Submillisievert coronary CT angiography with adaptive prospective ECG-triggered sequence acquisition and iterative reconstruction in patients with high heart rate on the dual-source CT.

PURPOSE: To assess the application value of submillisievert coronary CT angiography (CCTA) in patients with a high heart rate (HR) acquired with adaptive prospective ECG-triggered sequence acquisition and iterative reconstruction on the secondary generation dual-source CT. MATERIALS AND METHODS: A total of 120 consecutive high-HR patients suspected with coronary artery disease underwent CCTA and invasive coronary angiography (ICA) within two weeks. Patients were randomly assigned into three groups: group A (n = 40), where the patients underwent retrospectively ECG-triggered acquisition CCTA at 100 kVp; group B (n = 40), where the patients received adaptive prospective ECG-triggered sequence acquisition at 100 kVp; and group C (n = 40), where the patients performed adaptive prospective ECG-triggered sequence acquisition at 80 kVp with iterative reconstruction. The mean CT values, signal noise ratios (SNR) and contrast noise ratios (CNR) in the ascending aorta and coronary arteries of the three groups were measured and compared. The image quality and radiation dose among the three groups were compared. The consistency of displaying the coronary stenosis of each group was assessed compared with the results of ICA as the gold standard. RESULTS: There was no significant difference in gender, age and body mass index (BMI) (all P > 0.05). The mean attenuations, SNRs and CNRs in the ascending aorta and coronary artery were not significantly different between group A and group B (P > 0.05). The mean attenuations of group C were significantly higher than group A and group B (P < 0.01), but the image noise and CNR were significantly lower in group C (P < 0.01). The number of appreciable segments among the three groups was not significantly different on a per-segment and per-vessel basis (P > 0.05). The subjective image quality among the three groups was not significantly different (P > 0.05). With the ICA result as a reference standard, there was good consistency in the evaluation of the coronary stenosis degree between CCTA and ICA (r > 0.75), as well as in the assessment of the coronary stenosis rate using the Bland- Altman analysis. The mean radiation dose in group B was half of that in group A. Moreover, the mean radiation dose in group C was less than one sixth of that in group A and less than 1 mSv (0.7±0.2 mSv). CONCLUSIONS: For patients with high HR, adaptive prospective ECG-triggered sequence acquisition on the FLASH dual-source CT results in equal image quality and half of the radiation dose reduction compared with retrospectively ECG-triggered spiral acquisition at the same tube voltage (100 kVp) and same R-R interval of exposure. In addition, adaptive prospective ECG-triggered sequence acquisition combined with low tube voltage and iterative reconstruction can further reduce the radiation dose to the submillisievert level without compromising image quality and the accuracy of assessing the coronary stenosis degree, and can be popularized as a routine technique.

Unfolded protein response regulates yeast small GTPase Arl1p activation at late Golgi via phosphorylation of Arf GEF Syt1p.

ADP ribosylation factor (Arf) GTPases are key regulators of membrane traffic at the Golgi complex. In yeast, Arf guanine nucleotide-exchange factor (GEF) Syt1p activates Arf-like protein Arl1p, which was accompanied by accumulation of golgin Imh1p at late Golgi, but whether and how this function of Syt1p is regulated remains unclear. Here, we report that the inositol-requiring kinase 1 (Ire1p)-mediated unfolded protein response (UPR) modulated Arl1p activation at late Golgi. Arl1p activation was dependent on both kinase and endo-RNase activities of Ire1p. Moreover, constitutively active transcription factor Hac1p restored the Golgi localization of Arl1p and Imh1p inIRE1-deleted cells. Elucidating the mechanism of Ire1p-Hac1p axis actions, we found that it regulated phosphorylation of Syt1p, which enhances Arl1p activation, recruitment of Imh1p to the Golgi, and Syt1p interaction with Arl1p. Consistent with these findings, the induction of UPR by tunicamycin treatment increases phosphorylation of Syt1p, resulting in Arl1p activation. Thus, these findings clarify how the UPR influences the roles of Syt1p, Arl1p, and Imh1p in Golgi transport.

IL-1ß promotes malignant transformation and tumor aggressiveness in oral cancer.

Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1ß) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1ß expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1ß was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1ß secretion in an inflammasome-dependent manner. IL-1ß treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-α following IL-1ß stimulation. The conditioned medium of IL-1ß-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1ß increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1ß can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC.

Functional study of CLC-1 mutants expressed in Xenopus oocytes reveals that a C-terminal region Thr891-Ser892-Thr893 is responsible for the effects of protein kinase C activator.

ClC-1 plays an important part in the maintenance of membrane potential in the mammalian skeletal muscle. To investigate the phosphorylation sites responsible for the effect of PKC (protein kinase C) activator, we constructed 21 different ClC-1 mutants with mutations at predicted phosphorylation sites for PKC. The functional experiments were performed on both wild-type and mutant proteins (17 point mutants and 4 double mutants) expressed in Xenopus oocytes with two-electrode voltage-clamp recording. PMA (12-myristate 13-acetate), a PKC activator, caused a right shift of half-maximum activation potential (V(1/2)) significantly in the wild-type (from -42.9+/-4.4 to -13.7+/-1.7 mV; n = 8, P < 0.05) and most of the single mutants except the S892P (from -39.5+/-4.5 to -35.7+/-5.7 mV; n = 6) and S892D (from -10.2+/-4.9 to -9.6+/-3.5 mV; n = 4). S892D, a mutant mimicking PKC-mediated phosphorylation at position 892, can also mimic the effect of wild-type treated with PMA in V(1/2) value (-10.2+/-4.9 mV vs -13.7+/-1.7 mV, n = 4 - 8). However, S892A still had a significant response to PMA indicating that other sites responsible for PMA might exist. Thus double mutants are generated for the following analysis. The V(1/2) of double mutants, T891A/S892A, S892A/T893A and T891A/T893A, show no significant difference between before and after PMA treatment. We hypothesize that this structural modification results in the observed alteration of the gating properties of ClC-1 by PMA. In summary, our observations show that a C-terminal region Thr891-Ser892-Thr893, at least in part, responsible for the effect of PMA on ClC-1.