Stable anchoring of single rhodium atoms by indium in zeolite alkane dehydrogenation catalysts.

Maintaining the stability of single-atom catalysts in high-temperature reactions remains extremely challenging because of the migration of metal atoms under these conditions. We present a strategy for designing stable single-atom catalysts by harnessing a second metal to anchor the noble metal atom inside zeolite channels. A single-atom rhodium-indium cluster catalyst is formed inside zeolite silicalite-1 through in situ migration of indium during alkane dehydrogenation. This catalyst demonstrates exceptional stability against coke formation for 5500 hours in continuous pure propane dehydrogenation with 99% propylene selectivity and propane conversions close to the thermodynamic equilibrium value at 550°C. Our catalyst also operated stably at 600°C, offering propane conversions of >60% and propylene selectivity of >95%.

Biphasic Dose-Response of Mn-Induced Mitochondrial Damage, PINK1/Parkin Expression, and Mitophagy in SK-N-SH Cells.

Excessive manganese (Mn) exposure produces neurotoxicity with mitochondrial damage. Mitophagy is a protective mechanism to eliminate damaged mitochondria to protect cells. The aim of this study was to determine the dose-response of Mn-induced mitochondria damage, the expression of mitophagy-mediated protein PINK1/Parkin and mitophagy in dopamine-producing SK-N-SH cells. Cells were exposed to 0, 300, 900, and 1500 µM Mn2+ for 24 h, and ROS production, mitochondrial damage and mitophagy were examined. The levels of dopamine were detected by ELISA and neurotoxicity and mitophagy-related proteins (α-synuclein, PINK1, Parkin, Optineurin, and LC3II/I) were detected by western blot. Mn increased intracellular ROS and apoptosis and decreased mitochondrial membrane potential in a concentration-dependent manner. However, at the low dose of 300 µM Mn, autophagosome was increased 11-fold, but at the high dose of 1500 µM, autophagosome was attenuated to 4-fold, together with decreased mitophagy-mediated protein PINK1/Parkin and LC3II/I ratio and increased Optineurin expression, resulting in increased α-synuclein accumulation and decreased dopamine production. Thus, Mn-induced mitophagy exhibited a novel biphasic regulation: at the low dose, mitophagy is activated to eliminate damaged mitochondria, however, at the high dose, cells gradually loss the adaptive machinery, the PINK1/Parkin-mediated mitophagy weakened, resulting in neurotoxicity.

Structural dynamics of Ru clusters during nitrogen dissociation in ammonia synthesis.

The dynamic evolution of catalyst structures greatly influences the reactivity, especially sub-nanometer clusters, exhibiting complex configurational fluctuation. In the present work, we study the structural dynamics of a Ru19 cluster during the dissociation of N2 and calculate the reaction free energies using ab initio molecular dynamics (AIMD). Our AIMD calculation predicts a peak-shaped reaction entropy curve due to the adsorption-induced phase transition of the Ru19 cluster. The low melting points of sub-nanometer clusters make it possible to activate N2 at low temperatures. This work demonstrates that the dynamic changes of cluster structures have a non-negligible effect on reaction free energy and offer an opportunity for achieving ammonia synthesis under mild conditions.

Size-dependent phase transitions boost catalytic activity of sub-nanometer gold clusters.

The characterization and identification of the dynamics of cluster catalysis are crucial to unraveling the origin of catalytic activity. However, the dynamical catalytic effects during the reaction process remain unclear. Herein, we investigate the dynamic coupling effect of elementary reactions with the structural fluctuations of sub-nanometer Au clusters with different sizes using ab initio molecular dynamics and the free energy calculation method. It was found that the adsorption-induced solid-to-liquid phase transitions of the cluster catalysts give rise to abnormal entropy increase, facilitating the proceeding of reaction, and this phase transition catalysis exists in a range of clusters with different sizes. Moreover, clusters with different sizes show different transition temperatures, resulting in a non-trivial size effect. These results unveil the dynamic effect of catalysts and help understand cluster catalysis to design better catalysts rationally.

Manganese Intoxication Recovery and the Expression Changes of Park2/Parkin in Rats.

Occupational overexposure to manganese (Mn) produces Parkinson's disease-like manganism. Acute Mn intoxication in rats causes dopaminergic neuron loss, impairment of motor activity and reduction of the expression of Park2/Parkin. The expression of Park2/Parkin is also reduced. Whether these changes are reversible after cessation of Mn exposure is unknown, and is the goal of this investigation. Adult male rats were injected with Mn2+ at doses 1 mg/kg and 5 mg/kg in the form of MnCl2·4H2O, every other day for one-month to produce acute Mn neurotoxicity. For a half of rats Mn exposure was suspended for recovery for up to 5 months. Mn neurotoxicity was evaluated by the accumulation of Mn in blood and brain, behavioral activities, dopaminergic neuron loss, and the expression of Park2/Parkin in the blood cells and brain. Dose-dependent Mn neurotoxicity in rats was evidenced by Mn accumulation, rotarod impairments, reduction of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra, decreased level of Park2 mRNA in the blood and brain, and decreased Parkin protein in the brain. After cessation of Mn exposure, the amount of Park2 mRNA in the blood started to increase one month after the recovery. After 5-month of recovery, blood and brain Mn returned to normal, rotarod activity recovered, the reduction of TH-positive dopaminergic neurons ameliorated, and the level of Park2 mRNA in the blood and Park2/Parkin in the midbrain and striatum were returned to the normal. Mn neurotoxicity in rats is reversible after cessation of Mn exposure. The level of Park2 mRNA in the blood could be used as a novel biomarker for Mn exposure and recovery.

Atomic Scale Tracking of Single Layer Oxide Formation: Self-Peeling and Phase Transition in Solution.

Liquid phase electron microscopy (TEM) is used to track the formation of In2 O3 ultrathin nanosheet in solution at atomic scale. This observation reveals that the formation of few atomic layer nanosheet goes through a complicated phase transition process from InCl3 . 3H2 O to In(OH)3 and then to In2 O3 . Interestingly, the intermediate InCl3 . 3H2 O nanosheet can grow via either layer by layer or the strain-driven enation growth from precursor solution. Moreover, in situ TEM results and density functional theory (DFT) calculations demonstrate that the oleylamine is responsible for the self-peeling process. These findings can provide atomic-level insight for the understanding of how 2D nanomaterial grows and transforms in solution.

Size-Sensitive Dynamic Catalysis of Subnanometer Cu Clusters in CO2 Dissociation.

Small cluster catalysts are highly size-dependent and exhibit complex structural dynamic effects during catalytic reactions. Understanding their structural dynamics is of great importance in tuning the catalytic performances of small clusters that widely exist in supported catalysts. However, very little is known about the size dependence of the dynamic effect of small clusters. In this work, we systematically study the free energies and barriers of catalytic dissociation of CO2 at different temperatures on dynamical Cu clusters with different sizes by ab initio molecular dynamics. The reaction shows an abnormal entropic effect on Cu clusters, and more interestingly, it shows size sensitivity. On the Cu7 cluster, the entropy curve shows a reverse peak shape with increasing temperature, and it is surprising to find that it has a complex pulse shape on the Cu19 cluster. The detailed analysis shows that such temperature dependences can be attributable to the nontrivial behaviors of adsorption-induced phase transitions of the subnanometer Cu clusters during the dissociation of CO2. Our work not only demonstrates the complexity of the temperature dependence of the surface reaction on cluster sizes but also provides useful insight into the phase transition catalysis of dynamic clusters.

Molecular origin of negative component of Helmholtz capacitance at electrified Pt(111)/water interface.

Electrified solid/liquid interfaces are the key to many physicochemical processes in a myriad of areas including electrochemistry and colloid science. With tremendous efforts devoted to this topic, it is unexpected that molecular-level understanding of electric double layers is still lacking. Particularly, it is perplexing why compact Helmholtz layers often show bell-shaped differential capacitances on metal electrodes, as this would suggest a negative capacitance in some layer of interface water. Here, we report state-of-the-art ab initio molecular dynamics simulations of electrified Pt(111)/water interfaces, aiming at unraveling the structure and capacitive behavior of interface water. Our calculation reproduces the bell-shaped differential Helmholtz capacitance and shows that the interface water follows the Frumkin adsorption isotherm when varying the electrode potential, leading to a peculiar negative capacitive response. Our work provides valuable insight into the structure and capacitance of interface water, which can help understand important processes in electrocatalysis and energy storage in supercapacitors.

Adsorption-Induced Liquid-to-Solid Phase Transition of Cu Clusters in Catalytic Dissociation of CO2.

Sub-nanometer metal clusters widely existing in catalysts have a large ensemble of metastable isomers that can interconvert during catalytic reactions, exhibiting complex dynamical catalytic effects. In this work, we systematically investigate the temperature dependent structural dynamics of the Cu13 cluster in CO2 dissociation using ab initio molecular dynamics and the free energy calculation method. We find an abnormal entropic effect due to adsorption-induced liquid-to-solid phase transition of the cluster during the course of the elementary dissociation step at transition temperatures. In the dissociation product, the formation of a rigid Cu3O unit decreases the dynamical fluidity of the cluster and increases the melting temperature, causing a decrease in the entropy of the dissociation product. Our work demonstrates the nontrivial effects of surface adsorption on phase transition behaviors of dynamic clusters and offers a new perspective to dynamic catalysis.

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats.

Subacute exposure to manganese (Mn) produced Parkinson's disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1ß, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.

Subnanometer Bimetallic Platinum-Zinc Clusters in Zeolites for Propane Dehydrogenation.

Propane dehydrogenation (PDH) has great potential to meet the increasing global demand for propylene, but the widely used Pt-based catalysts usually suffer from short-term stability and unsatisfactory propylene selectivity. Herein, we develop a ligand-protected direct hydrogen reduction method for encapsulating subnanometer bimetallic Pt-Zn clusters inside silicalite-1 (S-1) zeolite. The introduction of Zn species significantly improved the stability of the Pt clusters and gave a superhigh propylene selectivity of 99.3 % with a weight hourly space velocity (WHSV) of 3.6-54 h-1 and specific activity of propylene formation of 65.5 mol C 3 H 6 gPt -1 h-1 (WHSV=108 h-1 ) at 550 °C. Moreover, no obvious deactivation was observed over PtZn4@S-1-H catalyst even after 13000 min on stream (WHSV=3.6 h-1 ), affording an extremely low deactivation constant of 0.001 h-1 , which is 200 times lower than that of the PtZn4/Al2 O3 counterpart under the same conditions. We also show that the introduction of Cs+ ions into the zeolite can improve the regeneration stability of catalysts, and the catalytic activity kept unchanged after four continuous cycles.

Characterization of bone aluminum, a potential biomarker of cumulative exposure, within an occupational population from Zunyi, China.

OBJECTIVES: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs). METHODS: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al. RESULTS: Median (interquartile range (IQR)) Al measurements were: 15 µg/g dry bone (IQR = 28) for bone Al; 34.9 µg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (ß = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (ß = 0.98, 95% CI: -0.14, 2.1; ß = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant. CONCLUSIONS: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.

The association of bone, fingernail and blood manganese with cognitive and olfactory function in Chinese workers.

Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [ß (95% confidence interval (CI)) = -0.65 (-1.21, -0.09)] and Animal Naming scores [ß (95% CI) = -1.54 (-3.00, -0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [ß (95% CI) = -0.35 (-0.70, -0.006)] and the difference in AVLT scores [ß (95% CI) = -0.40 (-0.77, -0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of the biomarkers were significantly associated with olfactory function.

Cyclic Penta-Twinned Rhodium Nanobranches as Superior Catalysts for Ethanol Electro-oxidation.

Developing active and durable electro-catalysts toward ethanol oxidation reaction (EOR) with high selectivity toward the C-C bond cleavage is an important issue for the commercialization of direct ethanol fuel cell. Unfortunately, current ethanol oxidation electro-catalysts (e.g., Pt, Pd) still suffer from poor selectivity for direct oxidation of ethanol to CO2, and rapid activity degradation. Here we report a facile route to the synthesis of a new kind of cyclic penta-twinned (CPT) Rh nanostructures that are self-supported nanobranches (NBs) built with 1-dimension CPT nanorods as subunits. Structurally, the as-prepared Rh NBs possess high percentage of open {100} facets with significant CPT-induced lattice strains. With these unique structural characteristics, the as-prepared CPT Rh NBs exhibit outstanding electrocatalytic performance toward EOR in alkaline solution. Most strikingly, the selectivity of complete conversion ethanol to CO2 on the CPT Rh NBs is measured to be as high as 14.5 ± 1.1% at -0.15 V, far exceeding that for single-crystal tetrahedral nanocrystals, icosahedral nanocrystals, and commercial Rh black, as well as majority of reported values for Pt or Pd-based electro-catalysts. By combining with density functional theory calculation, the effects of different structural features of Rh on EOR are definitively elucidated. It was found that the large amount of open Rh (100) facets dominantly contribute to the outstanding activity and exceptionally high selectivity, while the additional tensile strain on (100) planes can further boost the catalytic activity by enhancing the adsorption strength and lowering the reaction barrier of dehydrogenation process of ethanol. As a proof of concept, the present work shows that rationally optimizing surface and electronic structure of electro-catalysts by simultaneously engineering their surface and bulk structures is a promising strategy to promote the performance of electro-catalysts.

Theoretical insight into the vibrational spectra of metal-water interfaces from density functional theory based molecular dynamics.

Understanding the structures of electrochemical interfaces at the atomic level is key to developing efficient electrochemical cells for energy storage and conversion. Spectroscopic techniques have been widely used to investigate the structures and vibrational properties of the interfaces. The interpretation of these spectra is however not straightforward. In this work, density functional theory based molecular dynamics simulations were performed to study the vibrational properties of the Pt(111)- and Au(111)-water interfaces. It was found that the specific adsorption of some surface water on Pt(111) leads to a partial charge transfer to the metal, and strong hydrogen bonding with neighbouring water molecules, which resolves the interpretation of the elusive O-H stretching peak at around 3000 cm-1 observed in some experiments.

Reduced expression of PARK2 in manganese-exposed smelting workers.

Manganese (Mn) is widely used in modern industries. Occupational exposure to Mn is known to cause clinical syndromes similar, but not identical to, Parkinson's disease. This human cohort study was designed to investigate if workers exposed to Mn altered the PARK2 gene expression, leading to Mn-induced neurotoxicity. Workers (n=26) occupationally exposed to Mn were recruited from a Mn-iron (Fe) alloy smelter, and control workers (n=20) without Mn-exposure were from an Fe smelter from Zunyi City in China. Subjects were matched with socioeconomic status and background for environmental factors. Metal concentrations were determined by atomic absorption spectrophotometry (AAS). Total RNA from the blood samples was isolated and analyzed by RT-PCR to quantify PARK2. The data showed that Mn concentrations in plasma, red blood cell (RBC) and saliva, and the cumulative Mn-exposure were about 2.2, 2.0, 1.7 and 3.0 fold higher, respectively, in Mn-exposed workers than those in control subjects (p<0.01). The expression of PARK2 in Mn-exposed workers was significantly decreased by 42% as compared to controls (p<0.01). Linear regression analysis further established that the expression of PARK2 mRNA was inversely correlated with Mn levels in plasma, RBC and saliva, as well as the cumulative Mn exposure (p<0.01). Taken together, it seems likely that Mn exposure among smelters may lead to a reduced expression of PARK2, which may partly explain the Mn-induced Parkinsonian disorder.

Vanadium exposure-induced striatal learning and memory alterations in rats.

Occupational and environmental exposure to vanadium has been associated with toxicities in reproductive, respiratory, and cardiovascular systems. The knowledge on whether and how vanadium exposure caused neurobehavioral changes remains incomplete. This study was designed to investigate the changes in learning and memory following drinking water exposure to vanadium, and to conduct the preliminary study on underlying mechanisms. Male Sprague-Dawley rats were exposed to vanadium dissolved in drinking water at the concentration of 0.0, 0.5, 1.0 and 2.0g/L, as the control, low-, medium-, and high- dose groups, respectively, for 12 weeks. The results by the Morris water maze test showed that the time for the testing animal to find the platform in the high exposed group was increased by 82.9% and 49.7%, as compared to animals in control and low-dose groups (p<0.05). There were significantly fewer rats in the medium- and high- dose groups than in the control group who were capable of crossing the platform (p<0.05). Quantitation of vanadium by atomic absorption spectrophotometry revealed a significant dose-dependent accumulation of vanadium in striatum (r=0.931, p<0.01). Histopathological examination further demonstrated a degenerative damage in vanadium-exposed striatum. Interestingly, with the increase of the dose of vanadium, the contents of neurotransmitter ACh, 5-HT and GABA in the striatum increased; however, the levels of Syn1 was significantly reduced in the exposed groups compared with controls (p<0.05). These data suggest that vanadium exposure apparently reduces the animals' learning ability. This could be due partly to vanadium's accumulation in striatum and the ensuing toxicity to striatal structure and synaptic plasticity. Further research is warranted for mechanistic understanding of vanadium-induced neurotoxicity.

Repeated manganese administration produced abnormal expression of circadian clock genes in the hypothalamus and liver of rats.

Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment like Parkinson's disease (PD), and is called as Manganism. Circadian disruption is a non-motor symptom found in PD and Manganism. Clock genes are essential to drive and maintain circadian rhythm, but little is known about Mn exposure on circadian clock genes expression. Both the brain and liver are targets of Mn, we hypothesize that repeated Mn administration could affect clock gene expression in the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally injected Mn2+ 1mg and 5mg/kg as MnCl2·4H2O, every other day for 30 days. Mn neurotoxicity was evaluated by behavioral changes and loss of dopaminergic neurons via immunohistochemistry. The expression of circadian clock genes was determined via RT-qPCR. Repeated Mn administration dose-dependently retarded the body weight gain, impaired the rotarod activity, decreased the number of dopaminergic neurons in the substantia nigra, and activated microglia in the brain. Expressions of circadian core genes brain and muscle Arnt-like protein-1 (Bmal1), locomotor output cycles kaput (Clock) and neuronal PAS domain protein2 (Npas2), and clock feedback gene cryptochrome1 (Cry1), period genes (Per1 and Per2) in the hypothalamus and liver were decreased after exposure to Mn in a dose-dependent manner, while expressions of clock-targeted genes nuclear receptor Rev-Erbα (Nr1d1) and D-box-binding protein (Dbp) were increased. Peripheral clock in the liver appears to be more susceptible to Mn-induced abnormal clock gene expression. In summary, repeated Mn administration produced dysregulation of circadian clock gene expressions in both the brain and liver.

Cross-sectional study of expression of divalent metal transporter-1, transferrin, and hepcidin in blood of smelters who are occupationally exposed to manganese.

BACKGROUND: Manganese (Mn) is widely used in industries including the manufacture of Mn-iron (Fe) alloy. Occupational Mn overexposure causes manganism. Mn is known to affect Fe metabolism; this study was designed to test the hypothesis that workers exposed to Mn may have an altered expression of mRNAs encoding proteins in Fe metabolism. METHODS: Workers occupationally exposed to Mn (n = 71) from a Mn-Fe alloy factory and control workers without Mn-exposure (n = 48) from a pig-iron plant from Zunyi, China, were recruited for this study. Blood samples were collected into Trizol-containing tubes. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis. Metal concentrations were quantified by atomic absorption spectrophotometry. RESULTS: Working environment and genetic background of both groups were similar except for marked differences in airborne Mn concentrations (0.18 mg/m(3) in Mn-Fe alloy factory vs. 0.0022 mg/m(3) in pig-Fe plant), and in blood Mn levels (34.3 µg/L vs. 10.4 µg/L). Mn exposure caused a significant decrease in the expression of divalent metal transporter-1 (DMT1), transferrin (Tf) and hepcidin by 58.2%, 68.5% and 61.5%, respectively, as compared to controls, while the expression of transferrin receptor (TfR) was unaltered. Linear regression analysis revealed that expressions of DMT1, Tf and hepcidin were inversely correlated with the accumulative Mn exposure; the correlation coefficients (r) are -0.47, -0.54, and -0.49, respectively (p < 0.01). CONCLUSION: The data suggest that occupational Mn exposure causes decreased expressions of DMT1, Tf and hepcidin in blood cells; the finding will help understand the mechanism underlying Mn exposure-associated alteration in Fe homeostasis among workers.

Joint neurodevelopmental and behavioral effects of nonylphenol and estradiol on F1 male rats.

The purpose of present study is to examine whether gestational exposure of two major environmental endocrine-disrupting chemicals, nonylphenol (NP) and estradiol (E2), would affect nervous system development of offspring rats and explore the joint effects of NP and E2. After impregnation, dams were assigned to seven groups. The first and second groups received gavage with NP at dose levels of 50 mg/kg/day (NP-L) and 100 mg/kg/day (NP-H); the third and fourth groups were gavaged with E2 at dose levels of 10 µg/kg/day (E2-L) and 20 µg/kg/day (E2-H); the fifth and sixth groups were gavaged with joint NP and E2 [NP 50 mg/kg/day + E2 10 µg/kg/day (NP-E2-L) and NP 100 mg/kg/day+E2 20 µg/kg/day (NP-E2-H)] dissolved in groundnut oil; and the seventh group was orally administered with groundnut oil alone (vehicle control; 2 ml/kg/day), respectively, daily from gestational days 9 to 15 (transplacental exposures). Compared to the control, exclusive NP and E2 treatment groups, joint exposure to NP-E2-L and NP-E2-H has both produced a significant decrease in mean litter size and number of live pups per litter in dams; Offspring rats spent more time to perform cliff-drop aversion reflex, surface righting reflex, air righting reflex, auditory startle, and visual placing; In Morris water maze task, an increased escape latency was presented in offspring rats; In step-down avoidance test, offspring rats jointly exposed to NP and E2 spent more reaction time. Decrease in acetylcholinesterase activity and increase in choline acetyltransferase activity were observed in the hippocampus of offspring rats. Gestational joint exposure to NP and E2 might induce nervous development impairment of offspring rats. Moreover, additive toxic effects of NP and E2 on nervous development have been identified among offspring rats as well.