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Palladium Catalyzed Regioselective Cyclization of Arylcarboxylic Acids through Revolutionary Intermediates with Diaryliodonium Salt.
BACKGROUND AND AIM Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) may reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). However, it is not clear whether there is difference in the on-treatment HCC risks between ETV and TDF. METHODS In this retrospective cohort study, we compared the on-treatment HCC incidence of ETV and TDF in 1340 consecutive nucleos(t)ide analog-naïve CHB patients by propensity score (PS) matching analysis. PS was calculated by using age, sex, drinking history, diabetes, liver cirrhosis, hepatitis B e antigen positivity, hepatitis B virus DNA, hepatitis B s antigen titer, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein, albumin, bilirubin, prothrombin time, platelet count, and calendar year of treatment initiation as covariates. The HCC risk was assessed by Cox regression with death and liver transplantation as competing risks in the 11 PS-matched cohorts (n = 596). RESULTS TDF had higher cumulative virologic response (P = 0.027) whereas ETV showed higher AST and ALT normalization rates (P = 0.005 and less then 0.001, respectively) in PS-matched cohorts. HCC risk was similar between ETV and TDF, either by PS-matching analysis (hazard ratio [HR] for TDF over ETV = 2.06, 95% confidence interval [CI] = 0.98-4.33, P = 0.058) or inverse probability of treatment weighting analysis (HR = 1.30, 95% CI = 0.81-2.10; P = 0.276). CONCLUSIONS ETV and TDF treatment was associated with similar risk for HCC development in CHB patients. © 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.Stem water storage capacity and hydraulic capacitance (CS ) play a crucial role in tree survival under drought-stress. To investigate whether CS adjusts to increasing water deficit, variation in stem water content (StWC) was monitored in vivo for 2 years and related to periodical measurements of tree water potential in Mediterranean Quercus ilex trees subjected either to permanent throughfall exclusion (TE) or to control conditions. Seasonal reductions in StWC were larger in TE trees relative to control ones, resulting in greater seasonal CS (154 and 80 kg m-3 MPa-1 , respectively), but only during the first phase of the desorption curve, when predawn water potential was above -1.1 MPa. Below this point, CS decreased substantially and did not differ between treatments ( less then 20 kg m-3 MPa-1 ). The allometric relationship between tree diameter and sapwood area, measured via electrical resistivity tomography, was not affected by TE. Our results suggest that (a) CS response to water deficit in the drought-tolerant Q. ilex might be more important to optimize carbon gain during well-hydrated periods than to prevent drought-induced embolism formation during severe drought stress, and (b) enhanced CS during early summer does not result from proportional increases in sapwood volume, but mostly from increased elastic water. © 2020 John Wiley & Sons Ltd.BACKGROUND AND AIM The presence and severity of upper gastrointestinal mucosal lesions have not been evaluated using esophagogastroduodenoscopy (EGD) in patients receiving ticagrelor plus aspirin or alone after myocardial revascularization. We assessed upper gastrointestinal mucosal injury and the use of proton pump inhibitors (PPIs) in patients receiving 1 year of antiplatelet therapy after coronary artery bypass grafting (CABG). METHODS In this single-center prospective substudy of a randomized trial, 231 patients completing 1-year antiplatelet therapy (ticagrelor 90 mg twice daily plus aspirin 100 mg once daily, ticagrelor 90 mg twice daily, or aspirin 100 mg once daily, in 81, 80, and 70 patients, respectively) after CABG underwent 13 C urea breath testing and EGD. Gastroduodenal lesions were assessed by modified Lanza score, and reflux esophagitis was evaluated according to Los Angeles classification. Additionally, at least one ulcer ≥ 5 mm was separately analyzed. RESULTS Among 231 patients, EGD showed 28 (12.1%) with ulcers ≥ 5 mm, which were detected in 13.6% (11/81) of ticagrelor plus aspirin recipients, 8.8% (7/80) of ticagrelor recipients, and 14.3% (10/70) of aspirin recipients, and 24 (10.4%) had reflux esophagitis. Eighty-eight (38.1%) patients had a positive 13 C urea breath testing after 1 year of treatment, and one patient received eradication therapy during follow up. Nineteen (8.2%) patients received a PPI for ≥ 6 months. CONCLUSIONS Severe upper gastrointestinal mucosal lesions were more frequently observed in patients treated with ticagrelor plus aspirin and aspirin monotherapy than in patients treated with ticagrelor monotherapy for 1 year post-CABG. Prophylactic use of PPIs might be inadequate. © 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is associated with high malignancy rates. Recently, a known deacetylase SIRT1 is discovered in HCC, while its presence is positively correlated with malignancy and metastasis. N6 -methyladenosine (m6 A) is the most prominent modification but the exact mechanisms on how SIRT1 regulates m6 A modification to induce hepatocarcinogenesis remain unclear. CPI-1205 APPROACH & RESULTS Here we demonstrate that SIRT1 exerts oncogenic role by downregulating fat mass and obesity-associated protein (FTO), which is an m6 A demethylase. A crucial component of small ubiquitin-related modifiers (SUMOs) E3 ligase, RANBP2, is activated by SIRT1 and it is indispensable for FTO SUMOylation at Lysine (K)-216 site that promotes FTO degradation. Moreover, Guanine nucleotide-binding protein G (o) subunit alpha (GNAO1) is firstly identified as m6 A downstream targets of FTO and tumor suppressor in HCC, and depletion of FTO by SIRT1 improves m6 A+ GNAO1 and downregulates its mRNA expression. CONCLUSIONS We demonstrate an important mechanism whereby SIRT1 destabilizes FTO, steering the m6 A+ of downstream molecules and subsequent mRNA expression in HCC tumorigenesis. Our findings uncover a novel target of SIRT1 for therapeutic agents to treat HCC. This article is protected by copyright. All rights reserved.
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