Liu D

References (82)

Title : Isolation of four new monoterpenes from Ailanthus altissima (mill.) Swingle and their enzyme inhibitory effects - Song_2024_Fitoterapia_176_105984
Author(s) : Song Q , Duan ZK , Tan YN , Gao ZH , Liu D , Hao JL , Lin B , Huang XX , Song SJ
Ref : Fitoterapia , 176 :105984 , 2024
Abstract : A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking.
ESTHER : Song_2024_Fitoterapia_176_105984
PubMedSearch : Song_2024_Fitoterapia_176_105984
PubMedID: 38701870

Title : PED: a novel predictor-encoder-decoder model for Alzheimer drug molecular generation - Liu_2024_Front.Artif.Intell_7_1374148
Author(s) : Liu D , Song T , Na K , Wang S
Ref : Front Artif Intell , 7 :1374148 , 2024
Abstract : Alzheimer's disease (AD) is a gradually advancing neurodegenerative disorder characterized by a concealed onset. Acetylcholinesterase (AChE) is an efficient hydrolase that catalyzes the hydrolysis of acetylcholine (ACh), which regulates the concentration of ACh at synapses and then terminates ACh-mediated neurotransmission. There are inhibitors to inhibit the activity of AChE currently, but its side effects are inevitable. In various application fields where Al have gained prominence, neural network-based models for molecular design have recently emerged and demonstrate encouraging outcomes. However, in the conditional molecular generation task, most of the current generation models need additional optimization algorithms to generate molecules with intended properties which make molecular generation inefficient. Consequently, we introduce a cognitive-conditional molecular design model, termed PED, which leverages the variational auto-encoder. Its primary function is to adeptly produce a molecular library tailored for specific properties. From this library, we can then identify molecules that inhibit AChE activity without adverse effects. These molecules serve as lead compounds, hastening AD treatment and concurrently enhancing the AI's cognitive abilities. In this study, we aim to fine-tune a VAE model pre-trained on the ZINC database using active compounds of AChE collected from Binding DB. Different from other molecular generation models, the PED can simultaneously perform both property prediction and molecule generation, consequently, it can generate molecules with intended properties without additional optimization process. Experiments of evaluation show that proposed model performs better than other methods benchmarked on the same data sets. The results indicated that the model learns a good representation of potential chemical space, it can well generate molecules with intended properties. Extensive experiments on benchmark datasets confirmed PED's efficiency and efficacy. Furthermore, we also verified the binding ability of molecules to AChE through molecular docking. The results showed that our molecular generation system for AD shows excellent cognitive capacities, the molecules within the molecular library could bind well to AChE and inhibit its activity, thus preventing the hydrolysis of ACh.
ESTHER : Liu_2024_Front.Artif.Intell_7_1374148
PubMedSearch : Liu_2024_Front.Artif.Intell_7_1374148
PubMedID: 38690194

Title : Concentration-QTc Modeling of the DPP-4 Inhibitor HSK7653 in a First-in-Human Study of Chinese Healthy Volunteers - Wang_2024_Clin.Pharmacol.Drug.Dev__
Author(s) : Wang X , Liu H , Cui C , Niu X , Li H , Niu S , Yan P , Wu N , Li F , Wu Q , Chen K , Hu B , Liu D
Ref : Clin Pharmacol Drug Dev , : , 2024
Abstract : Cofrogliptin (HSK7653) is a long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus with a twice-monthly dosing regimen. This study included 62 participants (48 without food effect, 14 with food effect) receiving single doses of HSK7653 (5, 10, 25, 50, 100, and 150 mg) or placebo. Pharmacokinetic samples were collected over 24 hours postdosing and sampling times are aligned with 12-lead electrocardiograms (ECGs) which were derived from continuous ECG recordings. For the concentration-QT interval corrected for heart rate (C-QTc) analysis, we used linear mixed-effects modeling to characterize the correlation between plasma concentrations of HSK7653 and the change from baseline in the QT interval which was corrected by Fridericia's formula (deltaQTcF). The result showed that a placebo-corrected Fridericia corrected QT interval (deltadeltaQTcF) prolongation higher than 10 milliseconds is unlikely at the mean maximum observed concentration (C(max)) (411 ng/mL) associated with the recommended therapeutic doses (25 mg twice-monthly), even at the highest supratherapeutic concentration (2425 ng/mL). Thus, HSK7653 does not significantly affect QT prolongation at either recommended doses or the highest supratherapeutic concentration.
ESTHER : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedSearch : Wang_2024_Clin.Pharmacol.Drug.Dev__
PubMedID: 38757550

Title : ANGPTL4 accelerates ovarian serous cystadenocarcinoma carcinogenesis and angiogenesis in the tumor microenvironment by activating the JAK2\/STAT3 pathway and interacting with ESM1 - Li_2024_J.Transl.Med_22_46
Author(s) : Li YK , Gao AB , Zeng T , Liu D , Zhang QF , Ran XM , Tang ZZ , Li Y , Liu J , Zhang T , Shi GQ , Zhou WC , Zou WD , Peng J , Zhang J , Li H , Zou J
Ref : J Transl Med , 22 :46 , 2024
Abstract : BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
ESTHER : Li_2024_J.Transl.Med_22_46
PubMedSearch : Li_2024_J.Transl.Med_22_46
PubMedID: 38212795

Title : Identifying Sex-Specific Serum Patterns of Alzheimer's Mice through Deep TMT Profiling and a Concentration-Dependent Concatenation Strategy - Dey_2023_J.Proteome.Res__
Author(s) : Dey KK , Yarbro JM , Liu D , Han X , Wang Z , Jiao Y , Wu Z , Yang S , Lee D , Dasgupta A , Yuan ZF , Wang X , Zhu L , Peng J
Ref : J Proteome Res , : , 2023
Abstract : Alzheimer's disease (AD) is the most prevalent form of dementia, disproportionately affecting women in disease prevalence and progression. Comprehensive analysis of the serum proteome in a common AD mouse model offers potential in identifying possible AD pathology- and gender-associated biomarkers. Here, we introduce a multiplexed, nondepleted mouse serum proteome profiling via tandem mass-tag (TMTpro) labeling. The labeled sample was separated into 475 fractions using basic reversed-phase liquid chromatography (RPLC), which were categorized into low-, medium-, and high-concentration fractions for concatenation. This concentration-dependent concatenation strategy resulted in 128 fractions for acidic RPLC-tandem mass spectrometry (MS/MS) analysis, collecting -5 million MS/MS scans and identifying 3972 unique proteins (3413 genes) that cover a dynamic range spanning at least 6 orders of magnitude. The differential expression analysis between wild type and the commonly used AD model (5xFAD) mice exhibited minimal significant protein alterations. However, we detected 60 statistically significant (FDR < 0.05), sex-specific proteins, including complement components, serpins, carboxylesterases, major urinary proteins, cysteine-rich secretory protein 1, pregnancy-associated murine protein 1, prolactin, amyloid P component, epidermal growth factor receptor, fibrinogen-like protein 1, and hepcidin. The results suggest that our platform possesses the sensitivity and reproducibility required to detect sex-specific differentially expressed proteins in mouse serum samples.
ESTHER : Dey_2023_J.Proteome.Res__
PubMedSearch : Dey_2023_J.Proteome.Res__
PubMedID: 37910662

Title : The role of s-palmitoylation in neurological diseases: implication for zDHHC family - Liao_2023_Front.Pharmacol_14_1342830
Author(s) : Liao D , Huang Y , Liu D , Zhang H , Shi X , Li X , Luo P
Ref : Front Pharmacol , 14 :1342830 , 2023
Abstract : S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer's disease), HD (Huntington's disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.
ESTHER : Liao_2023_Front.Pharmacol_14_1342830
PubMedSearch : Liao_2023_Front.Pharmacol_14_1342830
PubMedID: 38293675

Title : Bioaccumulation, metabolism and toxicological effects of chiral insecticide malathion and its metabolites in zebrafish (Danio rerio) - Cui_2023_Chemosphere_318_137898
Author(s) : Cui J , Wei Y , Jiang J , Xiao S , Liu X , Zhou Z , Liu D , Wang P
Ref : Chemosphere , 318 :137898 , 2023
Abstract : The bioaccumulation, metabolism, tissue-specific distribution and toxicity of the widely used organophosphorous pesticide malathion to zebrafish were investigated on an enantiomeric level for evaluating the environmental risks. The metabolites were also monitored and evaluated. Malathion was metabolized by zebrafish very fast with the half-life of 0.12 d and showed a middle accumulation capacity in zebrafish with bioaccumulation factor (BCF) of 12.9 after a 15-d exposure. Brain could enrich higher concentration of malathion than other tissues. The metabolites malaoxon, malathion/malaoxon monocarboxylic acid (DMA), malathion/malaoxon dicarboxylic acid (DCA), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP) were found, in which DMTP and DCA were in higher level, indicating the metabolism was mainly induced by carboxylesterase degradation. The accumulation of malathion and malaoxon was stereoselective in zebrafish tissues, exhibiting S-enantiomer preferentially enriched. The acute toxicity test showed rac-malathion was low toxic to zebrafish, which was 1.2 and 1.6 folds more toxic than S-malathion and R-malathion respectively. Malaoxon was highly toxic to zebrafish and approximately 32 times more toxic than malathion. The toxicity of other metabolites was lower than malathion. Malathion could cause an apparent developmental toxicity to zebrafish embryo, including bradycardia, hatchability reduction and deformity, and abnormal movement patterns in zebrafish larva. Chronic toxicity indicated that malathion and malaoxon induced oxidative damage and neurotoxicity in the liver, brain and gill of zebrafish, and malaoxon exhibited a relatively high injury to the zebrafish brain. The results can provide information for the comprehensive assessment of the potential risk of malathion to aquatic organisms and highlight the necessity of consideration of stereoselectivity and metabolites when systemically evaluating pesticides.
ESTHER : Cui_2023_Chemosphere_318_137898
PubMedSearch : Cui_2023_Chemosphere_318_137898
PubMedID: 36702415

Title : Risk of resistance and the metabolic resistance mechanism of Laodelphax striatellus (Falln) to cyantraniliprole - Li_2023_Pestic.Biochem.Physiol_197_105685
Author(s) : Li Z , Wang X , Guo L , Yin T , Liu D , Liu S , You X , Xia X
Ref : Pestic Biochem Physiol , 197 :105685 , 2023
Abstract : Cyantraniliprole is a highly effective diamide insecticide used to control of Laodelphax striatellus (Fallen). This study aimed to assess the insecticide resistance risk of L. striatellus and its metabolic resistance mechanisms. After 25 continuous generations of selection, the resistance of L. striatellus to cyantraniliprole increased by 17.14-fold. The realistic heritability of resistance was 0.0751. After successive rearing for five generations without exposure to insecticides, the resistance ratio for the resistant strain of L. striatellus decreased by 3.47-fold, and the average resistance decline rate per generation was 0.0266. Cyantraniliprole-resistant strains did not exhibit cross-resistance to triflumezopyrim, pymetrozine, flonicamid, sulfoxaflor, dinotefuran, clothianidin, thiamethoxam, nitenpyram, or imidacloprid. Compared to those of the sensitive strain, the 2nd, 3rd, and 4th instars, nymphal stage durations, total preoviposition period, and average generation time of the resistant strain were markedly reduced. Furthermore, the activity of cytochrome P450 monooxygenase (P450) and carboxylesterase (CarE) were markedly increased. The upregulation of CYP419A1v2 expression was most evident among the P450 genes, with a 6.10-fold increase relative to that in the sensitive strain. The CarE gene LsCarE5 was significantly upregulated by 1.94-fold compared with that in the sensitive strain. With the continuous use of cyantraniliprole, L. striatellus may develop resistance to this insecticide. This resistance may be related to the increase in metabolic enzyme activities regulated by the overexpression of P450 and CarE genes.
ESTHER : Li_2023_Pestic.Biochem.Physiol_197_105685
PubMedSearch : Li_2023_Pestic.Biochem.Physiol_197_105685
PubMedID: 38072542

Title : A retrospective screening method for carbamate toxicant exposure based on butyrylcholinesterase adducts in human plasma with ultra-high performance liquid chromatography-tandem mass spectrometry - Ren_2023_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1225_123775
Author(s) : Ren Z , Chen B , Liang D , Liu D , Lei W , Liu S
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1225 :123775 , 2023
Abstract : Carbamate pesticides are extensively used in agriculture for their inhibition to acetylcholinesterase and damages to the insects' neural systems. Because of their toxicity, human poisoning incidents caused by carbamate pesticide exposure have occurred from time to time. What's more, some lethally toxic carbamate toxicants known as carbamate nerve agents (CMNAs) have been supplemented in Schedule 1 of the Annex on Chemicals in the Chemical Weapons Convention (CWC) by Organisation of the Prohibition of Chemical Weapons (OPCW) from 2020. And some other carbamates, like physostigmine, have been used in clinical treatment as anticholinergic drugs and their misuse may also cause damages to the body. Similar to organophosphorus toxicants, carbamate toxicants would react with butyrylcholinesterase (BChE) in plasma when entering the human body, resulting in the BChE adducts, based on which the exposure of carbamate toxicants could be detected retrospectively. In this study, methylcarbamyl nonapeptide and dimethylcarbamyl nonapeptide from pepsin digestion of BChE adducts were identified with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in product ion scan mode. Carbofuran was chosen as the target to establish the detection method of carbamate toxicant exposure based on methylcarbamyl nonapeptide digested from methylcarbamyl BChE. Procainamide-gel affinity purification, pepsin digestion and UHPLC-MS/MS analysis in multiple reaction monitoring (MRM) mode were applied. Under the optimized conditions of sample preparation and UHPLC-MS/MS MRM analysis, the limits of detection (LODs) reached 10.0 ng/mL of plasma exposed to carbofuran with satisfactory specificity. The quantitation approach was established with d(3)-carbofuran-exposed plasma as the internal standard (IS) and the linearity range was 30.0-1.00 x 10(3) nmol/L (R(2) >0.998) with the accuracy of 95.6%-107% and precision of >=9% relative standard deviation (RSD). The applicability was also evaluated by N,N-dimethyl-carbamates with the LODs of 30.0 nmol/L for pirimicarb-exposed plasma based on dimethylcarbamyl nonapeptide. Because most of carbamate toxicants has methylcarbamyl or dimethylcarbamyl groups, this approach could be applied on the retrospective screening of carbamate toxicant exposure including CMNAs, carbamate pesticides or carbamate drugs. This study could provide an effective means in the fields of CWC verification, toxicological mechanism investigation and down-selection of potential treatment options.
ESTHER : Ren_2023_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1225_123775
PubMedSearch : Ren_2023_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1225_123775
PubMedID: 37285767

Title : A model-informed approach to accelerate the clinical development of cofrogliptin (HSK7653), a novel ultralong-acting dipeptidyl peptidase-4 inhibitor - Cui_2023_Diabetes.Obes.Metab__
Author(s) : Cui C , Cao F , Kong, II , Wu Q , Li F , Li H , Liu D
Ref : Diabetes Obes Metab , : , 2023
Abstract : AIM: To employ a model-informed drug development approach in facilitating decision making and expediting the clinical progress of cofrogliptin (HSK7653), a novel ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, for the treatment of type 2 diabetes (T2D) via a biweekly dosing regimen. METHODS: Firstly, a population pharmacokinetics and pharmacodynamics (PopPKPD) model was developed using PK and PD data from a single ascending dose study to simulate the PK and PD time profiles of HSK7653 after multiple doses. Secondly, model-based meta-analysis (MBMA) was performed on published clinical studies of Eastern Asian subjects for all DPP-4 inhibitors. We hypothesized a consistent relationship between PK and DPP-4 inhibition in both healthy individuals and in those with T2D, establishing a quantitative correlation between DPP-4 inhibition and HbA1c. Finally, the predicted PK/DPP-4 inhibition/HbA1c profiles were validated by T2D patients in late clinical trials. RESULTS: The PK/DPP-4 inhibition/HbA1c profiles of T2D patients treated with HSK7653 matched the modelled data. Our PopPKPD and MBMA models predict multiple ascending dosing PK and PD characteristics from single ascending dosing data, as well as the long-term efficacy in T2D patients, based on healthy subjects. CONCLUSIONS: Successful waiver approval for the phase 2b dose-finding study was achieved through model-informed recommendations, facilitating the clinical development of HSK7653 and other DPP-4 inhibitors.
ESTHER : Cui_2023_Diabetes.Obes.Metab__
PubMedSearch : Cui_2023_Diabetes.Obes.Metab__
PubMedID: 37953687

Title : Developing a Two-Photon AND Logic Probe and Its Application in Alzheimer's Disease Differentiation - Guo_2023_Anal.Chem__
Author(s) : Guo J , Sun J , Liu D , Liu J , Gui L , Luo M , Kong D , Wusiman S , Yang C , Liu T , Yuan Z , Li R
Ref : Analytical Chemistry , : , 2023
Abstract : In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous acid and butyrylcholinesterase. In addition, single-response probes suffer from serious off-target effects and near-infrared probes do not easily penetrate the blood-brain barrier due to their excessive molecular weight. In this work, we constructed a two-photon fluorescent probe that recognizes hypochlorous acid and butyrylcholinesterase based on a dual-lock strategy. The thiocarbonyl group is oxidized in the presence of hypochlorous acid, and the hydrolysis occurs at the 7-position ester bond in the existence of butyrylcholinesterase, releasing a strongly fluorescent fluorophore, 4-methylumbelliferone. Excellent imaging was performed in PC12 cells using this probe, and deep two-photon imaging was observed in the brains of AD mice after tail vein injection with this probe. It indicates that the probe can provide a promising tool for the more precise diagnosis of Alzheimer's disease.
ESTHER : Guo_2023_Anal.Chem__
PubMedSearch : Guo_2023_Anal.Chem__
PubMedID: 37947381

Title : Carbamate-based N-Substituted tryptamine derivatives as novel pleiotropic molecules for Alzheimer's disease - Zhang_2022_Bioorg.Chem_125_105844
Author(s) : Zhang H , Wang Y , Liu D , Li J , Feng Y , Lu Y , Yin G , Li Z , Shi T , Wang Z
Ref : Bioorg Chem , 125 :105844 , 2022
Abstract : A novel series of carbamate-based N-substituted tryptamine derivatives were designed and synthesized based on functional group combination strategy, and possessed both cholinesterase inhibition and neuroprotective effects. After systematically evaluating the cholinesterase inhibitory activity of 24 synthesized compounds, compound 6H6, bearing n-heptyl residue as carbamate moiety, was highlighted due to its great BChE-selective inhibition (eeAChE IC(50) > 100 microM; eqBChE IC(50) = 7 nM), neuronal protection, antioxidation and anti-neuroinflammation efficacy. Cytotoxicity and acute toxicity assays confirmed the safety-efficacy profiles of compound 6H6. Besides, pharmacokinetic properties and blood-brain barrier (BBB) permeability of compound 6H6 were favorable and suitable for further study in vivo. The behavioral tests revealed that compound 6H6 could remarkably improve the scop-induced ethological changes and memory impairment, suggesting compound 6H6, as an attractive pleiotropic molecule, had great promise in treating Alzheimer's disease.
ESTHER : Zhang_2022_Bioorg.Chem_125_105844
PubMedSearch : Zhang_2022_Bioorg.Chem_125_105844
PubMedID: 35594720

Title : Discovery of carbamate-based N-salicyloyl tryptamine derivatives as novel pleiotropic agents for the treatment of Alzheimer's disease - Wang_2022_Bioorg.Chem_127_105993
Author(s) : Wang Y , Zhang H , Liu D , Li X , Long L , Peng Y , Qi F , Jiang W , Wang Z
Ref : Bioorg Chem , 127 :105993 , 2022
Abstract : In this work, based on the potential anti-AD molecule previously studied by our group, we continue to introduce different substituents at different positions to improve both drug-like properties and on target activities. 33 N-salicyloyl tryptamine-carbamate hybrids were designed, synthesized and evaluated as cholinesterase inhibitors. H327 was the most potent BChE inhibitor (eqBChE IC(50) = 0.057 +/- 0.005 microM), and showed threefold improved inhibitory potency than the positive drug rivastigmine (eqBChE IC(50) = 0.19 +/- 0.001 microM). In addition, H327 as a pseudo-irreversible BChE inhibitor was endowed with neuroprotective, antioxidative and anti-neuroinflammatory properties. Cytotoxicity and acute toxicity tests confirmed the safety of compound H327. The pharmacokinetics study showed that compound H327 had a longer T(1/2) time and higher bioavailability than the lead compound 1 g. Compound H327 was able to cross the blood-brain barrier (BBB) in vivo. Moreover, the behavioral tests showed that compound H327 could significantly improve scopolamine-induced cognitive impairment in vivo. Overall, these results demonstrated that compound H327 is a promising multi-target agent for the treatment of AD.
ESTHER : Wang_2022_Bioorg.Chem_127_105993
PubMedSearch : Wang_2022_Bioorg.Chem_127_105993
PubMedID: 35834980

Title : Sensitivity Differences and Biochemical Characteristics of Laodelphax striatellus (Falln) to Seven Insecticides in Different Areas of Shandong, China - Xue_2022_Insects_13_
Author(s) : Xue Y , Liu C , Liu D , Ding W , Li Z , Cao J , Xia X
Ref : Insects , 13 : , 2022
Abstract : Laodelphax striatellus Fallen is one of the main pests that can severely harm rice, corn, and wheat. Insecticides acting on the nicotinic acetylcholine receptor (nAChR) are the main type of pesticides used for the control of L. striatellus in Shandong Province, a major grain-producing region in China. In this study, the rice seedling dipping method was used to determine the sensitivities of six field L. striatellus populations in Shandong to seven insecticides acting on nAChR. The results showed that all the field populations were sensitive to clothianidin, nitenpyram, and triflumezopyrim, and the Jiaxiang population exhibited the lowest resistance ratio (RR) to imidacloprid, dinotefuran, sulfoxaflor, and thiamethoxam. The Donggang population showed a medium-level resistance to imidacloprid, with the highest RR of 17.48-fold. The Yutai population showed low-level resistance to imidacloprid and thiamethoxam, with RRs of 7.23- and 7.02-fold, respectively. The contents of cytochrome P450 monooxygenase (P450s), carboxylesterase (CarE), and glutathione S-transferase (GST) were the highest in the Donggang population and the lowest in the Jiaxiang population. The P450 gene CYP314A1 and the CarE gene LsCarE12 were highly up-regulated in all populations. No mutations of V62I, R81T, and K265E in the nAChR beta1 subunit were found in any of the populations. These results provide valuable information for the strategies of resistance management of L. striatellus in the field.
ESTHER : Xue_2022_Insects_13_
PubMedSearch : Xue_2022_Insects_13_
PubMedID: 36135481

Title : Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease - Liu_2022_Eur.J.Med.Chem_229_114044
Author(s) : Liu D , Zhang H , Wang Y , Liu W , Yin G , Wang D , Li J , Shi T , Wang Z
Ref : Eur Journal of Medicinal Chemistry , 229 :114044 , 2022
Abstract : In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-alpha, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Abeta(1-42). Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.
ESTHER : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedSearch : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedID: 34923430

Title : Isolation and acetylcholinesterase inhibitory activity of asterric acid derivatives produced by Talaromyces aurantiacus FL15, an endophytic fungus from Huperzia serrata - Xiao_2022_3.Biotech_12_60
Author(s) : Xiao Y , Liang W , Liu D , Zhang Z , Chang J , Zhu D
Ref : 3 Biotech , 12 :60 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease and the fourth leading cause of death after cardiovascular disease, tumors, and stroke. Acetylcholinesterase (AChE) inhibitors, which are based on cholinergic damage, remain the mainstream drugs to alleviate AD-related symptoms. This study aimed to explore novel AChE inhibitors produced by the endophytic fungus FL15 from Huperzia serrata. The fungus was identified as Talaromyces aurantiacus FL15 according to its morphological characteristics and ITS, 18S rDNA, and 28S rDNA sequence analysis. Subsequently, seven natural metabolites were isolated from strain FL15, and identified as asterric acid (1), methyl asterrate (2), ethyl asterrate (3), emodin (4), physcion (5), chrysophanol (6), and sulochrin (7). Compounds 1-3, which possess a diphenyl ether structure, exhibited highly selective and moderate AChE inhibitory activities with IC(50) values of 66.7, 23.3, and 20.1 microM, respectively. The molecular docking analysis showed that compounds 1-3 interacted with the active catalytic site and peripheral anionic site of AChE, and the esterification substitution groups at position 8 of asterric acid may contribute to its bioactivity. The asterric acid derivatives showed highly selective and moderate AChE inhibitory activities, probably via interaction with the peripheral anionic site and catalytic site of AChE. To the best of our knowledge, this study was the first report of the AChE inhibitory activity of asterric acid derivatives, which opens new perspectives for the design of more effective derivatives that could serve as a drug carrier for new chemotherapeutic agents to treat AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-022-03125-2.
ESTHER : Xiao_2022_3.Biotech_12_60
PubMedSearch : Xiao_2022_3.Biotech_12_60
PubMedID: 35186657

Title : Phlorizin alleviates cholinergic memory impairment and regulates gut microbiota in d-galactose induced mice - Su_2022_Exp.Gerontol__111863
Author(s) : Su YL , Liu D , Liu YJ , Ji YL , Liu GS , Wang JL , Wang B , Wang H
Ref : Experimental Gerontology , :111863 , 2022
Abstract : We explored the effect of phlorizin against cholinergic memory impairment and dysbacteriosis in D-galactose induced ICR mice. The control (CON) group, D-galactose model (DGM) group, and three groups (DG-PL, DG-PM, DG-PH) treated with phlorizin at 0.01%, 0.02%, and 0.04% (w/w) in diets were raised for 12 weeks. Supplementing with phlorizin reversed the loss of organ coefficient and body weight caused by D-galactose. The functional abilities of phlorizin on hippocampal-dependent spatial learning and memory, anti-oxidation, anti-inflammation were also observed. Meanwhile, phlorizin intervention upregulated the gene expression of Nrf2, GSH-PX, SOD1, decreased the gene expression of NF-kappaB, TLR-4, TNF-alpha, and IL-1beta in the hippocampus, while enhanced the gene expression of JAM-A, Mucin2, Occludin in the caecum. Furthermore, a neurotransmitter of acetylcholine (ACh) was enhanced, while acetylcholinesterase (AChE) activity was inhibited by phlorizin administration. Moreover, phlorizin administration increased short-chain fatty acids (SCFAs) content, and reduced lipopolysaccharides (LPS) levels, which may relate to the rebuilding of gut microbiota homeostasis. Treatment with phlorizin may be an effective intervention for alleviating cognitive decline and gut microbiota dysbiosis.
ESTHER : Su_2022_Exp.Gerontol__111863
PubMedSearch : Su_2022_Exp.Gerontol__111863
PubMedID: 35660419

Title : Screening and identification of anti-acetylcholinesterase ingredients from Tianzhi granule based on ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry and in silico analysis - Zhao_2022_J.Ethnopharmacol__115641
Author(s) : Zhao N , Liu D , Wang Y , Zhang X , Zhang L
Ref : J Ethnopharmacol , :115641 , 2022
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Tianzhi granule (TZG) is a traditional Chinese formula that is widely used for the treatment of vascular dementia (VaD). AIM OF THE STUDY: To discover the herbs in TZG possessing acetylcholinesterase (AChE) inhibitory activity and to screen the anti-acetylcholinesterase ingredients from active herbs. MATERIALS AND METHODS: In vitro AChE inhibitory activity assay of eleven herbal extracts was conducted. An ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry method was established to screen and identify the anti-acetylcholinesterase ingredients from active extracts. In addition, in vitro AChE inhibitory activity assay and molecular docking were adopted for further investigation. Moreover, ultra-performance liquid chromatography-mass spectrometry was performed for the content determination of active compounds in TZG. RESULTS: Three herbs in TZG showed significant AChE inhibitory activity. A total of thirteen active ingredients were screened out and identified, and all of these compounds were present in TZG. Five available commercial standards presented moderate AChE inhibitory activity, and all of which have a relatively high content in TZG. CONCLUSION: A number of herbs and compounds with acetylcholinesterase inhibitory activity were found in TZG, which provided a scientific basis for the material basis and quality control research of TZG.
ESTHER : Zhao_2022_J.Ethnopharmacol__115641
PubMedSearch : Zhao_2022_J.Ethnopharmacol__115641
PubMedID: 35973628

Title : Invasive Plants Have Higher Resistance to Native Generalist Herbivores Than Exotic Noninvasive Congeners - Wu_2022_Environ.Entomol__
Author(s) : Wu S , Chen L , Zhou Y , Xiao F , Liu D , Wang Y
Ref : Environ Entomol , : , 2022
Abstract : Research on the invasive plant Phytolacca americana (L.) mostly focuses on its medicinal value and enrichment of heavy metals. However, little is known regarding its impact on native herbivorous insects. In this study, we explored the effects of P. americana and the exotic noninvasive Phytolacca icosandra (L.) on the Spodoptera litura (Fabricius) (native tobacco cutworm) via bioassay, oviposition preference, detoxifying enzyme activity analysis, and phytochemical determination. We found that the oviposition preference index (OPI) of S. litura feeding on P. icosandra was higher than that of P. americana. The developmental duration of S. litura feeding on P. icosandra was shorter than that of P. americana. Additionally, the Acetylcholinesterase (AchE) and Glutathione-S-transferase (GST) activities of S. litura feeding on P. americana were higher than that of S. litura feeding on artificial diets or P. icosandra. The content of lignin and flavonoids in P. americana was relatively high, whereas starch content was relatively low. These findings suggest invasive plants have higher resistance to herbivores, thereby suffering less damage than exotic noninvasive plants.
ESTHER : Wu_2022_Environ.Entomol__
PubMedSearch : Wu_2022_Environ.Entomol__
PubMedID: 36545824

Title : IL-6 downregulates hepatic carboxylesterases via NF-kappaB activation in dextran sulfate sodium-induced colitis - Li_2021_Int.Immunopharmacol_99_107920
Author(s) : Li M , Lan L , Zhang S , Xu Y , He W , Xiang D , Liu D , Ren X , Zhang C
Ref : Int Immunopharmacol , 99 :107920 , 2021
Abstract : Ulcerative colitis (UC) is associated with increased levels of inflammatory factors, which is attributed to the abnormal expression and activity of enzymes and transporters in the liver, affecting drug disposition in vivo. This study aimed to examine the impact of intestinal inflammation on the expression of hepatic carboxylesterases (CESs) in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Two major CESs isoforms, CES1 and CES2, were down-regulated, accompanied by decreases in hepatic microsomal metabolism of clopidogrel and irinotecan. Meanwhile, IL-6 levels significantly increased compared with other inflammatory factors in the livers of UC mice. In contrast, using IL-6 antibody simultaneously reversed the down-regulation of CES1, CES2, pregnane X receptor (PXR), and constitutive androstane receptor (CAR), as well as the nuclear translocation of NF-kappaB in the liver. We further confirmed that treatment with NF-kappaB inhibitor abolished IL-6-induced down-regulation of CES1, CES2, PXR, and CAR in vitro. Thus, it was concluded that IL-6 represses hepatic CESs via the NF-kappaB pathway in DSS-induced colitis. These findings indicate that caution should be exercised concerning the proper and safe use of therapeutic drugs in patients with UC.
ESTHER : Li_2021_Int.Immunopharmacol_99_107920
PubMedSearch : Li_2021_Int.Immunopharmacol_99_107920
PubMedID: 34217990

Title : m(6) A transferase METTL3-induced lncRNA ABHD11-AS1 promotes the Warburg effect of non-small-cell lung cancer - Xue_2021_J.Cell.Physiol_236_2649
Author(s) : Xue L , Li J , Lin Y , Liu D , Yang Q , Jian J , Peng J
Ref : Journal of Cellular Physiology , 236 :2649 , 2021
Abstract : N(6) -methyladenosine (m(6) A) and long noncoding RNAs (lncRNAs) are both crucial regulators in non-small-cell lung cancer (NSCLC) tumorigenesis. However, the pathological roles of m(6) A and lncRNAs in NSCLC progression are still limited and undefined. Here, lncRNA ABHD11-AS1 was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients. Functionally, ABHD11-AS1 promoted the proliferation and Warburg effect of NSCLC. Mechanistically, m(6) A profile was analyzed by methylated RNA immunoprecipitation sequencing (MeRIP-Seq). MeRIP-Seq presented that there was m(6) A modification site in ABHD11-AS1. m(6) A methyltransferase-like 3 (METTL3) installed the m(6) A modification and enhanced ABHD11-AS1 transcript stability to increase its expression. In conclusion, our findings highlight the function and mechanism of METTL3-induced ABHD11-AS1 in NSCLC and inspire the understanding of m(6) A and lncRNA in cancer biology.
ESTHER : Xue_2021_J.Cell.Physiol_236_2649
PubMedSearch : Xue_2021_J.Cell.Physiol_236_2649
PubMedID: 32892348
Gene_locus related to this paper: human-ABHD11

Title : Characterization and structural analysis of a thermophilic GH11 xylanase from compost metatranscriptome - Yi_2021_Appl.Microbiol.Biotechnol_105_7757
Author(s) : Yi Y , Xu S , Kovalevsky A , Zhang X , Liu D , Wan Q
Ref : Applied Microbiology & Biotechnology , 105 :7757 , 2021
Abstract : Xylanase is efficient for xylan degradation and widely applied in industries. We found a GH11 family xylanase (Xyn11A) with high thermostability and catalytic activity from compost metatranscriptome. This xylanase has the optimal reaction temperature at 80 degreesC with the activity of 2907.3 U/mg. The X-ray crystallographic structure shows a typical "right hand" architecture, which is the characteristics of the GH11 family enzymes. Comparing it with the mesophilic XYN II, a well-studied GH11 xylanase from Trichoderma reesei, Xyn11A is more compact with more H-bonds. Our mutagenic results show that the electrostatic interactions in the thumb and palm region of Xyn11A could result in its high thermostability and activity. Introducing a disulfide bond at the N-terminus further increased its optimal reaction temperature to 90 degreesC with augmented activity. KEY POINTS: A hyperthermophilic xylanase with high activity was discovered using the metatranscriptomic method. The mechanisms of thermophilicity and high activity were revealed using X-ray crystallography, mutagenesis, and molecular dynamics simulations. The thermostability and activity were further improved by introducing a disulfide bond.
ESTHER : Yi_2021_Appl.Microbiol.Biotechnol_105_7757
PubMedSearch : Yi_2021_Appl.Microbiol.Biotechnol_105_7757
PubMedID: 34553251

Title : Carboxylesterase 1 polymorphisms are associated with clinical outcomes in gastroenteric cancer patients treated with capecitabine - Liu_2021_Cancer.Chemother.Pharmacol__
Author(s) : Liu D , Li X , Wang H , Dong M
Ref : Cancer Chemother Pharmacol , : , 2021
Abstract : OBJECTIVES: The aim of this study was to test whether CES1, UMPS, DPYS and TPYS polymorphisms influence the outcomes of gastroenteric cancer patients. METHODS: We consecutively enrolled 338 patients who were diagnosed with colorectal and gastric cancer from January 2016 to December 2018 at the Harbin Medical University Cancer Hospital, China. RESULTS: We found that the patients with CES1 rs7187684 CC genotype had a higher proportion of stage III-IV and relapse rate significantly compared with CT/TT genotype, and the patients with rs7187684 CC genotype had a higher level of CA199 than CT/TT genotype after adjusted for tumor stage, and medication, age, sex, smoking, and drinking. Moreover, the patients with rs7187684 CC genotype had shorter event-free survival (EFS) than CT/TT genotype, and a significant shorter EFS was also found in the patients with rs2244613 TT genotype than GG or GT genotype. Subset analysis results showed that the male, less-drinking or gastric cancer patients with rs7187684 CC genotype had shorter EFS than the patients with CT/TT genotype. Compared with the patients with CES1 rs2244613 TT genotype, the stage I-II patients with GG/GT genotype had longer progression-free survival (PFS), and the male patients with GG/GT genotype had longer EFS. Multivariate Cox regression analysis showed that stage III-IV and tumor metastasis could reduce the patients' PFS and EFS. CONCLUSIONS: The identified CES1 polymorphisms might provide guide for the identification of gastroenteric cancer patients who were likely to benefit from capecitabine-based chemotherapy.
ESTHER : Liu_2021_Cancer.Chemother.Pharmacol__
PubMedSearch : Liu_2021_Cancer.Chemother.Pharmacol__
PubMedID: 33586000

Title : Neuroligin 3 from common cutworm enhances the Gaba-induced current of recombinant Slrdl1 channel - Wang_2021_Pest.Manag.Sci__2
Author(s) : Wang Y , Zhang YC , Zhang KX , Jia ZQ , Tang T , Zheng LL , Liu D , Zhao CQ
Ref : Pest Manag Sci , : , 2021
Abstract : BACKGROUND: Neuroligin protein (NLG) is a nerve cell adhesion molecule and plays a key role in the precision apposition of presynaptic domains on inhibitory and excitatory synapses. Existing studies mainly focused on the function of NLG3 against the excitatory channel. However, the interaction between insect NLG3 and ionotropic GABA receptor, which is the main inhibitory channel, remains unclear. In this study, the Nlg3 of common cutworm (CCW), Spodoptera litura Fabricius, one important agricultural lepidopteron, is selected to explore its function in inhibitory channel. RESULTS: The SlNlg3 was obtained and the SlNLG3 contains the characteristic features including transmembrane domain, PDZ-binding motif and type-B carboxylesterases signature 2 motif. The SlNlg3 mRNA was most abundant in midgut, and exhibited multiple expression patterns in different developmental stages and tissues or body parts. Compared with the single injection of SlRDL1, the EC(50) value of GABA in activating currents was smaller in Xenopus laevis oocytes co-injected with SlRDL1 and SlNlg3. In addition, SlNlg3 could enhance the GABA-induced current of homomeric SlRDL1 channel from -391.86 +/- 15.41 nA to -2152.51 +/- 30.09 nA. DsSlNlg3 depressed the expression level of SlNlg3 mRNA more than 64.29% at 6 h. After exposure to LD(50) of fluralaner, the mortality of CCW injected with dsSlNlg3 was significantly decreased by 13.34% and 30.00% at 24 and 48 h, respectively, compared to injection of dsEGFP. CONCLUSION: NLG3 should have physiological function on ionotropic GABA receptor in vitro, which provided a favorable foundation for further research on the physiological function of Nlg gene in lepidopteron. This article is protected by copyright. All rights reserved.
ESTHER : Wang_2021_Pest.Manag.Sci__2
PubMedSearch : Wang_2021_Pest.Manag.Sci__2
PubMedID: 34619015
Gene_locus related to this paper: spofr-a0a2h1vmr3

Title : Biofilm polysaccharide display platform: A natural, renewable, and biocompatible material for improved lipase performance - Dong_2020_J.Agric.Food.Chem__
Author(s) : Dong H , Zhang W , Wang Y , Liu D , Wang P
Ref : Journal of Agricultural and Food Chemistry , : , 2020
Abstract : Most of microorganisms can form biofilms, which makes biofilms become an abundant bioresource to be exploited. Due to the application limitations of current immobilization methods onto biofilms, we developed an immobilization method called the Biofilm Polysaccharides Display (BPD) strategy while maintaining the native biofilm structure and catalytic microenvironment of C. acetobutylicum B3. Lipase Lip181 showed significant improvements in stability after chemical immobilization. For example, immobilized Lip181 retained 74.23% of its original activity after incubation for 14 days while free Lip181 was totally deactivated. In addition, immobilized Lip181 maintained high residual activity (pH 5.0pH 11.0), which showed improved resistance to pH changes. Notably, this method did not decrease but slightly increased the relative activity of Lip181 from 6.39 to 6.78 U/mg. Immobilized Lip181 was used to prepare cinnamyl acetate, and it showed a maximum yield of 85.09%. Overall, this biofilm immobilization method may promote the development of biocatalysis and biofilm materials.
ESTHER : Dong_2020_J.Agric.Food.Chem__
PubMedSearch : Dong_2020_J.Agric.Food.Chem__
PubMedID: 31927950

Title : Cell Wall Polysaccharide-Mediated Cadmium Tolerance Between Two Arabidopsis thaliana Ecotypes - Xiao_2020_Front.Plant.Sci_11_473
Author(s) : Xiao Y , Wu X , Liu D , Yao J , Liang G , Song H , Ismail AM , Luo JS , Zhang Z
Ref : Front Plant Sci , 11 :473 , 2020
Abstract : Cadmium (Cd) is a toxic metal element and the mechanism(s) underlying Cd tolerance in plants are still unclear. Increasingly more studies have been conducted on Cd binding to plant cell walls (CW) but most of them have focused on Cd fixation by CW pectin, and few studies have examined Cd binding to cellulose and hemicellulose. Here we found that Cd binding to CW pectin, cellulose, and hemicellulose was significantly higher in Tor-1, a Cd tolerant A. thaliana ecotype, than in Ph2-23, a sensitive ecotype, as were the concentrations of pectin, cellulose, and hemicellulose. Transcriptome analysis revealed that the genes regulating CW pectin, cellulose, and hemicellulose polysaccharide concentrations in Tor-1 differed significantly from those in Ph2-23. The expressions of most genes such as pectin methyl esterase inhibitors (PMEIs), pectin lyases, xyloglucan endotransglucosylase/hydrolase, expansins (EXPAs), and cellulose hydrolase were higher in Ph2-23, while the expressions of cellulose synthase-like glycosyltransferase 3 (CSLG3) and pectin ethyl esterase 4 (PAE4) were higher in Tor-1. The candidate genes identified here seem to regulate CW Cd fixation by polysaccharides. In conclusion, an increase in pectin demethylation activity, the higher concentration of cellulose and hemicellulose, regulated by related genes, in Tor-1 than in Ph2-23 are likely involved in enhanced Cd CW retention and reduce Cd toxicity.
ESTHER : Xiao_2020_Front.Plant.Sci_11_473
PubMedSearch : Xiao_2020_Front.Plant.Sci_11_473
PubMedID: 32477379

Title : Circumdatin D Exerts Neuroprotective Effects by Attenuating LPS-Induced Pro-Inflammatory Responses and Downregulating Acetylcholinesterase Activity In Vitro and In Vivo - Zhang_2020_Front.Pharmacol_11_760
Author(s) : Zhang C , Hu L , Liu D , Huang J , Lin W
Ref : Front Pharmacol , 11 :760 , 2020
Abstract : Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with multifactorial causes, of which systemic inflammation may play a key role to promote neurodegeneration, and acetylcholinesterase (AChE) is a target protein to induce cholinergic transmission. Inhibitors toward inflammation and targeting AChE are regarded to promote cholinergic signaling of the central nervous system in AD therapy. During the search for neuroprotection agents from marine-derived compounds, seven circumdatin-type alkaloids from a coral-associated fungus Aspergillus ochraceus LZDX-32-15 showed potent inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production and activation of NF-kappaB report gene along with anti-AChE activities. Among the tested compounds, circumdatin D showed the most potent inhibitory effect against AChE activity and NO production. In vivo experiments using AD-like nematode models demonstrated that circumdatin D effectively delayed paralysis of CL4176 worms upon temperature up-shift via suppression of AChE activity and inflammatory-related gene expression. Moreover, circumdatin D interfered with inflammatory response by inhibiting the secretion of pro-inflammatory cytokines in LPS-induced BV-2 and primary microglia cells. Mechanistically, circumdatin D modulated Toll-like receptor 4 (TLR4)-mediated NF-kappaB, MAPKs and JAK/STAT inflammatory pathways in LPS-stimulated BV-2 cells, and protected primary neurons cells from LPS-induced neurotoxicity. Thus, circumdatin D is a potential agent for neuroprotective effects by the multi-target strategy.
ESTHER : Zhang_2020_Front.Pharmacol_11_760
PubMedSearch : Zhang_2020_Front.Pharmacol_11_760
PubMedID: 32523534

Title : DPP4 Activities Are Associated with Osteopenia\/Osteoporosis and Fracture Risk in Newly Diagnosed Type 2 Diabetes - Qiu_2020_Int.J.Endocrinol_2020_8874272
Author(s) : Qiu M , Zhai S , Liu D
Ref : Int J Endocrinol , 2020 :8874272 , 2020
Abstract : BACKGROUND: Recent studies have shown the beneficial effect of dipeptidyl peptidase-4 (DPP4) inhibitor on bone turnover in diabetes mellitus. However, little clinical evidence for DPP4 activity in newly diagnosed type 2 diabetes is available. This study was designed to investigate the relationship between plasma DPP4 activity and osteoporosis/osteopenia and fracture risk in newly diagnosed type 2 diabetes. METHODS: A total of 147 subjects with newly diagnosed type 2 diabetes were enrolled for this cross-sectional study. The bone mineral density (BMD) at the lumbar spine (L1-4) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) was assessed by a modified fracture risk algorithm (FRAX) tool. The plasma DPP4 activity and clinical variables were measured. Correlation analyses between DPP4 activity and osteoporosis/osteopenia and fracture risk were performed. RESULTS: Elevated plasma DPP activities were significantly associated with a higher proportion of osteoporosis/osteopenia (50% for quartile-1, 56.4% for quartile-2, 65.8% for quartile-3 and 72.2% for quartile-4). With increasing plasma DPP activities, the incidence rate of osteoporosis/osteopenia is gradually increasing (P for the trend between quartiles = 0.04). Of note, a statistically significant linear correlation was found between plasma DPP4 activities and modified FRAX MOF (r = 0.20, P=0.02). Moreover, plasma DPP4 activities were also positively related to modified FRAX HF in newly diagnosed type 2 diabetic patients (r = 0.21, P=0.01). CONCLUSIONS: Elevated plasma DPP4 activity tended to be associated with a higher proportion of osteoporosis/osteopenia and increased the fracture risk in newly diagnosed type 2 diabetes.
ESTHER : Qiu_2020_Int.J.Endocrinol_2020_8874272
PubMedSearch : Qiu_2020_Int.J.Endocrinol_2020_8874272
PubMedID: 33312197

Title : Kinetics and Mechanism of Solvent Influence on the Lipase-Catalyzed 1,3-Diolein Synthesis - Wang_2020_ACS.Omega_5_24708
Author(s) : Wang Z , Dai L , Liu D , Liu H , Du W
Ref : ACS Omega , 5 :24708 , 2020
Abstract : 1,3-Diacylglycerol preparation has roused increasing attention in recent years as the 1,3-diacylglycerol-rich oils can suppress the deposition of visceral fat and prevent the body weight increasing. Lipozyme TL IM-mediated esterification of oleic acid with monoolein was effective for 1,3-diacylglycerol production. During the esterification process, the solvent shows obvious influence on the diolein synthesis as well as the 1,3-diolein production. This work investigated the related kinetics and mechanism of the solvent effect on the esterification and Lipozyme TL IM performance. The results indicated that both the esterification rate constant and the acyl migration rate constant positively correlated with the logP of the solvent, while the site specificity of lipase has negative correlation with solvent logP. The acylation toward the 2-position of 1-monoolein was more sensitive to the solvent logP compared to the 1-position of glycerides. Molecular dynamics simulation revealed that solvents with different logP influenced the structure of Lipozyme TL IM including RMSD, hydrogen bond, and radial distribution function to a large extent, which subsequently led to the catalytic activity and selectivity variation of the lipase.
ESTHER : Wang_2020_ACS.Omega_5_24708
PubMedSearch : Wang_2020_ACS.Omega_5_24708
PubMedID: 33015488

Title : Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2 - Yu_2019_Int.J.Mol.Sci_20_
Author(s) : Yu M , Zhang L , Liu Y , Liu D , Guo Z
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets alpha/beta-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2.
ESTHER : Yu_2019_Int.J.Mol.Sci_20_
PubMedSearch : Yu_2019_Int.J.Mol.Sci_20_
PubMedID: 31035455
Gene_locus related to this paper: human-ABHD2

Title : Unprecedented peroxidase-mimicking activity of single-atom nanozyme with atomically dispersed Fe-Nx moieties hosted by MOF derived porous carbon - Niu_2019_Biosens.Bioelectron_142_111495
Author(s) : Niu X , Shi Q , Zhu W , Liu D , Tian H , Fu S , Cheng N , Li S , Smith JN , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 142 :111495 , 2019
Abstract : Due to robustness, easy large-scale preparation and low cost, nanomaterials with enzyme-like characteristics (defined as 'nanozymes') are attracting increasing interest for various applications. However, most of currently developed nanozymes show much lower activity in comparison with natural enzymes, and the deficiency greatly hinders their use in sensing and biomedicine. Single-atom catalysts (SACs) offer the unique feature of maximum atomic utilization, providing a potential pathway to improve the catalytic activity of nanozymes. Herein, we propose a Fe-N-C single-atom nanozyme (SAN) that exhibits unprecedented peroxidase-mimicking activity. The SAN consists of atomically dispersed Fe horizontal line Nx moieties hosted by metal-organic frameworks (MOF) derived porous carbon. Thanks to the 100% single-atom active Fe dispersion and the large surface area of the porous support, the Fe-N-C SAN provided a specific activity of 57.76 U mg(-1), which was almost at the same level as natural horseradish peroxidase (HRP). Attractively, the SAN presented much better storage stability and robustness against harsh environments. As a proof-of-concept application, highly sensitive biosensing of butyrylcholinesterase (BChE) activity using the Fe-N-C SAN as a substitute for natural HRP was further verified.
ESTHER : Niu_2019_Biosens.Bioelectron_142_111495
PubMedSearch : Niu_2019_Biosens.Bioelectron_142_111495
PubMedID: 31310943

Title : Gamma-glutamyl transpeptidase to cholinesterase and platelet ratio in predicting significant liver fibrosis and cirrhosis of chronic hepatitis B - Liu_2019_Clin.Microbiol.Infect_25_514 e1
Author(s) : Liu D , Li J , Lu W , Wang Y , Zhou X , Huang D , Li X , Ding R , Zhang Z
Ref : Clin Microbiol Infect , 25 :514 e1 , 2019
Abstract : OBJECTIVES: To evaluate the performance of a new mathematical model gamma-glutamyl transpeptidase to cholinesterase and platelet ratio (GCPR) versus gamma-glutamyl transpeptidase to platelet ratio (GPR) in predicting significant fibrosis and cirrhosis of chronic hepatitis B. METHODS: A complete cohort of 2343 patients was divided into early and late cohort depending on the time of liver biopsy. With reference to the Scheuer standard, liver pathologic stage 2 or higher and stage 4 or higher were defined as significant fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curve was used to evaluate the performance of investigated models. RESULTS: In the early cohort, the areas under ROC curves (AUROCs) of GCPR in predicting significant fibrosis of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients (0.782 and 0.775) were both significantly greater than those of GPR (0.748 and 0.747) (Z = 8.198 and Z = 6.023, both p <0.0001); the AUROCs of GCPR in predicting cirrhosis of HBeAg-positive and HBeAg-negative patients (0.842 and 0.861) were both significantly greater than those of GPR (0.802 and 0.823) (Z = 6.686 and Z = 6.116, both p <0.0001). In early, late and complete cohorts, using a single cutoff of GCPR > 0.080, the specificities of GCPR in predicting significant fibrosis of HBeAg-positive patients were 83.3%, 88.2% and 85.0% and of HBeAg-negative patients were 87.6%, 87.4% and 87.6%, respectively; and the sensitivities of GCPR in predicting cirrhosis of HBeAg-positive patients were 81.9%, 88.7% and 84.2% and of HBeAg-negative patients were 83.1%, 82.1% and 82.7%, respectively. CONCLUSIONS: GCPR has higher performance than GPR in predicting significant fibrosis and cirrhosis of chronic hepatitis B.
ESTHER : Liu_2019_Clin.Microbiol.Infect_25_514 e1
PubMedSearch : Liu_2019_Clin.Microbiol.Infect_25_514 e1
PubMedID: 29906588

Title : Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2\/CES1 Signaling Pathway - He_2019_Dig.Dis.Sci_64_3182
Author(s) : He W , Xu Y , Ren X , Xiang D , Lei K , Zhang C , Liu D
Ref : Digestive Diseases & Sciences , 64 :3182 , 2019
Abstract : BACKGROUND: Vitamin E has been reported to have a beneficial effect on nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanism of action has not yet been clearly defined. AIM: We aimed to evaluate the effects and mechanisms of vitamin E on lipid and glucose homeostasis both in vivo and in vitro. METHODS: An NAFLD model was established in C57BL/6 mice fed a 30% fructose solution for 8 weeks. Subsequently, NAFLD mice were given vitamin E (70 mg/kg) for 2 weeks. In addition, L02 cells were treated with 5 mM fructose and 100 nM vitamin E to explore the potential mechanisms of action. RESULTS: Vitamin E reversed the impaired glucose tolerance of fructose-treated mice. Histopathological examination showed that liver steatosis was significantly relieved in vitamin E-treated mice. These effects may be attributed to the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2), carboxylesterase 1 (CES1), and downregulated proteins involved in lipid synthesis by vitamin E treatment. In vivo, vitamin E also significantly reduced lipid accumulation in fructose-treated L02 cells, and the Nrf2 inhibitor ML385 reversed the protective effects of vitamin E. CONCLUSION: These data indicated that the therapeutic effects of vitamin E on lipid and glucose homeostasis may be associated with activation of the Nrf2/CES1 signaling pathway.
ESTHER : He_2019_Dig.Dis.Sci_64_3182
PubMedSearch : He_2019_Dig.Dis.Sci_64_3182
PubMedID: 31076985

Title : Surface functionalization of graphene oxide by amino acids for Thermomyces lanuginosus lipase adsorption - Zhou_2019_J.Colloid.Interface.Sci_546_211
Author(s) : Zhou W , Zhuang W , Ge L , Wang Z , Wu J , Niu H , Liu D , Zhu C , Chen Y , Ying H
Ref : J Colloid Interface Sci , 546 :211 , 2019
Abstract : Graphene oxide (GO) with oxygen containing functional groups can be selectively modified by small biomolecules to achieve heterogeneous surface properties. To achieve a hyper-enzymatic activity, the surface functionality of GO should be tailored to the orientation adsorption of the Thermomyces lanuginosus (TL) lipase, and the active center can be covered by a relatively hydrophobic helical lid for protection. In this work, amino acids were used to interact with GO through reduction reaction, hydrophobic forces, electrostatic forces, or hydrogen bonding to alter the surface hydrophobicity and charge density. Characterization of the structure and surface properties confirmed that the GO samples decorated with phenylalanine (Phe) and glutamic acid (Glu) exhibited superior hydrophobicity than other modifications, whereas tryptophan (Trp) and cysteine (Cys) provided weaker reduction effects on GO. Moreover, the zeta potential of the samples modified by amino acids of lysine (Lys) and arginine (Arg) is higher than other modified samples. The adsorption amount of lipase on Glu-GO reached 172mg/g and the relative enzymatic activity reached up to 200%. The thermodynamic data and the Freundlich isotherm model fitting showed that the lipase adsorption process on modified samples was spontaneous, endothermic and entropy increase.
ESTHER : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedSearch : Zhou_2019_J.Colloid.Interface.Sci_546_211
PubMedID: 30921675

Title : Lipoprotein-Associated Phospholipase A2 Activity and Mass as Independent Risk Factor of Stroke: A Meta-Analysis - Hu_2019_Biomed.Res.Int_2019_8642784
Author(s) : Hu G , Liu D , Tong H , Huang W , Hu Y , Huang Y
Ref : Biomed Res Int , 2019 :8642784 , 2019
Abstract : BACKGROUND: The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and stroke risk is inconsistent. We conducted a meta-analysis to determine whether elevated Lp-PLA2 is a risk factor for stroke. METHODS: Studies were included if they reported Lp-PLA2 mass and/or activity levels and adjusted risk estimates of stroke. The primary outcome was overall stroke incidence. The combined results were shown as relative risks (RRs) with 95% confidence intervals (CI) for per 1 standard deviation (SD) higher value of Lp-PLA2 and the highest versus lowest Lp-PLA2 category. RESULTS: Twenty-two studies involving 157,693 participants were included for analysis. After adjusting for conventional risk factors, the RRs for overall stroke with 1 SD higher Lp-PLA2 activity and mass were 1.07 (95% CI 1.02-1.13) and 1.11 (95% CI 1.04-1.19), respectively. The RRs of ischemic stroke with 1 SD higher Lp-PLA2 activity and mass were 1.08 (95% CI 1.01-1.15) and 1.11 (95% CI 1.02-1.22), respectively. When comparing the highest and lowest levels of Lp-PLA2, the RRs of stroke for Lp-PLA2 activity and mass were 1.26 (95% CI 1.03-1.54) and 1.56 (95% CI 1.21-2.00), respectively. Finally, when comparing the highest and lowest levels of Lp-PLA2, the pooled RRs of ischemic stroke for Lp-PLA2 activity and mass were 1.29 (95% CI 1.07-1.56) and 1.68 (95% CI 1.12-2.53), respectively. CONCLUSIONS: Elevated baseline Lp-PLA2 levels, detected either by activity or mass, are associated with increased stroke risk.
ESTHER : Hu_2019_Biomed.Res.Int_2019_8642784
PubMedSearch : Hu_2019_Biomed.Res.Int_2019_8642784
PubMedID: 31236414
Gene_locus related to this paper: human-PLA2G7

Title : Detection techniques of carboxylesterase activity: An update review - Lan_2019_Bioorg.Chem__103388
Author(s) : Lan L , Ren X , Yang J , Liu D , Zhang C
Ref : Bioorg Chem , :103388 , 2019
Abstract : Mammalian carboxylesterases (CESs) are essential members of serine esterase hydrolase superfamily, which are widely distributed in many tissues including liver, intestine, lung and kidney. CESs play an important role in the metabolism of various xenobiotics including ester drugs and environmental toxicants, and also participate in lipid homeostasis, so the development of CESs activity detection techniques are of great significance for drug discovery and biomedical research. With the rapid development of separated and detection technologies such as chromatography, capillary electrophoresis, fluorescent probe-based detection technology, bioluminescent sensor and colorimetric sensor in recent decade, the research of physiological functions of CESs have make huge breakthrough. This review summarizes the development and application of CESs activity detection techniques, as well as comparatively analyzes the characteristics of various detection techniques. The information and knowledge represented here will help the researchers carry out various biochemical studies for understanding activation mechanism and role of CESs in drug metabolism.
ESTHER : Lan_2019_Bioorg.Chem__103388
PubMedSearch : Lan_2019_Bioorg.Chem__103388
PubMedID: 31676115

Title : Z-Ligustilide Exerted Hormetic Effect on Growth and Detoxification Enzymes of Spodoptera litura Larvae - Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
Author(s) : Yi Y , Dou G , Yu Z , He H , Wang C , Li L , Zhou J , Liu D , Shi J , Li G , Pang L , Yang N , Huang Q , Qi H
Ref : Evid Based Complement Alternat Med , 2018 :7104513 , 2018
Abstract : Plants have evolved a variety of phytochemicals to defense insect feeding, whereas insects have also evolved diverse detoxification enzymes, which are adaptively induced as a prosurvival mechanism. Herein, Z-ligustilide in Ligusticum chuanxiong Hort. was found to exhibit a similar trend in the accumulation from December to May as the occurrence of Spodoptera litura (Fabricius) larvae. Importantly, S. litura larvae feeding enhanced Z-ligustilide level in the stem and leaf (p < 0.01). Moreover, Z-ligustilide ranging from 1 to 5 mg.g(-1) exhibited remarkable larvicidal activity, antifeedant activity, and growth inhibition against S. litura larvae. The LC50 values of larvicidal activity for phthalides in L. chuanxiong were compared as follows: Z-ligustilide > levistilide A > senkyunolide A > 3-butylidenephthalide > senkyunolide I, implicating the critical role of conjugated structure. Notably, there was a biphasic dose response for glutathione S-transferase (GST), cytochrome P450 (CYP) 450, Acetylcholinesterase (AChE), and Carboxylesterase (CarE) activities and GSTs1, cytochrome P450 (CYP) 4S9, and CYP4M14 mRNA expression. Particularly, low dose (0.1 mg.g(-1)) of Z-ligustilide conferred the resistance of S. litura larvae against chlorpyrifos (p < 0.05). Together, our data suggest that Z-ligustilide may function in a hormetic way in the chemical defense of L. chuanxiong against S. litura larvae.
ESTHER : Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
PubMedSearch : Yi_2018_Evid.Based.Complement.Alternat.Med_2018_7104513
PubMedID: 30057645

Title : Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis - Stogsdill_2017_Nature_551_192
Author(s) : Stogsdill JA , Ramirez J , Liu D , Kim YH , Baldwin KT , Enustun E , Ejikeme T , Ji RR , Eroglu C
Ref : Nature , 551 :192 , 2017
Abstract : Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.
ESTHER : Stogsdill_2017_Nature_551_192
PubMedSearch : Stogsdill_2017_Nature_551_192
PubMedID: 29120426

Title : Structure Determination of Mycobacterium tuberculosis Serine Protease Hip1 (Rv2224c) - Naffin-Olivos_2017_Biochemistry_56_2304
Author(s) : Naffin-Olivos JL , Daab A , White A , Goldfarb NE , Milne AC , Liu D , Baikovitz J , Dunn BM , Rengarajan J , Petsko GA , Ringe D
Ref : Biochemistry , 56 :2304 , 2017
Abstract : The Mycobacterium tuberculosis (Mtb) serine protease Hip1 (hydrolase important for pathogenesis; Rv2224c) promotes tuberculosis (TB) pathogenesis by impairing host immune responses through proteolysis of a protein substrate, Mtb GroEL2. The cell surface localization of Hip1 and its immunomodulatory functions make Hip1 a good drug target for new adjunctive immune therapies for TB. Here, we report the crystal structure of Hip1 to a resolution of 2.6 A and the kinetic studies of the enzyme against model substrates and the protein GroEL2. The structure shows a two-domain protein, one of which contains the catalytic residues that are the signature of a serine protease. Surprisingly, a threonine is located within the active site close enough to hydrogen bond with the catalytic residues Asp463 and His490. Mutation of this residue, Thr466, to alanine established its importance for function. Our studies provide insights into the structure of a member of a novel family of proteases. Knowledge of the Hip1 structure will aid in designing inhibitors that could block Hip1 activity.
ESTHER : Naffin-Olivos_2017_Biochemistry_56_2304
PubMedSearch : Naffin-Olivos_2017_Biochemistry_56_2304
PubMedID: 28346784
Gene_locus related to this paper: myctu-ym24

Title : Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest - Cheng_2017_Nat.Ecol.Evol_1_1747
Author(s) : Cheng T , Wu J , Wu Y , Chilukuri RV , Huang L , Yamamoto K , Feng L , Li W , Chen Z , Guo H , Liu J , Li S , Wang X , Peng L , Liu D , Guo Y , Fu B , Li Z , Liu C , Chen Y , Tomar A , Hilliou F , Montagne N , Jacquin-Joly E , d'Alencon E , Seth RK , Bhatnagar RK , Jouraku A , Shiotsuki T , Kadono-Okuda K , Promboon A , Smagghe G , Arunkumar KP , Kishino H , Goldsmith MR , Feng Q , Xia Q , Mita K
Ref : Nat Ecol Evol , 1 :1747 , 2017
Abstract : The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
ESTHER : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedSearch : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedID: 28963452

Title : O-Linked N-acetylglucosamine transferase 1 regulates global histone H4 acetylation via stabilization of the nonspecific lethal protein NSL3 - Wu_2017_J.Biol.Chem_292_10014
Author(s) : Wu D , Zhao L , Feng Z , Yu C , Ding J , Wang L , Wang F , Liu D , Zhu H , Xing F , Conaway JW , Conaway RC , Cai Y , Jin J
Ref : Journal of Biological Chemistry , 292 :10014 , 2017
Abstract : The human males absent on the first (MOF)-containing histone acetyltransferase nonspecific lethal (NSL) complex comprises nine subunits including the O-linked N-acetylglucosamine (O-GlcNAc) transferase, isoform 1 (OGT1). However, whether the O-GlcNAc transferase activity of OGT1 controls histone acetyltransferase activity of the NSL complex and whether OGT1 physically interacts with the other NSL complex subunits remain unclear. Here, we demonstrate that OGT1 regulates the activity of the NSL complex by mainly acetylating histone H4 Lys-16, Lys-5, and Lys-8 via O-GlcNAcylation and stabilization of the NSL complex subunit NSL3. Knocking down or overexpressing OGT1 in human cells remarkably affected the global acetylation of histone H4 residues Lys-16, Lys-5, and Lys-8. Because OGT1 is a subunit of the NSL complex, we also investigated the function of OGT1 in this complex. Co-transfection/co-immunoprecipitation experiments combined with in vitro O-GlcNAc transferase assays confirmed that OGT1 specifically binds to and O-GlcNAcylates NSL3. In addition, wheat germ agglutinin affinity purification verified the occurrence of O-GlcNAc modification on NSL3 in cells. Moreover, O-GlcNAcylation of NSL3 by wild-type OGT1 (OGT1-WT) stabilized NSL3. This stabilization was lost after co-transfection of NSL3 with an OGT1 mutant, OGT1(C964A), that lacks O-GlcNAc transferase activity. Furthermore, stabilization of NSL3 by OGT1-WT significantly increased the global acetylation levels of H4 Lys-5, Lys-8, and Lys-16 in cells. These results suggest that OGT1 regulates the activity of the NSL complex by stabilizing NSL3.
ESTHER : Wu_2017_J.Biol.Chem_292_10014
PubMedSearch : Wu_2017_J.Biol.Chem_292_10014
PubMedID: 28450392
Gene_locus related to this paper: human-KANSL3

Title : Protective effects of kinetin against aluminum chloride and D-galactose induced cognitive impairment and oxidative damage in mouse - Wei_2017_Brain.Res.Bull_134_262
Author(s) : Wei Y , Liu D , Zheng Y , Li H , Hao C , Ouyang W
Ref : Brain Research Bulletin , 134 :262 , 2017
Abstract : Increasing evidence indicates that aluminum exposure and oxidative stress play crucial roles in the initiation and development of Alzheimer's disease (AD). Aluminum chloride (AlCl3) and d-galactose (d-gal) combined treatment of mice is considered as an easy and cheap way to obtain an animal model of AD. Kinetin is a plant cytokinin, which is also reported to exert neuro-protective effects in vivo and in vitro. Thus, in this study, neuro-protective effects of kinetin were investigated in an AD model of mice induced by AlCl3 and d-gal. The Morris water maze (MWM) test was performed to directly evaluate neuro-protective effects of kinetin on the memory and spatial learning abilities, while the histopathological changes were examined by hematoxylin and eosin (H & E) staining method. To further investigate mechanisms involved, Al content in cortex and hippocampus was determined. In addition, related detection kits were used to determine acetylcholine (ACh) content and activity of acetylcholinesterase (AChE). Activities of anti-oxidative enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), and the content of heme oxygenase-1 (HO-1) were also measured. Besides, the content of oxidative damage bio-markers including 8-iso-prostaglandin F (8-iso-PGF), advanced glycation end products (AGEs) and 8-hydroxy-2-deoxyguanosine (8-OHdG) were determined by ELISA kits. Finally, the distribution of beta-amyloid protein 1-42 (Abeta1-42) was detected by immunohistochemistry (IHC), while the expression levels of amyloidogenic proteins including beta-amyloid precursor protein (APP), beta-secretase, gamma-secretase and Abeta1-42 were detected by western blotting (WB) method. Results showed that kinetin improved performance in MWM test, attenuated histopathological changes, reduced Al level in cortex and hippocampus, increased ACh content and decreased AChE activity. In addition, kinetin elevated activities of anti-oxidative enzymes and reduced the levels of oxidative damage biomarkers in AD model of mice. Furthermore, kinetin also increased the content of HO-1, and inhibited the distribution of Abeta1-42 and the expressions of amyloidogenic proteins (APP, beta-secretase, gamma-secretase and Abeta1-42) in brain tissue of AD mice. Our results indicate that kinetin has neuro-protective effects on the AD model of mice induced by AlCl3 and d-gal, suggesting that kinetin may be a candidate drug for treatment of AD.
ESTHER : Wei_2017_Brain.Res.Bull_134_262
PubMedSearch : Wei_2017_Brain.Res.Bull_134_262
PubMedID: 28867383

Title : Association of Rare and Common Variation in the Lipoprotein Lipase Gene With Coronary Artery Disease - Khera_2017_JAMA_317_937
Author(s) : Khera AV , Won HH , Peloso GM , O'Dushlaine C , Liu D , Stitziel NO , Natarajan P , Nomura A , Emdin CA , Gupta N , Borecki IB , Asselta R , Duga S , Merlini PA , Correa A , Kessler T , Wilson JG , Bown MJ , Hall AS , Braund PS , Carey DJ , Murray MF , Kirchner HL , Leader JB , Lavage DR , Manus JN , Hartzel DN , Samani NJ , Schunkert H , Marrugat J , Elosua R , McPherson R , Farrall M , Watkins H , Lander ES , Rader DJ , Danesh J , Ardissino D , Gabriel S , Willer C , Abecasis GR , Saleheen D , Dewey FE , Kathiresan S
Ref : Jama , 317 :937 , 2017
Abstract : Importance: The activity of lipoprotein lipase (LPL) is the rate-determining step in clearing triglyceride-rich lipoproteins from the circulation. Mutations that damage the LPL gene (LPL) lead to lifelong deficiency in enzymatic activity and can provide insight into the relationship of LPL to human disease. Objective: To determine whether rare and/or common variants in LPL are associated with early-onset coronary artery disease (CAD). Design, Setting, and Participants: In a cross-sectional study, LPL was sequenced in 10 CAD case-control cohorts of the multinational Myocardial Infarction Genetics Consortium and a nested CAD case-control cohort of the Geisinger Health System DiscovEHR cohort between 2010 and 2015. Common variants were genotyped in up to 305699 individuals of the Global Lipids Genetics Consortium and up to 120600 individuals of the CARDIoGRAM Exome Consortium between 2012 and 2014. Study-specific estimates were pooled via meta-analysis. Exposures: Rare damaging mutations in LPL included loss-of-function variants and missense variants annotated as pathogenic in a human genetics database or predicted to be damaging by computer prediction algorithms trained to identify mutations that impair protein function. Common variants in the LPL gene region included those independently associated with circulating triglyceride levels. Main Outcomes and Measures: Circulating lipid levels and CAD. Results: Among 46891 individuals with LPL gene sequencing data available, the mean (SD) age was 50 (12.6) years and 51% were female. A total of 188 participants (0.40%; 95% CI, 0.35%-0.46%) carried a damaging mutation in LPL, including 105 of 32646 control participants (0.32%) and 83 of 14245 participants with early-onset CAD (0.58%). Compared with 46703 noncarriers, the 188 heterozygous carriers of an LPL damaging mutation displayed higher plasma triglyceride levels (19.6 mg/dL; 95% CI, 4.6-34.6 mg/dL) and higher odds of CAD (odds ratio = 1.84; 95% CI, 1.35-2.51; P < .001). An analysis of 6 common LPL variants resulted in an odds ratio for CAD of 1.51 (95% CI, 1.39-1.64; P = 1.1 x 10-22) per 1-SD increase in triglycerides. Conclusions and Relevance: The presence of rare damaging mutations in LPL was significantly associated with higher triglyceride levels and presence of coronary artery disease. However, further research is needed to assess whether there are causal mechanisms by which heterozygous lipoprotein lipase deficiency could lead to coronary artery disease.
ESTHER : Khera_2017_JAMA_317_937
PubMedSearch : Khera_2017_JAMA_317_937
PubMedID: 28267856
Gene_locus related to this paper: human-LPL

Title : An Ultrasensitive Biosensing Platform Employing Acetylcholinesterase and Gold Nanoparticles - Liu_2017_Methods.Mol.Biol_1530_307
Author(s) : Liu D , Chen X
Ref : Methods Mol Biol , 1530 :307 , 2017
Abstract : Enzyme-linked immunosorbent assay (ELISA) is a well-known strategy for biomarker detection with a color change, which can be seen by the naked eyes. However, the moderate sensitivity of conventional ELISA limits its applications in many cases where the concentrations of biomarker are very low, such as cancer diagnosis. Here we describe an ultrasensitive colorimetric assay based on acetylcholinesterase (AChE)-catalyzed hydrolysis reaction, whose products trigger the aggregation of gold nanoparticles (AuNPs), causing a distinct color change of the solution from red to purple. This enhanced colorimetric immunoassay offers extremely high sensitivity and specificity. In this study, we employed enterovirus 71 (EV71), the major cause of hand, foot, and mouth disease (HFMD), as a model to evaluate the analytical performance of the plasmonic immunoassay.
ESTHER : Liu_2017_Methods.Mol.Biol_1530_307
PubMedSearch : Liu_2017_Methods.Mol.Biol_1530_307
PubMedID: 28150210

Title : Comparative and population genomic landscape of Phellinus noxius: A hypervariable fungus causing root rot in trees - Chung_2017_Mol.Ecol_26_6301
Author(s) : Chung CL , Lee TJ , Akiba M , Lee HH , Kuo TH , Liu D , Ke HM , Yokoi T , Roa MB , Lu MJ , Chang YY , Ann PJ , Tsai JN , Chen CY , Tzean SS , Ota Y , Hattori T , Sahashi N , Liou RF , Kikuchi T , Tsai IJ
Ref : Mol Ecol , 26 :6301 , 2017
Abstract : The order Hymenochaetales of white rot fungi contain some of the most aggressive wood decayers causing tree deaths around the world. Despite their ecological importance and the impact of diseases they cause, little is known about the evolution and transmission patterns of these pathogens. Here, we sequenced and undertook comparative genomic analyses of Hymenochaetales genomes using brown root rot fungus Phellinus noxius, wood-decomposing fungus Phellinus lamaensis, laminated root rot fungus Phellinus sulphurascens and trunk pathogen Porodaedalea pini. Many gene families of lignin-degrading enzymes were identified from these fungi, reflecting their ability as white rot fungi. Comparing against distant fungi highlighted the expansion of 1,3-beta-glucan synthases in P. noxius, which may account for its fast-growing attribute. We identified 13 linkage groups conserved within Agaricomycetes, suggesting the evolution of stable karyotypes. We determined that P. noxius has a bipolar heterothallic mating system, with unusual highly expanded ~60 kb A locus as a result of accumulating gene transposition. We investigated the population genomics of 60 P. noxius isolates across multiple islands of the Asia Pacific region. Whole-genome sequencing showed this multinucleate species contains abundant poly-allelic single nucleotide polymorphisms with atypical allele frequencies. Different patterns of intra-isolate polymorphism reflect mono-/heterokaryotic states which are both prevalent in nature. We have shown two genetically separated lineages with one spanning across many islands despite the geographical barriers. Both populations possess extraordinary genetic diversity and show contrasting evolutionary scenarios. These results provide a framework to further investigate the genetic basis underlying the fitness and virulence of white rot fungi.
ESTHER : Chung_2017_Mol.Ecol_26_6301
PubMedSearch : Chung_2017_Mol.Ecol_26_6301
PubMedID: 28926153
Gene_locus related to this paper: 9homo-a0a286uk81

Title : Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism - Gunawardane_2016_J.Biol.Chem_291_2799
Author(s) : Gunawardane RN , Fordstrom P , Piper DE , Masterman S , Siu S , Liu D , Brown M , Lu M , Tang J , Zhang R , Cheng J , Gates A , Meininger D , Chan J , Carlson T , Walker N , Schwarz M , Delaney J , Zhou M
Ref : Journal of Biological Chemistry , 291 :2799 , 2016
Abstract : Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouse(TM) platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 A LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease.
ESTHER : Gunawardane_2016_J.Biol.Chem_291_2799
PubMedSearch : Gunawardane_2016_J.Biol.Chem_291_2799
PubMedID: 26644477
Gene_locus related to this paper: human-LCAT

Title : Regulations of Xenobiotics and Endobiotics on Carboxylesterases: A Comprehensive Review - Xu_2016_Eur.J.Drug.Metab.Pharmacokinet_41_321
Author(s) : Xu Y , Zhang C , He W , Liu D
Ref : Eur J Drug Metab Pharmacokinet , 41 :321 , 2016
Abstract : Carboxylesterases (CESs) play major roles in catalyzing the hydrolysis of a wide range of ester- and amide-containing compounds. CESs dominate both the biotransformation of numerous therapeutic drugs and the detoxification of environmental toxicants, and the activity alteration of CESs may be a determinant reason for modification of the resultant pharmacokinetic/pharmacodynamic profile when two or more drugs are concurrently used. Herein, we provide a comprehensive review of the current literature involving of induction and inhibition on CESs by both exogenous and endogenous compounds. In particular, the inhibition constant and inhibition pattern of inhibitors on CESs in studies using animal microsomes or human recombinant CESs are summarized. Further studies are needed to clarify the underlying regulation mechanism, and alterations in CESs activity should be taken into consideration for safe clinical therapy.
ESTHER : Xu_2016_Eur.J.Drug.Metab.Pharmacokinet_41_321
PubMedSearch : Xu_2016_Eur.J.Drug.Metab.Pharmacokinet_41_321
PubMedID: 26914100

Title : Engineering surface hydrophobicity improves activity of Bacillus thermocatenulatus lipase 2 enzyme - Tang_2015_Biotechnol.J_10_1762
Author(s) : Tang T , Yuan C , Hwang HT , Zhao X , Ramkrishna D , Liu D , Varma A
Ref : Biotechnol J , 10 :1762 , 2015
Abstract : Bacillus thermocatenulatus lipase 2 (BTL2) is a promising industrial enzyme used in biodiesel production. Although BTL2 has high thermostability and good resistance to organic solvents, the activity of BTL2 is suboptimal for industrial processes. To improve BTL2 activity, we engineered BTL2 lipase by modulating hydrophobicity of its lid domain. Through site-directed mutagenesis, we constructed three mutants, namely Y225F+S232A, S232A+T236V and Q185L, to cover all uncharged hydrophilic amino acids within the lid domain. Activities of these mutants were characterized. Our findings suggest that one mutant (Y225F+S232A) showed approximately 35% activity increase in catalyzing heterogeneous hydrolytic reactions relevant for industrial applications. A mathematical framework was established to account for different molecular events that contribute to the observed apparent catalytic activities. Increases in hydrophobicity of lid domains were associated with increased interfacial adsorption of lipases and lower molecular enzymatic activities. The measured apparent activities of lipases include contributions from both events. Lid hydrophobicity can thus result in different changes in lipase activities depending on the mutation site. Our work demonstrates the feasibility of increasing BTL2 activity by modulating the hydrophobicity of lid domains and provides some guidelines for further improving BTL2 activity.
ESTHER : Tang_2015_Biotechnol.J_10_1762
PubMedSearch : Tang_2015_Biotechnol.J_10_1762
PubMedID: 26097135
Gene_locus related to this paper: bactc-lipas

Title : Down-regulation of carboxylesterases 1 and 2 plays an important role in prodrug metabolism in immunological liver injury rats - Zhang_2015_Int.Immunopharmacol_24_153
Author(s) : Zhang C , Xu Y , Gao P , Lu J , Li X , Liu D
Ref : Int Immunopharmacol , 24 :153 , 2015
Abstract : Liver plays a central role in xenobiotics metabolism, thus affecting the in vivo disposition and therapeutic effects of drugs. Carboxylesterases (CESs), with the main isoforms CES1 and CES2, are important in the metabolism of ester-type prodrugs. However, influences of immunological liver injury on the activity of CES remain undefined. In the present study, we demonstrated treatment with lipopolysaccharide (LPS) suppressed the activities of CES1 and CES2. The decreased activities of CES1 and CES2 were preliminarily assessed by the hydrolysis assay for their common substrate p-nitrophenyl acetate (PNPA) with rat hepatic microsomal enzyme. Subsequently, RT-PCR results showed that the levels of CES1 mRNA and mRNA of CES2 (AB010635) and CES2 (AY034877) in the model group were significantly lower than those of the normal control group (P<0.05). Western blot results showed that the expressions of CES1 and CES2 proteins were decreased (P<0.05). To further clarify the effects of LPS on the metabolic activities of CESs, pharmacokinetic studies were performed in rats by utilizing imidapril and irinotecan (CPT-11) as the specific substrates for CES1 and CES2, respectively. After treatment with LPS, AUC0-inf and Cmax of imidaprilat were decreased from 2084.86+/-340.66ng.h(-1).mL(-1) and 234.66+/-68.85ng.mL(-1) to 983.87+/-315.34ng.h(-1).mL(-1) and 113.1+/-19.69ng.mL(-1) (P<0.05), respectively. Moreover, AUC0-inf and Cmax of SN-38 were decreased from 8100+/-918.6ng.h(-1).mL(-1) and 144.67+/-20.28ng.mL(-1) to 3270+/-500.5ng.h(-1).mL(-1) and 56.19+/-10.38ng.mL(-1) (P<0.05), respectively. In summary, immunological liver injury remarkably attenuated the expressions and metabolic activities of CES1 and CES2, which may be associated with the regulatory effects of cytokines under inflammation.
ESTHER : Zhang_2015_Int.Immunopharmacol_24_153
PubMedSearch : Zhang_2015_Int.Immunopharmacol_24_153
PubMedID: 25499727

Title : Genome-wide transcriptomic analysis of a superior biomass-degrading strain of A. fumigatus revealed active lignocellulose-degrading genes - Miao_2015_BMC.Genomics_16_459
Author(s) : Miao Y , Liu D , Li G , Li P , Xu Y , Shen Q , Zhang R
Ref : BMC Genomics , 16 :459 , 2015
Abstract : BACKGROUND: Various saprotrophic microorganisms, especially filamentous fungi, can efficiently degrade lignocellulose that is one of the most abundant natural materials on earth. It consists of complex carbohydrates and aromatic polymers found in the plant cell wall and thus in plant debris. Aspergillus fumigatus Z5 was isolated from compost heaps and showed highly efficient plant biomass-degradation capability. RESULTS: The 29-million base-pair genome of Z5 was sequenced and 9540 protein-coding genes were predicted and annotated. Genome analysis revealed an impressive array of genes encoding cellulases, hemicellulases and pectinases involved in lignocellulosic biomass degradation. Transcriptional responses of A. fumigatus Z5 induced by sucrose, oat spelt xylan, Avicel PH-101 and rice straw were compared. There were 444, 1711 and 1386 significantly differently expressed genes in xylan, cellulose and rice straw, respectively, when compared to sucrose as a control condition. CONCLUSIONS: Combined analysis of the genomic and transcriptomic data provides a comprehensive understanding of the responding mechanisms to the most abundant natural polysaccharides in A. fumigatus. This study provides a basis for further analysis of genes shown to be highly induced in the presence of polysaccharide substrates and also the information which could prove useful for biomass degradation and heterologous protein expression.
ESTHER : Miao_2015_BMC.Genomics_16_459
PubMedSearch : Miao_2015_BMC.Genomics_16_459
PubMedID: 26076650
Gene_locus related to this paper: neofi-a1d0b8

Title : Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer's Rodent Models - Wu_2015_Sci.Rep_5_15032
Author(s) : Wu Y , Luo X , Liu X , Liu D , Wang X , Guo Z , Zhu L , Tian Q , Yang X , Wang JZ
Ref : Sci Rep , 5 :15032 , 2015
Abstract : Although Alzheimer's disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated beta-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models.
ESTHER : Wu_2015_Sci.Rep_5_15032
PubMedSearch : Wu_2015_Sci.Rep_5_15032
PubMedID: 26463268

Title : Design of hyperthermophilic lipase chimeras by key motif-directed recombination - Zhou_2015_Chembiochem_16_455
Author(s) : Zhou X , Gao L , Yang G , Liu D , Bai A , Li B , Deng Z , Feng Y
Ref : Chembiochem , 16 :455 , 2015
Abstract : Recombination of diverse natural evolved domains within a superfamily offers greater opportunity for enzyme function leaps. How to recombine protein modules from distant parents with less disruption in cross-interfaces is a challenging issue. Here, we identified the existence of a key motif, the sequence VVSVN(D)YR, within a structural motif psi loop in the alpha/beta-hydrolase fold superfamily, by using a MEME server and the PROMOTIF program. To obtain thermostable lipase-like enzymes, two chimeras were engineered at the key motif regions through recombination of domains from a mesophilic lipase and a hyperthermophilic esterase/peptidase with amino acid identity less than 21 %. The chimeras retained the desirable substrate preference of their mesophilic parent and exhibited more than 100-fold increased thermostability at 50 degrees C. Through site-directed mutation, we further improved activity of the chimera by 4.6-fold. The recombination strategy presented here enables the creation of novel catalysts.
ESTHER : Zhou_2015_Chembiochem_16_455
PubMedSearch : Zhou_2015_Chembiochem_16_455
PubMedID: 25530200

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : A Novel alpha\/beta-Hydrolase Gene IbMas Enhances Salt Tolerance in Transgenic Sweetpotato - Liu_2014_PLoS.One_9_e115128
Author(s) : Liu D , Wang L , Zhai H , Song X , He S , Liu Q
Ref : PLoS ONE , 9 :e115128 , 2014
Abstract : Salt stress is one of the major environmental stresses in agriculture worldwide and affects crop productivity and quality. The development of crops with elevated levels of salt tolerance is therefore highly desirable. In the present study, a novel maspardin gene, named IbMas, was isolated from salt-tolerant sweetpotato (Ipomoea batatas (L.) Lam.) line ND98. IbMas contains maspardin domain and belongs to alpha/beta-hydrolase superfamily. Expression of IbMas was up-regulated in sweetpotato under salt stress and ABA treatment. The IbMas-overexpressing sweetpotato (cv. Shangshu 19) plants exhibited significantly higher salt tolerance compared with the wild-type. Proline content was significantly increased, whereas malonaldehyde content was significantly decreased in the transgenic plants. The activities of superoxide dismutase (SOD) and photosynthesis were significantly enhanced in the transgenic plants. H2O2 was also found to be significantly less accumulated in the transgenic plants than in the wild-type. Overexpression of IbMas up-regulated the salt stress responsive genes, including pyrroline-5-carboxylate synthase, pyrroline-5-carboxylate reductase, SOD, psbA and phosphoribulokinase genes, under salt stress. These findings suggest that overexpression of IbMas enhances salt tolerance of the transgenic sweetpotato plants by regulating osmotic balance, protecting membrane integrity and photosynthesis and increasing reactive oxygen species scavenging capacity.
ESTHER : Liu_2014_PLoS.One_9_e115128
PubMedSearch : Liu_2014_PLoS.One_9_e115128
PubMedID: 25501819
Gene_locus related to this paper: ipoba-a0a076l3m2

Title : Influence of butyl benzyl phthalate (BBP) exposure on nervous system and antioxidant system in zebrafish - Zhang_2014_Ecotoxicology_23_1854
Author(s) : Zhang C , Yang X , He Z , Zhong Q , Guo J , Hu XJ , Xiong L , Liu D
Ref : Ecotoxicology , 23 :1854 , 2014
Abstract : In order to observe the toxic effects of butyl benzyl phthalate (BBP) on zebrafish, the AChE and SOD activity of zebrafish exposed to different concentrations of BBP (0, 0.332, 0.665, 1.33 mg L(-1)) in a short-term (7d) test were determined. Semi-quantitative PCR was used to determine the mRNA transcript levels of the AChE and SOD gene in zebrafish brain and muscle. The results showed: AChE activity decreased with increased exposure concentration, and was significantly inhibited (p < 0.01) compared with the control group at 0.665 mg L(-1) concentration. Low BBP concentrations stimulated and high concentrations inhibited SOD activity with a concentration of 0.332 mg L(-1) resulting in a significant induction (p < 0.05) compared with the control, and 0.665 and 1.33 mg L(-1) concentrations resulting in significant inhibition (p < 0.05, p < 0.01) relative to the control group. The RT-PCR data showed a decrease in brain and muscle mRNA transcription of AChE gene with an increase in exposure concentration. The mRNA transcription of SOD in the brain was not different between the exposed groups and control group; in muscle, the mRNA transcription inhibition decreased and then increased: all differences from the control were statistically significant.
ESTHER : Zhang_2014_Ecotoxicology_23_1854
PubMedSearch : Zhang_2014_Ecotoxicology_23_1854
PubMedID: 25239577

Title : In Vitro Evaluation of the Inhibitory Potential of Pharmaceutical Excipients on Human Carboxylesterase 1A and 2 - Zhang_2014_PLoS.One_9_e93819
Author(s) : Zhang C , Xu Y , Zhong Q , Li X , Gao P , Feng C , Chu Q , Chen Y , Liu D
Ref : PLoS ONE , 9 :e93819 , 2014
Abstract : Two major forms of human carboxylesterase (CES), CES1A and CES2, dominate the pharmacokinetics of most prodrugs such as imidapril and irinotecan (CPT-11). Excipients, largely used as insert vehicles in formulation, have been recently reported to affect drug enzyme activity. The influence of excipients on the activity of CES remains undefined. In this study, the inhibitory effects of 25 excipients on the activities of CES1A1 and CES2 were evaluated. Imidapril and CPT-11 were used as substrates and cultured with liver microsomes in vitro. Imidapril hydrolase activities of recombinant CES1A1 and human liver microsomes (HLM) were strongly inhibited by sodium lauryl sulphate (SLS) and polyoxyl 40 hydrogenated castor oil (RH40) [Inhibition constant (Ki) = 0.04+/-0.01 mug/ml and 0.20+/-0.09 mug/ml for CES1A1, and 0.12+/-0.03 mug/ml and 0.76+/-0.33 mug/ml, respectively, for HLM]. The enzyme hydrolase activity of recombinant CES2 was substantially inhibited by Tween 20 and polyoxyl 35 castor oil (EL35) (Ki = 0.93+/-0.36 mug/ml and 4.4+/-1.24 mug/ml, respectively). Thus, these results demonstrate that surfactants such as SLS, RH40, Tween 20 and EL35 may attenuate the CES activity; such inhibition should be taken into consideration during drug administration.
ESTHER : Zhang_2014_PLoS.One_9_e93819
PubMedSearch : Zhang_2014_PLoS.One_9_e93819
PubMedID: 24699684

Title : Lipase-catalyzed process for biodiesel production: Protein engineering and lipase production - Hwang_2014_Biotechnol.Bioeng_111_639
Author(s) : Hwang HT , Qi F , Yuan C , Zhao X , Ramkrishna D , Liu D , Varma A
Ref : Biotechnol Bioeng , 111 :639 , 2014
Abstract : Biodiesel is an environment-friendly and renewable fuel produced by transesterification of various feedstocks. Although the lipase-catalyzed biodiesel production has many advantages over the conventional alkali catalyzed process, its industrial applications have been limited by high-cost and low-stability of lipase enzymes. This review provides a general overview of the recent advances in lipase engineering, including both protein modification and production. Recent advances in biotechnology such as in protein engineering, recombinant methods and metabolic engineering have been employed but are yet to impact lipase engineering for cost-effective production of biodiesel. A summary of the current challenges and perspectives for potential solutions are also provided. Biotechnol. Bioeng. 2014;111: 639-653. (c) 2013 Wiley Periodicals, Inc.
ESTHER : Hwang_2014_Biotechnol.Bioeng_111_639
PubMedSearch : Hwang_2014_Biotechnol.Bioeng_111_639
PubMedID: 24284881

Title : Nanoparticle-based immunochromatographic test strip with fluorescent detector for quantification of phosphorylated acetylcholinesterase: an exposure biomarker of organophosphorus agents - Zhang_2013_Analyst_138_5431
Author(s) : Zhang W , Ge X , Tang Y , Du D , Liu D , Lin Y
Ref : Analyst , 138 :5431 , 2013
Abstract : A nanoparticle-based fluorescence immunochromatographic test strip (FITS) coupled with a hand-held detector for highly selective and sensitive detection of phosphorylated acetylcholinesterase (AChE), an exposure biomarker of organophosphate (OP) pesticides and nerve agents, is reported. In this approach, OP-AChE adducts were selectively captured by quantum dot-tagged anti-AChE antibodies (Qdot-anti-AChE) and zirconia nanoparticles (ZrO2 NPs). The sandwich-like immunoreactions were performed among the Qdot-anti-AChE, OP-AChE and ZrO2 NPs to form a Qdot-anti-AChE-OP-AChE-ZrO2 complex, which was detected by recording the fluorescence intensity of Qdots captured during the test line. Paraoxon was used as the model OP pesticide. Under optimal conditions, this portable FITS immunosensor demonstrates a highly linear absorption response over the range of 0.01 nM to 10 nM OP-AChE, with a detection limit of 4 pM, coupled with good reproducibility. Moreover, the FITS immunosensor has been validated with OP-AChE spiked human plasma samples. This is the first report on the development of ZrO2 NP-based FITS for the detection of the OP-AChE adduct. The FITS immunosensor provides a sensitive and low-cost sensing platform for on-site screening/evaluating OP pesticides and nerve agents poisoning.
ESTHER : Zhang_2013_Analyst_138_5431
PubMedSearch : Zhang_2013_Analyst_138_5431
PubMedID: 23885349

Title : Lithium Attenuates Scopolamine-Induced Memory Deficits with Inhibition of GSK-3beta and Preservation of Postsynaptic Components - Wu_2013_J.Alzheimers.Dis_37_515
Author(s) : Wu YY , Wang X , Tan L , Liu D , Liu XH , Wang Q , Wang JZ , Zhu LQ
Ref : J Alzheimers Dis , 37 :515 , 2013
Abstract : Cholinergic dysfunction plays a crucial role in the memory deterioration of Alzheimer's disease, but the molecular mechanism is not fully understood. By employing a widely recognized cholinergic dysfunction rat model that was produced by intraperitoneal injection of scopolamine, we investigated the mechanisms underlying scopolamine-induced memory deficits. We found that scopolamine caused spatial learning and memory deficits that involved activation of glycogen synthase kinase-3beta (GSK-3beta) and impairments of dendrite arborization and spine formation/maturation associated with alterations of AMPAR, Homer1, and CREB. Pretreatment by intraperitoneal injection of lithium, an inhibitor of GSK-3, for one week prevented the synaptic changes and the learning and memory deficits induced by scopolamine. Lithium treatment also activated cholineacetyltransferase and inhibited acetylcholinesterase, which might have also contributed to the improved memory. Our findings suggest that GSK-3beta may be a key molecular mediator of cholinergic synaptic dysfunction, and that inhibition of GSK-3beta by lithium may be promising in protecting cholinergic synaptic functions.
ESTHER : Wu_2013_J.Alzheimers.Dis_37_515
PubMedSearch : Wu_2013_J.Alzheimers.Dis_37_515
PubMedID: 23948897

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Acetylcholinesterase-catalyzed hydrolysis allows ultrasensitive detection of pathogens with the naked eye - Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
Author(s) : Liu D , Wang Z , Jin A , Huang X , Sun X , Wang F , Yan Q , Ge S , Xia N , Niu G , Liu G , Hight Walker AR , Chen X
Ref : Angew Chem Int Ed Engl , 52 :14065 , 2013
Abstract : Seeing is believing: A rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction has been developed. Owing to signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of the assay is based on solution color change, which can be easily observed by the naked eye alone.
ESTHER : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedSearch : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedID: 24155243

Title : Dexamethasone regulates differential expression of carboxylesterase 1 and carboxylesterase 2 through activation of nuclear receptors - Zhang_2012_J.Huazhong.Univ.Sci.Technolog.Med.Sci_32_798
Author(s) : Zhang C , Gao P , Yin W , Xu Y , Xiang D , Liu D
Ref : J Huazhong Univ Sci Technolog Med Sci , 32 :798 , 2012
Abstract : Carboxylesterases (CESs) play important roles in the metabolism of endogenous and foreign compounds in physiological and pharmacological responses. The aim of this study was to investigate the effect of dexamethasone at different doses on the expression of CES1 and CES2. Imidapril and irinotecan hydrochloride (CPT-11) were used as special substrates for CES1 and CES2, respectively. Rat hepatocytes were cultured and treated with different concentrations of dexamethasone. The hydrolytic activity of CES1 and CES2 was tested by incubation experiment and their expression was quantitated by real-time PCR. A pharmacokinetic study was conducted in SD rats to further evaluate the effect of dexamethasone on CESs activity in vivo. Western blotting was performed to investigate the regulatory mechanism related to pregnane X receptor (PXR) and glucocorticoid receptor (GR). The results showed that exposure of cultured rat hepatocytes to nanomolar dexamethasone inhibited the imidapril hydrolase activity, which was slightly elevated by micromolar dexamethasone. For CES2, CPT-11 hydrolase activity was induced only when dexamethasone reached micromolar levels. The real-time PCR demonstrated that CES1 mRNA was markedly decreased by nanomolar dexamethasone and increased by micromolar dexamethasone, whereas CES2 mRNA was significantly increased by micromolar dexamethasone. The results of a complementary animal study showed that the concurrent administration of dexamethasone significantly increased the plasma concentration of the metabolite of imidapril while the ratio of CPT-11 to its metabolite SN-38 was significantly decreased. PXR protein was gradually increased by serial concentrations of dexamethasone. However, only nanomolar dexamethasone elevated the level of GR protein. The different concentrations of dexamethasone required suggested that suppression of CES1 may be mediated by GR whereas the induction of CES2 may result from the role of PXR. It was concluded that dexamethasone at different concentrations can differentially regulate CES1 and CES2.
ESTHER : Zhang_2012_J.Huazhong.Univ.Sci.Technolog.Med.Sci_32_798
PubMedSearch : Zhang_2012_J.Huazhong.Univ.Sci.Technolog.Med.Sci_32_798
PubMedID: 23271276

Title : A highly sensitive, dual-readout assay based on gold nanoparticles for organophosphorus and carbamate pesticides - Liu_2012_Anal.Chem_84_4185
Author(s) : Liu D , Chen W , Wei J , Li X , Wang Z , Jiang X
Ref : Analytical Chemistry , 84 :4185 , 2012
Abstract : This report presents a highly sensitive, rhodamine B-covered gold nanoparticle (RB-AuNP) -based assay with dual readouts (colorimetric and fluorometric) for detecting organophosphorus and carbamate pesticides in complex solutions. The detection mechanism is based on the fact that these pesticides can inhibit the activity of acetylcholinesterase (AChE), thus preventing the generation of thiocholine (which turns the RB-AuNP solutions blue and unquenches the fluorescence of RB simultaneously). The color of the RB-AuNP solution remains red and the fluorescence of RB remains quenched. By use of this dual-readout assay, the lowest detectable concentrations for several kinds of pesticides including carbaryl, diazinon, malathion, and phorate were measured to be 0.1, 0.1, 0.3, and 1 mug/L, respectively, all of which are much lower than the maximum residue limits (MRL) as reported in the European Union pesticides database as well as those from the U.S. Department Agriculture (USDA). This assay allows detection of pesticides in real samples such as agricultural products and river water. The results in detecting pesticide residues collected from food samples via this method agree well with those from high-performance liquid chromatography (HPLC). This simple assay is therefore suitable for sensing pesticides in complex samples, especially in combination with other portable platforms.
ESTHER : Liu_2012_Anal.Chem_84_4185
PubMedSearch : Liu_2012_Anal.Chem_84_4185
PubMedID: 22475016

Title : A highly sensitive gold-nanoparticle-based assay for acetylcholinesterase in cerebrospinal fluid of transgenic mice with Alzheimer's disease - Liu_2012_Adv.Healthc.Mater_1_90
Author(s) : Liu D , Chen W , Tian Y , He S , Zheng W , Sun J , Wang Z , Jiang X
Ref : Adv Healthc Mater , 1 :90 , 2012
Abstract : A highly sensitive, selective, and dual-readout (colorimetric and fluorometric) assay for acetylcholinesterase (AChE) based on Rhodamine B-modified gold nanoparticle is reported. Due to its good sensitivity and selectivity, the assay can be used for monitoring AChE levels in the cerebrospinal fluid of transgenic mice with Alzheimer's disease.
ESTHER : Liu_2012_Adv.Healthc.Mater_1_90
PubMedSearch : Liu_2012_Adv.Healthc.Mater_1_90
PubMedID: 23184691

Title : Characterization of a thermostable beta-glucosidase from Aspergillus fumigatus Z5, and its functional expression in Pichia pastoris X33 - Liu_2012_Microb.Cell.Fact_11_25
Author(s) : Liu D , Zhang R , Yang X , Zhang Z , Song S , Miao Y , Shen Q
Ref : Microb Cell Fact , 11 :25 , 2012
Abstract : BACKGROUND: Recently, the increased demand of energy has strongly stimulated the research on the conversion of lignocellulosic biomass into reducing sugars for the subsequent production, and beta-glucosidases have been the focus because of their important roles in a variety fundamental biological processes and the synthesis of useful beta-glucosides. Although the beta-glucosidases of different sources have been investigated, the amount of beta-glucosidases are insufficient for effective conversion of cellulose. The goal of this work was to search for new resources of beta-glucosidases, which was thermostable and with high catalytic efficiency.
RESULTS: In this study, a thermostable native beta-glucosidase (nBgl3), which is secreted by the lignocellulose-decomposing fungus Aspergillus fumigatus Z5, was purified to electrophoretic homogeneity. Internal sequences of nBgl3 were obtained by LC-MS/MS, and its encoding gene, bgl3, was cloned based on the peptide sequences obtained from the LC-MS/MS results. bgl3 contains an open reading frame (ORF) of 2622 bp and encodes a protein with a predicted molecular weight of 91.47 kDa; amino acid sequence analysis of the deduced protein indicated that nBgl3 is a member of the glycoside hydrolase family 3. A recombinant beta-glucosidase (rBgl3) was obtained by the functional expression of bgl3 in Pichia pastoris X33. Several biochemical properties of purified nBgl3 and rBgl3 were determined - both enzymes showed optimal activity at pH 6.0 and 60 degrees C, and they were stable for a pH range of 4-7 and a temperature range of 50 to 70 degrees C. Of the substrates tested, nBgl3 and rBgl3 displayed the highest activity toward 4-Nitrophenyl-beta-D-glucopyranoside (pNPG), with specific activities of 103.5 +/- 7.1 and 101.7 +/- 5.2 U mg-1, respectively. However, these enzymes were inactive toward carboxymethyl cellulose, lactose and xylan.
CONCLUSIONS: An native beta-glucosidase nBgl3 was purified to electrophoretic homogeneity from the crude extract of A. fumigatus Z5. The gene bgl3 was cloned based on the internal sequences of nBgl3 obtained from the LC-MS/MS results, and the gene bgl3 was expressed in Pichia pastoris X33. The results of various biochemical properties of two enzymes including specific activity, pH stability, thermostability, and kinetic properties (Km and Vmax) indicated that they had no significant differences.
ESTHER : Liu_2012_Microb.Cell.Fact_11_25
PubMedSearch : Liu_2012_Microb.Cell.Fact_11_25
PubMedID: 22340848

Title : Oxidative desorption of thiocholine assembled on core-shell Fe3O4\/AuNPs magnetic nanocomposites for highly sensitive determination of acetylcholinesterase activity: an exposure biomarker of organophosphates - Du_2011_Biosens.Bioelectron_26_4231
Author(s) : Du D , Tao Y , Zhang W , Liu D , Li H
Ref : Biosensors & Bioelectronics , 26 :4231 , 2011
Abstract : Acetylcholinesterase (AChE) activity is a well established biomarker for biomonitoring of exposures to organophosphates (OPs) pesticides and chemical nerve agents. In this work, we described a novel electrochemical oxidative desorption-process of thiocholine, the product of enzymatic reaction, for rapid and highly sensitive determination of AChE activity in human serum. This principle is based on self-assembling of produced thiocholine onto core-shell Fe(3)O(4)/Au nanoparticles (Fe(3)O(4)/AuNPs) magnetic nanocomposites and its oxidation at electrode surface. Fe(3)O(4) magnetic core is not only used for magnetic separation from sample solutions, but also carrying more AuNPs due to its large surface-to-volume ratio. The core-shell Fe(3)O(4)/AuNPs nanocomposites were characterized by UV-Vis spectroscopy, field-emission scanning electron microscopy (FE-SEM) and electrochemical measurements. A linear relationship was obtained between the AChE activity and its concentration from 0.05 to 5.0 mU mL(-1) with a detection limit of 0.02 mU mL(-1). The method showed good results for characterization of AChE spiked human serum and detection of OP exposures from 0.05 to 20 nM, with detection limit of 0.02 nM. This new oxidative desorption assay thus provides a sensitive and quantitative tool for biomonitoring of the exposure to OP pesticides and nerve agents.
ESTHER : Du_2011_Biosens.Bioelectron_26_4231
PubMedSearch : Du_2011_Biosens.Bioelectron_26_4231
PubMedID: 21514816

Title : Identification of carboxylesterases expressed in rat intestine and effects of their hydrolyzing activity in predicting first-pass metabolism of ester prodrugs - Liu_2011_Pharmazie_66_888
Author(s) : Liu D , Gao J , Zhang C , Ren X , Liu Y , Xu Y
Ref : Pharmazie , 66 :888 , 2011
Abstract : Carboxylesterases (CESs) located in the intestine play an unique role in the absorption of many drugs especially ester prodrugs. In order to determine the expression and hydrolyzing activity of CESs isozymes (CES1 and CES2) located in rat intestine, the activities of CES1 and CES2 were evaluated by the intestinal S9 incubation with imidapril and irinotecan (CPT-11), the substrates of CES1 and CES2, respectively. The distribution characteristics of CES1, CES2, Pregnane X Receptor (PXR) and Constitutive Androstane Receptor were analyzed by real-time polymerase chain reaction (RT-PCR) or Western blot. Imidaprilat metabolized from imidapril by CES1 was too low to be detected in rat intestinal S9 fractions, while there was little and even no expression of CES1 mRNA in intestinal segments. In contrast, Vmax values for CPT-11 diminished gradually from proximal to distal segments within the rat intestine which was consistent with the mRNA expression level of CES2. These results indicated that CES2 represents the major CESs isoform in the rat complete intestine and decreased from duodenum to colon, whereas the expression of CES1 was too low to influence the metabolism of ester prodrugs. The expression of PXR and CAR decreased slightly along the entire intestine on both mRNA and protein levels which indicated that PXR and CAR may be one of the major factors which contribute to the expression of CES1 and CES2. Thus, the knowledge about the characteristic and site-specific expression of CES1 and CES2 in rat intestine will help to predict the oral bioavailability of ester prodrugs.
ESTHER : Liu_2011_Pharmazie_66_888
PubMedSearch : Liu_2011_Pharmazie_66_888
PubMedID: 22204136

Title : Whole-genome sequences of four Mycobacterium bovis BCG vaccine strains - Pan_2011_J.Bacteriol_193_3152
Author(s) : Pan Y , Yang X , Duan J , Lu N , Leung AS , Tran V , Hu Y , Wu N , Liu D , Wang Z , Yu X , Chen C , Zhang Y , Wan K , Liu J , Zhu B
Ref : Journal of Bacteriology , 193 :3152 , 2011
Abstract : Mycobacterium bovis Bacille Calmette-Guerin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines.
ESTHER : Pan_2011_J.Bacteriol_193_3152
PubMedSearch : Pan_2011_J.Bacteriol_193_3152
PubMedID: 21478353
Gene_locus related to this paper: myctu-RV1215C

Title : Covalent coupling of organophosphorus hydrolase loaded quantum dots to carbon nanotube\/Au nanocomposite for enhanced detection of methyl parathion - Du_2010_Biosens.Bioelectron_25_1370
Author(s) : Du D , Chen W , Zhang W , Liu D , Li H , Lin Y
Ref : Biosensors & Bioelectronics , 25 :1370 , 2010
Abstract : An amperometric biosensor for highly selective and sensitive determination of methyl parathion (MP) was developed based on dual-signal amplification: (1) a large amount of introduced enzyme on the electrode surface and (2) synergistic effects of nanoparticles towards enzymatic catalysis. The fabrication process includes (1) electrochemical deposition of gold nanoparticles by a multi-potential step technique at multiwalled carbon nanotube (MWCNT) film pre-cast on a glassy carbon electrode and (2) immobilization of methyl parathion degrading enzyme (MPDE) onto a modified electrode through CdTe quantum dots (CdTe QDs) covalent attachment. The introduced MWCNT and gold nanoparticles significantly increased the surface area and exhibited synergistic effects towards enzymatic catalysis. CdTe QDs are further used as carriers to load a large amount of enzyme. As a result of these two important enhancement factors, the proposed biosensor exhibited extremely sensitive, perfectly selective, and rapid response to methyl parathion in the absence of a mediator. The detection limit was 1.0 ng/mL. Moreover, since MPDE hydrolyzes pesticides containing the P-S bond, it showed high selectivity for detecting MP and many interfering compounds, such as carbamate pesticides. Other organophosphorous pesticides and oxygen-containing inorganic ions (SO(4)(2-), NO(3)(-)) did not interfere with the determination. The proposed MPDE biosensor presents good reproducibility and stability, and the MPDE is not poisoned by organophosphate pesticides. Unlike cholinesterase-based biosensor, the MPDE biosensor can be potentially reused and is suitable for continuous monitoring.
ESTHER : Du_2010_Biosens.Bioelectron_25_1370
PubMedSearch : Du_2010_Biosens.Bioelectron_25_1370
PubMedID: 19926466

Title : Rational design of Pseudozyma antarctica lipase B yielding a general esterification catalyst - Liu_2010_Chembiochem_11_789
Author(s) : Liu D , Trodler P , Eiben S , Koschorreck K , Muller M , Pleiss J , Maurer SC , Branneby C , Schmid RD , Hauer B
Ref : Chembiochem , 11 :789 , 2010
Abstract : Pseudozyma antarctica lipase B (CALB) shows activity in the acrylation of hydroxypropylcarbamate, a racemic mixture of enantiomers of primary and secondary alcohols. However, full conversion is hampered by the slowly reacting S enantiomer of the secondary alcohol. The same is true for a wide range of secondary alcohols, for example, octan-2- and -3-ol. In order to get high conversion in these reactions in a short time, the stereospecificity pocket of CALB was redesigned by using predictions from molecular modeling. Positions 278, 104, and 47 were targeted, and a library for two-site saturation mutagenesis at positions 104 and 278 was constructed. The library was then screened for hydrolysis of acrylated hydroxypropylcarbamates. The best mutants L278A, L278V, L278A/W104F, and L278A/W104F/S47A showed an increased conversion in hydrolysis and transesterification of more than 30 %. While the wild-type showed only 73 % conversion in the acrylation of hydroxypropylcarbamate after 6 h, 97 % conversion was achieved by L278A in this time. Besides this, L278A/W104F reached >96 % conversion in the acrylation of octan-2- and -3-ol within 48 h and showed a significant decrease in stereoselectivity, while the wild-type reached only 68 and 59 % conversion, respectively. Thus the new biocatalysts can be used for efficient transformation of racemic alcohols and esters with high activity when the high stereoselectivity of the wild-type hampers complete conversion of racemic substrates in a short time.
ESTHER : Liu_2010_Chembiochem_11_789
PubMedSearch : Liu_2010_Chembiochem_11_789
PubMedID: 20209560

Title : Heterologous expression, characterization and site-directed mutagenesis of cutinase CUTAB1 from Alternaria brassicicola - Koschorreck_2010_Appl.Microbiol.Biotechnol_87_991
Author(s) : Koschorreck K , Liu D , Kazenwadel C , Schmid RD , Hauer B
Ref : Applied Microbiology & Biotechnology , 87 :991 , 2010
Abstract : The cutinase CUTAB1 was cloned from a cutin induced culture of Alternaria brassicicola and heterologously expressed in Pichia pastoris under the control of the methanol-inducible AOX1 promoter. From a 400-ml culture, 36 mg of purified recombinant enzyme were obtained. Biochemical characterization revealed highest catalytic activity of the enzyme at 40 degrees C and pH 7-9 using p-nitrophenyl palmitate (p-NPP) as substrate. Among several fatty acid methyl and ethyl esters, glycerol esters and p-nitrophenyl esters tested, CUTAB1 showed highest activity towards tributyrin (3,302 +/- 160 U mg(-1)) and the activity decreased with increase in chain length of the investigated esters. Lowest activity was found for p-NPP. Replacing Leu80, Leu181 and Ile183, respectively, by the smaller alanine in the hydrophobic binding loop of CUTAB1, drastically reduced the overall activity of the enzyme. On the other hand, mutation A84F located in the small helical flap of CUTAB1 significantly increased the activity of the enzyme towards longer chain substrates like p-NPP.
ESTHER : Koschorreck_2010_Appl.Microbiol.Biotechnol_87_991
PubMedSearch : Koschorreck_2010_Appl.Microbiol.Biotechnol_87_991
PubMedID: 20306187

Title : Pharmacokinetics and pharmacodynamics of vildagliptin in healthy Chinese volunteers - Hu_2009_J.Clin.Pharmacol_49_39
Author(s) : Hu P , Yin Q , Deckert F , Jiang J , Liu D , Kjems L , Dole WP , He YL
Ref : Journal of Clinical Pharmacology , 49 :39 , 2009
Abstract : Vildagliptin is an orally effective, potent, and selective inhibitor of dipeptidyl peptidase IV (DPP-4) that improves glycemic control in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled, time-lagged, parallel-group study in a total of 60 healthy Chinese participants. Single- and multiple-dose pharmacokinetics and pharmacodynamics, and safety and tolerability of vildagliptin were assessed following administration of 25, 50, 100, or 200 mg qd, or 50 mg bid. Vildagliptin was rapidly absorbed (tmax 1.5-2.0 hours) across the dose range of 25 to 200 mg and was quickly eliminated with a terminal elimination half-life (t1/2) of approximately 2 hours. Consistent with the short t1/2, no accumulation of vildagliptin was observed following the administration of multiple doses (accumulation factors were 1.00-1.05 across the 25- to 200-mg dose range). Vildagliptin AUC and Cmax values increased in an approximately dose-proportional fashion (dose proportionality constant beta 1.00-1.16). Administration of vildagliptin 25 to 200 mg led to rapid and near-complete (>95%) inhibition of DPP-4 activity for at least 4 hours after dosing, which was associated with increases in plasma active glucagon-like peptide-1 of up to 2- to 3-fold compared with placebo. The duration of DPP-4 inhibition increased with dose. Glucose and insulin levels were not affected by vildagliptin in healthy participants, consistent with the fact that the glucose-lowering effects of vildagliptin occur in a glucose-dependent fashion. Vildagliptin was well tolerated at the highest tested dose of 200 mg qd. Vildagliptin 25 to 200 mg qd exhibits approximately dose-proportional pharmacokinetics with no evidence of accumulation after multiple dosing in healthy Chinese participants. Vildagliptin demonstrates potent inhibition of DPP-4 activity with excellent tolerability at doses of up to and including 200 mg qd.
ESTHER : Hu_2009_J.Clin.Pharmacol_49_39
PubMedSearch : Hu_2009_J.Clin.Pharmacol_49_39
PubMedID: 18832295

Title : Integrated production for biodiesel and 1,3-propanediol with lipase-catalyzed transesterification and fermentation - Xu_2009_Biotechnol.Lett_31_1335
Author(s) : Xu Y , Liu H , Du W , Sun Y , Ou X , Liu D
Ref : Biotechnol Lett , 31 :1335 , 2009
Abstract : Biodiesel, a renewable alternative to fossil energy, has shown great prospects for global proliferation in the past decade. Lipase catalyzed transesterification for biodiesel production, as a biological process with many advantages has drawn increasing attention. As a by-product, glycerol accounts for about 10% w/w of biodiesel during the process of biodiesel production. As a result, the conversion of glycerol has become a common problem which has to be resolved if considering large amount of biodiesel production. Glycerol can be fermented into 1,3-propanediol, a high value added chemical with a promising future in the polymers, for example, polytrimethylene terephthalate, and also fermentation approaches for 1,3-propanediol production which have drawn more and more attention due to advantages such as relatively low investment, mild reaction conditions and using renewable sources as the starting materials. Based on the latest technology advancements in lipase-mediated transformation for biodiesel production, the aerobic fermentation technology and genetic engineering for 1,3-propanediol production, and the integrated production of 1,3-propanediol from crude glycerol could be a promising way to improve the profit of the whole process during biodiesel production.
ESTHER : Xu_2009_Biotechnol.Lett_31_1335
PubMedSearch : Xu_2009_Biotechnol.Lett_31_1335
PubMedID: 19466559

Title : The genome of the cucumber, Cucumis sativus L - Huang_2009_Nat.Genet_41_1275
Author(s) : Huang S , Li R , Zhang Z , Li L , Gu X , Fan W , Lucas WJ , Wang X , Xie B , Ni P , Ren Y , Zhu H , Li J , Lin K , Jin W , Fei Z , Li G , Staub J , Kilian A , van der Vossen EA , Wu Y , Guo J , He J , Jia Z , Tian G , Lu Y , Ruan J , Qian W , Wang M , Huang Q , Li B , Xuan Z , Cao J , Asan , Wu Z , Zhang J , Cai Q , Bai Y , Zhao B , Han Y , Li Y , Li X , Wang S , Shi Q , Liu S , Cho WK , Kim JY , Xu Y , Heller-Uszynska K , Miao H , Cheng Z , Zhang S , Wu J , Yang Y , Kang H , Li M , Liang H , Ren X , Shi Z , Wen M , Jian M , Yang H , Zhang G , Yang Z , Chen R , Ma L , Liu H , Zhou Y , Zhao J , Fang X , Fang L , Liu D , Zheng H , Zhang Y , Qin N , Li Z , Yang G , Yang S , Bolund L , Kristiansen K , Li S , Zhang X , Wang J , Sun R , Zhang B , Jiang S , Du Y
Ref : Nat Genet , 41 :1275 , 2009
Abstract : Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system.
ESTHER : Huang_2009_Nat.Genet_41_1275
PubMedSearch : Huang_2009_Nat.Genet_41_1275
PubMedID: 19881527
Gene_locus related to this paper: cucsa-a0a0a0ktw5 , cucsa-a0a0a0lnt6 , cucsa-a0a0a0kpn7 , cucsa-a0a0a0lvt9 , cucsa-a0a0a0kdx8 , cucsa-a0a0a0m228 , cucsa-a0a0a0kz31 , cucsa-a0a0a0k5t5 , cucsa-a0a0a0kfs7 , cucsa-a0a0a0kjj7 , cucsa-a0a0a0kzs7 , cucsa-a0a0a0l0a6 , cucsa-a0a0a0l4w4 , cucsa-a0a0a0lpz0 , cucsa-a0a0a0ls66

Title : Estrogen-enhanced gene expression of lipoprotein lipase in heart is antagonized by progesterone - Liu_2008_Endocrinology_149_711
Author(s) : Liu D , Deschamps A , Korach KS , Murphy E
Ref : Endocrinology , 149 :711 , 2008
Abstract : Although estrogen has effects on the heart, little is known regarding which genes in the heart are directly responsive to estrogen. We have shown previously that lipoprotein lipase (LPL) expression was increased in female hearts compared with male hearts. To test whether LPL gene expression in heart is regulated by estrogen, we perfused mouse hearts from ovariectomized females with 100 nM 17beta-estradiol or vehicle for 2 h, after which hearts were frozen, and RNA was isolated. The SYBR green real-time PCR method was used to detect LPL gene expression. We found that addition of 17beta-estradiol to hearts from ovariectomized females resulted in a significant increase in LPL mRNA. This estrogen effect on LPL gene expression in mouse heart can be blocked by the estrogen receptor (ER) antagonist ICI 182,780 or by progesterone. We also identified a potential estrogen receptor element (ERE) enhancer sequence located in the first intron of the mouse LPL gene. The potential ERE sequence was linked to a TATA-luciferase (LUC) reporter plasmid in HeLa cells. Both ERalpha and ERbeta stimulated strong activity on the heterologous promoter reporter in Hela cells upon estrogen addition. Both ERalpha and ERbeta activities on the LPL ERE reporter were abrogated by the ER antagonist ICI 182,780. Progesterone also dose dependently inhibited the estrogen-mediated increase in LPL ERE reporter activity. These results show that heart LPL is an estrogen-responsive gene exhibiting an intronic regulatory sequence.
ESTHER : Liu_2008_Endocrinology_149_711
PubMedSearch : Liu_2008_Endocrinology_149_711
PubMedID: 17974624

Title : A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates - Chen_2007_PLoS.One_2_e315
Author(s) : Chen C , Tang J , Dong W , Wang C , Feng Y , Wang J , Zheng F , Pan X , Liu D , Li M , Song Y , Zhu X , Sun H , Feng T , Guo Z , Ju A , Ge J , Dong Y , Sun W , Jiang Y , Yan J , Yang H , Wang X , Gao GF , Yang R , Yu J
Ref : PLoS ONE , 2 :e315 , 2007
Abstract : BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.
ESTHER : Chen_2007_PLoS.One_2_e315
PubMedSearch : Chen_2007_PLoS.One_2_e315
PubMedID: 17375201
Gene_locus related to this paper: strsu-a4vws4 , strsu-q302y4 , strsy-a4vus4 , strsy-a4vwf6

Title : Functional expression of Candida antarctica lipase B in the Escherichia coli cytoplasm--a screening system for a frequently used biocatalyst - Liu_2006_Appl.Microbiol.Biotechnol_72_1024
Author(s) : Liu D , Schmid RD , Rusnak M
Ref : Applied Microbiology & Biotechnology , 72 :1024 , 2006
Abstract : In this paper, we report for the first time the functional expression of lipase B from the yeast Candida antarctica (CalB) in the Escherichia coli cytoplasm. The enzyme possessing three disulfide bonds was functionally expressed in the strain Origami B. Expression under the control of a lac promoter yielded 2 U mg(-1), whereas expression of a thioredoxin-CalB fusion protein yielded 17 U mg(-1). The native enzyme was most efficiently expressed under control of the cspA promoter (11 U mg(-1)). Coexpression of different chaperones led to a strong increase in active protein formation (up to 61 U mg(-1)). A codon-optimized synthetic variant of calb did not show significant effects on functional protein yield. Functional CalB expression was not only achieved in shake flasks but also in microtiter plate scale. Therefore, this CalB expression system is suitable for high-throughput applications, including the screening of large gene libraries as those derived from directed evolution experiments.
ESTHER : Liu_2006_Appl.Microbiol.Biotechnol_72_1024
PubMedSearch : Liu_2006_Appl.Microbiol.Biotechnol_72_1024
PubMedID: 16703321

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Effect of alcohols and temperature on the direct chiral resolutions of fipronil, isocarbophos and carfentrazone-ethyl - Wang_2005_Biomed.Chromatogr_19_454
Author(s) : Wang P , Jiang S , Liu D , Jia G , Wang Q , Zhou Z
Ref : Biomedical Chromatography , 19 :454 , 2005
Abstract : The enantiomeric separations of three pesticides fipronil (asymmetric nitrogen), isocarbophos (asymmetric phosphorus) and carfentrazone-ethyl (asymmetric carbon) were studied on cellulose-tri(3,5-dimethylphenylcarbamate) chiral stationary phase using high-performance liquid chromatography under normal phase. The mobile phase was n-hexane with alcohols including ethanol, n-propanol, iso-propanol, n-butanol and iso-butanol as polar modifiers. The flow rate was 1.0 mL/min with UV detection at 280, 225 and 230 nm for fipronil, isocarbophos and carfentrazone-ethyl respectively. The influence of the modifiers and their volume content and temperature from 0 to 50 degrees C on the separations was investigated. The chiral stationary phase showed excellent stereoselectivity for the two enantiomers of fipronil and isocarbophos and certain chiral recognition for carfentrazone-ethyl. Iso-propanol was more suitable for the chiral separation of isocarbophos and carfentrazone-ethyl, and iso-butanol was better for fipronil. The resolutions increased with the decreasing modifier content and temperature for all the three chiral pesticides.
ESTHER : Wang_2005_Biomed.Chromatogr_19_454
PubMedSearch : Wang_2005_Biomed.Chromatogr_19_454
PubMedID: 16037928

Title : Lipase-catalysed enantioselective ammonolysis of phenylglycine methyl ester in organic solvent - Du_2003_Biotechnol.Appl.Biochem_38_107
Author(s) : Du W , Zong M , Guo Y , Liu D
Ref : Biotechnol Appl Biochem , 38 :107 , 2003
Abstract : Ammonium, provided by ammonium carbamate as a novel acyl acceptor, was adopted for enzymic enantioselective ammonolysis of racemic phenylglycine methyl ester in this paper and it has been found that the reaction conditions have profound effects on enzymic activity and enantioselectivity: the optimal concentration of ammonium carbamate was 80 mM; t-butanol was the most suitable reaction medium and the optimum initial water activity was found to be 0.75; relatively high reaction rate and enantioselectivity could be attained within the temperature range of 30-40 degrees C. Compared with the corresponding hydrolysis and alcoholysis, enzymic ammonolysis expressed rather high enzymic activity and enantioselectivity and 95% of enzymic activity remained after 10 batches of ammonolysis, which demonstrates that lipase-catalysed ammonolysis is a promising method for the preparation of optically pure (R)-phenylglycine and its derivatives.
ESTHER : Du_2003_Biotechnol.Appl.Biochem_38_107
PubMedSearch : Du_2003_Biotechnol.Appl.Biochem_38_107
PubMedID: 12749767

Title : Lipase-catalysed transesterification of soya bean oil for biodiesel production during continuous batch operation - Du_2003_Biotechnol.Appl.Biochem_38_103
Author(s) : Du W , Xu Y , Liu D
Ref : Biotechnol Appl Biochem , 38 :103 , 2003
Abstract : The effects of temperature, oil/alcohol molar ratio and by-product glycerol were studied during Lipozyme TL IM-catalysed continuous batch operation when short-chain alcohols were used as the acyl acceptor. In non-continuous batch operation, the optimal oil/alcohol ratio and temperature were 1:4 and 40-50 degrees C; however, during the continuous batch operation, the optimal oil/alcohol ratio and temperature were 1:1 and 30 degrees C; 95% of enzymic activity remained after 10 batches when isopropanol was adopted to remove by-product glycerol during repeated use of the lipase.
ESTHER : Du_2003_Biotechnol.Appl.Biochem_38_103
PubMedSearch : Du_2003_Biotechnol.Appl.Biochem_38_103
PubMedID: 12749768

Title : A novel enzymatic route for biodiesel production from renewable oils in a solvent-free medium - Xu_2003_Biotechnol.Lett_25_1239
Author(s) : Xu Y , Du W , Liu D , Zeng J
Ref : Biotechnol Lett , 25 :1239 , 2003
Abstract : A new enzymatic route for biodiesel production from soybean oil was developed using methyl acetate as a novel acyl acceptor. Novozym 435 (immobilized Candida antarctica lipase) gave the highest methyl ester (ME) yield of 92%. The optimum conditions of the transesterification were 30% enzyme based on oil weight; a molar ratio of methyl acetate/oil of 12:1; temperature 40 degrees C and reaction time 10 h. Since no glycerol was produced in the process, this method is very convenient for recycling the catalyst and by-product triacetylglycerol showed no negative effect on the fuel property.
ESTHER : Xu_2003_Biotechnol.Lett_25_1239
PubMedSearch : Xu_2003_Biotechnol.Lett_25_1239
PubMedID: 14514074