Yan X

References (55)

Title : Infiltration of porcine pancreatic lipase into magnetic hierarchical mesoporous UiO-66-NH(2) metal-organic frameworks for efficient detoxification of patulin from apple juice - Yan_2024_Food.Chem_431_137172
Author(s) : Yan X , Chen K , Jia H , Zhao Q , Du G , Guo Q , Chen H , Yuan Y , Yue T
Ref : Food Chem , 431 :137172 , 2024
Abstract : Patulin (PAT) is a mycotoxin known to globally contaminate fruits. The economic losses and health hazards caused by PAT desires a safe and efficient strategy for detoxifying PAT. Here, a magnetic core-shell hierarchical mesoporous metal-organic framework (Fe(3)O(4)@HMUiO-66-NH(2)) was synthesized via a salt-assisted nanoemulsion guided assembly method. This mesoporous structure (centered at 4.25 nm) allowed porcine pancreatic lipase (PPL) to infiltrate into the MOF shell at an immobilized amount of 255 mg/g, providing protection for PPL and enabling rapid separation and recovery. Compared with free PPL, PPL/Fe(3)O(4)@HMUiO-66-NH(2) at 70 degreesC possessed 4.7 folds improved thermal stability in terms of half-life. The detoxification rates of immobilized enzyme for PAT in neutral water, acidic water, and apple juice were 99.6%, 60.9%, and 52.6%, respectively. Moreover, the so designed PPL/Fe(3)O(4)@HMUiO-66-NH(2) showed extraordinary storage stability, reusability, and biocompatibility. Crucially, the quality of apple juice did not change significantly after PPL/Fe(3)O(4)@HMUiO-66-NH(2) treatment, which facilitated its application in apple juice. The magnetic core-shell mesoporous structure along with the revealed mechanism of immobilized enzyme detoxification of PAT provide tremendous opportunity for designing a safe and efficient PAT detoxification method.
ESTHER : Yan_2024_Food.Chem_431_137172
PubMedSearch : Yan_2024_Food.Chem_431_137172
PubMedID: 37603997

Title : Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry - Su_2024_Anal.Chem__
Author(s) : Su L , Gao K , Tian Y , Xiao X , Lu C , Xu J , Yan X
Ref : Analytical Chemistry , : , 2024
Abstract : Monitoring mitochondrial esterase activity is crucial not only for investigating mitochondrial metabolism but also for assessing the effectiveness of mitochondrial-targeting prodrugs. However, accurately detecting esterase activity within mitochondria poses challenges due to its ubiquitous presence in cells and the uncontrolled localization of fluorogenic probes. To overcome this hurdle and reveal variations among different mitochondria, we isolated mitochondria and preserved their activity and functionality in a buffered environment. Subsequently, we utilized a laboratory-built nano-flow cytometer in conjunction with an esterase-responsive calcein-AM fluorescent probe to measure the esterase activity of individual mitochondria. This approach enabled us to investigate the influence of temperature, pH, metal ions, and various compounds on the mitochondrial esterase activity without any interference from other cellular constituents. Interestingly, we observed a decline in the mitochondrial esterase activity following the administration of mitochondrial respiratory chain inhibitors. Furthermore, we found that mitochondrial esterase activity was notably higher in the presence of a high concentration of ATP compared to that of ADP and AMP. Additionally, we noticed a correlation between elevated levels of complex IV and increased mitochondrial esterase activity. These findings suggest a functional connection between the mitochondrial respiratory chain and mitochondrial esterase activity. Moreover, we detected an upsurge in mitochondrial esterase activity during the early stages of apoptosis, while cellular esterase activity decreased. This highlights the significance of analyzing enzyme activity within specific organelle subregions. In summary, the integration of a nano-flow cytometer and fluorescent dyes introduces a novel method for quantifying mitochondrial enzyme activity with the potential to uncover the alterations and unique functions of other mitochondrial enzymes.
ESTHER : Su_2024_Anal.Chem__
PubMedSearch : Su_2024_Anal.Chem__
PubMedID: 38173421

Title : Novel polyurethane-degrading cutinase BaCut1 from Blastobotrys sp. G-9 with potential role in plastic bio-recycling - Jiang_2024_J.Hazard.Mater_472_134493
Author(s) : Jiang Z , Chen X , Xue H , Li Z , Lei J , Yu M , Yan X , Cao H , Zhou J , Liu J , Zheng M , Dong W , Li Y , Cui Z
Ref : J Hazard Mater , 472 :134493 , 2024
Abstract : Environmental pollution caused by plastic waste has become global problem that needs to be considered urgently. In the pursuit of a circular plastic economy, biodegradation provides an attractive strategy for managing plastic wastes, whereas effective plastic-degrading microbes and enzymes are required. In this study, we report that Blastobotrys sp. G-9 isolated from discarded plastic in landfills is capable of depolymerizing polyurethanes (PU) and poly (butylene adipate-co-terephthalate) (PBAT). Strain G-9 degrades up to 60% of PU foam after 21 days of incubation at 28 degC by breaking down carbonyl groups via secretory hydrolase as confirmed by structural characterization of plastics and degradation products identification. Within the supernatant of strain G-9, we identify a novel cutinase BaCut1, belonging to the esterase family, that can reproduce the same effect. BaCut1 demonstrates efficient degradation toward commercial polyester plastics PU foam (0.5 mg enzyme/25 mg plastic) and agricultural film PBAT (0.5 mg enzyme/10 mg plastic) with 50% and 18% weight loss at 37 degC for 48 h, respectively. BaCut1 hydrolyzes PU into adipic acid as a major end-product with 42.9% recovery via ester bond cleavage, and visible biodegradation is also identified from PBAT, which is a beneficial feature for future recycling economy. Molecular docking, along with products distribution, elucidates a special substrate-binding modes of BaCut1 with plastic substrate analogue. BaCut1-mediated polyester plastic degradation offers an alternative approach for managing PU plastic wastes through possible bio-recycling.
ESTHER : Jiang_2024_J.Hazard.Mater_472_134493
PubMedSearch : Jiang_2024_J.Hazard.Mater_472_134493
PubMedID: 38696960
Gene_locus related to this paper: 9asco-BaCut1

Title : A randomized, double-blind, placebo controlled, phase 3 trial to evaluate the efficacy and safety of cetagliptin added to ongoing metformin therapy in patients with uncontrolled type 2 diabetes with metformin monotherapy - Ji_2023_Diabetes.Obes.Metab_25_3788
Author(s) : Ji L , Lu J , Gao L , Yan X , Li J , Cheng Z , Zhang L , Tian J , Li P , Bai J , Xie D , Zhao J , Ding J , Yu Q , Wang T
Ref : Diabetes Obes Metab , 25 :3788 , 2023
Abstract : AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100mg, cetagliptin 50mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50mg and placebo were switched to cetagliptin 100mg for 28weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17+/-0.794%, -1.23+/-0.896% in cetagliptin 100mg and 50mg plus metformin group, respectively. No difference was observed between the cetagliptin 100mg and 50mg plus metformin group. Patients with higher baseline HbA1c levels (<=8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100mg (49.4%) and cetagliptin 50mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment beta-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
ESTHER : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedSearch : Ji_2023_Diabetes.Obes.Metab_25_3788
PubMedID: 37724698

Title : Elucidation of Carboxylesterase Mediated Pharmacokinetic Interactions between Irinotecan and Oroxylin A in Rats via Physiologically Based Pharmacokinetic Modeling - Zhang_2023_Pharm.Res__
Author(s) : Zhang J , Zhang Y , Lai YS , Song Q , Xiao M , Ji X , Yan X , Zuo Z
Ref : Pharm Res , : , 2023
Abstract : PURPOSE: Our previous screening studies identified Oroxylin A (OXA) as a strong inhibitor on the carboxyolesterase mediated hydrolysis of irinotecan to SN-38. The current study employed a whole-body physiologically based pharmacokinetic (PBPK) modeling approach to investigate the underlying mechanisms of the carboxylesterase-mediated pharmacokinetics interactions between irinotecan and OXA in rats. METHODS: Firstly, rats received irinotecan intravenous treatment at 35 micromol/kg without or with oral OXA pretreatment (2800 micromol/kg) daily for 5 days. On day 5, blood and tissues were collected for analyses of irinotecan/SN-38 concentrations and carboxylesterase expression. In addition, effects of OXA on the enzyme kinetics of irinotecan hydrolysis and unbound fractions of irinotecan and SN-38 in rat plasma, liver and intestine were also determined. Finally, a PBPK model that integrated the physiological parameters, enzyme kinetics, and physicochemical properties of irinotecan and OXA was developed. RESULTS: Our PBPK model could accurately predict the pharmacokinetic profiles of irinotecan/SN-38, with AUC(0-6h) and C(max) values within +/-27% of observed values. When OXA was included as a carboxylesterase inhibitor, the model could also predict the irinotecan/SN-38 plasma concentrations within twofold of those observed. In addition, the PBPK model indicated inhibition of carboxylesterase-mediated hydrolysis of irinotecan in the intestinal mucosa as the major underlying mechanism for the pharmacokinetics interactions between irinotecan and OXA. CONCLUSION: A whole-body PBPK model was successfully developed to not only predict the impact of oral OXA pretreatment on the pharmacokinetics profiles of irinotecan but also reveal its inhibition on the intestinal carboxylesterase as the major underlying mechanism.
ESTHER : Zhang_2023_Pharm.Res__
PubMedSearch : Zhang_2023_Pharm.Res__
PubMedID: 37667147

Title : Exploring the inhibitory potential of KPHs-AL-derived GLLF peptide on pancreatic lipase and cholesterol esterase activities - Huang_2023_Food.Chem_439_138108
Author(s) : Huang F , Dai Q , Zheng K , Ma Q , Liu Y , Jiang S , Jiang W , Yan X
Ref : Food Chem , 439 :138108 , 2023
Abstract : The effective modulation of pancreatic lipase and cholesterol esterase activities proves critical in maintaining circulatory triglycerides and cholesterol levels within physiological boundaries. In this study, peptides derived from KPHs-AL, produced through the enzymatic hydrolysis of skipjack tuna dark muscle using alkaline protease, have a specific inhibitory effect on pancreatic lipase and cholesterol esterase. It is hypothesized that these peptides target and modulate the activities of enzymes by inducing conformational changes within their binding pockets, potentially impacting the catalytic functions of both pancreatic lipase and cholesterol esterase. Results revealed these peptides including AINDPFIDL, FLGM, GLLF and WGPL, were found to nestle into the binding site groove of pancreatic lipase and cholesterol esterase. Among these, GLLF stood out, demonstrating potent inhibition with IC(50) values of 0.1891 mg/mL and 0.2534 mg/mL for pancreatic lipase and cholesterol esterase, respectively. The kinetics studies suggested that GLLF competed effectively with substrates for the enzyme active sites. Spectroscopic analyses, including ultraviolet-visible, fluorescence quenching, and circular dichroism, indicated that GLLF binding induced conformational changes within the enzymes, likely through hydrogen bond formation and hydrophobic interactions, thereby increasing structural flexibility. Molecular docking and molecular dynamics simulations supported these findings, showing GLLF's stable interaction with vital active site residues. These findings position GLLF as a potent inhibitor of key digestive enzymes, offering insights into its role in regulating lipid metabolism and highlighting its potential as functional ingredient.
ESTHER : Huang_2023_Food.Chem_439_138108
PubMedSearch : Huang_2023_Food.Chem_439_138108
PubMedID: 38061297

Title : 4-Methylbenzylidene camphor triggers estrogenic effects via the brain-liver-gonad axis in zebrafish larvae - Xian_2023_Environ.Pollut__122260
Author(s) : Xian H , Li Z , Ye R , Dai M , Feng Y , Bai R , Guo J , Yan X , Yang X , Chen D , Huang Z
Ref : Environ Pollut , :122260 , 2023
Abstract : 4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 microg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (eralpha) mRNA, and an interaction between 4-MBC and ERalpha suggested ERalpha's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development.
ESTHER : Xian_2023_Environ.Pollut__122260
PubMedSearch : Xian_2023_Environ.Pollut__122260
PubMedID: 37506809

Title : Comparative Genomic Analysis of Carbofuran-Degrading Sphingomonads Reveals the Carbofuran Catabolism Mechanism in Sphingobium sp. Strain CFD-1 - Jiang_2022_Appl.Environ.Microbiol__e0102422
Author(s) : Jiang W , Zhang M , Gao S , Zhu Q , Qiu J , Yan X , Xin F , Jiang M , Hong Q
Ref : Applied Environmental Microbiology , :e0102422 , 2022
Abstract : The worldwide use of the carbamate insecticide carbofuran has caused considerable concern about its environmental fate. Degradation of carbofuran by Sphingobium sp. strain CFD-1 is initiated via the hydrolysis of its ester bond by carbamate hydrolase CehA to form carbofuran phenol. In this study, another carbofuran-degrading strain, Sphingobium sp. CFD-2, was isolated. Subsequently, a cfd gene cluster responsible for the catabolism of carbofuran phenol was predicted by comparing the genomes of strains CFD-1, CFD-2, and Novosphingobium sp. strain KN65.2. The key genes verified to be involved in the catabolism of carbofuran phenol within the cfd cluster include the hydroxylase gene cfdC, epoxide hydrolase gene cfdF, and ring cleavage dioxygenase gene cfdE and are responsible for the successive conversion of carbofuran phenol, resulting in complete ring cleavage. These carbofuran-catabolic genes (cehA and the cfd cluster) are distributed on two plasmids in strain CFD-1 and are highly conserved among the carbofuran-degrading sphingomonad strains. The mobile genetic element IS6100 flanks cehA and the cfd gene cluster, indicating the importance of horizontal gene transfer in the formation of carbofuran degradation gene clusters. The elucidation of the molecular mechanism of carbofuran catabolism provides insights into the evolutionary scenario of the conserved carbofuran catabolic pathway. IMPORTANCE Owing to the extensive use of carbofuran over the past 50 years, bacteria have evolved catabolic pathways to mineralize this insecticide, which plays an important role in eliminating carbofuran residue in the environment. In this study, the cfd gene cluster, responsible for the catabolism of carbofuran phenol, was predicted by comparing sphingomonad genomes. The function of key enzymatic genes in this gene cluster was identified. Furthermore, the carbamate hydrolase gene cehA and the cfd gene cluster are highly conserved in different carbofuran-degrading strains. Additionally, the horizontal gene transfer elements flanking the cfd gene cluster were investigated. These findings help elucidate the molecular mechanism of microbial carbofuran degradation and enhance our understanding of the evolutionary mechanism of the carbofuran catabolic pathway.
ESTHER : Jiang_2022_Appl.Environ.Microbiol__e0102422
PubMedSearch : Jiang_2022_Appl.Environ.Microbiol__e0102422
PubMedID: 36314801

Title : Expression and characterization of a novel lipase from Bacillus licheniformis NCU CS-5 for application in enhancing fatty acids flavor release for low-fat cheeses - Zhao_2022_Food.Chem_368_130868
Author(s) : Zhao J , Ma M , Yan X , Zhang G , Xia J , Zeng G , Tian W , Bao X , Zeng Z , Yu P , Gong D
Ref : Food Chem , 368 :130868 , 2022
Abstract : A novel lipase from Bacillus licheniformis NCU CS-5 was expressed in different Escherichia coli cells. The recombinant enzyme achieved a high activity (161.74 U/mL) with protein concentration of 0.27 mg/mL under optimal conditions at the large-scale expression of 12 h. The recombinant lipase showed optimal activity at 40 degC and pH 10.0, and maintained more than 80% relative activity after 96 h of incubation at pH 9.0-10.0. This typical alkaline lipase was activated under medium temperature conditions (30 and 45 degC for 96 h). The lipase exhibited a degree of adaptability in various organic solvents and metal ions, and showed high specificity towards triglycerides with short and medium chain fatty acids. Among different substrates, the lipase showed the strongest binding affinity towards pNPP (Km = 0.674 mM, Vmax = 950.196 microM/min). In the experiments of its application in enhancing fatty acids flavor release for low-fat cheeses, the lipase was found to hydrolyze cheeses and mainly increase the contents of butyric acid, hexanoic acid, caprylic acid and decanoic acid. The results from NMR and GC provided the possibility of enhancing fatty acids flavor released from low-fat cheeses by the lipolysis method.
ESTHER : Zhao_2022_Food.Chem_368_130868
PubMedSearch : Zhao_2022_Food.Chem_368_130868
PubMedID: 34438173
Gene_locus related to this paper: bacld-q65hr4

Title : Immobilization of lipase on beta-cyclodextrin grafted and aminopropyl-functionalized chitosan\/Fe(3)O(4) magnetic nanocomposites: An innovative approach to fruity flavor esters esterification - Zhao_2022_Food.Chem_366_130616
Author(s) : Zhao J , Ma M , Yan X , Wan D , Zeng Z , Yu P , Gong D
Ref : Food Chem , 366 :130616 , 2022
Abstract : The lipase from Bacillus licheniformis NCU CS-5 was immobilized onto beta-cyclodextrin (CD) grafted and aminopropyl-functionalized chitosan-coated Fe(3)O(4) magnetic nanocomposites (Fe(3)O(4)-CTS-APTES-GA-beta-CD). Fourier transform infrared spectroscopy, thermogravimetry analysis, X-ray diffraction, scanning electron microscopy and transmission electron microscopy showed that not only the functionalized magnetic nanoparticles were synthesized but also the immobilized lipase was successfully produced. The immobilized lipase exhibited higher optimal pH value (10.5) and temperature (60 degC) than the free lipase. The pH and thermal stabilities of the immobilized lipase were improved significantly compared to the free lipase. The immobilized lipase remained more than 80% of the relative activity at temperature of 60 degC and pH 12.0. The immobilized lipase also remained over 80% of its relative activity after 28 days of storage and 15 cycles of application. The application of the immobilized lipase in esterification of isoamyl acetate and pentyl valerate showed that maximum esterification efficiency was achieved in n-hexane having 68.0% and 89.2% respectively. Therefore, these results indicated that the Fe(3)O(4)-CTS-APTES-GA-beta-CD nanoparticles are novel carriers for immobilizing enzyme, and the immobilized lipase can be used as an innovative green approach to the synthesis of fruity flavor esters in food industry.
ESTHER : Zhao_2022_Food.Chem_366_130616
PubMedSearch : Zhao_2022_Food.Chem_366_130616
PubMedID: 34311240
Gene_locus related to this paper: bacld-q65hr4

Title : Green synthesis of polydopamine functionalized magnetic mesoporous biochar for lipase immobilization and its application in interesterification for novel structured lipids production - Zhao_2022_Food.Chem_379_132148
Author(s) : Zhao J , Ma M , Yan X , Zhang G , Xia J , Zeng Z , Yu P , Deng Q , Gong D
Ref : Food Chem , 379 :132148 , 2022
Abstract : In this study, the polydopamine functionalized magnetic mesoporous biochar (MPCB-DA) was prepared for immobilization of Bacillus licheniformis lipase via covalent immobilization. Under optimized immobilization conditions, the maximum immobilization yield, efficiency and immobilized lipase amount were found to be 45%, 54% and 36.9 mg/g, respectively. The immobilized lipase, MPCB-DA-Lipase showed good thermal stability and alkali resistance. The MPCB-DA-Lipase retained 56% initial activity after 10 reuse cycles, with more than 85% relative activity after 70 days' storage at 4 or 25 degreesC. The MPCB-DA-Lipase was efficiently applied in the interesterification of Cinnamomum camphora seed kernel oil and perilla seed oil, with maximum interesterification efficiency of 46%. The produced structured lipids belong to the S(2)U and U(2)S triacylglycerols, a novel medium-and long-chain triacylglycerol. These results demonstrated that the MPCB-DA-Lipase may be used as an efficient biocatalyst in lipid processing applications of food industries.
ESTHER : Zhao_2022_Food.Chem_379_132148
PubMedSearch : Zhao_2022_Food.Chem_379_132148
PubMedID: 35074745

Title : Effects of ABCG1 knockout on proteomic composition of HDL in mice on a chow diet and a high-fat diet - Wu_2022_Proteomics__e2100028
Author(s) : Wu Y , Chen L , Xie Z , Wang C , Zhang J , Yan X
Ref : Proteomics , :e2100028 , 2022
Abstract : ATP-binding cassette transporter G1 (ABCG1) is a cellular transmembrane protein that transports oxysterol efflux from cells to high-density lipoprotein (HDL) particles in the plasma. Previous studies have demonstrated that an ABCG1 deficiency exerts an antiatherosclerotic function through the effects of oxysterol accumulation in cells to enhance apoptosis and regulate inflammatory processes. However, whether the deficiency of ABCG1 and the corresponding changes in the efflux of oxysterols could take a series of impacts on the proteomic composition of HDL remains unclear. Here, plasma HDL of ABCG1(-/-) mice and their wild-type controls on a normal chow diet (NCD) or a high-fat diet (HFD) were isolated by ultracentrifugation. The proportion of 7-ketocholesterol and the proteomic composition of samples were comparatively analyzed by LC-MS/MS. In NCD-fed mice, lipid metabolism-related protein (arachidonate 12-lipoxygenase) and antioxidative protein (pantetheinase) exhibited increased accumulation, and inflammatory response protein (alpha-1-antitrypsin) was decreased in accumulation in ABCG1(-/-) mice HDL. In HFD-fed mice, fewer proteins were detected than that of NCD-fed mice. The ABCG1(-/-) mice HDL exhibited increased accumulation of lipid metabolism-related proteins (e.g., carboxylesterase 1C, apolipoprotein (apo)C-4) and decreased accumulation of alpha-1-antitrypsin, as well as significantly reduced proportion of 7-ketocholesterol. Additionally, positive correlations were found between 7-ketocholesterol and some essential proteins on HDL, such as alpha-1-antitrypsin, apoA-4, apoB-100, and serum amyloid A (SAA). These results suggest a detrimental impact of oxysterols on HDL composition, which might affect the antiatherosclerotic properties of HDL.
ESTHER : Wu_2022_Proteomics__e2100028
PubMedSearch : Wu_2022_Proteomics__e2100028
PubMedID: 35234362

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Carbon Dot-Anchored Cobalt Oxyhydroxide Composite-Based Hydrogel Sensor for On-Site Monitoring of Organophosphorus Pesticides - Li_2022_ACS.Appl.Mater.Interfaces__
Author(s) : Li H , Su C , Liu N , Lv T , Yang C , Lu Q , Sun C , Yan X
Ref : ACS Appl Mater Interfaces , : , 2022
Abstract : The development of a portable, quantitative, and user-friendly sensor for on-site monitoring of organophosphorus pesticides (OPs) is significantly urgent to guarantee food safety. Herein, a carbon dot/cobalt oxyhydroxide composite (CD/CoOOH)-based fluorescent hydrogel sensor is constructed for precisely quantifying OPs using a homemade portable auxiliary device. As a fluorescence signal indicator, the orange-emissive CD/CoOOH composite is encapsulated into an agarose hydrogel kit for amplifying the detection signals, shielding background interference, and enhancing stability. Acetylcholinesterase (AChE) catalyzes the hydrolysis of the substrate to produce thiocholine, which induces the decomposition of CoOOH and makes the fluorescence enhancement of the hydrogel platform possible. OPs can specifically block the AChE activity to limit thiocholine production, resulting in a decrease in platform fluorescence. The image color of the fluorescent hydrogel kit is transformed into digital information using a homemade auxiliary device, achieving on-site quantitative detection of paraoxon (model target) with a detection limit of 10 ng mL(-1). Harnessing CD/CoOOH composite signatures, hydrogel encapsulation, and portable optical devices, the proposed fluorescence hydrogel platform demonstrated high sensitivity and good anti-interference performance in agricultural sample analysis, indicating considerable potential in the on-site application.
ESTHER : Li_2022_ACS.Appl.Mater.Interfaces__
PubMedSearch : Li_2022_ACS.Appl.Mater.Interfaces__
PubMedID: 36380517

Title : Ratiometric fluorescent hydrogel for point-of-care monitoring of organophosphorus pesticide degradation - Li_2022_J.Hazard.Mater_432_128660
Author(s) : Li H , Zou R , Su C , Zhang N , Wang Q , Zhang Y , Zhang T , Sun C , Yan X
Ref : J Hazard Mater , 432 :128660 , 2022
Abstract : The residues of organophosphorus pesticides have caused the potential risk in environment and human health, arousing worldwidely great concern. Herein, we fabricated a robust gold nanoclusters/MnO(2) composites-based hydrogel portable kit for accurate monitoring of paraoxon residues and degradation in Chinese cabbages. With the immobilization of gold nanoclusters/MnO(2) composites into a hydrogel, a ratiometric fluorescent signal is generated by catalyzing the oxidation of o-phenylenediamine, which possesses a built-in correction with low background interference. Coupling with acetylcholinesterase catalytic reactions and pesticide inhibition effect, the portable kit can sensitively detect paraoxon residues with a detection limit of 5.0 ng mL(-1). For on-site quantification, the fluorescent color variations of portable kit are converted into digital information that exhibits applicative linear range toward pesticide. Notably, the hydrogel portable kit was successfully applied for precisely monitoring the residue and degradation of paraoxon in Chinese cabbage, providing a potential pathway toward practical point-of-care testing in food safety monitoring.
ESTHER : Li_2022_J.Hazard.Mater_432_128660
PubMedSearch : Li_2022_J.Hazard.Mater_432_128660
PubMedID: 35334266

Title : Characterization of a novel lipase from Bacillus licheniformis NCU CS-5 for applications in detergent industry and biodegradation of 2,4-D butyl ester - Zhao_2021_Int.J.Biol.Macromol__
Author(s) : Zhao J , Liu S , Gao Y , Ma M , Yan X , Cheng D , Wan D , Zeng Z , Yu P , Gong D
Ref : Int J Biol Macromol , : , 2021
Abstract : Enzymatic degradation has become the most promising approach to degrading organic ester compounds. In this study, Bacillus licheniformis NCU CS-5 was isolated from the spoilage of Cinnamomum camphora seed kernel, and its extracellular lipase was purified, with a specific activity of 192.98 U/mg. The lipase was found to be a trimeric protein as it showed a single band of 27 kDa in SDS-PAGE and 81 kDa in Native-PAGE. It was active in a wide range of temperatures (5-55 degreesC) and pH values (6.0-9.0), and the optimal temperature and pH value were 40 degreesC and 8.0, respectively. The enzyme was active in the presence of various organic solvents, metal ions, inhibitors and surfactants. Both crude and purified lipase retained more than 80% activity after 5 h in the presence of commercial detergents, suggesting its great application potential in detergent industry. The highest activity was found to be towards medium- and long-chain fatty acids (C(6)-C(18)). Peptide mass spectrometric analysis of the purified lipase showed similarity to the lipase family of B. licheniformis. Furthermore, it degraded more than 90% 2,4-D butyl ester to its hydrolysate 2,4-D within 24 h, indicating that the novel lipase may be applied to degrade organic ester pesticides.
ESTHER : Zhao_2021_Int.J.Biol.Macromol__
PubMedSearch : Zhao_2021_Int.J.Biol.Macromol__
PubMedID: 33548313
Gene_locus related to this paper: bacld-q65hr4

Title : Background-free sensing platform for on-site detection of carbamate pesticide through upconversion nanoparticles-based hydrogel suit - Su_2021_Biosens.Bioelectron_194_113598
Author(s) : Su D , Zhao X , Yan X , Han X , Zhu Z , Wang C , Jia X , Liu F , Sun P , Liu X , Lu G
Ref : Biosensors & Bioelectronics , 194 :113598 , 2021
Abstract : On-site monitoring of carbamate pesticide in complex matrix remians as a challenge in terms of the real-time control of food safety and supervision of environmental quality. Herein, we fabricated robust upconversion nanoparticles (UCNPS)/polydopamine (PDA)-based hydrogel portable suit that precisely quantified carbaryl in complex tea samples with smartphone detector. UCNPS/PDA nanoprobe was developed by polymerization of dopamine monomers on the surface of NaErF(4): 0.5% Tm(3+)@NaYF(4) through electrostatic interaction, leading to efficient red luminescence quenching of UCNPS under near-infrared excitation, which circumvented autofluorescence and background interference in complicated environment. Such a luminescence quenching could be suppressed by thiocholine that was produced by acetylcholinesterase-mediated catalytic reaction, thus enabling carbaryl bioassay by inhibiting the activity of enzyme. Bestowed with the feasibility analysis of fluorescent output, portable platform was designed by integrating UCNPS-embedded sodium alginate hydrogel with 3D-printed smartphone device for quantitatively on-site monitoring of carbaryl in the range of 0.5-200 ng mL(-1) in tea sample, accompanied by a detection limit of 0.5 ng mL(-1). Owing to specific UCNPS signatures and hydrogel immobilization, this modular platform displayed sensitive response, portability and anti-interference capability in complex matrix analysis, thus holding great potential in point-of-care application.
ESTHER : Su_2021_Biosens.Bioelectron_194_113598
PubMedSearch : Su_2021_Biosens.Bioelectron_194_113598
PubMedID: 34507097

Title : Acute benzo[a]pyrene exposure induced oxidative stress, neurotoxicity and epigenetic change in blood clam Tegillarca granosa - Guo_2021_Sci.Rep_11_18744
Author(s) : Guo B , Feng D , Xu Z , Qi P , Yan X
Ref : Sci Rep , 11 :18744 , 2021
Abstract : The blood clam (Tegillarca granosa) is being developed into a model bivalve mollusc for assessing and monitoring marine pollution on the offshore seabed. However, the information on the response of blood clam to PAHs, an organic pollutant usually deposited in submarine sediment, remains limited. Herein, we employed multiple biomarkers, including histological changes, oxidative stress, neurotoxicity and global DNA methylation, to investigate the effects of 10 and 100 microg/L Bap exposure on the blood clams under laboratory conditions, as well as the potential mechanisms. Acute Bap exposure can induce significant morphological abnormalities in gills as shown through hematoxylin-eosin (H.E) staining, providing an intuitive understanding on the effects of Bap on the structural organization of the blood clams. Meanwhile, the oxidative stress was significantly elevated as manifested by the increase of antioxidants activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) and glutathione-s-transferase (GST), lipid peroxidation (LPO) level and 8-hydroxy-2'-deoxyguanosine (8-OHdG) content. The neurotoxicity was also strengthened by Bap toxicity manifested as inhibited acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities. In addition, the global DNA methylation level was investigated, and a significant DNA hypomethylation was observed in Bap exposed the blood clam. The correlation analysis showed that the global DNA methylation was negatively correlated with antioxidants (SOD, CAT and POD) activities, but positively correlated choline enzymes (AChE and ChAT) activities. These results collectively suggested that acute Bap exposure can cause damage in gills structures in the blood clam possibly by generating oxidative stress and neurotoxicity, and the global DNA methylation was inhibited to increase the transcriptional expression level of antioxidants genes and consequently elevate antioxidants activities against Bap toxicity. These results are hoped to shed some new light on the study of ecotoxicology effect of PAHs on marine bivalves.
ESTHER : Guo_2021_Sci.Rep_11_18744
PubMedSearch : Guo_2021_Sci.Rep_11_18744
PubMedID: 34548601

Title : A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF(4): 0.5 \% Ho(3+)@NaYF(4) upconversion nano-probe - Zhao_2021_Talanta_235_122784
Author(s) : Zhao X , Zhang L , Yan X , Lu Y , Pan J , Zhang M , Wang C , Suo H , Jia X , Liu X , Lu G
Ref : Talanta , 235 :122784 , 2021
Abstract : Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF(4): 0.5 % Ho(3+)@NaYF(4) nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL(-) (1) for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL(-1), indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease.
ESTHER : Zhao_2021_Talanta_235_122784
PubMedSearch : Zhao_2021_Talanta_235_122784
PubMedID: 34517642

Title : Comprehensive Interrogation on Acetylcholinesterase Inhibition by Ionic Liquids Using Machine Learning and Molecular Modeling - Yan_2021_Environ.Sci.Technol__
Author(s) : Yan J , Yan X , Hu S , Zhu H , Yan B
Ref : Environ Sci Technol , : , 2021
Abstract : Quantitative structure-activity relationship (QSAR) modeling can be used to predict the toxicity of ionic liquids (ILs), but most QSAR models have been constructed by arbitrarily selecting one machine learning method and ignored the overall interactions between ILs and biological systems, such as proteins. In order to obtain more reliable and interpretable QSAR models and reveal the related molecular mechanism, we performed a systematic analysis of acetylcholinesterase (AChE) inhibition by 153 ILs using machine learning and molecular modeling. Our results showed that more reliable and stable QSAR models (R(2) > 0.85 for both cross-validation and external validation) were obtained by combining the results from multiple machine learning approaches. In addition, molecular docking results revealed that the cations and organic anions of ILs bound to specific amino acid residues of AChE through noncovalent interactions such as Pi interactions and hydrogen bonds. The calculation results of binding free energy showed that an electrostatic interaction (deltaE(ele) < -285 kJ/mol) was the main driving force for the binding of ILs to AChE. The overall findings from this investigation demonstrate that a systematic approach is much more convincing. Future research in this direction will help design the next generation of biosafe ILs.
ESTHER : Yan_2021_Environ.Sci.Technol__
PubMedSearch : Yan_2021_Environ.Sci.Technol__
PubMedID: 34636548

Title : Analysis of Differentially Expressed Transcripts in Apolygus lucorum (Meyer-Dur) Exposed to Different Temperature Coefficient Insecticides - An_2020_Int.J.Mol.Sci_21_658
Author(s) : An J , Liu C , Dou Y , Gao Z , Dang Z , Yan X , Pan W , Li Y
Ref : Int J Mol Sci , 21 :658 , 2020
Abstract : The existence of a temperature effect of insecticides frustrated the control of the green plant bug Apolygus lucorum (Meyer-Dur). Previous studies mostly focused on the application of insecticides, but the underlying mechanism remains incompletely understood. Here, we report a transcriptome profiling of A. lucorum treated by three kinds of temperature coefficient insecticides (TCIs) (positive TCI: imidacloprid, negative TCI: b-cypermethrin and non-effect TCI: phoxim) at 15 degrees C, 25 degrees C and 35 degrees C by using next- and third-generation RNA-Seq methods. A total of 34,739 transcripts were annotated from 277.74 Gb of clean data. There were more up-regulated transcripts than down-regulated transcripts in all three kinds of TCI treatments. Further Venn diagrams indicate the regulatory transcripts and regulatory modes were different at the three temperatures. The responses to imidacloprid involved more detox and stress response transcripts such as cytochrome P450 (CYP450), carboxylesterase (CarE) and catalase (CAT) at 35 degrees C, which was the case for beta-cypermethrin at 15 degrees C. UDP-glucuronyltransferase (UGT) and heat shock protein (HSP) transcripts were heavily involved, and thus deserve particular note in the temperature effect of insecticides. This high-confidence transcriptome atlas provides improved gene information for further study on the insecticide temperature effect related physiological and biochemical processes of A. lucorum.
ESTHER : An_2020_Int.J.Mol.Sci_21_658
PubMedSearch : An_2020_Int.J.Mol.Sci_21_658
PubMedID: 31963875

Title : Neuroprotective effects of the aerial parts of Polygala tenuifolia Willd extract on scopolamine-induced learning and memory impairments in mice - Wang_2020_Biomed.Rep_13_37
Author(s) : Wang X , Zhang D , Song W , Cai CF , Zhou Z , Fu Q , Yan X , Cao Y , Fang M
Ref : Biomed Rep , 13 :37 , 2020
Abstract : Alzheimer's disease is a common neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. Aerial parts of Polygala tenuifolia Willd (APT) is a traditional Chinese medicine used for the treatment of amnesia. The present study aimed to investigate the protective effects of APT on scopolamine-induced learning and memory impairments in mice. Scopolamine-induced mice were used to determine the effects of APT on learning and memory impairment. Mice were orally administered with APT (25, 50 and 100 mg/kg) and piracetam (750 mg/kg) for 14 days, and intraperitoneally injected with scopolamine (2 mg/kg) from days 8 to 14. Morris water maze and step-down tests were performed to evaluate learning and memory. Levels of acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase (AChE), interleukin (IL)-1beta, IL-10 and brain-derived neurotrophic factor (BDNF) in the hippocampus and frontal cortex were measured by ELISA. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were measured via biochemical detection. The results demonstrated that APT ameliorated learning and memory impairment in scopolamine-induced mice. Correspondingly, APT significantly increased ACh and ChAT levels in the hippocampus and prefrontal cortex of scopolamine-induced mice. Additionally, treatment with APT significantly increased BDNF and IL-10 levels, and decreased IL-1beta and AChE levels in the same mice. Furthermore, APT significantly increased SOD activity and GSH content, and decreased MDA levels in brain tissue. These results indicated that APT may ameliorate learning and memory impairment by regulating cholinergic activity, promoting BDNF and inhibiting neuroinflammation and oxidative stress.
ESTHER : Wang_2020_Biomed.Rep_13_37
PubMedSearch : Wang_2020_Biomed.Rep_13_37
PubMedID: 32874571

Title : Design of Red Emissive Carbon Dots: Robust Performance for Analytical Applications in Pesticide Monitoring - Li_2020_Anal.Chem_92_3198
Author(s) : Li H , Su D , Gao H , Yan X , Kong D , Jin R , Liu X , Wang C , Lu G
Ref : Analytical Chemistry , 92 :3198 , 2020
Abstract : Synthesis of red emissive carbon dots (CDs) is highly desirable for sensing applications, as they still remain as bottlenecks in terms of precursor synthesis and product purification. Herein, we have designed a new strategy for realizing efficient red emissive CD optimal emission at 610 nm (fluorescence quantum yield ca. 24.0%) based on solvothermal treatment of citric acid and thiourea using dimethylformamide as solvent. Further investigations reveal that the conjugating sp(2)-domain controlling the incorporation of nitrogen and surface engineering are mainly responsible for the obtained red emission of CDs. Taking advantage of optical properties and abundant surface functional groups, CDs were considered to facilely construct a ratiometric fluorescent platform for quantifying trace levels of organophosphorus pesticides (OPs). Combining the acetylcholinesterase-mediated polymerization of dopamine and the inhibition of pesticide toward the enzyme, the degree of polymerization of dopamine rationally depends on the concentration of OPs. By measuring the fluorescence intensity ratio, the proposed platform exhibited highly selective and robust performance toward OPs, displaying ultrasensitive recognition in the pg L(-1) level. The multiexcitation format could efficiently shield background interference from complex samples by introducing a self-calibrated reference signal, which affords accurate and reliable quantitative information, endowing CDs as a universal candidate for a biosensing application by combining target-specific recognition elements.
ESTHER : Li_2020_Anal.Chem_92_3198
PubMedSearch : Li_2020_Anal.Chem_92_3198
PubMedID: 32008315

Title : Ethanol extracts from Cinnamomum camphora seed kernel: Potential bioactivities as affected by alkaline hydrolysis and simulated gastrointestinal digestion - Zhang_2020_Food.Res.Int_137_109363
Author(s) : Zhang G , Yan X , Wu S , Ma M , Yu P , Gong D , Deng S , Zeng Z
Ref : Food Res Int , 137 :109363 , 2020
Abstract : The aim of the study was to evaluate the changes of potential bioactivities of ethanol extracts (EE) from Cinnamomum camphora seed kernel (CCSK) after alkaline hydrolysis and simulated gastrointestinal digestion. A total of 13 compounds in EE, mainly phenolics and saponins were tentatively identified using HPLC-ESI-QTOF-MS(2) analysis. The total phenolic and total flavonoid contents in EE decreased by 30.6%, 1%, 33% and 11.8% after hydrolysis and digestion, respectively. The total saponins content decreased by 17% after hydrolysis while increased by 48% after digestion. The total condensed tannin contents increased by 70.3% and 17.2% after hydrolysis and digestion, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), cupric ion reducing activity (CUPRAC), ferric reducing antioxidant power (FRAP) and metal chelating activity (MCA) were used to determine antioxidant activity. Overall, the changes of antioxidant activities by hydrolysis and digestion were consistent with the changes of their total phenolic and flavonoid contents. The alpha-amylase and alpha-glucosidase inhibitory activities in EE increased by 817% and 33.3% after digestion while decreased by 12.3% and 19% after hydrolysis, respectively. Although the inhibitory activities of cholinesterase, tyrosinase and xanthine oxidase were decreased by hydrolysis and digestion, most of these activities were retained. These results showed that CCSK ethanol extracts had strong bioactivities and were reasonably stable to alkali and digestive enzymes.
ESTHER : Zhang_2020_Food.Res.Int_137_109363
PubMedSearch : Zhang_2020_Food.Res.Int_137_109363
PubMedID: 33233066

Title : Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present) - Wang_2019_Curr.Med.Chem_26_5684
Author(s) : Wang N , Qiu P , Cui W , Yan X , Zhang B , He S
Ref : Curr Med Chem , 26 :5684 , 2019
Abstract : Since the last century, when scientists proposed the lock-and-key model, the discovery of drugs has focused on the development of drugs acting on single target. However, single-target drug therapies are not effective to complex diseases with multi-factorial pathogenesis. Moreover, the combination of single-target drugs readily causes drug resistance and side effects. In recent years, multi-target drugs have increasingly been represented among FDA-approved drugs. Alzheimer's Disease (AD) is a complex and multi-factorial disease for which the precise molecular mechanisms are still not fully understood. In recent years, rational multi-target drug design methods, which combine the pharmacophores of multiple drugs, have been increasingly applied in the development of anti-AD drugs. In this review, we give a brief description of the pathogenesis of AD and provide detailed discussions about the recent development of chemical structures of anti-AD agents (2013 up to present) that have multiple targets, such as amyloid-beta peptide, Tau protein, cholinesterases, monoamine oxidase, beta-site amyloid-precursor protein-cleaving enzyme 1, free radicals, metal ions (Fe2+, Cu2+, Zn2+) and so on. In this paper, we also added some novel targets or possible pathogenesis which have been reported in recent years for AD therapy. We hope that these findings may provide new perspectives for the pharmacological treatment of AD.
ESTHER : Wang_2019_Curr.Med.Chem_26_5684
PubMedSearch : Wang_2019_Curr.Med.Chem_26_5684
PubMedID: 30501591

Title : Fascaplysin Derivatives Are Potent Multitarget Agents against Alzheimer's Disease: in Vitro and in Vivo Evidence - Pan_2019_ACS.Chem.Neurosci_10_4741
Author(s) : Pan H , Qiu H , Zhang K , Zhang P , Liang W , Yang M , Mou C , Lin M , He M , Xiao X , Zhang D , Wang H , Liu F , Li Y , Jin H , Yan X , Liang H , Cui W
Ref : ACS Chem Neurosci , 10 :4741 , 2019
Abstract : Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a beta-carboline alkaloid isolated from marine sponge Fascaplysinopsis bergquist in 1988. Previous studies have shown that fascaplysin might act on acetylcholinesterase and beta-amyloid (Abeta) to produce anti-AD properties. In this study, a series of fascaplysin derivatives were synthesized. The cholinesterase inhibition activities, the neuronal protective effects, and the toxicities of these compounds were evaluated in vitro. Compounds 2a and 2b, the two most powerful compounds in vitro, were further selected to evaluate their cognitive-enhancing effects in animals. Both 2a and 2b could ameliorate cognitive dysfunction induced by scopolamine or Abeta oligomers without affecting locomotor functions in mice. We also found that 2a and 2b could prevent cholinergic dysfunctions, decrease pro-inflammatory cytokine expression, and inhibit Abeta-induced tau hyperphosphorylation in vivo. Most importantly, pharmacodynamics studies suggested that 2b could penetrate the blood-brain barrier and be retained in the central nervous system. All these results suggested that fascaplysin derivatives are potent multitarget agents against AD and might be clinical useful for AD treatment.
ESTHER : Pan_2019_ACS.Chem.Neurosci_10_4741
PubMedSearch : Pan_2019_ACS.Chem.Neurosci_10_4741
PubMedID: 31639294

Title : Evaluation of potential herb-drug interactions between oseltamivir and commonly used anti-influenza Chinese medicinal herbs - Zhang_2019_J.Ethnopharmacol__112097
Author(s) : Zhang Y , Lyu C , Fong S , Wang Q , Li C , Ho NJ , Chan KS , Yan X , Zuo Z
Ref : J Ethnopharmacol , :112097 , 2019
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: According to Traditional Chinese Medicine theory, influenza is categorized as a warm disease or Wen Bing. The Wen Bing formulas, such as Yin-Qiao-San and Sang-Ju-Yin, are still first-line herbal therapies in combating variant influenza virus. To continue our study on the pharmacokinetic and pharmacodynamic interactions between Wen Bing formulas and oseltamivir (OS), the first-line western drug for the treatment of influenza, further interactions between OS and the eight single herbs and their relevant marker components from Wen Bing formulas were investigated in the current study. AIM OF STUDY: To establish an in-vitro screening platform for investigation of the potential anti-influenza herbs/herbal components that may have pharmacokinetic and pharmacodynamic interactions with OS. MATERIALS AND METHODS: To screen potential inhibition on OS hydrolysis, 1mug/mL of OS is incubated with herbs/herbal components in diluted rat plasma, microsomes and human recombinant carboxylesterase 1(hCE1) under optimized conditions. MDCK-WT and MDCK-MDR1 cell lines are utilized to identify potential modification on P-gp mediated transport of OS by herbs/herbal components. Caco-2cells with and without Gly-Sar inhibition are performed to study the uptake of OS via PEPT1 transporters. Modification on OAT3 mediated transport is verified by the uptake of OS on HEK293-MOCK/HEK293-OAT3 cells. Anti-virus effects were evaluated using plaque reduction assay on H1N1 and H3N2 viruses. Potential pharmacokinetic and pharmacodynamic interaction between OS (30mg/kg) and the selected herb, Radix Scutellariae (RS), at 300-600mg/kg were carried out on rats. All samples are analyzed by an LC/MS/MS method for the contents of OS and OSA. A mechanistic PK model was developed to interpret the HDI between OS and RS in rats. RESULTS: Our developed platform was successfully applied to screen the eight herbal extracts and their ten marker components on metabolic inhibition of OS and modification of OS transport mediated by P-gp, OAT3 and PEPT1. Results from six in-vitro experiments were analyzed after converting raw data from each experiment to corresponding fold-change (FC) values, based on which Radix Scutellariae (RS) were selected to have the most HDI potential with OS. By analyzing the plasma and urine pharmacokinetic data after co-administration of OS with a standardized RS extract in rats using an integrated population pharmacokinetics model, it is suggested that RS could inhibit OS hydrolysis during absorption and increase the absorbed fraction of OS, which leads to the increased ratio of OS concentration versus that of OSA in both rat plasma and urine. Never the less, the anti-virus effects of 2.5h post-dose rat plasma were not influenced by co-administration of OS with RS. CONCLUSION: A six-dimension in-vitro screening platform has been developed and successfully applied to find RS as a potential herb that would influence the co-administrated OS in rats. Although co-administered RS could inhibit OS hydrolysis during absorption and increase the absorbed fraction of OS, which lead to the increased ratio of OS concentration versus that of OSA in both rat plasma and urine, the anti-virus effect of OS was not influenced by co-administered RS.
ESTHER : Zhang_2019_J.Ethnopharmacol__112097
PubMedSearch : Zhang_2019_J.Ethnopharmacol__112097
PubMedID: 31325600

Title : 9-Methylfascaplysin Is a More Potent Abeta Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells - Sun_2019_Mar.Drugs_17_
Author(s) : Sun Q , Liu F , Sang J , Lin M , Ma J , Xiao X , Yan S , Naman CB , Wang N , He S , Yan X , Cui W , Liang H
Ref : Mar Drugs , 17 : , 2019
Abstract : beta-Amyloid (Abeta) is regarded as an important pathogenic target for Alzheimer's disease (AD), the most prevalent neurodegenerative disease. Abeta can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Abeta aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Abeta fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Abeta fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Abeta directly reduced Abeta oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Abeta42 with polar binding energy. Hydrogen bonds and pi(-)pi interactions between the key amino acid residues of Abeta42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Abeta oligomer, Abeta modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Abeta neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Abeta aggregation along with other target mechanisms.
ESTHER : Sun_2019_Mar.Drugs_17_
PubMedSearch : Sun_2019_Mar.Drugs_17_
PubMedID: 30781608

Title : Transformation pathway and toxicity assessment of malathion in aqueous solution during UV photolysis and photocatalysis - Li_2019_Chemosphere_234_204
Author(s) : Li W , Zhao Y , Yan X , Duan J , Saint CP , Beecham S
Ref : Chemosphere , 234 :204 , 2019
Abstract : In drinking water treatment, complete mineralization of organophosphorus pesticides (OPPs) by UV-based advanced oxidation processes (UV AOPs) is rarely achieved. The formation of intermediate oxidation byproducts would likely have some profound effects on toxicity of the reaction solutions. This study investigated the intermediate oxidation byproducts, transformation pathway and toxicity of malathion solutions during the treatment processes of UV alone, UV/H2O2, UV/TiO2 and UV/Fenton. The main intermediate oxidation byproducts were derived using ultra-performance liquid chromatography - electrospray - time-of-flight mass spectrometry. Thereby the transformation pathway for each of these treatment processes was proposed. The results indicate that in UV photolysis, the transformation pathway of malathion proceeded initially via cleavage of the phosphorus-sulfur bonds while in photocatalysis, the desulfurization from a PS bond to a PO bond was the primary degradation pathway. Interestingly, only in the UV/TiO2 process a small fraction of malathion was found decomposed via a demethylation reaction. At the same time, a toxicity assessment of the treated solutions was conducted by both luminescence inhibition of Vibrio fischeri and inhibition of acetylcholinesterase (AChE). It was found that after UV AOP treatment, the toxicity of the malathion aqueous solution increased sharply. In contrast, no increase in toxicity was observed for the malathion aqueous solution after UV alone treatment. This study demonstrates that the high removal efficiency achieved by OPPs does not imply that detoxification of the water solution has been achieved. On the contrary, the toxicity of the treated solutions by OPPs may be increased significantly depending on the selected treatment processes.
ESTHER : Li_2019_Chemosphere_234_204
PubMedSearch : Li_2019_Chemosphere_234_204
PubMedID: 31220654

Title : New Dihydroisocoumarin Root Growth Inhibitors From the Sponge-Derived Fungus Aspergillus sp. NBUF87 - Huang_2019_Front.Microbiol_10_2846
Author(s) : Huang L , Ding L , Li X , Wang N , Cui W , Wang X , Naman CB , Lazaro JEH , Yan X , He S
Ref : Front Microbiol , 10 :2846 , 2019
Abstract : Six new dihydroisocoumarins, aspergimarins A-F (1-6), were discovered together with five known analogs (7-11) from a monoculture of the sponge-derived fungus Aspergillus sp. NBUF87. The structures of these compounds were elucidated through comprehensive spectroscopic methods, and absolute configurations were assigned after X-ray crystallography, use of the modified Mosher's method, and comparison of electronic circular dichroism (ECD) data with literature values for previously reported analogs. Compounds 1-11 were evaluated in a variety of bioassays, and at 100 muM, both 1 and 5 showed significant inhibitory effects on the lateral root growth of Arabidopsis thaliana Columbia-0 (Col-0). Moreover, at 100 muM, 5 also possessed notable inhibition against the primary root growth of Col-0. Meanwhile, 1-11 were all found to be inactive in vitro against acetylcholinesterase (AChE) (IC50 > 100 muM), four different types of human-derived cancer cell lines (IC50 > 50 muM), as well as methicillin-resistant Staphylococcus aureus and Escherichia coli (MIC > 50 mug/mL), and Plasmodium falciparum W2 (EC50 > 100 mug/mL), in phenotypic tests.
ESTHER : Huang_2019_Front.Microbiol_10_2846
PubMedSearch : Huang_2019_Front.Microbiol_10_2846
PubMedID: 31921029

Title : Integrating Target-Responsive Hydrogels with Smartphone for On-Site ppb-Level Quantitation of Organophosphate Pesticides - Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
Author(s) : Jin R , Kong D , Yan X , Zhao X , Li H , Liu F , Sun P , Lin Y , Lu G
Ref : ACS Appl Mater Interfaces , 11 :27605 , 2019
Abstract : Precise on-site profiling of organophosphate pesticides (OPs) is of significant importance for monitoring pollution and estimating poisoning. Herein, we designed a simple and convenient portable kit based on Ag(+)-responsive hydrogels for accurate detection of OPs. The newly developed hydrogels employed o-phenylenediamine (OPD) and silicon quantum dots (SiQDs) as indicator, which possessed ratiometric response. In this sensor, OPs as inhibitor of acetylcholinesterase prevented the generation of thiocholine, which blocked the formation of metal-polymer with Ag(+), further triggered the oxidation of OPD to yield yellow 2,3-diaminophenazine (DAP) with fluorescence emission at 557 nm. The fluorescence intensity of SiQDs (444 nm) was quenched by DAP through inner filter effect (IFE) process, emerging a typical ratiometric response. Interestingly, the ratiometric signal of kit, which was recorded by smartphone's camera, can be transduced by ImageJ software into the hue parameter that was linearly proportional to the concentration of OPs. The simplicity of portable kit combined with smartphone operation, which possessed high sensitivity (detection limit <10 ng mL(-1)) and rapid sample-to-answer detection time (45 min) in agricultural sample, indicating that the methodology offered a new sight for portable monitoring of food safety and human health.
ESTHER : Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
PubMedSearch : Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
PubMedID: 31291083

Title : Protein-Inorganic Hybrid Nanoflower-Rooted Agarose Hydrogel Platform for Point-of-Care Detection of Acetylcholine - Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
Author(s) : Kong D , Jin R , Zhao X , Li H , Yan X , Liu F , Sun P , Gao Y , Liang X , Lin Y , Lu G
Ref : ACS Appl Mater Interfaces , 11 :11857 , 2019
Abstract : Rapid and precise profiling of acetylcholine (ACh) has become important for diagnosing diseases and safeguarding health care because of its pivotal role in the central nervous system. Herein, we developed a new colorimetric sensor based on protein-inorganic hybrid nanoflowers as artificial peroxidase, comprising a test kit and a smartphone reader, which sensitively quantifies ACh in human serum. In this sensor, ACh indirectly triggered the substrate reaction with the help of a multienzyme system including acetylcholinesterase, choline oxidase, and mimic peroxidase (nanoflowers), accompanying the enhancement of absorbance intensity at 652 nm. Therefore, the multienzyme platform can be used to detect ACh via monitoring the change of the absorbance in a range from 0.0005 to 6.0 mmol L(-1). It is worth mentioning that the platform was used to prepare a portable agarose gel-based kit for rapid qualitative monitoring of ACh. Coupling with ImageJ program, the image information of test kits can be transduced into the hue parameter, which provides a directly quantitative tool to identify ACh. Based on the advantages of simple operation, good selectivity, and low cost, the availability of a portable kit for point-of-care testing will achieve the needs of frequent screening and diagnostic tracking.
ESTHER : Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
PubMedSearch : Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
PubMedID: 30830739

Title : Weighted Stochastic Block Models of the Human Connectome across the Life Span - Faskowitz_2018_Sci.Rep_8_12997
Author(s) : Faskowitz J , Yan X , Zuo XN , Sporns O
Ref : Sci Rep , 8 :12997 , 2018
Abstract : The human brain can be described as a complex network of anatomical connections between distinct areas, referred to as the human connectome. Fundamental characteristics of connectome organization can be revealed using the tools of network science and graph theory. Of particular interest is the network's community structure, commonly identified by modularity maximization, where communities are conceptualized as densely intra-connected and sparsely inter-connected. Here we adopt a generative modeling approach called weighted stochastic block models (WSBM) that can describe a wider range of community structure topologies by explicitly considering patterned interactions between communities. We apply this method to the study of changes in the human connectome that occur across the life span (between 6-85 years old). We find that WSBM communities exhibit greater hemispheric symmetry and are spatially less compact than those derived from modularity maximization. We identify several network blocks that exhibit significant linear and non-linear changes across age, with the most significant changes involving subregions of prefrontal cortex. Overall, we show that the WSBM generative modeling approach can be an effective tool for describing types of community structure in brain networks that go beyond modularity.
ESTHER : Faskowitz_2018_Sci.Rep_8_12997
PubMedSearch : Faskowitz_2018_Sci.Rep_8_12997
PubMedID: 30158553

Title : Yellow-Emissive Carbon Dot-Based Optical Sensing Platforms: Cell Imaging and Analytical Applications for Biocatalytic Reactions - Li_2018_ACS.Appl.Mater.Interfaces_10_7737
Author(s) : Li H , Yan X , Qiao S , Lu G , Su X
Ref : ACS Appl Mater Interfaces , 10 :7737 , 2018
Abstract : Carbon dots (CDs) have attracted increasing interest in bioimaging and sensing recently. Herein, we present a simple synthetic strategy to prepare yellow-emissive CDs (lambdaem = 535 nm) by one-pot hydrothermal treatment of p-phenylenediamine and aspartic acid. The as-prepared CDs possess outstanding optical features, excellent biocompatibility, and low cytotoxicity, especially for fluorescence (FL) cellular imaging. Interestingly, by combining the quenching and recognition ability of silver nanoparticles (AgNPs) with the optical capacity of CDs, a label-free strategy for specifically monitoring H2O2-generated biocatalytic processes was proposed, such as glucose oxidase-induced conversion of glucose, cholesterol oxidase-catalyzed oxidization of cholesterol, and bienzyme of acetylcholinesterase and choline oxidase-mediated reaction of acetylcholine. In this process, AgNPs act as a "nanoquencher" to decrease the FL intensity of CDs via surface plasmon-enhanced energy-transfer mechanism. The enzymatic oxidation product (H2O2) subsequently etches the AgNPs to silver ions, thus recovering the FL of CDs, which enabled this proposed nanosensor to sensitively detect H2O2-generated biocatalytic processes. The above results pave the way to implement CDs as FL labels for biosensors and biological imaging.
ESTHER : Li_2018_ACS.Appl.Mater.Interfaces_10_7737
PubMedSearch : Li_2018_ACS.Appl.Mater.Interfaces_10_7737
PubMedID: 29441784

Title : MnO2 Nanosheet-Carbon Dots Sensing Platform for Sensitive Detection of Organophosphorus Pesticides - Yan_2018_Anal.Chem_90_2618
Author(s) : Yan X , Song Y , Zhu C , Li H , Du D , Su X , Lin Y
Ref : Analytical Chemistry , 90 :2618 , 2018
Abstract : Carbon dots (CDs) combined with a nanomaterial-based quencher has created an innovative way for designing promising sensors. Herein, a novel fluorescent-sensing platform was designed for sensitive detection of organophosphorus pesticides (OPs). The preparation of CDs was based on one-step hydrothermal reaction of 3-aminobenzeneboronic acid. The fluorescence of CDs can be quenched by manganese dioxide (MnO2) nanosheets via the Forster resonance energy transfer (FRET). In the presence of butyrylcholinesterase (BChE) and acetylthiocholine, the enzymatic hydrolysate (thiocholine) can efficiently trigger the decomposition of MnO2 nanosheets, resulting in the recovery of CDs fluorescence. OPs as inhibitors for BChE activity can prevent the generation of thiocholine and decomposition of MnO2 nanosheets, accompanying the fluorescence "turn-off" of the system. So the BChE-ATCh-MnO2-CDs system can be utilized to detect OPs quantitatively based on the fluorescence turn "on-off". Under the optimum conditions, the present FRET-based approach can detect paraoxon ranging from 0.05 to 5 ng mL(-1) with a detection limit of 0.015 ng mL(-1). Meanwhile, the present strategy also showed a visual color change in a concentration-dependent manner. Thus, the proposed assay can potentially be a candidate for OPs detection.
ESTHER : Yan_2018_Anal.Chem_90_2618
PubMedSearch : Yan_2018_Anal.Chem_90_2618
PubMedID: 29237266

Title : Comparative Studies of the Biosynthetic Gene Clusters for Anthraquinone-Fused Enediynes Shedding Light into the Tailoring Steps of Tiancimycin Biosynthesis - Yan_2018_Org.Lett_20_5918
Author(s) : Yan X , Chen JJ , Adhikari A , Teijaro CN , Ge H , Crnovcic I , Chang CY , Annaval T , Yang D , Rader C , Shen B
Ref : Org Lett , 20 :5918 , 2018
Abstract : Comparative analyses of the four known anthraquinone-fused enediynes biosynthetic gene clusters identified four genes, tnmE6, tnmH, tnmL, and tnmQ, unique to the tnm gene cluster. Larger scale fermentation of both the S. sp. CB03234 wild-type and the delta tnmH and delta tnmL mutant strains resulted in the characterization of 20 new tiancimycin (TNM) congeners, including five enediynes. These findings enabled a proposal for the late stage of TNM biosynthesis featuring an intermediate possibly common for all anthraquinone-fused enediynes.
ESTHER : Yan_2018_Org.Lett_20_5918
PubMedSearch : Yan_2018_Org.Lett_20_5918
PubMedID: 30212211

Title : Study of the interactions of forsythiaside and rutin with acetylcholinesterase (AChE) - Yan_2018_Int.J.Biol.Macromol_119_1344
Author(s) : Yan X , Chen T , Zhang L , Du H
Ref : Int J Biol Macromol , 119 :1344 , 2018
Abstract : Acetylcholinesterase (AChE) inhibitors have been considered as candidates for the treatment of Alzheimer's disease (AD) and have been utilized in clinical trials. In the present study, the interactions of forsythiaside and rutin with AChE have been investigated, after discovering the inhibitory AChE activity of the two compounds. Forsythiaside and rutin both can bind to AChE to form forsythiaside-AChE and rutin-AChE complex, and thus quench the intrinsic fluorescence of AChE. The quenching mechanism, the binding sites, the binding forces, the binding constants and the energy transfer involved were studied in details. Forsythiaside and rutin show some properties in common, including the stoichiometric binding ratio of 1:1 with AChE and the full quenching of AChE fluorescence. At the same time, the two compounds distinctly present some different characters, for example, the binding constant of rutin is less than that of forsythiaside, and the interaction force and the affinity between forsythiaside and AChE are much bigger than that of rutin. Spectroscopy data and docking analysis powerfully support the findings that forsythiaside inhibit AChE activity more strongly than rutin. The current study will provide the better understanding on the nature of the possible interactions between forsythiaside and rutin with AChE.
ESTHER : Yan_2018_Int.J.Biol.Macromol_119_1344
PubMedSearch : Yan_2018_Int.J.Biol.Macromol_119_1344
PubMedID: 30048725

Title : Protective effects of Forsythoside A on amyloid beta-induced apoptosis in PC12 cells by downregulating acetylcholinesterase - Yan_2017_Eur.J.Pharmacol_810_141
Author(s) : Yan X , Chen T , Zhang L , Du H
Ref : European Journal of Pharmacology , 810 :141 , 2017
Abstract : Increasing the acetylcholine level and fighting the neuroinflammation has always been taken as a treatment strategy for Alzheimer's disease (AD). Forsythoside A is a major component in Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao in Chinese) that has been traditionally used as Chinese herbal medicine to treat the inflammation in China. This study examined the inhibitory acetylcholinesterase activities of Forsythoside A at chemical and biological level. Forsythoside A inhibited acetylcholinesterase in a mixed type of inhibition, with Ki of 47.68muM. Docking analysis strongly supported these findings. In PC12 cells Forsythoside A increased cell viability and suppressed acetylcholinesterase increased by Abeta25-35, thus alleviated the corresponding apoptosis. Taken together, these results suggest that Forsythoside A has the protective effects on Abeta25-35-induced apoptosis in PC12 cells by downregulating acetylcholinesterase, making it a potential functional food ingredient or drug candidate for the treatment of AD.
ESTHER : Yan_2017_Eur.J.Pharmacol_810_141
PubMedSearch : Yan_2017_Eur.J.Pharmacol_810_141
PubMedID: 28687196

Title : Synergistic toxicity of zno nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to zno nanoparticles - Yan_2017_Environ.Toxicol_32_1202
Author(s) : Yan X , Xu X , Guo M , Wang S , Gao S , Zhu S , Rong R
Ref : Environ Toxicol , 32 :1202 , 2017
Abstract : The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate (DM) have increased the risk of humans' co-exposure to nano ZnO and DM. Here, we report the synergistic effect of nano ZnO and DM on their biodistribution and subacute toxicity in mice. Nano ZnO and DM had a synergistic toxicity in mice. In contrast, bulk ZnO and DM did not cause an obvious synergistic toxicity in mice. Although nano ZnO was low toxic to mice, coexposure to nano ZnO and DM significantly enhanced DM-induced oxidative damage in the liver. Coadministration of nano ZnO with DM significantly increased Zn accumulation by 30.9 +/- 1.9% and DM accumulation by 45.6 +/- 2.2% in the liver, respectively. The increased accumulations of DM and Zn in the liver reduced its cholinesterase activity from 5.65 +/- 0.32 to 4.37 +/- 0.49 U/mg protein and induced hepatic oxidative stress. Nano ZnO had 3-fold or 2.4-fold higher binding capability for serum albumin or DM, respectively, than bulk ZnO. In addition, serum albumin significantly increased the binding capability of nano ZnO for DM by approximately four times via the interaction of serum albumin and DM. The uptake of serum albumin- and DM-bound nano ZnO by the macrophages significantly increased DM accumulation in mice. Serum albumins play an important role in the synergistic toxicity of nano ZnO and DM. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1202-1212, 2017.
ESTHER : Yan_2017_Environ.Toxicol_32_1202
PubMedSearch : Yan_2017_Environ.Toxicol_32_1202
PubMedID: 27441385

Title : Oxidase-mimicking activity of ultrathin MnO2 nanosheets in colorimetric assay of acetylcholinesterase activity - Yan_2017_Nanoscale_9_2317
Author(s) : Yan X , Song Y , Wu X , Zhu C , Su X , Du D , Lin Y
Ref : Nanoscale , 9 :2317 , 2017
Abstract : In the present study, a novel colorimetric sensing platform was constructed for quantitative detection of acetylcholinesterase (AChE) activity and its inhibitor. Manganese dioxide (MnO2) nanosheets as an oxidase-mimicking nanomaterial could directly oxidize 3,3',5,5'-tetramethylbenzidine (TMB) into oxTMB without the need for horseradish peroxidase and H2O2. When AChE was introduced, acetylthiocholine could be catalytically hydrolyzed to produce thiocholine, which easily triggers the decomposition of MnO2 nanosheets, causing the decrease of solution absorbance. Owing to the inhibition effect of organophosphorus pesticides, the enzymatic activity was suppressed, preventing the decomposition of MnO2 and resulting in the increase of absorbance. Under optimal conditions, the colorimetric platform shows sensitive responses to AChE and paraoxon in the range of 0.1-15 mU mL-1 and 0.001-0.1 mug mL-1, respectively. The detection limits of AChE and paraoxon reached 35 muU mL-1 and 1.0 ng mL-1, respectively. Furthermore, the MnO2-TMB platform has been used to fabricate test strips for rapid and convenient visual detection of AChE and its inhibitor with highly promising performance.
ESTHER : Yan_2017_Nanoscale_9_2317
PubMedSearch : Yan_2017_Nanoscale_9_2317
PubMedID: 28134376

Title : Carbon quantum dots as fluorescence resonance energy transfer sensors for organophosphate pesticides determination - Wu_2017_Biosens.Bioelectron_94_292
Author(s) : Wu X , Song Y , Yan X , Zhu C , Ma Y , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 94 :292 , 2017
Abstract : Carbon quantum dots (CQDs) obtained from natural organics attract significant attention due to the abundance of carbon sources, varieties of heteroatom doping (such as N, S, P) and good biocompatibility of precursor. In this study, tunable fluorescence emission CQDs originated from chlorophyll were synthesized and characterized. The fluorescence emission can be effectively quenched by gold nanoparticles (Au NPs) via fluorescence resonance energy transfer (FRET). Thiocholine, which was produced from acetylthiocholine (ATC) by the hydrolysis of butyrylcholinesterase (BChE), could cause the aggregation of Au NPs and the corresponding recovery of FRET-quenched fluorescence emission. The catalytic activity of BChE could be irreversibly inhibited by organophosphorus pesticides (OPs), thus, the recovery effect was reduced. By evaluating the fluorescence emission intensity of CQDs, a FRET-based sensing platform for OPs determination was established. Paraoxon was studied as an example of OPs. The sensing platform displayed a linear relationship with the logarithm of the paraoxon concentrations in the range of 0.05-50mugL-1 and the limit of detection (LOD) was 0.05mugL-1. Real sample study in tap and river water revealed that this sensing platform was repeatable and accurate. The results indicate that the OP sensor is promising for applications in food safety and environmental monitoring.
ESTHER : Wu_2017_Biosens.Bioelectron_94_292
PubMedSearch : Wu_2017_Biosens.Bioelectron_94_292
PubMedID: 28315592

Title : Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg) with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by Engineering the Substrate Entrance Tunnel - Yan_2016_Appl.Environ.Microbiol_82_6748
Author(s) : Yan X , Wang J , Sun Y , Zhu J , Wu S
Ref : Applied Environmental Microbiology , 82 :6748 , 2016
Abstract : Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical alpha/beta fold hydrolase, was previously reported to have both gamma-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from Pseudomonas fluorescens, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any gamma-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of alpha/beta fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies.
ESTHER : Yan_2016_Appl.Environ.Microbiol_82_6748
PubMedSearch : Yan_2016_Appl.Environ.Microbiol_82_6748
PubMedID: 27613682
Gene_locus related to this paper: 9mico-e3svs0

Title : Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro - Lin_2016_Mar.Drugs_14_
Author(s) : Lin J , Huang L , Yu J , Xiang S , Wang J , Zhang J , Yan X , Cui W , He S , Wang Q
Ref : Mar Drugs , 14 : , 2016
Abstract : Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 muM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer's disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression.
ESTHER : Lin_2016_Mar.Drugs_14_
PubMedSearch : Lin_2016_Mar.Drugs_14_
PubMedID: 27023569

Title : Strain Prioritization and Genome Mining for Enediyne Natural Products - Yan_2016_MBio_7_e02104
Author(s) : Yan X , Ge H , Huang T , Hindra , Yang D , Teng Q , Crnovcic I , Li X , Rudolf JD , Lohman JR , Gansemans Y , Zhu X , Huang Y , Zhao LX , Jiang Y , Van Nieuwerburgh F , Rader C , Duan Y , Shen B
Ref : MBio , 7 : , 2016
Abstract : The enediyne family of natural products has had a profound impact on modern chemistry, biology, and medicine, and yet only 11 enediynes have been structurally characterized to date. Here we report a genome survey of 3,400 actinomycetes, identifying 81 strains that harbor genes encoding the enediyne polyketide synthase cassettes that could be grouped into 28 distinct clades based on phylogenetic analysis. Genome sequencing of 31 representative strains confirmed that each clade harbors a distinct enediyne biosynthetic gene cluster. A genome neighborhood network allows prediction of new structural features and biosynthetic insights that could be exploited for enediyne discovery. We confirmed one clade as new C-1027 producers, with a significantly higher C-1027 titer than the original producer, and discovered a new family of enediyne natural products, the tiancimycins (TNMs), that exhibit potent cytotoxicity against a broad spectrum of cancer cell lines. Our results demonstrate the feasibility of rapid discovery of new enediynes from a large strain collection. IMPORTANCE: Recent advances in microbial genomics clearly revealed that the biosynthetic potential of soil actinomycetes to produce enediynes is underappreciated. A great challenge is to develop innovative methods to discover new enediynes and produce them in sufficient quantities for chemical, biological, and clinical investigations. This work demonstrated the feasibility of rapid discovery of new enediynes from a large strain collection. The new C-1027 producers, with a significantly higher C-1027 titer than the original producer, will impact the practical supply of this important drug lead. The TNMs, with their extremely potent cytotoxicity against various cancer cells and their rapid and complete cancer cell killing characteristics, in comparison with the payloads used in FDA-approved antibody-drug conjugates (ADCs), are poised to be exploited as payload candidates for the next generation of anticancer ADCs. Follow-up studies on the other identified hits promise the discovery of new enediynes, radically expanding the chemical space for the enediyne family.
ESTHER : Yan_2016_MBio_7_e02104
PubMedSearch : Yan_2016_MBio_7_e02104
PubMedID: 27999165
Gene_locus related to this paper: 9actn-a0a1q5ckn8 , 9actn-a0a1q5j3v0 , 9actn-a0a1q5kj90 , 9actn-a0a1q5jti2 , 9actn-a0a1q5luf4 , 9actn-a0a1q4w3c8 , 9actn-a0a1q4wvf2 , 9actn-a0a1q4yuw0 , 9actn-a0a1q5diu2 , 9actn-a0a1q5dxi1 , 9actn-a0a1q5ftj7 , 9actn-a0a1q5h9t1 , 9actn-a0a1q5k3r2 , 9actn-a0a1q5l4j4 , 9actn-a0a1q5l7v2 , 9actn-a0a1q5ltu8 , 9actn-a0a1q5m0p6 , 9actn-a0a1q5mza2 , 9pseu-a0a1q4yle9 , 9pseu-a0a1q4ylg6 , 9actn-a0a1q5hn40 , 9actn-a0a1q4zi93 , 9actn-a0a1q5d7w2 , 9actn-a0a1q5mn15 , 9pseu-a0a1q4xtq2 , 9actn-a0a1q5le62 , 9actn-a0a1q5fgx4 , strsp-TnmK1 , strsp-TnmK2 , strun-UcmK2 , 9actn-a0a1q4w6n9 , 9actn-a0a1q4yc91 , 9actn-a0a1q4yun2 , 9actn-a0a1q5g588 , 9actn-a0a1q5h571 , 9actn-a0a1q5kh06 , 9actn-a0a1q5lnf3 , 9actn-a0a1q5n7d1 , 9actn-a0a1q5n4g6

Title : Prolyl Oligopeptidase Enhances alpha-Synuclein Dimerization via Direct Protein-Protein Interaction - Savolainen_2015_J.Biol.Chem_290_5117
Author(s) : Savolainen MH , Yan X , Myohanen TT , Huttunen HJ
Ref : Journal of Biological Chemistry , 290 :5117 , 2015
Abstract : Prolyl oligopeptidase (PREP) accelerates the aggregation of alpha-synuclein (aSyn), a key protein involved in development of Parkinson disease and other synucleinopathies. PREP inhibitors reduce aSyn aggregation, but the mechanism has remained unknown. We have now used protein-fragment complementation assays (PCA) and microscale thermophoresis in parallel to show that PREP interacts directly with aSyn in both intact cells and in a cell-free system. Using split luciferase-based PCA, we first showed that PREP enhances the formation of soluble aSyn dimers in live Neuro-2A neuroblastoma cells. A PREP inhibitor, KYP-2047, reduced aSyn dimerization in PREP-expressing cells but not in cells lacking PREP expression. aSyn dimerization was also enhanced by PREP(S554A), an enzymatically inactive PREP mutant, but this was not affected by KYP-2047. PCA and microscale thermophoresis studies showed that aSyn interacts with both PREP and PREP(S554A) with low micromolar affinity. Neither the proline-rich, C-terminal domain of aSyn nor the hydrolytic activity of PREP was required for the interaction with PREP. Our results show that PREP binds directly to aSyn to enhance its dimerization and may thus serve as a nucleation point for aSyn aggregation. Native gel analysis showed that KYP-2047 shifts PREP to a compact monomeric form with reduced ability to promote aSyn nucleation. As PREP inhibition also enhances autophagic clearance of aSyn, PREP inhibitors may reduce accumulation of aSyn inclusions via a dual mechanism and are thus a novel therapeutic candidate for synucleinopathies. Our results also suggest that PREP has other cellular functions in addition to its peptidase activity.
ESTHER : Savolainen_2015_J.Biol.Chem_290_5117
PubMedSearch : Savolainen_2015_J.Biol.Chem_290_5117
PubMedID: 25555914
Gene_locus related to this paper: human-PREP

Title : Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities - Yan_2015_J.Agric.Food.Chem_63_10611
Author(s) : Yan X , Tang J , Dos Santos Passos C , Nurisso A , Simoes-Pires CA , Ji M , Lou H , Fan P
Ref : Journal of Agricultural and Food Chemistry , 63 :10611 , 2015
Abstract : Hemp seed is known for its content of fatty acids, proteins, and fiber, which contribute to its nutritional value. Here we studied the secondary metabolites of hemp seed aiming at identifying bioactive compounds that could contribute to its health benefits. This investigation led to the isolation of 4 new lignanamides, cannabisin M (2), cannabisin N (5), cannabisin O (8), and 3,3'-demethyl-heliotropamide (10), together with 10 known lignanamides, among which 4 was identified for the first time from hemp seed. Structures were established on the basis of NMR, HR-MS, UV, and IR as well as by comparison with the literature data. Lignanamides 2, 7, and 9-14 showed good antioxidant activity, among which 7, 10, and 13 also inhibited acetylcholinesterase in vitro. The newly identified compounds in this study add to the diversity of hemp seed composition, and the bioassays implied that hemp seed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds.
ESTHER : Yan_2015_J.Agric.Food.Chem_63_10611
PubMedSearch : Yan_2015_J.Agric.Food.Chem_63_10611
PubMedID: 26585089

Title : Effects of ZnO Nanoparticles on Dimethoate-Induced Toxicity in Mice - Yan_2015_J.Agric.Food.Chem_63_8292
Author(s) : Yan X , Rong R , Zhu S , Guo M , Gao S , Wang S , Xu X
Ref : Journal of Agricultural and Food Chemistry , 63 :8292 , 2015
Abstract : The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate have increased the risk of people's coexposure to nano ZnO and dimethoate. Therefore, we evaluated in this study the effects of nano or bulk ZnO on dimethoate-induced toxicity in mice. The serum biochemical parameters, biodistributions, oxidative stress responses, and histopathological changes in mice were measured after intragastric administration of nano or bulk ZnO and/or dimethoate for 14 days. Oral administration of nano or bulk ZnO at a dose of 50 mg/kg did not cause obvious injury in mice. In contrast, oral administration of dimethoate at a dose of 15 mg/kg induced observable oxidative damage in mice. Co-administration of nano or bulk ZnO with dimethoate significantly increased Zn accumulation by 30.7 +/- 1.7% or 29.7 +/- 2.4% and dimethoate accumulation by 42.8 +/- 2.1% or 46.6 +/- 2.9% in the liver, respectively. The increased accumulations of dimethoate and Zn in the liver reduced its cholinesterase activity from 5.64 +/- 0.45 U/mg protein to 4.67 +/- 0.42 U/mg protein or 4.76 +/- 0.45 U/mg protein for nano or bulk ZnO, respectively. Furthermore, the accumulations of dimethoate and Zn in liver also increased hepatic oxidative stress, resulting in severe liver damage. Both nano and bulk ZnO dissolved quickly in acidic gastric fluid, regardless of particle size; therefore, they had nearly identical enhanced effects on dimethoate-induced toxicity in mice.
ESTHER : Yan_2015_J.Agric.Food.Chem_63_8292
PubMedSearch : Yan_2015_J.Agric.Food.Chem_63_8292
PubMedID: 26335275

Title : A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'-dioxygenase in Sphingobium wenxiniae JZ-1 - Wang_2014_Appl.Environ.Microbiol_80_3811
Author(s) : Wang C , Chen Q , Wang R , Shi C , Yan X , He J , Hong Q , Li S
Ref : Applied Environmental Microbiology , 80 :3811 , 2014
Abstract : Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme activity in Escherichia coli was achieved only through the coexpression of pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate 1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the transcriptional level of pbaC was far less than that of pbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase.
ESTHER : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedSearch : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedID: 24747891
Gene_locus related to this paper: 9sphn-q0kjt3 , sphwj-a0a059u2z8

Title : Fe(3)O(4) magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent - Liang_2013_Anal.Chem_85_308
Author(s) : Liang M , Fan K , Pan Y , Jiang H , Wang F , Yang D , Lu D , Feng J , Zhao J , Yang L , Yan X
Ref : Analytical Chemistry , 85 :308 , 2013
Abstract : Rapid and sensitive detection methods are in urgent demand for the screening of extensively used organophosphorus pesticides and highly toxic nerve agents for their neurotoxicity. In this study, we developed a novel Fe(3)O(4) magnetic nanoparticle (MNP) peroxidase mimetic-based colorimetric method for the rapid detection of organophosphorus pesticides and nerve agents. The detection assay is composed of MNPs, acetylcholinesterase (AChE), and choline oxidase (CHO). The enzymes AChE and CHO catalyze the formation of H(2)O(2) in the presence of acetylcholine, which then activates MNPs to catalyze the oxidation of colorimetric substrates to produce a color reaction. After incubation with the organophosphorus neurotoxins, the enzymatic activity of AChE was inhibited and produced less H(2)O(2), resulting in a decreased catalytic oxidation of colorimetric substrates over MNP peroxidase mimetics, accompanied by a drop in color intensity. Three organophosphorus compounds were tested on the assay: acephate and methyl-paraoxon as representative organophosphorus pesticides and the nerve agent Sarin. The novel assay displayed substantial color change after incubation in organophosphorus neurotoxins in a concentration-dependent manner. As low as 1 nM Sarin, 10 nM methyl-paraoxon, and 5 muM acephate are easily detected by the novel assay. In conclusion, by employing the peroxidase-mimicking activity of MNPs, the developed colorimetric assay has the potential of becoming a screening tool for the rapid and sensitive assessment of the neurotoxicity of an overwhelming number of organophosphate compounds.
ESTHER : Liang_2013_Anal.Chem_85_308
PubMedSearch : Liang_2013_Anal.Chem_85_308
PubMedID: 23153113

Title : A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-beta(2)(5)(-)(3)(5)-treated rats following intranasal administration - Wu_2012_Eur.J.Pharm.Biopharm_80_368
Author(s) : Wu H , Li J , Zhang Q , Yan X , Guo L , Gao X , Qiu M , Jiang X , Lai R , Chen H
Ref : Eur J Pharm Biopharm , 80 :368 , 2012
Abstract : Because of the immunogenicity and toxicity in vivo of large molecules such as lectins, the application of these molecules is remarkably restricted in drug delivery systems. In this study, to improve the brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, Odorranalectin (OL, 1700 Da), a novel non-immunogenic small peptide, was selected to establish an OL-modified cubosomes (Cubs) system. The streptavidin (SA)-conjugated Cubs were prepared by incorporating maleimide-PEG-oleate and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothiolane thiolated SA; mono-biotinylated OL was then coupled with the SA-modified Cubs. The OL-decorated Cubs (OL-Cubs) devised via a non-covalent SA-biotin "bridge" made it easy to conjugate OL and determine the number of ligands on the surface of the Cubs using sensitive chemiluminescent detection. Retention of the bio-recognitive activity of OL after covalent coupling was verified by hemagglutination testing. Nose-to-brain delivery characteristic of OL-Cubs was investigated by in vivo fluorescent biodistribution using coumarin-6 as a marker. The relative uptake of coumarin carried by OL-Cubs was 1.66- to 3.46-fold in brain tissues compared to that incorporated in the Cubs. Besides, Gly14-Humanin (S14G-HN) as a model peptide drug was loaded into cubosomes and evaluated for its pharmacodynamics on Alzheimer's disease (AD) rats following intranasal administration by Morris water maze test and acetylcholinesterase activity determination. The results suggested that OL functionalization enhanced the therapeutic effects of S14G-HN-loaded cubosomes on AD. Thus, OL-Cubs might offer a novel effective and noninvasive system for brain drug delivery, especially for peptides and proteins.
ESTHER : Wu_2012_Eur.J.Pharm.Biopharm_80_368
PubMedSearch : Wu_2012_Eur.J.Pharm.Biopharm_80_368
PubMedID: 22061263

Title : Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population - Li_2011_Ann.Hum.Genet_75_605
Author(s) : Li L , Qi L , Lv N , Gao Q , Cheng Y , Wei Y , Ye J , Yan X , Dang A
Ref : Ann Hum Genet , 75 :605 , 2011
Abstract : The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.
ESTHER : Li_2011_Ann.Hum.Genet_75_605
PubMedSearch : Li_2011_Ann.Hum.Genet_75_605
PubMedID: 21834908
Gene_locus related to this paper: human-PLA2G7

Title : Codon optimization, expression and enzymatic comparison of Rhizopus oryzae lipases pro-ROL and m-ROL in Pichia pastoris - Yang_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_1780
Author(s) : Yang J , Yan X , Huang R , Zhang B
Ref : Sheng Wu Gong Cheng Xue Bao , 27 :1780 , 2011
Abstract : Rhizopus oryzae lipase (ROL) is not only a biocatalyst used in a broad range of biotechnological fields, but also a model to investigate the function of intramolecular chaperone in the post-translational processing of lipase. In this study, we cloned and expressed the mature lipase gene (m-ROL) containing the pre-sequence (pro-ROL) of R. oryzae HU3005 in Pichia pastoris GS115 and characterized their enzymatic activities. m-ROL exhibited higher hydrolysis activity towards middle-chain substrates (C10 and C12) at pH 9.0, whereas pro-ROL preferred short-chain substrates (C4) and displayed maximal activity at pH 8.0. Moreover, pro-ROL possessed better thermal stability than m-ROL. This enzymatic discrepancy between m-ROL and p-ROL may be due to the pre-sequence that affects the folding and conformation of the mature lipase domain. To improve the expression level of m-ROL in P. pastoris, overlap extension PCR was conducted to substitute eight less-frequently used codons of m-ROL with frequently used codons. After methanol-induced expression for 72 h, the activity and protein content of the codon optimized m-ROL reached 132.7 U/mL and 50.4 mg/L, while the activity of the parental m-ROL and pro-ROL are 28.7 U/mL and 14.4 mg/L, 29.6 U/mL and 14.1 mg/L, respectively.
ESTHER : Yang_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_1780
PubMedSearch : Yang_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_1780
PubMedID: 22506419

Title : Differential acetylcholine and choline concentrations in the cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia - Jia_2004_Chin.Med.J.(Engl)_117_1161
Author(s) : Jia JP , Jia JM , Zhou WD , Xu M , Chu CB , Yan X , Sun YX
Ref : Chinese Medical Journal (Engl) , 117 :1161 , 2004
Abstract : BACKGROUND: An important aspect of Alzheimer's disease (AD) is loss or impairment of cholinergic neurons. It is controversial whether there is a similar cholinergic impairment and cerebral deficit of acetylcholine (ACh) in the case of vascular dementia (VD). The purpose of this study was to explore the levels of ACh and choline (Ch) in the cerebrospinal fluid (CSF) of patients with AD and VD, and their possible relationship with cognitive impairment.
METHODS: Twenty-two AD patients, twenty-two VD patients, and twenty normal controls were recruited and scored with a Mini-Mental State Examination (MMSE). CSF concentrations of ACh and Ch were measured using high-performance liquid chromatography with an electrochemical detector (HPLC-ECD) and the results were then compared to cognitive status.
RESULTS: ACh concentrations in CSF of AD patients [(10.7 +/- 5.1) nmol/L] and VD patients [(16.8 +/- 7.4) nmol/L] were both significantly lower than in controls [(34.5 +/- 9.0) nmol/L, t = 10.67, P < 0.001; t = 6.91, P < 0.001]. Both results correlated positively with MMSE scores (rs = 0.88 and rs = 0.85, respectively, P < 0.01). The CSF concentration of Ch was significantly higher in VD patients [(887.4 +/- 187.4) nmol/L] compared to AD patients [(627.6 +/- 145.1) nmol/L, t = 6.4, P < 0.001] and controls [(716.0 +/- 159.4) nmol/L, t = 4.2, P = 0.002]. CSF Ch concentration showed no difference between AD patients and normal controls, nor did it correlate with MMSE score in any of the three groups.
CONCLUSIONS: The positive correlation between ACh deficit and cognitive impairment suggests that ACh is an important neurotransmitter for memory. The similar decrease in ACh concentration in AD and VD patients may imply a similar pathogenesis for the process of cognitive impairment involved in these two disorders. The elevated CSF levels of Ch in VD patients compared to AD patients may be useful diagnostically. Cholinesterase inhibitors may be helpful not only for AD patients, but also for VD patients.
ESTHER : Jia_2004_Chin.Med.J.(Engl)_117_1161
PubMedSearch : Jia_2004_Chin.Med.J.(Engl)_117_1161
PubMedID: 15361288

Title : A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome - Mural_2002_Science_296_1661
Author(s) : Mural RJ , Adams MD , Myers EW , Smith HO , Miklos GL , Wides R , Halpern A , Li PW , Sutton GG , Nadeau J , Salzberg SL , Holt RA , Kodira CD , Lu F , Chen L , Deng Z , Evangelista CC , Gan W , Heiman TJ , Li J , Li Z , Merkulov GV , Milshina NV , Naik AK , Qi R , Shue BC , Wang A , Wang J , Wang X , Yan X , Ye J , Yooseph S , Zhao Q , Zheng L , Zhu SC , Biddick K , Bolanos R , Delcher AL , Dew IM , Fasulo D , Flanigan MJ , Huson DH , Kravitz SA , Miller JR , Mobarry CM , Reinert K , Remington KA , Zhang Q , Zheng XH , Nusskern DR , Lai Z , Lei Y , Zhong W , Yao A , Guan P , Ji RR , Gu Z , Wang ZY , Zhong F , Xiao C , Chiang CC , Yandell M , Wortman JR , Amanatides PG , Hladun SL , Pratts EC , Johnson JE , Dodson KL , Woodford KJ , Evans CA , Gropman B , Rusch DB , Venter E , Wang M , Smith TJ , Houck JT , Tompkins DE , Haynes C , Jacob D , Chin SH , Allen DR , Dahlke CE , Sanders R , Li K , Liu X , Levitsky AA , Majoros WH , Chen Q , Xia AC , Lopez JR , Donnelly MT , Newman MH , Glodek A , Kraft CL , Nodell M , Ali F , An HJ , Baldwin-Pitts D , Beeson KY , Cai S , Carnes M , Carver A , Caulk PM , Center A , Chen YH , Cheng ML , Coyne MD , Crowder M , Danaher S , Davenport LB , Desilets R , Dietz SM , Doup L , Dullaghan P , Ferriera S , Fosler CR , Gire HC , Gluecksmann A , Gocayne JD , Gray J , Hart B , Haynes J , Hoover J , Howland T , Ibegwam C , Jalali M , Johns D , Kline L , Ma DS , MacCawley S , Magoon A , Mann F , May D , McIntosh TC , Mehta S , Moy L , Moy MC , Murphy BJ , Murphy SD , Nelson KA , Nuri Z , Parker KA , Prudhomme AC , Puri VN , Qureshi H , Raley JC , Reardon MS , Regier MA , Rogers YH , Romblad DL , Schutz J , Scott JL , Scott R , Sitter CD , Smallwood M , Sprague AC , Stewart E , Strong RV , Suh E , Sylvester K , Thomas R , Tint NN , Tsonis C , Wang G , Williams MS , Williams SM , Windsor SM , Wolfe K , Wu MM , Zaveri J , Chaturvedi K , Gabrielian AE , Ke Z , Sun J , Subramanian G , Venter JC , Pfannkoch CM , Barnstead M , Stephenson LD
Ref : Science , 296 :1661 , 2002
Abstract : The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
ESTHER : Mural_2002_Science_296_1661
PubMedSearch : Mural_2002_Science_296_1661
PubMedID: 12040188
Gene_locus related to this paper: mouse-ABH15 , mouse-Ces3b , mouse-Ces4a , mouse-dpp4 , mouse-FAP , mouse-Lipg , mouse-Q8C1A9 , mouse-rbbp9 , mouse-SERHL , mouse-SPG21 , mouse-w4vsp6

Title : The highly recombinogenic bz locus lies in an unusually gene-rich region of the maize genome - Fu_2001_Proc.Natl.Acad.Sci.U.S.A_98_8903
Author(s) : Fu H , Park W , Yan X , Zheng Z , Shen B , Dooner HK
Ref : Proceedings of the National Academy of Sciences of the United States of America , 98 :8903 , 2001
Abstract : The bronze (bz) locus exhibits the highest rate of recombination of any gene in higher plants. To investigate the possible basis of this high rate of recombination, we have analyzed the physical organization of the region around the bz locus. Two adjacent bacterial artificial chromosome clones, comprising a 240-kb contig centered around the Bz-McC allele, were isolated, and 60 kb of contiguous DNA spanning the two bacterial artificial chromosome clones was sequenced. We find that the bz locus lies in an unusually gene-rich region of the maize genome. Ten genes, at least eight of which are shown to be transcribed, are contained in a 32-kb stretch of DNA that is uninterrupted by retrotransposons. We have isolated nearly full length cDNAs corresponding to the five proximal genes in the cluster. The average intertranscript distance between them is just 1 kb, revealing a surprisingly compact packaging of adjacent genes in this part of the genome. At least 11 small insertions, including several previously described miniature inverted repeat transposable elements, were detected in the introns and 3' untranslated regions of genes and between genes. The gene-rich region is flanked at the proximal and distal ends by retrotransposon blocks. Thus, the maize genome appears to have scattered regions of high gene density similar to those found in other plants. The unusually high rate of intragenic recombination seen in bz may be related to the very high gene density of the region.
ESTHER : Fu_2001_Proc.Natl.Acad.Sci.U.S.A_98_8903
PubMedSearch : Fu_2001_Proc.Natl.Acad.Sci.U.S.A_98_8903
PubMedID: 11438686