To seek new protoporphyrinogen oxidase (PPO) inhibitors with better
biological activity, a series of novel diphenyl ether derivatives
containing tetrahydrophthalimide were designed based on the principle
of substructure splicing and bioisomerization. PPO inhibition experiments
exhibited that 6c is the most potential compound, with
the half-maximal inhibitory concentration (IC50) value
of 0.00667 mg/L, showing 7 times higher activity than Oxyfluorfen
(IC50 = 0.0426 mg/L) against maize PPO and similar herbicidal
activities to Oxyfluorfen in weeding experiments in greenhouses and
field weeding experiments. In view of the inspected bioactivities,
the structure–activity relationship (SAR) of this series of
compounds was also discussed. Crop selection experiments demonstrate
that compound 6c is safe for soybeans, maize, rice, peanuts,
and cotton at a dose of 300 g ai/ha. Accumulation analysis experiments
showed that the accumulation of 6c in some crops (soybeans,
peanuts, and cotton) was significantly lower than Oxyfluorfen. Current
work suggests that compound 6c may be developed as a
new herbicide candidate in fields.
Since microplastics (MPs) bring the potential risks to human health when plastics are ingested, more needs to be known about the presence and abundance of human ingestion of MPs. To address these issues, we reviewed 108 publications in Web of Science concerning abundances, sources, and analytical methods of MPs in human daily intake including fish, salt, drinking water, beverages, package food, and other food. The results demonstrate that aquatic food products (fish and bivalves) present a wide range of 0–10.5 items/g for bivalves and 0–20 items/individual for fish. Salt data in literatures present a concentration of 0–13,629 particles/kg. Drinking water is also a pathway of MPs exposure to human, presenting a concentration range from 0 to 61 particles/L for tap water and 0 to 6292 MPs/L for bottled water. Besides, MPs have been found in beverages, package food, sugar, honey, vegetables, and fruits. Therefore, human intake of MPs via ingestion is a nonnegligible exposure route.
We have recently shown that acetaminophen induces many of the apoptotic traits in hepatoma cells and lymphocytes (Boulares et al. (2002d). In an effort to further investigate the mechanism by which non-metabolized acetaminophen induces apoptosis, we have now examined the roles of caspase-3, the DNA fragmentation factor, and the poly(ADP-ribose) polymerase-1-regulated Ca 2π and Mg 2π -dependent endonuclease DNAS1L3 in the induction of such death process. This was achieved with the use of MCF-7 cells, a caspase-3-deficient breast adenocarcinoma cell line, thymocytes isolated from DFF45 (the inhibitory and chaperone subunit of the DNA fragmentation factor subunit, DFF40) deficient mice, and HeLa cells, a DNAS1L3-deficient cervical carcinoma cell line. MCF-7 exhibited a marked resistance to acetaminophen treatment. Ectopic expression of human caspase-3 significantly potentiated the cytotoxic effect of acetaminophen and promoted the release of cytochrome c into the cytosol of treated cells suggesting a direct role for caspase-3 in acetaminophen-induced apoptosis. Expression and cleavage of DFF45 were required but not sufficient for acetaminophen-induced internucleosomal DNA fragmentation. DFF45 gene knockout rendered thymocytes resistant against acetaminophen-induced generation of both large and internucleosomal DNA fragments. The treatment of HeLa cells with acetaminophen resulted in internuclesomal DNA fragmentation only after transfection of these cells with a plasmid encoding the DNAS1L3 gene suggesting that this endonuclease is required for acetaminophen-induced internucleosomal DNA fragmentation. DNAS1L3 expression potentiated the cytotoxic effect of acetaminophen in HeLa cells suggesting an active role in the death process induced by this drug. Altogether, these results demonstrate the specific roles of caspase-3, DNA fragmentation factor, and DNAS1L3 in the process of acetaminophen-induced apoptosis in cultured cells.
A digital light modulation microscope (DLMM) that utilizes a digital micromirror device (DMD) on an epifluorescence microscope has been developed to modulate excitation light in spatial and temporal domains for phosphorescence lifetime detection. Local O2 concentration can be inferred through the detected lifetime around an O2-quenching phosphorescent porphyrin microsensor. Combined with microsensor arrays, the DLMM can sequentially address light to each microsensor element to construct a discrete lifetime image or O2 distribution. In contrast to conventional phosphorescence lifetime imaging, the new method eliminates the need for a pulsed light source and a time-gated camera. To demonstrate O2 sensing with lab-on-a-chip devices, an array of 150-mum-diameter micro-wells coated with phosphorescent porphyrin were observed. The locations of the sensor elements were automatically identified though image analysis. The goal of this platform is to measure the O2 consumption of individual cells trapped in the microwells.
The herbicide fomesafen has the advantages of low toxicity and high selectivity, and the target of this compound is protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4). However, this herbicide has a long residual period and can have phytotoxic effects on succeeding crops. To protect maize from fomesafen, a series of thiazole phenoxypyridines were designed based on structure–activity relationships, active substructure combinations, and bioisosterism. Bioassays showed that thiazole phenoxypyridines could improve maize tolerance under fomesafen toxicity stress to varying degrees at a dose of 10 mg·kg−1. Compound 4i exhibited the best effects. After being treated by compound 4i, average recovery rates of growth index exceeded 72%, glutathione content markedly increased by 167% and glutathione S-transferase activity was almost 163% of fomesafen-treated group. More importantly, after being treated by compound 4i, the activity of PPO, the main target enzyme of fomesafen, recovered to 93% of the control level. The molecular docking result exhibited that the compound 4i could compete with fomesafen to bind with the herbicide target enzyme, which consequently attained the herbicide detoxification. The present work suggests that compound 4i could be developed as a potential safener to protect maize from fomesafen.
Understanding the behavior of fluorocarbon surfactants at the air/water interface is crucial for many applications, such as lubricants, paints, cosmetics, and fire-fighting foams. In this study, molecular dynamics (MD) simulations were employed to investigate the microscopic properties of non-ionic fluorocarbon surfactants at the air/water interface. Several properties, including the distribution of head groups, the distribution probability of the tilt angle between hydrophobic tails with respect to the xy plane, and the order parameter of surfactants, were computed to probe the structure of hydrophobic surfactants at the air/water interface. The effects of the monomer structure on interfacial phenomena of non-ionic surfactants were investigated as well. It is observed that the structure of fluorocarbon surfactants at the air/water interface is more ordered than that of hydrocarbons, which is dominated by the van der Waals interaction between surfactants and water molecules. However, replacing one or two CF2 with one or two CH2 group does not significantly influence the interfacial structure, suggesting that hydrocarbons may be promising alternatives to perfluorinated surfactants.
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