工艺改进与绿色制药

通过实例，从创新路线、新方法新技术的应用、叠缩工艺和系统思维4 个方面阐述药物合成工艺改进及其与绿色制药的关系。     

Combination of cell disruption technologies for lipid recovery from dry and wet biomass of Yarrowia lipolytica and using green solvents

This work aims to investigate the efficiency of bead milling combined or not with high-pressure homogenization on the cell disruption and lipid recovery from Yarrowia lipolytica oleaginous yeast. First, a simulation study involving the use of the Hansen solubility parameters’ approach was performed in order to identify, among 41 conventional and “green” solvents, the most promising ones that are able to replace n-hexane for lipid recovery from Y. lipolytica biomass. The results obtained showed that the pre-treatment involving both high-pressure homogenization and bead milling applied sequentially was more performant than that involving bead milling alone. In addition, bead-milling parameters were optimized showing an optimal bead size of 4.9 mm and a processing time of 30 s. Among the tested solvents, isoamyl acetate was selected as the most appropriate “green” solvent, maximizing the lipid extraction, compared to n-hexane. Despite the better performance of the dry route compared to the wet one, promising results were obtained towards 1) minimizing the energy consumed and 2) replacing n-hexane by “green” solvents for lipid recovery from Y. lipolytica yeast.     

Multiple introduction events and artificial long-distance dispersal of the exotic slug Ambigolimax valentianus in Japan

ABSTRACT

The three-band garden slug Ambigolimax valentianus, native to the Iberian Peninsula, is an exotic species distributed worldwide and was introduced to Japan into the 1950s. For control of this slug, it is necessary to elucidate its introduction sources and dispersal patterns since the introduction event occurred. However, knowledge about this slug in Japan remains poor. Thus, we attempted to estimate the origin and dispersal patterns of this slug using genetic approaches. We investigated the genetic diversity of the mitochondrial cytochrome c oxidase subunit I gene across 11 populations of A. valentianus in three prefectures in central Japan. Ten haplotypes were found in the Japanese populations, five of which were haplotypes found in foreign individuals. The same haplotypes were found in all three prefectures, whereas the average haplotype diversity was high across all populations. Significant genetic differentiation was detected among 22 of 55 population pairs, but there was no isolation by distance. These molecular results suggest that multiple introductions to Japan may have occurred in the past such that the founder effect in the early stage of introduction was diluted. Furthermore, long-distance dispersal of A. valentianus would have occurred after introduction into Japan because of human activities rather than natural dispersal.     

Establishment of tight junctions between cells from different animal species and different sealing capacities

Summary Epithelial cells establish tight junctions (TJs) that offer an ample range of transepithelial electrical resistances (TER), in adjustment to physiological requirements. In the present work, we demonstrate that cells from different animal origins, co-cultured in monolayers, can make sealed TJs, suggesting that this structure has a basic universal structure. TJs cannot be established, however, if one of the partners does not normally express TJs, indicating that each neighbor has to contribute its moiety. Furthermore, we observe that clones of the same cell line, with widely different values of TER, do not differ, in the number and length of their junctional trands, suggesting that the difference is due to their ability to express ionic channels traversing their strands. The value of TER achieved in mixed monolayers of cells of the same or different lines is the one that may be expected by taking into account the proportion of each type in the mixture and adding in parallel the electrical resistance that they exhibit in pure monolayers. Therefore, epithelial TJs appear to behave as parallel resistances.     

Mitogenome evidence shows two radiation events and dispersals of matrilineal ancestry from northern coastal China to the Americas and Japan

1. Download : Download high-res image (294KB)
2. Download : Download full-size image

     

Historical biogeography of Heteropterinae skippers via Beringian and post‐Tethyan corridors

Skippers are a species rich and widespread group of butterflies with evolutionary patterns and processes largely unstudied despite some recent efforts. Among Hesperiidae, the subfamily Heteropterinae is a moderately diverse clade comprising ca. 200 species distributed from North to South America and from Africa to the Palearctic region. While some regions are species rich, others are far less diverse. Using anchored phylogenomics, we infer a robust timetree and estimate ancestral ranges to understand the biogeographic history of these skippers. Inferences based on up to 383 exons recover a robust backbone for the subfamily along with the monophyly of all genera. Bayesian divergence time estimates suggest an origin of Heteropterinae in the late Eocene, ca. 40 million years ago. Maximum likelihood ancestral range estimates indicate an origin of the group in the New World. The eastern Palearctic was likely colonized via a Beringian route and a reverse colonization event resulted in two independent and extant American clades. We estimate a vicariant event between Central and South America that significantly predates estimates of the proto‐Caribbean seaway closure, indicating active overwater dispersal in the Oligocene. The colonization of Africa from the east Palearctic is synchronous with the closure of the Tethys Ocean, while the colonization of Madagascar appears to be comparatively recent. Our results shed light on the systematics and biogeography of Heteropterinae skippers and unveil the evolutionary history of a new leaf in the skipper tree‐of‐life.     

Noninvasive treatment of psoriasis and skin rejuvenation using an akermanite-type narrowband emitting phosphor

Psoriasis is a noncontagious, long-lasting skin infection that affects many people around the world. Numerous therapeutic artificial treatments are available for the treatment of psoriasis, such as photodynamic therapy using broadband ultraviolet (UV) lamps, which have harmful effects on human skin. Similarly, the natural healing systems such as sunlight have a higher risk of sunburn and can cause dangerous forms of skin cancer. Significant light emission of a specific wavelength (in the UV range), and phosphor-based devices demonstrate the effectiveness of treating psoriasis without damaging the skin. Gd³⁺-doped calcium magnesium silicate [Ca₂MgSi₂O₇:Gd³⁺,(CMS:Gd³⁺)] phosphor is one of the ideal phosphors that emit specific narrow UV wavelengths for curing psoriasis and is in great demand in the field of dermatology. Photoluminescence analysis at room temperature (~25°C) shows that the synthesized CMS:Gd³⁺ phosphor emits narrowband UV-B light with a peak intensity at 314 nm. Comparative studies of the standard action spectrum of psoriasis with the emission spectrum of the CMS:Gd³⁺ phosphor show that the synthesized phosphor was the most suitable material for treating a variety of diseases, including psoriasis, vitiligo, type-1 diabetes, dental disease, sleep and mood disorders, and other skin diseases.