Exosome miR-101-3p derived from bone marrow mesenchymal stem cells promotes radiotherapy sensitivity in non-small cell lung cancer by regulating DNA damage repair and autophagy levels through EZH2.

BACKGROUND AND OBJECTIVE: The morbidity rate of non-small cell lung cancer (NSCLC) increases with age, highlighting that NSCLC is a serious threat to human health. The aim of this study was mainly to describe the role of exosomal miR-101-3p derived from bone marrow mesenchymal stem cells (BMSCs) in NSCLC. METHODS: A549 or NCI-H1703 cells (1×105/mouse) were injected into nude mice to establish an NSCLC animal model. RTqPCR, Western blotting and comet assays were used to assess the changes in gene expression, proteins and DNA damage repair. RESULTS: miR-101-3p and RAI2 were found to be expressed at low levels in NSCLC, while EZH2 was highly expressed. In terms of function, miR-101-3p downregulated EZH2. In addition, exosomal miR-101-3p derived from BMSCs promoted the expression of RAI2, inhibited DNA damage repair, and inhibited the activation of the PI3K/AKT/mTOR signaling pathway by inhibiting EZH2, thereby promoting autophagy and decreasing cell viability and finally enhancing the sensitivity of NSCLC to radiotherapy and inhibiting the malignant biological behavior of NSCLC. CONCLUSION: Exosomal miR-101-3p derived from BMSCs can inhibit DNA damage repair, promote autophagy, enhance the radiosensitivity of NSCLC, and inhibit the progression of NSCLC by inhibiting EZH2.

Design and Mechanism Study of High-Safety and Long-Life Electrolyte for High-Energy-Density Lithium-Ion Batteries.

Although nonflammable electrolytes are beneficial for battery safety, they often adversely affect the electrochemical performance of lithium-ion batteries due to their poor compatibility with electrodes. Herein, we design a nonflammable electrolyte consisting of cyclic carbonate and 2,2-difluoroethyl acetate (DFEA) solvents paired with several surface-film-forming additives, significantly improving the safety and cycling performance of NMC811||SiOx/graphite pouch cells. The DFEA solvent exhibits not only good flame retardancy but also lower lowest unoccupied molecular orbital (LUMO) energy, promoting the formation of a robust inorganic-rich and gradient-architecture hybrid interface between the SiOx/graphite anode and electrolyte. The double insurance of good flame retardancy of the DFEA solvent and decreased exothermic effects of both bulk electrolyte and DFEA-derived solid electrolyte interphase (SEI) can ensure the high safety of the pouch cell. Moreover, the highly robust SEI can prevent the excessive reduction decomposition of the electrolyte and alleviate the structural decay of the anode, which can restrain the formation of lithium deposition on the anode surface and further suppress the structural decay of NMC materials. This contributes to the unprecedented cycling performance of the NMC811||SiOx/graphite pouch cells with a capacity retention of 80% after 1000 cycles at a 0.33C rate.

The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in patients worldwide. Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC. It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC. Here, we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients. We found that DMRTA1 was extremely upregulated in the non-pathologic complete response (non-pCR) group. The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression, which could increase cisplatin sensitivity in ESCC. Additionally, suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells. Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2, which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback. Therefore, DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.

Polypyrrole Modified MoS2 Nanorod Composites as Durable Pseudocapacitive Anode Materials for Sodium-Ion Batteries.

As a typical two-dimensional layered metal sulfide, MoS2 has a high theoretical capacity and large layer spacing, which is beneficial for ion transport. Herein, a facile polymerization method is employed to synthesize polypyrrole (PPy) nanotubes, followed by a hydrothermal method to obtain flower-rod-shaped MoS2/PPy (FR-MoS2/PPy) composites. The FR-MoS2/PPy achieves outstanding electrochemical performance as a sodium-ion battery anode. After 60 cycles under 100 mA g-1, the FR-MoS2/PPy can maintain a capacity of 431.9 mAh g-1. As for rate performance, when the current densities range from 0.1 to 2 A g-1, the capacities only reduce from 489.7 to 363.2 mAh g-1. The excellent performance comes from a high specific surface area provided by the unique structure and the synergistic effect between the components. Additionally, the introduction of conductive PPy improves the conductivity of the material and the internal hollow structure relieves the volume expansion. In addition, kinetic calculations show that the composite material has a high sodium-ion transmission rate, and the external pseudocapacitance behavior can also significantly improve its electrochemical performance. This method provides a new idea for the development of advanced high-capacity anode materials for sodium-ion batteries.

Achieving Cycling Durability of Lithium-Sulfur Batteries via Capturing Polysulfides through a Three-Dimensional Interconnected Carbon Network Anchored with Ultrafine FeS Nanoparticles.

Shuttle effect has always been a critical obstacle to the application of lithium-sulfur (Li-S) batteries for leading to unstable cycle performance and a short lifespan. To solve this problem, a particular strategy is put up to relieve shuttle effect by capturing soluble polysulfides through a three-dimensional interconnected carbon network. Due to the uniformly anchored ultrafine FeS nanoparticles on a 3D interconnected carbon network, the material could lock soluble polysulfides on the cathode side and promote electrochemical conversion reactions among sulfur species. By optimizing the active site exposure of FeS and designing a hierarchical porous and multichannel structure to ensure rapid migration of ions and electrons at the same time, the interlayer can effectively suppress the shuttle effect and enhance sulfur utilization. Thus, the Li-S battery presents excellent cycling stability and rate capability, namely, a reversible specific capacity of 560 mAh g-1 at 2.0 C over 500 cycles with a decay rate of 0.012% per cycle and a specific capacity of 597 mAh g-1 at a 5.0 C current rate. This study offers a promising strategy for designing the structure of an interlayer to achieve long-cycle stable Li-S batteries.

Fraxetin Suppresses Proliferation of Non-Small-Cell Lung Cancer Cells via Preventing Activation of Signal Transducer and Activator of Transcription 3.

Lung cancer represents the leading cause of cancer-associated mortality, and non-small-cell lung cancer (NSCLC) is the most frequent histologic sub-type. It is therefore urgent to develop novel agents for the treatment of NSCLC. Fraxetin (FXT) is a potent plant-derived product and has been recognized as a promising anticancer agent for breast cancer and osteosarcoma. However, the anti-cancer potential of FXT for NSCLC remains to be elucidated. Accordingly, in the present study, we evaluated the inhibitory effect of FXT on the proliferation and growth of NSCLC cells using six human NSCLC cell lines: A549, H460, HCC827, H1650, PC-9 and H1975. FXT exhibited significant inhibitory effects on the proliferation of these cancer cell lines. By contrast, no inhibitory effect was observed on the viability of non-cancer lung cell lines even at the highest concentration of FXT (100 µM). Among the NSCLC cell lines, HCC827 and H1650 cells showed the most sensitive to FXT. Accordingly, HCC827 and H1650 cells were used for the subsequent experiments. Flow cytometric analysis revealed that FXT caused a significant cell cycle arrest and pro-apoptotic effects. Mechanistically, FXT suppressed the IL-6-induced phosphorylation of tyrosine residue (Tyr705) of signal transducer and activator of transcription 3 (STAT3) probably by binding to STAT3. Molecular docking and molecular dynamic simulations studies indicated that FXT interacts with STAT3 through hydrogen bond and hydrophobic interaction. In conclusion, these findings suggest that FXT could be a promising lead compound to be used as a novel STAT3 inhibitor and potential antitumor agent for the treatment of NSCLC.