Determining the physical conditions of extremely young Class 0 circumbinary disk around VLA1623A

We present detailed analysis of high-resolution C18O (2-1), SO (88-77), CO (3-2) and DCO+ (3-2) data obtained by the Atacama Large Millimeter/sub-millimeter Array (ALMA) towards a Class 0 Keplerian circumbinary disk around VLA1623A, which represents one of the most complete analysis towards a Class 0 source. From the dendrogram analysis, we identified several accretion flows feeding the circumbinary disk in a highly anisotropic manner. Stream-like SO emission around the circumbinary disk reveals the complicated shocks caused by the interactions between the disk, accretion flows and outflows. A wall-like structure is discovered south of VLA1623B. The discovery of two outflow cavity walls at the same position traveling at different velocities suggests the two outflows from both VLA1623A and VLA1623B overlays on top of each other in the plane of sky. Our detailed flat and flared disk modeling shows that Cycle 2 C18O J = 2-1 data is inconsistent with the combined binary mass of 0.2 Msun as suggested by early Cycle 0 studies. The combined binary mass for VLA1623A should be modified to 0.3 ~ 0.5 Msun.Comment: 26 pages, 20 figures, accepted by ApJ 2020.2.2

α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

Fabrication of multianalyte CeO2 nanograin electrolyte–insulator–semiconductor biosensors by using CF4 plasma treatment

Multianalyte CeO2 biosensors have been demonstrated to detect pH, glucose, and urine concentrations. To enhance the multianalyte sensing capability of these biosensors, CF4 plasma treatment was applied to create nanograin structures on the CeO2 membrane surface and thereby increase the contact surface area. Multiple material analyses indicated that crystallization or grainization caused by the incorporation of flourine atoms during plasma treatment might be related to the formation of the nanograins. Because of the changes in surface morphology and crystalline structures, the multianalyte sensing performance was considerably enhanced. Multianalyte CeO2 nanograin electrolyte–insulator–semiconductor biosensors exhibit potential for use in future biomedical sensing device applications

Outcome for self-expandable metal stents in patients with malignant gastroduodenal obstruction: A single center experience

SummaryBackgroundMalignant gastric outlet obstruction causes significant malnutrition and morbidity. The implantation of a metallic stent is an alternative palliative treatment to allow the intake of food in these patients.Patients and MethodsThirty-eight consecutive patients with malignant gastric outlet obstruction who had received an uncovered metallic stent placement in our department from April 2010 to April 2012 were enrolled for analysis. The mean follow-up time was 6.3 months. Food intake, measured by the Gastric Outlet Obstruction Scoring System, complications, duration of stent patency, and survival were evaluated.ResultsThe technical and clinical success rates of the procedure were 100% and 94.7%, respectively. The Gastric Outlet Obstruction Scoring System scores were significantly improved at 1 day, 7 days, and 30 days after the implantation compared with those prior to the procedure (p < 0.001). Aspiration pneumonia developed in two patients (5.2%) after the procedure. One of these patients developed respiratory failure and died 3 days later. Stent dysfunction developed in 11 of 38 patients (28.9%) during the follow-up period; one patient (2.6%) experienced migration of the stent 38 days later due to resolution of the stricture; 10 patients (26.3%) had stent restenosis. The median time of stent patency was 120 days. The presence of peritoneal carcinomatosis when the procedure was carried out was a significantly poor predictive factor of stent patency [hazard ratio (HR) 7.9, p = 0.039]. The median survival of the patients was 156 days. Poor performance status ≥3; HR 2.647, p = 0.012) and nongastric cancer origin (HR 3.466, p = 0.008) were associated with a significantly short survival time.ConclusionMetallic stent placement is an effective and relatively safe treatment for patients with malignant gastric outlet obstruction

Case report: Cytokine and miRNA profiling in multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is an imperative pediatric inflammatory condition closely linked to COVID-19, which garners substantial attention since the onset of the pandemic. Like Kawasaki illness, this condition is characterized by an overactive immune response, leading to symptoms including pyrexia, cardiac and renal complications. To elucidate the pathogenesis of MIS-C and identify potential biomarkers, we conducted an extensive examination of specific cytokines (IL-6, IL-1β, IL-6R, IL-10, and TNF-α) and microRNA (miRNA) expression profiles at various intervals (ranging from 3 to 20 days) in the peripheral blood sample of a severely affected MIS-C patient. Our investigation revealed a gradual decline in circulating levels of IL-6, IL-1β, IL-10, and TNF-α following intravenous immune globulin (IVIG) therapy. Notably, IL-6 exhibited a significant reduction from 74.30 to 1.49 pg./mL, while IL-6R levels remained consistently stable throughout the disease course. Furthermore, we observed an inverse correlation between the expression of hsa-miR-596 and hsa-miR-224-5p and the aforementioned cytokines. Our findings underscore a robust association between blood cytokine and miRNA concentrations and the severity of MIS-C. These insights enhance our understanding of the genetic regulatory mechanisms implicated in MIS-C pathogenesis, offering potential avenues for early biomarker detection and therapy monitoring through miRNA analysis

Statistical identification of gene association by CID in application of constructing ER regulatory network

<p>Abstract</p> <p>Background</p> <p>A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating <it>in silico </it>inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor α (ERα) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A).</p> <p>Results</p> <p>The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's <it>t</it>-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays.</p> <p>Conclusion</p> <p>CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association predicted by CID are applicable to the construction of transcriptional regulatory networks. This study shows how information from different data sources and learning algorithms can be integrated to investigate whether relevant regulatory mechanisms identified in cell models can also be partially re-identified in clinical samples of breast cancers.</p> <p>Availability</p> <p>the implementation of CID in R codes can be freely downloaded from <url>http://homepage.ntu.edu.tw/~lyliu/BC/</url>.</p

Association between estradiol levels in early pregnancy and risk of preeclampsia after frozen embryo transfer

IntroductionThe failure of remodeling the spiral arteries is associated with the pathogenesis of preeclampsia. Estradiol (E2) plays a crucial role in placentation and may be involved in the development of preeclampsia. However, there is a lack of data in this area. This study aims to assess the association between serum estradiol levels in early pregnancy and the risk of preeclampsia.MethodsWe conducted a retrospective cohort study on patients who conceived after frozen embryo transfer (FET) using data from a database at a university-affiliated in vitro fertilization center. The study period spanned from January 1, 2010, to December 31, 2020. Multivariable logistic regression analyses were performed to determine the adjusted effect of E2 levels on the risk of preeclampsia. We compared the odds ratios of preeclampsia across quartiles of E2 levels and assessed their significance.ResultsSerum E2 levels at the fifth gestational week were significantly different between women with and without preeclampsia after FET programmed cycles (607.5 ± 245.4 vs. 545.6 ± 294.4 pg/ml, p=0.009). A multivariable logistic regression model demonstrated that E2 levels in early pregnancy were independent risk factors for preeclampsia. We observed an increased odds ratio of preeclampsia with increasing quartiles of estradiol levels after adjusting for potential confounders in FET programmed cycles. When comparing quartiles 3 and 4 (E2 &gt; 493 pg/ml at the fifth gestational week) to quartiles 1 and 2, the odds ratios of preeclampsia were significantly higher.ConclusionWe found that serum E2 levels in early pregnancy may impact the risk of preeclampsia, particularly following FET programmed cycles. The association between E2 levels in early pregnancy and preeclampsia deserves further investigation