be concluded that when an electric bus catches fire, opening 100% of the windows, the wind speed is 8 m/s, and opening the rear window of the electric bus first can minimize the fire risk. Through the numerical simulation of electric bus fires under various conditions, this study analyzed the impact of different ventilation conditions on electric bus fires, providing a theoretical basis for firefighting and rescue efforts as well as personnel evacuation in electric bus fire incidents, with the ultimate goal of maximizing public safety

Response to novel s in verse in Czech literature

This thesis is focused on response to novel in verse in Czech Literature of 19th century. The form of novel in verse becomes attractive for authors in Czech Literature since the second half of 19th century, especially after familiarizing with Puškin's Evžen Oněgin. In this work we try to cover questions of novel in verse, then to put near responses to Evžen Oněgin in Czech context (picked pieces by J. Neruda, B. Kaminský, F. Táborský, K. Leger, M. A. Šimáček). Subsequently there is more space given to first try of handling the genre - Pan Vyšínský - by Gustav Ptleger Moravský, and supreme realization of novel in verse - Josef Svatopluk Machar's Magdalena

Differentially proteins play a major role in cell migration, and invasion of PC-1.0 Metastatic.

<p>(A) Effect of three proteins on the migration after using siRNA or antibody blocking in highly metastatic PC-1.0 cells. The cells were incubated for 24h. The percentage migration was calculated and graphed. * Compared with the PC-1.0, <i>P</i>-value <0.01. (n = 3) (B) Quantification of transwell assay for treated group and control group. Cells were counted in triplicate wells and in three identical experiments, * Compared with the PC-1.0, <i>P</i>-value <0.01. (n = 3)</p