Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts

<p>Abstract</p> <p>Background</p> <p>Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.</p> <p>Methods</p> <p>A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.</p> <p>Results</p> <p>Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (<it>p </it>= 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).</p> <p>Conclusion</p> <p>Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.</p

Preparative Separation of Alkaloids from Stem of Euchresta tubulosa Dunn. by High-Speed Counter-Current Chromatography Using Stepwise Elution

Euchresta tubulosa Dunn. is a Chinese herbal medicine with biological activity, but there are few studies on its components at present. Alkaloids in the stem of Euchresta tubulosa Dunn. were isolated and purified by high-speed counter-current chromatography (HSCCC) using stepwise elution. First of all, liquid-liquid extraction (methylene chloride-methanol-water, 5:1:4, v/v) was used for the preliminary enrichment. According to the partition coefficient (K) of a target compound in a series of different two-phase solvents, the final result was that carbon tetrachloride-methylene chloride-methanol-water (2:3:3:2, v/v) (1) and methylene chloride-methanol-water (5:3:2, v/v) (2) were suitable for the HSCCC using stepwise elution. As a result, the purity was all higher than 93% and matrine (1), oxymatrine (2), N-formyl cytisine (3), and N-acetyl cytisine (4) can be eluted at one time by this mode. Cytisine-type alkaloids were isolated for the first time in this plant. Finally, the applicability of the mode was verified

Quantifiable Effect of Interparticle Plasmonic Coupling on Sensitivity and Tuning Range for Wavelength-Mode LSPR Fiber Sensor Fabricated by Simple Immobilization Method

Herein a gold nanosphere (AuNS)-coated wavelength-mode localized surface plasmon resonance (LSPR) fiber sensor was fabricated by a simple and time-saving electrostatic self-assembly method using poly(allylamine hydrochloride). Based on the localized enhanced coupling effect between AuNSs, the LSPR spectrums of the AuNS monolayer with good dispersity and high density exhibited a favourable capability for refractive index (RI) measurement. Based on the results obtained from the optimization for AuNS distribution, sensing length, and RI range, the best RI sensitivity of the fiber modified by 100 nm AuNS reached up to about 2975 nm/RIU, with the surrounding RI range from 1.3322 to 1.3664. Using an 80 nm AuNS-modified fiber sensor, the RI sensitivity of 3953 nm/RIU was achieved, with the RI range increased from 1.3744 to 1.3911. The effect of sensing length to RI sensitivity was proven to be negligible. Furthermore, the linear relationship between the RI sensitivity and plasma resonance frequency of the bulk metal, which was dependent on the interparticle plasmon coupling effect, was quantified. Additionally, the resonance peak was tuned from 539.18 nm to 820.48 nm by different sizes of AuNSs-coated fiber sensors at a RI of 1.3322, which means the spectrum was extended from VIS to NIR. It has enormous potential in hypersensitive biochemistry detection at VIS and NIR ranges

Research on the Spillover Effect of China’s Carbon Market from the Perspective of Regional Cooperation

After the official launch of China’s unified carbon market, the potential for carbon emission reduction is huge. The pilot regional markets urgently need to be connected with the national carbon market to form a regional synergy and linkage mechanism and further promote the development of a unified carbon market. Spillover effects can be used to analyze the interaction between multiple markets. In this context, this study focuses on the overall spillover relationship among regional carbon trading markets. Using the VAR-GARCH-BEKK model and social network analysis (SNA), this study empirically analyzes the mean spillover effect and volatility spillover effect of regional carbon markets, and it establishes a spillover network between markets. The results show that the spillover effect of China’s regional carbon markets is widespread. Among them, the mean spillover effect is weak, and the impact period is short;. The volatility spillover effect is strong and has various directions; the spillover network connection between regional carbon markets is strong, but the spillover intensity is weak. Spillover effects will spread to the overall carbon market through information spillover paths and risk spillover paths. The stronger spillover effect and the stronger linkage between markets can bring more resource integration and unified supervision. Finally, we put forward policy recommendations, such as improving the carbon market mechanism and enhancing the maturity of carbon market development, increasing the participation and activity of the carbon market to encourage more participants to join the carbon market, improving the institutional system of the carbon market, and effectively supervising the process of information and risk spillover between carbon markets

Revealing a Second Transmetalation Step in the Negishi Coupling and Its Competition with Reductive Elimination: Improvement in the Interpretation of the Mechanism of Biaryl Syntheses

This paper presents an experimental and theoretical investigation of the Pd-catalyzed Negishi coupling reaction and reveals a novel second transmetalation reaction between an Ar-1-Pd-Ar-2 species and the organozinc reagent Ar-2-ZnX. Understanding of this second step reveals how homocoupling and dehalogenation products are formed. Thus, the second transmetalation generates (ArPdAr2)-Pd-2 and (ArZnCl)-Zn-1, which upon reductive elimination and hydrolysis, respectively, give the homocoupling product Ar-2-Ar-2 and the dehalogenation product (ArH)-H-1. The ratio of the cross-coupling product Ar-1-Ar-2 and the homocoupling product Ar-2-Ar-2 is determined by competition between the second transmetalation and reductive elimination steps. This mechanism is further supported by density functional theoretical calculations. Calculations on a series of reactions suggest a strategy in controlling the selectivity of cross-coupling and homocoupling pathways, which we have experimentally verified

Anterior Gradient 2 (AGR2) Induced Epidermal Growth Factor Receptor (EGFR) Signaling Is Essential for Murine Pancreatitis-Associated Tissue Regeneration

<div><p>A recently published study identified <i>Anterior Gradient 2 (</i>AGR2) as a regulator of EGFR signaling by promoting receptor presentation from the endoplasmic reticulum to the cell surface. AGR2 also promotes tissue regeneration in amphibians and fish. Whether AGR2-induced EGFR signaling is essential for tissue regeneration in higher vertebrates was evaluated using a well-characterized murine model for pancreatitis. The impact of AGR2 expression and EGFR signaling on tissue regeneration was evaluated using the caerulein-induced pancreatitis mouse model. EGFR signaling and cell proliferation were examined in the context of the AGR2^-/- <i>null</i> mouse or with the EGFR-specific tyrosine kinase inhibitor, AG1478. In addition, the Hippo signaling coactivator YAP1 was evaluated in the context of AGR2 expression during pancreatitis. Pancreatitis-induced AGR2 expression enabled EGFR translocation to the plasma membrane, the initiation of cell signaling, and cell proliferation. EGFR signaling and tissue regeneration were partially inhibited by the tyrosine kinase inhibitor AG1478, but absent in the AGR2^-/- <i>null</i> mouse. AG1478-treated and AGR2^-/- <i>null</i> mice with pancreatitis died whereas all wild-type controls recovered. YAP1 activation was also dependent on pancreatitis-induced AGR2 expression. AGR2-induced EGFR signaling was essential for tissue regeneration and recovery from pancreatitis. The results establish tissue regeneration as a major function of AGR2-induced EGFR signaling in adult higher vertebrates. Enhanced AGR2 expression and EGFR signaling are also universally present in human pancreatic cancer, which support a linkage between tissue injury, regeneration, and cancer pathogenesis.</p></div

Pancreatitis induces AGR2 expression and EGFR translocation to the cell surface.

<p>(A-D) pancreatitis was induced with the 1-day protocol of 8 hourly caerulein injections in 6–8 week old wild-type (wt) and 3-week old AGR2^-/- (ko) mice. (A) total EGFR (green) subcellular localization with and without caerulein-induced pancreatitis as determined by immunohistochemistry and confocal imaging. The nuclei were identified with DAPI stain (blue). Scale bars = 50 μm. (A-B) calreticulin and E-cadherin served as markers for the endoplasmic reticulum and plasma membrane, respectively, and were used to quantify EGFR subcellular location. (B) Columns for wild-type (wt) represent the mean of 10 animals that each contributed 10 images. For the AGR2-ko, 3 animals were studied. Error bars represent the standard error of the mean. (C) AGR2 and EGFR RNA were determined by RT-qPCR. Values were normalized relative to wild-type mice injected with saline. The error bars represent 1 standard deviation. (D) protein immunoblots of pancreatic homogenates for total EGFR, phosphorylated EGFR, AGR2, and ß-actin as a loading control. wt = wild-type; sal = saline control; cae = caerulein; ko = AGR2^-/- <i>null</i>; NS = not statistically significant; **** = p-value < .00001.</p