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1.
Nat Commun ; 15(1): 4058, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744836

ABSTRACT

Research on the development of cognitive selectivity predominantly focuses on attentional selection. The present study explores another facet of cognitive selectivity-memory selection-by examining the ability to filter attended yet outdated information in young children and adults. Across five experiments involving 130 children and 130 adults, participants are instructed to use specific information to complete a task, and then unexpectedly asked to report this information in a surprise test. The results consistently demonstrate a developmental reversal-like phenomenon, with children outperforming adults in reporting this kind of attended yet outdated information. Furthermore, we provide evidence against the idea that the results are due to different processing strategies or attentional deployments between adults and children. These results suggest that the ability of memory selection is not fully developed in young children, resulting in their inefficient filtering of attended yet outdated information that is not required for memory retention.


Subject(s)
Attention , Memory , Humans , Female , Male , Adult , Attention/physiology , Child , Memory/physiology , Young Adult , Cognition/physiology , Child, Preschool
2.
Environ Int ; 184: 108480, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38341879

ABSTRACT

1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.


Subject(s)
Ethylene Dichlorides , Melatonin , Testis , Male , Mice , Animals , Pyroptosis , Melatonin/pharmacology , Melatonin/metabolism , Piwi-Interacting RNA , Interferon Regulatory Factor-7/metabolism , Interferon Regulatory Factor-7/pharmacology
4.
Behav Sci (Basel) ; 14(1)2024 Jan 07.
Article in English | MEDLINE | ID: mdl-38247693

ABSTRACT

Flexibly and actively updating expectations based on feedback is crucial for navigating daily life. Previous research has shown that people with schizophrenia (PSZ) have difficulty adjusting their expectations. However, there are studies suggesting otherwise. To explore this further, we used a novel trial-based expectation updating paradigm called attribute amnesia. In the task, the participants needed to report the location of a target stimulus among distractors in pre-surprise trials. In the surprise trial, they were unexpectedly asked to report the identity of the target before reporting its location. Afterward, control trials were conducted whereby the participants were asked the same questions as in the surprise trial. Notably, the surprise trial and control trials were nearly identical, except that the participants expected to be asked about identity information in the control trials but not in the surprise trial. Thus, an improvement in identity reporting accuracy in the control trials in comparison with the surprise trial indicated active updating of expectations. In the current study, a total of 63 PSZ and 60 healthy control subjects (HCS) were enrolled. We found that both the PSZ and the HCS were unable to report information that they had fully attended to (i.e., identity) in the surprise trial. However, both groups showed a significant improvement in reporting identity information even in the first control trial. Critically, there was no significant difference in the magnitude of improvement between the two groups. The current findings indicate that PSZ have the ability to update their expectations as quickly and flexibly as HCS, at least in the context of the current task. The possible factors that might contribute to the discrepancy regarding expectation updating are discussed.

5.
Adv Mater ; 36(6): e2308346, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37924272

ABSTRACT

The development of advanced solar energy technologies, which efficiently convert solar energy to heat and then to electricity, remains a significant challenge in the pursuit of clean energy production. Here, this challenge is addressed by designing a photothermal absorber composed of liquid gallium particles and a natural polyphenol-based coordination ink. The design of this composite takes advantage of the tuneable light absorption properties of the polyphenol inks and can also be applied onto flexible substrates. While the ink utilizes two types of coordination complexes to absorb light at different wavelengths, the liquid gallium particles with high thermal and electrical properties provide enhanced thermoelectric effect. As such, the photothermal composite exhibits a broad-spectrum light absorption and highly efficient solar-to-heat conversion. A thermoelectric generator coated with the photothermal composite exhibits an impressive voltage output of ≈185.3 mV when exposed to 1 Sun illumination, without requiring any optical concentration, which sets a new record for a power density at 345.5 µW cm-2 . This work showcases the synergistic combination of natural compound-based light-absorbing coordination complexes with liquid metals to achieve a strong photothermal effect and their integration into thermoelectric devices with powerful light harvesting capabilities.

6.
ACS Nano ; 17(24): 25532-25541, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38054450

ABSTRACT

The production of aluminum (Al) metal-organic frameworks (MOFs) by electrosynthesis using solid-state Al electrodes always faces significant challenges due to the formation of a passivating aluminum oxide layer in the process. Here, we developed a liquid-metal-based method to electrosynthesize an aluminum Al-MOF (MIL-53). This method uses a liquid-state gallium (Ga) anode as a reservoir and activator for a light metal, Al, in the form of Al-Ga alloys that releases Al3+ for the electrosynthesis of Al-MOFs. Introducing Ga into the system inhibits the formation of aluminum oxide passivation layer and promotes the electrochemical reaction for Al-MOF synthesis. The electrosynthesis using liquid Al-Ga alloy is conducted at ambient temperatures for long durations without requiring pretreatment for aluminum oxide removal. We show that the Al-MOF products synthesized from 0.40 wt % Al in liquid Ga lead to the highest crystallinity and possess a specific surface area greater than 800 m2 g-1 and a low capacity for CO2 adsorption that can be used as a potential matrix for CO2/N2 separation. This work provides evidence that employing liquid-metal electrodes offers a viable pathway to circumvent surface passivation effects that inevitably occur when using conventional solid metals. It also introduces an efficient electrosynthesis method based on liquid metals for producing atomically porous materials.

7.
ACS Nano ; 17(17): 17070-17081, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37590207

ABSTRACT

Metallic nanoarchitectures hold immense value as functional materials across diverse applications. However, major challenges lie in effectively engineering their hierarchical porosity while achieving scalable fabrication at low processing temperatures. Here we present a liquid-metal solvent-based method for the nanoarchitecting and transformation of solid metals. This was achieved by reacting liquid gallium with solid metals to form crystalline entities. Nanoporous features were then created by selectively removing the less noble and comparatively softer gallium from the intermetallic crystals. By controlling the crystal growth and dealloying conditions, we realized the effective tuning of the micro-/nanoscale porosities. Proof-of-concept examples were shown by applying liquid gallium to solid copper, silver, gold, palladium, and platinum, while the strategy can be extended to a wider range of metals. This metallic-solvent-based route enables low-temperature fabrication of metallic nanoarchitectures with tailored porosity. By demonstrating large-surface-area and scalable hierarchical nanoporous metals, our work addresses the pressing demand for these materials in various sectors.

10.
ACS Appl Mater Interfaces ; 14(26): 30112-30123, 2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35737904

ABSTRACT

Understanding the interfacial contacts between liquid metals and substrate materials is becoming increasingly important for the fast-rising liquid metal-enabled technologies. However, for such technologies, probing the contact behavior and interfacial charge transport has remained challenging due to the deformable nature of liquid metals and the presence of the surface oxide layer. Here, we encapsulate eutectic gallium indium (EGaIn) micro-/nanodroplets with tungsten trioxide (WO3) nanoparticles to form a WO3/EGaIn liquid metal marble network, in which the interfacial contact of the intrinsically semiconducting WO3 governs the charge transport. We investigate the interfacial structures and charge transport characteristics under different contact conditions and various gaseous environments. The results suggest that establishing a WO3/EGaIn heterostructure leads to near-ohmic contact behaviors and also the emergence of localized surface plasmon resonance. Density functional theory calculations of the WO3/EGaIn interface support the experiments by revealing atomistic attractions between EGaIn alloy and the O atoms from WO3, resulting in a Fermi level shift. We also show that the efficient interfacial charge transport of the liquid metal marble network results in an enhanced gas-sensing response. This work paves the way for the possibility of studying other liquid metal/semiconductor contacts for applications in soft electronics and optics.

11.
Toxicol Lett ; 322: 87-97, 2020 Apr 01.
Article in English | MEDLINE | ID: mdl-31935479

ABSTRACT

1,2-Dichloroethane (1,2-DCE) is a widely used chlorinated organic toxicant, but little is known about the cerebellar dysfunction induced by excessive exposure to it. To uncover 1,2-DCE-induced neurotoxicity in cerebellar granular cells (CGCs), and to investigate the underlying mechanisms, we explored this, both in vitro and in vivo. Our findings showed significant cell viability inhibition in human CGCs (HCGCs) treated with 1,2-DCE. Flow cytometry and mitochondrial membrane potential analyses discovered an increase in apoptotic-mediated cell death in HCGCs after 1,2-DCE treatment. This HCGC apoptosis was involved in the increases of protein expression in Cytochrome c, Caspase-3, Bad, Bim, transformation related protein 53, Caspase-8, tumor necrosis factor-α, and Survivin. Quantitative real-time PCR (qPCR) and western blot confirmed the increases in Cytochrome c, Caspase-3, cleaved Caspase-3, and Bad in HCGCs after 1,2-DCE treatment. Bax inhibitor peptide V5 rescued 1,2-DCE-induced HCGC apoptosis. Furthermore, 80 CD-1 male mice were exposed to 1,2-DCE by inhalation at 0, 100, 350, and 700 mg/m3 for 6 h/day for 4 weeks. An open field test found abnormal neurobehavioral changes in the mice exposed to 1,2-DCE. Histopathological examination showed significantly shrunken and hypereosinophilic cytoplasm with nuclear pyknosis in mouse CGCs from the 700 mg/m3 1,2-DCE group. TdT-mediated dUTP nick-end labeling assay verified significant increases in apoptotic positive cells in the mouse CGCs after 1,2-DCE exposure. We confirmed the increases in the expressions of Cytochrome c, Caspase-3, cleaved Caspase-3 and Bad in the mice exposed to 1,2-DCE. These findings suggest that 1,2-DCE exposure can induce CGC apoptosis and cerebellar dysfunction, at least in part, through mitochondrial pathway.


Subject(s)
Apoptosis/drug effects , Cerebellum/drug effects , Ethylene Dichlorides/toxicity , Mitochondria/drug effects , Neurons/drug effects , Animals , Apoptosis Regulatory Proteins/metabolism , Behavior, Animal/drug effects , Cells, Cultured , Cerebellum/metabolism , Cerebellum/pathology , Cerebellum/physiopathology , Humans , Locomotion/drug effects , Male , Membrane Potential, Mitochondrial/drug effects , Mice , Mitochondria/metabolism , Mitochondria/pathology , Neurons/metabolism , Neurons/pathology , Risk Assessment , Signal Transduction
12.
ACS Appl Mater Interfaces ; 11(17): 15478-15488, 2019 May 01.
Article in English | MEDLINE | ID: mdl-30950258

ABSTRACT

To enhance the removal of the negatively charged organophosphorus pesticide (OPP) glyphosate (GLY), we prepared a positively charged MnFe2O4@cellulose activated carbon (CAC) hybrid by immobilizing MnFe2O4 nanoparticles on the CAC surface via a simple one-pot solvothermal method, scanning electron microscopy, BET, transmission electron microscopy, IR, Raman, X-ray diffraction, and X-ray photoelectron spectroscopy analysis which proved the successful synthesis of MnFe2O4 with a particle size of 100-300 nm. The particles were distributed on the surface of CAC to form the MnFe2O4@CAC hybrid. MnFe2O4@CAC exhibited a positive charge at pH below 6 and had good magnetic properties and dispersion stability. The maximum GLY adsorption capacity of MnFe2O4@CAC (167.2 mg/g) was much higher than that of CAC (61.44 mg/g) and MnFe2O4 nanoparticles (93.48 mg/g). The adsorption process was dominated by chemisorption, and the formation of new chemical bonds between GLY and MnFe2O4 was confirmed by simulations. The newly formed chemical bonds were attributed to the conjugation between p electrons of the adsorbent and the d electrons of the adsorbate. Collectively, the results indicate that the as-prepared MnFe2O4@CAC is promising for anionic pollutant adsorption and the removal of OPPs, and our mechanistic results are of guiding significance in environmental cleanup.

13.
J Phys Chem A ; 123(17): 3718-3727, 2019 May 02.
Article in English | MEDLINE | ID: mdl-30986063

ABSTRACT

Heavy metal pollution in farmland soil reduces crop yield and quality and also potentially causes the crisis to human health. Formerly, the fact that silicon fertilizer could effectively reduce the residual concentration of heavy metal in crops has been identified at the tissue level. In this paper, molecular dynamics simulation was employed to investigate the effects of the degree of silicification of silicic acids [namely, the molar ratio of Si(OH)4 and SiO2] on the Cd(II) bound in the aspect of radial distribution functions and mean square displacements. The results demonstrated that Si(OH)4 attracted Cd(II) through the coordination, while SiO2 attracted Cd(II) by the adsorption. In particular, when the degree of silicification was 0, both the bound Cd(II) amount and strength were the maximum value, indicating that the silicon fertilizer had the best efficiency of Cd(II) bound as Si(OH)4. By comparing the adsorption energy and electronic transfer of Cd(II) and Si(OH)4 adsorption onto the SiO2 surface through the quantum chemical simulation, we concluded that Cd(II) adsorption onto the SiO2 surface was chemisorption, while the Si(OH)4 adsorption onto SiO2 surface was physisorption. Consequently, the adsorption capacity of Cd(II) on the SiO2 surface was higher than that of Si(OH)4 adsorption on the SiO2 surface. Moreover, the compact hydration layers around Cd(II) prevented the process of Cd(II) adsorption on the SiO2 surface; even so, the counterion Cl- in the system promoted the adsorption process. The mechanism of silicon fertilizer binding heavy metal Cd(II) was investigated and revealed at the molecular and electronic level. This work has expanded the possibility of theoretical guidance for the design of silicon fertilizer.

14.
Chemosphere ; 224: 509-518, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30831503

ABSTRACT

Heavy metal contamination directly threatened human life and health. In this work, a novel carboxyl, amide, carbonyl sulfide and secondary amino group grafted cellulose derivative adsorbent (modified-cellulose) was prepared in an attempt to remove heavy metal Cd2+. The XRD, FTIR, 13C NMR and XPS results showed that the carboxyl, amide, carbonyl sulfide and secondary amino group were grafted onto the cellulose backbone successfully. Effects of various factors on the adsorption performance were investigated as well as the adsorption mechanism. The Cd2+ adsorption capacity of modified-cellulose was pretty good, up to 401.1 mg/g and with 3 times enhancement. The adsorption process was spontaneous, well described by the Freundlich model (R2 = 0.994), confirmed to the pseudo-second-order model (R2 > 0.997), and mainly controlled by chemisorption. The density functional theory (DFT) calculations indicating that the Cd2+ binding ability of multi-functional groups modified cellulose was stronger than that of single-functional group modified cellulose. The preferential adsorption sites were analyzed based on the frontier orbital theory (FOT), and they were concentrated on the secondary amino groups and carbonyl sulfides. It is foreseeable that the as-prepared modified-cellulose adsorbent has great potential in heavy metal cadmium removal, and our conclusions could provide significant theoretical guidance in the due bioresource utilization.


Subject(s)
Cadmium/isolation & purification , Cadmium/metabolism , Cellulose/chemistry , Quantum Theory , Water Pollutants, Chemical/isolation & purification , Water Pollutants, Chemical/metabolism , Adsorption , Cellulose/metabolism , Hydrogen-Ion Concentration
16.
Toxicology ; 410: 59-64, 2018 12 01.
Article in English | MEDLINE | ID: mdl-30213540

ABSTRACT

Exposure to low-dose benzene may lead to hematotoxicity and cause health problems. Though peripheral blood cell count is widely used in benzene exposure assessment and health risk assessment, the reports regarding the effects of low-dose benzene exposure on blood cell count remain inconsistent. To uncover more sensitive biomarkers for low-dose benzene exposure, our previous study screened out three potential serum proteins-plasminogen (PLG), platelet basic protein (PBP) and apolipoprotein B100 (ApoB100)-as biomarkers from chronic benzene poisoning patients by using proteomic analysis. In the present study, we verify the three serum proteins as biomarkers for the effects of low-dose benzene exposure in a large low-dose benzene exposure population. The study showed that serum PLG increased in benzene exposed workers and was positively correlated with benzene exposure levels. However, no significant changes in serum PBP or ApoB100 were found in the benzene exposed workers. To explore whether the candidate serum proteins are associated with hematotoxicity, the study population was regrouped into two groups, based on their WBC counts. Our results showed that the workers with high serum PLG levels suffered higher risk of WBC abnormalities than did workers with low serum PLG levels. Taken together, these findings indicate that the increase in serum PLG might be associated with low-dose benzene exposure and benzene-induced hematotoxicity. Thus, we suggest serum PLG could be used as a potential biomarker for the effects of low-dose benzene exposure.


Subject(s)
Benzene/toxicity , Biomarkers/analysis , Occupational Exposure/analysis , Plasminogen/analysis , Adult , Apolipoprotein B-100/analysis , Benzene/analysis , Female , Humans , Leukocyte Count , Male , Middle Aged , Risk Assessment , beta-Thromboglobulin/analysis
17.
Mater Sci Eng C Mater Biol Appl ; 82: 1-9, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29025636

ABSTRACT

Increasing target to tumor sites and reducing accumulation at normal tissue sites of anticancer drugs are essential to improve the cancer chemotherapy efficiency. In this study, we have developed a novel pentablock polymeric poly(ethylene glycol)-b-(poly(2-(diethylamino) ethyl methacrylate)-b-poly (hydroxyethyl methacrylate)-g-folic acid)2 [PEG-b-(PDEAEMA-b-PHEMA-g-FA)2] micelles as anticancer drug nanocarrier. The carriers could target tumor cells rapidly, and response to the tumor sites pH to control drug release. The critical micelle concentration (CMC) of the intermediates copolymers was 4.37-7.08mg/L, which indicated that the self-assembled micelles had comparatively good internal circulation stability. The drug loaded micelles were prepared using dialysis method, resulting in an average particle size of below 120nm, and the drug loading content and entrapment efficiency were 21% and 48% respectively. The pH-responsiveness and in vitro drug release of the micelles were studied, and the results showed a higher doxorubicin (DOX) cumulative amount at pH5.0 (~90%) compared to pH7.4 (~20%) owing to the protonation of the tertiary amino groups. In vitro cytotoxicity and endocytosis experiments showed that the tumor-suppressing effect of drug-loaded micelles was close to those of free DOX. The loaded DOX could be delivered into the cancer cells in a short time, and about 80% of the tumor cells were killed after 48h incubation. The results indicate that the pentablock polymeric micelles have the potential to be applied for targeting anticancer drug delivery and control release.


Subject(s)
Folic Acid/chemistry , Polymers/chemistry , Antineoplastic Agents/chemistry , Doxorubicin/chemistry , Drug Delivery Systems/methods , Drug Liberation , Hydrogen-Ion Concentration , Micelles
18.
J Appl Toxicol ; 38(2): 292-303, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28960355

ABSTRACT

The identification of aberrant microRNA (miRNA) expression during chemical-induced hepatic dysfunction will lead to a better understanding of the substantial role of miRNAs in liver diseases. 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to hepatic abnormalities in occupationally exposed populations. To explore whether aberrant miRNA expression is involved in liver abnormalities mediated by 1,2-DCE exposure, we examined alterations in miRNA expression patterns in the livers of NIH Swiss mice after dynamic inhalation exposure to 350 or 700 mg m-3 1,2-DCE for 28 days. Using a microarray chip, we discovered that only mmumiR-451a was significantly upregulated in the liver tissue of mice exposed to 700 mg m-3 1,2-DCE; this finding was validated by quantitative real-time polymerase chain reaction. In vitro study revealed that it was metabolite 2-chloroacetic acid, not 1,2-DCE that resulted in the upregulation of mmu-miR-451a in the mouse AML12 cell line. Furthermore, our data showed that the upregulation of mmu-miR-451a induced by 2-chloroacetic acid could suppress the expression of glycerol kinase and lead to the inhibition of glycerol gluconeogenesis in mouse liver tissue and AML12 cells. These observations provide evidence that hepatic mmu-miR-451a responds to 1,2-DCE exposure and might induce glucose metabolism disorders by suppressing the glycerol gluconeogenesis process.


Subject(s)
Chemical and Drug Induced Liver Injury/genetics , Gluconeogenesis/drug effects , Glycerol Kinase/antagonists & inhibitors , Glycerol/metabolism , MicroRNAs/genetics , Animals , Cell Line , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Ethylene Dichlorides/toxicity , Gene Expression Profiling , Gene Ontology , Gluconeogenesis/genetics , Glucose/metabolism , Liver/drug effects , Liver/metabolism , Mice , Transcriptome , Up-Regulation
19.
Toxicol Sci ; 160(2): 299-314, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28973639

ABSTRACT

1,2-Dichloroethane (1,2-DCE) is a widely used chlorinated organic toxicant but little is known about the reproductive disorders induced by its excessive exposure. To reveal 1,2-DCE-induced male reproductive toxicity and to elucidate the underlying mechanisms, we exposed male National Institutes of Health Swiss mice to 1,2-DCE by inhalation at 0, 100, 350, and 700 mg/m3 for 6 h/day, for 1 and 4 weeks. Our findings showed a significant decrease in body weight with increased testis/body weight ratio, reduced sperm concentration and induced malformation of spermatozoa, and vacuolar degeneration of germ cells in the seminiferous tubules of testes in mice exposed to 1,2-DCE. Cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) and cAMP-response element modulator (CREM) were significantly inhibited by 1,2-DCE. This is consistent with the declines in the transducer of regulated CREB activity 1 and activator of CREM in testis, which results in the decrease in lactate dehydrogenase C and testis-specific kinase 1 in the testes. Moreover, the activation of p53 and Bax with the inhibition of Bcl-2 might be the reason for the upregulation of caspase-3 in the apoptosis, as detected by TdT-mediated dUTP nick-end labeling assay in the testes induced by 1,2-DCE. Finally, elevated testosterone levels were found along with increased levels of gonadotropin-releasing hormone, cAMP, luteinizing hormone (LH), and LH receptors in the testes. These findings suggest that 1,2-DCE inhibits CREM/CREB signaling cascade and subsequently induces apoptosis associated with p53 activation and mitochondrial dysfunction. This also results in induced malformation of spermatozoa, reduced sperm concentration, and pathological impairment of the testes.


Subject(s)
Air Pollutants/toxicity , Cyclic AMP Response Element Modulator/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Ethylene Dichlorides/toxicity , Signal Transduction/drug effects , Spermatogenesis/drug effects , Spermatozoa/drug effects , Testis/drug effects , Animals , Apoptosis/drug effects , Cyclic AMP Response Element Modulator/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Dose-Response Relationship, Drug , Female , Gene Expression Regulation, Enzymologic , Inhalation Exposure , Luteinizing Hormone/blood , Male , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Risk Assessment , Seminiferous Tubules/drug effects , Seminiferous Tubules/metabolism , Seminiferous Tubules/pathology , Sperm Count , Spermatozoa/metabolism , Spermatozoa/pathology , Testis/metabolism , Testis/pathology , Testosterone/biosynthesis , Testosterone/blood , Time Factors
20.
Toxicology ; 380: 38-49, 2017 04 01.
Article in English | MEDLINE | ID: mdl-28189721

ABSTRACT

Excessive exposure to 1,2-Dichloroethane (1,2-DCE), a chlorinated organic toxicant, can lead to liver dysfunction. To fully explore the mechanism of 1,2-DCE-induced hepatic abnormalities, 30 male National Institutes of Health (NIH) Swiss mice were exposed to 0, 350, or 700mg/m3 of 1,2-DCE, via inhalation, 6h/day for 28days. Increased liver/body weight ratios, as well as serum AST and serum ALT activity were observed in the 350 and 700mg/m3 1,2-DCE exposure group mice, compared with the control group mice. In addition, decreased body weights were observed in mice exposed to 700mg/m3 1,2-DCE, compared with control mice. Exposure to 350 and 700mg/m3 1,2-DCE also led to significant accumulation of hepatic glycogen, free fatty acids (FFA) and triglycerides, elevation of blood triglyceride and FFA levels, and decreases in blood glucose levels. Results from microarray analysis indicated that the decreases in glucose-6-phosphatase catalytic subunit (G6PC) and liver glycogen phosphorylase (PYGL) expression, mediated by the activation of AKT serine/threonine kinase 1 (Akt1), might be responsible for the hepatic glycogen accumulation and steatosis. Further in vitro study demonstrated that 2-chloroacetic acid (1,2-DCE metabolite), rather than 1,2-DCE, up-regulated Akt1 phosphorylation and suppressed G6PC and PYGL expression, resulting in hepatocellular glycogen accumulation. These results suggest that hepatic glucose and lipid homeostasis are impaired by 1,2-DCE exposure via down-regulation of PYGL and G6PC expression, which may be primarily mediated by the 2-chloroacetic acid-activated Akt1 pathway.


Subject(s)
Blood Glucose/metabolism , Ethylene Dichlorides/toxicity , Lipid Metabolism/drug effects , Liver/drug effects , Animals , Cell Line , Chemical and Drug Induced Liver Injury/genetics , Down-Regulation , Fatty Acids, Nonesterified/metabolism , Fatty Liver/chemically induced , Fatty Liver/genetics , Glucose-6-Phosphatase/genetics , Glucose-6-Phosphatase/metabolism , Glycogen/metabolism , Glycogen Phosphorylase, Liver Form/genetics , Glycogen Phosphorylase, Liver Form/metabolism , Hepatocytes/drug effects , Hepatocytes/metabolism , Homeostasis , Liver/metabolism , Male , Mice , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Triglycerides/metabolism , Up-Regulation
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