The recent rapid accumulation of knowledge on the dynamics and structure of the plasma membrane has prompted major modifications of the textbook fluid-mosaic model. However, because the new data have been obtained in a variety of research contexts using various biological paradigms, the impact of the critical conceptual modifications on biomedical research and development has been limited. In this review, we try to synthesize our current biological, chemical, and physical knowledge about the plasma membrane to provide new fundamental organizing principles of this structure that underlie every molecular mechanism that realizes its functions. Special attention is paid to signal transduction function and the dynamic aspect of the organizing principles. We propose that the cooperative action of the hierarchical three-tiered mesoscale (2-300 nm) domains--actin-membrane-skeleton induced compartments (40-300 nm), raft domains (2-20 nm), and dynamic protein complex domains (3-10 nm)--is critical for membrane function and distinguishes the plasma membrane from a classical Singer-Nicolson-type model.

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Chiral Lewis basic tertiary amines or phosphines can enable properly modified Morita-Baylis-Hillman (MBH) adducts to undergo asymmetric allylic substitutions with a wide range of nucleophiles. In addition, assisted by a Brønsted base, chiral Lewis bases can also catalytically convert modified MBH adducts into allylic ylides, which can be engaged in a variety of asymmetric annulation reactions. This tutorial review will focus on such chiral Lewis base-catalysed asymmetric transformations of MBH adducts, especially those developed over the past five years, allowing for the rapid construction of densely functionalised chiral molecules with high levels of regio- and stereoselectivities.

Living radical polymerization of styrene was conducted in a miniemulsion using TEMPO and the water-soluble initiator potassium persulfate (KPS). The effects of initiator concentration and the TEMPO:KPS ratio on conversion, molecular weight distribution, and particle size were studied. The miniemulsion polymerizations exhibit similar characteristics to bulk living radical systems but with unique features attributable to the heterogeneous nature of the system. There is a strong interaction between the KPS concentration and the TEMPO:KPS ratio, and therefore the effects of changing either variable depend strongly on the value of the other variable. Initiator efficiencies are considerably higher than in conventional KPS-initiated styrene emulsion or miniemulsion polymerizations, while the average number of active radicals per particle (∼10-2) is much lower. Aqueous-phase kinetics and nitroxide partitioning determine the number of chains initiated and therefore also affect the polymerization rate and molecular weight.

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1 The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L-glutamate (MSG) obese rats and to determine whether its lipidlowering effect is mediated through its activation of PPARa. 2 Chiglitazar is a PPARa/g dual agonist.3 The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats. 4 Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets. 5 Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein-cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARa, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. 6 These data suggest that PPARa/g coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARg agonists.

Background: The association between natural killer (NK) cells and survival in colorectal cancer (CRC) patients remains controversial. This study aimed to clarify the prognostic value of peripheral blood NK cells in CRC patients.Methods: A total of 447 CRC patients who underwent radical surgery and chemotherapy were retrospectively analyzed. Cox regression analyses were used to identify independent prognostic indicators. Correlation between NK cell percentage and other clinicopathological features (gender, age, histological grade, tumor stage, immune cells, and inflammatory indicators) was analyzed. The prognostic values of the combinations of NK cell percentage and other clinicopathological features were also determined. Results: Multivariate Cox regression analysis revealed that NK cell percentage in the peripheral blood was an independent prognostic indicator in CRC patients. A higher percentage of NK cells indicated a longer survival time than a lower percentage. NK cell percentage was positively correlated to the T and B lymphocyte counts and negatively correlated to the patients' age and albumin levels. With an area of 0.741 under a receiver operating characteristic curve, NK cells have a moderate predictive value for 3rd-year survival in CRC. This area increased to 0.851 by combining NK cell percentage with the B lymphocyte count. Elderly patients and those at an advanced clinical stage presented a lower percentage of NK cells than younger patients and those at an early clinical stage.Conclusions: This study demonstrated that NK cells in the blood were an independent predictor of survival in CRC patients, and the combined count of NK cells and B lymphocytes could increase the prognostic value.

Aim: To investigate the effect of the peroxisome proliferator-activator receptor (PPAR)-γ agonist, pioglitazone, on insulin resistance in low-dose streptozotocin and high sucrose-fat diet induced obese rats. Methods: Normal female Wistar rats were injected intraperitoneally with low-dose streptozotocin (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28 d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of the treatment, serums were collected for biochemical analysis. Glucose transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression in the liver and skeletal muscle were detected using Western blotting. Results: Significant insulin resistance and obesity were observed in low-dose STZ and high sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment significantly decreased serum insulin, triglyceride and free fatty acid levels, and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone also lowered the lipid contents in the liver and muscles of rats undergoing treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved markedly. The IRS-1 protein contents in the liver and skeletal muscles and the GLUT4 contents in skeletal muscle were elevated significantly. Conclusion: The data suggest that treatment with pioglitazone improves insulin sensitivity in low-dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing effect may be associated with ameliorating lipid metabolism, reducing hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4 protein expression in insulin-sensitive tissues.