Super-Resolution Imaging with Patchy Microspheres

The diffraction limit is a fundamental barrier in optical microscopy, which restricts the smallest resolvable feature size of a microscopic system. Microsphere-based microscopy has proven to be a promising tool for challenging the diffraction limit. Nevertheless, the microspheres have a low imaging contrast in air, which hinders the application of this technique. In this work, we demonstrate that this challenge can be effectively overcome by using partially Ag-plated microspheres. The deposited Ag film acts as an aperture stop that blocks a portion of the incident beam, forming a photonic hook and an oblique near-field illumination. Such a photonic hook significantly enhanced the imaging contrast of the system, as experimentally verified by imaging the Blu-ray disc surface and colloidal particle arrays

ARTICLE Shielding calculation for the CSNS target station

In this paper we firstly calculate the one-dimension shielding models to give the basic data for the Chinese Spallation Neutron Source (CSNS) target station. Then the three-dimensional shielding calculations have been performed for the detailed design of the CSNS target station. The gaps and void spaces in the CSNS target station are considered for precise estimation. We find that 4.8-meter-radius steel adding 1.2-meter-thick magnetite concrete can satisfy the shielding requirement in the horizontal direction. The dose rate on the top of the ceiling is a little higher than 2.5 Sv/h due to streaming effect, which originates from the moderator transfer lines. A thin sandwich structure will be adopted for decreasing residual radioactivity dose rate on the altitude directions after considering the engineering cost and maintenance. All these calculations lie on the Monte Carlo simulation code MCNPX2.5.0

Loss of PDZK1 expression activates PI3K/AKT signaling via PTEN phosphorylation in gastric cancer

Phosphorylation of PTEN plays an important role in carcinogenesis and progression of gastric cancer. However, the underlying mechanism of PTEN phosphorylation regulation remains largely elusive. In the present study, PDZK1 was identified as a novel binding protein of PTEN by association of PTEN through its carboxyl terminus and PDZ domains of PDZK1. By direct interaction with PTEN, PDZK1 inhibited the phosphorylation of PTEN at S380/T382/T383 cluster and further enhanced the capacity of PTEN to suppress PI3K/AKT activation. PDZK1 suppressed gastric cancer cell proliferation by diminishing PI3K/AKT activation via inhibition of PTEN phosphorylation in vitro and in vivo. The expression of PDZK1 was frequently downregulated in gastric cancer specimens and correlated with progression and poor prognosis of gastric cancer patients. Downregulation of PDZK1 was associated with PTEN inactivation, AKT signaling and cell proliferation activation in clinical specimens. Thus, low levels of PDZK1 in gastric cancer specimens lead to increase proliferation of gastric cancer cells via phosphorylation of PTEN at the S380/T382/T383 cluster and constitutively activation of PI3K/AKT signaling, which results in poor prognosis of gastric cancer patients

NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer

G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC

Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling

AbstractNa+/H+ exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to interact with a number of cancer-related proteins. nherf1 Mutations (K172N and D301V) were recently identified in breast cancer cells. To investigate the functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression suppressed the cellular malignant phenotypes, including proliferation, migration, and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRβ complex formation, inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and attenuating the tumor-suppressor effects of NHERF1-wt. These results further demonstrated the functional consequences of breast cancer-derived nherf1 mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor development and progression

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis

Abstract Background Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. Methods Differential gene analysis, protein−protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. Results F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. Conclusions Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis

Enhanced Strength and Electrical Conductivity in Graphite-Cement Mortars with Carbonized Titanium-Bearing Blast Furnace Slag as an Aggregate

Titanium-containing carbide slag (TCS) is the product obtained by high-temperature carbothermal reduction in Titanium-bearing blast furnace slag (TBFS), which contains a large amount of TiC phase with excellent electrical conductivity. In this paper, conductive cement mortar was prepared with TCS as an aggregate and graphite as a conductive phase. The content of graphite on the compressive strength and electrical resistivity of the prepared cement mortar was investigated. The results showed that the replacement of standard sand with TCS as an aggregate not only significantly reduced the electrical resistivity of the cement mortar, but also improved its compressive strength. When the graphite content was 10 wt%, the cement mortar with TCS as the aggregate exhibited excellent comprehensive performance with the 28d compressive strength of 34.0 MPa and the electrical resistivity of 2.9 Ω m in dry condition, respectively. The results of this paper provided a new way both for the utilization of TBFS and the preparation of conductive cement mortars