ABSTRACT
Analysis of extracellular vesicles (EVs) is a promising noninvasive liquid biopsy approach for breast cancer (BC) detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of BC-specific EVs from human samples is required to realize the potential of this strategy. In this study, we applied a mass spectrometry-based, data-independent acquisition (DIA) proteomic approach to characterize human serum EVs derived from patients with BC (n = 126) and healthy donors (HDs, n = 70) in a discovery cohort and validated the findings in five independent cohorts. Examination of the EV proteomes enabled construction of specific EV protein classifiers for diagnosing BC and distinguishing patients with metastatic disease. Of note, TALDO1 was found to be an EV biomarker of distant metastasis of BC. In vitro and in vivo analysis confirmed the role of TALDO1 in stimulating BC invasion and metastasis. Finally, high-throughput molecular docking and virtual screening of a library consisting of 271,380 small molecules identified a potent TALDO1 allosteric inhibitor, AO-022, which could inhibit BC migration in vitro and tumor progression in vivo. Together, this work elucidates the proteomic alterations in the serum EVs of BC patients to guide development of improved diagnosis, monitoring, and treatment strategies.
ABSTRACT
Topology created by quasi-continuous spatial variations of a local polarization direction represents an exotic state of matter, but field-driven manipulation has been hitherto limited to creation and destruction. Here we report that relatively small electric or mechanical fields can drive the non-volatile rotation of polar spirals in discretized microregions of the relaxor ferroelectric polymer poly(vinylidene fluoride-ran-trifluoroethylene). These polar spirals arise from the asymmetric Coulomb interaction between vertically aligned helical polymer chains, and can be rotated in-plane through various angles with robust retention. Given also that our manipulation of topological order can be detected via infrared absorption, our work suggests a new direction for the application of complex materials.
ABSTRACT
Owing to their excellent discharged energy density over a broad temperature range, polymer nanocomposites offer immense potential as dielectric materials in advanced electrical and electronic systems, such as intelligent electric vehicles, smart grids and renewable energy generation. In recent years, various nanoscale approaches have been developed to induce appreciable enhancement in discharged energy density. In this Review, we discuss the state-of-the-art polymer nanocomposites with improved energy density from three key aspects: dipole activity, breakdown resistance and heat tolerance. We also describe the physical properties of polymer nanocomposite interfaces, showing how the electrical, mechanical and thermal characteristics impact energy storage performances and how they are interrelated. Further, we discuss multi-level nanotechnologies including monomer design, crosslinking, polymer blending, nanofiller incorporation and multilayer fabrication. We conclude by presenting the current challenges and future opportunities in this field.