Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease phenotypes which start with simple steatosis and lipid accumulation in the hepatocytes - a typical histological lesions ...characteristic. It may progress to non-alcoholic steatohepatitis (NASH) that is characterized by hepatic inflammation and/or fibrosis and subsequent onset of NAFLD-related cirrhosis and hepatocellular carcinoma (HCC). Due to the central role of the liver in metabolism, NAFLD is regarded as a result of and contribution to the metabolic abnormalities seen in the metabolic syndrome. Peroxisome proliferator-activated receptors (PPARs) has three subtypes, which govern the expression of genes responsible for energy metabolism, cellular development, inflammation, and differentiation. The agonists of PPARα, such as fenofibrate and clofibrate, have been used as lipid-lowering drugs in clinical practice. Thiazolidinediones (TZDs) - ligands of PPARγ, such as rosiglitazone and pioglitazone, are also used in the treatment of type 2 diabetes (T2D) with insulin resistance (IR). Increasing evidence suggests that PPARβ/δ agonists have potential therapeutic effects in improving insulin sensitivity and lipid metabolism disorders. In addition, PPARs ligands have been considered as potential therapeutic drugs for hypertension, atherosclerosis (AS) or diabetic nephropathy. Their crucial biological roles dictate the significance of PPARs-targeting in medical research and drug discovery. Here, it reviews the biological activities, ligand selectivity and biological functions of the PPARs family, and discusses the relationship between PPARs and the pathogenesis of NAFLD and metabolic syndrome. This will open new possibilities for PPARs application in medicine, and provide a new idea for the treatment of fatty liver and related diseases.
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Highlights • The first study to summarize the global trends in incidence and mortality of NPC. • Decreased NPC incidence with maximum AAPCs of −5.4% in males and −4.1% in females. • Declines in NPC ...mortality rates worldwide with AAPCs varying from −0.8% to −6.5%.
The first enantioselective total synthesis of (−)‐aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly ...enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3‐disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C−H activation conditions.
The enantioselective total synthesis of (−)‐aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. cod=1,5‐cyclooctadiene, Tf=trifluoromethanesulfonyl.
Baseline drift always blurs or even swamps signals and deteriorates analytical results, particularly in multivariate analysis. It is necessary to correct baseline drift to perform further data ...analysis. Simple or modified polynomial fitting has been found to be effective to some extent. However, this method requires user intervention and is prone to variability especially in low signal-to-noise ratio environments. A novel algorithm named adaptive iteratively reweighted Penalized Least Squares (airPLS) that does not require any user intervention and prior information, such as peak detection etc., is proposed in this work. The method works by iteratively changing weights of sum squares errors (SSE) between the fitted baseline and original signals, and the weights of the SSE are obtained adaptively using the difference between the previously fitted baseline and the original signals. The baseline estimator is fast and flexible. Theory, implementation, and applications in simulated and real datasets are presented. The algorithm is implemented in R language and MATLAB, which is available as open source software (http://code.google.com/p/airpls).
Radiofrequency ablation (RFA) is the best choice for curative treatment of hepatocellular carcinoma (HCC) cases not suitable for surgical intervention, but efforts should be made to reduce the risk ...of tumor recurrence. We aimed to investigate the association between nucleos(t)ide analog (NA) therapy for hepatitis B virus (HBV) and the risk of HCC recurrence post‐RFA. Using the Taiwan National Health Insurance Research Database between July 1, 2004 and December 31, 2012, we screened 48,807 patients with newly diagnosed HBV‐related HCC. We identified 850 patients (200 patients who used NAs for more than 90 days and 650 who never used NA post‐RFA) who received RFA as a potentially curative treatment for HCC. Patients in the NA‐treated cohort were randomly matched 1:2 with patients in the untreated cohort by age, sex, cirrhosis, and the time period between RFA and initiation of NA therapy. Finally, 133 patients were recruited in the NA‐treated group and 266 in the untreated group for analysis. Cumulative incidences of and hazard ratios (HRs) for HCC recurrence were analyzed after adjusting for competing mortality. The HCC recurrence rate of the NA‐treated group was significantly lower than that of the untreated group (2‐year recurrence rate: 41.8%; 95% confidence interval CI: 32.9‐50.6 vs. 54.3%; 95% CI: 48.0‐60.6; modified log‐rank test: P < 0.05). In modified Cox's regression analysis, NA therapy was independently associated with a decreased risk of HCC recurrence (HR, 0.69; 95% CI: 0.50‐0.95; P < 0.05). Multivariate stratified analyses verified the association of NA therapy and decreased HCC recurrence in almost all patient subgroups. Conclusion: NA therapy was associated with a decreased risk of HCC recurrence among patients with HBV‐related HCC post‐RFA. (Hepatology 2016;63:1517‐1527)
Despite the promise of immune checkpoint blockade (ICB) therapy against cancer, challenges associated with low objective response rates and severe systemic side effects still remain and limit its ...clinical applications. Here, we described a cold atmospheric plasma (CAP)-mediated ICB therapy integrated with microneedles (MN) for the transdermal delivery of ICB. We found that a hollow-structured MN (hMN) patch facilitates the transportation of CAP through the skin, causing tumor cell death. The release of tumor-associated antigens then promotes the maturation of dendritic cells in the tumor-draining lymph nodes, subsequently initiating T cell-mediated immune response. Anti-programmed death-ligand 1 antibody (aPDL1), an immune checkpoint inhibitor, released from the MN patch further augments the antitumor immunity. Our findings indicate that the proposed transdermal combined CAP and ICB therapy can inhibit the tumor growth of both primary tumors and distant tumors, prolonging the survival of tumor-bearing mice.
Hybrid potassium‐ion capacitors (KICs) show great promise for large‐scale storage on the power grid because of cost advantages, the weaker Lewis acidity of K+ and low redox potential of K+/K. ...However, a huge challenge remains for designing high‐performance K+ storage materials since K+ ions are heavier and larger than Li+ and Na+. Herein, the synthesis of hierarchical Ca0.5Ti2(PO4)3@C microspheres by use of the electrospraying method is reported. Benefiting from the rich vacancies in the crystal structure and rational nanostructural design, the hybrid Ca0.5Ti2(PO4)3@C electrode delivers a high reversible capacity (239 mA h g−1) and superior rate performance (63 mA h g−1 at 5 A g−1). Moreover, the KIC employing a Ca0.5Ti2(PO4)3@C anode and activated carbon cathode, affords a high energy/power density (80 W h kg−1 and 5144 W kg−1) in a potential window of 1.0–4.0 V, as well as a long lifespan of over 4000 cycles. In addition, in situ X‐ray diffraction is used to unravel the structural transition in Ca0.5Ti2(PO4)3, suggesting a two‐phase transition above 0.5 V during the initial discharge and solid solution processes during the subsequent K+ insertion/extraction. The present study demonstrates a low‐cost potassium‐based energy storage device with high energy/power densities and a long lifespan.
A hybrid potassium‐ion capacitor using hierarchical Ca0.5Ti2(PO4)3@C microspheres as anode and activated carbon as cathode is shown. The potassium‐ion storage device delivers a high power density of 5144 W kg−1 at an energy density of 34 W h Kg−1 with a long lifespan of 4000 cycles in the potential range of 1.0–4.0 V.
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