Publications by authors named "Lixia Jia"

23 Publications

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Hydrated electrons mediated in-situ construction of cubic phase CdS/Cd thin layer on a millimeter-scale support for photocatalytic hydrogen evolution.

J Colloid Interface Sci 2021 Sep 8;607(Pt 1):769-781. Epub 2021 Sep 8.

TJU-NIMS International Collaboration Laboratory, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin 300072, People's Republic of China; International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.

In this study, non-noble metal Cd decorated cubic phase CdS (CdS/Cd) thin layer on a millimeter-scale chitosan-Mg(OH) xerogel beads (CMB) were elaborately designed and successfully synthesized via facile hydrated electrons (e) assistant strategy. The in-situ formation of metallic Cd was driven by e generated from UV/NaSO process. Owing to metallic Cd, [email protected]/Cd exhibited better visible-light absorption ability and more efficient separation capability for photo-induced carriers, its hydrogen production efficiency was about threefold improved compared to [email protected] Both characterization methods and density functional theory calculations determined a built-in electric field from metallic Cd to CdS and Ohmic-contact between Cd and CdS, which largely promoted the carriers transfer efficiency. Moreover, the introduction of metallic Cd on the CdS could reduce the ΔG, thus greatly boosting the photocatalytic hydrogen production efficiency. This work provides a simple and green approach to construct metallic Cd coupled semiconductor to achieve efficient photocatalytic applications.
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http://dx.doi.org/10.1016/j.jcis.2021.09.039DOI Listing
September 2021

Insight into heavy metals (Cr and Pb) complexation by dissolved organic matters from biochar: Impact of zero-valent iron.

Sci Total Environ 2021 Nov 24;793:148469. Epub 2021 Jun 24.

Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science & Engineering, Shandong University, Qingdao 266237, PR China. Electronic address:

In this study, batch experiments were conducted to investigate the immobilization of HMs (Cr and Pb) by DOM derived from biochar in the presence and absence of zero-valent iron (Fe) in nitrate and HMs co-contaminated groundwater. Both Cr and Pb were removed effectively in biochar-Fe aqueous systems, while only Pb could be mitigated in biochar systems. Excitation-emission spectrophotometry combined with parallel factor analysis (EEM-PARAFAC) revealed that DOM released from biochar mainly contained human-like and tryptophan-like substances. Moreover, the fluorescence of hemic-like components could be quenched differently by the complexation of HMs, which proved the different removal efficiencies of Cr and Pb in biochar aqueous phase. In biochar-Fe aqueous systems, Fe-C micro-electrolysis was formed in prior to the complexation of DOM-Fe hydroxides. Thus, the chemical reduction was the primary way to removal HMs in batch-Fe systems, which was corresponding with the less variation of DOM components when adding Cr and Pb into aqueous systems. Besides, the observed DOM components with higher aromaticity and humification after adding Cr and Pb, further indicated the complexation of DOM-HMs through the analysis of adsorption and fluorescence indices. These results will provide new insights into the HMs retention on biochar, particularly for the role of Fe on the complexation process.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148469DOI Listing
November 2021

Primary root and root hair development regulation by OsAUX4 and its participation in the phosphate starvation response.

J Integr Plant Biol 2021 Aug 28;63(8):1555-1567. Epub 2021 Jul 28.

State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.

Among the five members of AUX1/LAX genes coding for auxin carriers in rice, only OsAUX1 and OsAUX3 have been reported. To understand the function of the other AUX1/LAX genes, two independent alleles of osaux4 mutants, osaux4-1 and osaux4-2, were constructed using the CRISPR/Cas9 editing system. Homozygous osaux4-1 or osaux4-2 exhibited shorter primary root (PR) and longer root hair (RH) compared to the wild-type Dongjin (WT/DJ), and lost response to indoleacetic acid (IAA) treatment. OsAUX4 is intensively expressed in roots and localized on the plasma membrane, suggesting that OsAUX4 might function in the regulation of root development. The decreased meristem cell division activity and the downregulated expression of cell cycle genes in root apices of osaux4 mutants supported the hypothesis that OsAUX4 positively regulates PR elongation. OsAUX4 is expressed in RH, and osaux4 mutants showing longer RH compared to WT/DJ implies that OsAUX4 negatively regulates RH development. Furthermore, osaux4 mutants are insensitive to Pi starvation (-Pi) and OsAUX4 effects on the -Pi response is associated with altered expression levels of Pi starvation-regulated genes, and auxin distribution/contents. This study revealed that OsAUX4 not only regulates PR and RH development but also plays a regulatory role in crosstalk between auxin and -Pi signaling.
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http://dx.doi.org/10.1111/jipb.13142DOI Listing
August 2021

Pilot-scale two-stage constructed wetlands based on novel solid carbon for rural wastewater treatment in southern China: Enhanced nitrogen removal and mechanism.

J Environ Manage 2021 Aug 12;292:112750. Epub 2021 May 12.

Department of Environmental Science, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, PR China. Electronic address:

Constructed wetlands (CWs) have been proved to be an alternative to the treatment of various wastewater. However, there are few studies focused on the removal performance and mechanisms of pollutants in pilot-scale CWs packed with novel solid carbon. In this study, we investigated the effect of poly-3-hydroxybutyrate-co-3-hydroxyvalerate/polyacetic acid (PHBV/PLA) blends as carbon source on pollutant's transformation, microbial communities and functional genes in pilot-scale aeration-anoxic two-stage CWs for polishing rural runoff in southern China. Results showed a striking improvement of TN removal in CWs with PHBV/PLA blends (64.5%) compared to that in CWs with ceramsite (52.9%). NH-N (61.3-64.6%), COD (40.4-53.8%) and TP (43.6-47.1%) were also removed effectively in both two CWs. In addition, the strains of Rhodocyclaceae and Bacteroidetes were the primary denitrifiers on the surface of PHBV/PLA blends. Further, the aerobic stage induced gathering of 16 S and amoA genes and the anoxic zone with PHBV/PLA blends increased the nirS genes, which fundamentally explained the better denitrification performance in CW based on PHBV/PLA blends. Consequently, this study will provide straightforward guidance for the operation of engineering CWs packed with polymers to govern the low-C/N rural wastewater.
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http://dx.doi.org/10.1016/j.jenvman.2021.112750DOI Listing
August 2021

Enhanced pollutant removal from rural non-point source wastewater using a two-stage multi-soil-layering system with blended carbon sources: Insights into functional genes, microbial community structure and metabolic function.

Chemosphere 2021 Jul 20;275:130007. Epub 2021 Feb 20.

Department of Environmental Science, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, PR China. Electronic address:

A two-stage multi-soil-layering system with blended carbon sources (MSL-BCS) was constructed at pilot scale for treatment of rural non-point source wastewater. Results showed the MSL-BCS system had effective removal efficiencies with 64% of TN and 60% of TP, respectively. The addition of BCS could result in higher (1.6-3.1 fold) denitrification gene abundances (nirS and nosZ) for enhancing denitrification. High-throughput sequencing approach revealed that the higher abundance (>50%) of Epsilonbacteraeotra (Genus: Sulfuricurvum, Family: Thiovulaceae, Class: Campylobacteria, Phylum: Epsilonbacteraeota) enriched in the surface of BCS, which suggested that Epsilonbacteraeotra are the keystone species in achieving nitrogen removal through enhancing denitrification at oligotrophic level. KEGG analysis indicated that BCS might release some signaling molecules for enhancing the energy metabolism process, as well as stimulate the enzyme activities of histidine kinase, glycogen phosphorylase and ATPase, and thereby the denitrification processes were strengthened in MSL-BCS system. Consequently, this study could provide some valuable information on the removal performance and mechanism of engineering MSL systems packed with BCS to govern the rural wastewater treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130007DOI Listing
July 2021

Sulfonylurea antidiabetics are associated with lower risk of out-of-hospital cardiac arrest: Real-world data from a population-based study.

Br J Clin Pharmacol 2021 Sep 25;87(9):3588-3598. Epub 2021 Apr 25.

Department of Cardiology, Heart Center, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Aims: Out-of-hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP-regulated K channels (K channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes.

Methods: We conducted a population-based case-control study in 219 VT/VF-documented OHCA cases with diabetes and 697 non-OHCA controls with diabetes. We studied the association of SU drugs (alone or in combination with metformin) with OHCA risk compared to metformin monotherapy, and of individual SU drugs compared to glimepiride, using multivariable logistic regression analysis. We studied the effects of these drugs on APD during simulated ischaemia using patch-clamp studies in human induced pluripotent stem cell-derived cardiomyocytes.

Results: Compared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (OR 0.6 [95% CI 0.4-0.9], OR 0.6 [95% CI 0.4-0.9]). We found no differences in OHCA risk between SU drug users who suffered OHCA inside or outside the context of AMI. Reduction of OHCA risk compared to glimepiride was found with gliclazide (OR 0.5 [95% CI 0.3-0.9]), but not glibenclamide (OR 1.3 [95% CI 0.6-2.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (OR 0.6 [95% CI 0.3-1.002]). Glibenclamide attenuated simulated ischaemia-induced APD shortening, while the other SU drugs had no effect.

Conclusions: SU drugs were associated with reduced OHCA risk compared to metformin monotherapy, with gliclazide having a lower risk than glimepiride. The differential effects of SU drugs are not explained by differential effects on APD.
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http://dx.doi.org/10.1111/bcp.14774DOI Listing
September 2021

Metagenomic analyses of microbial structure and metabolic pathway in solid-phase denitrification systems for advanced nitrogen removal of wastewater treatment plant effluent: A pilot-scale study.

Water Res 2021 May 17;196:117067. Epub 2021 Mar 17.

Department of Environmental Science, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, PR China. Electronic address:

The pilot-scale solid-phase denitrification systems supporting with poly(3-hydroxybutyrateco-3-hydroxyvalerate) (PHBV) and PHBV-sawdust were constructed for advanced nitrogen removal from wastewater treatment plants (WWTPs) effluent, and the impacts of biomass blended carbon source on microbial community structure, functions and metabolic pathways were analyzed by metagenomic sequencing. PHBV-sawdust system achieved the optimal denitrification performance with higher NO-N removal efficiency (96.58%), less DOC release (9.00 ± 4.16 mg L  ) and NH-N accumulation (0.37 ± 0.32 mg L  ) than PHBV system. Metagenomic analyses verified the significant differences in the structure of microbial community between systems and the presence of four anaerobic anammox bacteria. Compared with PHBV, the utilization of PHBV-sawdust declined the relative abundance of genes encoding enzymes for NH-N generation and increased the relative abundance of genes encoding enzymes involved in anammox, which contributed to the reduction of NH-N in effluent. What's more, the encoding gene for electrons generation in glycolysis metabolism obtained higher relative abundance in PHBV-sawdust system. A variety of lignocellulase encoding genes were significantly enriched in PHBV-sawdust system, which guaranteed the stable carbon supply and continuous operation of system. The results of this study are expected to provide theoretical basis and data support for the promotion of solid-phase denitrification.
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http://dx.doi.org/10.1016/j.watres.2021.117067DOI Listing
May 2021

Antidepressant Effect of Blue Light on Depressive Phenotype in Light-Deprived Male Rats.

J Neuropathol Exp Neurol 2020 12;79(12):1344-1353

From the Department of Toxicology, School of Public Health, Peking University.

Blue light has been previously reported to play a salient role in the treatment of seasonal affective disorder. The present study aimed to investigate whether blue light had antidepressant effect on light-deprivation-induced depression model, and the underlying visual neural mechanism. Blue light mitigated depression-like behaviors induced by light deprivation as measured by elevated sucrose preference and reduced immobility time. Blue light enhanced melanopsin expression and light responses in the retina. We also found the upregulation of serotonin and brain derived neurotrophic factor expression in the c-fos-positive areas of rats treated with blue light compared with those maintained in darkness. The species gap between nocturnal albino (Sprague-Dawley rat) and diurnal pigmented animals (human) might have influenced extrapolating data to humans. Blue light has antidepressant effect on light-deprived Sprague-Dawley rats, which might be related to activating the serotonergic system and neurotrophic activity via the retinoraphe and retinoamygdala pathways. Blue light is the effective component of light therapy for treatment of depression.
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http://dx.doi.org/10.1093/jnen/nlaa143DOI Listing
December 2020

Enabling a Large Accessible Surface Area of a Pore-Designed Hydrophilic Carbon Nanofiber Fabric for Ultrahigh Capacitive Deionization.

ACS Appl Mater Interfaces 2020 Nov 23;12(44):49586-49595. Epub 2020 Oct 23.

Key Laboratory of Energy Materials Chemistry, Ministry of Education, Key Laboratory of Advanced Functional Materials, Autonomous Region, Institute of Applied Chemistry, College of Chemistry, Xinjiang University, Urumqi 830046, P. R. China.

Although porous carbons have been widely used for capacitive deionization, the low accessible surface area because of the hydrophobic microporous structure results in unsatisfied desalination capacity, which drastically hinders their practical application. Herein, a novel carbon nanofiber fabric with a large accessible surface area was prepared by electrospinning using the uniformly dispersed ferrocene as a pore former. The carbon nanofiber fabric with good mechanical strength and flexibility can be directly used as a filter membrane to filter simulated sandy seawater. The high content of heteroatoms increases the surface polarity of the carbon nanofiber, while the well-controlled interconnected mesoporous structure of the optimized sample facilitates fast transport and adsorption of hydrated Na and Cl. Thus, the hydrophilic carbon nanofiber fabric shows a Brunauer-Emmett-Teller surface area of 922 m g and a large accessible surface area of 405 m g, leading to a high capacitance of 263 F g in the NaCl electrolyte. Most importantly, it shows an ultrahigh desalination capacity of 19.34 mg g, which is much higher than most of the previously reported carbon materials. The high desalination capacity, fast adsorption rate, and good cycle stability make the as-prepared carbon nanofiber fabric an attractive candidate for practical application.
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http://dx.doi.org/10.1021/acsami.0c13503DOI Listing
November 2020

Microbial community responses to agricultural biomass addition in aerated constructed wetlands treating low carbon wastewater.

J Environ Manage 2020 Sep 9;270:110912. Epub 2020 Jun 9.

College of Resources and Environment, Northwest A&F University, Yangling, Shaanxi, 712100, PR China; Department of Bioscience, Aarhus University, Aarhus, 8000C, Denmark. Electronic address:

Using agricultural biomasses as solid carbon substrates in constructed wetlands (CWs) could be an effective way to achieve sustainable nitrogen removal for carbon-limited wastewater treatments. This study investigated the response of bacteria community in CWs to the addition of agricultural biomasses (wheat straw, walnut shell and apricot pit). Results indicated that the addition of different agricultural biomasses had distinct influence on bacterial communities in CWs. Both wheat straw and walnut shell increased the diversity of microbial communities and optimized the structure of microorganisms. The effect of apricot pit on the richness and evenness of microbial communities was not significant, but the composition of microorganisms was significantly affected at the phylum level, especially the relative abundance of phylum Saccharibacteria. Moreover, the addition of agricultural biomasses in CWs acclimatized more functional bacteria including nitrifier and denitrifier, which were proved to be positively correlated with the high-rate denitrification performance. The obtained results would be beneficial to understand the underlying microbial mechanism of nitrogen removal in CWs with agricultural biomass and provide some guidance on the practical application of CWs.
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http://dx.doi.org/10.1016/j.jenvman.2020.110912DOI Listing
September 2020

Interactions of high-rate nitrate reduction and heavy metal mitigation in iron-carbon-based constructed wetlands for purifying contaminated groundwater.

Water Res 2020 Feb 5;169:115285. Epub 2019 Nov 5.

College of Resources and Environment, Northwest A&F University, Yangling, Shaanxi, 712100, PR China; Department of Bioscience, Aarhus University, Aarhus, 8000C, Denmark. Electronic address:

Groundwater, as the most important drinking water source in arid regions of China, has been polluted seriously by accumulated nitrate and heavy metals. An economic alternative with capacity of simultaneous mitigation of nitrate and heavy metals is urgently needed. This study explored the incorporation of iron scraps and biochar into constructed wetlands (CWs) for enhancing purification performance and investigated interactions of effective nitrate reduction and heavy metals mitigation. The results showed that nitrate reduction performance could reach 87% in iron and carbon-based (Fe-C) CWs through Fe-C micro-electrolysis process, with lower nitrous oxide (NO) emission (4.6-11.75 μg m h) due to the complete denitrification process. Moreover, efficient heavy metals mitigation of 75-97% total chromium (Cr) and total lead (Pb) was obtained from Fe-C systems. However, the occurrence of heavy metals (Cr and Pb) in the influent posed an adverse impact on nitrate removal with the reduction rate of 19-43%. Biochemical characteristics of wetland plants indicated that the plants also suffered from the stress which induced from heavy metals. Overall, although the addition of iron and biochar in CWs enhanced nitrate and heavy metals removal in low carbon groundwater, further investigation is still needed to reveal the complex relationships between the removal of nitrate and heavy metals in CWs.
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http://dx.doi.org/10.1016/j.watres.2019.115285DOI Listing
February 2020

TAK1 knock-down in macrophage alleviate lung inflammation induced by black carbon and aged black carbon.

Environ Pollut 2019 Oct 3;253:507-515. Epub 2019 Jul 3.

Department of Toxicology, School of Public Health, Peking University, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Black carbon (BC) can combine with organic matter and form secondary pollutants known as aged BC. BC and aged BC can cause respiratory system inflammation and induce lesions at relevant sites, but the underlying mechanism has remained unknown. To gain insight into the potential mechanisms, we focused on macrophages and transforming growth factor β-activated kinase 1 (TAK1) which are a crucial factor in inflammation. Our research aims to determine the role of TAK1 in macrophages in pulmonary inflammation induced by particulate matter. In this study, BC and 1,4-naphthoquinone were mixed to model aged BC (1,4NQ-BC) in atmosphere. BC induced mice lung inflammation model, lung macrophage knock-down TAK1 animal model and primary macrophage knock-down TAK1 model were used to explore whether TAK1 in macrophage is a critical role in the process of inflammation. The results showed that the expressions of inflammatory cytokines (IL-1β, IL-6, IL-33) mRNA were significantly increased and the phosphorylation of MAPK and NF-κB signaling pathway related proteins were enhanced in RAW 264.7 cell lines. In vivo studies revealed that the indicators of pulmonary inflammation (pathology, inflammatory cell numbers) and related cytokines (IL-1β, IL-6, IL-33) mRNA expressions in CD11c-Map3k7 animals were significantly lower than wild-type animals after mice were instilled particles. In mice primary macrophages, the expressions of IL-6, IL-33 mRNA were inhibited after TAK1 gene was knock-down. These results unequivocally demonstrated that TAK1 plays a crucial role in BC induced lung inflammation in mice, and we can infer that BC and 1,4NQ-BC cause these inflammatory responses by stimulating pulmonary macrophages.
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http://dx.doi.org/10.1016/j.envpol.2019.06.096DOI Listing
October 2019

Exploring Utilization of Recycled Agricultural Biomass in Constructed Wetlands: Characterization of the Driving Force for High-Rate Nitrogen Removal.

Environ Sci Technol 2019 02 16;53(3):1258-1268. Epub 2019 Jan 16.

College of Resources and Environment , Northwest A&F University , Yangling , Shaanxi 712100 , PR China.

Improper treatment of various wastewaters with a low C/N ratio and management of abundant agricultural wastes may pose a serious threat to bodies of water and agricultural ecosystems in rural areas, especially in developing countries. Thus, a potential alternative for simultaneous mitigation of this pollution is needed to protect rural environments. This study investigated the feasibility and enhanced performance of applying typical agricultural wastes (such as wheat straw, apricot pits, and walnut shells) as carbon sources for nitrogen removal in constructed wetlands (CWs). The leaching experiment employed fluorescence excitation-emission spectrophotometry and revealed that the wheat straw material had the highest capability of carbon release with an average dissolved organic carbon release content and rate of 27.88 mg g and 5.24 mg g day, respectively. Dissolved organic matter released from different agricultural wastes mainly consisted of humic acid-like and fulvic acid-like compounds. Long-term assessment of lab-scale intermittent aeration CWs receiving agricultural wastes revealed a high total nitrogen removal of 66.75-93.67% in low carbon/nitrogen ratio wastewaters (C/N = 3). These findings can contribute to a better understanding of the driving mechanism through which agricultural wastes enhance nitrogen removal in CW wastewater treatments.
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http://dx.doi.org/10.1021/acs.est.8b04871DOI Listing
February 2019

An innovative biochar-amended substrate vertical flow constructed wetland for low C/N wastewater treatment: Impact of influent strengths.

Bioresour Technol 2018 Jan 8;247:844-850. Epub 2017 Sep 8.

College of Natural Resources and Environment, Northwest A&F University, Yangling, Shaanxi 712100, PR China; Key Laboratory of Plant Nutrition and the Agri-environment in Northwest China, Ministry of Agriculture, PR China. Electronic address:

Application of biochar can be an effective and low cost technique for wastewater treatment while reducing greenhouse gas emissions. In this study, biochar was used as substrates in Vertical flow constructed wetlands (VFCWs) for enhancing the removal of contaminant from low C/N wastewaters with different influent strengths. The removal of organic matter and nitrogen in biochar-added and non-biochar-added VFCWs with different low C/N influent strengths were evaluated systematically. The results demonstrated that combining VFCWs and biochar addition could be an appropriate strategy as compared to conventional VFCWs with average removal of organic pollutants (85%), NH-N (39%) and TN (39%) especially at high influent strengths. Meanwhile, NO emission was also significantly lower in biochar-added VFCWs (138-1008μgmh) than that in non-biochar-added VFCWs (164-1304μgmh) under different influent strengths. We believe that VFCWs by adding biochar can be a useful technology for treating low C/N wastewaters.
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http://dx.doi.org/10.1016/j.biortech.2017.09.044DOI Listing
January 2018

Black carbon particles and ozone-oxidized black carbon particles induced lung damage in mice through an interleukin-33 dependent pathway.

Sci Total Environ 2018 Dec 5;644:217-228. Epub 2018 Jul 5.

Department of Toxicology, School of Public Health, Peking University, Beijing 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China. Electronic address:

Black carbon (BC) is a key component of atmospheric particles which has adverse effects on human health. Oxidation could lead to chemical property and toxicity potency changes of BC. The key cytokines participating in lung damage in mice induced by BC and ozone-oxidized BC (oBC) particles have been investigated in this study. It was concluded that oBC has stronger potency of inducing lung damage in mice comparing to BC. IL-6 and IL-33 were hypothesized to play important roles in this damage. Accordingly, IL-6 and IL-33 neutralizing antibodies were used to explore which cytokine might play a key role in lung inflammation induced by BC and oBC. As a result, IL-6 neutralizing antibody did not alleviate the lung damage induced by BC and oBC. However, IL-33 neutralizing antibody prevented BC and oBC induced lung damage. Furthermore, IL-33 neutralizing antibody treatment reduced IL-6 mRNA expression. It is hypothesized that MAPK and PI3K-AKT pathways might be involved in the oBC particles caused lung damage. It was concluded that IL-33 plays a key role in BC and oBC induced lung damage in mice.
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http://dx.doi.org/10.1016/j.scitotenv.2018.06.329DOI Listing
December 2018

Pubertal chlorocholine chloride exposure inhibits testicular testosterone synthesis by down-regulating steroidogenic enzymes in adult rats.

Toxicol Lett 2018 May 12;288:17-24. Epub 2018 Feb 12.

Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing, 100191, PR China; Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Chlorocholine chloride (CCC) is widely used to regulate plant growth. Considerable attention has been focused on its reproductive and developmental toxicities. In order to investigate the effects of pubertal CCC exposure on testicular testosterone (T) synthesis, male SD rats were exposed to CCC by oral gavage at doses of 0, 75, 150 and 300 mg/kg bw/day from postnatal day 23 to 70. We observed that pubertal CCC exposure lowered the body weight and the mean Johnsen's score. The percentage of seminiferous tubules with deciduous spermatogenic cells was increased in the 75 and 150 mg/kg bw/day groups. In addition, pubertal CCC exposure reduced the testicular absolute weights in the 75 and 300 mg/kg bw/day groups as well as the sperm motility in epididymides in the 150 mg/kg bw/day group. A significant decrease of testicular T was observed while levels of hypothalamic gonadotropin-releasing-hormone (GnRH) and serum luteinizing hormone (LH) were increased. Protein levels of steroidogenic acute regulatory (StAR), cholesterol side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD) were decreased. Taken together, these results indicate that pubertal CCC exposure in rats might decrease testicular T synthesis by suppressing the expression of steroidogenic enzymes, which partially lead to an impairment on spermatogenesis.
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http://dx.doi.org/10.1016/j.toxlet.2018.02.015DOI Listing
May 2018

The skeletal developmental toxicity of chlormequat chloride and its underlying mechanisms.

Toxicology 2017 04 16;381:1-9. Epub 2017 Feb 16.

Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, PR China. Electronic address:

Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d. The results showed that the size of femurs and tibias, bone mineral density and biomechanical parameters were significantly decreased in the 300mg/kg bw/d group compared with the control group. The concentration of osteocalcin (OCN) and C-terminal telopeptide of type I collagen (CTX-I) in blood in the 150mg/kg bw/d group was also changed. The mRNA expression ratio of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) in 150 and 300mg/kg bw/d group was increased. Histological analysis of proximal and distal epiphyseal plates of the right femurs showed that both the proliferative zone and hypertrophic zone narrowed in CCC-treated groups. The concentration of IGF-I in blood was reduced with an increase in exposure doses of CCC. The mRNA expression of growth hormone receptor (GHR) in tibia was decreased in the CCC-treated group. The results indicated that CCC might indirectly impact the formation and activation of chondrocytes, osteoblasts and osteoclasts because of the decline of GHR and IGF-I, leading to skeletal development damage.
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http://dx.doi.org/10.1016/j.tox.2017.02.003DOI Listing
April 2017

A mechanism regulating G protein-coupled receptor signaling that requires cycles of protein palmitoylation and depalmitoylation.

J Biol Chem 2014 Feb 2;289(9):6249-57. Epub 2014 Jan 2.

From the Departments of Cell Biology and Physiology.

Reversible attachment and removal of palmitate or other long-chain fatty acids on proteins has been hypothesized, like phosphorylation, to control diverse biological processes. Indeed, palmitate turnover regulates Ras trafficking and signaling. Beyond this example, however, the functions of palmitate turnover on specific proteins remain poorly understood. Here, we show that a mechanism regulating G protein-coupled receptor signaling in neuronal cells requires palmitate turnover. We used hexadecyl fluorophosphonate or palmostatin B to inhibit enzymes in the serine hydrolase family that depalmitoylate proteins, and we studied R7 regulator of G protein signaling (RGS)-binding protein (R7BP), a palmitoylated allosteric modulator of R7 RGS proteins that accelerate deactivation of Gi/o class G proteins. Depalmitoylation inhibition caused R7BP to redistribute from the plasma membrane to endomembrane compartments, dissociated R7BP-bound R7 RGS complexes from Gi/o-gated G protein-regulated inwardly rectifying K(+) (GIRK) channels and delayed GIRK channel closure. In contrast, targeting R7BP to the plasma membrane with a polybasic domain and an irreversibly attached lipid instead of palmitate rendered GIRK channel closure insensitive to depalmitoylation inhibitors. Palmitate turnover therefore is required for localizing R7BP to the plasma membrane and facilitating Gi/o deactivation by R7 RGS proteins on GIRK channels. Our findings broaden the scope of biological processes regulated by palmitate turnover on specific target proteins. Inhibiting R7BP depalmitoylation may provide a means of enhancing GIRK activity in neurological disorders.
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http://dx.doi.org/10.1074/jbc.M113.531475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937690PMC
February 2014

Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7 family-binding protein.

J Biol Chem 2011 Apr 22;286(15):13695-703. Epub 2011 Feb 22.

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

R7BP (RGS7 family-binding protein) has been proposed to function in neurons as a palmitoylation-regulated protein that shuttles heterodimeric, G(i/o)α-specific GTPase-activating protein (GAP) complexes composed of Gβ5 and RGS7 (R7) isoforms between the plasma membrane and nucleus. To test this hypothesis we studied R7BP palmitoylation and localization in neuronal cells. We report that R7BP undergoes dynamic, signal-regulated palmitate turnover; the palmitoyltransferase DHHC2 mediates de novo and turnover palmitoylation of R7BP; DHHC2 silencing redistributes R7BP from the plasma membrane to the nucleus; and G(i/o) signaling inhibits R7BP depalmitoylation whereas G(i/o) inactivation induces nuclear accumulation of R7BP. In concert with previous evidence, our findings suggest that agonist-induced changes in palmitoylation state facilitate GAP action by (i) promoting Giα depalmitoylation to create optimal GAP substrates, and (ii) inhibiting R7BP depalmitoylation to stabilize membrane association of R7-Gβ5 GAP complexes. Regulated palmitate turnover may also enable R7BP-bound GAPs to shuttle between sites of low and high G(i/o) activity or the plasma membrane and nucleus, potentially providing spatio-temporal control of signaling by G(i/o)-coupled receptors.
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http://dx.doi.org/10.1074/jbc.M110.193763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075713PMC
April 2011

Mapping of the Saccharomyces cerevisiae Oxa1-mitochondrial ribosome interface and identification of MrpL40, a ribosomal protein in close proximity to Oxa1 and critical for oxidative phosphorylation complex assembly.

Eukaryot Cell 2009 Nov 25;8(11):1792-802. Epub 2009 Sep 25.

Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin 53233, USA.

The Oxa1 protein plays a central role in facilitating the cotranslational insertion of the nascent polypeptide chains into the mitochondrial inner membrane. Mitochondrially encoded proteins are synthesized on matrix-localized ribosomes which are tethered to the inner membrane and in physical association with the Oxa1 protein. In the present study we used a chemical cross-linking approach to map the Saccharomyces cerevisiae Oxa1-ribosome interface, and we demonstrate here a close association of Oxa1 and the large ribosomal subunit protein, MrpL40. Evidence to indicate that a close physical and functional relationship exists between MrpL40 and another large ribosomal protein, the Mrp20/L23 protein, is also provided. MrpL40 shares sequence features with the bacterial ribosomal protein L24, which like Mrp20/L23 is known to be located adjacent to the ribosomal polypeptide exit site. We propose therefore that MrpL40 represents the Saccharomyces cerevisiae L24 homolog. MrpL40, like many mitochondrial ribosomal proteins, contains a C-terminal extension region that bears no similarity to the bacterial counterpart. We show that this C-terminal mitochondria-specific region is important for MrpL40's ability to support the synthesis of the correct complement of mitochondrially encoded proteins and their subsequent assembly into oxidative phosphorylation complexes.
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http://dx.doi.org/10.1128/EC.00219-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772399PMC
November 2009

R9AP and R7BP: traffic cops for the RGS7 family in phototransduction and neuronal GPCR signaling.

Trends Pharmacol Sci 2009 Jan 29;30(1):17-24. Epub 2008 Nov 29.

Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.

RGS (regulator of G protein signaling) proteins have emerged as crucial regulators, effectors and integrators in G-protein-coupled receptor (GPCR) signaling networks. Many RGS proteins accelerate GTP hydrolysis by Galpha subunits, thereby regulating G protein activity, whereas certain RGS proteins also transduce Galpha signals to downstream targets. Particularly intriguing are members of the RGS7 (R7) family (RGS6, RGS7, RGS9 and RGS11), which heterodimerize with Gbeta5. In Caenorhabditis elegans, R7-Gbeta5 heterodimers regulate synaptic transmission, anesthetic action and behavior. In vertebrates, they regulate vision, postnatal development, working memory and the action of psychostimulants or morphine. Here we highlight R9AP and R7BP, a related pair of recently identified SNARE-like R7-family binding proteins, which regulate intracellular trafficking, expression and function of R7-Gbeta5 heterodimers in retina and brain. Emerging understanding of R7BP and R9AP promises to provide new insights into neuronal GPCR signaling mechanisms relevant to the causes and treatment of neurological disorders.
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http://dx.doi.org/10.1016/j.tips.2008.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776672PMC
January 2009

Oxa1 directly interacts with Atp9 and mediates its assembly into the mitochondrial F1Fo-ATP synthase complex.

Mol Biol Cell 2007 May 7;18(5):1897-908. Epub 2007 Mar 7.

Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA.

The yeast Oxa1 protein is involved in the biogenesis of the mitochondrial oxidative phosphorylation (OXPHOS) machinery. The involvement of Oxa1 in the assembly of the cytochrome oxidase (COX) complex, where it facilitates the cotranslational membrane insertion of mitochondrially encoded COX subunits, is well documented. In this study we have addressed the role of Oxa1, and its sequence-related protein Cox18/Oxa2, in the biogenesis of the F(1)F(o)-ATP synthase complex. We demonstrate that Oxa1, but not Cox18/Oxa2, directly supports the assembly of the membrane embedded F(o)-sector of the ATP synthase. Oxa1 was found to physically interact with newly synthesized mitochondrially encoded Atp9 protein in a posttranslational manner and in a manner that is not dependent on the C-terminal, matrix-localized region of Oxa1. The stable manner of the Atp9-Oxa1 interaction is in contrast to the cotranslational and transient interaction previously observed for the mitochondrially encoded COX subunits with Oxa1. In the absence of Oxa1, Atp9 was observed to assemble into an oligomeric complex containing F(1)-subunits, but its further assembly with subunit 6 (Atp6) of the F(o)-sector was perturbed. We propose that by directly interacting with newly synthesized Atp9 in a posttranslational manner, Oxa1 is required to maintain the assembly competence of the Atp9-F(1)-subcomplex for its association with Atp6.
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http://dx.doi.org/10.1091/mbc.e06-10-0925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855041PMC
May 2007

Yeast Oxa1 interacts with mitochondrial ribosomes: the importance of the C-terminal region of Oxa1.

EMBO J 2003 Dec;22(24):6438-47

Department of Biological Sciences, Marquette University, 530 N. 15th Street, Milwaukee, WI 53233, USA.

The yeast mitochondrial Oxa1 protein is a member of the conserved Oxa1/YidC/Alb3 protein family involved in the membrane insertion of proteins. Oxa1 mediates the insertion of proteins (nuclearly and mitochondrially encoded) into the inner membrane. The mitochondrially encoded substrates interact directly with Oxa1 during their synthesis as nascent chains and in a manner that is supported by the associated ribosome. We have investigated if the Oxa1 complex interacts with the mitochondrial ribosome. Evidence to support a physical association between Oxa1 and the large ribosomal subunit is presented. Our data indicate that the matrix-exposed C-terminal region of Oxa1 plays an important role supporting the ribosomal-Oxa1 interaction. Truncation of this C-terminal segment compromises the ability of Oxa1 to support insertion of substrate proteins into the inner membrane. Oxa1 can be cross-linked to Mrp20, a component of the large ribosomal subunit. Mrp20 is homologous to L23, a subunit located next to the peptide exit tunnel of the ribosome. We propose that the interaction of Oxa1 with the ribosome serves to enhance a coupling of translation and membrane insertion events.
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http://dx.doi.org/10.1093/emboj/cdg624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC291819PMC
December 2003
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