Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy. Our previous studies confirm that Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance. Targeted delivery of small interfering RNA (siRNA) without blood-brain barrier (BBB) restriction for eradication of GBM represents a promising approach for therapeutic interventions. In this study, we utilize the engineering technology to generate T7 peptide-decorated exosome (T7-exo). T7 is a peptide specifically binding to the transferrin receptor. T7-exo shows excellent packaging and protection of cholesterol-modified Cy3-siYY1 while quickly releasing payloads in a cytoplasmic reductive environment. The engineered exosomes T7-siYY1-exo could deliver more effciently to GBM cells both in vitro and in vivo. Notably, in vitro experiments demonstrate that T7-siYY1-exo can enhance chemoradiotherapy sensitivity and reverse therapeutic resistance. Moreover, T7-siYY1-exo and TMZ/IR exert synergistic anti-GBM effect and significantly improves the survival time of GBM bearing mice. Our findings indicate that T7-siYY1-exo may be a potential approach to reverse the chemoradiotherapy resistance in GBM.
Background and Objectives
Periodontitis is the top reason for tooth loss, and smoking significantly increases severe periodontitis risk. Defective autophagy has been reported to play a vital role in periodontitis. This study aimed to elucidate the relationship between autophagy and inflammation factors production in nicotine‐treated periodontal ligament stem cells (PDLSCs) and the underlying mechanism.
Methods
In this study, transmission electron microscopy, immunofluorescence, and the mCherry‐GFP‐LC3 plasmid were used to study autophagy flux. The gene levels of inflammation factors and long noncoding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) were detected by quantitative real‐time PCR (qRT‐PCR). Western blot was performed to assess the protein levels of autophagic markers and α7 nicotinic acetylcholine receptor (α7nAChR).
Results
We found that nicotine impaired autophagosome‐lysosome fusion and lysosome functions to block autophagy flux, contributing to inflammatory factors production in nicotine‐treated PDLSCs. Moreover, nicotine upregulated NEAT1 by activating α7nAChR. NEAT1 decreased autophagy flux by downregulating syntaxin 17 (STX17).
Conclusion
Our data indicate that NEAT1‐decreased autophagy flux is pivotal for inflammation factors production in nicotine‐treated PDLSCs.
To investigate the biaxial mechanical characteristics of reactive powder concrete (RPC), RPC plate specimens and bone-shaped specimens were tested under compression-compression and compression-tension loadings, respectively. The strengths and strains of the specimens were recorded, and the crack patterns and failure modes in various stress states were examined. Based on the test data, the characteristics of biaxial strength were analyzed, and a biaxial failure criterion was established. The characteristics of major stress-strain curves and failure modes in different biaxial stress states were determined. The results show that the ratio between the biaxial compression strength and the uniaxial compression strength was 1.44–1.58 for RPC. When the stress ratio under compression-tension was −0.05, the tensile strength decreased by 48%. Under compression-compression, the proportional limit of RPC was about 95%, and its peak strain was high. Under compression-tension, as the compressive stress increased, the elastic modulus decreased, and the peak strain in the tensile direction increased. When the RPC specimens were under compression-compression, the failure mode of RPC was splitting failure. Under compression-tension, the failure mode changed from single-crack tensile failure to multicrack compressive failure with increasing confining stress.
Innovation is the soul of a nation's progress, and is also a person's lifeblood in study and work. Competition in today's society is the competition of creativity, but the mainstream of today's China's education mode is still taking exams, the university is no exception. But American colleges and universities always pay much attention to the cultivation of students' thinking ability and practical ability. Since the higher education reform movement, the United States has been to cultivate all-round development of innovative talents as one of the goals of education reform. This article starts from the perspective of the two countries' attitudes to the cultivation of the innovative undergraduate status and education concept, with emphasis on the important role of entrepreneurial ability and scientific research ability, and some suggestions on the improvement of China's education are provided finally.
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