Synthesis and biological characterization of novel rose bengal derivatives with improved amphiphilicity for sono-photodynamic therapy.

Sono-Photodynamic therapy (SPDT) utilizing ultrasound and light has been demonstrated that this novel approach can lower dosage resulting in reduction of the potential side effects caused by sensitizers. Recently, a new formulation of rose bengal (RB) as an intralesional injection has completed clinical trials phase II for PDT treatment of melanoma cancer. However, the inherent unfavorable pharmacological properties of RB hindered its extensive clinical development. With the aim to identify new RB derivatives (RBDs) with enhanced photodynamic and sonodynamic anticancer efficiency, a series of amphiphilic RBDs have been designed, synthesized and biological characterized. Among them, RBD4 significantly improved cellular uptake and enhanced intracellular ROS generation efficiency upon light and ultrasound irradiation, resulting in dramatically improved anticancer potency. Notably, RBD4 has a relative potency similar to sinoporphyrin sodium (DVDMS), indicating its further potential application for SPDT.

Adaptation and selection in the Senecio (Asteraceae) hybrid zone on Mount Etna, Sicily.

Hybrid zone theory provides a powerful theoretical framework for measuring and testing gene flow and selection. The Senecio aethnensis and Senecio chrysanthemifolius hybrid zone on Mount Etna, Sicily, was investigated to identify phenotypic traits under divergent selection and to assess the contributions of intrinsic and extrinsic selection against hybrids to hybrid zone maintenance. Senecio samples from 14 sites across Mount Etna were analyzed for 24 quantitative traits classified into four groups (QTGs), six allozymes and seven simple sequence repeat (SSR) loci to describe patterns of variation throughout the hybrid zone. Narrower cline widths or shifts in cline centre position were observed for three QTGs relative to the molecular clines, indicating that these traits are likely to be under extrinsic environmental selection. Altitude was key to describing species distributions, but dispersal and intrinsic selection against hybrids explained patterns at smaller spatial scales. The hybrid zone was characterized by strong selection against hybrids, high dispersal rates, recent species contact and few loci differentiating QTGs based on indirect measures. These results support the hypothesis that extrinsic and intrinsic selection against hybrids maintains the hybrid zone and species distinctiveness despite gene flow between the two Senecio species on Mount Etna.

Radiation and diversification within the Ligularia-Cremanthodium-Parasenecio complex (Asteraceae) triggered by uplift of the Qinghai-Tibetan Plateau.

The Ligularia-Cremanthodium-Parasenecio (L-C-P) complex of the Tussilagininae (Asteraceae: Senecioneae) contains more than 200 species that are endemic to the Qinghai-Tibetan Plateau in eastern Asia. These species are morphologically distinct; however, their relationships appear complex. A phylogenetic analysis of members of the complex and selected taxa of the tribe Senecioneae was conducted using chloroplast (ndhF and trnL-F) and nuclear (ITS) sequences. Phylogenetic trees were constructed from individual and combined datasets of the three different sequences. All analyses suggested that Doronicum, a genus that has been included in the Tussilagininae, should be excluded from this subtribe and placed at the base of the tribe Senecioneae. In addition, the Tussilagininae should be broadly circumscribed to include the Tephroseridinae. Within the expanded Tussilagininae containing all 13 genera occurring in eastern Asia, Tussilago and Petasites diverged early as a separate lineage, while the remaining 11 genera comprise an expanded L-C-P complex clade. We suggest that the L-C-P clade, which is largely unresolved, most likely originated as a consequence of an explosive radiation. The few monophyletic subclades identified in the L-C-P clade with robust support further suggest that some genera of Tussilagininae from eastern Asia require generic re-circumscriptions given the occurrence of subclades containing species of the same genus in different parts of the phylogentic tree due to homoplasy of important morphological characters used to delimit them. Molecular-clock analyses suggest that the explosive radiation of the L-C-P complex occurred mostly within the last 20 million years, which falls well within the period of recent major uplifts of the Qinghai-Tibetan Plateau between the early Miocene to the Pleistocene. It is proposed that significant increases in geological and ecological diversity that accompanied such uplifting, most likely promoted rapid and continuous allopatric speciation in small and isolated populations, and allowed fixation or acquisition of similar morphological characters within unrelated lineages. This phenomenon, possibly combined with interspecific diploid hybridization because of secondary sympatry during relatively stable stages between different uplifts, could be a major cause of high species diversity in the Qinghai-Tibetan Plateau and adjacent areas of eastern Asia.