NDUFA12 as a Functional Target of the Anticancer Compound Ertredin in Human Hepatoma Cells As Revealed by Label-Free Chemical Proteomics.

Many attempts have been made to develop new agents that target EGFR mutants or regulate downstream factors in various cancers. Cell-based screening showed that a natural small molecule, Ertredin, inhibited the growth of EGFRvIII mutant cancer cells. Previous studies have shown that Ertredin effectively inhibits anchorage-independent 3D growth of sphere-forming cells transfected with EGFRvIII mutant cDNA. However, the underlying mechanism remains unclear. In this study, we investigated the target protein of Ertredin by combining drug affinity-responsive target stability (DARTS) assays with liquid chromatography-mass spectrometry using label-free Ertredin as a bait and HepG2 cell lysates as a proteome pool. NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 (NDUFA12) was identified as an Ertredin-binding protein that was responsible for its biological activity. The interaction between NDUFA12 and Ertredin was validated by DARTS and cellular thermal shift assays. In addition, the genetic knockdown of the identified target, NDUFA12, was shown to suppress cell proliferation. NDUFA12 was identified as a biologically relevant target protein of Ertredin that is responsible for its antitumor activity, and these results provide insights into the role of NDUFA12 as a downstream factor in EGFRvIII mutants.

Rice straw cover decreases soil erosion and sediment-bound C, N, and P losses but increases dissolved organic C export from upland maize fields as evidenced by δ13C.

Soil surface with crop residue is effective in reducing soil erosion and carbon (C), nitrogen (N), and phosphorus (P) losses from sloping fields. However, there is a high possibility that surface cover increases export of dissolved organic C (DOC) though relevant field studies under natural rainfall are lacking. In this study, the effects of surface cover with rice (Oryza sativa L.) straw on soil and CNP losses in both dissolved and sediment-bound forms from maize (Zea mays L.) fields were investigated under two fertilization levels (standard and double) × two types of runoff experiments (natural rainfall and artificial irrigation). Changes in soil properties including moisture, temperature, nutrients, and C concentration as well as maize yield were also examined. Surface cover decreased soil and total CNP losses by up to 82% across the experimental plots with some exceptions. However, surface cover increased DOC export in both natural (by 68-82% in total across all events) and artificial (by 3-4 fold) runoff, suggesting that crop residue cover may act as a DOC pollution source of water bodies. The contribution of rice straw to DOC, which was calculated using the δ13C of DOC from covered plots (-24.1 to -28.0‰) and control plots (-19.6 to -25.1‰), was 52.5-95.8%. The concentrations of K2SO4-extractable and microbial biomass C of the soils did not differ between covered and control plots, suggesting that DOC produced from rice straw was not incorporated into the soils, but rather, was washed out with surface runoff in this study. Surface cover increased maize growth and yield, particularly in double fertilization plots, through improved soil moisture, temperature, and nutrient conditions. To take full advantage of surface cover with crop residue, a further study on reducing DOC loss from crop residue needs to be conducted.

Fly ash and zeolite decrease metal uptake but do not improve rice growth in paddy soils contaminated with Cu and Zn.

Fly ash (FA) and zeolite (Z) are known to reduce bioavailability of metals in soils via immobilization; however, these amendments may not only immobilize metals such as copper (Cu) and zinc (Zn), but also reduce nitrogen (N) and phosphorus (P) availability in the soils via sorption (for N by Z) and precipitation (for P by FA). This study was conducted to evaluate the effects of application of FA and Z (0, 5, and 10% rate) on the availability of nutrients as well as metals in the metal-contaminated soils cultivated with paddy rice (Oryza sativa L.). Both FA and Z reduced Cu and Zn uptake by rice while increasing metal retention in the soils regardless of the application rates. However, reduced uptake of metals did not translate into increase in rice growth, especially at the 10% of amendment rates, due to decreased nutrient uptake as indicated by higher NH4+ and available P concentration in the soils amended with Z and FA, respectively, which inhibited tillering in the early rice growth period and thus reduced biomass accumulation at maturity. Our results suggest that FA and Z may reduce Cu and Zn uptake by rice in the soils contaminated with the metals; however, the availability of N and P is likely to be co-decreased. We suggest that the capacities of FA and Z to immobilize nutrients as well as metals need to be considered prior to using the amendments in metal-contaminated rice paddies.