Ultrafast laser bursts welding glass and metal with solder paste to create an ultra-large molten pool.

A novel, to our knowledge, method is proposed for the welding of glass and metal with a large gap filled with solder paste using ultrafast laser bursts. The addition of solder paste enables a reliable glass-metal connection even at gaps of hundreds of microns, while the position of the glass can be flexibly adjusted. By ultrafast laser bursts, the volume of the molten pool increases significantly, and the height of the molten pool reaches approximately 350 µm, which is more than an order of magnitude higher than that of conventional ultrafast lasers (10-20 µm). Cross-sectional analysis of the welded region shows that extensive material mixing and element diffusion occur, and stable connections are achieved at multiple interfaces. An analysis of the interaction between the ultrafast laser bursts and the material, as well as the mixing of multiple materials during the welding process, leads to a clear welding mechanism.

Lactate-induced MRP1 expression contributes to metabolism-based etoposide resistance in non-small cell lung cancer cells.

BACKGROUND: Metabolic reprogramming contributes significantly to tumor development and is tightly linked to drug resistance. The chemotherapeutic agent etoposide (VP-16) has been used clinically in the treatment of lung cancer but possess different sensitivity and efficacy towards SCLC and NSCLC. Here, we assessed the impact of etoposide on glycolytic metabolism in SCLC and NSCLC cell lines and investigated the role of metabolic rewiring in mediating etoposide resistance. METHODS: glycolytic differences of drug-treated cancer cells were determined by extracellular acidification rate (ECAR), glucose consumption, lactate production and western blot. DNA damage was evaluated by the comet assay and western blot. Chemoresistant cancer cells were analyzed by viability, apoptosis and western blot. Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction. RESULTS: Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1α-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer (NSCLC). We identified lactic acidosis as the key that confers multidrug resistance through upregulation of multidrug resistance-associated protein 1 (MRP1, encoded by ABCC1), a member of ATP-binding cassette (ABC) transporter family. Mechanistically, lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to induce formation of Snail/TAZ/AP-1 complex at the MRP1/ABCC1 promoter. Induction of MRP1 expression inhibits genotoxic and apoptotic effects of chemotherapeutic drugs by increasing drug efflux. Furthermore, titration of lactic acid with NaHCO3 was sufficient to overcome resistance. CONCLUSIONS: The chemotherapeutic drug etoposide induces the shift toward aerobic glycolysis in the NSCLC rather than SCLC cell lines. The increased lactic acid in extracellular environment plays important role in etoposide resistance through upregulation of MRP expression. These data provide first evidence for the increased lactate production, upon drug treatment, contributes to adaptive resistance in NSCLC and reveal potential vulnerabilities of lactate metabolism and/or pathway suitable for therapeutic targeting. Video Abstract The chemotherapeutic drug etoposide induces metabolic reprogramming towards glycolysis in the NSCLC cells. The secreted lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to activate the expression of MRP1/ABCC1 protein, thus contributing to chemoresistance in NSCLC.