Organisms have sophisticated subcellular compartments containing enzymes that function in tandem. These confined compartments ensure effective chemical transformation and transport of molecules, and the elimination of toxic metabolic wastes1,2. Creating functional enzyme complexes that are confined in a similar way remains challenging. Here we show that two or more enzymes with complementary functions can be assembled and encapsulated within a thin polymer shell to form enzyme nanocomplexes. These nanocomplexes exhibit improved catalytic efficiency and enhanced stability when compared with free enzymes. Furthermore, the co-localized enzymes display complementary functions, whereby toxic intermediates generated by one enzyme can be promptly eliminated by another enzyme. We show that nanocomplexes containing alcohol oxidase and catalase could reduce blood alcohol levels in intoxicated mice, offering an alternative antidote and prophylactic for alcohol intoxication.

Quinoxalin-2(1H)-one based design and synthesis produced several series of aldose reductase (ALR2) inhibitor candidates. In particular, phenolic structure was installed in the compounds for the combination of antioxidant activity and strengthening the ability to fight against diabetic complications. Most of the series 6 showed potent and selective effects on ALR2 inhibition with IC50 values in the range of 0.032-0.468 μM, and 2-(3-(2,4-dihydroxyphenyl)-7-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid (6e) was the most active. More significantly, most of the series 8 revealed not only good activity in the ALR2 inhibition but also potent antioxidant activity, and 2-(3-(3-methoxy-4-hydroxystyryl)-2-oxoquinoxalin-1(2H)-yl)acetic acid (8d) was even as strong as the well-known antioxidant Trolox at a concentration of 100 μM, verifying the C3 p-hydroxystyryl side chain as the key structure for alleviating oxidative stress. These results therefore suggest an achievement of multifunctional ALR2 inhibitors having both potency for ALR2 inhibition and as antioxidants.

Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti‐human immunodeficiency virus (HIV) drugs and alcohol‐induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir‐boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes. In the RL‐treated cells, ATF6 localization in the Golgi apparatus required for its activation was reduced; this was followed by Golgi fragmentation and dislocation/redistribution of Golgi‐resident enzymes. Severities of Golgi fragmentation induced by other anti‐HIV drugs varied and were correlated with the ER stress response. In the liver of mice fed RL, alcohol feeding deteriorated the Golgi fragmentation, which was correlated with ER stress, elevated alanine aminotransferase, and liver steatosis. The Golgi stress response (GSR) markers GCP60 and HSP47 were increased in RL‐treated liver cells, and knockdown of transcription factor for immunoglobulin heavy‐chain enhancer 3 of the GSR by small interfering RNA worsened RL‐induced cell death. Cotreatment of pharmacological agent H89 with RL inhibited the RL‐induced Golgi enzyme dislocation and ER stress. Moreover, the coat protein complex II (COPII) complexes that mediate ER‐to‐Golgi trafficking accumulated in the RL‐treated liver cells; this was not due to interference of RL with the initial assembly of the COPII complexes. RL also inhibited Golgi fragmentation and reassembly induced by short treatment and removal of brefeldin A. Conclusion: Our study indicates that ER‐to‐Golgi trafficking is disrupted by anti‐HIV drugs and/or alcohol, and this contributes to subsequent ER stress and hepatic injury. (Hepatology Communications 2017;1:122‐139)

No abstract

To develop rainfed agriculture in northern China, we conducted field experiments with three straw mulching rates (0, 6, and 12 t/ha) on two plant types (a compact type, Chaoshi1, and a flat type, Danyu86) during the summer maize-growing season in 2009 and 2010 to study soil moisture content, evapotranspiration, grain yield, and water-use efficiency (WUE). The results indicated that straw mulching could significantly (LSD, P < 0.05) improve soil moisture content at a depth of 20-80 cm below the ground surface during the anthesis-silking stage; however, at maturity, straw mulching decreased the soil moisture content at a depth of 0-60 cm below the ground surface. In 2009, straw mulching at the rate of 12 t/ha significantly (LSD, P < 0.05) increased the evapotranspiration in Chaoshi1 and Danyu86. In 2010, straw mulching at the rate of 6 t/ha significantly (LSD, P < 0.05) increased evapotranspiration in Danyu86 alone. The grain yields of Danyu86 in 2009 and Chaoshi1 in 2010 were significantly (LSD, P < 0.05) higher with straw mulching at the rate of 12 t/ha than on the application of other treatments. Irrespective of whether precipitation was concentrated during the beginning or the latter half of the summer maize growing stage, straw mulching increased the WUE of Chaoshi1, but not of Danyu86. These results indicated that under rainfed conditions in northern China, straw mulching could increase the grain yield and WUE of compact-type maize.