sLe^(x) expression in invasive micropapillary breast carcinoma is associated with poor prognosis and can be combined with MUC1/EMA as a supplementary diagnostic indicator

Objective: Mucin 1(MUC1/EMA) and sialyl Lewis X(sLe^(x)) indicate polarity reversal in invasive micropapillary carcinoma(IMPC). The purpose of this study was to evaluate the expression of MUC1/EMA and sLe^(x) and to assess their diagnostic and prognostic value in patients with IMPC.Methods: The expression of sLe^(x) and MUC1/EMA in 100 patients with IMPC and a control group of 89 patients with invasive ductal carcinoma not otherwise specified(IDC-NOS) were analyzed with IHC. Fresh tumor tissues were collected from patients with IMPC or IDC-NOS for primary culture and immunofluorescence analysis.Results: The rate of nodal metastasis was higher in patients with IMPC than those with IDC-NOS, and IMPC cells tended to express more sLe^(x) and MUC1/EMA in the cytomembranes(the stroma-facing surfaces of the micropapillary clusters) than IDC-NOS cells. In IMPC, high cytomembrane expression of sLe^(x), but not MUC1/EMA, indicated poor prognosis. In addition, among the 100 patients with IMPC, 10 patients had sLe^(x)+/EMA-expression patterns, and 8 patients had sLe^(x)-/EMA+ expression patterns. The primary IMPC cells were suspended, non-adherent tumor cell clusters, whereas the primary IDC cells were adherent tumor cells. Immunofluorescence analysis showed that MUC1/EMA and sLe^(x) were co-expressed on the cytomembranes in IMPC cell clusters and in the cytoplasm in IDC-NOS cells.Conclusions: sLe^(x) can be used as a prognostic indicator and can be combined with MUC1/EMA as a complementary diagnostic indicator to avoid missed IMPC diagnosis.

Preliminary design of high power magnet converter for CRAFT

In order to test the superconducting magnet performance for the Comprehensive Research Facility for Fusion Technology(CRAFT)project of China,a power supply converter needs to be designed.In this paper,short circuits upstream and downstream of the direct current(DC)reactor are analyzed,and the thyristor style and the parallel number are determined by the limit analysis of junction temperature and fault current I^2t.On this basis,the over current and voltage verification of fast fuse are finished to protect the thyristor at fault cases by considering the short circuit of the bridge arm.Then,the resistor and capacitor parameters of thyristor snubber are committed to decreasing the reverse over voltage.These analysis results will be used as the preliminary design of high power magnet converter for CRAFT.

High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic disorders.However,the underlying mechanism remains elusive.In the present study,by comparing HFD-and normal diet(ND)-treated mice,we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier.Metagenomic sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions,as confirmed by the increased reactive oxygen species(ROS)levels in fecal microbiota incubation in vitro and in the lumen,which were detected using in vivo fluorescence imaging.This microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT)into germ-free(GF)mice,downregulating the gut barrier tight junctions.Similarly,mono-colonizing GF mice with an Enterococcus strain excelled in ROS production,damaged the gut barrier,induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells,and exacerbated fatty liver,compared with other low-ROS-producing Enterococcus strains.Oral administration of recombinant high-stability-superoxide dismutase(SOD)significantly reduced intestinal ROS,protected the gut barrier,and improved fatty liver against the HFD.In conclusion,our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

The gut microbial metabolite, 3,4-dihydroxyphenylpropionic acid, alleviates hepatic ischemia/reperfusion injury via mitigation of macrophage pro-inflammatory activity in mice

Hepatic ischemia/reperfusion injury(HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI.Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16 S r RNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening(ZT12, 20:00) when compared with the morning(ZT0, 08:00);however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase(HDAC) inhibition in macrophages.

Evaluating user cognition of network diagrams

Edges crossing and nodes overlapping have a significant effect on the users’recognition and comprehension of network diagrams.In this study,we propose a visual evaluation method for users’cognition of network diagrams.First,this method carries out a set of cognitive experiments to collect the user’s cognitive performance that affects the variables,including accuracy and response time.The user’s pupil diameter is measured through an eye tracker to reflect their cognitive load.Second,the significance test points out the visual features as independent variables and then establishes an evaluation regression model.The experimental results show that the number of edges,edge length,node visual interference,and edge occlusion contribute to the evaluation models of response time,and edge occlusion and the number of node connections contribute to the accuracy model.Finally,these evaluation models demonstrate good predictability when assessing users’cognition of network diagrams and provide practical recommendations for their use.