Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Utility of S100A12 as an Early Biomarker in Patients With ST-Segment Elevation Myocardial Infarction

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis. Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort. Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, MI, stroke, or hospitalization for heart failure. Results: A total of 438/1023 patients (42.8%) in the diagnosis cohort were adjudicated as STEMI, among whom plasma S100A12 levels increased within 30 min and peaked 1–2 h after symptom onset. Compared with high-sensitivity cardiac troponin T and creatine kinase-MB isoenzyme, S100A12 more accurately identified STEMI, especially within the first 2 h after symptom onset (area under the curve 0.963 compared with 0.860 for hscTnT and 0.711 for CK-MB, both P \u3c 0.05). These results were consistent in the 243-patient validation cohort. The 1-year rate of MACCE was greatest in patients in the highest peak S100A12 tertile, intermediate in the middle tertile and least in the lowest tertile (9.3 vs. 5.7 vs. 3.0% respectively, Ptrend = 0.0006). By multivariable analysis the peak plasma concentration of S100A12 was an independent predictor of MACCE within 1 year after STEMI (HR, 1.001, 95%CI, 1.000–1.002; P = 0.0104). Zhang et al. S100A12 as a STEMI Biomarker Conclusions and Relevance: S100A12 rapidly identified patients with STEMI, more accurately than other cardiac biomarkers, especially within the first 2 h after symptom onset. The peak plasma S100A12 level was a strong predictor of 1-year prognosis after STEMI

Pu-erh Tea Regulates Fatty Acid Metabolism in Mice Under High-Fat Diet

Pu-erh tea has been extensively reported to possess lipid lowering effects but the underlying mechanisms remained unclear. Free fatty acids (FFAs) are generally correlated with the development of obesity, leading to increased risk for type 2 diabetes mellitus and cardiovascular diseases. To investigate whether Pu-erh tea treatment alters FA metabolism, we treated HFD induced obese mice with Pu-erh tea for 22 weeks and analyzed FFA profiles of experimental mice using a UPLC-QTOF-MS platform. Results showed remarkable changes in metabolic phenotypes and FFA compositions in mice treated with or without Pu-erh tea. HFD induced a marked obese phenotype in mice as revealed by significantly increased body weight, liver and adipose tissue weight, lipid levels in serum and liver, and these parameters were markedly reduced by Pu-erh tea treatment. Several FFA or FFA ratios, such as DGLA, palmitoleic acid, and OA/SA ratio, were significantly increased while the levels of SA/PA and AA/DGLA were significantly reduced in HFD-induced obese mice. Interestingly, these differential FFAs or FFA ratios were previous identified as key markers in human obese subjects, and their changes observed in the HFD group were reversed by Pu-erh tea treatment. Moreover, a panel of FFA markers including C20:3 n6/C18:3 n6 and C20:3 n6/C20:2 n6, C18:3 n6/C18:2 n6, C18:3 n3/C18:2 n6 and C24:1 n9/C22:1 n9, which were previously identified as biomarkers in predicting the remission of obesity and diabetes in human subjects who underwent metabolic surgery procedures, were reversed by Pu-erh tea intervention. Pu-erh tea significantly improved glucose homeostasis and insulin tolerance compared to the HFD group. Additionally, Pu-erh tea treatment significantly decreased FFA synthesis genes and increased the expression of genes involved in FFA uptake and β-oxidation including FATP2, FATP5, PPARα, CPT1α, and ACOX-1. These finding confirmed the beneficial effects of Pu-erh tea on regulating lipid and glucose metabolism, and further validated a panel of FFA markers with diagnostic and prognostic value for obesity and diabetes

Aqueous electrosynthesis of an electrochromic material based water-soluble EDOT-MeNH2 hydrochloride

2\u27-Aminomethyl-3,4-ethylenedioxythiophene (EDOT-MeNH2) showed unsatisfactory results when its polymerization occurred in organic solvent in our previous report. Therefore, a water-soluble EDOT derivative was designed by using hydrochloric modified EDOT-MeNH2 (EDOT-MeNH2·HCl) and electropolymerized in aqueous solution to form the corresponding polymer with excellent electrochromic properties. Moreover, the polymer was systematically explored, including electrochemical, optical properties and structure characterization. Cyclic voltammetry showed low oxidation potential of EDOT-MeNH2·HCl (0.85 V) in aqueous solution, leading to the facile electrodeposition of uniform the polymer film with outstanding electroactivity. Compared with poly(2′-aminomethyl- 3,4-ethylenedioxythiophene) (PEDOT-MeNH2), poly(2′-aminomethyl-3,4-ethylenedioxythiophene salt) (PEDOT-MeNH3 +A-) revealed higher efficiencies (156 cm2 C-1), lower bandgap (1.68 eV), and faster response time (1.4 s). Satisfactory results implied that salinization can not only change the polymerization system, but also adjust the optical absorption, thereby increase the electrochromic properties

A 7.5–9 GHz GaAs Two-Channel Multi-Function Chip

Based on the 0.5 μm GaAs enhancement/depletion (E/D) Pseudomorphic High Electron Mobility Transistor (pHEMT) process, a 7.5–9 GHz two-channel amplitude phase control multi-function chip (MFC) was developed successfully. The chip was integrated with a 6-bit digital phase shifter, a 6-bit digital attenuator, and a single pole single throw (SPST) switch in each channel. A design for the absorptive SPST switch is deployed to optimize the return loss and control channel array calibration. In the 8 dB and 16 dB attenuation bit, a switched-path-type topology is employed in order to obtain a good flatness of attenuation characteristic and achieve low additive phase shift. A 27-bit serial-to-parallel converter (SPC) was introduced to decrease the control lines and pads of the chip, and the power consumption was less than 70 mW. The measurement result shows that the insertion loss is less than −13 dB and the return loss is better than −19 dB. In both channels, the 64-state root mean square (RMS) errors of the phase shifter is less than 2° and the RMS parasitic amplitude error is less than 0.2 dB. The RMS attenuation error is less than 0.45 dB and the RMS parasitic phase error is less than 2.4°. The size of the chip is 3.5 mm × 4.5 mm