Publications by authors named "Yuan-Yuan Cheng"

60 Publications

Population-based high-throughput toxicity screen of human iPSC-derived cardiomyocytes and neurons.

Cell Rep 2022 04;39(1):110643

Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Institute of Medical Genomics and Proteomics and Institute of Clinical Medicine, National Taiwan University, Taipei 106, Taiwan. Electronic address:

In this study, we establish a population-based human induced pluripotent stem cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 1,000 healthy donors and screening for high-frequency human leukocyte antigen (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the population. These "super donors" are also expected to represent at least 477,611,135 of the global population. By differentiating these representative hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput toxicity screen. To validate hit compounds, we demonstrate dose-dependent toxicity of the hit compounds and assess functional modulation. We also show reproducible in vivo drug toxicity results using mouse models with select hit compounds. This study shows the feasibility of using a population-based hiPSC drug screening platform to assess cytotoxicity, which can be used as an innovative tool to study inter-population differences in drug toxicity and adverse drug reactions in drug discovery applications.
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http://dx.doi.org/10.1016/j.celrep.2022.110643DOI Listing
April 2022

YgfY Contributes to Stress Tolerance in Neither as an Antitoxin Nor as a Flavinylation Factor of Succinate Dehydrogenase.

Microorganisms 2021 Nov 9;9(11). Epub 2021 Nov 9.

School of Life Sciences, Anhui University, Hefei 230602, China.

YgfY(SdhE/CptB) is highly conserved while has controversial functions in bacteria. It works as an antitoxin and composes a type IV toxin-antitoxin system with YgfX(CptA) typically in , while functions as an flavinylation factor of succinate dehydrogenase and fumarate reductase typically in sp. In this study, we report the contribution of YgfY in MR-1 to tolerance of low temperature and nitrite. YgfY deficiency causes several growth defects of MR-1 at low temperature, while YgfX do not cause a growth defect or morphological change of MR1-1 and . YgfY do not interact with FtsZ and MreB nor with YgfX examined by bacterial two-hybrid assay. YgfY effect on growth under low temperature is not attributed to succinate dehydrogenase (SDH) because a mutant without SDH grows comparably with the wild-type strain in the presence of succinate. The mutant shows impaired tolerance to nitrite. Transcription of nitrite reductase and most ribosome proteins is significantly decreased in the mutant, which is consistent with the phenotypes detected above. Effects of YgfY on growth and nitrite tolerance are closely related to the RGXXE motif in YgfY. In summary, this study demonstrates pleiotropic impacts of YgfY in MR-1, and sheds a light on the physiological versatility of YgfY in bacteria.
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http://dx.doi.org/10.3390/microorganisms9112316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621075PMC
November 2021

LGR6 promotes glioblastoma malignancy and chemoresistance by activating the Akt signaling pathway.

Exp Ther Med 2021 Dec 27;22(6):1364. Epub 2021 Sep 27.

Department of Neurosurgery, The Second Affiliated Hospital of Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, Shandong 270000, P.R. China.

Chemoresistance is the primary cause of the poor outcome of glioblastoma multiforme (GBM) therapy. Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) is involved in the growth and proliferation of several types of cancer, including gastric cancer and ovarian cancer. Therefore, the aim of the present study was to investigate the role of LGR6 in GBM malignancy and chemoresistance. Cell counting kit-8 and Matrigel-Transwell assays were conducted to assess GBM cell viability and invasion. The effect of LGR6 on cell cycle progression and activation of Akt signaling was analyzed by performing propidium iodide staining and western blotting, respectively. The results demonstrated that LGR6, a microRNA-1236-3p target candidate, promoted GBM cell viability and invasion, and mediated temozolomide sensitivity in SHG-44 and U251 GBM cells. In addition, LGR6 triggered the activation of the Akt signaling pathway during GBM progression. Collectively, the results of the present study suggested that LGR6 promoted GBM malignancy and chemoresistance, at least in part, by activating the Akt signaling pathway. The results may aid with the identification of a novel therapeutic target and strategy for GBM.
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http://dx.doi.org/10.3892/etm.2021.10798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515564PMC
December 2021

Direct C-H Thiolation for Selective Cross-Coupling of Arenes with Thiophenols via Aerobic Visible-Light Catalysis.

Org Lett 2021 Oct 5;23(20):8082-8087. Epub 2021 Oct 5.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

An aerobic metal-free, visible-light-induced regioselective thiolation of phenols with thiophenols is reported. The cross-coupling protocol exhibits great functional group tolerance and high regioselectivity. Mechanistic studies reveal that the disulfide radical cation plays a crucial role in the visible-light catalysis of aerobic thiolation. Simply controlling the equivalent ratio of substrates enables the selective formation of sulfide or sulfoxide products with high activity in a one-pot reaction.
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http://dx.doi.org/10.1021/acs.orglett.1c03090DOI Listing
October 2021

Direct 1,2-Dicarbonylation of Alkenes towards 1,4-Diketones via Photocatalysis.

Angew Chem Int Ed Engl 2021 12 16;60(51):26822-26828. Epub 2021 Nov 16.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, The Chinese Academy of Sciences, Beijing, 100190, P. R. China.

1,4-Dicarbonyl compounds are intriguing motifs and versatile precursors in numerous pharmaceutical molecules and bioactive natural compounds. Direct incorporation of two carbonyl groups into a double bond at both ends is straightforward, but also challenging. Represented herein is the first example of 1,2-dicarbonylation of alkenes by photocatalysis. Key to success is that N(n-Bu) not only associates with the alkyl anion to avoid protonation, but also activates the α-keto acid to undergo electrophilic addition. The α-keto acid is employed both for acyl generation and electrophilic addition. By tuning the reductive and electrophilic ability of the acyl precursor, unsymmetric 1,4-dicarbonylation is achieved for the first time. This metal-free, redox-neutral and regioselective 1,2-dicarbonylation of alkenes is executed by a photocatalyst for versatile substrates under extremely mild conditions and shows great potential in biomolecular and drug molecular derivatization.
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http://dx.doi.org/10.1002/anie.202112370DOI Listing
December 2021

Pyruvate accelerates palladium reduction by regulating catabolism and electron transfer pathway in .

Appl Environ Microbiol 2021 Jan 29. Epub 2021 Jan 29.

Information Materials and Intelligent Sensing Laboratory of Anhui Province, Anhui University, China

is a model strain of the electrochemical active bacteria (EAB) because of its strong capability of extracellular electron transfer (EET) and genetic tractability. In this study, we investigated the effect of carbon sources on EET in by using reduction of palladium ions (Pd(II)) as a model and found that pyruvate greatly accelerated the Pd(II) reduction compared with lactate by resting cells. Both Mtr pathway and hydrogenases played a role in Pd(II) reduction when pyruvate was used as a carbon source. Furthermore, in comparison with lactate-feeding , the transcriptional levels of formate dehydrogenases involving in pyruvate catabolism, Mtr pathway, and hydrogenases in pyruvatefeeding were up-regulated. Mechanistically, the enhancement of electron generation from pyruvate catabolism and electron transfer to Pd(II) explains the pyruvate effect on Pd(II) reduction. Interestingly, a 2-h time window is required for pyruvate to regulate transcription of these genes and profoundly improve Pd(II) reduction capability, suggesting a hierarchical regulation for pyruvate sensing and response in The unique respiration of EET is crucial for the biogeochemical cycling of metal elements and diverse applications of EAB. Although a carbon source is a determinant factor of bacterial metabolism, the research into the regulation of carbon source on EET is rare. In this work, we reported the pyruvate-specific regulation and improvement of EET in and revealed the underlying mechanism, which suggests potential targets to engineer and improve the EET efficiency of this bacterium. This study sheds light on the regulatory role of carbon sources in anaerobic respiration in EAB, providing a way to regulate EET for diverse applications from a novel perspective.
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http://dx.doi.org/10.1128/AEM.02716-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091111PMC
January 2021

Therapeutic potential of ALKB homologs for cardiovascular disease.

Biomed Pharmacother 2020 Nov 14;131:110645. Epub 2020 Sep 14.

Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China. Electronic address:

Cardiovascular diseases (CVDs) are the leading causes of human death. Recently, ALKB homologs, including ALKBH1-8 and FTO, have been found to have a variety of biological functions, such as histone demethylation, RNA demethylation, and DNA demethylation. These functions may regulate the physiological and pathological processes of CVDs, including inflammation, oxidative stress, cell apoptosis, and mitochondrial, endothelial, and fat metabolism dysfunction. In the present review, we summarize the biological functions of ALKB homologs and the relationship between the ALKB homologs and CVDs. Importantly, we discuss the roles of ALKB homologs in the regulation of oxidative stress, inflammation, autophagy, and DNA damage in CVDs, as well as the practical applications of ALKB homologs inhibitors or agonists in treating CVDs. In conclusion, the ALKBH family might be a promising target for CVDs therapy.
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http://dx.doi.org/10.1016/j.biopha.2020.110645DOI Listing
November 2020

Modification-bioremediation of copper, lead, and cadmium-contaminated soil by combined ryegrass (Lolium multiflorum Lam.) and Pseudomonas aeruginosa treatment.

Environ Sci Pollut Res Int 2020 Oct 30;27(30):37668-37676. Epub 2020 Jun 30.

College of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou, 215009, China.

The principal objective of this study was to investigate the strengthened remediation effect and relevant mechanism of P. aeruginosa on ryegrass (Lolium multiflorum Lam.) for soil contaminated by Cu-Pb-Cd compound heavy metals. The results showed that the complex heavy metals' contamination had remarkable inhibiting effect on the growth of plants (P < 0.01), and the biomass of ryegrass's stem and leaves declined by 28.2%, while that of roots decreased by 34.7% after 45 days. The inoculation of P. aeruginosa promoted the growth of ryegrass in polluted soil, in which the biomass recovered to the same level of that in normal plant; the activity of both catalase and urease in the soil also increased strikingly (by 29.3% and 75.7%, respectively); the ratio of residual heavy metals in the soil decreased, while the acid extractable heavy metals increased notably. Therefore, the absorption and accumulation of ryegrass to the heavy metals in soil were improved to some extent; the bioconcentration factor of Cu, Pb, and Cd in ryegrass increased by 35.9%, 55.6%, and 283.5%, respectively. The exterior microorganism allowed the accumulation of Cu, Pb, and Cd in shoots of ryegrass increasing remarkably, while in roots, only the accumulation of Pb increased by 16.3%, and that of both Cu and Cd decreased. Besides, in the P. aeruginosa-inoculated system, the transfer factor of Cu and Cd in plants increased strikingly, while that of Pb decreased.
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http://dx.doi.org/10.1007/s11356-020-09846-2DOI Listing
October 2020

Cobaloxime Catalysis for Enamine Phosphorylation with Hydrogen Evolution.

Org Lett 2020 07 25;22(14):5385-5389. Epub 2020 Jun 25.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, The Chinese Academy of Sciences, Beijing 100190, P.R. China.

Direct phosphorylation of enamine and enamide with hydrogen evolution was realized via cobaloxime catalysis under visible-light irradiation. Control experiments and spectroscopic studies demonstrated a reductive quenching pathway of cobaloxime catalyst to produce phosphinoyl radical, which underwent cross-coupling with various enamines (and enamides) to give diverse β-phosphinoyl products in good to excellent yields. More interestingly, / mixture of acyclic enamines could convert into single -products with good reactivity.
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http://dx.doi.org/10.1021/acs.orglett.0c01709DOI Listing
July 2020

T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration.

Atherosclerosis 2020 03 22;297:64-73. Epub 2020 Jan 22.

The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. Electronic address:

Background And Aims: Atherosclerosis is a serious cardiovascular disease, featuring inflammation, abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). During atherosclerosis, inflammation may cause low pH. T-cell death-associated gene 8 (Tdag8) is a proton-sensing receptor, however, the role of Tdag8 in VSMCs remains unknown. This study aimed to investigate the potential effects of Tdag8 in VSMCs during atherosclerosis.

Methods: We examined the expression of Tdag8 in an atherosclerotic model of high-fat-diet-fed ApoE mice, while the role and mechanism of Tdag8 in phenotype transformation, proliferation and migration of VSMCs were investigated in a series of in vivo and in vitro experiments.

Results: We first found that Tdag8 expression at the mRNA and protein level was significantly increased in atherosclerotic ApoE mice. Immunofluorescence staining showed that Tdag8 was primarily distributed in PCNA-positive VSMCs and the phenotype of VSMCs switching from contractile phenotype to synthetic phenotype. Additionally, the protein level of Tdag8 was upregulated in FBS-treated VSMCs. VSMCs proliferation and migration were inhibited by Tdag8 silencing and increased by Tdag8 overexpression. Further mechanistic studies showed that cAMP level was increased in Tdag8-overexpressing VSMCs and ApoE mice. However, the PKA inhibitor H-89 reversed Tdag8-induced VSMC proliferation and migration.

Conclusions: The results demonstrate that Tdag8 mediated phenotype transformation, proliferation and migration of VSMCs via the cAMP/PKA signaling pathway, thus partially contributing to atherosclerosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.01.017DOI Listing
March 2020

Visible Light Irradiation of Acyl Oxime Esters and Styrenes Efficiently Constructs β-Carbonyl Imides by a Scission and Four-Component Reassembly Process.

Org Lett 2019 Nov 17;21(21):8789-8794. Epub 2019 Oct 17.

Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry , The Chinese Academy of Sciences , Beijing , 100190 , P. R. China.

Acyl radical triggered difunctionalizations of aryl olefins have been realized using oxime ester as the acyl precursor for the first time. Irradiation of -Ir(ppy) and oxime ester by visible light caused scission into three components, which recombined with olefins to yield significant β-carbonyl imides showing good functional group tolerance and high atom economy. Control experiments as well as spectroscopic and electrochemical studies revealed the efficient intermolecular reorganization of oxime ester into styrene with the aid of solvent exchange.
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http://dx.doi.org/10.1021/acs.orglett.9b03409DOI Listing
November 2019

CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression.

Apoptosis 2019 08;24(7-8):673-685

National Translational Science Center for Molecular Medicine, Xi'an, 710032, China.

Chemotherapeutic resistance always results in poor clinical outcomes of cancer patients and its intricate mechanisms are large obstacles in overcoming drug resistance. CCR4-NOT transcription complex subunit 3 (CNOT3), a post-translational regulator, is suggested to be involved in cancer development and progression. However, its role in chemotherapeutic resistance is not well understood. In this study, after screening the CNOT3 mRNA in a cancer microarray database called Oncomine and examining the expression levels of CNOT3 mRNA in normal tissues and lung cancer tissues, we found that CNOT3 was up-regulated in lung cancer tissues. Besides, its high-expression was associated with poor prognosis of lung cancer patients. We also found higher expression level of CNOT3 and lower expression level of receptor-interacting protein kinase 3 (RIPK3) in cisplatin-resistant A549 (A549/DDP) cells, and knocking down CNOT3 expression could sensitize A549/DDP cells to cisplatin-induced apoptosis. We demonstrated that CNOT3 depletion up-regulated the expression level of RIPK3 and the enhanced apoptosis was mediated by the elevated RIPK3 to further trigger Caspase 8 activation. Taken together, our results reveal a role of CNOT3 in cisplatin resistance of lung cancer and provide a potential target for lung cancer therapy.
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http://dx.doi.org/10.1007/s10495-019-01550-yDOI Listing
August 2019

Luciferin Regeneration in Firefly Bioluminescence via Proton-Transfer-Facilitated Hydrolysis, Condensation and Chiral Inversion.

Chemphyschem 2019 07 12;20(13):1719-1727. Epub 2019 Jun 12.

Key Laboratory of Theoretical and Computational Photochemistry Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, P. R. China.

Firefly bioluminescence is produced via luciferin enzymatic reactions in luciferase. Luciferin has to be unceasingly replenished to maintain bioluminescence. How is the luciferin reproduced after it has been exhausted? In the early 1970s, Okada proposed the hypothesis that the oxyluciferin produced by the previous bioluminescent reaction could be converted into new luciferin for the next bioluminescent reaction. To some extent, this hypothesis was evidenced by several detected intermediates. However, the detailed process and mechanism of luciferin regeneration remained largely unknown. For the first time, we investigated the entire process of luciferin regeneration in firefly bioluminescence by density functional theory calculations. This theoretical study suggests that luciferin regeneration consists of three sequential steps: the oxyluciferin produced from the last bioluminescent reaction generates 2-cyano-6-hydroxybenzothiazole (CHBT) in the luciferin regenerating enzyme (LRE) via a hydrolysis reaction; CHBT combines with L-cysteine in vivo to form L-luciferin via a condensation reaction; and L-luciferin inverts into D-luciferin in luciferase and thioesterase. The presently proposed mechanism not only supports the sporadic evidence from previous experiments but also clearly describes the complete process of luciferin regeneration. This work is of great significance for understanding the long-term flashing of fireflies without an in vitro energy supply.
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http://dx.doi.org/10.1002/cphc.201900306DOI Listing
July 2019

Mediation of functional gene and bacterial community profiles in the sediments of eutrophic Chaohu Lake by total nitrogen and season.

Environ Pollut 2019 Jul 10;250:233-240. Epub 2019 Apr 10.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Applied Chemistry, University of Science & Technology of China, Hefei, 230026, China. Electronic address:

Microbes in sediments contribute to nutrient release and play an important role in lake eutrophication. However, information about the profiles of functional genes and bacterial communities and the most important environmental factor affecting them in the sediments of eutrophic lake remains unrevealed. In this work, the real-time fluorescent quantitative polymerase chain reaction (qPCR) assay and 16S ribosomal RNA gene next generation sequencing analysis were used to explore the profiles of functional genes and bacterial communities in the sediments of Chaohu Lake. The selected 18 functional genes involved in C, N and P cycles were detected in most of samples. Seasonal variation and sediment variables were found to affect the profiles of functional genes and bacterial communities, and total nitrogen was the dominant environmental factor to drive the formation of bacterial community structure. Proteobacteria and Firmicutes were observed to be the two dominant phyla in the sediments with relative abundance ranging from 10.8% to 36.0% and 7.7%-46.7%, respectively. Three bacterial phyla, i.e., Actinobacteria, Proteobacteria, and Spirochaetes, were found to be significantly positively correlated with the C, N and P-cycle related functional genes. Bacterial community structure was the most important driver to shape the profiles of functional genes. Seasonal variation also influenced the co-occurrence patterns between functional genes and bacterial taxa as revealed by network analysis. The findings from this work facilitate a better understanding about the C, N, and P cycles in the sediments of eutrophic lakes.
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http://dx.doi.org/10.1016/j.envpol.2019.04.028DOI Listing
July 2019

Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation.

Mol Immunol 2019 01 27;105:76-85. Epub 2018 Nov 27.

School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China. Electronic address:

Activation of NLRP3 inflammasomes is crucial in the pathological process of Ulcerative colitis (UC), which could be negatively regulated by PINK1/Parkin-driven mitophagy. Palmatine is a herb derived isoquinoline alkaloid with potent anti-inflammatory and anti-bacteria activities. In present study, we evaluated the effect of palmatine on dextran sulfate sodium (DSS)-induced mice colitis and examined whether its effect is exerted by promoting mitophagy-mediated NLRP3 inflammasome inactivation. The result showed that palmatine (40, 100 mg/kg) significantly prevented bodyweight loss and colonic shortening in DSS mice, and reduced the disease activity index and histopathologic score. The levels of MPO, IL-1β, TNF-α and the number of F4/80+ cells in colon of DSS mice were remarkably decreased by palmatine. Moreover, palmatine suppressed NLRP3 inflammasomes activation, but enhanced the expression of the mitophagy-related proteins involving LC3, PINK1 and Parkin in colonic tissue of DSS mice. These effects was consistent with the in vitro data revealing that palmatine inhibited the activation of NLRP3 inflammasomes, while promoted the expression and mitochondrial recruitment of PINK1 and Parkin in THP-1 cell differentiated macrophages. Furthermore, the effect of palmatine on THP-1 cells was neutralized by a mitophagy inhibitor Cyclosporin A (CsA) and PINK1-siRNA. In parallel, CsA significantly attenuated the therapeutic effect of palmatine in DSS mice, illustrating that the anti-colitis effect of palmatine is closely related to mitophagy. Taken together, the current results demonstrated that palmatine protected mice against DSS-induced colitis by facilitating PINK1/Parkin-driven mitophagy and thus inactivating NLRP3 inflammasomes in macrophage.
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http://dx.doi.org/10.1016/j.molimm.2018.10.015DOI Listing
January 2019

Prostaglandin E Receptor 2 Modulates Macrophage Activity for Cardiac Repair.

J Am Heart Assoc 2018 10;7(19):e009216

1 Institute of Basic Medical Sciences and Institute of Clinical Medicine National Cheng Kung University Tainan Taiwan.

Background Prostaglandin E has long been known to be an immune modulator. It is released after tissue injury and plays a role in modulating macrophage activities, which are essential for tissue regeneration. However, the involvement of prostaglandin E receptor 2 ( EP 2)-dependent regulation of macrophages in postischemic heart is unclear. This study aims to evaluate the role of EP 2 in damaged heart. Methods and Results The effect of EP 2 in postischemic heart was evaluated using EP 2-deficient transgenic mice. We demonstrated that cardiac function was worse after myocardial injury on loss of EP 2. Furthermore, EP 2 deficiency also altered proinflammatory response and resulted in a defect in macrophage recruitment to the injured myocardium. Transcriptome analysis revealed that the expression of erythroid differentiation regulator 1 ( Erdr1) was significantly induced in EP 2-deficient macrophages. Knocking down Erdr1 expression restored migration ability of EP 2-deficient cells both in vitro and in vivo. By using a genetic fate-mapping approach, we showed that abolishment of EP 2 expression effectively attenuated cell replenishment. Conclusions The EP 2-dependent signaling pathway plays a critical role in regulating macrophage recruitment to the injured myocardium, thereby exerting a function in modulating the inflammatory microenvironment for cardiac repair.
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http://dx.doi.org/10.1161/JAHA.118.009216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404869PMC
October 2018

Abundance and diversity of iron reducing bacteria communities in the sediments of a heavily polluted freshwater lake.

Appl Microbiol Biotechnol 2018 Dec 17;102(24):10791-10801. Epub 2018 Oct 17.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Chemistry, University of Science & Technology of China, Hefei, 230026, China.

Iron reduction mediated by Fe(III)-reducing bacteria (FeRB) occurs in aqueous environments and plays an essential role in removing contaminates in polluted freshwater lakes. Two model FeRB species, Shewanella and Geobacter, have been intensively studied because of their functions in bioremediation, iron reduction, and bioelectricity production. However, the abundance and community diversity of Shewanella and Geobacter in eutrophic freshwater lakes remain largely unknown. In this work, the distribution, abundance and biodiversity of Shewanella, Geobacter and other FeRB in the sediments of a heavily polluted lake, Chaohu Lake, China, across four successive seasons were investigated. Shewanella, Geobacter, and other FeRB were found to be widely distributed in the sediment of this heavily eutrophic lake. Geobacter was abundant with at least one order of magnitude more than Shewanella in cold seasons. Three Shewanella-related operational taxonomic units were detected and sixty one Geobacter-related operational taxonomic units were grouped into three phylogenetic clades. Thiobacillus, Desulfuromonas and Geobacter were identified as the main members of FeRB in the lake sediments. Interestingly, nutrients like carbon, nitrogen, and phosphorus were found to be the key factors governing the abundance and diversity of FeRB. Total FeRB, as well as Geobacter and Shewanella, were more abundant in the heavily eutrophic zone than those in the lightly eutrophic zone. The abundance and diversity of FeRB in the sediments of freshwater lakes were highly related with the degree of eutrophication, which imply that FeRB might have a great potential in alleviating the eutrophication and contamination in aqueous environments.
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http://dx.doi.org/10.1007/s00253-018-9443-1DOI Listing
December 2018

[Physiological Responses of Ryegrass in Cadmium-Nonylphenol Co-contaminated Water and the Phytoremediation Effects].

Huan Jing Ke Xue 2018 Oct;39(10):4512-4518

College of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.

Physiological responses of ryegrass in cadmium-nonylphenol (Cd-NP) co-contaminated water, as well as the phytoremediation effect were studied under laboratory conditions. The experiment revealed that the biomass and chlorophyll content of ryegrass significantly declined at high concentrations of Cd(10 mg·L), while POD and PPO activities significantly increased. No significant changes to the biomass, chlorophyll content and MDA of ryegrass were observed in the presence of NP. POD activities significantly increased at high concentrations of NP (5 mg·L). The addition of high NP concentrate reduced the inhibition of Cd under co-contaminated stress, the MDA content and PPO activities both reduced. The experiment also revealed that the removal rate of Cd by ryegrass reached 55.3% after 12 h. The absorption efficiency was improved by high NP concentration. Absorption efficiency of Cd by the subterranean part of the plant significantly increased in presence of NP, and the absorption efficiency increased with the increase of NP concentration. The absorption rate of NP was 44.6% after 24 h at NP concentration of 5 mg·L. The removal rate was slightly influenced at low concentrations of Cd, but significant inhibition of absorption and degradation was observed at high concentrations of Cd.
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http://dx.doi.org/10.13227/j.hjkx.201712234DOI Listing
October 2018

Estimates of abundance and diversity of Shewanella genus in natural and engineered aqueous environments with newly designed primers.

Sci Total Environ 2018 Oct 12;637-638:926-933. Epub 2018 May 12.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Chemistry, University of Science & Technology of China, Hefei 230026, China. Electronic address:

Shewanella species have a diverse respiratory ability and wide distribution in environments and play an important role in bioremediation and the biogeochemical cycles of elements. Primers with more accuracy and broader coverage are required with consideration of the increasing number of Shewanella species and evaluation of their roles in various environments. In this work, a new primer set of 640F/815R was developed to quantify the abundance of Shewanella species in natural and engineered environments. In silico tools for primer evaluation, quantitative polymerase chain reaction (qPCR) and clone library results showed that 640F/815R had a higher specificity and coverage than the previous primers in quantitative analysis of Shewanella. Another newly developed primer pair of 211F/815cR was also adopted to analyze the Shewanella diversity and demonstrated to be the best candidate in terms of specificity and coverage. We detected more Shewanella-related species in freshwater environments and found them to be substantially different from those in marine environments. Abundance and diversity of Shewanella species in wastewater treatment plants were largely affected by the process and operating conditions. Overall, this study suggests that investigations of abundance and diversity of Shewanella in various environments are of great importance to evaluate their ecophysiology and potential ecological roles.
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http://dx.doi.org/10.1016/j.scitotenv.2018.05.051DOI Listing
October 2018

Theoretical Development of Near-Infrared Bioluminescent Systems.

Chemistry 2018 Jul 7;24(37):9340-9352. Epub 2018 Jun 7.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, 100875, P. R. China.

The luciferin/luciferase system of the firefly has been used in bioluminescent imaging to monitor biological processes. In order to enhance the efficiency and expand the application range, some efforts have been made to tune the light emission, especially the effort to obtain NIR light. However, those case-by-case studies have not together revealed the nature and mechanism of the color tuning. In this paper, we theoretically investigated the fluorescence of all kinds of typical oxyluciferin analogues. The present systematical modifications of both oxyluciferin and luciferase indicate that the essential factor affecting the emission color is the charge distribution (or the electric dipole moment) on the oxyluciferin, which impacts on the charge transfer to form the light emitter and, subsequently, influence the strength and wavelength of the emission light. More negative charge distributed on the "thiazolone moiety" of the oxyluciferin or its analogues leads to a redshift. Based on this conclusion, we theoretically designed optimal pairs of luciferin analogue and luciferase for emitting NIR light, which could inspire new synthetic procedures and practical applications.
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http://dx.doi.org/10.1002/chem.201800416DOI Listing
July 2018

Reduction pathway and mechanism of chloronitrobenzenes synergistically catalyzed by bioPd and Shewanella oneidensis MR-1 assisted by calculation.

Chemosphere 2017 Nov 31;187:62-69. Epub 2017 Jul 31.

School of Resources and Environmental Engineering, Anhui University, China; Mining Environmental Restoration and Wetland Ecological Security Collaborative Innovation Center, Anhui University, China. Electronic address:

Although microbial synthesized palladium nanoparticles (bioPd) have been demonstrated to exhibit a great activity toward dechlorination of several chlorinated pollutants, there is no systematic investigation into the substituent effect on dechlorination. Chloronitrobenzenes are widely used for manufacturing and known as persistent pollutants with recalcitrance of biodegradation for nitro groups. In this work, bioPd was synthesized by Shewanella oneidensis MR-1. The dechlorination of 2-chloronitrobenzene, 4-chloronitrobenzene and 2,4-dichloronitrobenzene catalyzed by bioPd were investigated. Simultaneous dechlorination and nitro reduction were observed by synergistic catalysis of bioPd and S. oneidensis MR-1. Pd concentration was optimized for the reduction. Producing profiles of intermediates changed with the ratio of Pd to cell, supporting a size- or shape-controlled catalytic activity of bioPd. The removal of chloro atoms at para-position was easier than that at ortho-position in 2,4-DCNB, suggesting a position effect on the reduction, which was further supported by the frontier molecular orbital and frontier electron density of 2,4-DCNB according to density functional theory.
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http://dx.doi.org/10.1016/j.chemosphere.2017.07.155DOI Listing
November 2017

[Effect of Xinfeng Capsule on Pulmonary Function, Thi/Th2 Cells, and Regulatory T Cells of Adjuvant Arthritis Rats].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2017 Feb;37(2):225-231

Objective To observe the effects of Xinfeng Capsule (XFC) at different doses on lung function, Thl/Th2 cells, regulatory T cells (Treg) in adjuvant arthritis (AA) rats. Methods Totally 84 rats were randomly divided into 5 groups, i.e., the normal control group (NC) , the model group (M) , the methotrexate (MTX) group, the Tripterygium Glycosides Table (TGT) group, the low dose XFC (XFC- L) group, the medium dose XFC (XFC-M) group, the high dose XFC (XFC-H) group, 12 in each group. Freund's complete adjuvant (FCA; 0. 1 mL) was intradermally injected to all rats except those in the NC group from right rear paw to induce inflammation. Medication was started from the 19th day after inflam- mation. Normal saline was administered to rats in the NC group and the M group. Rats in the rest groups were correspondingly administered with MTX, TGT, XFC, respectively. Changes of each index were ob- served in all groups. Results (1) Compared with the NC group, rat paw swelling degree (E) , arthritis index (AI) , lung index (LI) , average expiratory flow in 1 second (FEV1/FVC%) , alveolitis integral, TNF- α, Th1/Th2 cells, transforming growth factor-β₁ ( TGF-β₁ ) expression significantly increased in the M group (P <0. 01) ; forced vital capacity (FVC) , peak expiratory flow 25% of vital capacity (FEF25), peak expiratory flow 50% of vital capacity (FEF50), peak expiratory flow 75% of vital capacity (FEF75), the maximum mid-expiratory flow (MMF) , peak expiratory flow (PEF) , CD4 ⁺Treg, CD4⁺CD25 ⁺Treg, IL-10, and Foxp3 expression significantly decreased in the M group (P <0. 01). (2) Compared with the M group, body weight, FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10, Treg, and Foxp3 expression increased in all treatment groups; E, Al, LI, FEV1/FVC%, TNF-α, Th1/Th2 cells, and TGF-β₁ expression decreased in all treatment groups (P <0. 05, P <0. 01). (3) Compared with the XFC-M group, LI, alveolitis integral, TNF- α, Th1/Th2 cells, and TGF-β1 increased; FVC, FEF25, FEF50, FEF75, IL-10, CD4⁺Treg, CD4⁺CD25⁺ Treg, and Foxp3 decreased in other treatment groups (P <0. 05, P <0. 01). Conclusions AA rats had local swollen paws and decreased lung function. XFC could significantly improve paw swelling and Al of AA rats, and improve lung function. It could reduce inflammatory reaction and immune complexes on tis- sue and organ damage, improve joint and pulmonary symptoms possibly through promoting expressions of IL-10, CD4⁺Treg, CD4⁺CD25⁺Treg, and Foxp3, and inhibiting TNF-α,Th1/Th2 cells, and TGF-β₁ ex- pression.
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February 2017

[Effect of Cadmium on Biodegradation of Nonylphenol by ].

Huan Jing Ke Xue 2017 Jan;38(1):294-300

College of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China.

The influence of Cd on the degradation of nonylphenol (NP) by SH1 was investigated in this study.The investigation revealed that biomass of the strain was significantly declined with the increase of Cd concentration.The biomass was declined by 27.1% in the presence of 10 mg·LCd after 24 h.The addition of Cd had a great influence on adsorption of NP by the strain.As for the effect of living stain,adsorption by SH1 cells was stimulated at low concentrations of Cd(0.5 mg·L),while inhibited at higher levels (≥5 mg·L).As for inactivation of microbes,adsorption by cells was stimulated at higher concentrations,but was only slightly influenced at low levels.The results showed that the intracellular enzymes had much greater degradation rate than the living cells.Different concentrations of Cd had different effects on bacteria and intracellular enzyme degradation of NP separately.The degradation efficiency when using intracellular enzymes and bacteria was inhibited at higher levels of Cd and the intracellular enzyme inhibition was more significant.Degradation by cells was stimulated at low concentrations of Cd,but no significant impact was found on that by intracellular enzymes.The degradation process of NP by intracellular enzymes of the strain conformed to the first-order kinetic model.The highest reaction rate was achieved when the concentrations of Cd was 0.5 mg·L and the half-life of this substrate was 5.5 h.However,the degradation process of NP by the strain did not conform to the first-order kinetic model.
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http://dx.doi.org/10.13227/j.hjkx.201607107DOI Listing
January 2017

Reprogramming-derived gene cocktail increases cardiomyocyte proliferation for heart regeneration.

EMBO Mol Med 2017 02;9(2):251-264

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up-regulation of several mitosis-related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3-shRNA (FIJs), induced CMs to re-enter the cell cycle and complete mitosis and cytokinesis in vitro More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction. Collectively, our findings present a cocktail FIJs that may be useful in cardiac regeneration and also provide a practical strategy for probing reprogramming assays for regeneration of other tissues.
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http://dx.doi.org/10.15252/emmm.201606558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286362PMC
February 2017

Mechanisms of pluripotency maintenance in mouse embryonic stem cells.

Cell Mol Life Sci 2017 05 20;74(10):1805-1817. Epub 2016 Dec 20.

Institute of Biomedical Sciences, Academia Sinica, IBMS Rm.417, 128 Academia Road, Section 2, Nankang, Taipei, 115, Taiwan.

Mouse embryonic stem cells (mESCs), characterized by their pluripotency and capacity for self-renewal, are driven by a complex gene expression program composed of several regulatory mechanisms. These mechanisms collaborate to maintain the delicate balance of pluripotency gene expression and their disruption leads to loss of pluripotency. In this review, we provide an extensive overview of the key pillars of mESC pluripotency by elaborating on the various essential transcription factor networks and signaling pathways that directly or indirectly support this state. Furthermore, we consider the latest developments in the role of epigenetic regulation, such as noncoding RNA signaling or histone modifications.
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http://dx.doi.org/10.1007/s00018-016-2438-0DOI Listing
May 2017

Redox properties of extracellular polymeric substances (EPS) from electroactive bacteria.

Sci Rep 2016 12 19;6:39098. Epub 2016 Dec 19.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China.

Although the capacity for electroactive bacteria to convert environmental metallic minerals and organic pollutants is well known, the role of the redox properties of microbial extracellular polymeric substances (EPS) in this process is poorly understood. In this work, the redox properties of EPS from two widely present electroactive bacterial strains (Shewanella oneidensis and Pseudomonas putida) were explored. Electrochemical analysis demonstrates that the EPS extracted from the two strains exhibited redox properties. Spectroelectrochemical and protein electrophoresis analyses indicate that the extracted EPS from S. oneidensis and P. putida contained heme-binding proteins, which were identified as the possible redox components in the EPS. The results of heme-mediated behavior of EPS may provide an insight into the important roles of EPS in electroactive bacteria to maximize their redox capability for biogeochemical cycling, environmental bioremediation and wastewater treatment.
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http://dx.doi.org/10.1038/srep39098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5171820PMC
December 2016

FlrA Represses Transcription of the Biofilm-Associated bpfA Operon in Shewanella putrefaciens.

Appl Environ Microbiol 2017 02 1;83(4). Epub 2017 Feb 1.

School of Life Sciences, Anhui University, Hefei, China.

Manipulation of biofilm formation in Shewanella is beneficial for application to industrial and environmental biotechnology. BpfA is an adhesin largely responsible for biofilm formation in many Shewanella species. However, the mechanism underlying BpfA production and the resulting biofilm remains vaguely understood. We previously described the finding that BpfA expression is enhanced by DosD, an oxygen-stimulated diguanylate cyclase, under aerobic growth. In the present work, we identify FlrA as a critical transcription regulator of the bpfA operon in Shewanella putrefaciens CN32 by transposon mutagenesis. FlrA acted as a repressor of the operon promoter by binding to two boxes overlapping the -10 and -35 sites recognized by σ DosD regulation of the expression of the bpfA operon was mediated by FlrA, and cyclic diguanylic acid (c-di-GMP) abolished FlrA binding to the operon promoter. We also demonstrate that FlhG, an accessory protein for flagellum synthesis, antagonized FlrA repression of the expression of the bpfA operon. Collectively, this work demonstrates that FlrA acts as a central mediator in the signaling pathway from c-di-GMP to BpfA-associated biofilm formation in S. putrefaciens CN32.

Importance: Motility and biofilm are mutually exclusive lifestyles, shifts between which are under the strict regulation of bacteria attempting to adapt to the fluctuation of diverse environmental conditions. The FlrA protein in many bacteria is known to control motility as a master regulator of flagellum synthesis. This work elucidates its effect on biofilm formation by controlling the expression of the adhesin BpfA in S. putrefaciens CN32 in response to c-di-GMP. Therefore, FlrA plays a dual role in controlling motility and biofilm formation in S. putrefaciens CN32. The cooccurrence of flrA, bpfA, and the FlrA box in the promoter region of the bpfA operon in diverse Shewanella strains suggests that bpfA is a common mechanism that controls biofilm formation in this bacterial species.
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http://dx.doi.org/10.1128/AEM.02410-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288817PMC
February 2017

In Vivo Cardioprotective Effects and Pharmacokinetic Profile of N-Propyl Caffeamide Against Ischemia Reperfusion Injury.

Arch Immunol Ther Exp (Warsz) 2017 Apr 1;65(2):145-156. Epub 2016 Aug 1.

School of Chinese Medicine, University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.

Caffeic acid derivatives constitute a class of potent anti-inflammatory and cardioprotective drug candidates. We recently synthesized a new caffeic acid derivative N-propyl caffeamide (PCA). Our pilot experiments demonstrated that PCA enhanced the survival of rat cardiomyocyte H9c2 cells against oxygen glucose deprivation and reoxygenation challenge in a concentration-dependent manner. Interestingly, PCA exhibited better cardioprotective potential than caffeic acid phenethyl ester and propyl caffeate. Thus, we hypothesized that PCA could protect heart against ischemia reperfusion (I/R) injury in mice. We first determined the stability and pharmacokinetic profile of PCA in male Sprague-Dawley rats by ultra-performance liquid chromatography coupled with UV and MS/MS detections. The stability of PCA in rat plasma was defined by the half-life of 31.39, 7.19 and 1.37 h in rat plasma at 25, 37 and 60 °C, respectively. To study the pharmacokinetic profiles, PCA was injected into male SD rats at the dose of 15 mg/kg via intravenous bolus administration. PCA showed the elimination half-life of approximate 235 min in rats. We subsequently evaluated the cardioprotective potential of PCA in mice model of myocardial infarction. Our results demonstrated that PCA effectively reduced infarct size and release of myocardial enzymes (e.g., CK, CK-MB and LDH). Biochemical analyses suggested that PCA increased the activities of antioxidant enzymes (e.g., CAT and SOD) while attenuated lipid peroxidation. Moreover, PCA profoundly reduced the number of apoptotic cells in infarcted myocardium. Consistently, PCA increased the expression level of anti-apoptotic protein Bcl2 whereas suppressed the expression of pro-apoptotic protein Bax in cardiac tissues. Collectively, PCA appears to be a novel bioavailable and stable pharmacological treatment for myocardial infarction.
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http://dx.doi.org/10.1007/s00005-016-0413-yDOI Listing
April 2017

Vibrationally Resolved Absorption and Fluorescence Spectra of Firefly Luciferin: A Theoretical Simulation in the Gas Phase and in Solution.

Photochem Photobiol 2016 07 8;92(4):552-60. Epub 2016 Jun 8.

Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.

Firefly bioluminescence has been applied in several fields. However, the absorption and fluorescence spectra of the substrate, luciferin, have not been observed at the vibrational level. In this study, the vibrationally resolved absorption and fluorescence spectra of firefly luciferin (neutral form LH2 , phenolate ion form LH(-) and dianion form L(2-) ) are simulated using the density functional method and convoluted by a Gaussian function, with displacement, distortion and Duschinsky effects in the framework of the Franck-Condon approximation. Both neutral and anionic forms of the luciferin are considered in the gas phase and in solution. The simulated spectra have desired band maxima with the experimental ones. The vibronic structure analysis reveals that the features of the most contributive vibrational modes coincide with the key geometry-changing region during transition between the ground state and the first singlet excited state.
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http://dx.doi.org/10.1111/php.12601DOI Listing
July 2016

What Exactly Is the Light Emitter of a Firefly?

J Chem Theory Comput 2015 Nov;11(11):5360-70

Firefly bioluminescence attracts people by its glaring beauty and fascinating applications, but what is the light emitter of a firefly? The answer to this question has been explored since before the 1960s. The unanimously accepted answer is that excited-state oxyluciferin is the light emitter. The complexity of this question arises from the existence of six chemical forms (keto, enol, keto-1, enol-1, enol-1′, and enol-2) of oxyluciferin. After decades of experimental and theoretical efforts, a consistent conclusion was almost reached in 2011: excited-state keto-1 is the only light emitter in fireflies. However, the debate is raised again by the latest in vitro experimental results. This study will solve this contradiction via hybrid quantum mechanics and molecular mechanics (QM/MM) calculations combined with molecular dynamics (MD). The calculations were performed in the real protein for the six chemical forms of oxyluciferin and their corresponding analogues employed in the latest experiments. By considering the real environment, the pH value, and a possible equilibrium of the chemical forms of oxyluciferin in vivo, the calculated results indicate that the main emitter is still the excited-state keto-1 form.
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http://dx.doi.org/10.1021/acs.jctc.5b00659DOI Listing
November 2015
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