NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice. We reversed these changes in db/db mice by administering a peritoneal injection of MitoQ, an antioxidant targeting mtROS. Similar results were observed in human tubular HK-2 cells subjected to high-glucose (HG) conditions and treated with MitoQ. Treating HK-2 cells with MitoQ suppressed the dissociation of TRX from TXNIP and subsequently blocked the interaction between TXNIP and NLRP3, leading to the inhibition of NLRP3 inflammasome activation and IL-1β maturation. The effects of MitoQ were enhanced by pretreatment with TXNIP siRNA and abolished by pretreatment with monosodium urate (MSU) and TRX siRNA in vitro. These results suggest that mitochondrial ROS-TXNIP/NLRP3/IL-1β axis activation is responsible for tubular oxidative injury, which can be ameliorated by MitoQ via the inhibition of mtROS overproduction.

Dicyandiamide (DCD) and 3, 4-dimethypyrazole phosphate (DMPP) are often claimed to be efficient in regulating soil N transformations and influencing plant productivity, but the difference of their performances across field sites is less clear. Here we applied a meta-analysis approach to compare effectiveness of DCD and DMPP across field trials. Our results showed that DCD and DMPP were equally effective in altering soil inorganic N content, dissolve inorganic N (DIN) leaching and nitrous oxide (N2O) emissions. DCD was more effective than DMPP on increasing plant productivity. An increase of crop yield by DMPP was generally only observed in alkaline soil. The cost and benefit analysis (CBA) showed that applying fertilizer N with DCD produced additional revenues of $109.49 ha−1 yr−1 for maize farms, equivalent to 6.02% increase in grain revenues. In comparisons, DMPP application produced less monetary benefit of $15.67 ha−1 yr−1. Our findings showed that DCD had an advantage of bringing more net monetary benefit over DMPP. But this may be weakened by the higher toxicity of DCD than DMPP especially after continuous DCD application. Alternatively, an option related to net monetary benefit may be achieved through applying DMPP in alkaline soil and reducing the cost of purchasing DMPP products.