Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease.

Materials demonstrating a photorefractive effect are principal candidates for numerous applications, including high-density optical data storage, optical image processing, phase conjugated mirrors and lasers, dynamic holography, optical computing, pattern recognition, etc. Considerable progress has been made in the research on photorefractive polymers and composite materials in the last few years. These materials have many advantages over inorganic photorefractive crystals, including large optical nonlinearities, low dielectric constants, low cost and ease of fabrication. A large number of materials, including those exhibiting an extremely large photorefractive effect, have been developed. In addition, a number of interesting phenomena particular to polymeric photorefractive materials have been reported and corresponding mechanisms have been proposed to account for these phenomena. Possible applications of these materials have been explored with the demonstration of a volume holographic storage device based on photorefractive polymers. This paper reviews the latest developments of the young and exciting field of polymeric photorefractive materials.

Chemotherapy is commonly used in the treatment of cancers. However, the mechanism of action of many of these agents is not well understood. We present the synthesis of a two-photon f luorophore (C625) and its biological application when chemically linked to a chemotherapeutic agent (AN-152). By using two-photon laser-scanning microscopy, the drug:f luorophore conjugate can be observed directly as it interacts with receptor-positive cell lines. The results of this project visually show the receptor-mediated entry of AN-152 into the cell cytoplasm and subsequently into the nucleus. These observations will allow for better understanding of the drug's therapeutic mechanism, which is a subject of ongoing research aimed at improving present methods for cancer therapy.Two-photon processes have been drawing a great deal of attention in the last decade because of their wide range of applications. Pioneering works by Rentzepis and coworkers (1-3) have established the utility of two-photon processes in three-dimensional data storage and microfabrication. Twophoton laser-scanning microscopy (4 -7), introduced by Webb's group, has already been shown to be a powerful technique for probing the three-dimensional structure of a cell and to have inherent optical-sectioning capability without any significant interference from autofluorescence. Our recent efforts on design and synthesis of two-photon chromophores have produced highly efficient two-photon up-converters (which emit photons of a frequency higher than that of the absorbed photons); some of them even exhibit up-conversion lasing (8-10). In this paper, we report the synthesis of a two-photon fluorophore, which was coupled to a chemotherapeutic agent and used in optical tracking of its interaction and entrance in to the target cells by two-photon laser-scanning microscopy.Chemotherapy has been used widely in the treatment of cancers. However, the cellular mechanism of these agents is often not well understood. For example, whether certain chemotherapeutic drugs attach to the membrane of a cancer cell, enter the cell, or enter the nucleus affecting the DNA replication process is not well understood. Such an understanding at the cellular and molecular level will be a major advancement in biology and will lead to ways of enhancing the efficacy of chemotherapy.Chemotherapeutic agent AN-152 was made by coupling the cytotoxic agent doxorubicin (Dox) to the luteinizing hormone-releasing hormone (LH-RH) analog, ]LH-RH (11). Its design is based on the fact that specific high-affinity membrane receptors for LH-RH have been found to be expressed in many sex-linked tissue-derived cancers (12) and expressed de novo in many other cancers (13-16). In the last decade, Schally and coworkers (17-20) have developed and tested several cytotoxic LH-RH conjugates in which a wide variety of cytotoxic agents were linked to LH-RH analogs. As one of the most widely used anticancer drugs, Dox has shown to have a broad spectrum of antitumor effects (21). Its complex cytotoxic mechanism has ...

We report the synthesis and characterization of a new, low-T, polymer exhibiting the photorefractive effect. The photorefractive polymer contains a second-order nonlinear optical chromophore, a charge transporting group, and a long aliphatic chain covalently linked to the polymer backbone. A sensitizer (CSO) was molecularly doped into the polymer to facilitate photocharge generation. The photoconductivity, electrooptic (Pockels) effect, and photorefractive properties of the polymer are reported.

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