Nanodelivery of a functional membrane receptor to manipulate cellular phenotype.

Modification of membrane receptor makeup is one of the most efficient ways to control input-output signals but is usually achieved by expressing DNA or RNA-encoded proteins or by using other genome-editing methods, which can be technically challenging and produce unwanted side effects. Here we develop and validate a nanodelivery approach to transfer in vitro synthesized, functional membrane receptors into the plasma membrane of living cells. Using β2-adrenergic receptor (β2AR), a prototypical G-protein coupled receptor, as an example, we demonstrated efficient incorporation of a full-length β2AR into a variety of mammalian cells, which imparts pharmacologic control over cellular signaling and affects cellular phenotype in an ex-vivo wound-healing model. Our approach for nanodelivery of functional membrane receptors expands the current toolkit for DNA and RNA-free manipulation of cellular function. We expect this approach to be readily applicable to the synthesis and nanodelivery of other types of GPCRs and membrane receptors, opening new doors for therapeutic development at the intersection between synthetic biology and nanomedicine

Cucurbitacin E inhibits the Yes‑associated protein signaling pathway and suppresses brain metastasis of human non‑small cell lung cancer in a murine model.

Human non‑small cell lung cancer (NSCLC) is associated with an extremely poor prognosis especially for the 40% of patients who develop brain metastasis, and few treatment strategies exist. Cucurbitacin E (CuE), an oxygenated tetracyclic triterpenoid isolated from plants particularly of the family Cucurbitaceae, has shown anti‑tumorigenic properties in several types of cancer, yet the mechanism remains unclear. Yes‑associated protein (YAP), a main mediator of the Hippo signaling pathway, promotes tumorigenesis, drug resistance and metastasis in human NSCLC. The present study was designed to ascertain whether CuE inhibits YAP and its downstream gene expression in the human NSCLC cell lines H2030‑BrM3 (K‑rasG12C mutation) and PC9‑BrM3 (EGFRΔexon19 mutation), which have high potential for brain metastasis. The efficacy of CuE in suppressing brain metastasis of H2030‑BrM3 cells in a murine model was also investigated. It was found that after CuE treatment in H2030‑BrM3 and PC9‑BrM3 cells, YAP protein expression was decreased, and YAP signaling GTIIC reporter activity and expression of the downstream genes CTGF and CYR61 were significantly (P<0.01) decreased. CuE treatment also reduced the migration and invasion abilities of the H2030‑BrM3 and PC9‑BrM3 cells. Finally, our in vivo study showed that CuE treatment (0.2 mg/kg) suppressed H2030‑BrM3 cell brain metastasis and that mice treated with CuE survived longer than the control mice treated with 10% DMSO (P=0.02). The present study is the first to demonstrate that CuE treatment inhibits YAP and the signaling downstream gene expression in human NSCLC in vitro, and suppresses brain metastasis of NSCLC in a murine model. More studies to verify the promising efficacy of CuE in inhibiting brain metastasis of NSCLC and various other cancers may be warranted

A Study of Developing a System Dynamics Model for the Learning Effectiveness Evaluation

[[abstract]]This study used the research method of system dynamics and applied the Vensim software to develop a learning effectiveness evaluation model. This study developed four cause-and-effect chains affecting learning effectiveness, including teachers’ teaching enthusiasm, family involvement, school’s implementation of scientific activities, and creative teaching method, as well as the system dynamics model based on the four cause-and-effect chains. Based on the developed system dynamic model, this study performed simulation to investigate the relationship among family involvement, learning effectiveness, teaching achievement, creative teaching method, and students’ learning interest. The results of this study verified that there are positive correlations between family involvement and students’ learning effectiveness, as well as students’ learning effectiveness and teachers’ teaching achievements. The results also indicated that the use of creative teaching method is able to increase students’ learning interest and learning achievement.[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]Y[[booktype]]電子版[[countrycodes]]US

Could the compact remnant of SN 1987A be a quark star?

The standard model for Type II supernovae explosions, confirmed by the detection of neutrinos emitted during the supernova explosion, predicts the formation of a compact object, usually assumed to be a neutron star. However, the lack of detection of a neutron star or pulsar formed in the SN 1987A still remains an unsolved mystery. In this paper, we suggest that the newly formed neutron star at the center of SN 1987A may undergo a phase transition after the neutrino trapping timescale (∼10 s). Consequently the compact remnant of SN 1987A may be a strange quark star, which has a softer equation of state than that of neutron star matter. Such a phase transition can induce stellar collapse and result in large amplitude stellar oscillations.We use a three-dimensional Newtonian hydrodynamic code to study the time evolution of the temperature and density at the neutrinosphere. Extremely intense pulsating neutrino fluxes, with submillisecond period and with neutrino energy (greater than 30 MeV), can be emitted because the oscillations of the temperature and density are out of phase almost 180◦. If this is true we predict that the current X-ray emission from the compact remnant of SN 1987A will be lower than 1034 erg s−1, and it should be a thermal bremsstrahlung spectrum for a bare strange star with a surface temperature of around ∼107 K.published_or_final_versio