This paper compares the efficiency of flowing polymer- and lipid-shelled microbubbles (MBs) in the heating and cavitation during focused ultrasound exposures. Temperature and cavitation activity were simultaneously measured as the two types of shelled MBs and saline flowing through a 3 mm diameter vessel in the phantom with varying flow velocities (0-20 cm/s) at different acoustic power levels (0.6-20 W) with each exposure for 5 s. Temperature and cavitation for the lipid-shelled MBs were higher than those for the polymer-shelled MBs. Temperature rise decreased with increasing flow velocities for the two types of shelled MBs and saline at acoustic power 1.5 W. At acoustic power 11.1 W, temperature rise increased with increasing flow velocities for the lipid-shelled MBs. For the polymer-shelled MBs, the temperature rise increased with increasing flow velocities from 3-15 cm/s and decreased at 20 cm/s. Cavitation increased with increasing flow velocity for the two shelled MBs and there were no significant changes of cavitation with increasing flow velocities for saline. These results suggested that lipid-shelled MBs may have a greater efficiency than polymer-shelled MBs in heating and cavitation during focused ultrasound exposures.

Highlights d CaMKIIa phosphorylates GluN2A at Ser-1459 in response to glycine stimulation d CaMKIIa and SNX27 are required for the glycine-induced increase in surface GluN2A d GluN2A Ser-1459 is a critical residue that controls the gating of NMDA receptors d The epilepsy-associated GluN2A S1459G variant prolongs open channel duration

Fabrication of multifunctional nanoprobes, which integrate tumor targeting, imaging, and effective treatment, has been widely explored in nanomedicine. In the present study, we fabricated tumor-targeting polymer folic acid-terminated polyethylene glycol thiol-modified gold nanostars (GNS-FA), which could realize X-ray computed tomography (CT) imaging and PTT/RT synergistic therapy. The synthesized GNS-FA exhibited good biocompatibility. GNS-FA could be used as a CT imaging contrast agent due to the strong X-ray attenuation of Au. GNS-FA exhibited good near-infrared (NIR) light absorption and excellent photothermal conversion performance, making them promising photothermal transduction agents (PTAs). Furthermore, GNS-FA could be used as an RT sensitizer to enhance the radio-mediated cell death due to the high atomic number (high Z) of gold. Hence, GNS-FA were used as the CT imaging agent, PTA, and radiosensitizer in this work. The in vitro antitumor experiments showed that the PTT/RT combined treatment had enhanced anticancer efficacy compared with the monotherapy (PTT or RT). Our results indicated that the bioconjugated GNS could offer an excellent nanoplatform for CT imaging-guided PTT/RT combined cancer therapy in the future.

In order to create a hemodynamic environment that can simulate the physiological condition of arteries, an in vitro experiment apparatus was designed whose key modules were compliance chamber and after-load. These two modules were developed based on the theories of hemodynamics. Both the normal and shear stress to which endothelial cells are exposed can be controlled with these modules, thus facilitating the research of endothelial cells subjected to stresses.

Context: Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. Objective: We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. Materials and methods: We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0-50 lM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. Results: Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC 50 ¼ 5.4-6.1 lM for A549 and 3.9-5.7 lM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. Conclusion: UA232 induced apoptosis through the ER stress pathway, and showed stronger growthinhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.