Pleiotropic Effects of APOB Variants on Lipid Profiles,Metabolic Syndrome,and the Risk of Diabetes Mellitus

Apolipoprotein B (ApoB) plays a crucial role in lipid and lipoprotein metabolism. The effects of APOB locus variants on lipid profiles, metabolic syndrome, and the risk of diabetes mellitus (DM) in Asian populations are unclear. We included 1478 Taiwan Biobank participants with whole-genome sequence (WGS) data and 115,088 TWB participants with Axiom genome-wide CHB array data and subjected them to genotype–phenotype analyses using APOB locus variants. Five APOB nonsynonymous mutations, including Asian-specific rs144467873 and rs13306194 variants, were selected from participants with the WGS data. Using a combination of regional association studies, a linkage disequilibrium map, and multivariate analysis, we revealed that the APOB locus variants rs144467873, rs13306194, and rs1367117 were independently associated with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol levels; rs1318006 was associated with HDL cholesterol levels; rs13306194 and rs35131127 were associated with serum triglyceride levels; rs144467873, rs13306194, rs56213756, and rs679899 were associated with remnant cholesterol levels; and rs144467873 and rs4665709 were associated with metabolic syndrome. Mendelian randomization (MR) analyses conducted using weighted genetic risk scores from three or two LDL-cholesterol-level-associated APOB variants revealed significant association with prevalent DM (p = 0.0029 and 8.2 × 10⁻⁵, respectively), which became insignificant after adjustment for LDL-C levels. In conclusion, these results indicate that common and rare APOB variants are independently associated with various lipid levels and metabolic syndrome in Taiwanese individuals. MR analyses supported APOB variants associated with the risk of DM through their associations with LDL cholesterol levels.     

Compound C Inhibits Renca Renal Epithelial Carcinoma Growth in Syngeneic Mouse Models by Blocking Cell Cycle Progression,Adhesion and Invasion

Compound C (CompC), an inhibitor of AMP-activated protein kinase, reduces the viability of various renal carcinoma cells. The molecular mechanism underlying anti-proliferative effect was investigated by flow cytometry and western blot analysis in Renca cells. Its effect on the growth of Renca xenografts was also examined in a syngeneic BALB/c mouse model. Subsequent results demonstrated that CompC reduced platelet-derived growth factor receptor signaling pathways and increased ERK1/2 activation as well as reactive oxygen species (ROS) production. CompC also increased the level of active Wee1 tyrosine kinase (P-Ser⁶⁴²-Wee1) and the inactive form of Cdk1 (P-Tyr¹⁵-Cdk1) while reducing the level of active histone H3 (P-Ser¹⁰-H3). ROS-dependent ERK1/2 activation and sequential alterations in Wee1, Cdk1, and histone H3 might be responsible for the CompC-induced G2/M cell cycle arrest and cell viability reduction. In addition, CompC reduced the adhesion, migration, and invasion of Renca cells in the in vitro cell systems, and growth of Renca xenografts in the BALB/c mouse model. Taken together, the inhibition of in vivo tumor growth by CompC may be attributed to the blockage of cell cycle progression, adhesion, migration, and invasion of tumor cells. These findings suggest the therapeutic potential of CompC against tumor development and progression.     

The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy

Interleukin-7 (IL-7) is a multipotent cytokine that maintains the homeostasis of the immune system. IL-7 plays a vital role in T-cell development, proliferation, and differentiation, as well as in B cell maturation through the activation of the IL-7 receptor (IL-7R). IL-7 is closely associated with tumor development and has been used in cancer clinical research and therapy. In this review, we first summarize the roles of IL-7 and IL-7Rα and their downstream signaling pathways in immunity and cancer. Furthermore, we summarize and discuss the recent advances in the use of IL-7 and IL-7Rα as cancer immunotherapy tools and highlight their potential for therapeutic applications. This review will help in the development of cancer immunotherapy regimens based on IL-7 and IL-7Rα, and will also advance their exploitation as more effective and safe immunotherapy tools.     

Context retrieval and context change in free recall: Recalling from long-term memory drives list isolation.

Three experiments used the "list-before-the-last" free recall paradigm (Shiffrin, 1970) to investigate retrieval for context and the manner in which context changes. This paradigm manipulates target and intervening list lengths to measure the interference from each list, providing a measure of list isolation. Correct target list recall was only affected by the target list length when participants engaged in recall between the lists, whereas there were effects of both list lengths with other activities. This suggests that the act of recalling drives context change, thus isolating the target list from interference. Correspondingly, incorrect recall of intervening list items was affected only by the length of the intervening list when recall occurred between the lists, but was otherwise affected by both list lengths. Concurrent with these changes in context similarity, there were apparent changes in context retrieval, as indicated by the overall levels of target retrieval versus intervening recall. A multinomial model of sampling and recovery was implemented to assess the adequacy of this account and to quantify context similarity and context retrieval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pressure distributions of gaseous slip flow in straight and uniform rectangular microchannels

This paper presents analytical derivations of the pressure distribution in straight and uniform rectangular microchannels in the slip flow regime and new experimental data in those channels. The flow is to be steady state, two-dimensional, isothermal, and to have negligible transverse velocities with a first order slip boundary condition. The measured pressure distributions of airflows are compared with newly derived analytical results. There is close agreement between the measurements and calculation by the slip flow formula. The dimensionless location of the maximum deviation from the linear pressure distribution is found analytically and compared with the measurements. This dimensionless location of the maximum deviation increases with the increasing pressure ratios in the slip flow regime. The effect of several parameters such as the channel aspect ratio and the Knudsen number on the locations of maximum deviation from linearity are investigated. The nonlinearity of the pressure distribution is also discussed.     

Coherent interaction of atoms with a beam of light confined in a light cage

Controlling coherent interaction between optical fields and quantum systems in scalable, integrated platforms is essential for quantum technologies. Miniaturise...     

Analysis of thinning algorithms using mathematical morphology

A precise definition of digital skeletons and a mathematical framework for the analysis of a class of thinning algorithms, based on morphological set transformation, are presented. A particular thinning algorithm (algorithm A) is used as an example in the analysis. Precise definitions and analyses associated with the thinning process are presented, including the proof of convergence, the condition for one-pixel-thick skeletons, and the connectedness of skeletons. In addition, a necessary and sufficient condition for the thinning process in general is derived, and an algorithm (algorithm B) based on this condition is developed. Experimental results are used to compare the two thinning algorithms, and issues involving noise immunity and skeletal bias are addressed     

Lactobacillus pentosus MJM60383 Inhibits Lipid Accumulation in Caenorhabditis elegans Induced by Enterobacter cloacae and Glucose

Gut microbiota are known to play an important role in obesity. Enterobacter cloacae, a Gram-negative bacterium, has been considered a pathogenic bacterium related to obesity in the gut. In this study, we established an obesity model of C. elegans by feeding E. cloacae combined with a high glucose diet (HGD), which significantly induced lipid accumulation. An anti-lipid mechanism study revealed that the fatty acid composition and the expression level of fat metabolism-related genes were altered by feeding E. cloacae to C. elegans under HGD conditions. Lactic acid bacteria that showed antagonistic activity against E. cloacae were used to screen anti-obesity candidates in this model. Among them, L. pentosus MJM60383 (MJM60383) showed good antagonistic activity. C. eleans fed with MJM60383 significantly reduced lipid accumulation and triglyceride content. The ratio of C18:1Δ9/C18:0 was also changed in C. elegans by feeding MJM60383. In addition, the expression level of genes related to fatty acid synthesis was significantly decreased and the genes related to fatty acid β-oxidation were up-regulated by feeding MJM60383. Moreover, MJM60383 also exhibited a high adhesive ability to Caco-2 cells and colonized the gut of C. elegans. Thus, L. pentosus MJM60383 can be a promising candidate for anti-obesity probiotics. To the best of our knowledge, this is the first report that uses E. cloacae combined with a high-glucose diet to study the interactions between individual pathogens and probiotics in C. elegans.     

Evaluation of physicochemical properties and fermenting qualities of apple wines added with medicinal herbs

To evaluate the possibility for development of apple wine containing medicinal herbs, we have prepared ‘Fuji’ apple (Malus domestica) wines containing pine (Pinus densiflora Siebold et Zuccarini) needle and hwanggi (Radix Astragali)/mistletoe (Viscum album). Normal apple wine was fermented rapidly, but after 40 days fermentation/maturation, the final ethanol content, pH, total acidity, and contents of sugar/organic acid showed similar levels in 3 kinds of apple wines. In other hands, the total phenols content, antocyanins content, and brightness were higher in apple-pine wine and apple-herb wine than in normal apple wine. Apple-herb wine had higher values in total phenol contents, brightness, free amino acid contents, and quenching activity for ABTS free radicals than normal apple wine, and had similar sensory evaluation values with normal apple wine. Taken together, it is supposed that hwanggi and mistletoe might provide functional components to normal apple wine and might be applied to development of functional apple wines.     

Antioxidant potentials of buntan pumelo (Citrus grandis Osbeck) and its ethanolic and acetified fermentation products

The antioxidant potentials of buntan pumelo (Citrus grandis Osbeck) and its fermented products were determined. The essential oil from peel had higher total phenolic (214 mM) and flavonoid (134 mg QE/g of dried material) contents than those of different solvent extracts from fruit pulp. In addition, DPPH free radical-scavenging activity and ferric-reducing antioxidant power values determined for the essential oil were 26.1 ± 1.2% and 2.3 ± 0.3 mM, respectively, which were significantly higher than those of various fruit pulp extracts. The ethanol-fermented products of pumelo juice had higher total phenolic and flavonoid contents than those of fresh juice. For maintenance of the substantial antioxidant properties of pumelo products, ethanol-fermented juice rather than fresh or acetate-fermented juice is recommended. Through correlation analysis, the phenolic compounds in the fermented pumelo products were found to be the major contributors to the free radical-scavenging activity and ferric-reducing power.