Janus TMD materials have out-of-plane second harmonic generation behavior with their broken symmetry. It can be tuned and enhanced by patterns of stacking.

Background: Nitrate is one of the most common chemical contaminants of groundwater, and it is an important unqualified factor of rural groundwater in Yantai. In order to assess the risk of exposure to drinking water nitrate for adults and juveniles, in recent years, we monitored the nitrate concentrations in rural drinking water,a model was also used to assess the human health risk of nitrate pollution in groundwater. Methods: From the year 2015 to 2018, the drinking water in rural areas of Yantai was tested according to the "Sanitary Standard for Drinking Water" (GB5749-2006). The principal component analysis was used to analyze the relationship between groundwater chemicals and nitrate. The model was used to assess human health risks of groundwater nitrate through the drinking water and skin contact. Results: A total of 2348 samples were tested during the year 2015-2018.Nitrate and total dissolved solids, total hardness, chloride are all relevant, the above indicators may come from the same source of pollution; The median nitrate content (C EXP50) was 17.8 mg / L; the risk of exposure in each group was ranked as: Juveniles > Adult female > Adult male;the median health risk (HQ 50) for minors and adults exceed 1. Conclusions: The concentrations of nitrate is stable and does not change over time. The high concentration of nitrate in rural areas of Yantai may be the result of the interaction of fertilizers and geological factors. The risk of exposure to nitrate in juveniles and adults is above the limit, so it is necessary to be on the alert for the high levels of nitrate.

Graphical abstract

Histone deacetylase 6 (HDAC6) plays a key role in a variety of neurological disorders, which makes it attractive drug target for the treatment of Alzheimer’s disease, Parkinson’s disease, and memory/learning impairment. The selectivity of HDAC6 inhibitors (sHDAC6Is) are widely considered to be susceptible to the sizes of their Cap group and the physicochemical properties of their linker or zinc-binding group, which makes the discovery of new sHDAC6Is extremely difficult. With the discovery of the distinct selectivity between Trichostatin A (TSA) enantiomers, the chirality residing in the connective units between TSA’s Cap and linker shows a great impact on its selectivity. However, the mechanism underlining (S)-TSA’s selectivity is still elusive, and the way chirality switches the selective (S)-TSA to nonselective (R)-TSA is unknown. In this study, multiple computational approaches were collectively applied to explore, validate, and differentiate the binding modes of two TSA enantiomers in HDACs (especially the HDAC6) at atomic level. First, two nonconservative residues (G200/M205 and Y197/F202 in HDAC1/6) in loop3 and four conservative residues deep inside the hydrophobic binding pocket were discovered as the decisive residues of (S)-TSA’s selectivity toward HDAC6. Then, a novel mechanism underlying the selectivity of (S)-TSA toward HDAC6 was proposed, which was composed of the trigger by two nonconservative residues F202 and M205 in HDAC6 and a subsequently improved fit of (S)-TSA deep inside HDAC6’s hydrophobic binding pocket. TSA enantiomers were used as a molecular probe to explore the mechanism underlying sHDAC6Is’ selectivity in this study. Because of their decisive roles in (S)-TSA’s selectivity to HDAC6, both F202 and M205 in HDAC6 should be especially considered in the discovery of novel sHDAC6Is.