A review on polyhydroxyalkanoates synthesis in activated sludge system: the effects of dissolved organic compounds by using anaerobic fermentation liquid from waste activated sludge / 生物工程学报

Polyhydroxyalkanoates (PHA) synthesis by activated sludge using volatile fatty acids (VFAs) in fermentation liquid of excess sludge as carbon source is a hotspot in the field of environmental biotechnology. However, there is no unified conclusion on the effects of non-VFAs, mainly dissolved organic matter (DOM), on PHA production. Thus, this critical review mainly introduces the main characteristics and common analysis methods of DOM in anaerobic fermentation liquid. The effects of DOM on PHA production are analyzed from the aspects of microbiology, metabolic regulation and sludge properties. The results of different studies showed that high concentration of DOM is bad for PHA production, but an appropriate amount of DOM is conducive to the stability of sludge properties, reducing the final PHA purification cost. Finally, suitable strategies were proposed to regulate the PHA synthesis by activated sludge with DOM for PHA production by anaerobic fermentation liquid.

Advances in risk assessment systems from non-clinical to clinical arrhythmia stages / 中国临床药理学与治疗学

The withdrawal of drugs from the market due to serious adverse reactions arising from the risk of cardiac arrhythmia has been a major concern for regulatory authorities in recent years. In 2005, the International Council for the Harmonisation of Registration of Medicinal Products for Human Use (ICH) issued preclinical S7B and clinical E14 guidelines for the evaluation of arrhythmia risk. The former includes in vitro hERG experiments and in vivo animal-based QT studies, while the latter is the TQT study (thorough QT study, TQT study). The high cost and conservative results of TQT studies have led to the introduction of new alternative methods, and the E14 guidelines were revised in 2015 and introduced concentration-QT analysis (C-QTc), based on the PK/PD (pharmacokinetics/pharmacodynamics) concept, by making full use of high-quality double-negative data from the non-clinical phase (double-negative, low risk of hERG tests at high clinical exposure, and low risk of QTc prolongation in vivo QTc study) makes it possible to substitute TQT studies based on specific situations. This article reviews the history of the development of E14 and its latest developments, analyses the specific situations in which C-QT can replace TQT studies through case studies, introduces the preclinical-clinical arrhythmia risk stage assessment system and compares the drug assessment process and decision making under different versions of E14 guidelines, with a view to providing a reference for the arrhythmia risk assessment system in China.