Glioblastoma
(GBM) is one of the deadliest and most invasive brain
cancers/gliomas, and there is currently no established way to treat
this disease. The treatment of GBM typically involves intracranial
surgery followed by chemotherapy. However, the blood–brain
barrier (BBB) impedes the delivery of the chemotherapeutic drug, making
the treatment challenging. In this study, we embedded a chemotherapeutic
drug and other nanomaterials into a nanobubble (NB), utilized active
tracking and other guidance mechanisms to guide the nanocomposite
to the tumor site, and then used high-intensity focused ultrasound
oscillation to burst the nanobubbles, generating a transient cavitation
impact on the BBB and allowing the drug to bypass it and reach the
brain. FePt enhances the resolution of T2-weighted magnetic resonance
imaging images and has magnetic properties that help guide the nanocomposite
to the tumor location. FePt nanoparticles were loaded into the hydrophobic
core of the NBs along with doxorubicin to form a bubble-based drug
delivery system (Dox-FePt@NB). The surface of the NBs is modified
with a targeting ligand, transferrin (Dox-FePt@NB-Tf), giving the
nanocomposite active tracking abilities. The Dox-FePt@NB-Tf developed
in the present study represents a potential breakthrough in GBM treatment
through improved drug delivery and biological imaging.
Phosphoglycerate kinase (PGK) is involved in glycolytic and various metabolic events. Dysfunction of PGK may induce metabolic reprogramming and the Warburg effect. In this study, we demonstrated that PGK1, but not PGK2, may play a key role in tumorigenesis and is associated with metastasis. We observed an inverse correlation between PGK1 and the survival rate in several clinical cohorts through bioinformatics statistical and immunohistochemical staining analyses. Surprisingly, we found that PGK1 was significantly increased in adenocarcinoma compared with other subtypes. Thus, we established a PGK1-based proteomics dataset by a pull-down assay. We further investigated HIV-1 Tat Specific Factor 1 (HTATSF1), a potential binding partner, through protein–protein interactions. Then, we confirmed that PGK1 indeed bound to HTATSF1 by two-way immunoprecipitation experiments. In addition, we generated several mutant clones of PGK1 through site-directed mutagenesis, including mutagenesis of the N-terminal region, the enzyme catalytic domain, and the C-terminal region. We observed that even though the phosphoglycerate kinase activity had been inhibited, the migration ability induced by PGK1 was maintained. Moreover, our immunofluorescence staining also indicated the translocation of PGK1 from the cytoplasm to the nucleus and its colocalization with HTATSF1. From the results presented in this study, we propose a novel model in which the PGK1 binds to HTATSF1 and exerts functional control of cancer metastasis. In addition, we also showed a nonenzymatic function of PGK1.
Multi-wire sawing process with free abrasive slurry or called multi-wire slurry wire sawing (MW-SWS) process has been popularly adopted in slicing of silicon substrates for solar cell application. However, the chipping or edge cracking of thin thickness as 200 μm of such silicon substrates need to be improved in current mass production. The potential subsurface cracks induced by previous edge grinding or brush polishing of silicon brick may be the main cause. This paper is to develop a rapid thermal annealing (RTA) process for thermal annealing of the surface quality of silicon brick before MR-SWS. In this study, a RTA furnace is designed and used to improve the material property of surface of silicon brick. A quartz crucible is used as heating source with the maximum heated specimen size of 156×156×100 mm (W×H×L). The bulk silicon brick used in this study is selected with a size of 20×10×20 mm (W×H×L) and supplied by the Sino-American Silicon Ltd. (SAS) in Hsinchu, Taiwan. The nitrogen gas is also injected as a protective gas for target heating temperature around 550°C with rapid heating rate of 50°C per second. The micro-Vickers (Akashi MVK-H1) and SEM (JSM-6500F, JOEL) instruments have been used to observe the improvement of rectified material properties of bulk silicon substrate. Experiments of silicon wafers have been first performed for obtaining the recipe of RTA testing and then adjusting for silicon brick testing. Results have been verified by the lower surface hardness and larger crystal grain size after RTA treatment. Furthermore, such treated silicon brick can be further adopted for MW-SWS process to identify the effects of reducing chipping or edge cracking of silicon substrates for solar cell application.
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