Application of 3D-PCASL combined with t-ASL and MRA in the diagnosis of patients with isolated vertigo induced by posterior circulation ischemia.

OBJECTIVES: Isolated vertigo induced by posterior circulation ischemia (PCIV) can further progress into posterior circulation infarction. This study aimed to explore the diagnostic values of three-dimensional pseudo-continuous arterial spin labeling (3D-PCASL) combined with territorial arterial spin labeling (t-ASL) and magnetic resonance angiography (MRA) in visualizing and evaluating PCIV, seeking improved diagnostic tools for clinical guidance. METHODS: 28 PCIVs (11 males, 17 females, aged from 55 to 83 years, mean age: 69.68 ± 9.01 years) and 28 healthy controls (HCs, 12 male, 16 female, aged from 56 to 87 years, mean age: 66.75 ± 9.86 years) underwent conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), MRA, 3D-PCASL, and t-ASL. We compared the incidence of anatomic variants of the posterior circle of Willis in MRA, cerebral blood flow (CBF) and anterior collateral blood flow on postprocessing maps obtained from 3D-PCASL and t-ASL sequence between PCIVs and HCs. Chi-square test and paired t-test were analyzed statistically with SPSS 24.0 software. RESULTS: 7 PCIVs (7/28, 25%) and 6 HCs (6/28, 21%) showed fetal posterior cerebral artery (FPCA) on MRA, including 1 HC, and 6 PCIVs with FPCA appeared hypoperfusion. 18 PCIVs (64%) and 2 HCs (7%) showed hypoperfusion in the posterior circulation (PC), including 1 HC and 7 PCIVs displayed anterior circulation collateral flow. Chi-square analyses demonstrated a difference in PC hypoperfusion between PCIVs and HCs, whether in the whole or FPCA-positive group assessment (P < 0.05). Paired t-test showed that the CBF values were significant difference for the bilateral PC asymmetrical perfusion in the PCIVs (P < 0.01). When compared to the bilateral PC symmetrical non-hypoperfusion area in the PCIVs and HCs, the CBF values were not significant (P > 0.05). The CBF values of the PC in PCIVs were lower than in HCs (P < 0.05). The reduction rate in the hypoperfusion side of the bilateral PC asymmetrical perfusion of the PCIVs ranged from 4% to 37%, while the HCs reduction rate was 7.7%. The average PC symmetrical perfusion average reduction rate of the PCIVs was 52.25%, while the HCs reduction rate was 42.75%. CONCLUSION: 3D-PCASL is a non-invasive and susceptible method for detecting hypoperfusion in PC, serving as a potential biomarker of PCIV. The suspected hypoperfusion in PC may be attributed to the emergence of FPCA and the manifestation of anterior collateral flow when combining t-ASL and MRA sequences. These findings demonstrated that 3D-PCASL combined with t-ASL and MRA sequences are the potential method to identify PCIV, leading to early diagnosis of PCIV and reducing the risk of progressing into infarction.

ILKAP Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inhibiting ß-Catenin Degradation and Enhancing the WNT Signaling Pathway.

The incidence of Hepatocellular carcinoma (HCC) and HCC-related deaths have remarkably increased over the recent decades. It has been reported that ß-catenin activation can be frequently observed in HCC cases. This study identified the integrin-linked kinase-associated phosphatase (ILKAP) as a novel ß-catenin-interacting protein. ILKAP is localized both in the nucleus and cytoplasm and regulates the WNT pathway in different ways. First, it is demonstrated that ILKAP activates the WNT pathway in HCC cells by increasing the protein level of ß-catenin and other proteins associated with the WNT signaling, such as c-Myc and CyclinD1. Next, it is shown that ILKAP promotes the metastasis of HCC both in vitro and in vivo in a zebrafish xenograft model. It is also found that ILKAP dephosphorylates the GSK3ß and CK1, contributing to the reduced ubiquitination of ß-catenin. Furthermore, it is identified that ILKAP functions by mediating binding between TCF4 and ß-catenin to enhance expression of WNT target genes. Taken together, the study demonstrates a critical function of ILKAP in metastasis of HCC, since ILKAP is crucial for the activation of the WNT pathway via stabilization of ß-catenin and increased binding between TCF4 and ß-catenin.

RUNDC1 inhibits autolysosome formation and survival of zebrafish via clasping ATG14-STX17-SNAP29 complex.

Autophagy serves as a pro-survival mechanism for a cell or a whole organism to cope with nutrient stress. Our understanding of the molecular regulation of this fusion event remains incomplete. Here, we identified RUNDC1 as a novel ATG14-interacting protein, which is highly conserved across vertebrates, including zebrafish and humans. By gain and loss of function studies, we demonstrate that RUNDC1 negatively modulates autophagy by blocking fusion between autophagosomes and lysosomes via inhibiting the assembly of the STX17-SNAP29-VAMP8 complex both in human cells and the zebrafish model. Moreover, RUNDC1 clasps the ATG14-STX17-SNAP29 complex via stimulating ATG14 homo-oligomerization to inhibit ATG14 dissociation. This also prevents VAMP8 from binding to STX17-SNAP29. We further identified that phosphorylation of RUNDC1 Ser379 is crucial to inhibit the assembly of the STX17-SNAP29-VAMP8 complex via promoting ATG14 homo-oligomerization. In line with our findings, RunDC1 is crucial for zebrafish in their response to nutrient-deficient conditions. Taken together, our findings demonstrate that RUNDC1 is a negative regulator of autophagy that restricts autophagosome fusion with lysosomes by clasping the ATG14-STX17-SNAP29 complex to hinder VAMP8 binding.

A sensitive gold nanoparticle-based colorimetric aptasensor for Staphylococcus aureus.

In this study, a gold nanoparticle-based colorimetric aptasensor for Staphylococcus aureus (S. aureus) using tyramine signal amplification (TSA) technology has been developed. First, the biotinylated aptamer specific for S. aureus was immobilized on the surface of the wells of the microtiter plate via biotin-avidin binding. Then, the target bacteria (S. aureus), biotinylated-aptamer-streptavidin-HRP conjugates, biotinylated tyramine, hydrogen peroxide and avidin-catalase were successively introduced into the wells of the microtiter plate. After that, the existing catalase consumed the hydrogen peroxide. Finally, the freshly prepared gold (III) chloride trihydrate was added, the color of the reaction production would be changed and the absorbance at 550 nm could be measured with a plate reader. Under optimized conditions, there was a linear relationship between the absorbance at 550 nm and the concentration of S. aureus over the range from 10 to 10(6) cfu mL(-1) (with an R² of 0.9947). The limit of the developed method was determined to be 9 cfu mL(-1).