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During the development of a pharmaceutical formulation, a powerful tool is needed to extract the key points from the complicated process parameters and material attributes. Artificial neural networks (ANNs), a promising and more flexible modeling technique, can address real intricate questions in a high parallelism and distributed pattern in the manner of biological neural networks. The data mined and analyzing based on ANNs have the ability to replace hundreds of trial and error experiments. ANNs have been used for data analysis by pharmaceutics researchers since the 1990s and it has now become a research method in pharmaceutical science. This review focuses on the latest application progress of ANNs in the prediction, characterization and optimization of pharmaceutical formulation to provide a reference for the further interdisciplinary study of pharmaceutics and ANNs.

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor alpha (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARalpha-induced liver hypertrophy is supported by their ability to predict non-PPARalpha-induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events.

Presents a study that investigated the capability of oligodendrocytes (OLG) in the central nervous system to play a trophic role in the development of the basal forebrain (BF). Assessment of neurotrophin expression; Examination of the influence of OLG on BF cholinergic neurons; Discussion on the trophic effects of an OLG conditioned medium.

Color-stable white organic light-emitting diode (WOLED) with bipolar mixed spacer based on ultrathin non-doped phosphorescent emitting layers was investigated. We find that the location and thickness of Bis(3,5-difluoro-2-(2-pyridyl) phenyl-(2-carboxypyridyl)iridium(III) (FIrPic) play a critical role on the spectral stability. Transient PL lifetime results show that the spectral variations with the driving voltage can be effectively controlled by enhanced energy transfer or weakened energy transfer respectively depending on different location of FIrPic. Meanwhile, green layer, located between blue layer and orange layer, acts an indispensable role in keeping the color stability by alleviating triplet–triplet annihilation and maintaining sequential energy transfer. The most stable spectrum of WOLED can be obtained with the change in Commission Internationale de L’Eclairage coordinates less than (0.001, 0.002) as the luminance increase from 697 cd m−2 to about 16 550 cd m−2 when FIrPic is on anode side. This discovery provides a significant method for achieving high-quality WOLEDs with superior color stability. [ABSTRACT FROM AUTHOR]

Tetra-chromatic (Blue–Green–Red–Orange) white organic light-emitting diodes (WOLEDs) with superior color stability was demonstrated. Strong carrier trapping effects of red dyes cause significant color shift in multi-color WOLEDs. The high color stability here is attributed to the decrease of red dye trapping sites and enhancement of effective energy transfer to red dye while maintaining appropriate exciton concentration near red dye. As luminance increased from 1000 to 10 000 cd m−2, variations in Commission Internationale de L’Eclairage are merely (0.007, 0.007). Furthermore, this color-stable WOLED achieved a color rendering index close to 90 simultaneously. Our work shows the manipulation of red dye is crucial for achieving superior color stability in multi-color WOLEDs. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transition (EMT) is a key process associated with tumor progression and metastasis. To define molecular features associated with EMT states, we undertook an integrative approach combining mRNA, miRNA, DNA methylation, and proteomic profiles of 38 cell populations representative of the genomic heterogeneity in lung adenocarcinoma. The resulting data were integrated with functional profiles consisting of cell invasiveness, adhesion, and motility. A subset of cell lines that were readily defined as epithelial or mesenchymal based on their morphology and E-cadherin and vimentin expression elicited distinctive molecular signatures. Other cell populations displayed intermediate/hybrid states of EMT, with mixed epithelial and mesenchymal characteristics. A dominant proteomic feature of aggressive hybrid cell lines was upregulation of cytoskeletal and actin-binding proteins, a signature shared with mesenchymal cell lines. Cytoskeletal reorganization preceded loss of E-cadherin in epithelial cells in which EMT was induced by TGFβ. A set of transcripts corresponding to the mesenchymal protein signature enriched in cytoskeletal proteins was found to be predictive of survival in independent datasets of lung adenocarcinomas. Our findings point to an association between cytoskeletal and actinbinding proteins, a mesenchymal or hybrid EMT phenotype and invasive properties of lung adenocarcinomas. [ABSTRACT FROM AUTHOR]