[Key techniques for granulation and flavor masking of innovative Chinese medicinal preparations for children: a review].

There are many kinds of pharmaceutical preparations for children in China, which are generally divided into oral solid preparations and oral liquid preparations. Solid preparations, such as microtablets, pellets, dispersible tablets, and fine granules, have become the development trend of pediatric drugs. Liquid preparations mainly include syrup, suspension, oral solution, and drops. The poor taste and the treatment of drugs in children of different ages are the key factors affecting the efficacy, safety, and compliance of pediatric drugs. To reduce the risk caused by the fluctuation of blood concentration and improve the oral compliance of pediatric drugs, it is urgent to develop new techniques for granulation and flavor maskingto improve the poor taste of solid preparations. For liquid pre-parations with poor taste, the flavor correction technique should be used. This paper summarized the new pharmaceutical techniques for granulation and flavor masking, and it was found that sustained/controlled-releasegranules, fine granules, and chewing solid mini-tablets became the mainstream of oral solid preparations for children. Generally, multiparticle preparation, coating, microencapsulation, and other granulating techniques were involved in these preparations. Granulation and flavor masking are closely related and synergetic. Flavor masking techniques mask the bitter taste of Chinese medicine from four aspects, including confusing the brain taste, changing the compounds, reducing the exposure of bitter molecules to bitter receptors in the mouth, and numbing the taste cells to increase the threshold of bitter perception. At present, the main drugs for children on the market mainly inhibit the oral release of bitter drugs.

Nested dynamic network data envelopment analysis models with infinitely many decision making units for portfolio evaluation.

Portfolio performance evaluation is a major data envelopment analysis (DEA) application in the finance field. Most proposed DEA approaches focus on single-period portfolio performance assessment based on aggregated historical data. However, such an evaluation setting may result in the loss of valuable information in past individual time periods, and violate real-world portfolio managers' and investors' decision making, which generally involves multiple time periods. Furthermore, to our knowledge, all proposed DEA approaches treat the financial assets comprising a portfolio as a "black box": thus there is no information about their individual performance. Moreover, ideal portfolio evaluation models should enable the target portfolio to compare with all possible portfolios, i.e., enabling full diversification of portfolios across all financial assets. Hence, this research aims at developing nested dynamic network DEA models, an additive model being nested within a slacks-based measure (SBM) DEA model, that explicitly utilizes the information in each individual time period to fully and simultaneously measure the multi-period efficiency of a portfolio and its comprised financial assets. The proposed nested dynamic network DEA models, referred to as NDN DEA models, are linear programs with conditional value-at-risk (CVaR) constraints, and infinitely many decision making units (DMUs). In conducting the empirical study, this research applies the NDN DEA models to a real-world case study, in which Markov chain Monte Carlo Bayesian algorithms are used to obtain future performance forecasts in today's highly volatile investment environments.

Fructose Metabolism in Tumor Endothelial Cells Promotes Angiogenesis by Activating AMPK Signaling and Mitochondrial Respiration.

Angiogenesis is vital for tumor growth and metastasis. Emerging evidence suggests that metabolic reprogramming in endothelial cells (EC) may affect angiogenesis. Here, we showed that multiple regulators in the fructose metabolism pathway, especially fructose transporter SLC2A5 and fructose-metabolizing enzyme ketohexokinase (KHK), were upregulated in tumor endothelial cells from hepatocellular carcinoma (HCC). In mouse models with hepatoma xenografts or with Myc/sgp53-induced liver cancer, dietary fructose enhanced tumor angiogenesis, tumor growth, and metastasis, which could be attenuated by treatment with an inhibitor of SLC2A5. Furthermore, vessel growth was substantially increased in fructose-containing Matrigel compared with PBS-Matrigel. Inhibiting fructose metabolism in EC cells in vivo using EC-targeted nanoparticles loaded with siRNA against KHK significantly abolished fructose-induced tumor angiogenesis. Fructose treatment promoted the proliferation, migration, and tube formation of ECs and stimulated mitochondrial respiration and ATP production. Elevated fructose metabolism activated AMPK to fuel mitochondrial respiration, resulting in enhanced EC migration. Fructose metabolism was increased under hypoxic conditions as a result of HIF1α-mediated upregulation of multiple genes in the fructose metabolism pathway. These findings highlight the significance of fructose metabolism in ECs for promoting tumor angiogenesis. Restricting fructose intake or targeting fructose metabolism is a potential strategy to reduce angiogenesis and suppress tumor growth. SIGNIFICANCE: Fructose metabolism in endothelial cells fuels mitochondrial respiration to stimulate tumor angiogenesis, revealing fructose metabolism as a therapeutic target and fructose restriction as a dietary intervention for treating cancer.