Xu L


Full name : Xu Li

First name : Li

Mail : Research Center for Eco-Environmental Sciences\; Chinese Academy of Sciences\; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Beijing

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Country : China

Email : lixu@rcees.ac.cn

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References (152)

Title : Soluble epoxide hydrolase inhibitor (TPPU) alleviates ferroptosis by regulating CCL5 after intracerebral hemorrhage in mice - Wu_2024_Biomed.Pharmacother_172_116301
Author(s) : Wu Q , Jiang N , Wang Y , Song G , Li P , Fang Y , Xu L , Wang W , Xie M
Ref : Biomed Pharmacother , 172 :116301 , 2024
Abstract : Soluble epoxide hydrolase (sEH) inhibition has been shown multiple beneficial effects against brain injuries of Intracerebral hemorrhage (ICH). However, the underlying mechanism of its neuroprotective effects after ICH has not been explained fully. Ferroptosis, a new form of iron-dependent programmed cell death, has been shown to be implicated in the secondary injuries after ICH. In this study, We examined whether sEH inhibition can alleviate brain injuries of ICH through inhibiting ferroptosis. Expression of several markers for ferroptosis was observed in the peri-hematomal brain tissues in mice after ICH. lip-1, a ferroptosis inhibitor, alleviated iron accumulation, lipid peroxidation and the secondary damages post-ICH in mice model. Intraperitoneal injection of 1-Trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl)urea (TPPU), a highly selective sEH inhibitor, could inhibit ferroptosis and alleviate brain damages in ICH mice. Furthermore, RNA-sequencing was applied to explore the potential regulatory mechanism underlying the effects of TPPU in ferroptosis after ICH. C-C chemokine ligand 5 (CCL5) may be the key factor by which TPPU regulated ferroptosis after ICH since CCL5 antagonist could mimic the effects of TPPU and CCL5 reversed the inhibitive effect of TPPU on ferroptosis and the neuroprotective effects of TPPU on secondary damage after ICH. Taken together, these data indicate that ferroptosis is a key pathological feature of ICH and Soluble epoxide hydrolase inhibitor can exert neuroprotective effect by preventing ferroptosis after ICH.
ESTHER : Wu_2024_Biomed.Pharmacother_172_116301
PubMedSearch : Wu_2024_Biomed.Pharmacother_172_116301
PubMedID: 38377737

Title : Identification and biochemical characterization of a carboxylesterase gene associated with beta-cypermethrin resistance in Dermanyssus gallinae - Zhang_2024_Poult.Sci_103_103612
Author(s) : Zhang X , Zhang Y , Xu K , Qin J , Wang D , Xu L , Wang C
Ref : Poult Sci , 103 :103612 , 2024
Abstract : Dermanyssus gallinae is a major hematophagous ectoparasite in layer hens. Although the acaricide beta-cypermethrin has been used to control mites worldwide, D. gallinae has developed resistance to this compound. Carboxylesterases (CarEs) are important detoxification enzymes that confer resistance to beta-cypermethrin in arthropods. However, CarEs associated with beta-cypermethrin resistance in D. gallinae have not yet been functionally characterized. Here, we isolated a CarE gene (Deg-CarE) from D. gallinae and assayed its activity. The results revealed significantly higher expression of Deg-CarE in the beta-cypermethrin-resistant strain (RS) than in the susceptible strain (SS) toward alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA). These findings suggest that enhanced esterase activities might have contributed to beta-cypermethrin resistance in D. gallinae. Quantitative real-time PCR analysis revealed that Deg-CarE expression levels were significantly higher in adults than in other life stages. Although Deg-CarE was upregulated in the RS, significant differences in gene copy numbers were not observed. Additionally, Deg-CarE expression was significantly induced by beta-cypermethrin in both the SS and RS. Moreover, silencing Deg-CarE via RNA interference decreased the enzyme activity and increased the susceptibility of the RS to beta-cypermethrin, confirming that Deg-CarE is crucial for beta-cypermethrin detoxification. Finally, recombinant Deg-CarE (rDeg-CarE) expressed in Escherichia coli displayed high enzymatic activity toward alpha/beta-NA. However, metabolic analysis indicated that rDeg-CarE did not directly metabolize beta-cypermethrin. The collective findings indicate that D. gallinae resistance to beta-cypermethrin is associated with elevated CarEs protein activity and increased Deg-CarE expression levels. These findings provide insights into the metabolic resistance of D. gallinae and offer scientific guidance for the management and control of D. gallinae.
ESTHER : Zhang_2024_Poult.Sci_103_103612
PubMedSearch : Zhang_2024_Poult.Sci_103_103612
PubMedID: 38492248

Title : SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to beta-cypermethrin with stereoselectivity - Xu_2024_Bull.Entomol.Res__1
Author(s) : Xu L , Liu H , Li B , Li G , Liu R , Li D
Ref : Bull Entomol Res , :1 , 2024
Abstract : Carboxylesterases (CarEs) is an important detoxification enzyme system in phase participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to beta-cypermethrin showed stereoselectivity, with higher metabolic activity to -cypermethrin than the enantiomer alpha-cypermethrin. The metabolite of beta-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that beta-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of beta-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in beta-cypermethrin resistance in S. litura.
ESTHER : Xu_2024_Bull.Entomol.Res__1
PubMedSearch : Xu_2024_Bull.Entomol.Res__1
PubMedID: 38708572
Gene_locus related to this paper: spolt-SlCarE054

Title : In silico design of multipoint mutants for enhanced performance of Thermomyces lanuginosus lipase for efficient biodiesel production - Huang_2024_Biotechnol.Biofuels.Bioprod_17_33
Author(s) : Huang J , Xie X , Zheng W , Xu L , Yan J , Wu Y , Yang M , Yan Y
Ref : Biotechnol Biofuels Bioprod , 17 :33 , 2024
Abstract : BACKGROUND: Biodiesel, an emerging sustainable and renewable clean energy, has garnered considerable attention as an alternative to fossil fuels. Although lipases are promising catalysts for biodiesel production, their efficiency in industrial-scale application still requires improvement. RESULTS: In this study, a novel strategy for multi-site mutagenesis in the binding pocket was developed via FuncLib (for mutant enzyme design) and Rosetta Cartesian_ddg (for free energy calculation) to improve the reaction rate and yield of lipase-catalyzed biodiesel production. Thermomyces lanuginosus lipase (TLL) with high activity and thermostability was obtained using the Pichia pastoris expression system. The specific activities of the mutants M11 and M21 (each with 5 and 4 mutations) were 1.50- and 3.10-fold higher, respectively, than those of the wild-type (wt-TLL). Their corresponding melting temperature profiles increased by 10.53 and 6.01 degreesC, [Formula: see text] (the temperature at which the activity is reduced to 50% after 15 min incubation) increased from 60.88 to 68.46 degreesC and 66.30 degreesC, and the optimum temperatures shifted from 45 to 50 degreesC. After incubation in 60% methanol for 1 h, the mutants M11 and M21 retained more than 60% activity, and 45% higher activity than that of wt-TLL. Molecular dynamics simulations indicated that the increase in thermostability could be explained by reduced atomic fluctuation, and the improved catalytic properties were attributed to a reduced binding free energy and newly formed hydrophobic interaction. Yields of biodiesel production catalyzed by mutants M11 and M21 for 48 h at an elevated temperature (50 degreesC) were 94.03% and 98.56%, respectively, markedly higher than that of the wt-TLL (88.56%) at its optimal temperature (45 degreesC) by transesterification of soybean oil. CONCLUSIONS: An integrating strategy was first adopted to realize the co-evolution of catalytic efficiency and thermostability of lipase. Two promising mutants M11 and M21 with excellent properties exhibited great potential for practical applications for in biodiesel production.
ESTHER : Huang_2024_Biotechnol.Biofuels.Bioprod_17_33
PubMedSearch : Huang_2024_Biotechnol.Biofuels.Bioprod_17_33
PubMedID: 38402206

Title : Neuroprotection of macamide in a mouse model of Alzheimer's disease involves Nrf2 signaling pathway and gut microbiota - Xia_2024_Eur.J.Pharmacol_975_176638
Author(s) : Xia N , Xu L , Huang M , Xu D , Li Y , Wu H , Mei Z , Yu Z
Ref : European Journal of Pharmacology , 975 :176638 , 2024
Abstract : The underlying mechanisms of macamide's neuroprotective effects in Alzheimer's disease (AD) were investigated in the paper. Macamides are considered as unique ingredients in maca. Improvement effects and mechanisms of macamide on cognitive impairment have not been revealed. In this study, Vina 1.1.2 was used for docking to evaluate the binding abilities of 12 main macamides to acetylcholinesterase (AChE). N-benzyl-(9Z,12Z)-octadecadienamide (M 18:2) was selected to study the following experiments because it can stably bind to AChE with a strong binding energy. The animal experiments showed that M 18:2 prevented the scopolamine (SCP)-induced cognitive impairment and neurotransmitter disorders, increased the positive rates of Nrf2 and HO-1 in hippocampal CA1, improved the synaptic plasticity by maintaining synaptic morphology and increasing the synapse density. Moreover, the contents of IL-1beta, IL-6, and TNF-alpha in the hippocampus, serum, and colon were reduced by M 18:2. Furthermore, M 18:2 promoted colonic epithelial integrity and partially restored the composition of the gut microbiota to normal, including decreased genera Clostridiales_unclassified and Lachnospiraceae_unclassified, as well as increased genera Muribaculaceae_unclassified, Muribaculum, Alistipes, and Bacteroides, which may be the possible biomarkers of cognitive aging. In summary, M 18:2 exerted neuroprotective effects on SCP-induced AD mice possibly via activating the Nrf2/HO-1 signaling pathway and modulating the gut microbiota.
ESTHER : Xia_2024_Eur.J.Pharmacol_975_176638
PubMedSearch : Xia_2024_Eur.J.Pharmacol_975_176638
PubMedID: 38734297

Title : New advances in clinical application of neostigmine: no longer focusing solely on increasing skeletal muscle strength - Si_2023_Front.Pharmacol_14_1227496
Author(s) : Si S , Zhao X , Su F , Lu H , Zhang D , Sun L , Wang F , Xu L
Ref : Front Pharmacol , 14 :1227496 , 2023
Abstract : Neostigmine is a clinical cholinesterase inhibitor, that is, commonly used to enhance the function of the cholinergic neuromuscular junction. Recent studies have shown that neostigmine regulates the immune-inflammatory response through the cholinergic anti-inflammatory pathway, affecting perioperative neurocognitive function. This article reviews the relevant research evidence over the past 20 years, intending to provide new perspectives and strategies for the clinical application of neostigmine.
ESTHER : Si_2023_Front.Pharmacol_14_1227496
PubMedSearch : Si_2023_Front.Pharmacol_14_1227496
PubMedID: 37601044

Title : Visualizing Dipeptidyl Peptidase-IV with an Advanced Non--Conjugated Fluorescent Probe for Early Thyroid Disease Diagnosis - Li_2023_Anal.Chem_95_17577
Author(s) : Li J , Ma M , Xu L , Song D , Ma P , Fei Q
Ref : Analytical Chemistry , 95 :17577 , 2023
Abstract : Early detection and effective treatment of thyroid cancer are vital due to the aggressiveness and high mortality rate of the cancer. Nevertheless, the exploration of dipeptidyl peptidase-IV (DPP-IV) as a biomarker for thyroid diseases has not been widely conducted. In this study, we developed a novel non-Pi-conjugated near-infrared fluorescent probe, MB-DPP4, specifically designed to visualize and detect endogenous DPP-IV. Traditional DPP-IV-specific fluorescent probes rely primarily on the intramolecular charge transfer mechanism. For this reason, these probes are often hampered by high background levels that can inhibit their ability to achieve a fluorescence turn-on effect. MB-DPP4 successfully surmounts several drawbacks of traditional DPP-IV probes, boasting unique features such as exceptional selectivity, ultrahigh sensitivity (0.29 ng/mL), innovative structure, low background, and long-wavelength fluorescence. MB-DPP4 is an "off-on" chemosensor that exhibits strong fluorescence at 715 nm and releases a methylene blue (MB) fluorophore upon interacting with DPP-IV, resulting in a visible color change from colorless to blue. Given these remarkable attributes, MB-DPP4 shows great promise as a versatile tool for advancing research on biological processes and for evaluating the physiological roles of DPP-IV in living systems. Finally, we conducted a comprehensive investigation of DPP-IV expression in human serum, urine, thyroid cells, and mouse thyroid tumor models. Our findings could potentially establish a foundation for the early diagnosis and treatment of thyroid diseases.
ESTHER : Li_2023_Anal.Chem_95_17577
PubMedSearch : Li_2023_Anal.Chem_95_17577
PubMedID: 38050673

Title : Analysis of the human kidney transcriptome and plasma proteome identifies markers of proximal tubule maladaptation to injury - Wen_2023_Sci.Transl.Med_15_eade7287
Author(s) : Wen Y , Su E , Xu L , Menez S , Moledina DG , Obeid W , Palevsky PM , Mansour SG , Devarajan P , Cantley LG , Cahan P , Parikh CR
Ref : Sci Transl Med , 15 :eade7287 , 2023
Abstract : Acute kidney injury (AKI) is a major risk factor for long-term adverse outcomes, including chronic kidney disease. In mouse models of AKI, maladaptive repair of the injured proximal tubule (PT) prevents complete tissue recovery. However, evidence for PT maladaptation and its etiological relationship with complications of AKI is lacking in humans. We performed single-nucleus RNA sequencing of 120,985 nuclei in kidneys from 17 participants with AKI and seven healthy controls from the Kidney Precision Medicine Project. Maladaptive PT cells, which exhibited transcriptomic features of dedifferentiation and enrichment in pro-inflammatory and profibrotic pathways, were present in participants with AKI of diverse etiologies. To develop plasma markers of PT maladaptation, we analyzed the plasma proteome in two independent cohorts of patients undergoing cardiac surgery and a cohort of marathon runners, linked it to the transcriptomic signatures associated with maladaptive PT, and identified nine proteins whose genes were specifically up- or down-regulated by maladaptive PT. After cardiac surgery, both cohorts of patients had increased transforming growth factor-beta2 (TGFB2), collagen type XXIII-alpha1 (COL23A1), and X-linked neuroligin 4 (NLGN4X) and had decreased plasminogen (PLG), ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6), and protein C (PROC). Similar changes were observed in marathon runners with exercise-associated kidney injury. Postoperative changes in these markers were associated with AKI progression in adults after cardiac surgery and post-AKI kidney atrophy in mouse models of ischemia-reperfusion injury and toxic injury. Our results demonstrate the feasibility of a multiomics approach to discovering noninvasive markers and associating PT maladaptation with adverse clinical outcomes.
ESTHER : Wen_2023_Sci.Transl.Med_15_eade7287
PubMedSearch : Wen_2023_Sci.Transl.Med_15_eade7287
PubMedID: 38091407

Title : Elucidating the Impact of Bacterial Lipases, Human Serum Albumin, and FASII Inhibition on the Utilization of Exogenous Fatty Acids by Staphylococcus aureus - Pruitt_2023_bioRxiv__
Author(s) : Pruitt EL , Zhang R , Ross DH , Ashford NK , Chen X , Alonzo F , Bush MF , Werth BJ , Xu L
Ref : Biorxiv , : , 2023
Abstract : Staphylococcus aureus only synthesizes straight-chain or branched-chain saturated fatty acids (SCFAs or BCFAs) via the type II fatty acid synthesis (FASII) pathway, but as a highly adaptive pathogen, S. aureus can also utilize host-derived exogenous fatty acids (eFAs), including SCFAs and unsaturated fatty acids (UFAs). S. aureus secretes three lipases, Geh, sal1, and SAUSA300_0641, which could perform the function of releasing fatty acids from host lipids. Once released, the FAs are phosphorylated by the fatty acid kinase, FakA, and incorporated into the bacterial lipids. In this study, we determined the substrate specificity of S. aureus secreted lipases, the effect of human serum albumin (HSA) on eFA incorporation, and the effect of FASII inhibitor, AFN-1252, on eFA incorporation using comprehensive lipidomics. When grown with major donors of fatty acids, cholesteryl esters (CEs) and triglycerides (TGs), Geh was found to be the primary lipase responsible for hydrolyzing CEs, but other lipases could compensate for the function of Geh in hydrolyzing TGs. Lipidomics showed that eFAs were incorporated into all major S. aureus lipid classes and that fatty acid-containing HSA can serve as a source of eFAs. Furthermore, S. aureus grown with UFAs displayed decreased membrane fluidity and increased production of reactive oxygen species (ROS). Exposure to AFN-1252 enhanced UFAs in the bacterial membrane, even without a source of eFAs, indicating a FASII pathway modification. Thus, the incorporation of eFAs alters the S. aureus lipidome, membrane fluidity, and ROS formation, which could affect host-pathogen interactions and susceptibility to membrane-targeting antimicrobials. IMPORTANCE: Incorporation of host-derived exogenous fatty acids (eFAs), particularly unsaturated fatty acids (UFAs), by Staphylococcus aureus could affect the bacterial membrane fluidity and susceptibility to antimicrobials. In this work, we found that Geh is the primary lipase hydrolyzing cholesteryl esters and, to a less extent, triglycerides (TGs) and that human serum albumin (HSA) could serve as a buffer of eFAs, where low levels of HSA facilitate the utilization of eFAs, but high levels of HSA inhibit it. The fact that the FASII inhibitor, AFN-1252, leads to an increase in UFA content even in the absence of eFA suggests that membrane property modulation is part of its mechanism of action. Thus, Geh and/or the FASII system look to be promising targets to enhance S. aureus killing in a host environment by restricting eFA utilization or modulating membrane property, respectively.
ESTHER : Pruitt_2023_bioRxiv__
PubMedSearch : Pruitt_2023_bioRxiv__
PubMedID: 37425828

Title : Combined exposure to titanium dioxide and tetracycline induces neurotoxicity in zebrafish - Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562
Author(s) : Xu L , Yang X , He Y , Hu Q , Fu Z
Ref : Comparative Biochemistry & Physiology C Toxicol Pharmacol , :109562 , 2023
Abstract : In aquatic environment, engineered materials may inevitably interact with the coexisted organic pollutants, which affect their bioavailability and toxicity. In this contribution, the combined impacts of tetracycline (TC) and titanium dioxide nanoparticles (TiO(2) NPs) on the neurodevelopment of zebrafish larvae were investigated, and the underlying mechanisms were further elucidated. Firstly, it was confirmed that the co-existence of TC would increase the size and decrease the zeta potential of TiO(2) NPs. Following, developmental indicators and motor behaviors were investigated. Our results indicated that co-exposure to TC and TiO(2) NPs exhibited enhanced embryonic malformation rates and abnormal nervous system development in zebrafish embryos. Meanwhile, the locomotor behavior was increased upon treatment of TC and TiO(2) NP. Further, pathway enrichment analyses of transcriptomic sequencing provided detailed information that either lipid metabolism or PPAR signaling pathway were significantly affected in the co-exposure group. Also, TC + TiO(2) NP exposure significantly changed the mRNA expression of neural development-related genes and up-regulated the expression levels of neurotransmitters like 5-hydroxytryptamine, dopamine, acetylcholinesterase, and gamma-aminobutyric acid. Taken together, our results demonstrated that the co-exposure of TC and TiO(2) NPs had the potential to cause neurotoxicity in zebrafish embryos.
ESTHER : Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562
PubMedSearch : Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562
PubMedID: 36764589

Title : Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta - Li_2023_Front.Plant.Sci_14_1074184
Author(s) : Li J , Li F , Wu G , Gui F , Li H , Xu L , Hao X , Zhao Y , Ding X , Qin X
Ref : Front Plant Sci , 14 :1074184 , 2023
Abstract : Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3-8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 +/- 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.
ESTHER : Li_2023_Front.Plant.Sci_14_1074184
PubMedSearch : Li_2023_Front.Plant.Sci_14_1074184
PubMedID: 36844064

Title : Alteration of Chain-Length Selectivity and Thermostability of Rhizopus oryzae Lipase via Virtual Saturation Mutagenesis Coupled with Disulfide Bond Design - Huang_2023_Appl.Environ.Microbiol__e0187822
Author(s) : Huang J , Dai S , Chen X , Xu L , Yan J , Yang M , Yan Y
Ref : Applied Environmental Microbiology , :e0187822 , 2023
Abstract : Rhizopus oryzae lipase (ROL) is one of the most important enzymes used in the food, biofuel, and pharmaceutical industries. However, the highly demanding conditions of industrial processes can reduce its stability and activity. To seek a feasible method to improve both the catalytic activity and the thermostability of this lipase, first, the structure of ROL was divided into catalytic and noncatalytic regions by identifying critical amino acids in the crevice-like binding pocket. Second, a mutant screening library aimed at improvement of ROL catalytic performance by virtual saturation mutagenesis of residues in the catalytic region was constructed based on Rosetta's Cartesian_ddg protocol. A double mutant, E265V/S267W (with an E-to-V change at residue 265 and an S-to-W change at residue 267), with markedly improved catalytic activity toward diverse chain-length fatty acid esters was identified. Then, computational design of disulfide bonds was conducted for the noncatalytic amino acids of E265V/S267W, and two potential disulfide bonds, S61C-S115C and E190C-E238C, were identified as candidates. Experimental data validated that the variant E265V/S267W/S61C-S115C/E190C-E238C had superior stability, with an increase of 8.5 degreesC in the melting temperature and a half-life of 31.7 min at 60 degreesC, 4.2-fold longer than that of the wild-type enzyme. Moreover, the variant improved the lipase activity toward five 4-nitrophenyl esters by 1.5 to 3.8 times, exhibiting a potential to modify the catalytic efficiency. IMPORTANCE Rhizopus oryzae lipase (ROL) is very attractive in biotechnology and industry as a safe and environmentally friendly biocatalyst. Functional expression of ROL in Escherichia coli facilitates effective high-throughput screening for positive variants. This work highlights a method to improve both selectivity and thermostability based on a combination of virtual saturation mutagenesis in the substrate pocket and disulfide bond prediction in the noncatalytic region. Using the method, ROL thermostability and activity to diverse 4-nitrophenyl esters could be substantially improved. The strategy of rational introduction of multiple mutations in different functional domains of the enzyme is a great prospect in the modification of biocatalysts.
ESTHER : Huang_2023_Appl.Environ.Microbiol__e0187822
PubMedSearch : Huang_2023_Appl.Environ.Microbiol__e0187822
PubMedID: 36602359
Gene_locus related to this paper: rhidl-lipas

Title : Customized fluorescent probe for peering into the expression of butyrylcholinesterase in thyroid cancer - Kang_2023_Anal.Chim.Acta_1282_341932
Author(s) : Kang W , Ma M , Xu L , Tang S , Li J , Ma P , Song D , Sun Y
Ref : Anal Chim Acta , 1282 :341932 , 2023
Abstract : BACKGROUND: Thyroid cancer has been increasingly prevalent in recent years. The main diagnostic methods for thyroid are B-ultrasound scan, serum detection and puncture detection. However, these methods are invasive and complex. It is a pressing need to develop non-invasive or minimally invasive methods for thyroid cancer diagnosis. Fluorescence method as a non-invasive detection method has attracted much attention. Butyrylcholinesterase (BChE) is a common enzyme in the human body, and many diseases affect its reduction. We found that BChE is also a marker for thyroid cancer. Therefore, it is of certain clinical value to explore the expression of BChE in thyroid cancer cells through a customized fluorescent probe to provide valuable experimental data and clues for studying the expression of thyroid cancer marker to reflect thyroid status. RESULTS: In this study, we customized a fluorescent probe named Kang-BChE, which is easy to synthesize with a high yield. The experimental results show that the probe Kang-BChE can detect BChE in the linear range of 0-900 U L(-1) (R(2) = 0.9963), and the detection limit is as low as 3.93 U L(-1) (lambda(ex/em) = 550/689 nm). In addition, Kang-BChE probes have low cytotoxicity, good specificity, and can completely eliminate interference from acetylcholinesterase (AChE). Kang-BChE showed excellent stability in the detection of complex biological samples in serum recovery experiments (95.64-103.12 %). This study was the first time using Kang-BChE to study the low expression of BChE in thyroid cancer cells (Tpc-1 cells). In addition, we observed that H(2)O(2) concentration in Tpc-1 cells was positively correlated with BChE activity. SIGNIFICANCE: Kang-BChE is expected to be an important tool for monitoring the change of BChE content in complex biological environments due to its excellent performance. Kang-BChE can also be used to explore the influence of molecules in more organisms on the change of BChE content due to its excellent anti-interference ability. We expect that Kang-BChE can play a significant role in the clinical diagnosis and treatment of thyroid cancer.
ESTHER : Kang_2023_Anal.Chim.Acta_1282_341932
PubMedSearch : Kang_2023_Anal.Chim.Acta_1282_341932
PubMedID: 37923409

Title : De Novo Computational Design of a Lipase with Hydrolysis Activity towards Middle-Chained Fatty Acid Esters - Huang_2023_Int.J.Mol.Sci_24_8581
Author(s) : Huang J , Xie X , Zheng Z , Ye L , Wang P , Xu L , Wu Y , Yan J , Yang M , Yan Y
Ref : Int J Mol Sci , 24 :8581 , 2023
Abstract : Innovations in biocatalysts provide great prospects for intolerant environments or novel reactions. Due to the limited catalytic capacity and the long-term and labor-intensive characteristics of mining enzymes with the desired functions, de novo enzyme design was developed to obtain industrial application candidates in a rapid and convenient way. Here, based on the catalytic mechanisms and the known structures of proteins, we proposed a computational protein design strategy combining de novo enzyme design and laboratory-directed evolution. Starting with the theozyme constructed using a quantum-mechanical approach, the theoretical enzyme-skeleton combinations were assembled and optimized via the Rosetta "inside-out" protocol. A small number of designed sequences were experimentally screened using SDS-PAGE, mass spectrometry and a qualitative activity assay in which the designed enzyme 1a8uD(1) exhibited a measurable hydrolysis activity of 24.25 +/- 0.57 U/g towards p-nitrophenyl octanoate. To improve the activity of the designed enzyme, molecular dynamics simulations and the RosettaDesign application were utilized to further optimize the substrate binding mode and amino acid sequence, thus keeping the residues of theozyme intact. The redesigned lipase 1a8uD(1)-M8 displayed enhanced hydrolysis activity towards p-nitrophenyl octanoate-3.34 times higher than that of 1a8uD(1). Meanwhile, the natural skeleton protein (PDB entry 1a8u) did not display any hydrolysis activity, confirming that the hydrolysis abilities of the designed 1a8uD(1) and the redesigned 1a8uD(1)-M8 were devised from scratch. More importantly, the designed 1a8uD(1)-M8 was also able to hydrolyze the natural middle-chained substrate (glycerol trioctanoate), for which the activity was 27.67 +/- 0.69 U/g. This study indicates that the strategy employed here has great potential to generate novel enzymes exhibiting the desired reactions.
ESTHER : Huang_2023_Int.J.Mol.Sci_24_8581
PubMedSearch : Huang_2023_Int.J.Mol.Sci_24_8581
PubMedID: 37239928
Gene_locus related to this paper: 9zzzz-1a8uD1

Title : Characterization of a New Thermostable and Organic Solution-Tolerant Lipase from Pseudomonas fluorescens and Its Application in the Enrichment of Polyunsaturated Fatty Acids - Hu_2023_Int.J.Mol.Sci_24_8924
Author(s) : Hu Z , Jiao L , Xie X , Xu L , Yan J , Yang M , Yan Y
Ref : Int J Mol Sci , 24 :8924 , 2023
Abstract : The search for and characterization of new lipases with excellent properties has always been urgent and is of great importance to meet industrial needs. In this study, a new lipase, lipB, from Pseudomonas fluorescens SBW25, belonging to the lipase subfamily I.3, was cloned and expressed in Bacillus subtilis WB800N. Enzymatic properties studies of recombinant LipB found that it exhibited the highest activity towards p-nitrophenyl caprylate at 40 degreesC and pH 8.0, retaining 73% of its original activity after incubation at 70 degreesC for 6 h. In addition, Ca(2+), Mg(2+), and Ba(2+) strongly enhanced the activity of LipB, while Cu(2+), Zn(2+), Mn(2+), and CTAB showed an inhibiting effect. The LipB also displayed noticeable tolerance to organic solvents, especially acetonitrile, isopropanol, acetone, and DMSO. Moreover, LipB was applied to the enrichment of polyunsaturated fatty acids from fish oil. After hydrolyzing for 24 h, it could increase the contents of polyunsaturated fatty acids from 43.16% to 72.18%, consisting of 5.75% eicosapentaenoic acid, 19.57% docosapentaenoic acid, and 46.86% docosahexaenoic acid, respectively. The properties of LipB render it great potential in industrial applications, especially in health food production.
ESTHER : Hu_2023_Int.J.Mol.Sci_24_8924
PubMedSearch : Hu_2023_Int.J.Mol.Sci_24_8924
PubMedID: 37240270
Gene_locus related to this paper: psefs-c3kbe9

Title : A molecular imaging tool for monitoring carboxylesterase 2 during early diagnosis of liver-related diseases - Li_2023_Sens.Actuators.B.Chem_377_133122
Author(s) : Li J , Cao J , Wu W , Xu L , Zhang S , Ma P , Wu Q , Song D
Ref : Sensors and Actuators B: Chemical , 377 :133122 , 2023
Abstract : Early disease diagnosis is crucial for human health and successful therapy. Carboxylesterase 2 (CES2), the main enzyme found in many tumor tissues, is closely associated with many malignant diseases. Therefore, the ability to detect endogenous CES2-associated diseases can be of therapeutic significance. In this study, we designed a novel mitochondria-targeting near-infrared (NIR) chemosensor (YDT) to visualize the endogenous CES2. This is the first study to track CES2 at the mitochondrial level and present the currently most sensitive CES2 detection sensor. With various features including large Stokes shift, quick response time, excellent selectivity, and ultrahigh sensitivity, the sensor can overcome numerous limitations faced by traditional CES2 probes. YDT is an "off-on" chemosensor that releases fluorophore YD-1 upon interacting with CES2, emits strong fluorescence at 660 nm. Importantly, YDT can dynamically monitor immediate changes in CES2 level under external stimuli. Moreover, we used YDT to systematically study the CES2 expression in drug-induced liver injury and its remediation model, as well as in an inflammation model. With these outstanding characteristics, YDT is a considerably promising tool for further research on biological processes and for examining the physiological roles of CES2 in living systems
ESTHER : Li_2023_Sens.Actuators.B.Chem_377_133122
PubMedSearch : Li_2023_Sens.Actuators.B.Chem_377_133122
Gene_locus related to this paper: human-CES2

Title : Polysaccharide from Polygala tenuifolia alleviates cognitive decline in Alzheimer's disease mice by alleviating Abeta damage and targeting the ERK pathway - Li_2023_J.Ethnopharmacol__117564
Author(s) : Li Y , Wu H , Liu M , Zhang Z , Ji Y , Xu L , Liu Y
Ref : J Ethnopharmacol , :117564 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb. AIM OF THE STUDY: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs. MATERIALS AND METHODS: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus. The levels of acetylcholine (ACh) and acetylcholinesterase (AChE) were measured by ELISA. Immunofluorescence was used to reflect beta-amyloid (Abeta) levels in brain tissue. Apoptosis was evaluated by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. The status of dendritic branches and spines was observed by Golgi staining. Meanwhile, the expression levels of recombinant human insulin-degrading enzyme (IDE), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular regulated protein kinases (ERK), and cAMP-response element binding protein (CREB) proteins were determined by Western blotting. RESULTS: PTPS improves spatial cognitive deficits in AD mice, reduces cellular damage in the CA3 region of the hippocampus, maintains the balance of the cholinergic system, and exerts an anti-AD effect in vivo. The molecular mechanism of its action may be related to the reduction of Abeta deposition as well as the activation of ERK pathway-related proteins with enhanced synaptic plasticity. CONCLUSIONS: PTPS is able to exert anti-AD activity in vivo by mitigating Abeta damage and targeting the ERK pathway.
ESTHER : Li_2023_J.Ethnopharmacol__117564
PubMedSearch : Li_2023_J.Ethnopharmacol__117564
PubMedID: 38081400

Title : Synthesis and Characterization of Epoxidized Silkworm Pupae Oil and Its Application as Polyvinyl Chloride - Ji_2022_Appl.Biochem.Biotechnol_194_1290
Author(s) : Ji Y , Xu L , Xu Q , Liu X , Lin S , Liao S , Wang W , Lan D
Ref : Appl Biochem Biotechnol , 194 :1290 , 2022
Abstract : More and more industries demand environmental friendliness. Silkworm pupae oil (SPO), extracted from the desilked silkworm pupae, can serve as a promising substrate alternative to use in plasticization. This study aimed to prepare epoxidized silkworm pupae oil (ESPO) and investigate their effects on the thermal stability and plasticization of polyvinyl chloride (PVC) films. A chemo-enzymatic method of ESPO was developed in the presence of Lipase SMG1-F278N and H(2)O(2) in natural deep eutectic solvents (DESs). Lipase SMG1-F278N could initiate the epoxidation reaction effectively at room temperature with a negligible loss of activities 10 batches. A maximum oxirane value of 6.94% was obtained. The formation of oxirane ring in ESPO was confirmed by FTIR and (13)C NMR spectra. Moreover, ESPO showed a better thermal stability and lower freezing point than epoxidized soybean oil (ESO). It was demonstrated that ESPO had a good frost resistance. In addition, ESPO showed a significantly improved plasticizing effect on flexible polyvinyl chloride (PVC). Compared with ESO, ESPO could increase the tensile elongation at break effectively. A significantly lower migration rate of plasticizer was observed in PVC plasticized with ESPO.
ESTHER : Ji_2022_Appl.Biochem.Biotechnol_194_1290
PubMedSearch : Ji_2022_Appl.Biochem.Biotechnol_194_1290
PubMedID: 34677760
Gene_locus related to this paper: malgo-a8puy1

Title : Preparation and Characterization of Magnetic Metal-Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase - Li_2022_Molecules_27_6800
Author(s) : Li M , Dai X , Li A , Qi Q , Wang W , Cao J , Jiang Z , Liu R , Suo H , Xu L
Ref : Molecules , 27 :6800 , 2022
Abstract : Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal-organic framework composite, IL-Fe(3)O(4)@UiO-66-NH(2), was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe(3)O(4)@UiO-66-NH(2)) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) reached 74.4%, which was higher than that of PPL-Fe(3)O(4)@UiO-66-NH(2) (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe(3)O(4)@UiO-66-NH(2) had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe(3)O(4)@UiO-66-NH(2) modified by ionic liquids has great potential for immobilized enzymes.
ESTHER : Li_2022_Molecules_27_6800
PubMedSearch : Li_2022_Molecules_27_6800
PubMedID: 36296392

Title : Dioscin alleviates Alzheimer's disease through regulating RAGE\/NOX4 mediated oxidative stress and inflammation - Guan_2022_Biomed.Pharmacother_152_113248
Author(s) : Guan L , Mao Z , Yang S , Wu G , Chen Y , Yin L , Qi Y , Han L , Xu L
Ref : Biomed Pharmacother , 152 :113248 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Abeta) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dioscin, a natural steroidal saponin which exists in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in Alzheimer's disease (AD) is still unknown. In the present work, effect of dioscin on AD was evaluated in injured SH-SY5Y cells induced by H(2)O(2) and C57BL/6 mice with AD challenged with AlCl combined with D-galactose. Results showed that dioscin obviously increased cell viability and decreased reactive oxygen species (ROS) level in injured SH-SY5Y cells. In vivo, dioscin obviously improved the spatial learning and memory abilities as well as gait and interlimb coordination disorders of mice with AD. Moreover, dioscin distinctly restored the levels of malondialdehyde (MDA), superoxide dismutase (SOD), amyloid beta 42 (Abeta(42)), acetylcholine (ACh) and acetylcholinesterase (AChE) of mice, and reversed the histopathological changes of brain tissue. Mechanism studies revealed that dioscin markedly down-regulated the expression levels of RAGE and NOX4. Subsequently, dioscin markedly up-regulated the expression levels of Nrf2 and HO-1 related to oxidative stress, and down-regulated the levels of p-NF-kappaB(p-p65)/NF-kappaB(p65), AP-1 and inflammatory factors involved in inflammatory pathway. RAGE siRNAs transfection further clarified that the pharmacological activity of dioscin in AD was achieved by regulating RAGE/NOX4 pathway. In conclusion, dioscin showed excellent anti-AD effect by adjusting RAGE/NOX4-mediated oxidative stress and inflammation, which provided the basis for the further research and development against AD.
ESTHER : Guan_2022_Biomed.Pharmacother_152_113248
PubMedSearch : Guan_2022_Biomed.Pharmacother_152_113248
PubMedID: 35691153

Title : The Catalytic Domain of Neuropathy Target Esterase Influences Lipid Droplet Biogenesis and Lipid Metabolism in Human Neuroblastoma Cells - He_2022_Metabolites_12_
Author(s) : He L , Huang F , Wang Y , Wu Y , Xu L , Chang P
Ref : Metabolites , 12 : , 2022
Abstract : As an endoplasmic reticulum (ER)-anchored phospholipase, neuropathy target esterase (NTE) catalyzes the deacylation of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). The catalytic domain of NTE (NEST) exhibits comparable activity to NTE and binds to lipid droplets (LD). In the current study, the nucleotide monophosphate (cNMP)-binding domains (CBDs) were firstly demonstrated not to be essential for the ER-targeting of NTE, but to be involved in the normal ER distribution and localization to LD. NEST was associated with LD surface and influenced LD formation in human neuroblastoma cells. Overexpression of NEST enhances triacylglycerol (TG) accumulation upon oleic acid loading. Quantitative targeted lipidomic analysis shows that overexpression of NEST does not alter diacylglycerol levels but reduces free fatty acids content. NEST not only lowered levels of LPC and acyl-LPC, but not PC or alkyl-PC, but also widely altered levels of other lipid metabolites. Qualitative PCR indicates that the increase in levels of TG is due to the expression of diacylglycerol acyltransferase 1 gene by NEST overexpression. Thus, NTE may broadly regulate lipid metabolism to play roles in LD biogenesis in cells.
ESTHER : He_2022_Metabolites_12_
PubMedSearch : He_2022_Metabolites_12_
PubMedID: 35888761

Title : Structural Basis for the Regiospecificity of a Lipase from Streptomyces sp. W007 - Zhao_2022_Int.J.Mol.Sci_23_5822
Author(s) : Zhao Z , Chen S , Xu L , Cai J , Wang J , Wang Y
Ref : Int J Mol Sci , 23 :5822 , 2022
Abstract : The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a alpha-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases.
ESTHER : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedSearch : Zhao_2022_Int.J.Mol.Sci_23_5822
PubMedID: 35628632
Gene_locus related to this paper: 9actn-h0b8d4

Title : Resistance to Beta-cypermethrin, Azadirachtin, and Matrine, and Biochemical Characterization of Field Populations of Oedaleus asiaticus (Bey-Bienko) in Inner Mongolia, Northern China - Gao_2022_J.Insect.Sci_22_
Author(s) : Gao S , Tan Y , Han H , Guo N , Gao H , Xu L , Lin K
Ref : J Insect Sci , 22 : , 2022
Abstract : Oedaleus asiaticus (Bey-Bienko) is an economically devastating locust species found in grassland and pastoral areas of the Inner Mongolia region of northern China. In this study, resistance to three frequently used insecticides (beta-cypermethrin, matrine, and azadirachtin) was investigated in six field populations of O. asiaticus using the leaf-dip bioassay method. The inhibitory effects of synergists and the activities of detoxification enzyme activities in the different populations were determined to explore potential biochemical resistance mechanisms. The results showed that the field populations SB (resistance ratio [RR]=7.85), ZB (RR=5.64), and DB (RR=6.75) had developed low levels of resistance to beta-cypermethrin compared with a susceptible control strain. Both the SB (RR=5.92) and XC (RR=6.38) populations had also developed low levels of resistance against matrine, with the other populations remaining susceptible to both beta-cypermethrin and matrine. All field populations were susceptible to azadirachtin. Synergism analysis showed that triphenyl phosphate (TPP) and diethyl-maleate (DEM) increased the toxicity of beta-cypermethrin significantly in the SB population, while the synergistic effects of TPP, piperonyl butoxide (PBO), and DEM on the toxicity of matrine were higher in SB (SR 3.86, 4.18, and 3.07, respectively) than in SS (SR 2.24, 2.86, and 2.29, respectively), but no synergistic effects of TPP, PBO, and DEM on azadirachtin were found. Biochemical assays showed that the activities of carboxylesterases (CarEs) and glutathione-S-transferases (GSTs) were significantly raised in all field populations of O. asiaticus, with a significant positive correlation observed between beta-cypermethrin resistance and CarE activity. The activities of cytochrome P450 monooxygenases (P450) and multi-function oxidases (MFO) were elevated in all six field populations, and P450 activity displayed strong positive correlations with the three insecticides. Our findings suggest that resistance to beta-cypermethrin in O. asiaticus may be mainly attributed to elevated CarE and GST activities, while P450 plays an important role in metabolizing matrine and azadirachtin. Our study provides insights that will help improve insecticide resistance management strategies.
ESTHER : Gao_2022_J.Insect.Sci_22_
PubMedSearch : Gao_2022_J.Insect.Sci_22_
PubMedID: 36374481

Title : A network pharmacology-based approach to explore the therapeutic potential of Sceletium tortuosum in the treatment of neurodegenerative disorders - Luo_2022_PLoS.One_17_e0273583
Author(s) : Luo Y , Shan L , Xu L , Patnala S , Kanfer I , Li J , Yu P , Jun X
Ref : PLoS ONE , 17 :e0273583 , 2022
Abstract : Sceletium tortuosum (SCT) has been utilized medicinally by indigenous Koi-San people purportedly for mood elevation. SCT extracts are reported to be neuroprotective and have efficacy in improving cognition. However, it is still unclear which of the pharmacological mechanisms of SCT contribute to the therapeutic potential for neurodegenerative disorders. Hence, this study investigated two aspects-firstly, the abilities of neuroprotective sub-fractions from SCT on scavenging radicals, inhibiting some usual targets relevant to Alzheimer's disease (AD) or Parkinson's disease (PD), and secondly utilizing the network pharmacology related methods to search probable mechanisms using Surflex-Dock program to show the key targets and corresponding SCT constituents. The results indicated sub-fractions from SCT could scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, inhibit acetylcholinesterase (AChE), monoamine oxidase type B (MAO-B) and N-methyl-D-aspartic acid receptor (NMDAR). Furthermore, the results of gene ontology and docking analyses indicated the key targets involved in the probable treatment of AD or PD might be AChE, MAO-B, NMDAR subunit2B (GluN2B-NMDAR), adenosine A2A receptor and cannabinoid receptor 2, and the corresponding constituents in Sceletium tortuosum might be N-trans-feruloyl-3-methyldopamine, dihydrojoubertiamine and other mesembrine type alkaloids. In summary, this study has provided new evidence for the therapeutic potential of SCT in the treatment of AD or PD, as well as the key targets and notable constituents in SCT. Therefore, we propose SCT could be a natural chemical resource for lead compounds in the treatment of neurodegenerative disorders.
ESTHER : Luo_2022_PLoS.One_17_e0273583
PubMedSearch : Luo_2022_PLoS.One_17_e0273583
PubMedID: 36006974

Title : Surface Modification of Magnetic ZIF-90 Nanoparticles Improves the Microenvironment of Immobilized Lipase and Its Application in Esterification - Suo_2022_Langmuir__
Author(s) : Suo H , Geng X , Sun Y , Zhang L , Yang J , Yang F , Yan H , Hu Y , Xu L
Ref : Langmuir , : , 2022
Abstract : Interactions of enzymes with supports significantly affect the activity and stability of immobilized enzymes. Herein, amino-functionalized ionic liquid (IL)-grafted magnetic zeolitic imidazolate framework-90 (MZIF-90) was prepared and used to immobilize porcine pancreatic lipase (PPL). The nanocomposites were fully characterized; meanwhile, the interactions between ILs and ZIF-90 were calculated based on density functional theory. The prepared biocatalyst (PPL-ILs/MZIF-90) had a lipase loading of 178.3 mg/g and hydrolysis activity up to 287.5 U/g. When the biocatalyst was used to synthesize isoamyl acetate, the reaction media, molar ratio of alcohol/acid, temperature, and reaction time were optimized. Under the optimized reaction conditions (in hexane, alcohol/acid = 3:1, under 45 degreesC, reacted for 9 h), the ester yield reached 85.5%. The results of the stability test showed that PPL-ILs/MZIF-90 retained 88.7% of the initial activity after storing for 35 days and 92.5% of the initial activity after reusing for seven cycles for synthesizing isoamyl acetate. Moreover, the secondary structure analysis showed that the synthesized supports protected the active conformation of immobilized lipase, which lead to the enhanced catalytic performance. Additionally, the biocatalyst can be easily separated with a magnet, which facilitated the reusability. This study provides insights regarding the application of metal organic framework composites in the field of enzyme catalysis.
ESTHER : Suo_2022_Langmuir__
PubMedSearch : Suo_2022_Langmuir__
PubMedID: 36448653

Title : Design, synthesis, and evaluation of 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for Alzheimer's disease - Chen_2022_Ann.Transl.Med_10_303
Author(s) : Chen Z , Yu X , Chen L , Xu L , Cai Y , Hou S , Zheng M , Liu F
Ref : Ann Transl Med , 10 :303 , 2022
Abstract : BACKGROUND: Alzheimer's disease (AD) is thought to be a complex, multifactorial syndrome with many related molecular lesions contributing to its pathogenesis. Thus, multi-target-directed ligands are considered an effective way of treating AD. This study sought to evaluate 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for AD. METHODS: Thioflavin-T fluorescence assays were used to detect the inhibitory potency of 8-aminoquinoline-melatonin hybrids (a1-a5, b1-b5, and c1-c5) on self- and acetylcholinesterase (AChE)-induced amyloid-beta (Abeta) aggregation. The AChE and butyrylcholinesterase (BuChE) inhibitory potency within the compounds was evaluated by Ellman's assays. Methyl thiazolyl tetrazolium (MTT) assays were performed to evaluate the cytotoxicity of the compounds to C17.2 cells. MTT assay was used to detect the cell viability of HT22 cells to evaluate the antioxidant effect of the compounds. Metal chelation property was measured by ultraviolet-visible spectrophotometry. RESULTS: Compounds c3 and c5 had superior inhibitory activity against self-induced Abeta aggregation (with inhibitory rates of 41.4+/-2.1 and 25.5+/-3.2 at 10 microM, respectively) compared to the other compounds. Compounds in the carbamate group (i.e., a4, a5, b4, b5, c4, and c5) showed significant BuChE inhibitory activity and excellent selectivity over AChE. Most of the compounds exhibited low cytotoxicity in the C17.2 cells. Notably, a2, a3, b2, and b3 and series c (c1-c5) exhibited strong protective effects. Additionally, a3 and c1 specifically chelated with copper ions. CONCLUSIONS: Taking all of the promising results together, 8-aminoquinoline-melatonin hybrids can serve as lead molecules in the further development of new multi-functional anti-AD agents.
ESTHER : Chen_2022_Ann.Transl.Med_10_303
PubMedSearch : Chen_2022_Ann.Transl.Med_10_303
PubMedID: 35433950

Title : Paper-Based Distance Sensor for the Detection of Lipase via a Phase Separation-Induced Viscosity Change - Xia_2022_Anal.Chem__
Author(s) : Xia S , Yin F , Xu L , Zhao B , Wu W , Ma Y , Lin JM , Liu Y , Zhao M , Hu Q
Ref : Analytical Chemistry , : , 2022
Abstract : Human pancreatic lipase is a symbolic biomarker for the diagnosis of acute pancreatitis, which has profound significance for clinical detection and disease treatment. Herein, we first demonstrate a paper-based lipase sensor via a phase separation-induced viscosity change. Lipase catalyzes triolein to produce oleic acid and glycerol. Adding an excess of Ca(2+) produces calcium oleate. The remaining Ca(2+) binds with sodium alginate, triggering hydrogelation with an "egg-box" structure. The viscosity change of the aqueous solution induced by the phase separation process can be quantified by measuring the solution flow distance on a pH test paper. The paper-based lipase sensor has high sensitivity with a detection limit of 0.052 U/mL and also shows excellent specificity. Additionally, it is also utilized for quantitative lipase analysis in human serum samples to exhibit its potency in acute pancreatitis detection. This method overcomes the drawbacks of low sensitivity, slow response, and poor reproducibility caused by the nonuniform distribution of the highly viscous hydrogel on the sensing interface in existing approaches. In conclusion, thanks to the prominent characteristics of high portability, low cost, and easy operation, it is prospective for simple quantitative detection of lipase and has great potential for commercialization.
ESTHER : Xia_2022_Anal.Chem__
PubMedSearch : Xia_2022_Anal.Chem__
PubMedID: 36455011

Title : Genome-wide identification and functional analysis of long non-coding RNAs in Chilo suppressalis reveal their potential roles in chlorantraniliprole resistance - Huang_2022_Front.Physiol_13_1091232
Author(s) : Huang S , Jing D , Xu L , Luo G , Hu Y , Wu T , Li F , He K , Qin W , Sun Y , Liu H
Ref : Front Physiol , 13 :1091232 , 2022
Abstract : Long non-coding RNAs, referred to as lncRNAs, perform essential functions in some biological processes, including reproduction, metamorphosis, and other critical life functions. Yet, lncRNAs are poorly understood in pesticide resistance, and no reports to date have characterized which lncRNAs are associated with chlorantraniliprole resistance in Chilo suppressalis. Here, RNA-seq was performed on two strains of C. suppressalis exposed to chlorantraniliprole: one is a susceptible strain (S), and the other is a resistant strain (R). In total, 3,470 lncRNAs were identified from 40,573 merged transcripts in six libraries, including 1,879 lincRNAs, 245 intronic lncRNAs, 853 sense lncRNAs, and 493 antisense lncRNAs. Moreover, differential expression analysis revealed 297 and 335 lncRNAs upregulated in S and R strains, respectively. Differentially expressed (DE) lncRNAs are usually assumed to be involved in the chlorantraniliprole resistance in C. suppressalis. As potential targets, adjacent protein-coding genes (within <1000 kb range upstream or downstream of DE lncRNAs), especially detoxification enzyme genes (cytochrome P450s, carboxyl/cholinesterases/esterases, and ATP-binding cassette transporter), were analyzed. Furthermore, the strand-specific RT-PCR was conducted to confirm the transcript orientation of randomly selected 20 DE lincRNAs, and qRT-PCR was carried out to verify the expression status of 8 out of them. MSTRG.25315.3, MSTRG.25315.6, and MSTRG.7482.1 were upregulated in the R strain. Lastly, RNA interference and bioassay analyses indicated overexpressed lincRNA MSTRG.7482.1 was involved in chlorantraniliprole resistance. In conclusion, we represent, for the first time, the genome-wide identification of chlorantraniliprole-resistance-related lncRNAs in C. suppressalis. It elaborates the views underlying the mechanism conferring chlorantraniliprole resistance in lncRNAs.
ESTHER : Huang_2022_Front.Physiol_13_1091232
PubMedSearch : Huang_2022_Front.Physiol_13_1091232
PubMedID: 36699669

Title : Fabrication of immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoylglycerol - He_2022_Food.Chem_408_135236
Author(s) : He L , Zeng C , Wei L , Xu L , Song F , Huang J , Zhong N
Ref : Food Chem , 408 :135236 , 2022
Abstract : This study aims to fabricate immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) through acidolysis of glycerol tripalmitate (PPP). Twelve (three types) supports and five lipases were studied carefully. Among them, the immobilized Thermomyces lanuginosa lipase (TLL) samples exhibited overall better performance than that of other immobilized lipases. Particularly, organic groups functionalized SBA-15 (R-SBA-15) supported TLL (TLL@R-SBA-15) samples gave PPP conversion from 97.70 to 99.00s% and OPO content from 59.52 to 64.73s%. After optimization, PPP conversion up to 99.07s%, OPO content 73.15s% and sn-2 palmitic acid content 90.09s% were obtained with TLL@C(18)H(37)-SBA-15 as catalyst. Moreover, TLL@C(18)H(37)-SBA-15 exhibited better acidolysis performance from 50s degreesC than that from 60 to 80s degreesC, which helped inhibit acyl migration. In addition, after 5 cycles of reuse, TLL@C(18)H(37)-SBA-15 retained 81.04s% (based on OPO content) and 98.88s% (based on sn-2 palmitic acid content) of its initial activity, indicating it had an attractive prospect in future applications.
ESTHER : He_2022_Food.Chem_408_135236
PubMedSearch : He_2022_Food.Chem_408_135236
PubMedID: 36549162

Title : Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity - Huang_2022_Science_377_eabq3297
Author(s) : Huang S , Jia A , Song W , Hessler G , Meng Y , Sun Y , Xu L , Laessle H , Jirschitzka J , Ma S , Xiao Y , Yu D , Hou J , Liu R , Sun H , Liu X , Han Z , Chang J , Parker JE , Chai J
Ref : Science , 377 :eabq3297 , 2022
Abstract : Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR signaling requires helper NLRs N requirement gene 1 (NRG1) and Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1) that forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene101 (SAG101). Here, we show that TIR-containing proteins catalyze production of 2'-(5''-phosphoribosyl)-5'-adenosine mono-/di-phosphate (pRib-AMP/ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP, which allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity.
ESTHER : Huang_2022_Science_377_eabq3297
PubMedSearch : Huang_2022_Science_377_eabq3297
PubMedID: 35857645
Gene_locus related to this paper: arath-eds1 , arath-PAD4

Title : Monoacylglycerol lipase from marine Geobacillus sp. showing lysophospholipase activity and its application in efficient soybean oil degumming - Liu_2022_Food.Chem_406_134506
Author(s) : Liu X , Wang W , Zhao Z , Xu L , Yang B , Lan D , Wang Y
Ref : Food Chem , 406 :134506 , 2022
Abstract : Enzymatic degumming is an essential refining process to improve oil quality. In this study, a monoacylglycerol lipase GMGL was derived from marine Geobacillus sp., and was found that not only took monoacylglycerol (MAG) as substrate, but also had activity toward lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) and glycerolphosphatidylcholine (GPC). Binding free energy showed LPC and LPE could bind with enzyme stably as MAG. It presented great potential in the field of enzymatic degumming. The phosphorus content in crude soybean oil decreased from 680.50 to 2.01 mg/kg and the yield of oil reached to 98.80 % after treating with phospholipase A1 (Lecitase Ultra) combined with lipase GMGL. An ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was developed to identify 21 differential phospholipids between crude soybean oil and enzymatic treatment. This work might shed some light on understanding the catalytic mechanism of monoacylglycerol lipase and provide an effective strategy for enzymatic degumming.
ESTHER : Liu_2022_Food.Chem_406_134506
PubMedSearch : Liu_2022_Food.Chem_406_134506
PubMedID: 36463594

Title : Enhancing bio-catalytic performance of lipase immobilized on ionic liquids modified magnetic polydopamine - Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960
Author(s) : Suo H , Li M , Liu R , Xu L
Ref : Colloids Surf B Biointerfaces , 206 :111960 , 2021
Abstract : In this study, imidazolium-based ionic liquid with [tf(2)N](-) as the anion was successfully grafted to magnetic polydopamine nanoparticles (MPDA). The prepared materials were well characterized and used as supports for lipase immobilization. The immobilized lipase (PPL-ILs-MPDA) exhibited excellent activity and stability. The specific activity of PPL-ILs-MPDA was 2.15 and 1.49 folds higher than that of free PPL and PPL-MPDA. In addition, after 10 rounds of reuse, the residual activity of PPL-ILs-MPDA was 86.2 % higher than that of PPL-MPDA (75.4 %). Furthermore, the kinetic assay indicated that the affinity between PPL-ILs-MPDA and substrate had increased. Analysis of the secondary structure using circular dichroism was used to explain the mechanism underlying the improvement in the performance of PPL-ILs-MPDA. In addition, the immobilized lipase can be easily separated from the reaction system with a magnet. The observations regarding the development of new supports for lipase immobilization may provide new ideas regarding further studies in this field.
ESTHER : Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960
PubMedSearch : Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960
PubMedID: 34224932

Title : Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice - Tian_2021_Neurochem.Int_150_105197
Author(s) : Tian Y , Yuan X , Wang Y , Wu Q , Fang Y , Zhu Z , Song G , Xu L , Wang W , Xie M
Ref : Neurochem Int , 150 :105197 , 2021
Abstract : Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity. Soluble epoxide hydrolase (sEH) is the key enzyme in the epoxyeicosatrienoic acids (EETs) signaling. sEH inhibition has been demonstrated to have neuroprotective effects against multiple brain injuries. However, its role in the secondary injuries after ICH has not been fully elucidated. Here we tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and the secondary injuries after ICH. Adult male C57BL/6 mice were subjected to a collagenase-induced ICH model. TPPU alleviated blood-brain barrier damage, inhibited inflammatory response, increased M2 polarization of microglial cells, reduced the infiltration of peripheral neutrophils. In addition, TPPU attenuated neuronal injury and promoted functional recovery. The results suggest that sEH may represent a potential therapeutic target for the treatment of ICH.
ESTHER : Tian_2021_Neurochem.Int_150_105197
PubMedSearch : Tian_2021_Neurochem.Int_150_105197
PubMedID: 34592333

Title : Berberine Ameliorates Glucose Metabolism in Diabetic Rats through the alpha7 Nicotinic Acetylcholine Receptor-Related Cholinergic Anti-Inflammatory Pathway - Wang_2021_Planta.Med__
Author(s) : Wang D , Ren Y , Sun W , Gong J , Zou X , Dong H , Xu L , Wang K , Lu F
Ref : Planta Med , : , 2021
Abstract : Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1beta and TNF-alpha in the serum and downregulated nuclear factor kappaB expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.
ESTHER : Wang_2021_Planta.Med__
PubMedSearch : Wang_2021_Planta.Med__
PubMedID: 33682914

Title : UPLC-MS\/MS Profiling, Antioxidant, alpha-Glucosidase Inhibitory, Cholinesterase Inhibitory, and Cardiovascular Protection Potentials of Jialing 20 (Morus multicaulis Perr.) Mulberry Branch Extract - Xiang_2021_Foods_10_
Author(s) : Xiang W , Xia Z , Xu L
Ref : Foods , 10 : , 2021
Abstract : As a by-product in the sericulture industry, mulberry branches are not currently utilized effectively. Jialing 20 is an artificial triploids mulberry that widely cultivated in southwest China. In this study, the chemical composition of the Jialing 20 mulberry branch extract (MBE) was first analyzed by UPLC-MS/MS, and 42 components, including alkaloids, flavonoids, and coumarins, were obtained. Then, the antioxidant activities, hypoglycemic effect, Alzheimer's disease inhibition, and cardiovascular protection of MBE were also evaluated in vitro. The IC(50) values for the scavenging DPPH and ABTS radicals were, respectively, 31.23 +/- 0.57 microg/mL and 8.88 +/- 0.36 microg/mL (IC(50) values of positive Vc were, respectively, 4.41 +/- 0.19 microg/mL and 8.79 +/- 0.41 microg/mL). The IC(50) value for inhibiting alpha-glucosidase was 1.90 +/- 0.05 microg/mL (IC(50) value of positive acarbose was 0.03 microg/mL). The IC(50) values for inhibiting acetylcholinesterase and butyrylcholinesterase were, respectively, 179.47 +/- 0.38 microg/mL and 101.82 +/- 3.37 microg/mL (IC(50) values of positive berberine were, respectively, 1.27 +/- 0.03 microg/mL and 57.41 +/- 0.21 microg/mL). MBE (10 microg/mL and 40 microg/mL) significantly increased the survival rate of oxidized low-density lipoprotein- (ox-LDL) induced human umbilical vein endothelial cells (HUVECs) and significantly decreased the intracellular reactive oxygen species. These results suggest that the extracts of Jialing 20 mulberry branches could be used as a functional food additive.
ESTHER : Xiang_2021_Foods_10_
PubMedSearch : Xiang_2021_Foods_10_
PubMedID: 34828948

Title : Nanozyme-Participated Biosensing of Pesticides and Cholinesterases: A Critical Review - Zhu_2021_Biosensors.(Basel)_11_
Author(s) : Zhu H , Liu P , Xu L , Li X , Hu P , Liu B , Pan J , Yang F , Niu X
Ref : Biosensors (Basel) , 11 : , 2021
Abstract : To improve the output and quality of agricultural products, pesticides are globally utilized as an efficient tool to protect crops from insects. However, given that most pesticides used are difficult to decompose, they inevitably remain in agricultural products and are further enriched into food chains and ecosystems, posing great threats to human health and the environment. Thus, developing efficient methods and tools to monitor pesticide residues and related biomarkers (acetylcholinesterase and butylcholinesterase) became quite significant. With the advantages of excellent stability, tailorable catalytic performance, low cost, and easy mass production, nanomaterials with enzyme-like properties (nanozymes) are extensively utilized in fields ranging from biomedicine to environmental remediation. Especially, with the catalytic nature to offer amplified signals for highly sensitive detection, nanozymes were finding potential applications in the sensing of various analytes, including pesticides and their biomarkers. To highlight the progress in this field, here the sensing principles of pesticides and cholinesterases based on nanozyme catalysis are definitively summarized, and emerging detection methods and technologies with the participation of nanozymes are critically discussed. Importantly, typical examples are introduced to reveal the promising use of nanozymes. Also, some challenges in the field and future trends are proposed, with the hope of inspiring more efforts to advance nanozyme-involved sensors for pesticides and cholinesterases.
ESTHER : Zhu_2021_Biosensors.(Basel)_11_
PubMedSearch : Zhu_2021_Biosensors.(Basel)_11_
PubMedID: 34677338

Title : Protection studies of an excretory-secretory protein HcABHD against Haemonchus contortus infection - Lu_2021_Vet.Res_52_3
Author(s) : Lu M , Tian X , Zhang Y , Wang W , Tian AL , Aimulajiang K , Liu L , Li C , Yan R , Xu L , Song X , Li X
Ref : Vet Res , 52 :3 , 2021
Abstract : Unlike the successful immunization of native H. contortus antigens that contributed to the realization of the first commercial vaccine Barbervax, not many studies revealed the encouraging protective efficacies of recombinant H. contortus antigens in laboratory trials or under field conditions. In our preliminary study, H. contortus alpha/beta-hydrolase domain protein (HcABHD) was demonstrated to be an immunomodulatory excretory-secretory (ES) protein that interacts with goat T cells. We herein evaluated the protective capacities of two HcABHD preparations, recombinant HcABHD (rHcABHD) antigen and anti-rHcABHD IgG, against H. contortus challenge via active and passive immunization trials, respectively. Parasitological parameter, antibody responses, hematological pathology and cytokine profiling in unchallenged and challenged goats were monitored and determined throughout both trials. Subcutaneous administration of rHcABHD with Freund adjuvants elicited protective immune responses in challenged goats, diminishing cumulative fecal egg counts (FEC) and total worm burden by 54.0% and 74.2%, respectively, whereas passive immunization with anti-rHcABHD IgG conferred substantial protection to challenged goats by generating a 51.5% reduction of cumulative FEC and a 73.8% reduction of total worm burden. Additionally, comparable changes of mucosal IgA levels, circulating IgG levels, hemoglobin levels, and serum interleukin (IL)-4 and IL-17A levels were observed in rHcABHD protein/anti-rHcABHD IgG immunized goats in both trials. Taken together, the recombinant version of HcABHD might have further application under field conditions in protecting goats against H. contortus infection, and the integrated immunological pipeline of ES antigen identification, screening and characterization may provide new clues for further development of recombinant subunit vaccines to control H. contortus.
ESTHER : Lu_2021_Vet.Res_52_3
PubMedSearch : Lu_2021_Vet.Res_52_3
PubMedID: 33407892
Gene_locus related to this paper: haeco-CDJ88804

Title : New perspective on the regulation of acetylcholinesterase via the aryl hydrocarbon receptor - Xie_2021_J.Neurochem_158_1254
Author(s) : Xie HQ , Ma Y , Fu H , Xu T , Luo Y , Liu Y , Chen Y , Xu L , Xia Y , Zhao B
Ref : Journal of Neurochemistry , 158 :1254 , 2021
Abstract : Acetylcholinesterase (AChE, EC plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in-depth understanding of the effects of dioxin on AChE and the related mechanisms of action might help to shed light on the molecular bases of dioxin impacts on the nervous system. In the past decade, the effects of dioxins on AChE have been revealed in cultured cells of different origins and in rodent animal models. Unlike OP and carbamate pesticides, dioxin-induced AChE disturbance is not due to direct inhibition of enzymatic activity; instead, dioxin causes alterations of AChE expression in certain models. As a widely accepted mechanism for most dioxin effects, the aryl hydrocarbon receptor (AhR)-dependent pathway has become a research focus in studies on the mechanism of action of dioxin-induced AChE dysregulation. In this mini-review, the effects of dioxin on AChE and the diverse roles of the AhR pathway in AChE regulation are summarized. Additionally, the involvement of AhR in AChE regulation during different neurodevelopmental processes is discussed. These AhR-related findings might also provide new insight into AChE regulation triggered by diverse xenobiotics capable of interacting with AhR.
ESTHER : Xie_2021_J.Neurochem_158_1254
PubMedSearch : Xie_2021_J.Neurochem_158_1254
PubMedID: 33278027

Title : Neuroprotective effects of maize tetrapeptide-anchored gold nanoparticles in Alzheimer's disease - Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
Author(s) : Zhang J , Liu R , Zhang D , Zhang Z , Zhu J , Xu L , Guo Y
Ref : Colloids Surf B Biointerfaces , 200 :111584 , 2021
Abstract : Nanopeptide assembled from peptide-anchored nanoparticles possess an enormous research potential in the field of cellular medicine and disease treatment. The aim of this study was to explore the neuroprotective effects of maize tetrapeptide anchored gold nanoparticles against l-glutamic acid-induced PC12 cell apoptosis and a murine Alzheimer's disease model induced by aluminum chloride and d-galactose. The results revealed that the nanopeptide antioxidant inhibited intracellular ROS accumulation and promoted cell differentiation than that of maize bioactive tetrapeptide. Compared with untreated Alzheimer's disease model mice, nanopeptide administration shortened the escape latency time in a water maze test and improved the movements in the autonomic activity test. After 16 days of nanopeptide administration, the central cholinergic system function of acetylcholine and cholineacetyltransferase were enhanced, and the level of acetylcholinesterase was reduced. It also increased superoxide dismutase and glutathione peroxidase activity in sera and hypothalami. Moreover, nanopeptide treatment upregulated cerebral nuclear factor erythroid 2-related factor 2 and heme-oxygenase-1 and downregulated kelch-like ECH-associated protein 1 relative to untreated Alzheimer's disease model mice. Thus, the novel nanopeptide is expected to be used as the neuroprotective agent to prevent Alzheimer's disease.
ESTHER : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedSearch : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedID: 33508658

Title : Hydrogen-bonded lipase-hydrogel microspheres for esterification application - Qin_2021_J.Colloid.Interface.Sci_606_1229
Author(s) : Qin Z , Feng N , Li Y , Fei X , Tian J , Xu L , Wang Y
Ref : J Colloid Interface Sci , 606 :1229 , 2021
Abstract : Lipase is the most widely used enzyme in industry. Due to its unique "lid" structure, lipase can only show high activity at the oil-water interface, which means that water is needed in the catalytic esterification process. However, the traditional lipase catalytic system cannot effectively control "micro-water" in the esterification environment, resulting in the high content of free water, which hinders the esterification reaction and reduces the yield. In this paper, a promising strategy of esterification catalyzed by polyacrylamide hydrogel immobilized lipase is reported. The porous polyacrylamide hydrogel microspheres (PHM) prepared by inverse emulsion polymerization are used as carrier to adsorb lipase by hydrogen bonding interaction. These hydrogel microspheres provide a "micro-water environment" for lipase in the anhydrous reaction system, and further provide an oil-water interface for "interface activation" of lipase. The obtained lipase-porous polyacrylamide hydrogel microspheres (L-PHMs) exhibit higher temperature and pH stability compared with free lipase, and the optimum enzymatic activity reach 1350 U/g (pH 6, 40 degreesC). L-PHMs can still remain about 49% of their original activity after 20 reuses. Furthermore, L-PHMs have been successfully applied to catalyze the synthesis of conjugated linoleic acid ethyl ester. The results suggest that this immobilization method opens up a new way for the application of lipase in ester synthesis.
ESTHER : Qin_2021_J.Colloid.Interface.Sci_606_1229
PubMedSearch : Qin_2021_J.Colloid.Interface.Sci_606_1229
PubMedID: 34492461

Title : Micro\/nano-plastics cause neurobehavioral toxicity in discus fish (Symphysodon aequifasciatus): Insight from brain-gut-microbiota axis - Huang_2021_J.Hazard.Mater_421_126830
Author(s) : Huang JN , Wen B , Xu L , Ma HC , Li XX , Gao JZ , Chen ZZ
Ref : J Hazard Mater , 421 :126830 , 2021
Abstract : Numerous studies have investigated neurobehavioral toxicity of microplastics, but no studies have illustrated mechanism via brain-gut axis. Here, juvenile discus fish (Symphysodon aequifasciatus) were exposed for 96 h to microfibers (900 microm, fiber, MFs) or nanoplastics (~88 nm, bead, NPs) with three concentrations (0, 20 and 200 microg/L). Accumulation in fish gut was independent of plastics type and concentration. MFs reduced growth performance while NPs weakened swimming and predatory performance of post-exposed discus. For brain cholinesterase activity, acetylcholinesterase was activated by NPs while NPs/MFs exposure inhibited butyrylcholinesterase. Concentrations of neurotransmitters (acetylcholine, dopamine and gamma-aminobutyric acid) increased in brain but decreased in gut after NPs or MFs exposure. For gut microbiota, increased richness under MFs exposure was observed. At phylum level, Proteobacteria proportion was lower in NPs but higher in MFs. Abundance of Clostridia and Fusobacteriia (Bacillus), potentially secreting neurotransmitters, increased in NPs but decreased in MFs. Brain transcriptomics revealed seven upregulated and four downregulated genes concerning neural-activities. Pathways of neuroactive ligand-receptor interaction and serotonergic synapse were enriched in both MFs and NPs, but dopaminergic synapse pathway was enriched only in MFs. These results established a novel mechanism by which microplastics might cause behavioral toxicities via brain-gut-microbiota axis.
ESTHER : Huang_2021_J.Hazard.Mater_421_126830
PubMedSearch : Huang_2021_J.Hazard.Mater_421_126830
PubMedID: 34396975

Title : A novel sn-1,3 specific lipase from Janibacter sp. as catalysts for the high-yield synthesis of long-medium-long type structured triacylglycerols - Cui_2021_Food.Chem_366_130523
Author(s) : Cui R , Xu L , Lan D , Yang B , Wang Y
Ref : Food Chem , 366 :130523 , 2021
Abstract : Our study offers a novel sn-1,3 specific lipase MAJ1 from marine member Janibacter sp. strain HTCC2649 for preparing long-medium-long (LML) type structured triacylglycerols (TAGs). Firstly, the resin ECR1030 was selected as a suitable support for the immobilization of lipase MAJ1. An efficient synthesis of LML-type structured TAGs by the immobilized lipase MAJ1-catalyzed interesterification of methyl palmitate and tricaprylin was studied in a solvent-free system. The reaction conditions, including substrate molar ratio, temperature and enzyme loading, were optimized. Under the optimum conditions (immobilized lipase MAJ1 of 45 U/g, substrate molar ratio of 4:1, temperature of 35 degreesC, reaction time of 24 h), the structured TAGs with double long chains (DLCST) were obtained in a yield of 44.3 mol%. Secondly, multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) was employed to quantify each TAG positional isomer in DLCST. The content of 1,3-dipalmitoyl-2-capryloyl-sn-glycerol in DLCST was 97.6% determined by the MDMS-SL technology.
ESTHER : Cui_2021_Food.Chem_366_130523
PubMedSearch : Cui_2021_Food.Chem_366_130523
PubMedID: 34303206
Gene_locus related to this paper: 9mico-a3tmr7

Title : Phlorizin exerts potent effects against aging induced by D-galactose in mice and PC12 cells - Liu_2021_Food.Funct__
Author(s) : Liu Y , Guo Y , Xu L , Wang H
Ref : Food Funct , : , 2021
Abstract : Phlorizin is the main active ingredient of apple peel and has potential utilization value. Some recent studies have suggested that phlorizin may have antioxidant capacity and protect the liver. The injection of a low dose of d-galactose can cause some changes that resemble accelerated aging in mice. This study explored the protective effects of phlorizin on d-galactose-induced mice and PC12 cells. In this study, ICR mice were divided into a normal group (NOR), a d-galactose model group (d-gal) and phlorizin treatment groups (100 mg kg-1, 200 mg kg-1 and 400 mg kg-1). In addition to the NOR group, four other groups were injected with d-galactose (120 mg kg-1) for 12 weeks. The results showed that phlorizin reduced the decline of strength, coordination and spatial memory caused by aging, increased the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), increased total antioxidant capacity (T-AOC), and reduced the content of malondialdehyde (MDA). On the other hand, phlorizin increased the levels of interleukin-2 (IL-2) and acetylcholine (ACh), reduced the release of interleukin-6 (IL-6), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and decreased the activity of acetylcholinesterase (AChE) in the brain, improved the expression of antioxidant genes related to the nuclear factor E2-related factor 2 (Nrf2) pathway, and reduced the occurrence of morphological lesions in the hippocampus and liver. In addition, phlorizin improved cell viability and reduced the cytotoxicity of d-galactose-induced oxidative stress in PC12 cells. Meanwhile, the protective effect of phlorizin was abolished in Nrf2 gene knockdown PC12 cells. Furthermore, molecular docking showed that phlorizin could bind Keap1 protein, which can interact with Nrf2 protein. Therefore, these results suggest that phlorizin may delay senescence and enhance antioxidant capacity through the Nrf2 pathway.
ESTHER : Liu_2021_Food.Funct__
PubMedSearch : Liu_2021_Food.Funct__
PubMedID: 33565551

Title : Vitamins A and D fail to protect against tuberculosis-drug-induced liver injury: A post hoc analysis of a previous randomized controlled trial - Xiong_2021_Nutrition_86_111155
Author(s) : Xiong K , Wang J , Zhang B , Xu L , Hu Y , Ma A
Ref : Nutrition , 86 :111155 , 2021
Abstract : OBJECTIVES: Vitamins A and D provided protection from xenobiotic-induced liver injury in previous animal studies. We conducted a post hoc analysis of our previous randomized controlled trial to investigate the effects of vitamin A and D supplementation on tuberculosis-drug-induced liver injury. METHODS: The trial was conducted in a hospital in Qingdao, China, from October 2012 to March, 2015. The control group received only tuberculosis treatment. The vitamin A, vitamin D, and vitamins A & D groups received, respectively, additional supplementation of 2000 IU/d vitamin A, 400 IU/d vitamin D, and a combination of 2000 IU/d vitamin A and 400 IU/d vitamin D. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase were monitored throughout the treatment. Liver injury was defined as ALT or AST three times higher than the upper limit of normal, which was defined for AST, ALT, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase, respectively, as 40 U/L, 40 U/L, 150 U/L, 40 U/L, and 10 500 U/L. RESULTS: Among the 753 participants, 11% exhibited liver injury. No significant effect of vitamin A or D supplementation was observed on the incidence of liver injury or on elevated liver indices including ALT, AST, alkaline phosphatase, gamma-glutamyltransferase, and cholinesterase. The interaction between vitamin A and D supplementation was not significant. CONCLUSIONS: Vitamin A and D supplementation did not protect against tuberculosis-drug-induced liver injury. Future work should evaluate the effects of higher dosages of vitamins A and D and the effects of different genotypes for vitamin A and D metabolic enzymes or receptors.
ESTHER : Xiong_2021_Nutrition_86_111155
PubMedSearch : Xiong_2021_Nutrition_86_111155
PubMedID: 33601121

Title : An efficient and robust continuous-flow bioreactor for the enzymatic preparation of phytosterol esters based on hollow lipase microarray - Xu_2021_Food.Chem_372_131256
Author(s) : Xu L , Wang J , Huang F , Zheng M
Ref : Food Chem , 372 :131256 , 2021
Abstract : In this study, a continuous-flow bioreactor packed with well-organized lipase microarrays was developed for the sustainable synthesis of functional lipid-phytosterol esters (PEs). Hollow mesoporous silicon spheres with a suitable pore size were prepared for lipase immobilization, and the hydrophobic modification endowed the lipase with excellent catalytic activity and stability. The results showed that the condensely packed lipase microarrays offered large specific surface areas and guaranteed the thorough interaction between the lipase and substrates in the continuous-flow bioreactor. Meanwhile, the substrate could pass through the reactor at 1 mL/min with a high conversion of 93.6% due to the hollow structure of the packing spheres. Moreover, the reactors were able to produce 1564 g PEs/g catalyst in a continuous 30-day processing period, which set the highest records for PEs synthesis. This sustainable and highly-converting flow system provided a feasible path for scale-up production of PEs in the food processing area.
ESTHER : Xu_2021_Food.Chem_372_131256
PubMedSearch : Xu_2021_Food.Chem_372_131256
PubMedID: 34627092

Title : Algorithm-based coevolution network identification reveals key functional residues of the alpha\/beta hydrolase subfamilies - Wu_2020_FASEB.J_34_1983
Author(s) : Wu Z , Liu H , Xu L , Chen HF , Feng Y
Ref : FASEB Journal , 34 :1983 , 2020
Abstract : Covariant residues identified by computational algorithms have provided new insights into enzyme evolutionary routes. However, the reliability and accuracy of routine statistical coupling analysis (SCA) are unable to satisfy the needs of protein engineering because SCA depends only on sequence information. Here, we set up a new SCA algorithm, SCA.SIM, by integrating structure information and MD simulation data. The more reliable covariant residues with high-quality scores are obtained from sequence alignment weighted by residual movement for eight related subfamilies, belonging to alpha/beta hydrolase family, with Candida antarctica lipase B (CALB). The 38 predicted covariant residues are tested for function by high-throughput quantitative evaluation in combination with activity and thermostability assays of a mutant library and deep sequencing. Based on the landscapes of both activity and thermostability, most mutants play key roles in catalysis, and some mutants gain 2.4- to 6-fold increase in half-life at 50 degrees C and 9- to 12-fold improvement in catalytic efficiency. The activity of double mutants for A225F/T103A is higher than those of A225F and T103A which means that SCA.SIM method might be useful for identifying the allosteric coupling. The SCA.SIM algorithm can be used for protein coevolution and enzyme engineering research.
ESTHER : Wu_2020_FASEB.J_34_1983
PubMedSearch : Wu_2020_FASEB.J_34_1983
PubMedID: 31907985

Title : A Novel alpha\/beta Hydrolase Domain Protein Derived From Haemonchus contortus Acts at the Parasite-Host Interface - Lu_2020_Front.Immunol_11_1388
Author(s) : Lu M , Tian X , Tian AL , Li C , Yan R , Xu L , Song X , Li X
Ref : Front Immunol , 11 :1388 , 2020
Abstract : The alpha/beta-hydrolase domain (ABHD) proteins belonging to alpha/beta-hydrolase (ABH) superfamily are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signaling, growth and development. In our preliminary work, we identified a novel ABHD protein derived from Haemonchus contortus excretory-secretory (ES) proteins (HcESPs) that interacted with host T cells. Here, we demonstrated that H. contortus ABHD (HcABHD) protein, expressed in all life-cycle stages of H. contortus, is a mammalian ABHD17 homolog with immunodiagnostic utility and lipase activity. Given its catalytic activities and immunomodulatory potentials, we further investigated the functional diversity of HcABHD as an individual ES protein in parasite-host interactions. HcABHD protein may serve as depalmitoylase or thioesterase to suppress cell viability, inhibit cell proliferation, induce intrinsic and extrinsic T cell apoptosis, and cause cell cycle arrested at G1 phase. Moreover, recombinant HcABHD stimuli exerted critical controls on T cell cytokine production profiles, predominantly by inhibiting the secretions of interleukin (IL)-4, interferon-gamma (IFN-gama) and transforming growth factor-beta (TGF-beta) 1, and promoting IL-10 production. As the immunomodulator acting at the parasite-host interface, HcABHD protein may have potential applications for the vaccine development of therapeutic intervention. Together, these findings may help illuminate the molecular and particularly immunomodulatory aspects of ES proteins and contribute to an enhanced understanding of parasite immune evasion in H. contortus-host biology.
ESTHER : Lu_2020_Front.Immunol_11_1388
PubMedSearch : Lu_2020_Front.Immunol_11_1388
PubMedID: 32695121
Gene_locus related to this paper: haeco-CDJ88804

Title : FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling - Chen_2020_Biol.Open_9_bio048462
Author(s) : Chen Y , Liu P , Shen D , Liu H , Xu L , Wang J , Sun H , Wu H
Ref : Biol Open , 9 : , 2020
Abstract : FAM172A, as a newly discovered gene, is little known in cancer development, especially in pancreatic cancer (PC). We investigated the potential role and molecular mechanism of FAM172A in epithelial to mesenchymal transition (EMT) in both human clinical samples and PC cells. FAM172A was downregulated in human PC tissues compared with that in non-cancerous pancreas cells by immunohistochemistry and qRT-PCR. FAM172A expression was negatively associated with tumor size (P=0.015), T stage (P=0.006), lymph node metastasis (P=0.028) and the worst prognosis of PC patients (P=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, P=0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (P=0.014). FAM172A silencing induced EMT in both AsPC-1 and BxPC-3 cells, including inducing the increase of Vimentin, MMP9 and pERK and the decrease of E-cad and beta-catenin expression, stimulating EMT-like cell morphology and enhancing cell invasion and migration in PC cells. However, MEK1 inhibitor PD98059 reversed FAM172A silencing-enhanced EMT in PC cells. We conclude that FAM172A inhibits EMT of PC cells via ERK-MAPK signaling.
ESTHER : Chen_2020_Biol.Open_9_bio048462
PubMedSearch : Chen_2020_Biol.Open_9_bio048462
PubMedID: 31988090
Gene_locus related to this paper: human-f172a

Title : Gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice: Neurobehavioral effects on female offspring - Sha_2020_Sci.Total.Environ_752_141784
Author(s) : Sha R , Chen Y , Wang Y , Luo Y , Liu Y , Ma Y , Li Y , Xu L , Xie HQ , Zhao B
Ref : Sci Total Environ , 752 :141784 , 2020
Abstract : Emerging evidence suggests that perinatal dioxin exposure affects neurodevelopment and impairs multiple brain functions, including cognitive, language, learning and emotion, in the offspring. However, the impacts of gestational and lactational exposure to dioxin on behavior and related molecular events are still not fully understood. In this study, female C57BL/6J mice were orally administered three doses of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (0.1 or 10 mug/kg body weight (bw)) during the pregnancy and lactation periods. The locomotion, exploration and anxiety-related behaviors were examined by an open field test of the young adult female offspring at postnatal day 68. We found that the maternal TCDD exposure, particularly at a low dose, increased movement ability, novelty-exploration and certain anxiety-related behaviors in the offspring. Such hyperactivity-like behaviors were accompanied by the upregulation of certain genes associated with cholinergic neurotransmission or synaptogenesis in the offspring brain. In accordance with the potential enhancement of cholinergic neurotransmission due to the gene upregulations, the enzymatic activity of acetylcholinesterase was decreased, which might lead to excess acetylcholine and consequent hyper-excitation at the synapses. Thus, we found that gestational and lactational TCDD exposure at low dose caused hyperactivity-like behaviors in young adult female offspring and speculated the enhancement of cholinergic neurotransmission and synaptogenesis as potential molecular events underlying the neurobehavioral effects.
ESTHER : Sha_2020_Sci.Total.Environ_752_141784
PubMedSearch : Sha_2020_Sci.Total.Environ_752_141784
PubMedID: 32889265

Title : Transcriptome analysis of Spodoptera litura reveals the molecular mechanism to pyrethroids resistance - Xu_2020_Pestic.Biochem.Physiol_169_104649
Author(s) : Xu L , Mei Y , Liu R , Chen X , Li D , Wang C
Ref : Pestic Biochem Physiol , 169 :104649 , 2020
Abstract : Spodoptera litura is a destructive agricultural pest and has evolved resistance to multiple insecticides, especially pyrethroids. At present, the resistance mechanism to pyrethroids remains unclear. Four field-collected populations, namely CZ, LF, NJ and JD, were identified to have high resistance to pyrethroids comparing to pyrethroid-susceptible population (GX), with resistant ratio ranging from 11.5- to 9123.5-fold. To characterize pyrethroid resistance mechanism, the transcriptomes between two pyrethroid-resistant (LF and NJ) and a pyrethroid-susceptible (GX) populations were compared by RNA-sequencing. Results showed that multiple differentially expressed genes were enriched in metabolism-related GO terms and KEGG pathways. 35 up-regulated metabolism-related unigenes were selected to verify by qRT-PCR and 15 unigenes, including 4 cytochrome P450s (P450s), 5 glutathione S-transferase (GSTs), 1 UDP-glycosyltransferase (UGT), 4 carboxylesterases (COEs) and 1 and ATP-binding cassette transporters (ABC), were all up-regulated in the four pyrethroid-resistant populations. The expression levels of CYP3 and GST3, which were annotated as CYP6A13 and GSTE1, respectively, showed positive correlation with their pyrethroid resistance levels among the four pyrethroid-resistant populations. While the expression levels of CYP5, CYP12, COE4 and ABC5 showed good correlation with their pyrethroid resistance levels in at least three populations. UGT5 had the highest expression level among the tested UGT genes in the four pyrethroid-resistant populations. RNAi mediated silencing of CYP6 increased the cumulative mortality treated by beta cypermethrin and cyhalothrin significantly, while silencing of GST3 increased the cumulative mortality treated by fenvalerate significantly. CYP3, CYP5, CYP6, CYP12, GST3, COE4, UGT5 and ABC5 play important roles in pyrethroid resistance among the four pyrethroid-resistant populations. Our work provides a valuable clue for further study of pyrethroid resistance mechanisms in S. litura.
ESTHER : Xu_2020_Pestic.Biochem.Physiol_169_104649
PubMedSearch : Xu_2020_Pestic.Biochem.Physiol_169_104649
PubMedID: 32828367

Title : Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties - Zhang_2020_Nat.Commun_11_3719
Author(s) : Zhang W , Zhang Y , Qiu H , Guo Y , Wan H , Zhang X , Scossa F , Alseekh S , Zhang Q , Wang P , Xu L , Schmidt MH , Jia X , Li D , Zhu A , Guo F , Chen W , Ni D , Usadel B , Fernie AR , Wen W
Ref : Nat Commun , 11 :3719 , 2020
Abstract : Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds.
ESTHER : Zhang_2020_Nat.Commun_11_3719
PubMedSearch : Zhang_2020_Nat.Commun_11_3719
PubMedID: 32709943
Gene_locus related to this paper: camsi-a0a7j7g2i2 , camsi-a0a7j7hil4

Title : 2,3,7,8-Tetrachlorodibenzo-p-dioxin and up-regulation of neurofilament expression in neuronal cells: Evaluation of AhR and MAPK pathways - Chen_2020_Environ.Int_134_105193
Author(s) : Chen Y , Xie HQ , Sha R , Xu T , Zhang S , Fu H , Xia Y , Liu YY , Xu L , Zhao B
Ref : Environ Int , 134 :105193 , 2020
Abstract : Dioxin exposure is reported to affect nervous system development and increase the risk of neurodegenerative diseases. Generally, dioxin exerts its neurotoxicity via aryl hydrocarbon receptor (AhR). Neurofilament (NF) light (NFL) protein is a biomarker for both neuronal differentiation and neurodegeneration and its expression is controlled by the mitogen-activated protein kinase (MAPK) pathway. However, the effects of dioxin on NFL expression and involved mechanisms are incompletely understood. We aimed to investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on NFL expression and elucidate the underlining signaling pathways and their potential crosstalk, specifically between MAPK and AhR pathway. We employed primary cultured rat cortical neurons to evaluate the effect of TCDD exposure on NFL expression. We also used nerve growth factor (NGF)-treated PC12 cells with specific inhibitors to investigate the involvement of and potential crosstalk between the MAPK pathway and the AhR pathway in mediating the effects of TCDD on NFL expression. After TCDD exposure, NFL mRNA and protein levels were upregulated in cultured neurons. NFL protein was preferentially found in the cell body compared with neurites of the cultured neurons. In PC12 cells, TCDD enhanced both NGF-induced NFL expression and phosphorylation of ERK1/2 and p38. The addition of MAPK-pathway inhibitors (PD98059 and SB230580) partially blocked the TCDD-induced NFL upregulation. CH223191, an AhR antagonist, reversed the upregulation of NFL and phosphorylation of ERK1/2 and p38 induced by TCDD. This study demonstrated TCDD-induced upregulation of NFL in cultured neurons, with protein retained in the cell body. TCDD action was dependent on activation of AhR and MAPK, while crosstalk was found between these two signaling pathways.
ESTHER : Chen_2020_Environ.Int_134_105193
PubMedSearch : Chen_2020_Environ.Int_134_105193
PubMedID: 31775093

Title : Lipidomic and Ultrastructural Characterization of the Cell Envelope of Staphylococcus aureus Grown in the Presence of Human Serum - Hines_2020_mSphere_5_
Author(s) : Hines KM , Alvarado G , Chen X , Gatto C , Pokorny A , Alonzo F, 3rd , Wilkinson BJ , Xu L
Ref : mSphere , 5 : , 2020
Abstract : Staphylococcus aureus can incorporate exogenous straight-chain unsaturated and saturated fatty acids (SCUFAs and SCFAs, respectively) to replace some of the normally biosynthesized branched-chain fatty acids and SCFAs. In this study, the impact of human serum on the S. aureus lipidome and cell envelope structure was comprehensively characterized. When S. aureus was grown in the presence of 20% human serum, typical human serum lipids, such as cholesterol, sphingomyelin, phosphatidylethanolamines, and phosphatidylcholines, were present in the total lipid extracts. Mass spectrometry showed that SCUFAs were incorporated into all major S. aureus lipid classes, i.e., phosphatidylglycerols, lysyl-phosphatidylglycerols, cardiolipins, and diglucosyldiacylglycerols. Heat-killed S. aureus retained fewer serum lipids and failed to incorporate SCUFAs, suggesting that association and incorporation of serum lipids with S. aureus require a living or nondenatured cell. Cytoplasmic membranes isolated from lysostaphin-produced protoplasts of serum-grown cells retained serum lipids, but washing cells with Triton X-100 removed most of them. Furthermore, electron microscopy studies showed that serum-grown cells had thicker cell envelopes and associated material on the surface, which was partially removed by Triton X-100 washing. To investigate which serum lipids were preferentially hydrolyzed by S. aureus lipases for incorporation, we incubated individual serum lipid classes with S. aureus and found that cholesteryl esters (CEs) and triglycerides (TGs) are the major donors of the incorporated fatty acids. Further experiments using purified Geh lipase confirmed that CEs and TGs were the substrates of this enzyme. Thus, growth in the presence of serum altered the nature of the cell surface with implications for interactions with the host.IMPORTANCE Comprehensive lipidomics of S. aureus grown in the presence of human serum suggests that human serum lipids can associate with the cell envelope without being truly integrated into the lipid membrane. However, fatty acids derived from human serum lipids, including unsaturated fatty acids, can be incorporated into lipid classes that can be biosynthesized by S. aureus itself. Cholesteryl esters and triglycerides are found to be the major source of incorporated fatty acids upon hydrolysis by lipases. These findings have significant implications for the nature of the S. aureus cell surface when grown in vivo Changes in phospholipid and glycolipid abundances and fatty acid composition could affect membrane biophysics and function and the activity of membrane-targeting antimicrobials. Finally, the association of serum lipids with the cell envelope has implications for the physicochemical nature of the cell surface and its interaction with host defense systems.
ESTHER : Hines_2020_mSphere_5_
PubMedSearch : Hines_2020_mSphere_5_
PubMedID: 32554713

Title : Identification of a Bacillus amyloliquefaciens H6 Thioesterase Involved in Zearalenone Detoxification by Transcriptomic Analysis - Xu_2020_J.Agric.Food.Chem_68_10071
Author(s) : Xu L , Sun X , Wan X , Li H , Yan F , Han R , Li Z , Tian Y , Liu X , Kang X , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 68 :10071 , 2020
Abstract : Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin produced by Fusarium graminearum, induces hyperestrogenic responses in mammals and can cause reproductive disorders in farm animals. In this study, a transcriptome analysis of Bacillus amyloliquefaciens H6, which was previously identified as a ZEA-degrading bacterium, was conducted with high-throughput sequencing technology, and the differentially expressed genes were subjected to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Among the 16 upregulated genes, BAMF_RS30125 was predicted to be the key gene responsible for ZEA degradation. The protein encoded by BAMF_RS30125 was then expressed in Escherichia coli, and this recombinant protein (named ZTE138) significantly reduced the ZEA content, as determined by the enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), and decreased the proliferating activity of ZEA in MCF-7 cells. What is more, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) results showed that the relative molecular mass and the structure of ZEA also changed. Sequence alignment of the ZTE138 protein showed that it is a protease that belongs to the YBGC/FADM family of coenzyme A thioesterases, and thus, the protein can presumably cleave the ZEA lactone bond and break down its macrolide ring.
ESTHER : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedSearch : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedID: 32815728

Title : DL0410 attenuates oxidative stress and neuroinflammation via BDNF\/TrkB\/ERK\/CREB and Nrf2\/HO-1 activation - Zhang_2020_Int.Immunopharmacol_86_106729
Author(s) : Zhang B , Zhao J , Wang Z , Xu L , Liu A , Du G
Ref : Int Immunopharmacol , 86 :106729 , 2020
Abstract : Oxidative stress and neuroinflammation have been deeply associated with Alzheimer's disease. DL0410 is a novel acetylcholinesterase inhibitor with potential anti-oxidative effects in AD-related animal models, while the specific mechanism has not been fully clarified. In this study, DL0410 was predicted to be related to the modification of cell apoptosis, oxidation-reduction process, inflammatory response and ERK1/ERK2 cascade by in silico target fishing and GO enrichment analysis. Then the possible protective effects of DL0410 were evaluated by hydrogen peroxide (H2O2)-induced oxidative stress model and lipopolysaccharides (LPS)-induced neuroinflammation model H2O2 decreased the viability of SH-SY5Y cells, induced malondialdehyde (MDA) accumulation, mitochondrial membrane potential (Deltapsim) loss and cell apoptosis, which could be reversed by DL0410 dose-dependently, indicating that DL0410 protected SH-SY5Y cells against H2O2-mediated oxidative stress. Western blot analysis showed that DL0410 increased the H2O2-triggered down-regulated TrkB, ERK and CREB phosphorylation and the expression of BDNF. In addition, TrkB inhibitor ANA-12, ERK inhibitor SCH772984 and CREB inhibitor 666-15 eliminated the inhibition of DL0410 on MDA accumulation and Deltapsim loss. Furthermore, DL0410 attenuates inflammatory responses and ROS production in LPS-treated BV2 cells, which is responsible for Nrf2 and HO-1 up-regulation. The present study demonstrates that DL0410 is a potential activator of the BDNF/TrkB/ERK/CREB and Nrf2/HO-1 pathway and may be a potential candidate for regulating oxidative stress and neuroinflammatory response in the brain. Together, the results showed that DL0410 is a promising drug candidate for treating AD and possibly other nervous system diseases associated with oxidative stress and neuroinflammation.
ESTHER : Zhang_2020_Int.Immunopharmacol_86_106729
PubMedSearch : Zhang_2020_Int.Immunopharmacol_86_106729
PubMedID: 32645628

Title : A De Novo Designed Esterase with p-Nitrophenyl Acetate Hydrolysis Activity - Li_2020_Molecules_25_4658
Author(s) : Li G , Xu L , Zhang H , Liu J , Yan J , Yan Y
Ref : Molecules , 25 :4658 , 2020
Abstract : Esterases are a large family of enzymes with wide applications in the industry. However, all esterases originated from natural sources, limiting their use in harsh environments or newly- emerged reactions. In this study, we designed a new esterase to develop a new protocol to satisfy the needs for better biocatalysts. The ideal spatial conformation of the serine catalytic triad and the oxygen anion hole at the substrate-binding site was constructed by quantum mechanical calculation. The catalytic triad and oxygen anion holes were then embedded in the protein scaffold using the new enzyme protocol in Rosetta 3. The design results were subsequently evaluated, and optimized designs were used for expression and purification. The designed esterase had significant lytic activities towards p-nitrophenyl acetate, which was confirmed by point mutations. Thus, this study developed a new protocol to obtain novel enzymes that may be useful in unforgiving environments or novel reactions.
ESTHER : Li_2020_Molecules_25_4658
PubMedSearch : Li_2020_Molecules_25_4658
PubMedID: 33066055
Gene_locus related to this paper: aspor-cutas , fusso-cutas , hevbr-hnl

Title : Synthesis of functional ionic liquid modified magnetic chitosan nanoparticles for porcine pancreatic lipase immobilization - Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
Author(s) : Suo H , Gao Z , Xu L , Xu C , Yu D , Xiang X , Huang H , Hu Y
Ref : Mater Sci Eng C Mater Biol Appl , 96 :356 , 2019
Abstract : We developed magnetic chitosan nanoparticles (CSFe3O4) with mean diameter of 15-20nm. Subsequently, these inorganic-organic composite nanoparticles were modified using an imidazole-based functional ionic liquid (IL). The prepared support (ILCSFe3O4), which was used to immobilize porcine pancreatic lipase (PPL), was characterized using Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and X-ray diffraction (XRD). Circular dichroism (CD) was used to analyze the secondary structure of immobilized PPL. The immobilized PPL (PPLILCSFe3O4) exhibited 1.93-fold higher specific activity than PPLCS-Fe3O4 when triacetin was used as the substrate, and showed 95mg/g of lipase immobilization capacity and 382% of activity recovery. The residual activity of PPLILCSFe3O4 was above 60% of the initial activity after incubation at 50 degrees C for 6h, as was higher than that of PPLCSFe3O4 which showed 40% of the initial activity. In addition, PPLILCSFe3O4 retained 84.6% of the initial activity after 10cycles, whereas PPLCSFe3O4 retained only 75.5% activity. Furthermore, the kinetic parameters, apparent Km and Vmax of PPLILCSFe3O4 were 2.51mg/mL and 1.395U/mg respectively, these results indicated that the immobilized PPL had better affinity towards the substrate, especially when the nanoparticles were modified by functional IL. Besides, the magnetic chitosan nanoparticles loaded with PPL were easily recovered. A novel, efficient, and practical method for enzyme immobilization was developed.
ESTHER : Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
PubMedSearch : Suo_2019_Mater.Sci.Eng.C.Mater.Biol.Appl_96_356
PubMedID: 30606543

Title : Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on acetylcholinesterase during myogenic differentiation of contractile rat primary skeletal muscle cells - Luo_2019_Chem.Biol.Interact_13ChEPon_308_164
Author(s) : Luo Y , Xie HQ , Chen Y , Xia Y , Sha R , Liu YY , Ma Y , Xu T , Xu L , Tsim KWK , Zhao B
Ref : Chemico-Biological Interactions , 308 :164 , 2019
Abstract : Emerging data indicate that prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could interfere with myogenic differentiation in vivo. Acetylcholinesterase (EC3.1.1.7; AChE), an enzyme critical for cholinergic neurotransmission, is abundantly expressed in neurons and mature myotubes, and we recently found that muscle AChE expression was suppressed in parallel with the inhibition of myogenic differentiation upon TCDD treatment in mouse C2C12cells. This TCDD-induced suppression of muscle AChE was proposed to involve an aryl hydrocarbon receptor (AhR)-independent mechanism, but the precise underlying mechanism remains unclear. Considering the widely recognized role of muscular activity in AChE expression and its potential crosstalk with the AhR signaling pathway, we sought to investigate the effect of TCDD on muscle AChE expression in the presence of muscular activity. Therefore, we employed a highly contractile rat primary skeletal muscle culture system in which AChE activity and the expression of genes related to it (AChE T subunit and collagen Q (ColQ)) were increased during the myogenic differentiation process. Although TCDD treatment successfully induced the expression of genes regulated by AhR activation, the treatment exerted no notable effects on myogenic differentiation. Moreover, muscle AChE enzymatic activity and mRNA level remained unchanged following TCDD treatment, and only ColQ mRNA expression was slightly increased after 4-day treatment with TCDD (10(-10)M). The compensatory role of muscle-contraction-related signaling pathways in this newly identified unresponsiveness of muscle AChE to TCDD warrants further investigation.
ESTHER : Luo_2019_Chem.Biol.Interact_13ChEPon_308_164
PubMedSearch : Luo_2019_Chem.Biol.Interact_13ChEPon_308_164
PubMedID: 31100272

Title : Polydatin suppresses VEGF-induced angiogenesis through binding with VEGF and inhibiting its receptor signaling - Hu_2019_FASEB.J_33_532
Author(s) : Hu WH , Wang HY , Kong XP , Xiong QP , Poon KK , Xu L , Duan R , Chan GK , Dong TTX , Tsim KWK
Ref : FASEB Journal , 33 :532 , 2019
Abstract : Polydatin, also called piceid, is a stilbenoid glucoside of a resveratrol derivative. It derives mainly from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. Although the role of P. cuspidatum root in angiogenesis has been reported, the active chemical or chemicals responsible for such function is not known. Here, polydatin was proposed to bind VEGF, which therefore altered the functions of VEGF in angiogenesis. Several lines of evidence supported the pharmaceutical effects of polydatin in VEGF-induced angiogenesis. In human umbilical vein endothelial cells, polydatin inhibited VEGF-stimulated cell proliferation, cell migration, and tube formation. Moreover, polydatin showed suppressive effects on the subintestinal vessel formation in zebrafish embryos. In signaling cascades, polydatin application attenuated VEGF-induced phosphorylations of VEGF receptor 2 and JNK. Moreover, the VEGF-induced phosphorylations of Akt, eNOS, and Erk were significantly decreased in the presence of polydatin. In parallel, the formation of reactive oxygen species, triggered by VEGF, was markedly decreased under polydatin application. Thus, our results supported the angiogenic roles of polydatin, as well as its signaling mechanism in blocking VEGF-mediated responses. The current study provides support for the possible development of polydatin as a potential therapeutic agent for treatment and prevention of angiogenesis-related diseases.-Hu, W.-H., Wang, H.-Y., Kong, X.-P., Xiong, Q.-P., Poon, K. K.-M., Xu, L., Duan, R., Chan, G. K.-L., Dong, T. T.-X., Tsim, K. W.-K. Polydatin suppresses VEGF-induced angiogenesis through binding with VEGF and inhibiting its receptor signaling.
ESTHER : Hu_2019_FASEB.J_33_532
PubMedSearch : Hu_2019_FASEB.J_33_532
PubMedID: 29989844

Title : Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations - Zhou_2019_Molecules_24_
Author(s) : Zhou Y , Lu X , Yang H , Chen Y , Wang F , Li J , Tang Z , Cheng X , Yang Y , Xu L , Xia Q
Ref : Molecules , 24 : , 2019
Abstract : As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 muM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.
ESTHER : Zhou_2019_Molecules_24_
PubMedSearch : Zhou_2019_Molecules_24_
PubMedID: 31757047

Title : Effects of astrocyte conditioned medium on neuronal AChE expression upon 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure - Sha_2019_Chem.Biol.Interact_13ChEPon_309_108686
Author(s) : Sha R , Chen Y , Luo Y , Liu YY , Xu L , Xie HQ , Zhao B
Ref : Chemico-Biological Interactions , 309 :108686 , 2019
Abstract : Acetylcholinesterase (EC3.1.1.7; AChE) is a key enzyme in the cholinergic system. Emerging evidence has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a typical persistent organic pollutant, suppressed neuronal AChE activity via dysregulation of different biosynthesis processes in human and rat neuronal cells. In the nervous system, astrocytes protect neurons from environmental pollutants. As a known target cell of TCDD, the astrocyte might be involved in TCDD effects on neuronal AChE. Therefore, in the present study, we found astrocyte-derived conditioned medium (ACM) could induce AChE activity preferentially in mature neurons in the absence of TCDD. The enzymatic activity of AChE was generally decreased in cultured cortical neurons upon direct treatment with TCDD (0.003-0.01nM). This trend of changes in AChE activity was not significantly altered in immature neurons exposed to ACM produced in the presence of TCDD (TACM group), but reversed in mature neurons. Compared with effects of treatment with ACM plus TCDD (ACMT), a significant differential effect on AChE activity was found in the TACM group in response to TCDD treatment specifically in immature neurons, suggesting the presence of a TCDD-specific active component derived from the astrocyte. Inconsistent alterations in expression and enzymatic activities of the AChE T subunit (AChET) and the proline-rich membrane anchor (PRiMA) were found, suggesting that a mechanism of action beyond the transcriptional level might be involved. These data indicate that the astrocyte might play a protective role in TCDD-induced alterations of neuronal AChE in certain stages of differentiation.
ESTHER : Sha_2019_Chem.Biol.Interact_13ChEPon_309_108686
PubMedSearch : Sha_2019_Chem.Biol.Interact_13ChEPon_309_108686
PubMedID: 31152735

Title : Enhanced catalytic performance of lipase covalently bonded on ionic liquids modified magnetic alginate composites - Suo_2019_J.Colloid.Interface.Sci_553_494
Author(s) : Suo H , Xu L , Xu C , Qiu X , Huang H , Hu Y
Ref : J Colloid Interface Sci , 553 :494 , 2019
Abstract : We prepared ionic liquids (ILs) modified magnetic alginate nanoparticles and used these as supports for lipase immobilization. The novel supports were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance ((1)HNMR), vibrating sample magnetometry (VSM), thermogravimetry (TG), transmission electron microscopy (TEM) and water contact angle (WCA) measurements. The immobilized lipase (PPL-IL-MSA) exhibited high activity, 2.1-fold higher than that compared to free lipase and 1.59-fold higher compared to immobilized lipase without IL (PPL-MSA). In addition, the pH and temperature application range of PPL-IL-MSA were both found to be broader than that of free lipase and PPL-MSA. The thermal stability, denaturation stability, and reusing stability of PPL-IL-MSA were also higher than those of other samples. After 10 times of reuse, the residual activity of PPL-IL-MSA was 89.7% higher than that of PPL-MSA (84.4%). Furthermore, the kinetic constant Km of PPL-IL-MSA was 13.7mg/mL lower than that of free lipase (21.2mg/mL) and PPL-MSA (18.4mg/mL). Circular dichroism (CD) was used to study the secondary structure of enzymes in order to explain the mechanism of the performance improvement of PPL-IL-MSA. This work involving the development of a new supports for enzyme immobilization may serve as a reference for further studies in this field.
ESTHER : Suo_2019_J.Colloid.Interface.Sci_553_494
PubMedSearch : Suo_2019_J.Colloid.Interface.Sci_553_494
PubMedID: 31229868

Title : Colletotryptins A-F, new dimeric tryptophol derivatives from the endophytic fungus Colletotrichum sp. SC1355 - Shao_2019_Fitoterapia__104465
Author(s) : Shao L , Wu P , Xu L , Xue J , Li H , Wei X
Ref : Fitoterapia , :104465 , 2019
Abstract : Seven new dimeric tryptophol-related alkaloids (1-4, 5a, 5b, and 6) were isolated from solid cultures of the endophytic fungus Colletotrichum sp. SC1355. The structures and absolute configurations of these compounds were determined by NMR spectroscopic analyses in combination with quantum chemical calculations of NMR (GIAO) shifts and ECD spectra. This is the first report of fungus-derived tryptophol dimers. In addition, the isolated compounds were evaluated for acetylcholinesterase (AchE) inhibitory activity.
ESTHER : Shao_2019_Fitoterapia__104465
PubMedSearch : Shao_2019_Fitoterapia__104465
PubMedID: 31870947

Title : Determination of Genetic Effects of LIPK and LIPJ Genes on Milk Fatty Acids in Dairy Cattle - Shi_2019_Genes.(Basel)_10_
Author(s) : Shi L , Han B , Liu L , Lv X , Ma Z , Li C , Xu L , Li Y , Zhao F , Yang Y , Sun D
Ref : Genes (Basel) , 10 : , 2019
Abstract : In our previous genome-wide association study (GWAS) on milk fatty acids (FAs) in Chinese Holstein, we discovered 83 genome-wide significant single nucleotide polymorphisms (SNPs) associated with milk FAs. Two of them were close to lipase family member K (LIPK) and lipase family member J (LIPJ), respectively. Hence, this study is a follow-up to verify whether the LIPK and LIPJ have significant genetic effects on milk FAs in dairy cattle. By re-sequencing the entire exons, and 3 kb of 5' and 3' flanking regions, two and seven SNPs were identified in LIPK and LIPJ, respectively, including a novel SNP, ss158213049726. With the Haploview 4.1 software, we found that five of the SNPs in LIPJ formed a haplotype block (D' = 0.96 ~ 1.00). Single-locus association analyses revealed that each SNP in LIPK and LIPJ was significantly associated with at least one milk FA (p = < 1.00x10(-4) ~ 4.88x10(-2)), and the haplotype-based association analyses showed significant genetic effects on nine milk FAs (p = < 1.00x10(-4) ~ 3.98x10(-2)). Out of these SNPs, the missense mutation in LIPK gene, rs42774527, could change the protein secondary structure and function predicted by SOPMA, SIFT, and PROVEAN softwares. With the Genomatix software, we predicted that two SNPs, rs110322221 in LIPK and rs211373799 in LIPJ, altered the transcription factors binding sites (TFBSs), indicating their potential regulation on promoter activity of the genes. Furthermore, we found that both LIPK and LIPJ had relatively high expressions in the mammary gland. In conclusion, our research is the first to demonstrate that LIPK and LIPJ genes have significant associations with milk FAs, and the identified SNPs might be served as genetic markers to optimize breeding programs for milk FAs in dairy cattle. This research deserves in-depth verification.
ESTHER : Shi_2019_Genes.(Basel)_10_
PubMedSearch : Shi_2019_Genes.(Basel)_10_
PubMedID: 30696079
Gene_locus related to this paper: bovin-e1bnt1 , bovin-f1msa3 , human-LIPJ , human-LIPK

Title : Enhancing the Thermostability of Rhizomucor miehei Lipase with a Limited Screening Library by Rational-Design Point Mutations and Disulfide Bonds - Li_2018_Appl.Environ.Microbiol_84_
Author(s) : Li G , Fang X , Su F , Chen Y , Xu L , Yan Y
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Rhizomucor miehei lipase (RML), as a kind of eukaryotic protein catalyst, plays an important role in the food, organic chemical, and biofuel industries. However, RML retains its catalytic activity below 50 degrees C, which limits its industrial applications at higher temperatures. Soluble expression of this eukaryotic protein in Escherichia coli not only helps to screen for thermostable mutants quickly but also provides the opportunity to develop rapid and effective ways to enhance the thermal stability of eukaryotic proteins. Therefore, in this study, RML was engineered using multiple computational design methods, followed by filtration via conservation analysis and functional region assessment. We successfully obtained a limited screening library (only 36 candidates) to validate thermostable single point mutants, among which 24 of the candidates showed higher thermostability and 13 point mutations resulted in an apparent melting temperature ([Formula: see text]) of at least 1 degrees C higher. Furthermore, both of the two disulfide bonds predicted from four rational-design algorithms were further introduced and found to stabilize RML. The most stable mutant, with T18K/T22I/E230I/S56C-N63C/V189C-D238C mutations, exhibited a 14.3 degrees C-higher [Formula: see text] and a 12.5-fold increase in half-life at 70 degrees C. The catalytic efficiency of the engineered lipase was 39% higher than that of the wild type. The results demonstrate that rationally designed point mutations and disulfide bonds can effectively reduce the number of screened clones to enhance the thermostability of RML.IMPORTANCER. miehei lipase, whose structure is well established, can be widely applied in diverse chemical processes. Soluble expression of R. miehei lipase in E. coli provides an opportunity to explore efficient methods for enhancing eukaryotic protein thermostability. This study highlights a strategy that combines computational algorithms to predict single point mutations and disulfide bonds in RML without losing catalytic activity. Through this strategy, an RML variant with greatly enhanced thermostability was obtained. This study provides a competitive alternative for wild-type RML in practical applications and further a rapid and effective strategy for thermostability engineering.
ESTHER : Li_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Li_2018_Appl.Environ.Microbiol_84_
PubMedID: 29101200
Gene_locus related to this paper: rhimi-lipas

Title : Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients - Xu_2018_Mediators.Inflamm_2018_5201652
Author(s) : Xu L , Zhu B , Huang Y , Yang Z , Sun J , Xu Y , Zheng J , Kinloch S , Yin MT , Weng H , Wu N
Ref : Mediators Inflamm , 2018 :5201652 , 2018
Abstract : Background: Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. Methods: BChE levels (in U/L) were measured in 505 patients; <4500 was defined as "low" and >/=4500 as "normal." Associations between BChE level and CD4 count, WHO stage, body mass index (BMI), C-reactive protein (CRP) level, and duration of hospitalization were assessed. Kaplan-Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. Results: A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P < 0.001). Eighty-four patients (16.6%) died in the first year of follow-up. One-year survival was 64.5 +/- 4.5% for patients with low BChE and 87.6 +/- 1.8% for those with normal BChE (log-rank, P < 0.001). After adjustment for sex, age, BMI, WHO stage, and CD4 count, as well as serum levels of hemoglobin, sodium, and albumin, the hazard ratio was 1.8 (95% confidence interval, 1.0-3.2) for patients with a low BChE compared with those with a normal BChE (P = 0.035). Conclusion: BChE level is associated with HIV/AIDS severity and is an independent risk factor for increased mortality in AIDS patients.
ESTHER : Xu_2018_Mediators.Inflamm_2018_5201652
PubMedSearch : Xu_2018_Mediators.Inflamm_2018_5201652
PubMedID: 29736152

Title : Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B - Wu_2018_Liver.Int_38_1930
Author(s) : Wu D , Rao Q , Chen W , Ji F , Xie Z , Huang K , Chen E , Zhao Y , Ouyang X , Zhang S , Jiang Z , Zhang L , Xu L , Gao H , Li L
Ref : Liver Int , 38 :1930 , 2018
Abstract : BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis.
ESTHER : Wu_2018_Liver.Int_38_1930
PubMedSearch : Wu_2018_Liver.Int_38_1930
PubMedID: 29654711

Title : Benzo(a)pyrene inhibits the accumulation and toxicity of cadmium in subcellular fractions of Eisenia fetida - Zhang_2018_Chemosphere_219_740
Author(s) : Zhang L , Zhou L , Han L , Zhao C , Norton JM , Li H , Hu F , Xu L
Ref : Chemosphere , 219 :740 , 2018
Abstract : Cadmium (Cd) and benzo [a]pyrene (BaP) often co-occur in the environment, and the critical body residue of organisms is used as an indicator of the toxic effects of contaminants. However, little is known about their distributions and toxicities when pollution of Cd and BaP are combined. Semi-static solution culture experiment was used to study the impacts of BaP on the subcellular distribution of the toxic metal Cd in the earthworm Eisenia fetida. We explored the mechanisms by which this organism responds to combined exposure to these pollutants by measuring the protein content of each of three subcellular fractions, as well as acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities. The subcellular partitioning of Cd was heterogeneous and Cd mainly accumulated in the cytosolic fraction (Fraction C), which was previously reported to be involved in metal immobilization. In Fraction C, Cd accumulation was correlated with the external concentration to which the earthworm had been exposed; however, in the presence of BaP, Cd accumulation was inhibited and plateaued at high external Cd concentrations. A principal component analysis revealed that this decreased Cd accumulation might be caused by increases in GST activity, which likely increased the excretion of Cd. BaP was also found to stimulate protein biosynthesis and upregulate AChE and GST activities in the debris fraction (Fraction E), indicating other potential detoxification mechanisms in this fraction. Granule fraction (Fraction D) had a lower protein content, AChE and GST activities than the other subcellular fractions, supporting previous findings that Fraction D is largely inert.
ESTHER : Zhang_2018_Chemosphere_219_740
PubMedSearch : Zhang_2018_Chemosphere_219_740
PubMedID: 30557731

Title : 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces alterations in myogenic differentiation of C2C12 cells - Xie_2018_Environ.Pollut_235_965
Author(s) : Xie HQ , Xia Y , Xu T , Chen Y , Fu H , Li Y , Luo Y , Xu L , Tsim KWK , Zhao B
Ref : Environ Pollut , 235 :965 , 2018
Abstract : Dioxin-induced toxicities that affect the development of the motor system have been proposed since many years. However, cellular evidence and the molecular basis for the effects are limited. In this study, a cultured mouse myoblast cell line, C2C12, was utilized to examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on myogenic differentiation and expression of acetylcholinesterase (AChE), a neuromuscular transmission-related gene. The results showed that TCDD exposure at 10(-10)M repressed the myotube formation of C2C12cells by disturbing the fusion process and suppressing the expression of myosin heavy chain, a myobute structural protein, and not by induction of cytotoxicity. Furthermore, TCDD dose dependently suppressed the transcriptional expression and enzymatic activity of AChE during the myogenic differentiation, particularly in the middle stage. However, the administration of aryl hydrocarbon receptor antagonists, CH223191 and alpha-naphthoflavone, did not completely reverse the TCDD-induced downregulation of muscular AChE during myogenic differentiation. These findings suggest that low dose exposure to dioxin may result in disturbances of muscle differentiation and neuromuscular transmission.
ESTHER : Xie_2018_Environ.Pollut_235_965
PubMedSearch : Xie_2018_Environ.Pollut_235_965
PubMedID: 29751400

Title : Genistein: A Dual Inhibitor of Both Amyloid beta and Human Islet Amylin Peptides - Ren_2018_ACS.Chem.Neurosci_9_1215
Author(s) : Ren B , Liu Y , Zhang Y , Cai Y , Gong X , Chang Y , Xu L , Zheng J
Ref : ACS Chem Neurosci , 9 :1215 , 2018
Abstract : Abnormal misfolding and aggregation of amyloid peptides into amyloid fibrils are common and critical pathological events in many neurodegenerative diseases. Most inhibitors or drugs have been developed to prevent amyloid aggregation of a specific peptide, showing sequence-dependent inhibition mechanisms. It is more challenging to develop or discover inhibitors capable of preventing the aggregation of two or more different amyloid peptides. Genistein, a major phytoestrogen in soybean, has been widely used as an anti-inflammation and cerebrovascular drug due to its antioxidation and antiacetylcholinesterase effects. Herein, we examine the inhibitory effects of genistein on the aggregation of amyloid-beta (Abeta, associated with Alzheimer's disease) and human islet amylin (hIAPP, associated with type 2 diabetes) and Abeta- and hIAPP-induced neurotoxicity using a combination of experimental and computational approaches. Collective experimental results from thioflavin T (ThT), atomic force microscopy (AFM), and circular dichroism (CD) demonstrate that genistein shows strong inhibition ability to prevent the conformational transition of both Abeta and hIAPP monomers to beta-sheet structures, thus reducing final amyloid fibrillization from Abeta and hIAPP monomer aggregation by 40-63%. Further 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and large unilamellar vesicle (LUV) assays show that genistein helps to increase cell viability, decrease cell apoptosis, and reduce cell membrane leakage, where the cell protection effect of genistein is likely correlated with its reduced membrane leakage. Comparative molecular dynamics (MD) simulations reveal that genistein prefers to bind the beta-sheet groove, a common structural motif of amyloid fibrils, of both Abeta and hIAPP oligomers to interfere with their self-aggregation. This work for the first time demonstrates genistein as a dual inhibitor of Abeta and hIAPP aggregation. Further structural optimization and refinement of genistein may generate a series of effective sequence-independent inhibitors against the aggregation and toxicity of different amyloid peptides.
ESTHER : Ren_2018_ACS.Chem.Neurosci_9_1215
PubMedSearch : Ren_2018_ACS.Chem.Neurosci_9_1215
PubMedID: 29432676

Title : High expression of NDRG3 associates with unfavorable overall survival in non-small cell lung cancer - Luo_2018_Cancer.Biomark_21_461
Author(s) : Luo X , Hou N , Chen X , Xu Z , Xu J , Wang L , Yang S , Liu S , Xu L , Chen Y , Xiong L , Wang J , Fan W
Ref : Cancer Biomark , 21 :461 , 2018
Abstract : BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p= 0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis.
ESTHER : Luo_2018_Cancer.Biomark_21_461
PubMedSearch : Luo_2018_Cancer.Biomark_21_461
PubMedID: 29171988

Title : Dioxin induces expression of hsa-miR-146b-5p in human neuroblastoma cells - Xu_2018_J.Environ.Sci.(China)_63_260
Author(s) : Xu T , Xie HQ , Li Y , Xia Y , Sha R , Wang L , Chen Y , Xu L , Zhao B
Ref : J Environ Sci (China) , 63 :260 , 2018
Abstract : Dioxin can cause a series of neural toxicological effects. MicroRNAs (miRs) play important roles in regulating nervous system function and mediating cellular responses to environmental pollutants, such as dioxin. Hsa-miR-146b-5p appears to be involved in neurodegenerative diseases and brain tumors. However, little is known about effects of dioxin on the expression of hsa-miR-146b-5p. We found that the hsa-miR-146b-5p expression and its promoter activity were significantly increased in dioxin treated SK-N-SH cells, a human-derived neuroblastoma cell line. Potential roles of hsa-miR-146b-5p in mediating neural toxicological effects of dioxin may be due to the regulation of certain target genes. We further confirmed that hsa-miR-146b-5p significantly suppressed acetylcholinesterase (AChE) activity and targeted the 3'-untranslated region of the AChE T subunit, which has been down-regulated in dioxin treated SK-N-SH cells. Functional bioinformatic analysis showed that the known and predicted target genes of hsa-miR-146b-5p were involved in some brain functions or cyto-toxicities related to known dioxin effects, including synapse transmission, in which AChE may serve as a responsive gene for mediating the effect.
ESTHER : Xu_2018_J.Environ.Sci.(China)_63_260
PubMedSearch : Xu_2018_J.Environ.Sci.(China)_63_260
PubMedID: 29406108

Title : Protein-mimicking nanowire-inspired electro-catalytic biosensor for probing acetylcholinesterase activity and its inhibitors - Zhang_2018_Talanta_183_258
Author(s) : Zhang Q , Hu Y , Wu D , Ma S , Wang J , Rao J , Xu L , Xu H , Shao H , Guo Z , Wang S
Ref : Talanta , 183 :258 , 2018
Abstract : A highly sensitive electrochemical biosensor based on the synthetized L-Cysteine-Ag(I) coordination polymer (L-Cys-Ag(I) CP), which looks like a protein-mimicking nanowire, was constructed to detect acetylcholinesterase (AChE) activity and screen its inhibitors. This sensing strategy involves the reaction of acetylcholine chloride (ACh) with acetylcholinesterase (AChE) to form choline that is in turn catalytically oxidized by choline oxidase (ChOx) to produce hydrogen peroxide (H2O2), thus L-Cys-Ag(I) CP possesses the electro-catalytic property to H2O2 reduction. Herein, the protein-mimicking nanowire-based platform was capable of investigating successive of H2O2 effectively by amperometric i-t (current-time) response, and was further applied for the turn-on electrochemical detection of AChE activity. The proposed sensor is highly sensitive (limit of detection is 0.0006 U/L) and is feasible for screening inhibitors of AChE. The model for AChE inhibition was further established and two traditional AChE inhibitors (donepezil and tacrine) were employed to verify the feasibility of the system. The IC50 of donepezil and tacrine were estimated to be 1.4nM and 3.5nM, respectively. The developed protocol provides a new and promising platform for probing AChE activity and screening its inhibitors with low cost, high sensitivity and selectivity.
ESTHER : Zhang_2018_Talanta_183_258
PubMedSearch : Zhang_2018_Talanta_183_258
PubMedID: 29567174

Title : Muscarinic cholinergic signaling and overactive bladder-like symptoms associated with invasive bladder cancer - Wei_2018_Oncol.Lett_16_775
Author(s) : Wei W , Wang M , Li Y , Meng Q , Tang Y , Lu H , Yu W , Cheng Q , Xu L , Jian S , Wu Y , Yi X , Xie K
Ref : Oncol Lett , 16 :775 , 2018
Abstract : The objective of the present study was to explore the association between muscarinic cholinergic signaling and urothelial bladder tumors. Possible associations among overactive bladder (OAB) symptoms and bladder tumors were retrospectively investigated using a multicenter Chinese database with prospectively collected data since 2010. Firstly, it was demonstrated that OAB symptoms, such as urgency, were more severe in patients with invasive bladder cancer and were associated with a reduced prognosis. Following this, muscarinic cholinergic receptor 3 (M3R) expression in urothelium was determined to be lower in invasive cancer tissue than in adjacent non-cancerous tissue, yet M3R upregulation was associated with a reduced progression free survival (PFS) time. Additionally, it was also demonstrated that muscarinic cholinergic receptor 2 (M2R) was upregulated in the sub-urothelium, and this was also associated with a reduced PFS time. Furthermore, it was determined that cholinesterase and acetylcholinesterase were lower in invasive cancer than in non-invasive cancer. In conclusion, the results indicated that M3R expression was downregulated in invasive bladder cancer, which may have a role as a protective anti-oncogene, in contrast to its oncogenic role in numerous other cancer types. Therefore, muscarinic cholinergic signaling may be a novel therapeutic target for treating bladder cancer.
ESTHER : Wei_2018_Oncol.Lett_16_775
PubMedSearch : Wei_2018_Oncol.Lett_16_775
PubMedID: 29963145

Title : Acetylcholinesterase Is a Potential Biomarker for a Broad Spectrum of Organic Environmental Pollutants - Fu_2018_Environ.Sci.Technol_52_8065
Author(s) : Fu H , Xia Y , Chen Y , Xu T , Xu L , Guo Z , Xu H , Xie HQ , Zhao B
Ref : Environ Sci Technol , 52 :8065 , 2018
Abstract : Acetylcholinesterase (AChE, EC is a classical biomarker for monitoring contamination and intoxication of organophosphate (OP) and carbamate pesticides. In addition to these classical environmental AChE inhibitors, other organic toxic substances have been found to alter AChE activity in various species. These emerging organic AChE disruptors include certain persistent organic pollutants (POPs), polycyclic aromatic hydrocarbons (PAHs), and wildly used chemicals, most of which have received considerable public health concern in recent years. It is necessary to re-evaluate the environmental significances of AChE in terms of these toxic substances. Therefore, the present review is aiming to summarize correlations of AChE activity of certain organisms with the level of the contaminants in particular habitats, disruptions of AChE activity upon treatment with the emerging disruptors in vivo and in vitro, and action mechanisms underlying the effects on AChE. Over 40 chemicals belonging to six main categories were reviewed, including 12 POPs listed in the Stockholm Convention. AChE activity in certain organisms has been found to be well correlated with the contamination level of certain persistent pesticides and PAHs in particular habitats. Moreover, it has been documented that most of the listed toxic chemicals could inhibit AChE activity in diverse species ranging from invertebrates to mammals. Besides directly inactivating AChE, the mechanisms in terms of interference with the biosynthesis have been recognized for some emerging AChE disruptors, particularly for dioxins. The collected evidence suggests that AChE could serve as a potential biomarker for a diverse spectrum of organic environmental pollutants.
ESTHER : Fu_2018_Environ.Sci.Technol_52_8065
PubMedSearch : Fu_2018_Environ.Sci.Technol_52_8065
PubMedID: 29995397

Title : Multi-Protection of DL0410 in Ameliorating Cognitive Defects in D-Galactose Induced Aging Mice - Lian_2017_Front.Aging.Neurosci_9_409
Author(s) : Lian W , Jia H , Xu L , Zhou W , Kang , Liu A , Du G
Ref : Front Aging Neurosci , 9 :409 , 2017
Abstract : D-galactose has been reported to accelerate senescence in rodents, accompanied by a decline in learning and memory. We used a model of D-galactose-induced amnesia for the efficacy evaluation and pharmacologic studies of active compounds against Alzheimer's disease (AD). DL0410 is a potent inhibitor against acetylcholinesterase (AChE) and, in the present study, the effect of DL0410 was evaluated in this model. We found that DL0410 could significantly improve the learning and memory of D-galactose induced aging mice in a series of behavioral tests: novel-object recognition test, nest-building test, Morris water maze test and step-through test. Pharmacologic studies were conducted from several aspects: the cholinergic system, mitochondrial respiration, oxidative stress, neuroinflammation, apoptosis and synaptic loss. The acetylcholine level and AChE activity were not altered by D-galactose but were slightly affected by DL0410 in the brain. DL0410 could significantly improve decreased mitochondrial respiration in the NADH chain and FADH2 chain, and protect mitochondrial ultrastructure. DL0410 reduced the accumulation of advanced glycation end products (AGEs) and malondialdehyde (MDA) and increase the total antioxidant capability of the brain via an increase in activity of catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD). RAGE expression was inhibited by DL0410, followed by the decreased activation of astrocytes and microglia. Subsequent phosphorylation of NF-kappaB was also reversed by DL0410, with lower expression of cyclooxygenase-2 (COX2) and iNOS. With respect to apoptosis, the activation of caspase 3 and cleavage of PARP were downregulated significantly by DL0410, after the inhibition of phosphorylation of JNK induced by inflammation and oxidative stress. Synaptic protection by DL0410 was also demonstrated. These data suggest that mitochondrial protection has a primary role in the ameliorating effect of DL0410 on the impaired learning and memory, oxidative stress, inflammation, apoptosis and synaptic loss induced by D-galactose. DL0410 is a promising candidate for the treatment of aging-related AD, and this study lays an important foundation for its further research and development.
ESTHER : Lian_2017_Front.Aging.Neurosci_9_409
PubMedSearch : Lian_2017_Front.Aging.Neurosci_9_409
PubMedID: 29276489

Title : Arabidopsis thaliana EPOXIDE HYDROLASE1 (AtEH1) is a cytosolic epoxide hydrolase involved in the synthesis of poly-hydroxylated cutin monomers - Pineau_2017_New.Phytol_215_173
Author(s) : Pineau E , Xu L , Renault H , Trolet A , Navrot N , Ullmann P , Legeret B , Verdier G , Beisson F , Pinot F
Ref : New Phytol , 215 :173 , 2017
Abstract : Epoxide hydrolases (EHs) are present in all living organisms. They have been extensively characterized in mammals; however, their biological functions in plants have not been demonstrated. Based on in silico analysis, we identified AtEH1 (At3g05600), a putative Arabidopsis thaliana epoxide hydrolase possibly involved in cutin monomer synthesis. We expressed AtEH1 in yeast and studied its localization in vivo. We also analyzed the composition of cutin from A. thaliana lines in which this gene was knocked out. Incubation of recombinant AtEH1 with epoxy fatty acids confirmed its capacity to hydrolyze epoxides of C18 fatty acids into vicinal diols. Transfection of Nicotiana benthamiana leaves with constructs expressing AtEH1 fused to enhanced green fluorescent protein (EGFP) indicated that AtEH1 is localized in the cytosol. Analysis of cutin monomers in loss-of-function Ateh1-1 and Ateh1-2 mutants showed an accumulation of 18-hydroxy-9,10-epoxyoctadecenoic acid and a concomitant decrease in corresponding vicinal diols in leaf and seed cutin. Compared with wild-type seeds, Ateh1 seeds showed delayed germination under osmotic stress conditions and increased seed coat permeability to tetrazolium red. This work reports a physiological role for a plant EH and identifies AtEH1 as a new member of the complex machinery involved in cutin synthesis.
ESTHER : Pineau_2017_New.Phytol_215_173
PubMedSearch : Pineau_2017_New.Phytol_215_173
PubMedID: 28497532
Gene_locus related to this paper: arath-At2g26740 , arath-At2g26750 , arath-dl4016c.1 , arath-At3g05600 , arath-At3g51000 , arath-T14P8.15

Title : Structural insight into catalytic mechanism of PET hydrolase - Han_2017_Nat.Commun_8_2106
Author(s) : Han X , Liu W , Huang JW , Ma J , Zheng Y , Ko TP , Xu L , Cheng YS , Chen CC , Guo RT
Ref : Nat Commun , 8 :2106 , 2017
Abstract : PET hydrolase (PETase), which hydrolyzes polyethylene terephthalate (PET) into soluble building blocks, provides an attractive avenue for the bioconversion of plastics. Here we present the structures of a novel PETase from the PET-consuming microbe Ideonella sakaiensis in complex with substrate and product analogs. Through structural analyses, mutagenesis, and activity measurements, a substrate-binding mode is proposed, and several features critical for catalysis are elucidated.
ESTHER : Han_2017_Nat.Commun_8_2106
PubMedSearch : Han_2017_Nat.Commun_8_2106
PubMedID: 29235460
Gene_locus related to this paper: idesa-peth

Title : Pancreatic lipase-related protein 2 is essential for egg hatching in the brown planthopper, Nilaparvata lugens - Xu_2017_Insect.Mol.Biol_26_277
Author(s) : Xu L , Huang HJ , Zhou X , Liu CW , Bao YY
Ref : Insect Molecular Biology , 26 :277 , 2017
Abstract : In this study, we identified a pancreatic lipase-related protein 2 (PLRP2) gene through searching the transcriptome data of the brown planthopper, Nilaparvata lugens, a monophagous rice pest. PLRP2 mRNAs were first isolated in the human pancreas and play an important role in hydrolysis of galactolipids from the diet. Although homologous PLRP2 genes have been identified in many insect species, their physiological functions remain unknown. The present study for the first time reports the functional role of PLRP2 in an insect species. Differing from mammal PLRP2s, N. lugens PLRP2 was highly expressed in developing oocytes of the ovaries of female adults and little expressed in laid eggs. Suppression of N. lugens PLRP2 expression using RNA interference significantly inhibited egg hatching in rice seedlings, implying that N. lugens PLRP2 was important for oocyte maturation and development. This novel finding will improve our understanding of the reproductive strategies in insects and provides a potential target for future management of crop pests.
ESTHER : Xu_2017_Insect.Mol.Biol_26_277
PubMedSearch : Xu_2017_Insect.Mol.Biol_26_277
PubMedID: 28032922
Gene_locus related to this paper: nillu-a0a1s5vg83

Title : Granularity and Laxative Effect of Ultrafine Powder of Dendrobium officinale - Luo_2017_J.Med.Food_20_180
Author(s) : Luo D , Qu C , Zhang Z , Xie J , Xu L , Yang H , Li C , Lin G , Wang H , Su Z
Ref : J Med Food , 20 :180 , 2017
Abstract : Constipation is a common disorder that is a significant source of morbidity among people around the world ranging from 2% to 28%. Dendrobium officinale Kimura et Migo is a traditional herbal medicine and health food used for tonicity of the stomach and promotion of body fluid production in China. This study aimed to prepare the ultrafine powder of Dendrobium officinale (UDO) and investigate its laxative effect and potential mechanism in mice with diphenoxylate-induced constipation. Results indicated that the mean diameter (d50) of UDO obtained by ball milling was 6.56 mum. UDO (62.5, 125, and 250 mg/kg, p.o.) could significantly enhance the gastrointestinal transit ratio and promote fecal output. Moreover, UDO treatment resulted in significant increases in the serum levels of acetylcholinesterase (AChE), gastrin (Gas), motilin (MTL), and substance P (SP), and obviously decreased serum contents of somatostatin (SS). Taken together, UDO, which can be easily obtained through milling to a satisfactory particle size, exhibited obvious laxative effect in diphenoxylate-induced constipated mice, and the mechanism might be associated with elevated levels of AChE, Gas, MTL, SP, and reduced production of SS. UDO has the potential for further development into an alternative effective diet therapy for constipation.
ESTHER : Luo_2017_J.Med.Food_20_180
PubMedSearch : Luo_2017_J.Med.Food_20_180
PubMedID: 28146409

Title : Transcriptional responses in the hepatopancreas of Eriocheir sinensis exposed to deltamethrin - Yang_2017_PLoS.One_12_e0184581
Author(s) : Yang Z , Zhang Y , Jiang Y , Zhu F , Zeng L , Wang Y , Lei X , Yao Y , Hou Y , Xu L , Xiong C , Yang X , Hu K
Ref : PLoS ONE , 12 :e0184581 , 2017
Abstract : Deltamethrin is an important pesticide widely used against ectoparasites. Deltamethrin contamination has resulted in a threat to the healthy breeding of the Chinese mitten crab, Eriocheir sinensis. In this study, we investigated transcriptional responses in the hepatopancreas of E. sinensis exposed to deltamethrin. We obtained 99,087,448, 89,086,478, and 100,117,958 raw sequence reads from control 1, control 2, and control 3 groups, and 92,094,972, 92,883,894, and 92,500,828 raw sequence reads from test 1, test 2, and test 3 groups, respectively. After filtering and quality checking of the raw sequence reads, our analysis yielded 79,228,354, 72,336,470, 81,859,826, 77,649,400, 77,194,276, and 75,697,016 clean reads with a mean length of 150 bp from the control and test groups. After deltamethrin treatment, a total of 160 and 167 genes were significantly upregulated and downregulated, respectively. Gene ontology terms "biological process," "cellular component," and "molecular function" were enriched with respect to cell killing, cellular process, other organism part, cell part, binding, and catalytic. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes showed that the metabolic pathways were significantly enriched. We found that the CYP450 enzyme system, carboxylesterase, glutathione-S-transferase, and material (including carbohydrate, lipid, protein, and other substances) metabolism played important roles in the metabolism of deltamethrin in the hepatopancreas of E. sinensis. This study revealed differentially expressed genes related to insecticide metabolism and detoxification in E. sinensis for the first time and will help in understanding the toxicity and molecular metabolic mechanisms of deltamethrin in E. sinensis.
ESTHER : Yang_2017_PLoS.One_12_e0184581
PubMedSearch : Yang_2017_PLoS.One_12_e0184581
PubMedID: 28910412

Title : Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non-small cell lung cancer (NSCLC) - Tang_2017_Int.J.Cancer_140_1620
Author(s) : Tang Z , Li J , Shen Q , Feng J , Liu H , Wang W , Xu L , Shi G , Ye X , Ge M , Zhou X , Ni S
Ref : International Journal of Cancer , 140 :1620 , 2017
Abstract : Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra-enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non-small-cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial-mesenchymal transition (EMT). The epithelial markers E-cadherin and MUC1 were significantly increased, while mesenchymal markers vimentin and S100A4 were markedly decreased in DPP9 knockdown cells. The downregulation of DPP9 in the NSCLC cells induced the expression of apoptosis-associated proteins both in vitro and in vivo. We investigated the protein expression levels of DPP9 by tissue microarray immunohistochemical assay (TMA-IHC) (n = 217). Further we found mRNA expression levels of DPP9 in 30 pairs of clinical NSCLC tissues were significantly lower than in the adjacent non-cancerous tissues. Survival analysis showed that the overexpression of DPP9 was a significant independent factor for poor 5-year overall survival in patients with NSCLC (p = 0.003). Taken together, DPP9 expression correlates with poor overall survival in NSCLC.
ESTHER : Tang_2017_Int.J.Cancer_140_1620
PubMedSearch : Tang_2017_Int.J.Cancer_140_1620
PubMedID: 27943262

Title : Soluble epoxide hydrolase inhibition Promotes White Matter Integrity and Long-Term Functional Recovery after chronic hypoperfusion in mice - Chen_2017_Sci.Rep_7_7758
Author(s) : Chen Y , Tian H , Yao E , Tian Y , Zhang H , Xu L , Yu Z , Fang Y , Wang W , Du P , Xie M
Ref : Sci Rep , 7 :7758 , 2017
Abstract : Chronic cerebral hypoperfusion induced cerebrovascular white matter lesions (WMLs) are closely associated with cognitive impairment and other neurological deficits. The mechanism of demyelination in response to hypoperfusion has not yet been fully clarified. Soluble epoxide hydrolase (sEH) is an endogenous key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids. Inhibition of sEH has been suggested to represent a prototype "combination therapy" targeting multiple mechanisms of stroke injury with a single agent. However, its role in the pathological process after WMLs has not been clarified. The present study was to investigate the role of a potent sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on multiple elements in white matter of mice brain after chronic hypoperfusion. Adult male C57BL/6 mice were subjected to bilateral carotid artery stenosis (BCAS) to induce WMLs. Administration of TPPU significantly inhibited microglia activation and inflammatory response, increased M2 polarization of microglial cells, enhanced oligodendrogenesis and differentiation of oligodendrocytes, promoted white matter integrity and remyelination following chronic hypoperfusion. Moreover, these cellular changes were translated into a remarkable functional restoration. The results suggest that sEH inhibition could exert multi-target protective effects and alleviate cognitive impairment after chronic hypoperfusion induced WMLs in mice.
ESTHER : Chen_2017_Sci.Rep_7_7758
PubMedSearch : Chen_2017_Sci.Rep_7_7758
PubMedID: 28798352

Title : DL0410 Ameliorates Memory and Cognitive Impairments Induced by Scopolamine via Increasing Cholinergic Neurotransmission in Mice - Lian_2017_Molecules_22_
Author(s) : Lian W , Fang J , Xu L , Zhou W , Kang , Xiong W , Jia H , Liu AL , Du GH
Ref : Molecules , 22 : , 2017
Abstract : Deficiency of the cholinergic system is thought to play a vital role in cognitive impairment of dementia. DL0410 was discovered as a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinestease (BuChE), with potent efficiency in in-vitro experiments, but its in vivo effect on the cholinergic model has not been evaluated, and its action mechanism has also not been illustrated. In the present study, the capability of DL0410 in ameliorating the amnesia induced by scopolamine was investigated, and its effect on the cholinergic system in the hippocampus and its binding mode in the active site of AChE was also explored. Mice were administrated DL0410 (3 mg/kg, 10 mg/kg, and 30 mg/kg), and mice treated with donepezil were used as a positive control. The Morris water maze, escape learning task, and passive avoidance task were used as behavioral tests. The test results indicated that DL0410 could significantly improve the learning and memory impairments induced by scopolamine, with 10 mg/kg performing best. Further, DL0410 inhibited the AChE activity and increased acetylcholine (ACh) levels in a dose-dependent manner, and interacted with the active site of AChE in a similar manner as donepezil. However, no difference in the activity of BuChE was found in this study. All of the evidence indicated that its AChE inhibition is an important mechanism in the anti-amnesia effect. In conclusion, DL0410 could be an effective therapeutic drug for the treatment of dementia, especially Alzheimer's disease.
ESTHER : Lian_2017_Molecules_22_
PubMedSearch : Lian_2017_Molecules_22_
PubMedID: 28272324

Title : ADCOMS: a composite clinical outcome for prodromal Alzheimer's disease trials - Wang_2016_J.Neurol.Neurosurg.Psychiatry_87_993
Author(s) : Wang J , Logovinsky V , Hendrix SB , Stanworth SH , Perdomo C , Xu L , Dhadda S , Do I , Rabe M , Luthman J , Cummings J , Satlin A
Ref : Journal of Neurology Neurosurg Psychiatry , 87 :993 , 2016
Abstract : BACKGROUND: Development of new therapies for Alzheimer's disease (AD) is increasingly focused on more mildly affected populations, and requires new assessment and outcome strategies. Patients in early stages of AD have mild cognitive decline and no, or limited, functional impairment. To respond to these assessment challenges, we developed a measurement approach based on established scale items that exhibited change in previous amnestic Mild Cognitive Impairment (aMCI) trials.
METHODS: Partial least squares regression with a longitudinal clinical decline model identified items from commonly used clinical scales with the highest combined sensitivity to change over time in aMCI and weighted these items according to their relative contribution to detecting clinical progression in patients' early stages of AD. The resultant AD Composite Score (ADCOMS) was assessed for its ability to detect treatment effect in aMCI/prodromal AD (pAD) clinical trial populations.
RESULTS: ADCOMS consists of 4 Alzheimer's Disease Assessment Scale-cognitive subscale items, 2 Mini-Mental State Examination items, and all 6 Clinical Dementia Rating-Sum of Boxes items. ADCOMS demonstrated improved sensitivity to clinical decline over individual scales in pAD, aMCI and in mild AD dementia. ADCOMS also detected treatment effects associated with the use of cholinesterase inhibitors in these populations. Improved sensitivity predicts smaller sample size requirements when ADCOMS is used in early AD trials.
CONCLUSIONS: ADCOMS is proposed as new standard outcome for pAD and mild AD dementia trials, and is progressing in a CAMD-sponsored qualification process for use in registration trials of pAD.
ESTHER : Wang_2016_J.Neurol.Neurosurg.Psychiatry_87_993
PubMedSearch : Wang_2016_J.Neurol.Neurosurg.Psychiatry_87_993
PubMedID: 27010616

Title : De novo transcriptome analysis in radish (Raphanus sativus L.) and identification of critical genes involved in bolting and flowering - Nie_2016_BMC.Genomics_17_389
Author(s) : Nie S , Li C , Xu L , Wang Y , Huang D , Muleke EM , Sun X , Xie Y , Liu L
Ref : BMC Genomics , 17 :389 , 2016
Abstract : BACKGROUND: The appropriate timing of bolting and flowering is pivotal for reproductive success in Brassicaceae crops including radish (Raphanus sativus L.). Although several flowering regulatory pathways had been described in some plant species, no study on genetic networks of bolting and flowering regulation was performed in radish. In this study, to generate dataset of radish unigene sequences for large-scale gene discovery and functional pathway identification, a cDNA library from mixed radish leaves at different developmental stages was subjected to high-throughput RNA sequencing (RNA-seq). RESULTS: A total of 54.64 million clean reads and 111,167 contigs representing 53,642 unigenes were obtained from the radish leaf transcriptome. Among these, 50,385 unigenes were successfully annotated by BLAST searching against the public protein databases. Functional classification and annotation indicated that 42,903 and 15,382 unique sequences were assigned to 55 GO terms and 25 COG categories, respectively. KEGG pathway analysis revealed that 25,973 unigenes were classified into 128 functional pathways, among which 24 candidate genes related to plant circadian rhythm were identified. Moreover, 142 potential bolting and flowering-related genes involved in various flowering pathways were identified. In addition, seven critical bolting and flowering-related genes were isolated and profiled by T-A cloning and RT-qPCR analysis. Finally, a schematic network model of bolting and flowering regulation and pathways was put forward in radish. CONCLUSIONS: This study is the first report on systematic identification of bolting and flowering-related genes based on transcriptome sequencing and assembly in radish. These results could provide a foundation for further investigating bolting and flowering regulatory networks in radish, and facilitate dissecting molecular genetic mechanisms underlying bolting and flowering in Brassicaceae vegetable crops.
ESTHER : Nie_2016_BMC.Genomics_17_389
PubMedSearch : Nie_2016_BMC.Genomics_17_389
PubMedID: 27216755
Gene_locus related to this paper: rapsa-a0a6j0lzs2

Title : 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppress AChE activity in NGF treated PC12 cells - XuL_2016_Chem.Biol.Interact_259_282
Author(s) : Xu L , Chen Y , Xie HQ , Xu T , Fu H , Zhang S , Tsim KWK , Bi CWC , Zhao B
Ref : Chemico-Biological Interactions , 259 :282 , 2016
Abstract : PC12 is a well studied cell model for neuronal differentiation. AChE is also considered as a marker for neuronal differentiation. In this study, we detected the change of AChE activity during the NGF induced differentiation of PC 12 cells, and targeted on the ratio of the activity of AChE on the cell surface, and found that NGF mainly increased the intracellular AChE activity. Dioxin is a kind of persistent organic pollutants which have extreme impact on human health and widely distributed all over the world. Recently, AChE was reported as a target of the toxicity of dioxin. Here we investigated the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on AChE activity in the PC12 cells, and found that at the later stage of differentiation, TCDD could decrease the AChE activity. This down regulation might not related to transcriptional regulation.
ESTHER : XuL_2016_Chem.Biol.Interact_259_282
PubMedSearch : XuL_2016_Chem.Biol.Interact_259_282
PubMedID: 27502150

Title : A novel eurythermic and thermostale lipase LipM from Pseudomonas moraviensis M9 and its application in the partial hydrolysis of algal oil - Yang_2015_BMC.Biotechnol_15_94
Author(s) : Yang W , Cao H , Xu L , Zhang H , Yan Y
Ref : BMC Biotechnol , 15 :94 , 2015
Abstract : BACKGROUND: Lipases are regularly used in biotechnology to catalyse the hydrolysis of triglycerides and the synthesis of esters. Microbial lipases in particular have been widely used in a variety of industrial applications. However, the current commercial microbial lipases cannot meet industrial demand due to rapid inactivation under harsh conditions. Therefore, in order to identify more stable enzymes, we isolated novel eurythermic and thermostable lipase(s) from Pseudomonas moraviensis M9. METHODS: Cloning of lipM was based on Touchdown PCR and genome walking, and then recombinant LipM was purified by guanidine hydrochloride and the nickel-nitrilotriacetic acid resins affinity chromatography. Finally, the hydrolysis of algal oil by LipM was analyzed by gas chromatograph-mass spectrometer, thin layer chromatography and gas chromatograph. RESULTS: The lipM gene was first cloned from Pseudomonas moraviensis M9 via Touchdown PCR and genome walking. Sequence analysis reveals that LipM is a member of subfamily I.3 of lipases, and the predicted amino acid sequences of LipM has 82 % identity to lipase LipT from Pseudomonas mandelii JR-1, and 54 % identity to lipase PML from Pseudomonas sp. MIS38 and lipase Lip I.3 from Pseudomonas sp. CR-611. LipM was expressed in Escherichia coli, purified from inclusion bodies, and further biochemically characterized. Purified LipM differed significantly from previously reported subfamily I.3 lipases, and was eurythermic between 10 degreesC-95 degreesC. LipM activity was enhanced by Ca(2+), Sr(2+), Mn(2+), and Ba(2+), but sharply inhibited by Cu(2+), Zn(2+), Co(2+), Ni(2+), and EDTA. Compared with other lipases, LipM exhibited medium tolerance to methanol, ethanol, and isopropanol. When applied for hydrolysis of algal oil, LipM could enrich 65.88 % polyunsaturated fatty acids, which include 1.25 % eicosapentaenoic acid, 17.61 % docosapentaenoic acid, and 47.02 % docosahexaenoic acid with derivative glycerides containing 32.46 % diacylglycerols. CONCLUSIONS: A novel eurythermic I.3 subfamily lipase with high tolerance and stability was identified from Pseudomonas moraviensis and biochemically characterized. It will not only improve our understanding of subfamily I.3 lipases, but also provides an ideal biocatalyst for the enrichment of polyunsaturated fatty acids. Pseudomonas moraviensis have been investigated as a potential resource of lipases.
ESTHER : Yang_2015_BMC.Biotechnol_15_94
PubMedSearch : Yang_2015_BMC.Biotechnol_15_94
PubMedID: 26463643

Title : Draft Genome Sequence of Rhodobacteraceae Strain PD-2, an Algicidal Bacterium with a Quorum-Sensing System, Isolated from the Marine Microalga Prorocentrum donghaiense - Zheng_2015_Genome.Announc_3_
Author(s) : Zheng L , Cui Z , Xu L , Sun C , Powell RJ , Hill RT
Ref : Genome Announc , 3 : , 2015
Abstract : Rhodobacteraceae strain PD-2 was isolated from the marine microalga Prorocentrum donghaiense. It has algicidal activity toward its host and could produce N-acylhomoserine lactone signals. Here, we present the draft genome of strain PD-2, which contains 5,227,214 bp with an average GC content of 66.19%. There were 4,864 encoding gene sequences and two clusters of luxI and luxR homologues identified.
ESTHER : Zheng_2015_Genome.Announc_3_
PubMedSearch : Zheng_2015_Genome.Announc_3_
PubMedID: 25700405
Gene_locus related to this paper: 9rhob-x6l117 , 9rhob-x6kvi3

Title : Isolation of an aryloxyphenoxy propanoate (AOPP) herbicide-degrading strain Rhodococcus ruber JPL-2 and the cloning of a novel carboxylesterase gene (feh) - Hongming_2015_Braz.J.Microbiol_46_425
Author(s) : Hongming L , Xu L , Zhaojian G , Fan Y , Dingbin C , Jianchun Z , Jianhong X , Shunpeng L , Qing H
Ref : Braz J Microbiol , 46 :425 , 2015
Abstract : The strain JPL-2, capable of degrading fenoxaprop-P-ethyl (FE), was isolated from the soil of a wheat field and identified as Rhodococcus ruber. This strain could utilize FE as its sole carbon source and degrade 94.6% of 100 mg L(-1) FE in 54 h. Strain JPL-2 could also degrade other aryloxyphenoxy propanoate (AOPP) herbicides. The initial step of the degradation pathway is to hydrolyze the carboxylic acid ester bond. A novel esterase gene feh, encoding the FE-hydrolyzing carboxylesterase (FeH) responsible for this initial step, was cloned from strain JPL-2. Its molecular mass was approximately 39 kDa, and the catalytic efficiency of FeH followed the order of FE > quizalofop-P-ethyl > clodinafop-propargyl > cyhalofop-butyl > fluazifop-P-butyl > haloxyfop-P-methyl > diclofop-methy, which indicated that the chain length of the alcohol moiety strongly affected the hydrolysis activity of the FeH toward AOPP herbicides.
ESTHER : Hongming_2015_Braz.J.Microbiol_46_425
PubMedSearch : Hongming_2015_Braz.J.Microbiol_46_425
PubMedID: 26273257

Title : Bactericidal Dendritic Polycation Cloaked with Stealth Material via Lipase-Sensitive Intersegment Acquires Neutral Surface Charge without Losing Membrane-Disruptive Activity - Xu_2015_ACS.Appl.Mater.Interfaces_7_27602
Author(s) : Xu L , He C , Hui L , Xie Y , Li JM , He WD , Yang L
Ref : ACS Appl Mater Interfaces , 7 :27602 , 2015
Abstract : Net cationicity of membrane-disruptive antimicrobials is necessary for their activity but may elicit immune attack when administered intravenously. By cloaking a dendritic polycation (G2) with poly(caprolactone-b-ethylene glycol) (PCL-b-PEG), we obtain a nanoparticle antimicrobial, G2-g-(PCL-b-PEG), which exhibits neutral surface charge but kills >99.9% of inoculated bacterial cells at >=8 microg/mL. The observed activity may be attributed PCL's responsive degradation by bacterial lipase and the consequent exposure of the membrane-disruptive, bactericidal G2 core. Moreover, G2-g-(PCL-b-PEG) exhibits good colloidal stability in the presence of serum and insignificant hemolytic toxicity even at <=2048 microg/mL. suggesting good blood compatibility required for intravenous administration.
ESTHER : Xu_2015_ACS.Appl.Mater.Interfaces_7_27602
PubMedSearch : Xu_2015_ACS.Appl.Mater.Interfaces_7_27602
PubMedID: 26632646

Title : Probing role of key residues in the divergent evolution of Yarrowia lipolytica lipase 2 and Aspergillus niger eruloyl esterase A - Wang_2015_Microbiol.Res_178_27
Author(s) : Wang G , Liu Z , Xu L , Zhang H , Yan Y
Ref : Microbiol Res , 178 :27 , 2015
Abstract : Yarrowia lipolytica lipase 2 (YLLip2) and Aspergillus niger feruloyl esterase A (AnFaeA) are enzymes of similar structures but with different functions. They are both classified into the same homologous family in Lipase Engineering Database (LED). The major difference between the two enzymes is that YLLip2 exhibits interfacial activity while AnFaeA does not. In order to better understand the interfacial activation mechanisms of YLLip2, structure guided site-directed mutagenesis were performed, mutants were constructed, kinetics parameters and lipase properties were detected. Mutant enzymes showed enhanced catalytic efficiency towards p-nitrophenyl butyrin (pNPB) but their catalytic efficiency decreased towards p-nitrophenyl palmitate (pNPP), their catalysis behavior was more close to feruloyl esterase. Moreover, the mutant enzymes exhibited enhanced thermostability compared with their wild type. These results indicate that I100 and F129 are probably cut-off point of divergent functions between the two enzymes during evolution.
ESTHER : Wang_2015_Microbiol.Res_178_27
PubMedSearch : Wang_2015_Microbiol.Res_178_27
PubMedID: 26302844

Title : Disruption of the Arabidopsis Defense Regulator Genes SAG101, EDS1, and PAD4 Confers Enhanced Freezing Tolerance - Chen_2015_Mol.Plant_8_1536
Author(s) : Chen QF , Xu L , Tan WJ , Chen L , Qi H , Xie LJ , Chen MX , Liu BY , Yu LJ , Yao N , Zhang JH , Shu W , Xiao S
Ref : Mol Plant , 8 :1536 , 2015
Abstract : In Arabidopsis, three lipase-like regulators, SAG101, EDS1, and PAD4, act downstream of resistance protein-associated defense signaling. Although the roles of SAG101, EDS1, and PAD4 in biotic stress have been extensively studied, little is known about their functions in plant responses to abiotic stresses. Here, we show that SAG101, EDS1, and PAD4 are involved in the regulation of freezing tolerance in Arabidopsis. With or without cold acclimation, the sag101, eds1, and pad4 single mutants, as well as their double mutants, exhibited similarly enhanced tolerance to freezing temperatures. Upon cold exposure, the sag101, eds1, and pad4 mutants showed increased transcript levels of C-REPEAT/DRE BINDING FACTORs and their regulons compared with the wild type. Moreover, freezing-induced cell death and accumulation of hydrogen peroxide were ameliorated in sag101, eds1, and pad4 mutants. The sag101, eds1, and pad4 mutants had much lower salicylic acid (SA) and diacylglycerol (DAG) contents than the wild type, and exogenous application of SA and DAG compromised the freezing tolerance of the mutants. Furthermore, SA suppressed the cold-induced expression of DGATs and DGKs in the wild-type leaves. These findings indicate that SAG101, EDS1, and PAD4 are involved in the freezing response in Arabidopsis, at least in part, by modulating the homeostasis of SA and DAG.
ESTHER : Chen_2015_Mol.Plant_8_1536
PubMedSearch : Chen_2015_Mol.Plant_8_1536
PubMedID: 26149542

Title : Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia - Xu_2015_Mar.Drugs_13_3653
Author(s) : Xu L , Dong W , Zhao J , Xu Y
Ref : Mar Drugs , 13 :3653 , 2015
Abstract : Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs), isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA). PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0) till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE) activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression.
ESTHER : Xu_2015_Mar.Drugs_13_3653
PubMedSearch : Xu_2015_Mar.Drugs_13_3653
PubMedID: 26058015

Title : Characterizing LipR from Pseudomonas sp. R0-14 and Applying in Enrichment of Polyunsaturated Fatty Acids from Algal Oil - Yang_2015_J.Microbiol.Biotechnol_25_1880
Author(s) : Yang W , Xu L , Zhang H , Yan Y
Ref : J Microbiol Biotechnol , 25 :1880 , 2015
Abstract : In this study, Pseudomonas R0-14, which was isolated from Arctic soil samples, showed a clear halo when grown on M9 medium agarose plates containing olive oil-rhodamine B as substrate, suggesting that it expressed putative lipase(s). A putative lipase gene, lipR, was cloned from R0-14 by genome walking and Touchdown PCR. lipR encodes a 562-amino-acid polypeptide showing a typical alpha/beta hydrolase structure with a catalytic triad consisting of Ser153-Asp202-His260 and one alpha-helical lid (residues 103-113). A phylogenetic analysis revealed that LipR belongs to the lipase subfamily I.3. LipR was successfully expressed in Escherichia coli, purified, and biochemically characterized. Recombinant LipR exhibited its maximum activity towards p-nitrophenyl butyrate at pH 8.5 and 60 degrees C with a Km of 0.37 mM and a kcat of 6.42 s(-1). It retained over 90% of its original activity after incubation at 50 degrees C for 12 h. In addition, LipR was activated by Ca(2+), Mg(2+), Ba(2+), and Sr(2+), while strongly inhibited by Cu(2+), Zn(2+), Mn(2+), and ethylenediaminetetraacetic acid. Moreover, it showed a certain tolerance to organic solvents, including acetonitrile, isopropanol, acetone, methanol, and tert-butanol. When algal oil was hydrolyzed by LipR for 24 h, there was an enrichment of n-3 long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (1.22%, 1.65-fold), docosapentaenoic acid (21.24%, 2.04-fold), and docosahexaenoic acid (36.98%, 1.33-fold), and even a certain amount of diacylglycerols was also produced. As a result, LipR has great prospect in industrial applications, especially in food and/or cosmetics applications.
ESTHER : Yang_2015_J.Microbiol.Biotechnol_25_1880
PubMedSearch : Yang_2015_J.Microbiol.Biotechnol_25_1880
PubMedID: 26215266

Title : Protein-Coated Microcrystals from Candida rugosa Lipase: Its Immobilization, Characterization, and Application in Resolution of Racemic Ibuprofen - Huang_2015_Appl.Biochem.Biotechnol_177_36
Author(s) : Huang S , Li X , Xu L , Ke C , Zhang R , Yan Y
Ref : Appl Biochem Biotechnol , 177 :36 , 2015
Abstract : In this study, an economical heterogeneous biocatalyst, protein-coated microcrystals (PCMCs), was prepared from a commercial Candida rugosa lipase (CRL) and used for catalyzing esterification of (R, S)-ibuprofen enantiomers with isooctanol in isooctane. The main variables controlling the process (precipitating solvents, pH, saturated K2SO4 solution, and water content) were optimized via single-factorial experiments. Under optimum conditions, the enantiomeric excess of active S(+)-ibuprofen and total conversion rate were 97.34 and 49.83 %, respectively, and the corresponding enzyme (PCMC-CRL) activity attained 387.29 mumol/min/g protein, a 5.78-fold enhancement over the free lipase powder. Additionally, the thermostability, organic-solvent tolerance, and operational stability of PCMC-CRL were greatly improved as compared to the free enzyme. Fourier transform infrared (FTIR) spectroscopy was employed to reveal the correlation between conformation and enzyme activity enhancement. Moreover, the PCMC-CRL retained most of its original activity following use in more than 15 successive batches, suggesting that it exhibits adequate operational stability. These results indicate that PCMC-CRL is of great potential use in industrial applications.
ESTHER : Huang_2015_Appl.Biochem.Biotechnol_177_36
PubMedSearch : Huang_2015_Appl.Biochem.Biotechnol_177_36
PubMedID: 26137875

Title : Biochemical and molecular characterisation and cross-resistance in field and laboratory chlorpyrifos-resistant strains of Laodelphax striatellus (Hemiptera: Delphacidae) from eastern China - Xu_2014_Pest.Manag.Sci_70_1118
Author(s) : Xu L , Wu M , Han Z
Ref : Pest Manag Sci , 70 :1118 , 2014
Abstract : BACKGROUND: Laboratory selection is often employed in resistance mechanism studies because field-derived populations commonly do not have high enough resistance for such studies. In the present study, a field-collected Laodelphax striatellus population from eastern China was laboratory selected for chlorpyrifos resistance and susceptibility, and the developed strains, along with a field population, were studied for cross-resistance and resistance mechanisms at biochemical and molecular levels.
RESULTS: A 158.58-fold chlorpyrifos-resistant strain (JH-chl) and a chlorpyrifos-susceptible strain (JHS) were established after laboratory selection of 25 generations. Cross-resistance to deltamethrin, diazinon, methomyl, carbosulfan, acephate and imidacloprid were detected in JH-chl and a field-collected strain (JHF). Synergism and enzyme activity data suggested potential involvement of P450s and esterases in JH-chl as well as AChE alteration. Furthermore, CYP6AY3v2, CYP306A2v2, CYP353D1v2 and LSCE36 genes were significantly overexpressed in JH-chl (6.87-12.14-fold). Feeding of dsRNAs reduced the expression of the four target genes (35.6-56.8%) and caused significant adult mortality (75.21-88.45%), implying resistance reduction. However, mechanism(s) conferring chlorpyrifos resistance in JHF were unclear. CONCLUSION: In contrast to previous reports, multiple overexpressed detoxification genes were potentially associated with chlorpyrifos resistance, as confirmed by RNAi feeding tests. Chlorpyrifos resistance exhibits cross-resistance with insecticides in the same and different classes.
ESTHER : Xu_2014_Pest.Manag.Sci_70_1118
PubMedSearch : Xu_2014_Pest.Manag.Sci_70_1118
PubMedID: 24115461

Title : Biochemical Characterization of a Carboxylesterase from the Archaeon Pyrobaculum sp. 1860 and a Rational Explanation of Its Substrate Specificity and Thermostability - Shao_2014_Int.J.Mol.Sci_15_16885
Author(s) : Shao H , Xu L , Yan Y
Ref : Int J Mol Sci , 15 :16885 , 2014
Abstract : In this work, genome mining was used to identify esterase/lipase genes in the archaeon Pyrobaculum sp. 1860. A gene was cloned and functionally expressed in Escherichia coli as His-tagged protein. The recombinant enzyme (rP186_1588) was verified by western blotting and peptide mass fingerprinting. Biochemical characterization revealed that rP186_1588 exhibited optimum activity at pH 9.0 and 80 degrees C towards p-nitrophenyl acetate (Km: 0.35 mM, kcat: 11.65 s-1). Interestingly, the purified rP186_1588 exhibited high thermostability retaining 70% relative activity after incubation at 90 degrees C for 6 h. Circular dichroism results indicated that rP186_1588 showed slight structure alteration from 60 to 90 degrees C. Structural modeling showed P186_1588 possessed a typical alpha/beta hydrolase's fold with the catalytic triad consisting of Ser97, Asp147 and His172, and was further confirmed by site-directed mutagenesis. Comparative molecular simulations at different temperatures (300, 353, 373 and 473 K) revealed that its thermostability was associated with its conformational rigidity. The binding free energy analysis by MM-PBSA method revealed that the van der Waals interaction played a major role in p-NP ester binding for P186_1588. Our data provide insights into the molecular structures of this archaeal esterase, and may help to its further protein engineering for industrial applications.
ESTHER : Shao_2014_Int.J.Mol.Sci_15_16885
PubMedSearch : Shao_2014_Int.J.Mol.Sci_15_16885
PubMedID: 25250909

Title : Maternal supplementation of nucleotides improves the behavioral development of prenatal ethanol-exposed mice - Dong_2014_Cogn.Affect.Behav.Neurosci_14_879
Author(s) : Dong W , Wu Z , Xu L , Fang Y , Xu Y
Ref : Cogn Affect Behavioral Neuroscience , 14 :879 , 2014
Abstract : Maternal ethanol consumption during pregnancy can induce learning deficits in the offspring. The objective of this study was to assess whether supplementation of exogenous nucleotides during pregnancy and lactation would ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, and to explore the possible mechanisms. In the present study, pregnant C57BL/6J mice were exposed to ethanol (5 g/kg body weight) intragastrically from gestational day (GD) 6 to GD15. The dams in exogenous nucleotide intervention groups were fed with feed containing 0.01 %, 0.04 %, or 0.16 % nucleotide powder, with control and ethanol groups receiving normal feed. The dams were allowed to deliver naturally and to breast feed their offspring. After weaning, behavioral tests were carried out in the offspring of each group. Serum oxidation indexes were analyzed, and the hippocampus of each offspring was collected and detected for acetyl cholinesterase (AChE) activity and the expression of p-CREB, CREB, and BDNF. The results showed that maternal supplementation with exogenous nucleotides during pregnancy could ameliorate prenatal ethanol-induced learning and memory deficits in the offspring of mice, through improving their antioxidant capacity, reversing hippocampus AChE levels, and allowing the expression of some proteins related to learning and memory. However, different sensitivities were found between the two sexes.
ESTHER : Dong_2014_Cogn.Affect.Behav.Neurosci_14_879
PubMedSearch : Dong_2014_Cogn.Affect.Behav.Neurosci_14_879
PubMedID: 24146316

Title : Quantification of the Transcripts Encoding Different Forms of AChE in Various Cell Types: Real-Time PCR Coupled with Standards in Revealing the Copy Number - Bi_2014_J.Mol.Neurosci_53_461
Author(s) : Bi CWC , Luk WK , Campanari ML , Liu YH , Xu L , Lau KM , Xu ML , Choi RC , Saez-Valero J , Tsim KWK
Ref : Journal of Molecular Neuroscience , 53 :461 , 2014
Abstract : Acetylcholinesterase (AChE) is encoded by a single gene, and the alternative splicing at the 3' end produces different isoforms, including tailed (AChET), read-through (AChER), and hydrophobic (AChEH). Different forms of this enzyme exist in different cell types. Each AChE form has been proposed to have unique function, and all of them could be found in same cell type. Thus, the splicing process of different AChE forms remains unclear. Here, we aimed to establish a quantification method in measuring the absolute amount of each AChE splicing variants within a cell type. By using real-time PCR coupled with standard curves of defined copy of AChE variants, the copies of AChET transcript per 100 ng of total RNA were 5.7 x 10(4) in PC12 (rat neuronal cell), 1.3 x 10(4) in Caco-2 (human intestinal cell), 0.67 x 10(4) in TF-1 (human erythropoietic precursor), 133.3 in SH-SY5Y (human neuronal cell), and 56.7 in human umbilical vein endothelial cells (human endothelial cells). The copies of AChEH in these cell types were 0.3 x 10(4), 3.3 x 10(4), 2.7 x 10(4), 133.3, and 46.7, respectively, and AChER were 0.07 x 10(4), 0.13 x 10(4), 890, 3.3, and 2.7, respectively. Furthermore, PC12 and TF-1 cells were chosen for the analysis of AChE splicing pattern during differentiation. The results demonstrated a selective increase in AChET mRNA but not AChER or AChEH mRNAs in PC12 upon nerve growth factor-induced neuronal differentiation. PC12 cells could therefore act as a good cell model for the study on alternative splicing mechanism and regulation of AChET.
ESTHER : Bi_2014_J.Mol.Neurosci_53_461
PubMedSearch : Bi_2014_J.Mol.Neurosci_53_461
PubMedID: 24385197

Title : A sensitive LC-MS\/MS method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine with application to a clinical pharmacokinetic study - Zhou_2014_Biomed.Chromatogr_28_994
Author(s) : Zhou T , Zhao T , Cheng Q , Liu S , Xu L , Tan W
Ref : Biomedical Chromatography , 28 :994 , 2014
Abstract : A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of R-bambuterol and its active metabolite R-terbutaline in human plasma and urine was established. The inhibition for the biotransformation of R-bambuterol in plasma was fully investigated. Plasma samples were prepared on ice and neostigmine metilsulfate added as a cholinesterase inhibitor immediately after sample collection. All samples were extracted with ethyl acetate and separated on a C18 column under gradient elution with a mobile phase consisting of methanol and water containing 5 mm ammonium acetate at a flow rate of 0.6 mL/min. The analytes were detected by an API 4000 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 10.00 pg/mL for each analyte in plasma. In urine samples, the LLOQs were 20.00 and 500.0 pg/mL for R-bambuterol and R-terbutaline, respectively. The intra- and inter-day precisions were <12.7 and <8.6% for plasma and urine, respectively. The analytical runtime within 6.0 min per sample made this method suitable for high-throughput determination. The validated method has been successfully applied to the human pharmacokinetic study of R-bambuterol involving 10 healthy volunteers. Copyright (c) 2013 John Wiley & Sons, Ltd.
ESTHER : Zhou_2014_Biomed.Chromatogr_28_994
PubMedSearch : Zhou_2014_Biomed.Chromatogr_28_994
PubMedID: 24357101

Title : A highly selective long-wavelength fluorescent probe for the detection of human carboxylesterase 2 and its biomedical applications - Feng_2014_Chem.Commun.(Camb)_50_14519
Author(s) : Feng L , Liu ZM , Xu L , Lv X , Ning J , Hou J , Ge GB , Cui JN , Yang L
Ref : Chem Commun (Camb) , 50 :14519 , 2014
Abstract : A highly selective long-wavelength fluorescent probe TCFB has been developed for the detection of hCE2. The probe can be used for real-time monitoring of hCE2 activity in complex biological systems.
ESTHER : Feng_2014_Chem.Commun.(Camb)_50_14519
PubMedSearch : Feng_2014_Chem.Commun.(Camb)_50_14519
PubMedID: 25303144
Gene_locus related to this paper: human-CES2

Title : Silencing of an aphid carboxylesterase gene by use of plant-mediated RNAi impairs Sitobion avenae tolerance of Phoxim insecticides - Xu_2014_Transgenic.Res_23_389
Author(s) : Xu L , Duan X , Lv Y , Zhang X , Nie Z , Xie C , Ni Z , Liang R
Ref : Transgenic Res , 23 :389 , 2014
Abstract : RNA interference (RNAi) describes the ability of double-stranded RNA (dsRNA) to inhibit homologous gene expression at the RNA level. Its specificity is sequence-based and depends on the sequence of one strand of the dsRNA corresponding to part or all of a specific gene transcript. In this study we adopted plant-mediated RNAi technology that targets Sitobion avenae (S. avenae) to enable gene silencing in the aphid and to minimize handling of the insects during experiments. S. avenae was selected for this study because it causes serious economic losses to wheat throughout the world. The carboxylesterase (CbE E4) gene in S. avenae was homologously cloned, which increased synthesis of a protein known to be critical to the resistance (tolerance) this species has developed to a wide range of pesticides. A plant RNAi vector was constructed, and transgenic Triticum aesticum (dsCbE1-5 and dsCbE2-2 lines) expressing CbE E4 dsRNA were developed. S. avenae were fed on dsCbE1-5 and dsCbE2-2 lines stably producing the CbE E4 dsRNA. CbE E4 gene expression in S. avenae was reduced by up to 30-60 %. The number of aphids raised on dsCbE1-5 and dsCbE2-2 was lower than the number raised on non-transgenic plants. A solution of CbE E4 enzyme from S. avenae fed on dsCbE1-5 and dsCbE2-2 plants hydrolyzed only up to 20-30 % Phoxim solution within 40 min whereas a solution of the enzyme from CbE E4 fed on control plants hydrolyzed 60 % of Phoxim solution within 40 min. CbE E4 gene silencing was achieved by our wheat-mediated RNAi approach. This plant-mediated RNAi approach for addressing degradation-based pesticide resistance mechanisms in aphids and may prove useful in pest management for diverse agro-ecosystems.
ESTHER : Xu_2014_Transgenic.Res_23_389
PubMedSearch : Xu_2014_Transgenic.Res_23_389
PubMedID: 24242160

Title : N-terminal transmembrane domain of lipase LipA from Pseudomonas protegens Pf-5: A must for its efficient folding into an active conformation - Zha_2014_Biochimie_105_165
Author(s) : Zha D , Zhang H , Xu L , Yan Y
Ref : Biochimie , 105 :165 , 2014
Abstract : LipA from Pseudomonas protegens Pf-5 has been proven not to be secreted into the extracytoplasmic space, proposing that it is a membrane protein in virtue of its N-terminal transmembrane domain predicted by the TMHMM 2.0. However, LipA was confirmed to be an intracellular protein through determining the effects of lipA deletion or overexpression on the lipase activities in the whole-cell, lysis supernatant and lysis pellet, even through its transmembrane domain being able to make heterologous LacZ locate on the cytoplasmic membrane via construction of beta-galactosidase reporter strains. Subsequently, lipase activity assays showed that the transmembrane domain played an indispensable role for the catalytic function of LipA through construction of the markerless deletion mutant of transmembrane domain sequence of lipA and the expression and purification of LipA and LipADeltaTMD. To further investigate why the transmembrane domain lost its membrane localization function and significantly affected the catalytic function of LipA, the 3D structures of LipA and LipADeltaTMD were constructed. The results indicated that the transmembrane domain, located in the interior of LipA, helped the alpha-helical lid to form an open conformation by the mediation of alpha5 helix. It seems to act as a kind of intramolecular chaperone like the beta-roll motif of subfamily I.3 lipases, which is novel and is the first to notify the intramolecular chaperone of a subfamily I.1 lipase.
ESTHER : Zha_2014_Biochimie_105_165
PubMedSearch : Zha_2014_Biochimie_105_165
PubMedID: 25038570
Gene_locus related to this paper: psef5-q4kj24

Title : Aromatic Amino Acid Mutagenesis at the Substrate Binding Pocket of Yarrowia lipolytica Lipase Lip2 Affects Its Activity and Thermostability - Wang_2014_ScientificWorldJournal_2014_382581
Author(s) : Wang G , Liu Z , Xu L , Yan Y
Ref : ScientificWorldJournal , 2014 :382581 , 2014
Abstract : The lipase2 from Yarrowia lipolytica (YLLip2) is a yeast lipase exhibiting high homologous to filamentous fungal lipase family. Though its crystal structure has been resolved, its structure-function relationship has rarely been reported. By contrast, there are two amino acid residues (V94 and I100) with significant difference in the substrate binding pocket of YLLip2; they were subjected to site-directed mutagenesis (SDM) to introduce aromatic amino acid mutations. Two mutants (V94W and I100F) were created. The enzymatic properties of the mutant lipases were detected and compared with the wild-type. The activities of mutant enzymes dropped to some extent towards p-nitrophenyl palmitate (pNPC16) and their optimum temperature was 35 degrees C, which was 5 degrees C lower than that of the wild-type. However, the thermostability of I100F increased 22.44% after incubation for 1 h at 40 degrees C and its optimum substrate shifted from p-nitrophenyl laurate (pNPC12) to p-nitrophenyl caprate (pNPC10). The above results demonstrated that the two substituted amino acid residuals have close relationship with such enzymatic properties as thermostability and substrate selectivity.
ESTHER : Wang_2014_ScientificWorldJournal_2014_382581
PubMedSearch : Wang_2014_ScientificWorldJournal_2014_382581
PubMedID: 25197700

Title : Complete Genome Sequence of Neisseria meningitidis Serogroup A Strain NMA510612, Isolated from a Patient with Bacterial Meningitis in China - Zhang_2014_Genome.Announc_2_e00360
Author(s) : Zhang Y , Yang J , Xu L , Zhu Y , Liu B , Shao Z , Zhang X , Jin Q
Ref : Genome Announc , 2 :e00360 , 2014
Abstract : Serogroup A meningococcal strains have been involved in several pandemics and a series of epidemics worldwide in the past. Determination of the genome sequence of the prevalent genotype strain will help us understand the genetic background of the evolutionary and epidemiological properties of these bacteria. We sequenced the complete genome of Neisseria meningitidis NMA510612, a clinical isolate from a patient with meningococcal meningitis.
ESTHER : Zhang_2014_Genome.Announc_2_e00360
PubMedSearch : Zhang_2014_Genome.Announc_2_e00360
PubMedID: 24812217
Gene_locus related to this paper: neime-r0tza2

Title : Genome of the Chinese tree shrew - Fan_2013_Nat.Commun_4_1426
Author(s) : Fan Y , Huang ZY , Cao CC , Chen CS , Chen YX , Fan DD , He J , Hou HL , Hu L , Hu XT , Jiang XT , Lai R , Lang YS , Liang B , Liao SG , Mu D , Ma YY , Niu YY , Sun XQ , Xia JQ , Xiao J , Xiong ZQ , Xu L , Yang L , Zhang Y , Zhao W , Zhao XD , Zheng YT , Zhou JM , Zhu YB , Zhang GJ , Wang J , Yao YG
Ref : Nat Commun , 4 :1426 , 2013
Abstract : Chinese tree shrews (Tupaia belangeri chinensis) possess many features valuable in animals used as experimental models in biomedical research. Currently, there are numerous attempts to employ tree shrews as models for a variety of human disorders: depression, myopia, hepatitis B and C virus infections, and hepatocellular carcinoma, to name a few. Here we present a publicly available annotated genome sequence for the Chinese tree shrew. Phylogenomic analysis of the tree shrew and other mammalians highly support its close affinity to primates. By characterizing key factors and signalling pathways in nervous and immune systems, we demonstrate that tree shrews possess both shared common and unique features, and provide a genetic basis for the use of this animal as a potential model for biomedical research.
ESTHER : Fan_2013_Nat.Commun_4_1426
PubMedSearch : Fan_2013_Nat.Commun_4_1426
PubMedID: 23385571
Gene_locus related to this paper: tupch-l9l8p0 , tupch-l9l7d8.1 , tupch-l9l7d8.2 , tupch-l9l7d8.3 , tupch-l8y4e3 , tupch-l9jqg5 , tupch-l9l3m0 , tupch-l9kxg8 , tupch-l9knn8 , tupch-l9kf47 , tupch-l9ja32 , tupch-l9l5b1 , tupch-l9khv5

Title : Isolation and characterization of a thermostable esterase from a metagenomic library - Shao_2013_J.Ind.Microbiol.Biotechnol_40_1211
Author(s) : Shao H , Xu L , Yan Y
Ref : J Ind Microbiol Biotechnol , 40 :1211 , 2013
Abstract : A novel esterase gene was isolated by functional screening of a metagenomic library prepared from an activated sludge sample. The gene (est-XG2) consists of 1,506 bp with GC content of 74.8 %, and encodes a protein of 501 amino acids with a molecular mass of 53 kDa. Sequence alignment revealed that Est-XG2 shows a maximum amino acid identity (47 %) with the carboxylesterase from Thermaerobacter marianensis DSM 12885 (YP_004101478). The catalytic triad of Est-XG2 was predicted to be Ser192-Glu313-His412 with Ser192 in a conserved pentapeptide (GXSXG), and further confirmed by site-directed mutagenesis. Phylogenetic analysis suggested Est-XG2 belongs to the bacterial lipase/esterase family VII. The recombinant Est-XG2, expressed and purified from Escherichia coli, preferred to hydrolyze short and medium length p-nitrophenyl esters with the best substrate being p-nitrophenyl acetate (K m and k cat of 0.33 mM and 36.21 s(-1), respectively). The purified enzyme also had the ability to cleave sterically hindered esters of tertiary alcohols. Biochemical characterization of Est-XG2 revealed that it is a thermophilic esterase that exhibits optimum activity at pH 8.5 and 70 degrees C. Est-XG2 had moderate tolerance to organic solvents and surfactants. The unique properties of Est-XG2, high thermostability and stability in the presence of organic solvents, may render it a potential candidate for industrial applications.
ESTHER : Shao_2013_J.Ind.Microbiol.Biotechnol_40_1211
PubMedSearch : Shao_2013_J.Ind.Microbiol.Biotechnol_40_1211
PubMedID: 23934105
Gene_locus related to this paper: 9bact-s5tby8

Title : Solvent-free enzymatic synthesis of 1, 3-diacylglycerols by direct esterification of glycerol with saturated fatty acids - Zhong_2013_Lipids.Health.Dis_12_65
Author(s) : Zhong N , Gui Z , Xu L , Huang J , Hu K , Gao Y , Zhang X , Xu Z , Su J , Li B
Ref : Lipids Health Dis , 12 :65 , 2013
Abstract : BACKGROUND: Pure 1, 3-diacylglycerols (1, 3-DAG) have been considered to be significant surfactants in food, cosmetics and pharmaceutical industries, as well as the effect on obesity prevention. METHODS: In this study, a vacuum-driven air bubbling operation mode was developed and evaluated for the enzymatic synthesis of 1, 3-DAG of saturated fatty acids, by direct esterification of glycerol with fatty acids in a solvent-free system. The employed vacuum-driven air bubbling operation mode was comparable to vacuum-driven N2 bubbling protocol, in terms of lauric acid conversion and 1, 3-dilaurin content. RESULTS: Some operation parameters were optimized, and 95.3% of lauric acid conversion and 80.3% of 1, 3-dilaurin content was obtained after 3-h reaction at 50 degC, with 5 wt% of Lipozyme RM IM (based on reactants) amount. Of the lipases studied, both Lipozyme RM IM and Novozym 435 exhibited good performance in terms of lauric acid conversion. Lipozyme TL IM, however, showed low activity. Lipozyme RM IM showed good operational stability in this operation protocol, 80.2% of the original catalytic activity remained after 10 consecutive batch applications. Some other 1, 3-DAG were prepared and high content was obtained after purification: 98.5% for 1, 3-dicaprylin, 99.2% for 1, 3-dicaprin, 99.1% for 1, 3-dilaurin, 99.5 for 1, 3-dipalmitin and 99.4% for 1, 3-disterin. CONCLUSION: The established vacuum-driven air bubbling operation protocol had been demonstrated to be a simple-operating, cost-effective, application practical and efficient methodology for 1, 3-DAG preparation.
ESTHER : Zhong_2013_Lipids.Health.Dis_12_65
PubMedSearch : Zhong_2013_Lipids.Health.Dis_12_65
PubMedID: 23656739

Title : Improving activity and enantioselectivity of lipase via immobilization on macroporous resin for resolution of racemic 1- phenylethanol in non-aqueous medium - Li_2013_BMC.Biotechnol_13_92
Author(s) : Li X , Huang S , Xu L , Yan Y
Ref : BMC Biotechnol , 13 :92 , 2013
Abstract : BACKGROUND: Burkholderia cepacia lipase (BCL) has been proved to be capable of resolution reactions. However, its free form usually exhibits low stability, bad resistance and no reusability, which restrict its further industrial applications. Therefore, it is of great importance to improve the catalytic performance of free lipase in non-aqueous medium.
RESULTS: In this work, macroporous resin NKA (MPR-NKA) was utilized as support for lipase immobilization. Racemic transesterification of 1-phenylethanol with vinyl acetate was chosen as model reaction. Compared with its free form, the enzyme activity and enantioselectivity (ees) of the immobilized lipase have been significantly enhanced. The immobilized BCL exhibited a satisfactory thermostability over a wide range of temperature (from 10 to 65[degree sign]C) and an excellent catalytic efficiency. After being used for more than 30 successive batches, the immobilized lipase still kept most of its activity. In comparison with other immobilized lipases, the immobilized BCL also exhibits better catalytic efficiency, which indicates a significant potential in industrial applications. CONCLUSION: The results of this study have proved that MPR-NKA was an excellent support for immobilization of lipase via the methods of N2 adsorption--desorption, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Fourier transform-infrared spectroscopy (FT-IR). The improvement of enzyme activity and ees for the immobilized lipase was closely correlated with the alteration of its secondary structure. This information may contribute to a better understanding of the mechanism of immobilization and enzymatic biotransformation in non-aqueous medium.
ESTHER : Li_2013_BMC.Biotechnol_13_92
PubMedSearch : Li_2013_BMC.Biotechnol_13_92
PubMedID: 24168516
Gene_locus related to this paper: burce-lipaa

Title : The evolution and pathogenic mechanisms of the rice sheath blight pathogen - Zheng_2013_Nat.Commun_4_1424
Author(s) : Zheng A , Lin R , Zhang D , Qin P , Xu L , Ai P , Ding L , Wang Y , Chen Y , Liu Y , Sun Z , Feng H , Liang X , Fu R , Tang C , Li Q , Zhang J , Xie Z , Deng Q , Li S , Wang S , Zhu J , Wang L , Liu H , Li P
Ref : Nat Commun , 4 :1424 , 2013
Abstract : Rhizoctonia solani is a major fungal pathogen of rice (Oryza sativa L.) that causes great yield losses in all rice-growing regions of the world. Here we report the draft genome sequence of the rice sheath blight disease pathogen, R. solani AG1 IA, assembled using next-generation Illumina Genome Analyser sequencing technologies. The genome encodes a large and diverse set of secreted proteins, enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, which probably reflect an exclusive necrotrophic lifestyle. We find few repetitive elements, a closer relationship to Agaricomycotina among Basidiomycetes, and expand protein domains and families. Among the 25 candidate pathogen effectors identified according to their functionality and evolution, we validate 3 that trigger crop defence responses; hence we reveal the exclusive expression patterns of the pathogenic determinants during host infection.
ESTHER : Zheng_2013_Nat.Commun_4_1424
PubMedSearch : Zheng_2013_Nat.Commun_4_1424
PubMedID: 23361014
Gene_locus related to this paper: thaca-l8wvp3 , thaca-l8wv47 , thaca-l8wp17 , thaca-l8x532

Title : Conformation and Catalytic Properties Studies of Candida rugosa Lip7 via Enantioselective Esterification of Ibuprofen in Organic Solvents and Ionic Liquids - Li_2013_ScientificWorldJournal_2013_364730
Author(s) : Li X , Huang S , Xu L , Yan Y
Ref : ScientificWorldJournal , 2013 :364730 , 2013
Abstract : Enantioselective esterification of ibuprofen was conducted to evaluate the enzyme activity and ees of lipase from Candida rugosa (CRL7) in ten conventional organic solvents and three ionic liquids. Different alcohols were tested for selecting the most suitable acyl acceptor due to the fact that the structure of alcohols (branch and length of carbon chains; location of -OH functional group) could affect the enzyme activity and ees. The results of alcohol and solvent selection revealed that 1-isooctanol and isooctane were the best substrate and reaction medium, respectively, because of the highest enzyme activity and ees. Compared with the control, conformational studies via FT-IR indicate that the variations of CRL7's secondary structure elements are probably responsible for the differences of enzyme activity and ees in the organic solvents and ionic liquids. Moreover, the effects of reaction parameters, such as molar ratio, water content, temperature, and reaction time, in the selected reaction medium, were also examined.
ESTHER : Li_2013_ScientificWorldJournal_2013_364730
PubMedSearch : Li_2013_ScientificWorldJournal_2013_364730
PubMedID: 24381516

Title : Sequencing, annotation, and characterization of the influenza ferret infectome - Leon_2013_J.Virol_87_1957
Author(s) : Leon AJ , Banner D , Xu L , Ran L , Peng Z , Yi K , Chen C , Xu F , Huang J , Zhao Z , Lin Z , Huang SH , Fang Y , Kelvin AA , Ross TM , Farooqui A , Kelvin DJ
Ref : J Virol , 87 :1957 , 2013
Abstract : Ferrets have become an indispensable tool in the understanding of influenza virus virulence and pathogenesis. Furthermore, ferrets are the preferred preclinical model for influenza vaccine and therapeutic testing. Here we characterized the influenza infectome during the different stages of the infectious process in ferrets with and without prior specific immunity to influenza. RNA from lung tissue and lymph nodes from infected and naive animals was subjected to next-generation sequencing, followed by de novo data assembly and annotation of the resulting sequences; this process generated a library comprising 13,202 ferret mRNAs. Gene expression profiles during pandemic H1N1 (pdmH1N1) influenza virus infection were analyzed by digital gene expression and solid support microarrays. As expected during primary infection, innate immune responses were triggered in the lung tissue; meanwhile, in the lymphoid tissue, genes encoding antigen presentation and maturation of effector cells of adaptive immunity increased dramatically. After 5 days postinfection, the innate immune gene expression was replaced by the adaptive immune response, which correlates with viral clearance. Reinfection with homologous pandemic influenza virus resulted in a diminished innate immune response, early adaptive immune gene regulation, and a reduction in clinical severity. The fully annotated ferret infectome will be a critical aid to the understanding of the molecular events that regulate disease severity and host-influenza virus interactions among seasonal, pandemic, and highly pathogenic avian influenzas.
ESTHER : Leon_2013_J.Virol_87_1957
PubMedSearch : Leon_2013_J.Virol_87_1957
PubMedID: 23236062
Gene_locus related to this paper: muspf-m1ejm3 , muspf-m3xwe4 , muspf-m3y1u3 , muspf-m3y1w0 , muspf-m3yex5 , muspf-m3ywm4 , muspf-m3yzl3 , muspf-g9kcw3 , muspf-m1efe2 , muspf-g9kdq4 , muspf-m3z0x2 , muspf-g9khi6 , muspf-m3yaj5 , muspf-g9k8i1 , muspf-m3xnu7 , muspf-m3yi69 , muspf-m3ywu1 , muspf-m3yy03 , muspf-g9l4j3 , muspf-m1ejz6

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : Visible-light-activated photoelectrochemical biosensor for the study of acetylcholinesterase inhibition induced by endogenous neurotoxins - Huang_2013_Biosens.Bioelectron_45C_292
Author(s) : Huang Q , Chen H , Xu L , Lu D , Tang L , Jin L , Xu Z , Zhang W
Ref : Biosensors & Bioelectronics , 45C :292 , 2013
Abstract : In this report, a novel visible-light-activated photoelectrochemical biosensor was fabricated to study the inhibition of acetylcholinesterase (AChE) activity induced by two endogenous neurotoxins, 1(R)-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-Sal] and 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline [(R)-NMSal], which have drawn much attention in the study of the pathogenesis of neurodegenerative diseases such as Parkinson's disease. The photoelectrode was prepared by three steps, as follows. At first, nitrogen and fluorine co-doped TiO2 nanotubes (TNs) were obtained by anodic oxidation of a Ti sheet. Secondly, silver nanoparticles (AgNPs) were deposited onto the TNs through a microwave-assisted heating polyol (MAHP) process. At last, AChE was immobilized on the obtained photoelectrode and the biosensor was marked as AChE/Ag/NFTNs. Due to the nitrogen and fluorine co-doping, the photoelectrochemical biosensors can produce high photocurrent under visible light irradiation. Moreover, the presence of AgNPs greatly increased the photocurrent response of the biosensor. AChE/Ag/NFTNs hybrid system was used to study AChE inhibition induced by (R)-Sal and (R)-NMSal. The result proved that both (R)-Sal and (R)-NMSal exhibited mixed and reversible inhibition against AChE. This strategy is of great significance for the development of novel photoelectrochemical biosensors in the future.
ESTHER : Huang_2013_Biosens.Bioelectron_45C_292
PubMedSearch : Huang_2013_Biosens.Bioelectron_45C_292
PubMedID: 23500378

Title : Lipase-coated K2SO4 micro-crystals: preparation, characterization, and application in biodiesel production using various oil feedstocks - Zheng_2012_Bioresour.Technol_110_224
Author(s) : Zheng J , Xu L , Liu Y , Zhang X , Yan Y
Ref : Bioresour Technol , 110 :224 , 2012
Abstract : This study investigated the preparation and characteristics of protein-coated microcrystals (PCMCs) from Pseudomonas cepacia lipase (PS) and K(2)SO(4), and their application in biodiesel synthesis, via single factorial experiments and response surface methodology (RSM), the optimized PCMC-PS exhibited high activity and stability; the optimal temperature was 60 degrees C (which gave 99.83% conversion), although fairly high activity was exhibited after incubation at different temperatures (25-70 degrees C). The organic solvents stability of the PCMC-PS was improved, and it significantly reduced ethanol toxicity. Circular dichroism (CD) analysis revealed the correlation between the conformation and the enzyme activity. The morphology of the PCMC-PS was also confirmed via scanning electron microscopy (SEM). When catalyzed by PCMC-PS, above 83% biodiesel yield was obtained for most of the seven oils tested. The PCMC-PS (washed with hexane) activity remained relatively stable after eight batch reactions, with only a 15.73% reduction in the conversion (from 99.02% to 83.29%).
ESTHER : Zheng_2012_Bioresour.Technol_110_224
PubMedSearch : Zheng_2012_Bioresour.Technol_110_224
PubMedID: 22330591

Title : Constitutive expression of Yarrowia lipolytica lipase LIP2 in Pichia pastoris using GAP as promoter - Wang_2012_Appl.Biochem.Biotechnol_166_1355
Author(s) : Wang X , Sun Y , Ke F , Zhao H , Liu T , Xu L , Liu Y , Yan Y
Ref : Appl Biochem Biotechnol , 166 :1355 , 2012
Abstract : A gene encoding Yarrowia lipolytica lipase LIP2 (YlLIP2) was cloned into a constitutive expression vector pGAPZalphaA and electrotransformed into the Pichia pastoris X-33 strain. The high-yield clones obtained by high copy and enzyme activity screening were chosen as the host strains for shaking flask and fermentor culture. The results showed that glucose was the optimum carbon source for YlLIP2 production, and the maximum hydrolytic activity of recombinant YlLIP2 reached 1,315 U/ml under the flask culture at 28 degrees C, pH 7.0, for 48 h. The fed-batch fermentation was carried out in 3- and 10-l bioreactors by continuously feeding glucose into the growing medium for achieving high cell density and YlLIP2 yields. The maximum hydrolytic activity of YlLIP2 and cell density obtained in the 3-l bioreactor were 10,300 U/ml and 116 g dry cell weight (DCW)/l, respectively. The peak hydrolytic activity of YlLIP2 and cell density were further improved in the 10-l fermentor where the values respectively attained were 13,500 U/ml and 120 g DCW/l. The total protein concentration in the supernatant reached 3.3 g/l and the cell viability remained approximately 99% after 80 h of culture. Furthermore, the recombinant YlLIP2 produced in P. pastoris pGAP and pAOX1 systems have similar content of sugar (about 12%) and biochemical characteristics. The above results suggest that the GAP promoter-derived expression system of P. pastoris is effective for the expression of YlLIP2 by high cell density culture and is probably an alternative to the conventional AOX1 promoter expression system in large-scale production of industrial lipases.
ESTHER : Wang_2012_Appl.Biochem.Biotechnol_166_1355
PubMedSearch : Wang_2012_Appl.Biochem.Biotechnol_166_1355
PubMedID: 22246727

Title : Bone marrow-derived mesenchymal stem cells up-regulate acetylcholine receptor delta subunit through NRG\/ErbB3-mediated mitogen-activated protein kinase pathway - Chen_2012_Clin.Transl.Sci_5_27
Author(s) : Chen L , Jiang J , Xu J , Gu Y , Xu L
Ref : Clin Transl Sci , 5 :27 , 2012
Abstract : To investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on the expression of acetylcholine receptor delta subunit (AChRd), the murine skeletal muscle cell line Sol8 were grown in DMEM with 20% fetal bovine serum added with (conditional medium group) or without (control group) conditional medium of BMSC cells for 48 hours. RT-PCR and Western blot were performed to access the mRNA and protein levels of AChRd in Sol8 cells, respectively. Western blot was used to detect total and phosphorylated protein levels of Ras, Raf-1, Mek1/2, and Erk1/2, respectively. NRG-1 antibody added in conditional medium of BMSCs, si-ErbB3, and four Ras/Raf/MEK/ERK pathway inhibitors (FTS, Sulindac, U0126, and PD98059) were using to investigate the effect of AChRd levels. Our studies indicated that expression of AChRd was significantly enhanced in the conditional medium group when compared with those in control group and phosphorylation of Ras, Raf, Erk1/2 in Sol8 cells was also increased. Although gene silencing for ErbB3 gene, adding of NRG-1 antibody in conditional medium of BMSCs or treatment of Ras/Raf/MEK/ERK pathway inhibitors can down-regulate expression of AChRd and phosphorylation, which suggesting that the Ras/Raf/MEK/ERK pathway may be involved in BMSCs-induced expression of AChRd.
ESTHER : Chen_2012_Clin.Transl.Sci_5_27
PubMedSearch : Chen_2012_Clin.Transl.Sci_5_27
PubMedID: 22376253

Title : Efficient display of active Geotrichum sp. lipase on Pichia pastoris cell wall and its application as a whole-cell biocatalyst to enrich EPA and DHA in fish oil - Pan_2012_J.Agric.Food.Chem_60_9673
Author(s) : Pan XX , Xu L , Zhang Y , Xiao X , Wang XF , Liu Y , Zhang HJ , Yan YJ
Ref : Journal of Agricultural and Food Chemistry , 60 :9673 , 2012
Abstract : Geotrichum sp. lipase (GSL) was first displayed on the cell wall of Pichia pastoris on the basis of the a-agglutinin anchor system developed in Saccharomyces cerevisiae . Surface display levels were monitored using Western blotting, immunofluorescence miscroscopy, and fluorescence-activated cell sorting analysis. Lipase activity of the yeast whole cells reached a maximum at 273 +/- 2.4 U/g of dry cells toward olive oil after 96 h of culture at 30 degrees C, with optimal pH and temperature at 7.5 and 45 degrees C, respectively. Displayed GSL exhibited relatively high stability between pH 6.0 and 8.0 and retained >70% of the maximum activity. The surface-displayed lipase retained 80% of its original activity after incubation at 45 degrees C for 4 h. Moreover, the GSL-displaying yeast whole cells were then used as a biocatalyst to enrich eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil on the basis of selective hydrolysis. As a result, EPA and DHA increased from 1.53 and 24.1% in the original fish oil to 1.85 and 30.86%, which were increases of 1.21- and 1.29-fold, respectively. The total yield of EPA and DHA reached 46.62%.
ESTHER : Pan_2012_J.Agric.Food.Chem_60_9673
PubMedSearch : Pan_2012_J.Agric.Food.Chem_60_9673
PubMedID: 22934819

Title : [Effect of sailuotong capsule on intervening cognitive dysfunction of multi-infarct dementia in rats] - Xu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2943
Author(s) : Xu L , Lin CR , Liu JX , Ren JX , Li JM , Wang M , Li HH , Song WT , Yao MJ , Wang GR
Ref : Zhongguo Zhong Yao Za Zhi , 37 :2943 , 2012
Abstract : OBJECTIVE: To study the effect of Sailuotong capsule (Sailuotong) on learning and memory functions of multi-infarct dementia (MID) rats and its mechanism. METHOD: All SD rats were divided into five groups, namely the sham operation group, the model group, the positive group, the low dosage Sailuotong-treated group and the high dosage Sailuotong-treated group. The multi-infarct dementia model was established by injecting the micro-sphere vascular occlusive agent. On the 10th day after the successful operation, the rats were administered intragastrically with distilled water, memantine hydrochloride (20 mg x kg(-1)) and Sailuotong (16.5 mg x kg(-1) and 33.0 mg x kg(-1)) once a day for 60 days respectively, in order to detect the effect of Sailuotong in different doses on the latent period and route length in Morris water maze and the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) in brain tissues. RESULT: Compared with the sham operation rats, it had been observed that the latent period and route length of MID rats in Morris water maze were significantly increased (P < 0.05 or P < 0.01), and the activity of ChAT in brain tissues was significantly decreased (P < 0.05). After the intervention with Sailuotong for sixty days, the latent period and route length of MID rats in Morris water maze significantly shrank (P < 0.05 or P < 0.01). Additionally, Sailuotong decreased AchE activity, while increasing ChAT activity in brain tissues of MID rats (P < 0.05 or P < 0.01). CONCLUSION: Sailuotong capsule can improve cognitive dysfunction of MID rats to some extent. Its mechanism may be related to its different regulation of activities of ChAT and AchE in brain tissues.
ESTHER : Xu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2943
PubMedSearch : Xu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2943
PubMedID: 23270238

Title : Three-dimensional ordered macroporous (3DOM) composite for electrochemical study on acetylcholinesterase inhibition induced by endogenous neurotoxin - Teng_2012_J.Phys.Chem.B_116_11180
Author(s) : Teng Y , Fu Y , Xu L , Lin B , Wang Z , Xu Z , Jin L , Zhang W
Ref : J Phys Chem B , 116 :11180 , 2012
Abstract : In this paper, an electrochemical acetylcholinesterase (AChE) inhibition assay based on three-dimensional ordered macroporous (3DOM) composite was conducted. The 3DOM composite was first fabricated on the glassy carbon electrode by electropolymerization of aniline in the presence of ionic liquid (IL) on a sacrificial silica nanospheres template. After the silica nanospheres were etched, an IL-doped polyaniline (IL-PANI) film with 3DOM morphology was formed. Then, gold nanoparticles (AuNPs) were decorated on the IL-PANI film by electrodeposition. The immobilized AChE on the 3DOM composite displayed favorable affinity to substrate acetylthiocholine chloride (ATCh), and the 3DOM composite showed excellent electrocatalytic effect on thiocholine, the hydrolysis product of ATCh. The presence of IL and AuNPs could improve the sensitivity by accelerating the electron transfer. The designed AChE biosensor was successfully applied to evaluate the AChE inhibition induced by endogenous neurotoxin 1(R),2N-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-NMSal]. The results demonstrate that (R)-NMSal exerts a considerable effect on AChE activity, and the inhibition is reversible. The developed method offers a new approach for AChE inhibition assay, which is of great benefit in understanding the mechanism behind neurotoxin-induced neurodegenerative disorders.
ESTHER : Teng_2012_J.Phys.Chem.B_116_11180
PubMedSearch : Teng_2012_J.Phys.Chem.B_116_11180
PubMedID: 22946763

Title : Complete genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28 - Guan_2012_J.Bacteriol_194_6975
Author(s) : Guan P , Ai P , Dai X , Zhang J , Xu L , Zhu J , Li Q , Deng Q , Li S , Wang S , Liu H , Wang L , Li P , Zheng A
Ref : Journal of Bacteriology , 194 :6975 , 2012
Abstract : Bacillus thuringiensis is an important microbial insecticide used in the control of agricultural pests. Here we report the finished, annotated genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28, which can form parasporal crystals consisting of Cry4Cc1, Cry30Fa1, Cry53Ab1, Cry54Aa1, Cry54Ab1, Cry68Aa1, Cry69Aa1, Cry69Aa2, Cry70Ba1, Cyt1Da1, and Cyt2Aa3. It is also highly toxic to lepidopterous and dipterous insects.
ESTHER : Guan_2012_J.Bacteriol_194_6975
PubMedSearch : Guan_2012_J.Bacteriol_194_6975
PubMedID: 23209229

Title : Benzopyranones from the endophytic fungus Hyalodendriella sp. Ponipodef12 and their bioactivities - Meng_2012_Molecules_17_11303
Author(s) : Meng X , Mao Z , Lou J , Xu L , Zhong L , Peng Y , Zhou L , Wang M
Ref : Molecules , 17 :11303 , 2012
Abstract : The endophytic fungus Hyalodendriella sp. Ponipodef12 was isolated from the hybrid 'Neva' of Populus deltoides Marsh x P. nigra L. In this study, four benzopyranones were isolated from the ethyl acetate extract of Hyalodendriella sp. Ponipodef12, and identified as palmariol B (1), 4-hydroxymellein (2), alternariol 9-methyl ether (3), and botrallin (4) by means of physicochemical and spectroscopic analysis. All the compounds were evaluated for their antibacterial, antifungal, antinematodal and acetylcholinesterase inhibitory activities. 4-Hydroxymellein (2) exhibited stronger antibacterial activity than the other compounds. Palmariol B (1) showed stronger antimicrobial, antinematodal and acetylcholinesterase inhibitory activities than alternariol 9-methyl ether (3) which indicated that the chlorine substitution at position 2 may contribute to its bioactivity. The results indicate the potential of this endophytic fungus as a source of bioactive benzopyranones.
ESTHER : Meng_2012_Molecules_17_11303
PubMedSearch : Meng_2012_Molecules_17_11303
PubMedID: 23011274

Title : Fo Shou San, an ancient Chinese herbal decoction, protects endothelial function through increasing endothelial nitric oxide synthase activity - Bi_2012_PLoS.One_7_e51670
Author(s) : Bi CWC , Xu L , Tian XY , Liu J , Zheng KY , Lau CW , Lau DT , Choi RC , Dong TTX , Huang Y , Tsim KWK
Ref : PLoS ONE , 7 :e51670 , 2012
Abstract : Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+) levels in HUVECs, and the Ca(2+) chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+) and a reduction of ROS.
ESTHER : Bi_2012_PLoS.One_7_e51670
PubMedSearch : Bi_2012_PLoS.One_7_e51670
PubMedID: 23284736

Title : Fo shou san, an ancient herbal decoction prepared from angelicae sinensis radix and chuanxiong rhizoma, induces erythropoietin expression: a signaling mediated by the reduced degradation of hypoxia-inducible factor in cultured liver cells - Bi_2012_Planta.Med_78_122
Author(s) : Bi CWC , Xu L , Zhang WL , Zhan JY , Fu Q , Zheng KY , Chen VP , Lau DT , Choi RC , Wang TJ , Dong TTX , Tsim KWK
Ref : Planta Med , 78 :122 , 2012
Abstract : Fo Shou San (FSS) is an ancient herbal decoction composed of Angelicae Sinensis Radix (ASR; Danggui) and Chuanxiong Rhizoma (CR; Chuanxiong) in a ratio of 3:2. FSS is mainly prescribed for patients having a deficiency of blood supply, and it indeed has been shown to stimulate the production of erythropoietin (EPO) in cultured cells. In order to reveal the mechanism of this FSS-induced EPO gene expression, the upstream regulatory cascade, via hypoxia-induced signaling, was revealed here in cultured hepatocellular carcinoma cell line Hep3B. The induction of EPO gene expression, triggered by FSS, was revealed in cultured hepatocytes by: (i) the increase of EPO mRNA; and (ii) the activation of the hypoxia response element (HRE), an upstream regulator of the EPO gene. The FSS-induced EPO gene expression was triggered by an increased expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein; however, the mRNA expression of HIF-1 alpha was not altered by the treatment of FSS. The increased HIF-1 alpha was a result of reduced protein degradation after the FSS treatment. The current results therefore provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.
ESTHER : Bi_2012_Planta.Med_78_122
PubMedSearch : Bi_2012_Planta.Med_78_122
PubMedID: 22095261

Title : Biodiesel synthesis and conformation of lipase from Burkholderia cepacia in room temperature ionic liquids and organic solvents - Liu_2011_Bioresour.Technol_102_10414
Author(s) : Liu Y , Chen D , Yan Y , Peng C , Xu L
Ref : Bioresour Technol , 102 :10414 , 2011
Abstract : Biodiesel synthesis and conformation of Burkholderia cepacia lipase (BCL) were studied in 19 different room temperature ionic liquids (RTLLs) with a range of cation and anion structures. Overall, anion selection had a greater influence on biodiesel conversion than cation choice. RTILs containing Tf2N- and PF6- anions were suitable reaction media, while RTIL of [OmPy][BF4] was the best reaction medium with a biodiesel yield of 82.2+/-1.2%. RTILs with strong water miscible properties showed very low biodiesel yields. Conformational analysis by FT-IR revealed that higher biodiesel conversion in RTILs was correlated with a low tendency in alpha-helix content of BCL. An ultrasound-assisted biocatalysis process in RTILs was used to improve mass transfer rate, leading to 83% reduction of the reaction time for biodiesel production.
ESTHER : Liu_2011_Bioresour.Technol_102_10414
PubMedSearch : Liu_2011_Bioresour.Technol_102_10414
PubMedID: 21955878

Title : Crystal structure of a novel esterase Rv0045c from Mycobacterium tuberculosis - Zheng_2011_PLoS.One_6_e20506
Author(s) : Zheng X , Guo J , Xu L , Li H , Zhang D , Zhang K , Sun F , Wen T , Liu S , Pang H
Ref : PLoS ONE , 6 :e20506 , 2011
Abstract : There are at least 250 enzymes in Mycobacterium tuberculosis (M. tuberculosis) involved in lipid metabolism. Some of the enzymes are required for bacterial survival and full virulence. The esterase Rv0045c shares little amino acid sequence similarity with other members of the esterase/lipase family. Here, we report the 3D structure of Rv0045c. Our studies demonstrated that Rv0045c is a novel member of alpha/beta hydrolase fold family. The structure of esterase Rv0045c contains two distinct domains: the alpha/beta fold domain and the cap domain. The active site of esterase Rv0045c is highly conserved and comprised of two residues: Ser154 and His309. We proposed that Rv0045c probably employs two kinds of enzymatic mechanisms when hydrolyzing C-O ester bonds within substrates. The structure provides insight into the hydrolysis mechanism of the C-O ester bond, and will be helpful in understanding the ester/lipid metabolism in M. tuberculosis.
ESTHER : Zheng_2011_PLoS.One_6_e20506
PubMedSearch : Zheng_2011_PLoS.One_6_e20506
PubMedID: 21637775
Gene_locus related to this paper: myctu-RV0045C

Title : [Heterologous expression and characterization of Yarrowia lipolytica lipase 4 and lipase 5 in Pichia pastoris] - Zhao_2011_Wei.Sheng.Wu.Xue.Bao_51_1374
Author(s) : Zhao H , Xiao X , Xu L , Liu Y , Yan Y
Ref : Wei Sheng Wu Xue Bao , 51 :1374 , 2011
Abstract : OBJECTIVE: To clone cDNA sequences of lipase 4 (LIP4) and lipase 5 (LIPS), analyze gene structures and express them in Pichia pastoris so as to investigate their enzymatic characteristics. METHODS: We first cloned cDNA sequences of LIP4 and LIP5 by reverse transcription PCR and analyzed their gene structures by SignalP 3.0. Then, intracellular expression vectors pPIC3. 5K-Lip4, pPIC3. 5K-Lip5 and inducible secretion vectors pPIC9K-Lip4, pPIC9K-Lip5 were constructed. All vectors were transformed into Pichia pastoris GS115 by electroporation, resulting in a series of engineered strains. After fermentation and NTA-Ni resin purification, the enzymatic properties of LIP4 and LIP5 were examined. RESULTS: The cloned cDNA sequences revealed that there was no intron in both of Lip4 and Lip5. The two lipases both contained catalytic triads and conserved GHSLG motifs. Their optimal substrate, pH, temperature were respectively pNP-caprylate (C8), 7.0 and 40 degrees C. The activities of LIP4 and LIPS were 10.16 U/mg and 5.1 U/mg, respectively. It was found that LIP4 was more sensitive to the variations of pH and temperature than LIP5. LIP4 and LIP5 could both be stimulated by Ca2+, besides LIPS could also be activated by Mg2+. They were both strongly inhibited by Hg2+, Phenylmethanesulfonyl fluoride (PMSF) and Dithiothreitol (DTT). CONCLUSION: The cloning of Lip4 and Lip5, expression in P. pastoris and characterization of their properties would offer a solid basis for their large-scale production and future application. In addition, the results also enriched the data for a systematic research on the lipase gene family of Y. lipolytica.
ESTHER : Zhao_2011_Wei.Sheng.Wu.Xue.Bao_51_1374
PubMedSearch : Zhao_2011_Wei.Sheng.Wu.Xue.Bao_51_1374
PubMedID: 22233059

Title : Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: discovery of quinoxaline-based hybrid compounds with AChE, H(3)R and BACE 1 inhibitory activities - Huang_2011_Bioorg.Med.Chem_19_7158
Author(s) : Huang W , Tang L , Shi Y , Huang S , Xu L , Sheng R , Wu P , Li J , Zhou N , Hu Y
Ref : Bioorganic & Medicinal Chemistry , 19 :7158 , 2011
Abstract : A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H(3)R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT-25. A virtual database consisting of quinoxaline derivatives was first screened on a pharmacophore model of BACE 1 inhibitors, and then filtered by a molecular docking model of AChE. Seventeen quinoxaline derivatives with high score values were picked out, synthesized and evaluated for their biological activities. Compound 11a, the most effective MTDL, showed the potent activity to H(3)R/AChE/BACE 1 (H(3)R antagonism, IC(50)=280.0 +/- 98.0 nM; H(3)R inverse agonism, IC(50)=189.3 +/- 95.7 nM; AChE, IC(50)=483 +/- 5 nM; BACE 1, 46.64+/-2.55% inhibitory rate at 20 muM) and high selectivity over H(1)R/H(2)R/H(4)R. Furthermore, the protein binding patterns between 11a and AChE/BACE 1 showed that it makes several essential interactions with the enzymes.
ESTHER : Huang_2011_Bioorg.Med.Chem_19_7158
PubMedSearch : Huang_2011_Bioorg.Med.Chem_19_7158
PubMedID: 22019465

Title : Cloning of a novel lipase gene, lipJ08, from Candida rugosa and expression in Pichia pastoris by codon optimization - Xu_2010_Biotechnol.Lett_32_269
Author(s) : Xu L , Jiang X , Yang J , Liu Y , Yan Y
Ref : Biotechnol Lett , 32 :269 , 2010
Abstract : A novel lipase gene, lipJ08, was cloned from Candida rugosa ATCC14830, along with the already reported five lipase genes (lip1-lip5). Nucleotide sequencing indicated that the lipJ08 gene contains a 1650 bp open reading frame (ORF) without introns. The deduced amino acid sequence corresponds to 534 amino acid residues, including a putative signal sequence of 15 amino acid residues. Seventeen of the non-universal serine codons (CTG) of lipJ08 were converted into universal serine codons (TCT) by PCR-based mutagenesis. The native and codon-optimized lipJ08 genes were expressed in Pichia pastoris. The hydrolytic activity of the recombinant LIPJ08 was 4.7 U/ml, whereas the activity of the recombinant wild-type lipase could not be detected.
ESTHER : Xu_2010_Biotechnol.Lett_32_269
PubMedSearch : Xu_2010_Biotechnol.Lett_32_269
PubMedID: 19841868

Title : Enantioselective cytotoxicity of isocarbophos is mediated by oxidative stress-induced JNK activation in human hepatocytes - Liu_2010_Toxicology_276_115
Author(s) : Liu H , Liu J , Xu L , Zhou S , Li L , Liu W
Ref : Toxicology , 276 :115 , 2010
Abstract : Recent studies have shown the enantioselectivity of chiral pesticides in environmental fate, aquatic toxicity, endocrine disruption and cytotoxicity. Thus it is of significance to investigate the molecular mechanisms of chiral pesticides enantioselectivity in cytotoxicity. In the present study, we used Hep G2 cells as in vitro model to assay cytotoxicity of enantiomers of isocarbophos (ICP), a widely used chiral organophosphorus pesticide. The results of cell viability assay and cytoflow assay indicated an obvious enantioselective hepatocyte toxicity of ICP: (-)-ICP was about two times more toxic than (+)-ICP in Hep G2 cells. We found that (-)-ICP, but not (+)-ICP, up-regulated Bax protein expression and down-regulated Bcl-2 expression levels, which resulted in an increase in Bax/Bcl-2 ratio with the apoptosis co-ordination. Although (-)-ICP enantioselectively activated both ERK and JNK, only the specific inhibitor for JNK could completely reverse (-)-ICP-induced apoptosis of Hep G2 cells. It suggests that (-)-ICP-induced hepatocyte toxicity was more dominantly through the sustained activation of JNK pathway, but only partially via ERK cascade. Furthermore, (-)-ICP induced ROS production, while (+)-ICP had no effect on ROS generation. The antioxidant MnTBAP attenuated (-)-ICP-induced activation of JNK and ERK, indicating that the outcome from challenge with (-)-ICP enantiomer depends on the oxidative stress-induced activation of a series of signaling cascades that promote hepatocyte apoptosis. In conclusion, (-)-ICP enantioselectively causes the change of Bax/Bcl-2 ratio, triggers the generation of intracellular ROS and sequentially induces sustainable activation of JNK, which in turn, results in a decrease in cell viability and an increase in cell apoptosis. Our observations provide further insight into enantiomers toxicity pathway which is able to differentiate between enantiomer activities at molecular level.
ESTHER : Liu_2010_Toxicology_276_115
PubMedSearch : Liu_2010_Toxicology_276_115
PubMedID: 20688129

Title : Crystallization and preliminary X-ray analysis of a novel esterase Rv0045c from Mycobacterium tuberculosis. - Xu_2010_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_66_1579
Author(s) : Xu L , Guo J , Zheng X , Wen T , Sun F , Liu S , Pang H
Ref : Acta Crystallographica Sect F Struct Biol Cryst Commun , 66 :1579 , 2010
Abstract : The Rv0045c protein is predicted to be an esterase that is involved in lipid metabolism in Mycobacterium tuberculosis. The protein was overproduced in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The Rv0045c protein crystals diffracted to a resolution of 2.7A using a synchrotron-radiation source and belonged to space group P3(1) or P3(2), with unit-cell parameters a=b=73.465, c=48.064A, alpha=beta=90, =120deg. Purified SeMet-labelled Rv0045c protein was also crystallized and formed crystals that diffracted to a resolution of 3.0A using an in-house X-ray radiation source.
ESTHER : Xu_2010_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_66_1579
PubMedSearch : Xu_2010_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_66_1579
PubMedID: 21139199
Gene_locus related to this paper: myctu-RV0045C

Title : Characterization of a novel esterase Rv0045c from Mycobacterium tuberculosis - Guo_2010_PLoS.One_5_
Author(s) : Guo J , Zheng X , Xu L , Liu Z , Xu K , Li S , Wen T , Liu S , Pang H
Ref : PLoS ONE , 5 : , 2010
Abstract : BACKGROUND: It was proposed that there are at least 250 enzymes in M. tuberculosis involved in lipid metabolism. Rv0045c was predicted to be a hydrolase by amino acid sequence similarity, although its precise biochemical characterization and function remained to be defined. METHODOLOGY/PRINCIPAL FINDINGS: We expressed the Rv0045c protein to high levels in E. coli and purified the protein to high purity. We confirmed that the prepared protein was the Rv0045c protein by mass spectrometry analysis. Circular dichroism spectroscopy analysis showed that the protein possessed abundant beta-sheet secondary structure, and confirmed that its conformation was stable in the range pH 6.0-10.0 and at temperatures <= 40 degrees C. Enzyme activity analysis indicated that the Rv0045c protein could efficiently hydrolyze short chain p-nitrophenyl esters (C(2)-C(8)), and its suitable substrate was p-nitrophenyl caproate (C(6)) with optimal catalytic conditions of 39 degrees C and pH 8.0. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that the Rv0045c protein is a novel esterase. These experiments will be helpful in understanding ester/lipid metabolism related to M. tuberculosis.
ESTHER : Guo_2010_PLoS.One_5_
PubMedSearch : Guo_2010_PLoS.One_5_
PubMedID: 20957207
Gene_locus related to this paper: myctu-RV0045C

Title : Surface display of active lipase in Saccharomyces cerevisiae using Cwp2 as an anchor protein - Liu_2010_Biotechnol.Lett_32_255
Author(s) : Liu W , Zhao H , Jia B , Xu L , Yan Y
Ref : Biotechnol Lett , 32 :255 , 2010
Abstract : Lipase Lip2 from Yarrowia lipolytica was displayed on the cell surface of Saccharomyces cerevisiae using Cwp2 as an anchor protein. Successful display of the lipase on the cell surface was confirmed by immunofluorescence microscopy and halo assay. The length of linker sequences was further examined to confirm that the correct conformation of Lip2 was maintained. The results showed that the displayed Lip2 exhibited the highest activity at 7.6 +/- 0.4 U/g (dry cell) when using (G(4)S)(3) sequence as the linker, with an optimal temperature and pH at 40 degrees C and pH 8.0. The displayed lipase did not lose any activity after being treated with 0.1% Triton X-100 and 0.1% Tween 80 for 30 min, and it retained 92% of its original activity after incubation in 10% DMSO for 30 min. It also exhibited better thermostability than free Lip2 as reported previously.
ESTHER : Liu_2010_Biotechnol.Lett_32_255
PubMedSearch : Liu_2010_Biotechnol.Lett_32_255
PubMedID: 19821073

Title : Regulation of gene expression by FSP27 in white and brown adipose tissue - Li_2010_BMC.Genomics_11_446
Author(s) : Li D , Zhang Y , Xu L , Zhou L , Wang Y , Xue B , Wen Z , Li P , Sang J
Ref : BMC Genomics , 11 :446 , 2010
Abstract : BACKGROUND: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereas FSP27 deficient mice have improved insulin sensitivity and are resistant to diet-induced obesity. In addition, FSP27-deficient white adipocytes have reduced lipid storage, smaller lipid droplets, increased mitochondrial activity and a higher expression of several BAT-selective genes. To elucidate the molecular mechanism by which FSP27 controls lipid storage and gene expression in WAT and BAT, we systematically analyzed the gene expression profile of FSP27-deficient WAT by microarray analysis and compared the expression levels of a specific set of genes in WAT and BAT by semi-quantitative real-time PCR analysis.
RESULTS: BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of FSP27-deficient mice. The expression of the BAT-selective genes was also dramatically up-regulated in the WAT of leptin/FSP27 double deficient mice. In addition, the expression levels of genes involved in multiple metabolic pathways, including oxidative phosphorylation, the TCA cycle, fatty acid synthesis and fatty acid oxidation, were increased in the FSP27-deficient WAT. In contrast, the expression levels for genes involved in extracellular matrix remodeling, the classic complement pathway and TGF-beta signaling were down-regulated in the FSP27-deficient WAT. Most importantly, the expression levels of regulatory factors that determine BAT identity, such as CEBP alpha/beta, PRDM16 and major components of the cAMP pathway, were markedly up-regulated in the WAT of FSP27-deficient mice. The expression levels of these regulatory factors were also up-regulated in leptin/FSP27 double deficient mice. Interestingly, distinct gene expression profiles were observed in the BAT of FSP27-deficient mice. Taken together, these data suggest that the WAT of FSP27-deficient mice have a gene expression profile similar to that of BAT.
CONCLUSIONS: FSP27 acts as a molecular determinant that controls gene expression for a diversity of metabolic and signaling pathways and, in particular, the expression of regulatory factors, including CEBP alpha/beta, PRDM16 and components of the cAMP signaling pathway, that control the identity of WAT and BAT.
ESTHER : Li_2010_BMC.Genomics_11_446
PubMedSearch : Li_2010_BMC.Genomics_11_446
PubMedID: 20649970

Title : Surface display of active lipases Lip7 and Lip8 from Yarrowia lipolytica on Saccharomyces cerevisiae - Liu_2010_Appl.Microbiol.Biotechnol_88_885
Author(s) : Liu WS , Pan XX , Jia B , Zhao HY , Xu L , Liu Y , Yan YJ
Ref : Applied Microbiology & Biotechnology , 88 :885 , 2010
Abstract : Lipase has been used widely in industry. In this study, we have constructed two recombinant Saccharomyces cerevisiae strains displaying two active lipases on the cell surface by cell surface engineering. The genes encoding Yarrowia lipolytica lipases Lip7 and Lip8 were fused with the gene encoding small binding subunit Aga2 of a-agglutinin. Localization of the Lip7 and Lip8 on the cell surface was confirmed by immunofluorescence microscopy. Besides, the putative signal sequences of Lip7 and Lip8 were removed to compare their effect on the activities of surface-displayed lipases. The results showed that the activities towards p-nitrophenyl caprylate of surface-displayed Lip7 and Lip8 were 283 U/g (dry cell) and 121 U/g (dry cell), much higher than that using Flo1 as anchor protein in Pichia pastoris, and the putative signal sequences have significant effect on the activities of the displayed lipases; when deleted, the lipases' activities were declined to 65 U/g (dry cell) and 80 U/g (dry cell), respectively. The displayed lipases exhibit a preference for middle chain fatty acids and a high thermal stability. Additionally, from the study, to surface-display a target protein, it is recommendable that the structure feature of the protein should be assayed through bioinformatics methods and then the cell wall proteins with the anchor domain far away from the activity center should be chosen as anchor proteins.
ESTHER : Liu_2010_Appl.Microbiol.Biotechnol_88_885
PubMedSearch : Liu_2010_Appl.Microbiol.Biotechnol_88_885
PubMedID: 20676630
Gene_locus related to this paper: yarli-LIP8

Title : Fo shou san, an ancient herbal decoction prepared from rhizoma chuanxiong and radix angelicae sinensis, stimulates the production of hemoglobin and erythropoietin in cultured cells - Bi_2010_Planta.Med_76_1525
Author(s) : Bi CWC , Xie HQ , Xu L , Li J , Cheung AW , Zhu JT , Zheng YZ , Chen VP , Lau DT , Choi RC , Wang TJ , Dong TTX , Tsim KWK
Ref : Planta Med , 76 :1525 , 2010
Abstract : Fo Shou San (FSS) is an ancient herbal decoction comprised of Rhizoma Chuanxiong (RC; Chuanxiong) and Radix Angelicae Sinensis (RAS; Danggui) in a ratio of 2 : 3. It is mainly prescribed for patients having a blood deficiency. This combination is considered the most popular herb pair among Chinese medicines; however, the rationale of having these two chemically similar herbs within the decoction has historically not been made clear. Here, we attempted to reveal the chemical and biological properties of this decoction as a means to deduce its mechanism of action. The effects of FSS were determined in different cell culture models. With respect to stimulation of blood circulation, FSS inhibited ADP-mediated platelet aggregation in a dose-dependent manner. In order to reveal the hematopoietic effect of this decoction, FSS was applied onto cultured K562 human leukemia cells and Hep3B human hepatocellular carcinoma cells. Application of FSS in cultured K562 cells inhibited cell proliferation and subsequently induced the production of hemoglobin. Additionally, the mRNA expression of erythropoietin (EPO) was induced in a dose-dependent manner when FSS was applied to Hep3B cells. The current results reveal the effects of FSS in different cell models, paving a direction for mechanistic studies.
ESTHER : Bi_2010_Planta.Med_76_1525
PubMedSearch : Bi_2010_Planta.Med_76_1525
PubMedID: 20309798

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Genetic study of capsular switching between Neisseria meningitidis sequence type 7 serogroup A and C strains - Wang_2010_Infect.Immun_78_3883
Author(s) : Wang Q , Shao Z , Wang X , Gao Y , Li M , Xu L , Xu J , Wang L
Ref : Infect Immun , 78 :3883 , 2010
Abstract : Neisseria meningitidis is a leading cause of septicemia and meningitis worldwide. N. meningitidis capsular polysaccharides have been classified into 13 distinct serogroups which are defined by antibody reactivity and structural analysis, and the capsule plays an important role in virulence. Serogroups A, B, C, W135, and Y have been reported to be clinically important. Several newly identified serogroup C isolates belonging to the unique sequence type 7 (ST-7) were identified in China. Since most ST-7 isolates from China belonged to serogroup A, the newly identified ST-7 serogroup C strains were proposed to have arisen from those belonging to ST-7 serogroup A. In this study, six ST-7 serogroup C and three ST-7 serogroup A isolates were analyzed by pulsed-field gel electrophoresis to confirm their sequence type. In order to clarify the genetic basis of capsular switching between ST-7 serogroup A and C strains, the whole capsular gene clusters and surrounding genes of the two representative ST-7 strains belonging to serogroups A and C, respectively, were sequenced and compared. Potential recombination sites were analyzed using the RDP3 beta software, and recombination-related regions in two other ST-7 serogroup A and five ST-7 serogroup C strains were also sequenced and compared to the representative ST-7 serogroup A and C strain sequences.
ESTHER : Wang_2010_Infect.Immun_78_3883
PubMedSearch : Wang_2010_Infect.Immun_78_3883
PubMedID: 20624905
Gene_locus related to this paper: neime-r0tza2

Title : Genome sequence of the versatile fish pathogen Edwardsiella tarda provides insights into its adaptation to broad host ranges and intracellular niches - Wang_2009_PLoS.One_4_e7646
Author(s) : Wang Q , Yang M , Xiao J , Wu H , Wang X , Lv Y , Xu L , Zheng H , Wang S , Zhao G , Liu Q , Zhang Y
Ref : PLoS ONE , 4 :e7646 , 2009
Abstract : BACKGROUND: Edwardsiella tarda is the etiologic agent of edwardsiellosis, a devastating fish disease prevailing in worldwide aquaculture industries. Here we describe the complete genome of E. tarda, EIB202, a highly virulent and multi-drug resistant isolate in China. METHODOLOGY/PRINCIPAL FINDINGS: E. tarda EIB202 possesses a single chromosome of 3,760,463 base pairs containing 3,486 predicted protein coding sequences, 8 ribosomal rRNA operons, and 95 tRNA genes, and a 43,703 bp conjugative plasmid harboring multi-drug resistant determinants and encoding type IV A secretion system components. We identified a full spectrum of genetic properties related to its genome plasticity such as repeated sequences, insertion sequences, phage-like proteins, integrases, recombinases and genomic islands. In addition, analysis also indicated that a substantial proportion of the E. tarda genome might be devoted to the growth and survival under diverse conditions including intracellular niches, with a large number of aerobic or anaerobic respiration-associated proteins, signal transduction proteins as well as proteins involved in various stress adaptations. A pool of genes for secretion systems, pili formation, nonfimbrial adhesions, invasions and hemagglutinins, chondroitinases, hemolysins, iron scavenging systems as well as the incomplete flagellar biogenesis might feature its surface structures and pathogenesis in a fish body. CONCLUSION/SIGNIFICANCE: Genomic analysis of the bacterium offered insights into the phylogeny, metabolism, drug-resistance, stress adaptation, and virulence characteristics of this versatile pathogen, which constitutes an important first step in understanding the pathogenesis of E. tarda to facilitate construction of a practical effective vaccine used for combating fish edwardsiellosis.
ESTHER : Wang_2009_PLoS.One_4_e7646
PubMedSearch : Wang_2009_PLoS.One_4_e7646
PubMedID: 19865481
Gene_locus related to this paper: edwte-d0zav8 , edwte-d0zg19 , edwtf-e0t1p5 , edwte-d0za01 , edwte-d0z9v1

Title : Aspergillus niger lipase: Heterologous expression in Pichia pastoris, molecular modeling prediction and the importance of the hinge domains at both sides of the lid domain to interfacial activation - Shu_2009_Biotechnol.Prog_25_409
Author(s) : Shu Z , Duan M , Yang J , Xu L , Yan Y
Ref : Biotechnol Prog , 25 :409 , 2009
Abstract : Aspergillus niger lipase (ANL) is an important biocatalyst in the food processing industry. However, there is no report of its detailed three-dimensional structure because of difficulties in crystallization. In this article, based on experimental data and bioinformational analysis results, the structural features of ANL were simulated. Firstly, two recombinant ANLs expressed in Pichia pastoris were purified to homogeneity and their corresponding secondary structure compositions were determined by circular dichroism spectra. Secondly, the primary structure, the secondary structure and the three-dimensional structure of ANL were modeled by comparison with homologous lipases with known three-dimensional structures using the BioEdit software, lipase engineering database (http://www.led.uni-stuttgart.de/), PSIPRED server and SwissModel server. The predicted molecular structure of ANL presented typical features of the alpha/beta hydrolase fold including positioning of the putative catalytic triad residues and the GXSXG signature motif. Comparison of the predicted three-dimensional structure of ANL with the X-ray three-dimensional structure of A. niger feruloyl esterase showed that the functional difference of interfacial activation between lipase and esterase was concerned with the difference in position of the lid. Our three-dimensional model of ANL helps to modify lipase structure by protein engineering, which will further expand the scope of application of ANL.
ESTHER : Shu_2009_Biotechnol.Prog_25_409
PubMedSearch : Shu_2009_Biotechnol.Prog_25_409
PubMedID: 19248178

Title : Effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on beta-cell function in patients with type 2 diabetes: a model-based approach - Xu_2008_Diabetes.Obes.Metab_10_1212
Author(s) : Xu L , Man CD , Charbonnel B , Meninger G , Davies MJ , Williams-Herman D , Cobelli C , Stein PP
Ref : Diabetes Obes Metab , 10 :1212 , 2008
Abstract : PURPOSE: The purpose of this exploratory analysis was to assess the effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on pancreatic beta-cell function using a model-based analysis. METHODS: Data for this analysis were from three large, placebo-controlled clinical studies that examined sitagliptin 100 mg q.d. as add-on to metformin therapy or as monotherapy over 18 or 24 weeks. In these studies, subsets of patients consented to undergo extensive blood sampling as part of a nine-point meal tolerance test performed at baseline and study end-point. Blood samples were collected at -10, 0, 10, 20, 30, 60, 90, 120 and 180 min relative to the start of a meal and subsequently were assayed for plasma glucose and serum C-peptide concentrations. Parameters for beta-cell function were calculated using the C-peptide minimal model, which estimates insulin secretion rate (ISR) and partitions the ISR into basal (Phi(b); ISR at basal glucose concentrations), static (Phi(s); ISR at above basal glucose concentrations following a meal) and dynamic (Phi(d); ISR in response to the rate of increase in above basal glucose concentrations following a meal) components. The total responsivity index (Phi(total); average ISR over the average glucose concentration) is calculated as a function of Phi(s), Phi(d )and Phi(b. )Insulin sensitivity was assessed with a validated composite index (ISI). Disposition indices (DI), which assess insulin secretion in the context of changes in insulin sensitivity, were calculated as the product of Phiand ISI. RESULTS: When administered in combination with ongoing metformin therapy or as monotherapy, sitagliptin was associated with substantial reductions in postprandial glycaemic excursion following a meal challenge relative to placebo. Sitagliptin produced significant (p < 0.05 vs. placebo) improvements in Phi(s )and Phi(total), regardless of treatment regimen (add-on to metformin or as monotherapy). For Phi(d), there was a numerical, but not statistically significant, improvement with sitagliptin relative to placebo. Treatment with sitagliptin increased Phi(b), but the difference relative to placebo was only significant with monotherapy. ISI was not significantly different between sitagliptin and placebo. The DIs for the static, dynamic and total measures were significantly (p < 0.05) increased with sitagliptin treatment relative to placebo. CONCLUSIONS: In this model-based analysis, sitagliptin improved beta-cell function relative to placebo in both fasting and postprandial states in patients with type 2 diabetes.
ESTHER : Xu_2008_Diabetes.Obes.Metab_10_1212
PubMedSearch : Xu_2008_Diabetes.Obes.Metab_10_1212
PubMedID: 18476982

Title : Ion-pair liquid-liquid-liquid microextraction of nerve agent degradation products followed by capillary electrophoresis with contactless conductivity detection - Xu_2008_J.Chromatogr.A_1205_158
Author(s) : Xu L , Gong XY , Lee HK , Hauser PC
Ref : Journal of Chromatography A , 1205 :158 , 2008
Abstract : The four nerve agent degradation products methylphosphonic acid (MPA), ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA) and cyclohexyl methylphosphonic acid (CMPA) have been successfully extracted from aqueous sample solution by ion-pair liquid-liquid-liquid microextraction. In this procedure, the target analytes in the sample solution were converted into their ion-pair complexes with tri-n-butyl amine and then extracted by an organic solvent (1-octanol) layer on top of the sample solution. Simultaneously, the analytes were back-extracted into a drop of an aqueous acceptor solution which was suspended in the organic phase at a microsyringe needle tip. The factors influential to extraction: type of organic solvent, type of ion-pair reagent and its concentration, pH values of sample solution and acceptor aqueous phase, stirring rate and extraction time were investigated in detail. After extraction, the drop of the acceptor solution was withdrawn into the syringe and injected into a capillary electrophoresis system for analysis. Using contactless conductivity detection, direct quantification of these compounds is possible. Moreover, large-volume sample injection was employed for further preconcentration. Improvements in the limits of detection between 2.5 and 4 orders of magnitude could be achieved and concentrations at the ng/mL level can be determined. This newly established approach was successfully applied to a spiked river water sample.
ESTHER : Xu_2008_J.Chromatogr.A_1205_158
PubMedSearch : Xu_2008_J.Chromatogr.A_1205_158
PubMedID: 18721925

Title : Neurite outgrowth and in vivo sensory innervation mediated by a Ca(V)2.2-laminin beta 2 stop signal - Sann_2008_J.Neurosci_28_2366
Author(s) : Sann SB , Xu L , Nishimune H , Sanes JR , Spitzer NC
Ref : Journal of Neuroscience , 28 :2366 , 2008
Abstract : Axons and dendrites of developing neurons establish distributed innervation patterns enabling precise discrimination in sensory systems. We describe the role of the extracellular matrix molecule, laminin beta2, interacting with the Ca(V)2.2 calcium channel in establishing appropriate sensory innervation. In vivo, Ca(V)2.2 is expressed on the growth cones of Xenopus laevis sensory neurites and laminin beta2 is expressed in the skin. Culturing neurons on a laminin beta2 substrate inhibits neurite outgrowth in a specific and calcium-dependent manner. Blocking signaling between laminin beta2 and Ca(V)2.2 leads to increased numbers of sensory terminals in vivo. These findings suggest that interactions between extracellular matrix molecules and calcium channels regulate connectivity in the developing nervous system.
ESTHER : Sann_2008_J.Neurosci_28_2366
PubMedSearch : Sann_2008_J.Neurosci_28_2366
PubMedID: 18322083

Title : [Cell surface display of Yarrowia lipolytica lipase Lip2 in Saccharomyces cerevisiae with a-agglutinin as carrier protein] - Liu_2008_Wei.Sheng.Wu.Xue.Bao_48_1543
Author(s) : Liu W , Xu L , Zhao H , Yang J , Yan Y
Ref : Wei Sheng Wu Xue Bao , 48 :1543 , 2008
Abstract : OBJECTIVE: In order to display extracellular.lipase Lip2 from Yarrowia lipolytica on the surface of yeast Saccharomyces cerevisiae for whole cell catalysts. METHODS: The mature Lip2 encoding fragment was amplified from Yarrowia lipolytica total DNA, and was inserted into the 3'terminal of AGA2 to give the plasmid pCTLIP2 for surface display of Lip2. Olive oil, tributyrin and p-nitrophenyl palmitate (pNPP) were used as substrates to measure lipase activity. Moreover, the characterization of displayed lipase and its free form was analyzed. RESULTS: The surface displayed lipase was confirmed to be active towards olive oil, tributyrin and p-nitrophenyl palmitate (pNPP), and reached its highest expression level at 182 U/g dry cell after induced by galactose for 72h. The optimum temperature of cell surface displayed Lip2 was 40 degrees C After incubated at 50 degrees C for 4h, the surface displayed lipase retained 23.2% of its full activity, improved a little compared to free Lip2. The surface displayed lipase showed a preference to medium-chain and long-chain fatty acids p-nitrophenyl esters (C8-C16). CONCLUSION: The cell surface display system based on a-agglutinin is an effective system for displaying Lip2, and the whole cell EBY100-pCTLIP2 will be probably suited to a different range of applications.
ESTHER : Liu_2008_Wei.Sheng.Wu.Xue.Bao_48_1543
PubMedSearch : Liu_2008_Wei.Sheng.Wu.Xue.Bao_48_1543
PubMedID: 19149173

Title : [Cloning and overexpression of lipase gene from Geotrichum candidum Y162] - Yan_2008_Wei.Sheng.Wu.Xue.Bao_48_184
Author(s) : Yan J , Yang J , Xu L , Yan Y
Ref : Wei Sheng Wu Xue Bao , 48 :184 , 2008
Abstract : By means of bioinformatics, we aligned nucleotide sequence of reported lipase gene from Geotrichum. Primers were designed based on the conservative nucleotide sequence, and the lipase gene of G. candidum Y162 was cloned for the first time in China. Nucleotide sequencing revealed that the open reading frame has 1692 nucleotides without any introns, encoding 563 amino acid residues including a signal sequence of 19 amino acid residues, which is 86% identical to lipase I of G. fermentans. Subsequently, we cloned the lipase gene into expression vector pPIC9K, and then transformed into Pichia pastoris GS115. Cultures of recombined P. pastoris accumulated active enzyme in the supernatant to levels of 55 U/mL after induction for 96 hours in shake flasks. The purified lipase exhibited maximum activity at 50 degrees C and pH 8.0, and was stable between pH 6.0 and 10.0 and below 60 degrees C. Lipase activity was compatible with the presence of organic solvents such as methanol, n-heptane, hexane, cyclohexane, glycerol, benzene and diethyl ether. Lipase showed hydrolysis preference for triacylglycerol substrates containing cis-9 unsaturated fatty acid. The results suggest that the lipase could be a candidate for industrial applications.
ESTHER : Yan_2008_Wei.Sheng.Wu.Xue.Bao_48_184
PubMedSearch : Yan_2008_Wei.Sheng.Wu.Xue.Bao_48_184
PubMedID: 18437999

Title : Nonaqueous and aqueous-organic media for the enantiomeric separations of neutral organophosphorus pesticides by CE - Huang_2007_Electrophoresis_28_2758
Author(s) : Huang L , Lin J , Xu L , Chen G
Ref : Electrophoresis , 28 :2758 , 2007
Abstract : The enantiomeric separation of some poorly water-soluble organophosphorus pesticides (OPs) has been investigated using nonaqueous solvent and aqueous-organic solvent systems. In this work, sodium cholate (SC) either with SDS or gamma-CD was used to achieve enantiomeric separations of four neutral and poorly water-soluble OPs, i.e., profenofos, prothiofos, sulprofos, and pyraclofos. Electrophoretic medium consisted of a mixture of methanol (MeOH) with ACN (4:1 v/v) or a mixture of MeOH with H(2)O and ACN (5:4:1 v/v/v). On one hand, NACE was applied for enantiomeric separation of pyraclofos using a large amount of chiral and achiral surfactants (SC and SDS). On the other hand, H(2)O was added to act as a solvent additive to increase the solubility of gamma-CD in the organic solvents such as MeOH and ACN, in which the solubility of gamma-CD was very low. The presence of H(2)O was found to be particularly useful for the enantiomeric separation of profenofos, prothiofos, and sulprofos. In this way, the range of application of the neutral CDs in CE has been extended. In addition, SC was used as the only electrolyte. The proposed method has been applied for the analysis of soil samples.
ESTHER : Huang_2007_Electrophoresis_28_2758
PubMedSearch : Huang_2007_Electrophoresis_28_2758
PubMedID: 17592615

Title : Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus - Raz_2006_Diabetologia_49_2564
Author(s) : Raz I , Hanefeld M , Xu L , Caria C , Williams-Herman D , Khatami H
Ref : Diabetologia , 49 :2564 , 2006
Abstract : AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA(1c) > or =7% and < or =10%) on exercise and diet.
METHODS: A total of 521 patients aged 27-76 years with a mean baseline HbA(1c) of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks. The efficacy analysis was based on an all-patients-treated population using an analysis of covariance, excluding data obtained after glycaemic rescue.
RESULTS: After 18 weeks, HbA(1c) was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo (placebo-subtracted HbA(1c) reduction: -0.60% and -0.48%, respectively). Sitagliptin also significantly decreased fasting plasma glucose relative to placebo. Patients with higher baseline HbA(1c) (> or =9%) experienced greater placebo-subtracted HbA(1c) reductions with sitagliptin (-1.20% for 100 mg and -1.04% for 200 mg) than those with HbA(1c) <8% (-0.44% and -0.33%, respectively) or > or =8% to 8.9% (-0.61% and -0.39%, respectively). Homeostasis model assessment beta cell function index and fasting proinsulin:insulin ratio, markers of insulin secretion and beta cell function, were significantly improved with sitagliptin. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight. CONCLUSIONS/INTERPRETATION: Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet.
ESTHER : Raz_2006_Diabetologia_49_2564
PubMedSearch : Raz_2006_Diabetologia_49_2564
PubMedID: 17001471

Title : Roles for nicotinic acetylcholine receptor subunit large cytoplasmic loop sequences in receptor expression and function - Kuo_2005_J.Pharmacol.Exp.Ther_314_455
Author(s) : Kuo YP , Xu L , Eaton JB , Zhao L , Wu J , Lukas RJ
Ref : Journal of Pharmacology & Experimental Therapeutics , 314 :455 , 2005
Abstract : To evaluate possible physiological roles of the large cytoplasmic loops (C2) and neighboring transmembrane domains of nicotinic acetylcholine receptor (nAChR) subunits, we generated novel fusion constructs in which human nAChR alpha4, beta2, or beta4 subunit C2 or C2 and neighboring sequences were replaced by corresponding sequences from the mouse serotonin type 3A (5-HT3A) receptor subunit. Following stable expression in human SH-EP1 cells, we found that extensive sequence substitutions involving third and fourth transmembrane domains and neighboring "proximal" C2 sequences (e.g., beta2 H322-V335 and V449-R460) did not allow functional expression of nAChR containing chimeric subunits. However, expression of functional nAChR was achieved containing wild-type alpha4 subunits and chimeric beta2 (beta2chi) subunits whose "nested" C2 domain sequences K336-S448 were replaced with the corresponding 5-HT3A subunit sequences. Whereas these findings suggested indispensable roles for M3/M4 transmembrane and/or proximal C2 sequences in alpha4beta2-nAChR function, nested C2 sequences in the beta2 subunit are not essential for functional receptor expression. Ligand-binding analyses also revealed only subtle differences in pharmacological profiles of alpha4beta2-nAChR compared with alpha4beta2chi-nAChR. Nevertheless, there was heightened emergence of agonist-mediated self-inhibition of alpha4beta2chi function, greater sensitivity to functional blockade by a number of antagonists, and faster and more complete acute desensitization of alpha4beta2chi-nAChR than for alpha4beta2-nAChR. These studies are consistent with unexpected roles of nested C2 sequences in nAChR function.
ESTHER : Kuo_2005_J.Pharmacol.Exp.Ther_314_455
PubMedSearch : Kuo_2005_J.Pharmacol.Exp.Ther_314_455
PubMedID: 15833891

Title : Electrophysiological, pharmacological, and molecular evidence for alpha7-nicotinic acetylcholine receptors in rat midbrain dopamine neurons - Wu_2004_J.Pharmacol.Exp.Ther_311_80
Author(s) : Wu J , George AA , Schroeder KM , Xu L , Marxer-Miller S , Lucero L , Lukas RJ
Ref : Journal of Pharmacology & Experimental Therapeutics , 311 :80 , 2004
Abstract : Dopamine (DA) neurons located in the mammalian midbrain have been generally implicated in reward and drug reinforcement and more specifically in nicotine dependence. However, roles played by nicotinic acetylcholine receptors, including those composed of alpha7-subunits [alpha7-nicotinic acetylcholine receptors (nAChRs)], in modulation of DA signaling and in nicotine dependence are not clearly understood. Although midbrain slice recording has been used previously to identify functional alpha7-nAChRs, these preparations are not optimally designed for extremely rapid and reproducible drug application, and rapidly desensitized, alpha7-nAChR-mediated currents may have been underestimated or not detected. Here, we use patch-clamp, whole-cell current recordings from single neurons acutely dissociated from midbrain nuclei and having features of DA neurons to characterize acetylcholine-induced, inward currents that rapidly activate and desensitize, are mimicked by the alpha7-nAChR-selective agonist, choline, blocked by the alpha7-nAChR-selective antagonists, methyllycaconitine and alpha-bungarotoxin, and are similar to those of heterologously expressed, human alpha7-nAChRs. We also use reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunocytochemical staining to demonstrate nAChR alpha7 subunit gene expression as message and protein in the rat substantia nigra pars compacta and ventral tegmental area. Expression of alpha7 subunit message and of alpha7-nAChR-mediated responses is developmentally regulated, with both being absent in samples taken from rats at postnatal day 7, but later becoming present and increasing over the next 2 weeks. Collectively, this electrophysiological, pharmacological, and molecular evidence indicates that nAChR alpha7 subunits and functional alpha7-nAChRs are expressed somatodendritically by midbrain DA neurons, where they may play important physiological roles and contribute to nicotine reinforcement and dependence.
ESTHER : Wu_2004_J.Pharmacol.Exp.Ther_311_80
PubMedSearch : Wu_2004_J.Pharmacol.Exp.Ther_311_80
PubMedID: 15178698

Title : beta-Amyloid directly inhibits human alpha4beta2-nicotinic acetylcholine receptors heterologously expressed in human SH-EP1 cells - Wu_2004_J.Biol.Chem_279_37842
Author(s) : Wu J , Kuo YP , George AA , Xu L , Hu J , Lukas RJ
Ref : Journal of Biological Chemistry , 279 :37842 , 2004
Abstract : Amyloid-beta (Abeta) accumulation and aggregation are thought to contribute to the pathogenesis of Alzheimer's disease (AD). In AD, there is a selective decrease in the numbers of radioligand binding sites corresponding to the most abundant nicotinic acetylcholine receptor (nAChR) subtype, which contains human alpha4 and beta2 subunits (halpha4beta2-nAChR). However, the relationships between these phenomena are uncertain, and effects of Abeta on halpha4beta2-nAChR function have not been investigated in detail. We first confirmed expression of halpha4 and hbeta2 subunits as messenger RNA in transfected, human SHEP1 cells by reverse transcription-polymerase chain reaction and mRNA fluorescence in situ hybridization analyses. Immunoprecipitation Western analyses confirmed alpha4 and beta2 subunit protein expression and co-assembly. Whole cell current recording demonstrated heterologous expression in SH-EP1-halpha4beta2 cells of functional halpha4beta2-nAChRs with characteristic responses to nicotinic agonists or antagonists. Nicotine-induced whole cell currents were suppressed by Abeta(1-42) in a dose-dependent manner. Functional inhibition was selective for Abeta(1-42) compared with the functionally inactive, control peptide Abeta(40-1).Abeta(1-42)-mediated inhibition of halpha4beta2-nAChR function was non-competitive, voltage-independent, and use-independent. Pre-loading of cells with guanyl-5'-yl thiophosphate failed to prevent Abeta(1-42)-induced inhibition, suggesting that down-regulation of halpha4beta2-nAChR function by Abeta(1-42) is not mediated by nAChR internalization. Sensitivity to Abeta(1-42) antagonism at 1 nm was evident for halpha4beta2-nAChRs, but not for heterologously expressed human alpha7-nAChRs, although both nAChR subtypes were functionally inhibited by 100 nm Abeta(1-42), with the magnitude of functional block being higher for 100 nm Abeta(1-42) acting on halpha7-nAChRs. These findings suggest that halpha4beta2-nAChRs are sensitive and perhaps pathophysiologically relevant targets for Abeta neurotoxicity in AD.
ESTHER : Wu_2004_J.Biol.Chem_279_37842
PubMedSearch : Wu_2004_J.Biol.Chem_279_37842
PubMedID: 15234980

Title : Intermediate myasthenia syndrome following acute organophosphates poisoning--an analysis of 21 cases - He_1998_Hum.Exp.Toxicol_17_40
Author(s) : He F , Xu H , Qin F , Xu L , Huang J , He X
Ref : Hum Exp Toxicol , 17 :40 , 1998
Abstract : 1. Twenty-one cases out of 272 patients of acute organophosphates poisoning were diagnosed as intermediate syndrome (IMS) with a prevalence at 7.7%. The responsible OP insecticides included parathion, omethoate and some OP containing pesticide mixtures. IMS occurred mainly in severe OP poisoning patients who recovered from the acute cholinergic crisis at 7-75 h after the onset of acute poisoning. 2. Muscular weakness appeared in the following three categories of muscles: (1) neck flexors and proximal limb muscles; (2) muscles innervated by motor cranial nerves and/or (3) respiratory muscles. Blood acetylcholinesterase activity was persistently inhibited. Electroneuromyography (ENMG) with repetitive nerve stimulation (RNS) at frequencies of 20 Hz or 30 Hz in seven patients showed decrements of common muscle action potentials during the presence of myasthenia in five patients and became normal when their muscle strength recovered. 3. Mild IMS recovered within 2-7 days and had a favorable prognosis. Severe IMS patients with respiratory paralysis needed immediate endotracheal intubation and mechanical ventilation. Recovery of weakness of the respiratory muscles and proximal limb muscles took longer, the slowest being 30 days. Four of the patients died of respiratory paralysis and the fatality rate was 19%. 4. The mechanism of IMS remains to be further investigated. The RNS/ENMG changes indicate a post-synaptic block at the neuromuscular junctions. 5. In order to promote the recognition of this syndrome, we proposed to name the syndrome as Intermediate Myasthenia Syndrome (IMS).
ESTHER : He_1998_Hum.Exp.Toxicol_17_40
PubMedSearch : He_1998_Hum.Exp.Toxicol_17_40
PubMedID: 9491337