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Chiral organophosphorus pollutants are found abundantly in the environment, but the neurotoxicity risks of these asymmetric chemicals to human health have not been fully assessed. Using cellular, molecular, and computational toxicology methods, this story is to explore the static and dynamic toxic actions and its stereoselective differences of chiral isocarbophos toward SH-SY5Y nerve cells mediated by acetylcholinesterase (AChE) and further dissect the microscopic basis of enantioselective neurotoxicity. Cell-based assays indicate that chiral isocarbophos exhibits strong enantioselectivity in the inhibition of the survival rates of SH-SY5Y cells and the intracellular AChE activity, and the cytotoxicity of ( S )-isocarbophos is significantly greater than that of ( R )-isocarbophos. The inhibitory effects of isocarbophos enantiomers on the intracellular AChE activity are dose-dependent, and the half-maximal inhibitory concentrations (IC 50 ) of ( R )-/( S )-isocarbophos are 6.179/1.753 μM, respectively. Molecular experiments explain the results of cellular assays, namely, the stereoselective toxic actions of isocarbophos enantiomers on SH-SY5Y cells are stemmed from the differences in bioaffinities between isocarbophos enantiomers and neuronal AChE. In the meantime, the modes of neurotoxic actions display that the key amino acid residues formed strong noncovalent interactions are obviously different, which are related closely to the molecular structural rigidity of chiral isocarbophos and the conformational dynamics and flexibility of the substrate binding domain in neuronal AChE. Still, we observed that the stable "sandwich-type π-π stacking" fashioned between isocarbophos enantiomers and aromatic Trp-86 and Tyr-337 residues is crucial, which notably reduces the van der Waals' contribution (Δ G vdW ) in the AChE-( S )-isocarbophos complexes and induces the disparities in free energies during the enantioselective neurotoxic conjugations and thus elucidating that ( S )-isocarbophos mediated by synaptic AChE has a strong toxic effect on SH-SY5Y neuronal cells. Clearly, this effort can provide experimental insights for evaluating the neurotoxicity risks of human exposure to chiral organophosphates from macroscopic to microscopic levels.

Ultrathin nanosheets of two-dimensional covalent organic frameworks covered a quartz nanopipette and then acted as a nanopore device for single-molecule DNA sensing. Our results showed that a single DNA homopolymer as short as 6 bases could be detected. The dwell times of 30-mer DNA homopolymers were obviously longer than the times of 10- or 6-mer ones. For different bases, poly(dA) 6 showed the slowest transport speed (∼595 μs/base) compared with cytosine (∼355 μs/base) in poly(dC) 6 and thymine (∼220 μs/base) in poly(dT) 6 . Such translocation speeds are the slowest ever reported in two-dimensional material-based nanopores. Poly(dA) 6 also showed the biggest current blockade (94.74 pA) compared with poly(dC) 6 (79.54 pA) and poly(dT) 6 (71.41 pA). However, the present difference in blockade current was not big enough to distinguish the four DNA bases. Our study exhibits the shortest single DNA molecules that can be detected by COF nanopores at the present stage and lights the way for DNA sequencing based on solid-state nanopores.