Dual-modality Imaging of Angiogenesis in Unstable Atherosclerotic Plaques with VEGFR2-Targeted Upconversion Nanoprobes in vivo.

AIM: Angiogenesis plays a major role in atherosclerotic plaque development and instability. Our study aims to develop a novel optical and magnetic resonance (MR) dual-modality molecular imaging probe to early detect unstable plaques in vivo by targeting biomarkers of angiogenesis in murine models of atherosclerosis (AS). METHODS: Immunofluorescence and western blot were used to detect the expression of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in activated Human Umbilical Vein Endothelial Cells (HUVECs). After synthesis and identification of novel short peptide VRBP1-targeted VEGFR2, HUVECs were co-cultured with FITC-VRBP1 to test specific affinity of VRBP1. Then VRBP1-UCNPstargeting VEGFR2 were constructed by conjugating VRBP1 to the surface of NaGdF4:Yb,Er@NaGdF4 nanoparticles. The characterization of the nanoparticles was performed by transmission electron microscopy (TEM), distribution of size, hydrodynamic size, zeta potential, absorption spectra, emission spectra, imaging intensity of different concentrations, binding affinity and cytotoxicity of nanoprobes in vitro. The upconversion luminescence (UCL) and MR imaging were performed to identify unstable atherosclerotic plaque in ApoE-/- mice in vivo and ex vivo. Morphological staining was used to verify AS model and angiogenesis, and Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) was used to confirm accumulation of the nanoparticles after imaging. RESULTS: After induced by hypoxia and ox-LDL, the expression of VEGFR2 in activated HUVECs was enhanced. FITC-VRBP1 can specifically bind to the HUVECs. Characterization of the nanoparticles showed that particles size is uniform with a stable structure, specific optical and MR signal, good binding affinity to VEGFR2 and low cytotoxicity. In vivo and ex vivo UCL imaging and quantitative analysis revealed that distinctive optical signal was observed in the regions of left carotid common arteries (LCCAs) of AS group after injection of VRBP1-UCNPs. Higher signal intensity on T1-weighted MR imaging appeared in the LCCA wall of AS group after injection. The results of morphological staining demonstrated angiogenesis in the atherosclerotic plaques, Gd ions in LCCAs, aortic arch and renal arteries bifurcations detected by ICP-AES confirmed accumulation of the nanoparticles in plaque. CONCLUSIONS: We successfully design and synthesize a novel UCNPs using peptide VRBP1 targeting to VEGFR2. In vivo imaging demonstrates that VRBP1-UCNPs can be used to perform optical/MR dual-modality imaging targeting angiogenesis in plaques, which is a promising technique to early detect unstable atherosclerosis.

Student Self-Assessment and Faculty Assessment of Performance in an Interprofessional Error Disclosure Simulation Training Program.

Objectives. To conduct a prospective evaluation for effectiveness of an error disclosure assessment tool and video recordings to enhance student learning and metacognitive skills while assessing the IPEC competencies. Design. The instruments for assessing performance (planning, communication, process, and team dynamics) in interprofessional error disclosure were developed. Student self-assessment of performance before and after viewing the recordings of their encounters were obtained. Faculty used a similar instrument to conduct real-time assessments. An instrument to assess achievement of the Interprofessional Education Collaborative (IPEC) core competencies was developed. Qualitative data was reviewed to determine student and faculty perceptions of the simulation. Assessment. The interprofessional simulation training involved a total of 233 students (50 dental, 109 nursing and 74 pharmacy). Use of video recordings made a significant difference in student self-assessment for communication and process categories of error disclosure. No differences in student self-assessments were noted among the different professions. There were differences among the family member affects for planning and communication for both pre-video and post-video data. There were significant differences between student self-assessment and faculty assessment for all paired comparisons, except communication in student post-video self-assessment. Students' perceptions of achievement of the IPEC core competencies were positive. Conclusion. The use of assessment instruments and video recordings may have enhanced students' metacognitive skills for assessing performance in interprofessional error disclosure. The simulation training was effective in enhancing perceptions on achievement of IPEC core competencies. This enhanced assessment process appeared to enhance learning about the skills needed for interprofessional error disclosure.

Polyketides from mantis-associated fungus Daldinia eschscholzii IFB-TL01.

Three new polyketides, named daldinone F (1), nodulisporin G (2), and dalmanol C (3), together with five known compounds, 4-8, were isolated from cultures of Daldinia eschscholzii. The structures of the new compounds were elucidated by extensive NMR and MS analyses. Compound 1 showed moderate cytotoxic activity against SW480 cancer cells with an IC50 value of 9.59 µM, and its absolute configuration was determined by single crystal X-ray diffraction.