Optical substrates for drug-metabolizing enzymes: Recent advances and future perspectives

Drug-metabolizing enzymes(DMEs),a diverse group of enzymes responsible for the metabolic elimination of drugs and other xenobiotics,have been recognized as the critical determinants to drug safety and efficacy.Deciphering and understanding the key roles of individual DMEs in drug metabolism and toxicity,as well as characterizing the interactions of central DMEs with xenobiotics require reliable,practical and highly specific tools for sensing the activities of these enzymes in biological systems.In the last few decades,the scientists have developed a variety of optical substrates for sensing human DMEs,parts of them have been successfully used for studying target enzyme(s)in tissue preparations and living systems.Herein,molecular design principals and recent advances in the development and applications of optical substrates for human DMEs have been reviewed systematically.Furthermore,the challenges and future perspectives in this field are also highlighted.The presented information offers a group of practical approaches and imaging tools for sensing DMEs activities in complex biological systems,which strongly facilitates high-throughput screening the modulators of target DMEs and studies on drug/herb-drug interactions,as well as promotes the fundamental researches for exploring the relevance of DMEs to human diseases and drug treatment outcomes.

Low substrate temperature deposition of transparent and conducting ZnO:Al thin films by RF magnetron sputtering

Transparent and conducting Al-doped ZnO（ZnO：Al） films were prepared on glass substrate using the RF sputtering method at different substrate temperatures from room temperature（RT） to 200 ℃. The structural,morphological, electrical and optical properties of these films were investigated using a variety of characterization techniques such as low angle XRD, Raman spectroscopy, X-ray photoelectron spectroscopy（XPS）, field-emission scanning electron microscopy（FE-SEM）, Hall measurement and UV–visible spectroscopy. The electrical properties showed that films deposited at RT have the lowest resistivity and it increases with an increase in the substrate temperature whereas carrier mobility and concentration decrease with an increase in substrate temperature. Low angle XRD and Raman spectroscopy analysis reavealed that films are highly crystalline with a hexagonal wurtzite structure and a preferred orientation along the c-axis. The FE-SEM analysis showed that the surface morphology of films is strongly dependent on the substrate temperature. The band gap decreases from 3.36 to 3.29 e V as the substrate temperature is increased from RT to 200 ℃. The fundamental absorption edge in the UV region shifts towards a longer wavelength with an increase in substrate temperature and be attributed to the Burstein-Moss shift. The synthesized films showed an average transmission（〉 85%） in the visible region, which signifies that synthesized ZnO：Al films can be suitable for display devices and solar cells as transparent electrodes.

Rationally engineered IR-783 octanoate as an enzyme-activatable fluorogenic tool for functional imaging of h Notum in living systems

As a vital negative regulator of Wnt signaling pathway,human Notum(hNotum)plays a crucial regulatory role in the progression of many human diseases.Deciphering the relevance of h Notum to human diseases requires practical and reliable tools for visualizing h Notum activity in living systems.Herein,an enzyme-activatable fluorogenic tool(IR-783 octanoate)was rationally engineered for sensing and imaging h Notum activity in living systems by integrating computer-aided molecular design and biochemical assays.IR-783 octanoate showed good optical properties,excellent specificity and high binding-affinity towards h Notum(K_(m)=0.98μmol/L).IR-783 octanoate could be well up-taken into the cancerous cells or tumors that over-expressed organic anion transporting polypeptides(OATPs),and then hydrolyzed by cellular h Notum to release free IR-783 ketone,which created brightly fluorescent signals around 646 nm.Further investigations showed that IR-783 octanoate achieved a good performance for in-situ functional imaging of h Notum in both living cells,cancerous tissues and organs.It was also found that some SW620cells with multipolar spindles could be stained by IR-783 octanoate to emit extremely bright signals,suggesting that this agent could be used as a novel visualizing tool for tracing the cells undergoing abnormal cell mitoses.Collectively,this study devises a highly specific fluorogenic tool for in-situ functional imaging of hNotum in living systems,which offers a practical and reliable tool to dynamically track the changes in h Notum activity under various conditions.