Competitive Inhibition Mechanism of Acetylcholinesterase without Catalytic Active Site Interaction: Study on Functionalized C₆₀ Nanoparticles via in Vitro and in Silico Assays

Acetylcholinesterase (AChE) activity regulation by chemical agents or, potentially, nanomaterials is important for both toxicology and pharmacology. Competitive inhibition via direct catalytic active sites (CAS) binding or noncompetitive inhibition through interference with substrate and product entering and exiting has been recognized previously as an AChE-inhibition mechanism for bespoke nanomaterials. The competitive inhibition by peripheral anionic site (PAS) interaction without CAS binding remains unexplored. Here, we proposed and verified the occurrence of a presumed competitive inhibition of AChE without CAS binding for hydrophobically functionalized C₆₀ nanoparticles (NPs) by employing both experimental and computational methods. The kinetic inhibition analysis distinguished six competitive inhibitors, probably targeting the PAS, from the pristine and hydrophilically modified C₆₀ NPs. A simple quantitative nanostructure–activity relationship (QNAR) model relating the pocket accessible length of substituent to inhibition capacity was then established to reveal how the geometry of the surface group decides the NP difference in AChE inhibition. Molecular docking identified the PAS as the potential binding site interacting with the NPs via a T-shaped plug-in mode. Specifically, the fullerene core covered the enzyme gorge as a lid through π–π stacking with Tyr72 and Trp286 in the PAS, while the hydrophobic ligands on the fullerene surface inserted into the AChE active site to provide further stability for the complexes. The modeling predicted that inhibition would be severely compromised by Tyr72 and Trp286 deletions, and the subsequent site-directed mutagenesis experiments proved this prediction. Our results demonstrate AChE competitive inhibition of NPs without CAS participation to gain further understanding of both the neurotoxicity and the curative effect of NPs

Spatiotemporal Distribution and Alpine Behavior of Short Chain Chlorinated Paraffins in Air at Shergyla Mountain and Lhasa on the Tibetan Plateau of China

Pristine high-altitude mountains are ideal areas for studying the potential mechanism behind the long-range transport and environmental behavior of persistent organic pollutants in remote areas. Short chain chlorinated paraffins (SCCPs) are the most complex halogenated contaminants in the environment, and have attracted extensive worldwide interest in recent years. In this study, the spatiotemporal concentrations and distributions of SCCPs in air collected from Shergyla Mountain (located in the southeast of the Tibetan Plateau) and Lhasa were investigated during 2012–2015. Generally, the total SCCP levels at Shergyla Mountain and Lhasa were between 130 and 1300 pg/m³ and 1100–14440 pg/m³, respectively. C₁₀ and C₁₁ components were the most abundant homologue groups, indicating that lighter SCCP homologue groups are capable of relatively long-range atmospheric transport. Relatively high but insignificant atmospheric SCCP concentrations at Shergyla Mountain area and Lhasa were observed from 2013 to 2015 compared with 2012. At Shergyla Mountain, SCCP concentrations on the eastern and western slopes increased with altitude, implying that “mountain cold-trapping” might occur for SCCPs. A back-trajectory model showed that SCCP sources at Shergyla Mountain and Lhasa were primarily influenced by the tropical monsoon from Southwest and South Asia

Influence of E‑Waste Dismantling and Its Regulations: Temporal Trend, Spatial Distribution of Heavy Metals in Rice Grains, and Its Potential Health Risk

Enhanced regulations, centralized dismantling processes, and sophisticated recycling technologies have been implemented in some e-waste dismantling areas in China with regard to environmental and economic aspects since 2005. In this study, rice grain samples were collected from 2006 to 2010 in an e-waste dismantling area to investigate the temporal trends and spatial distribution of As, Cd, Cu, and Pb. Geometric means of As, Cd, Cu, and Pb in rice samples from the e-waste dismantling area were 111, 217, 4676, and 237 ng g^–1, respectively. Levels of Pb showed a significant decreasing trend during the sampling period, whereas the other three elements remained relatively constant or even increased. Concentrations of Cd, Cu, and Pb in the e-waste dismantling area were significantly higher than those in the non-e-waste dismantling area (<i>p</i> < 0.05), which showed a close connection between e-waste dismantling activities and elevated Pb, Cu, and Cd contents. Risk assessment for human via rice consumption indicated that over 60% of the hazard quotient of Cd exceeded 1 in the e-waste dismantling area. Our study implied that stricter implementation of regulatory measures might lead to positive effects in controlling the release of some heavy metals to the environment. However, environmental behaviors differed with geochemical characteristics of individual elements. Further remediation actions to reduce heavy metal pollution to the surrounding environment might still be needed

Differential Accumulation and Elimination Behavior of Perfluoroalkyl Acid Isomers in Occupational Workers in a Manufactory in China

In this study, serum and urine samples were collected from 36 occupational workers in a fluorochemical manufacturing plant in China from 2008 to 2012 to evaluate the body burden and possible elimination of linear and branched perfluoroalkyl acids (PFAAs). Indoor dust, total suspended particles (TSP), diet, and drinking water samples were also collected to trace the occupational exposure pathway to PFAA isomers. The geometric mean concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) isomers in the serum were 1386, 371, and 863 ng mL^–1, respectively. The linear isomer of PFOS, PFOA, and PFHxS was the most predominant PFAA in the serum, with mean proportions of 63.3, 91.1, and 92.7% respectively, which were higher than the proportions in urine. The most important exposure routes to PFAA isomers in the occupational workers were considered to be the intake of indoor dust and TSP. A renal clearance estimation indicated that branched PFAA isomers had a higher renal clearance rate than did the corresponding linear isomers. Molecular docking modeling implied that linear PFOS (<i>n</i>-PFOS) had a stronger interaction with human serum albumin (HSA) than branched isomers did, which could decrease the proportion of <i>n</i>-PFOS in the blood of humans via the transport of HSA

Short Chain Chlorinated Paraffins in Mollusks from Coastal Waters in the Chinese Bohai Sea

As an extremely complex group of persistent organic pollutants (POPs) candidates in the Stockholm Convention, short chain chlorinated paraffins (SCCPs) have been of extensive concern in recent years. In this study, nine bivalve and two gastropod species were collected in 2009 to evaluate the spatial distributions and potential factors influencing the bioaccumulation of SCCPs in mollusks in the Chinese Bohai Sea. The concentrations of ∑ SCCPs in the mollusks were in the range 64.9–5510 ng/g (dry weight) with an average chlorine content of 61.1%. C₁₀ and C₁₁ were the predominant homologue groups of SCCPs, which accounted for about 29.7% and 34.9% of ∑ SCCPs, respectively. Six and seven chlorinated substituents were the main congener groups. Mya arenaria (Mya), Mactra veneriformis (Mac), and Crassostrea talienwhanensis (Oyster, Ost) had higher average concentrations of SCCPs than other species, implying that these bivalves could be used as sentinels to indicate SCCPs contamination in this coastal region. A significant positive linear relationship was found between SCCP concentrations and lipid content of the mollusks, whereas the lipid-normalized SCCP concentrations were negatively linear-related to the trophic levels (TL), which implied that SCCPs did not show biomagnification in mollusks in this region

Remarkable Contamination of Short- and Medium-Chain Chlorinated Paraffins in Free-Range Chicken Eggs from Rural Tibetan Plateau

Rapid social-economic development introduces modern lifestyles into rural areas, not only bringing numerous modern products but also new pollutants, such as chlorinated paraffins (CPs). The rural Tibetan Plateau has limited industrial activities and is a unique place to investigate this issue. Herein we collected 90 free-range chicken egg pool samples across the rural Tibetan Plateau to evaluate the pollution status of CPs. Meanwhile, CPs in related soils, free-range chicken eggs from Jiangxi, and farmed eggs from markets were also analyzed. The median concentrations of SCCPs (159 ng g–1 wet weight (ww)) and MCCPs (1390 ng g–1 ww) in Tibetan free-range chicken eggs were comparable to those from Jiangxi (259 and 938 ng g–1 ww) and significantly higher than those in farmed eggs (22.0 and 81.7 ng g–1 ww). In the rural Tibetan Plateau, the median EDI of CPs via egg consumption by adults and children were estimated to be 81.6 and 220.2 ng kg–1 bw day–1 for SCCPs and 483.4 and 1291 ng kg–1 bw day–1 for MCCPs, respectively. MCCPs might pose potential health risks for both adults and children in the worst scenario. Our study demonstrates that new pollutants should not be ignored and need further attention in remote rural areas

Tris(2,3-dibromopropyl) Isocyanurate, Hexabromocyclododecanes, and Polybrominated Diphenyl Ethers in Mollusks from Chinese Bohai Sea

A novel brominated flame retardant (BFR), tris­(2,3-dibromopropyl) isocyanurate (TBC), as well as hexabromocyclododecanes (HBCDs) and polybrominated diphenyl ethers (PBDEs), were analyzed in 11 species of mollusks collected from nine coastal cities around the Chinese Bohai Sea in 2009 and 2010. The detection frequencies were 100%, 99%, and 77% for PBDEs, HBCDs, and TBC, respectively. Concentrations of ∑HBCDs ranged from below detection limit (nd) to 28.8 ng g^–1 on a dry weight (dw) basis, followed by ∑₁₂PBDE (0.01–20.4 ng g^–1 dw) and TBC (nd–12.1 ng g^–1 dw). Statistically significant linear correlations were found among the three BFRs. Positive correlations were found between BFRs concentrations and lipid content in mollusks. The concentrations tend to decrease with increasing trophic levels of the mollusks, implying trophic dilution rather than biomagnifications of the BFRs in the aquatic food chains of the sampling area. Among the 11 mollusks species, Mytilus edulis showed higher bioaccumulation capability than others and was therefore considered to be an appropriate bioindicator of contamination by the BFRs in the Chinese Bohai Sea, in agreement with its previous selection for the biomonitoring of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). A dramatic decrease in PBDE concentrations in mollusks of the area was found for the time period from 2003 to 2010, with a half-life of only 2.3 ± 1.7 years, reflecting a rapid response of mollusks to the change in pollution of the marine environment

Identification of Tetrabromobisphenol A Allyl Ether and Tetrabromobisphenol A 2,3-Dibromopropyl Ether in the Ambient Environment near a Manufacturing Site and in Mollusks at a Coastal Region

Tetrabromobisphenol A (TBBPA) is one of the most widely used brominated flame retardants (BFRs) and has been frequently detected in the environment and biota. Recent studies have found that derivatives of TBBPA, such as TBBPA bis­(allyl) ether (TBBPA BAE) and TBBPA bis­(2,3-dibromopropyl) ether (TBBPA BDBPE) are present in various environmental compartments. In this work, using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) and liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC–Q-TOF-MS), TBBPA allyl ether (TBBPA AE) and TBBPA 2,3-dibromopropyl ether (TBBPA DBPE) were identified in environmental samples and further confirmed by synthesized standards. Soil, sediment, rice hull, and earthworm samples collected near a BFR manufacturing plant were found to contain these two compounds. In sediments, the concentrations of TBBPA AE and TBBPA DBPE ranged from 1.0 to 346.6 ng/g of dry weight (dw) and from 0.7 to 292.7 ng/g of dw, respectively. TBBPA AE and TBBPA DBPE in earthworm and rice hull samples were similar to soil samples, which ranged from below the method limit of detection (LOD, <0.002 ng/g of dw) to 0.064 ng/g of dw and from below the LOD (<0.008 ng/g of dw) to 0.58 ng/g of dw, respectively. Furthermore, mollusks collected from the Chinese Bohai Sea were used as a bioindicator to investigate the occurrence and distribution of these compounds in the coastal environment. The detection frequencies of TBBPA AE and TBBPA DBPE were 41 and 32%, respectively, and the concentrations ranged from below LOD (<0.003 ng/g of dw) to 0.54 ng/g of dw, with an average of 0.09 ng/g of dw, for TBBPA AE, and from below LOD (<0.008 ng/g of dw) to 1.41 ng/g of dw, with an average of 0.15 ng/g of dw, for TBBPA DBPE