Nonreciprocal ultrastrong magnon-photon coupling in the bandgap of photonic crystals

We observe a nonreciprocal ultrastrong magnon-photon coupling in the bandgap of photonic crystals by introducing a single crystal YIG cylinder into copper photonic crystals cavity as a point defect. The coupling strength reaches up to 1.18 GHz, which constitutes about 10.9% of the photon energy compared to the photon frequency around 10.8 GHz. It is fascinating that the coupling achieves unidirectional signal transmission in the whole bandgap. This study demonstrates the possibility of controlling nonreciprocal magnon-photon coupling by manipulating the structure of photonic crystals, providing new methods to investigate the influence of magnetic point defects on microwave signal transmission.Comment: 6 pages, 5 figure

Metformin Inhibits Tumor Metastasis through Suppressing Hsp90α Secretion in an AMPKα1-PKCγ Dependent Manner

Metformin has been documented in epidemiological studies to mitigate tumor progression. Previous reports show that metformin inhibits tumor migration in several cell lines, such as MCF-7 and H1299, but the mechanisms whereby metformin exerts its inhibitory effects on tumor metastasis remain largely unknown. The secreted proteins in cancer cell-derived secretome have been reported to play important roles in tumor metastasis, but whether metformin has an effect on tumor secretome remains unclear. Here we show that metformin inhibits tumor metastasis by suppressing Hsp90α (heat shock protein 90α) secretion. Mass spectrometry (MS) analysis and functional validation identify that eHsp90α (extracellular Hsp90α) is one of the most important secreted proteins for metformin to inhibit tumor cells migration, invasion and metastasis both in vitro and in vivo. Moreover, we find that metformin inhibits Hsp90α secretion in an AMPKα1 dependent manner. Our data elucidate that AMPKα1 (AMP-activated protein kinase α1) decreases the phosphorylation level of Hsp90α by inhibiting the kinase activity of PKCγ (protein kinase Cγ), which suppresses the membrane translocation and secretion of Hsp90α. Collectively, our results illuminate that metformin inhibits tumor metastasis by suppressing Hsp90α secretion in an AMPKα1 dependent manner

Dissipative Particle Dynamics Study on the Aggregation Behavior of Asphaltenes under Shear Fields

In the present work, the effects of shear fields on the aggregation of asphaltene molecules in heptane were investigated by means of dissipative particle dynamics simulations. The geometries of asphaltene aggregates without shear fields were studied, and the simulation results provide an interpretation of the experimental results on the microscopic level. The effects of shear fields on asphaltene aggregates were also investigated by accessing the radial distribution functions, spatial orientation correlation functions, and the radii of gyrations. We show that the shear fields can destroy the conformational order of the aggregates by damaging the organized structure and isolating the asphaltenes. As the radius of gyration results show, the asphaltene molecules are elongated to be alike-polymers by shear fields. Moreover, the reason why the viscosity decreases under shear fields is that the shear fields lead to the increase of dimerization free energies

Targeting the functional interplay between endoplasmic reticulum oxidoreductin-1α and protein disulfide isomerase suppresses the progression of cervical cancerResearch in context

Background: Endoplasmic reticulum (ER) oxidoreductin-1α (Ero1α) and protein disulfide isomerase (PDI) constitute the pivotal pathway of oxidative protein folding, and are highly expressed in many cancers. However, whether targeting the functional interplay between Ero1α and PDI could be a new approach for cancer therapy remains unknown. Methods: We performed wound healing assays, transwell migration and invasion assays and xenograft assays to assess cell migration, invasion and tumorigenesis; gel filtration chromatography, oxygen consumption assay and in cells folding assays were used to detect Ero1α-PDI interaction and Ero1α oxidase activity. Findings: Here, we report that elevated expression of Ero1α is correlated with poor prognosis in human cervical cancer. Knockout of ERO1A decreases the growth, migration and tumorigenesis of cervical cancer cells, through downregulation of the H2O2-correlated epithelial-mesenchymal transition. We identify that the conserved valine (Val) 101 of Ero1α is critical for Ero1α-PDI complex formation and Ero1α oxidase activity. Val101 of Ero1α is specifically involved in the recognition of PDI catalytic domain. Mutation of Val101 results in a reduced ER, retarded oxidative protein folding and decreased H2O2 levels in the ER of cervical cancer cells and further impairs cell migration, invasion, and tumor growth. Interpretation: Our study identifies the critical residue of Ero1α for recognizing PDI, which underlines the molecular mechanism of oxidative protein folding for tumorigenesis and provides a proof-of-concept for cancer therapy by targeting Ero1α-PDI interaction. Fund: This work was supported by National Key R&D Program of China, National Natural Science Foundation of China, and Youth Innovation Promotion Association, CAS. Keywords: Cervical cancer, Ero1α, PDI, Protein interaction, Redo

The regulatory mechanism of Hsp90α secretion and its function in tumor malignancy

Heat shock protein 90-α (Hsp90α) is an intracellular molecular chaperone. However, it can also be secreted with the underlying regulatory mechanism remaining far from clear. Here we show that the secreted Hsp90α is a C-terminal truncated form and its secretion is regulated by the C-terminal EEVD motif via interacting with proteins containing tetratricopeptide repeat domains. We also demonstrate that secretion of Hsp90α is determined by the phosphorylation status at residue Thr-90, regulated by protein kinase A and protein phosphatase 5. We further demonstrate that the secretion of Hsp90α is a prerequisite for its proinvasiveness function and blocking the secreted Hsp90α results in significant inhibition of tumor metastasis. Meanwhile, the level of plasma Hsp90α is positively correlated with tumor malignancy in clinical cancer patients. In sum, our results reveal the regulatory mechanism of Hsp90α secretion, and its function in tumor invasiveness, indicating it can be a promising diagnostic marker for tumor malignancy in clinical application