Lin Y

References (106)

Title : Identification of Acyl-Protein Thioesterase-1 as a Polysorbate-degrading Host Cell Protein in a Monoclonal Antibody Formulation Using Activity-based Protein Profiling - Sprager_2024_J.Pharm.Sci__
Author(s) : Sprager E , Moller J , Lin Y , Reisinger V , Bratkovic T , Lunder M , Vasl J , Krajnc A
Ref : J Pharm Sci , : , 2024
Abstract : Polysorbate (PS) degradation in monoclonal antibody (mAb) formulations poses a significant challenge in the biopharmaceutical industry. PS maintains protein stability during drug product's shelf life but is vulnerable to breakdown by low-abundance residual host cell proteins (HCPs), particularly hydrolytic enzymes such as lipases and esterases. In this study, we used activity-based protein profiling (ABPP) coupled with mass spectrometry to identify acyl-protein thioesterase-1 (APT-1) as a polysorbate-degrading HCP in one case of mAb formulation with stability problems. We validated the role of APT1 by matching the polysorbate degradation fingerprint in the mAb formulation with that of a recombinant APT1 protein. Furthermore, we found an agreement between APT1 levels and PS degradation rates in the mAb formulation, and we successfully halted PS degradation using APT1-specific inhibitors ML348 and ML211. APT1 was found to co-purify with a specific mAb via hitchhiking mechanism. Our work provides a streamlined approach to identifying critical HCPs in PS degradation, supporting quality-by-design principles in pharmaceutical development.
ESTHER : Sprager_2024_J.Pharm.Sci__
PubMedSearch : Sprager_2024_J.Pharm.Sci__
PubMedID: 38772451
Gene_locus related to this paper: human-LYPLA1

Title : Combinatorial preparation and structural characterization of anthocyanins and aglycones from Purple-heart Radish for evaluation of physicochemical stability and pancreatic lipase inhibitory activity - Yuan_2024_Food.Chem_446_138832
Author(s) : Yuan T , Wang L , Chen L , Zhong J , Lin Y , Wang Y , Lin C , Fan H
Ref : Food Chem , 446 :138832 , 2024
Abstract : In this study, an efficient approach to preparation of different anthocyanins from Purple-heart Radish was developed by combining microwave-assisted extraction (MAE), macroporous resin purification (MRP) and ultrasound-assisted acid hydrolysis (UAAH) for evaluation of physicochemical stability and pancreatic lipase (PL) inhibitory activity. By optimization of MAE, MRP and UAAH processes, the anthocyanins reached the yield of 6.081 +/- 0.106 mg/g, the purity of 78.54 +/- 0.62 % (w/w) and the content of 76.29 +/- 1.31 % (w/w), respectively. With high-resolution UHPLC-Q-Orbitrap/MS, 15 anthocyanins were identified as pelargonins with diverse glucosides and confirmed by pelargonidin standard. By glycosylation, pelargonins exhibited higher stability in different pH, temperature, light, metal ions environments than that of pelargonidin. However, PL inhibitory assay, kinetic analysis and molecular docking demonstrated that pelargonidin had higher PL inhibitory activity than pelargonins even though with similar binding sites and a dose-effect relationship. The above results revealed that the effect of glycosylation and deglycosylation on PL inhibitory activity and physicochemical stability.
ESTHER : Yuan_2024_Food.Chem_446_138832
PubMedSearch : Yuan_2024_Food.Chem_446_138832
PubMedID: 38412808

Title : Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis - Lin_2024_Medicine.(Baltimore)_103_e38018
Author(s) : Lin Y , Xu G , Li L , Xiang J , Zhai L
Ref : Medicine (Baltimore) , 103 :e38018 , 2024
Abstract : Incretin-based drugs, a class of Antidiabetic medications (ADMs) used in the treatment of type 2 diabetes, may affect the incidence of prostate cancer (PCa). But real-world evidence for this possible effect is lacking. Therefore, the aim of this study is to assess the effect of incretin-based drugs on the incidence of PCa, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. We searched PubMed, Embase, and Cochrane Library databases for eligible studies through September 2023. Two independent reviewers performed screening and data extraction. We used the Cochrane Handbook for Systematic Reviews and the Newcastle-Ottawa Scale (NOS) to assess the quality of included randomized controlled trials (RCTs) and cohort studies. We did a meta-analysis of available trial data to calculate overall risk ratios (RRs) for PCa. A total of 1238 articles were identified in our search. After screening for eligibility, 7 high-quality studies met the criteria for meta-analysis, including 2 RCTs and 5 cohort studies, with a total of 1165,738 patients. Compared with the control group, we found that incretin-based drugs reduced the relative risk of PCa by 35% (95% confidence interval (CI), 0.17-0.49; P=.0006). In subgroup analysis, the RR values for GLP-1 receptor agonists and DPP-4 inhibitors were 62% (95% CI, 0.45-0.85; P=.003) and 72% (95% CI, 0.46-1.12; P=.14), respectively. Incretin-based drugs are associated with lower incidence of prostate cancer and may have a preventive effect on prostate cancer in patients with type 2 diabetes.
ESTHER : Lin_2024_Medicine.(Baltimore)_103_e38018
PubMedSearch : Lin_2024_Medicine.(Baltimore)_103_e38018
PubMedID: 38758855

Title : Bifunctional enzyme-mimicking metal-organic frameworks for sensitive acetylcholine analysis - Wen_2024_Talanta_275_126112
Author(s) : Wen Y , Xu W , Wu Y , Tang Y , Liu M , Sha M , Li J , Xiao R , Hu L , Lin Y , Zhu C , Gu W
Ref : Talanta , 275 :126112 , 2024
Abstract : The development of nanomaterials with multi-enzyme-like activity is crucial for addressing challenges in multi-enzyme-based biosensing systems, including cross-talk between different enzymes and the complexities and costs associated with detection. In this study, Pt nanoparticles (Pt NPs) were successfully supported on a Zr-based metal-organic framework (MOF-808) to create a composite catalyst named MOF-808/Pt NPs. This composite catalyst effectively mimics the functions of acetylcholinesterase (AChE) and peroxidase (POD). Leveraging this capability, we replaced AChE and POD with MOF-808/Pt NPs and constructed a biosensor for sensitive detection of acetylcholine (ACh). The MOF-808/Pt NPs catalyze the hydrolysis of ACh, resulting in the production of acetic acid. The subsequent reduction in pH value further enhances the POD-like activity of the MOFs, enabling signal amplification through the oxidation of a colorimetric substrate. This biosensor capitalizes on pH variations during the reaction to modulate the different enzyme-like activities of the MOFs, simplifying the detection process and eliminating cross-talk between different enzymes. The developed biosensor holds great promise for clinical diagnostic analysis and offers significant application value in the field.
ESTHER : Wen_2024_Talanta_275_126112
PubMedSearch : Wen_2024_Talanta_275_126112
PubMedID: 38677169

Title : Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria - Wu_2024_Faseb.j_38_e23641
Author(s) : Wu Q , Xia Y , Guo MS , Au TY , Yuen GKW , Kong I , Wang Z , Lin Y , Dong TTX , Tsim KWK
Ref : Faseb j , 38 :e23641 , 2024
Abstract : Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.
ESTHER : Wu_2024_Faseb.j_38_e23641
PubMedSearch : Wu_2024_Faseb.j_38_e23641
PubMedID: 38690717

Title : Association of lipoprotein lipase (LPL) gene variants with hyperlipidemic acute pancreatitis in southeastern Chinese population - Li_2024_Arch.Endocrinol.Metab_68_e230195
Author(s) : Li Y , Cai H , Lin Y , Huang Z , Zhou A , Huang T , Zeng YE , Ye M , Guo G
Ref : Arch Endocrinol Metab , 68 :e230195 , 2024
Abstract : OBJECTIVE: The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. SUBJECTS AND METHODS: In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. RESULTS: The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). CONCLUSION: Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.
ESTHER : Li_2024_Arch.Endocrinol.Metab_68_e230195
PubMedSearch : Li_2024_Arch.Endocrinol.Metab_68_e230195
PubMedID: 38530959
Gene_locus related to this paper: human-LPL

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2024_Ther.Apher.Dial_28_141
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , 28 :141 , 2024
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2024_Ther.Apher.Dial_28_141
PubMedSearch : Wan_2024_Ther.Apher.Dial_28_141
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease - Park_2023_Chem.Sci_14_9293
Author(s) : Park S , Kim M , Lin Y , Hong M , Nam G , Mieczkowski A , Kardos J , Lee YH , Lim MH
Ref : Chem Sci , 14 :9293 , 2023
Abstract : The underlying causes of Alzheimer's disease (AD) remain a mystery, with multiple pathological components, including oxidative stress, acetylcholinesterase, amyloid-beta, and metal ions, all playing a role. Here we report a strategic approach to designing flavonoids that can effectively tackle multiple pathological elements involved in AD. Our systematic investigations revealed key structural features for flavonoids to simultaneously target and regulate pathogenic targets. Our findings led to the development of a highly promising flavonoid that exhibits a range of functions, based on a complete structure-activity relationship analysis. Furthermore, our mechanistic studies confirmed that this flavonoid's versatile reactivities are driven by its redox potential and direct interactions with pathogenic factors. This work highlights the potential of multi-target-directed flavonoids as a novel solution in the fight against AD.
ESTHER : Park_2023_Chem.Sci_14_9293
PubMedSearch : Park_2023_Chem.Sci_14_9293
PubMedID: 37712013

Title : Association between Neuroligin-1 polymorphism and plasma glutamine levels in individuals with autism spectrum disorder - Lee_2023_EBioMedicine_95_104746
Author(s) : Lee IH , Walker DI , Lin Y , Smith MR , Mandl KD , Jones DP , Kong SW
Ref : EBioMedicine , 95 :104746 , 2023
Abstract : BACKGROUND: Unravelling the relationships between candidate genes and autism spectrum disorder (ASD) phenotypes remains an outstanding challenge. Endophenotypes, defined as inheritable, measurable quantitative traits, might provide intermediary links between genetic risk factors and multifaceted ASD phenotypes. In this study, we sought to determine whether plasma metabolite levels could serve as endophenotypes in individuals with ASD and their family members. METHODS: We employed an untargeted, high-resolution metabolomics platform to analyse 14,342 features across 1099 plasma samples. These samples were collected from probands and their family members participating in the Autism Genetic Resource Exchange (AGRE) (N = 658), compared with neurotypical individuals enrolled in the PrecisionLink Health Discovery (PLHD) program at Boston Children's Hospital (N = 441). We conducted a metabolite quantitative trait loci (mQTL) analysis using whole-genome genotyping data from each cohort in AGRE and PLHD, aiming to prioritize significant mQTL and metabolite pairs that were exclusively observed in AGRE. FINDINGS: Within the AGRE group, we identified 54 significant associations between genotypes and metabolite levels (P < 5.27 x 10(-)(11)), 44 of which were not observed in the PLHD group. Plasma glutamine levels were found to be associated with variants in the NLGN1 gene, a gene that encodes post-synaptic cell-adhesion molecules in excitatory neurons. This association was not detected in the PLHD group. Notably, a significant negative correlation between plasma glutamine and glutamate levels was observed in the AGRE group, but not in the PLHD group. Furthermore, plasma glutamine levels showed a negative correlation with the severity of restrictive and repetitive behaviours (RRB) in ASD, although no direct association was observed between RRB severity and the NLGN1 genotype. INTERPRETATION: Our findings suggest that plasma glutamine levels could potentially serve as an endophenotype, thus establishing a link between the genetic risk associated with NLGN1 and the severity of RRB in ASD. This identified association could facilitate the development of novel therapeutic targets, assist in selecting specific cohorts for clinical trials, and provide insights into target symptoms for future ASD treatment strategies. FUNDING: This work was supported by the National Institute of Health (grant numbers: R01MH107205, U01TR002623, R24OD024622, OT2OD032720, and R01NS129188) and the PrecisionLink Biobank for Health Discovery at Boston Children's Hospital.
ESTHER : Lee_2023_EBioMedicine_95_104746
PubMedSearch : Lee_2023_EBioMedicine_95_104746
PubMedID: 37544204
Gene_locus related to this paper: human-NLGN1

Title : DAGLbeta is the principal synthesizing enzyme of 2-AG and promotes aggressive intrahepatic cholangiocarcinoma via AP-1\/DAGLbeta\/miR4516 feedforward circuitry - Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
Author(s) : Ma M , Zeng G , Tan B , Zhao G , Su Q , Zhang W , Song Y , Liang J , Xu B , Wang Z , Chen J , Hou M , Yang C , Yun J , Huang Y , Lin Y , Chen D , Han Y , DeMorrow S , Liang L , Lai J , Huang L
Ref : American Journal of Physiology Gastrointest Liver Physiol , : , 2023
Abstract : The endocannabinoid system (ECS) is dysregulated in various liver diseases. Previously we had shown that the major endocannabinoid 2-arachidonoyl glycerol (2-AG) promoted tumorigenesis of intrahepatic cholangiocarcinoma (ICC). However, biosynthesis regulation and clinical significance of 2-AG remain elusive. In present study we quantified 2-AG by gas chromatography/mass spectrometry (GC/MS) and showed that 2-AG was enriched in ICC patients' samples as well as in thioacetamide-induced orthotopic rat ICC model. Moreover, we found that diacylglycerol lipase beta (DAGLbeta) was the principal synthesizing enzyme of 2-AG which significantly upregulated in ICC. DAGLbeta promoted tumorigenesis and metastasis of ICC in vitro and in vivo, and positively correlated with clinical stage and poor survival in ICC patients. Functional studies showed that AP-1 (heterodimers of c-Jun and FRA1) directly binded to the promoter and regulated transcription of DAGLbeta, which can be enhanced by lipopolysaccharide (LPS). miR-4516 was identified as the tumor-suppressing miRNA of ICC which can be significantly suppressed by LPS, 2-AG or ectopic DAGLbeta overexpression. FRA1 and STAT3 were targets of miR-4516 and overexpression of miRNA-4516 significantly suppressed expression of FRA1, SATA3 and DAGLbeta. Expression of miRNA-4516 was negatively correlated with FRA1, SATA3 and DAGLbeta in ICC patients' samples. Our findings identify DAGLbeta as the principal synthesizing enzyme of 2-AG in ICC. DAGLbeta promotes oncogenesis and metastasis of ICC and is transcriptionally regulated by a novel AP-1/DAGLbeta/miR4516 feedforward circuitry.
ESTHER : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedSearch : Ma_2023_Am.J.Physiol.Gastrointest.Liver.Physiol__
PubMedID: 37366545
Gene_locus related to this paper: human-DAGLB

Title : The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis - Wan_2023_Ther.Apher.Dial__
Author(s) : Wan W , Pan Y , Chen Y , Bai S , Yao X , Lin Y , Wu J , Ni L , Mei Y , Qiu H , Zhou Y , Hao Y , Guan Y
Ref : Ther Apher Dial , : , 2023
Abstract : INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.
ESTHER : Wan_2023_Ther.Apher.Dial__
PubMedSearch : Wan_2023_Ther.Apher.Dial__
PubMedID: 37461148
Gene_locus related to this paper: human-DPP6

Title : The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes - Wu_2023_Nat.Commun_14_3132
Author(s) : Wu SA , Shen C , Wei X , Zhang X , Wang S , Chen X , Torres M , Lu Y , Lin LL , Wang HH , Hunter AH , Fang D , Sun S , Ivanova MI , Lin Y , Qi L
Ref : Nat Commun , 14 :3132 , 2023
Abstract : Endoplasmic reticulum (ER)-associated degradation (ERAD) and ER-phagy are two principal degradative mechanisms for ER proteins and aggregates, respectively; however, the crosstalk between these two pathways under physiological settings remains unexplored. Using adipocytes as a model system, here we report that SEL1L-HRD1 protein complex of ERAD degrades misfolded ER proteins and limits ER-phagy and that, only when SEL1L-HRD1 ERAD is impaired, the ER becomes fragmented and cleared by ER-phagy. When both are compromised, ER fragments containing misfolded proteins spatially coalesce into a distinct architecture termed Coalescence of ER Fragments (CERFs), consisted of lipoprotein lipase (LPL, a key lipolytic enzyme and an endogenous SEL1L-HRD1 substrate) and certain ER chaperones. CERFs enlarge and become increasingly insoluble with age. Finally, we reconstitute the CERFs through LPL and BiP phase separation in vitro, a process influenced by both redox environment and C-terminal tryptophan loop of LPL. Hence, our findings demonstrate a sequence of events centered around SEL1L-HRD1 ERAD to dispose of misfolded proteins in the ER of adipocytes, highlighting the profound cellular adaptability to misfolded proteins in the ER in vivo.
ESTHER : Wu_2023_Nat.Commun_14_3132
PubMedSearch : Wu_2023_Nat.Commun_14_3132
PubMedID: 37253728

Title : The effects of carvacrol on development and gene expression profiles in Spodoptera frugiperda - Liu_2023_Pestic.Biochem.Physiol_195_105539
Author(s) : Liu J , Lin Y , Huang Y , Liu L , Cai X , Lin J , Shu B
Ref : Pestic Biochem Physiol , 195 :105539 , 2023
Abstract : The fall armyworm, Spodoptera frugiperda, is a highly polyphagous agricultural pest that is widely distributed around the world and causes severe crop yield loss. Carvacrol showed adverse effects on many pests, such as larval death and growth inhibition. While the effects of carvacrol on S. frugiperda larvae are not yet known. In this study, the effects of carvacrol on S. frugiperda, including larval growth inhibition and mortality induction, were observed. The detoxification and digestive enzyme activities of larvae with 1.0 and 2.0 g/kg carvacrol treatments were analyzed. Carvacrol boosted the enzyme activities of carboxylesterase (CarE) and glutathione S-transferase (GST) while decreasing the activities of alpha-amylase (AMS), lipase (LIP), and trypsin. A total of 3422 differentially expressed genes were identified in the larvae treated with 2.0 g/kg carvacrol, of which the DEGs involved in xenobiotic detoxification, food digestion, and insecticidal targets were further examined. These results suggest that carvacrol could regulate growth and development by affecting the process of food digestion, and exert its toxicity on the larvae through interaction with a variety of insecticidal targets. While the altered expressions of detoxification enzymes might be related to the detoxification and metabolism of carvacrol. Our findings offer a theoretical foundation for the use of carvacrol for S. frugiperda control in the field.
ESTHER : Liu_2023_Pestic.Biochem.Physiol_195_105539
PubMedSearch : Liu_2023_Pestic.Biochem.Physiol_195_105539
PubMedID: 37666589

Title : Sclerotinia sclerotiorum SsCut1 Modulates Virulence and Cutinase Activity - Gong_2022_J.Fungi.(Basel)_8_
Author(s) : Gong Y , Fu Y , Xie J , Li B , Chen T , Lin Y , Chen W , Jiang D , Cheng J
Ref : J Fungi (Basel) , 8 : , 2022
Abstract : The plant cuticle is one of the protective layers of the external surface of plant tissues. Plants use the cuticle layer to reduce water loss and resist pathogen infection. Fungi release cell wall-degrading enzymes to destroy the epidermis of plants to achieve the purpose of infection. Sclerotinia sclerotiorum secretes a large amount of cutinase to disrupt the cuticle layer of plants during the infection process. In order to further understand the role of cutinase in the pathogenic process of S. sclerotiorum, the S. sclerotiorum cutinsae 1 (SsCut1) gene was cloned and analyzed. The protein SsCut1 contains the conserved cutinase domain and a fungal cellulose-binding domain. RT-qPCR results showed that the expression of SsCut1 was significantly upregulated during infection. Split-Marker recombination was utilized for the deletion of the SsCut1 gene, deltaSsCut1 mutants showed reduced cutinase activity and virulence, but the deletion of the SsCut1 gene had no effect on the growth rate, colony morphology, oxalic acid production, infection cushion formation and sclerotial development. Complementation with the wild-type SsCut1 allele restored the cutinase activity and virulence to the wild-type level. Interestingly, expression of SsCut1 in plants can trigger defense responses, but it also enhanced plant susceptibility to SsCut1 gene knock-out mutants. Taken together, our finding demonstrated that the SsCut1 gene promotes the virulence of S. sclerotiorum by enhancing its cutinase activity.
ESTHER : Gong_2022_J.Fungi.(Basel)_8_
PubMedSearch : Gong_2022_J.Fungi.(Basel)_8_
PubMedID: 35628781
Gene_locus related to this paper: scls1-a7erz9

Title : Maternal Low-Protein Diet during Puberty and Adulthood Aggravates Lipid Metabolism of Their Offspring Fed a High-Fat Diet in Mice - Huang_2022_Nutrients_14_
Author(s) : Huang X , Zhuo Y , Jiang D , Zhu Y , Fang Z , Che L , Lin Y , Xu S , Hua L , Zou Y , Huang C , Li L , Wu D , Feng B
Ref : Nutrients , 14 : , 2022
Abstract : A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring's liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7alpha hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.
ESTHER : Huang_2022_Nutrients_14_
PubMedSearch : Huang_2022_Nutrients_14_
PubMedID: 36235710

Title : Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins - Liu_2022_J.Transl.Med_20_418
Author(s) : Liu X , Hua F , Yang D , Lin Y , Zhang L , Ying J , Sheng H , Wang X
Ref : J Transl Med , 20 :418 , 2022
Abstract : Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins.
ESTHER : Liu_2022_J.Transl.Med_20_418
PubMedSearch : Liu_2022_J.Transl.Med_20_418
PubMedID: 36088343

Title : Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative - Zeng_2022_Front.Immunol_13_1113070
Author(s) : Zeng Z , Liu R , Cao W , Yang L , Lin Y , Bi X , Jiang T , Deng W , Wang S , Lu H , Sun F , Shen G , Chang M , Lu Y , Wu S , Hao H , Xu M , Chen X , Hu L , Zhang L , Wan G , Xie Y , Li M
Ref : Front Immunol , 13 :1113070 , 2022
Abstract : AIMS: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. METHODS: We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. RESULTS: 85 HBV DNA-negative and HBeAg-negative patients were 37.90 +/- 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 +/- 10.70 vs 34.80 +/- 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) micromol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 +/- 2156.00 vs 8988.00 +/- 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 +/- 61.40 vs 194.00 +/- 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. CONCLUSIONS: A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology.
ESTHER : Zeng_2022_Front.Immunol_13_1113070
PubMedSearch : Zeng_2022_Front.Immunol_13_1113070
PubMedID: 36685494

Title : Ethanol and its nonoxidative metabolites promote acute liver injury by inducing ER stress, adipocyte death and lipolysis - Park_2022_Cell.Mol.Gastroenterol.Hepatol__
Author(s) : Park SH , Seo W , Xu MJ , Mackowiak B , Lin Y , He Y , Fu Y , Hwang S , Kim SJ , Guan Y , Feng D , Yu L , Lehner R , Liangpunsakul S , Gao B
Ref : Cell Mol Gastroenterol Hepatol , : , 2022
Abstract : BACKGROUND & AIMS: Binge drinking in patients with metabolic syndrome accelerates the development of alcohol-associated liver disease (ALD). However, the underlying mechanisms remain elusive. We investigated if oxidative and non-oxidative alcohol metabolism pathways, diet-induced obesity, and adipose tissues influence the development of acute liver injury in a single ethanol binge model. METHODS & RESULTS: A single ethanol binge was administered to chow-fed or high-fat diet (HFD)-fed wild-type and genetically modified mice. Oral administration of a single dose of ethanol induced acute liver injury and hepatic ER stress in chow- or HFD-fed mice. Disruption of the alcohol dehydrogenase 1 (Adh1) gene elevated blood ethanol concentration and exacerbated acute ethanol-induced ER stress and liver injury in both chow-fed and HFD-fed mice, while disruption of the aldehyde dehydrogenase 2 (Aldh2) gene did not affect such hepatic injury despite high blood acetaldehyde levels. Mechanistic studies revealed that alcohol, not acetaldehyde, promoted hepatic ER stress, fatty acid synthesis, increased adipocyte death and lipolysis, contributing to acute liver injury. Elevated serum fatty acid ethyl esters (FAEEs), which are formed by an enzyme-mediated esterification of ethanol with fatty acids, were detected in mice post ethanol gavage with higher levels in Adh1 knockout mice than that in wild-type mice. Deletion of the carboxylesterase 1d (Ces1d) gene in mice markedly reduced acute ethanol-induced elevation of blood FAEE levels with slight but significant reduction of serum aminotransferase levels. CONCLUSION: Ethanol and its non-oxidative metabolites, FAEEs, not acetaldehyde, promoted acute alcohol-induced liver injury by inducing ER stress, adipocyte death, and lipolysis.
ESTHER : Park_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedSearch : Park_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedID: 36243320

Title : The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial - Liu_2022_BMC.Anesthesiol_22_267
Author(s) : Liu F , Lin X , Lin Y , Deng X , Guo Y , Wang B , Dong R , Bi Y
Ref : BMC Anesthesiol , 22 :267 , 2022
Abstract : BACKGROUND: Postoperative delirium (POD) is a critical complication in patients accepting colon carcinoma surgery. Neostigmine, as a cholinesterase inhibitor, can enhance the transmission of cholinergic transmitters in synaptic space, and play an important role in maintaining the normal level of cognition, attention and consciousness. The objective of this study was to investigate the effect of neostigmine on POD and clinical prognosis. METHODS: A randomized, double-blind controlled trial was implemented in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 454 patients aged 40 to 90 years old accepted colon carcinoma surgery were enrolled between June 7, 2020, and June 7, 2021, with final follow-up on December 8, 2021. Patients were randomly assigned to two groups: the neostigmine group (group N) and the placebo group (group P), the patients in group N were injected with 0.04 mg/kg neostigmine and 0.02 mg/kg atropine intravenously. The primary endpoint was the incidence of POD, researchers evaluated the occurrence of POD by the Confusion Assessment Method (CAM) twice daily (at 10 a.m. and 2 p.m.) during the first 7 postoperative days, POD severity was assessed by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the extubating time, postanesthesia care unit (PACU) time, the incidence of various postoperative complications, length of hospital stays, and 6 months postoperative mortality. RESULTS: The incidence of POD was 20.20% (81/401), including 19.39% (38/196) in group N and 20.98% (43/205) in group P. There was no significant statistical significance in the incidence of POD between group N and group P (P > 0.05); Compared to group P, the extubating time and PACU time in group N were significantly reduced (P < 0.001), the incidence of postoperative pulmonary complications (POPCs) decreased significantly in group N (P < 0.05), while no significant differences were observed in postoperative hospital stay and mortality in 6 months between the two groups (P > 0.05). CONCLUSION: For patients accepted colon carcinoma surgery, neostigmine did not significantly reduce the incidence of POD, postoperative mortality and postoperative hospital stay, while it indeed reduced the extubating time, PACU time and the incidence of POPCs. TRIAL REGISTRATION: The randomized, double-blind, controlled trial was registered retrospectively at on 07/06/2020 (ChiCTR2000033639).
ESTHER : Liu_2022_BMC.Anesthesiol_22_267
PubMedSearch : Liu_2022_BMC.Anesthesiol_22_267
PubMedID: 35996073

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

Title : Enhancement of Fear Extinction Memory and Resistance to Age-Related Cognitive Decline in Butyrylcholinesterase Knockout Mice and (R)-Bambuterol Treated Mice - Liu_2021_Biology.(Basel)_10_
Author(s) : Liu W , Cao Y , Lin Y , Tan KS , Zhao H , Guo H , Tan W
Ref : Biology (Basel) , 10 : , 2021
Abstract : Butyrylcholinesterase (BChE) is detected in plaques preferentially in Alzheimer's disease (AD) and may be associated with stress disorders. However, the physiological function of BChE in the central nervous system remains to be further investigated. BChE knockout (KO) mice and wild-type (WT) mice with orally or intranasal administration of (R)-bambuterol were used to explore the effect of BChE on behavior changes. (R)-bambuterol is a specific and reversible inhibitor of BChE. The behavior changes were evaluated and compared among 3-10 month old mice. Our finding showed that BChE KO and (R)-bambuterol administration enhanced episodic memory, including fear conditioning memory and fear extinction memory in fear conditioning and fear extinction test. BChE KO and (R)-bambuterol administered mice rescued age-related spatial memory and general activity in the water maze test and open field test. The brain metabolomics were imaged using a desorption electrospray ionization mass spectrometry imaging (DESI-MSI). The image of DESI-MS demonstrated that glutamine content increased in the brain of BChE KO mice. In conclusion, this study found that inhibition of BChE ameliorated episodic and spatial memories. This study also suggested that (R)-bambuterol as a BChE inhibitor has the potential application in the treatment of post-traumatic stress disorder (PTSD) and early cognitive decline.
ESTHER : Liu_2021_Biology.(Basel)_10_
PubMedSearch : Liu_2021_Biology.(Basel)_10_
PubMedID: 34062954

Title : Rivastigmine Regulates the HIF-1alpha\/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats - Liu_2021_Front.Pharmacol_12_818907
Author(s) : Liu Y , Li W , Ma X , He J , Lin Y , Lin D
Ref : Front Pharmacol , 12 :818907 , 2021
Abstract : Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia-reperfusion injury (IRI) and inflammation. This study was performed to examine the effect of rivastigmine on flap survival. Sixty male Sprague-Dawley rats with a modified McFarland flap were randomly divided into three groups: control group, 1 ml of solvent (10% DMSO + 90% corn oil); low-dose rivastigmine group (Riv-L), 1.0 mg/kg; and high-dose rivastigmine group (Riv-H), 2.0 mg/kg. All rats were treated once a day. On day 7, the skin flap survival area was measured. After staining with hematoxylin and eosin (H&E), the pathological changes and microvessel density (MVD) were examined. The expression of inflammatory factors IL-1beta and IL-18, CD34, hypoxia-inducible factor-1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were examined to determine the degree of oxidative stress. Lead oxide/gelatin angiography showed neovascularization and laser Doppler blood flowmetry showed the blood filling volume. Rivastigmine significantly increased the flap survival area and improved neovascularization. CD34, VEGF, and HIF-1alpha expression were increased, These changes were more pronounced in the Riv-H group. Treatment with rivastigmine reduced the level of MDA, improved SOD activity, and reduced expression of IL-1beta and IL-18. Our results indicate that Rivastigmine can increase angiogenesis and significantly improve flap survival.
ESTHER : Liu_2021_Front.Pharmacol_12_818907
PubMedSearch : Liu_2021_Front.Pharmacol_12_818907
PubMedID: 35126151

Title : An ABHD17-like hydrolase screening system to identify de-S-acylation enzymes of protein substrates in plant cells - Liu_2021_Plant.Cell__
Author(s) : Liu X , Li M , Li Y , Chen Z , Zhuge C , Ouyang Y , Zhao Y , Lin Y , Xie Q , Yang C , Lai J
Ref : Plant Cell , : , 2021
Abstract : Protein S-acylation is an important post-translational modification in eukaryotes, regulating the subcellular localization, trafficking, stability, and activity of substrate proteins. The dynamic regulation of this reversible modification is mediated inversely by protein S-acyltransferases and de-S-acylation enzymes, but the de-S-acylation mechanism remains unclear in plant cells. Here we characterized a group of putative protein de-S-acylation enzymes in Arabidopsis thaliana, including 11 members of ABHD17 (Alpha/Beta Hydrolase Domain-containing Protein 17)-like Acyl Protein Thioesterases (ABAPTs). A robust system was then established for the screening of de-S-acylation enzymes of protein substrates in plant cells, based on the effects of substrate localization and confirmed via the protein S-acylation levels. Using this system, the ABAPTs, which specifically reduced the S-acylation levels and disrupted the plasma membrane localization of five immunity-related proteins, were identified respectively in Arabidopsis. Further results indicated that the de-S-acylation of RIN4 (RPM1 Interacting Protein 4), which was mediated by ABAPT8, resulted in an increase of cell death in Arabidopsis and Nicotiana benthamiana, supporting the physiological role of the ABAPTs in plants. Collectively, our current work provides a powerful and reliable system to identify the pairs of plant protein substrates and de-S-acylation enzymes for further studies on the dynamic regulation of plant protein S-acylation.
ESTHER : Liu_2021_Plant.Cell__
PubMedSearch : Liu_2021_Plant.Cell__
PubMedID: 34338800
Gene_locus related to this paper: arath-AT1G66900 , arath-AT2G24320 , arath-AT4G31020 , arath-AT5G20520 , arath-AT5G38220 , arath-F3C3.3 , arath-AT1G13610 , arath-At5g14390 , arath-F22K18.40 , arath-At3g01690 , arath-Q9LI62

Title : Repressed OsMESL expression triggers reactive oxygen species mediated broad-spectrum disease resistance in rice - Hu_2021_Plant.Biotechnol.J__
Author(s) : Hu B , Zhou Y , Zhou Z , Sun B , Zhou F , Yin C , Ma W , Chen H , Lin Y
Ref : Plant Biotechnol J , : , 2021
Abstract : A few reports have indicated that a single gene confer resistance to bacterial blight, sheath blight, and rice blast. In this study, we identified a novel disease resistance mutant gene, methyl esterase-like (osmesl) in rice. Mutant rice with T-DNA insertion displayed significant resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo), sheath blight caused by Rhizoctonia solani and rice blast caused by Magnaporthe oryzae. Additionally, CRISPR-Cas9 knockout mutants and RNAi lines displayed resistance to these pathogens. Complementary T-DNA mutants demonstrated a phenotype similar to the wild type (WT), thereby indicating that osmesl confers resistance to pathogens. Protein interaction experiments revealed that OsMESL affects reactive oxygen species (ROS) accumulation by interacting with thioredoxin OsTrxm in rice. Moreover, qRT-PCR results showed significantly reduced mRNA levels of multiple ROS scavenging-related genes in osmesl mutants. Nitroblue tetrazolium staining showed that the pathogens cause ROS accumulation, and quantitative detection revealed significantly increased levels of H(2) O(2) in the leaves of osmesl mutants and RNAi lines after infection. The abundance of JA, a hormone associated with disease resistance, was significantly more in osmesl mutants than in WT plants. Overall, these results suggested that osmesl enhances disease resistance to Xoo, R. solani and M. oryzae by modulating the ROS balance.
ESTHER : Hu_2021_Plant.Biotechnol.J__
PubMedSearch : Hu_2021_Plant.Biotechnol.J__
PubMedID: 33567155
Gene_locus related to this paper: orysj-q0d4u5

Title : Efficient Improvement of Surface Displayed Lipase from Rhizomucor miehei in PichiaPink(TM) Protease-deficient System - Li_2020_Protein.Expr.Purif__105804
Author(s) : Li Z , Miao Y , Yang J , Zhao F , Lin Y , Han S
Ref : Protein Expr Purif , :105804 , 2020
Abstract : Lipase from Rhizomucor miehei (RML) is a versatile biocatalyst used in food industry, fine chemicals, and biodiesel production. Yeast surface display allows direct application of lipase in form of whole-cell biocatalyst, avoiding purification and immobilization process, but the protease of the host cell may affect the activity of displayed lipase. Herein, we used the protease-deficient Pichia pastoris, PichiaPink(TM) to efficiently display RML. RML gene, GCW21 gene and alpha-factor gene were co-cloned into plasmid pPink LC/HC and transformed into protease-deficient P. pastoris. After inducible expression for 96 h, the lipase activity of displayed RML reached 121.72 U/g in proteinase-A-deficient P. pastoris harboring high-copy plasmid, which exhibited 46.7% higher than recombinant P. pastoris without protease defect. Displayed RML occurred the maximum activity at pH 8.0 and 45 degC and the optimal substrate was p-nitrophenyl octanoate. Metal ions Li(+), Na(+), K(+), and Mg(2+) of 1-10 mM had activation towards displayed RML. Displayed RML was effectively improved in PichiaPink(TM) protease-deficient system, which may promote the further research and development of the industrial application of RML.
ESTHER : Li_2020_Protein.Expr.Purif__105804
PubMedSearch : Li_2020_Protein.Expr.Purif__105804
PubMedID: 33276128

Title : Pharmacological Activity, Pharmacokinetics, and Toxicity of Timosaponin AIII, a Natural Product Isolated From Anemarrhena asphodeloides Bunge: A Review - Lin_2020_Front.Pharmacol_11_764
Author(s) : Lin Y , Zhao WR , Shi WT , Zhang J , Zhang KY , Ding Q , Chen XL , Tang JY , Zhou ZY
Ref : Front Pharmacol , 11 :764 , 2020
Abstract : Anemarrhena asphodeloides Bunge is a famous Chinese Materia Medica and has been used in traditional Chinese medicine for more than two thousand years. Steroidal saponins are important active components isolated from A. asphodeloides Bunge. Among which, the accumulation of numerous experimental studies involved in Timosaponin AIII (Timo AIII) draws our attention in the recent decades. In this review, we searched all the scientific literatures using the key word "timosaponin AIII" in the PubMed database update to March 2020. We comprehensively summarized the pharmacological activity, pharmacokinetics, and toxicity of Timo AIII. We found that Timo AIII presents multiple-pharmacological activities, such as anti-cancer, anti-neuronal disorders, anti-inflammation, anti-coagulant, and so on. And the anti-cancer effect of Timo AIII in various cancers, especially hepatocellular cancer and breast cancer, is supposed as its most potential activity. The anti-inflammatory activity of Timo AIII is also beneficial to many diseases. Moreover, VEGFR, X-linked inhibitor of apoptosis protein (XIAP), B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), thromboxane (Tx) A2 receptor, mTOR, NF-kappaB, COX-2, MMPs, acetylcholinesterase (AChE), and so on are identified as the crucial pharmacological targets of Timo AIII. Furthermore, the hepatotoxicity of Timo AIII was most concerned, and the pharmacokinetics and toxicity of Timo AIII need further studies in diverse animal models. In conclusion, Timo AIII is potent as a compound or leading compound for further drug development while still needs in-depth studies.
ESTHER : Lin_2020_Front.Pharmacol_11_764
PubMedSearch : Lin_2020_Front.Pharmacol_11_764
PubMedID: 32581782

Title : Cell Surface Display of Thermomyces lanuginosus Lipase in Pichia pastoris - Yang_2020_Front.Bioeng.Biotechnol_8_544058
Author(s) : Yang J , Huang K , Xu X , Miao Y , Lin Y , Han S
Ref : Front Bioeng Biotechnol , 8 :544058 , 2020
Abstract : A cell surface displayed system in Pichia pastoris GS115 was developed by using GCW61, a glycosylphosphatidylinositol-modified cell wall protein from P. pastoris, as the anchor protein. Thermomyces lanuginosus lipase (TLL) was successfully displayed on the P. pastoris cell wall by fusing GCW61 gene with TLL2 gene (NCBI Accession: O59952) that was optimized with codon bias and synthesized. Cell surface displayed TLL2 was confirmed by the immunofluorescence microscopy. Flask fermentation was performed for 144 h with lipase activity up to 1964.76 U/g. Enzymatic properties of cell surface displayed TLL2 were also investigated. Displayed TLL2 occurred the maximum activity at pH 9 and 55 degC and demonstrated characteristics of wide thermal adaptability and alkaline pH resistance. The optimum substrate was p-nitrophenyl hexanoate. Bivalent metal ions Ca(2+), Mn(2+), and Zn(2+) had the activation effect on displayed TLL2, while Cu(2+), Fe(2+), Fe(3+), K(+), Li(+), Na(+), and Co(2+) ions had the inhibitory effect on it. Since cell surface displayed TLL2 required less purification steps compared with free enzyme and showed high enzyme activities, it would be able to be further applied in various potential applications.
ESTHER : Yang_2020_Front.Bioeng.Biotechnol_8_544058
PubMedSearch : Yang_2020_Front.Bioeng.Biotechnol_8_544058
PubMedID: 33195113

Title : Discovery and Biological Evaluation of New Selective Acetylcholinesterase Inhibitors with Anti-Abeta Aggregation Activity through Molecular Docking-Based Virtual Screening - Liu_2020_Chem.Pharm.Bull.(Tokyo)_68_161
Author(s) : Liu G , Jiao Y , Lin Y , Hao H , Dou Y , Yang J , Jiang CS , Chang P
Ref : Chem Pharm Bull (Tokyo) , 68 :161 , 2020
Abstract : Discovery of novel multifunctional inhibitors targeting acetylcholinesterase (AChE) has becoming a hot spot in anti-Alzheimer's disease (AD) drug development. In the present study, four potent small molecule inhibitors (A01, A02, A03 and A04) of AChE with new chemical scaffold were identified. Inhibitor A03 displayed the most potent inhibition activity on AChE at enzymatic level with IC50 value of 180 nM, and high selectivity towards AChE over butyrylcholinesterase (BChE) by more than 100-fold. The binding modes of compounds A01-A04 were carefully analyzed by molecular docking and molecular dynamics (MD) simulation to provide informative clues for further structure modification. Finally, the anti-amyloid beta (Abeta) aggregation and neuroprotective activity were also well investigated. Our findings highlighted the therapeutic promise of AChE inhibitors A01-A04 for AD treatment.
ESTHER : Liu_2020_Chem.Pharm.Bull.(Tokyo)_68_161
PubMedSearch : Liu_2020_Chem.Pharm.Bull.(Tokyo)_68_161
PubMedID: 31813907

Title : Complete metabolic study by dibutyl phthalate degrading Pseudomonas sp. DNB-S1 - Yu_2020_Ecotoxicol.Environ.Saf_194_110378
Author(s) : Yu H , Wang L , Lin Y , Liu W , Tuyiringire D , Jiao Y , Zhang L , Meng Q , Zhang Y
Ref : Ecotoxicology & Environmental Safety , 194 :110378 , 2020
Abstract : The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics.
ESTHER : Yu_2020_Ecotoxicol.Environ.Saf_194_110378
PubMedSearch : Yu_2020_Ecotoxicol.Environ.Saf_194_110378
PubMedID: 32146194

Title : Inhibitory Activity of Quercetin 3-O-Arabinofuranoside and 2-Oxopomolic Acid Derived from Malus domestica on Soluble Epoxide Hydrolase - Cho_2020_Molecules_25_
Author(s) : Cho IS , Kim JH , Lin Y , Su XD , Kang JS , Yang SY , Kim YH
Ref : Molecules , 25 : , 2020
Abstract : Flavonoids and triterpenoids were revealed to be the potential inhibitors on soluble epoxide hydrolase (sEH). The aim of this study is to reveal sEH inhibitors from Fuji apples. A flavonoid and three triterpenoids derived from the fruit of Malus domestica were identified as quercetin-3-O-arabinoside (1), ursolic acid (2), corosolic acid (3), and 2-oxopomolic acid (4). They had half-maximal inhibitory concentration of the inhibitors (IC(50)) values of 39.3 +/- 3.4, 84.5 +/- 9.5, 51.3 +/- 4.9, and 11.4 +/- 2.7 muM, respectively, on sEH. The inhibitors bound to allosteric sites of enzymes in mixed (1) and noncompetitive modes (2-4). Molecular simulations were carried out for inhibitors 1 and 4 to calculate the binding force of ligands to receptors. The inhibitors bound to the left (1) and right (4) pockets next to the enzyme's active site. Based on analyses of their molecular docking and dynamics, it was shown that inhibitors 1 and 4 can stably bind sEH at 1 bar and 300 K. Finally, inhibitors 1 and 4 are promising candidates for further studies using cell-based assays and in vivo cardiovascular tests.
ESTHER : Cho_2020_Molecules_25_
PubMedSearch : Cho_2020_Molecules_25_
PubMedID: 32972033

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

Title : Polydopamine-Capped Bimetallic AuPt Hydrogels Enable Robust Biosensor for Organophosphorus Pesticide Detection - Wu_2019_Small__e1900632
Author(s) : Wu Y , Jiao L , Xu W , Gu W , Zhu C , Du D , Lin Y
Ref : Small , :e1900632 , 2019
Abstract : Noble metal hydrogels/aerogels with macroscopic nanoassemblies characterized by ultralow density, profuse continuous porosity, and extremely large surface area have gained abundant interest due to not only their tunable physicochemical properties, but also promising applications in catalysis and sensing. Coupling the increased reaction temperature with dopamine-induced effect, herein, a one-step synthetic approach with accelerated gelation kinetics is reported for the synthesis of polydopamine-capped bimetallic AuPt hydrogels. 3D porous nanowire networks with surface functionalization of polydopamine make them a promising biocompatible microenvironment for immobilizing acetylcholinesterase (AChE) and constructing enzyme-based biosensors for sensitive detection of organophosphorus compounds. Taking advantage of their favorable structure and composition, the optimized product exhibits superior electrochemical activity toward thiocholine produced by AChE-catalyzed hydrolysis of acetylthiocholine. Based on the inhibition of organophosphorus pesticide on the enzymatic activity of AChE, the inhibition mode for the detection of paraoxon-ethyl is established, displaying linear regions over the range of 0.5-1000 ng L(-1) with a low detection limit of 0.185 ng L(-1) .
ESTHER : Wu_2019_Small__e1900632
PubMedSearch : Wu_2019_Small__e1900632
PubMedID: 30938485

Title : Multifunctional Cellular Beacons with in Situ Synthesized Quantum Dots Make Pathogen Detectable with the Naked Eye - Wang_2019_Anal.Chem_91_7280
Author(s) : Wang JJ , Lin Y , Jiang YZ , Zheng Z , Xie HY , Lv C , Chen ZL , Xiong LH , Zhang ZL , Wang H , Pang DW
Ref : Analytical Chemistry , 91 :7280 , 2019
Abstract : The rapid and sensitive detection of pathogens is extremely crucial for timely clinical diagnosis and diseases control. Here, by employing cellular beacons with in situ synthesized QDs created from Staphylococcus aureus ( S. aureus), we efficiently fabricated an antibody (Ab) and acetylcholinesterase (AChE)-functionalized nanobioprobe, i.e., multifunctional cellular beacons (MCBs), avoiding complicated modification. Coupled with magnetic separation, a novel method for pathogen detection with the naked eye is established. With this method, enterovirus 71 (EV71) can be detected by the naked eye through the aggregation of gold nanoparticles that is triggered by the product of AChE catalyzed acetylthiocholine, with a detection limit of 0.5 ng/mL. Moreover, due to the MCBs have high luminance with perfect uniformity, the detection can also be realized by counting the number of MCBs, with a detection limit of 1 ng/mL. The method is validated with human throat swabs, resulting in a complete consistence with reverse transcription-polymerase chain reaction results. This study reports the first cellular beacons-based method for pathogen detection by the naked eye and broadens the applicability of cell self-synthesized nanoparticles-based immunoassays. Moreover, the MCBs-based method will provide a powerful tool for clinical detection.
ESTHER : Wang_2019_Anal.Chem_91_7280
PubMedSearch : Wang_2019_Anal.Chem_91_7280
PubMedID: 31050409

Title : Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity - Lin_2019_Int.J.Nanomedicine_14_5817
Author(s) : Lin Y , Wang Y , Lv J , Wang N , Wang J , Li M
Ref : Int J Nanomedicine , 14 :5817 , 2019
Abstract : Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.
ESTHER : Lin_2019_Int.J.Nanomedicine_14_5817
PubMedSearch : Lin_2019_Int.J.Nanomedicine_14_5817
PubMedID: 31440049

Title : Ambient light sensor based colorimetric dipstick reader for rapid monitoring organophosphate pesticides on a smart phone - Fu_2019_Anal.Chim.Acta_1092_126
Author(s) : Fu Q , Zhang C , Xie J , Li Z , Qu L , Cai X , Ouyang H , Song Y , Du D , Lin Y , Tang Y
Ref : Anal Chim Acta , 1092 :126 , 2019
Abstract : Organophosphate pesticides (OPs) are widely used around the world to control pests in agricultural, residential, and commercial settings. Ingestion of high-dose OPs could lead to acute toxicity, and persistent influence on health could result from acute poisoning or long-term exposure to low dose OPs. An easy to operate, low cost and home available OPs testing platform is urgently needed. Ambient light sensor (ALS) based smart phone colorimetric reader has the advantages of easy to operate, low cost, high accuracy and versatility. In this work, a novel ALS based smart phone colorimetric dipsticks (CDs) reader was reported for rapid monitoring OPs. In this method, acetylcholinesterase (ACHE) CDs was used to test OPs and results were analyzed using an ALS based reader according to the absorbance of ACHE CDs. The results obtained using the ALS based CDs reader were comparable to those obtained using gas chromatography-mass spectrometry (GC-MS) and Ellman assay. The ALS based CDs reader has the advantages of portable, low cost, and high accuracy, and therefore could act an effective platform for OPs monitoring.
ESTHER : Fu_2019_Anal.Chim.Acta_1092_126
PubMedSearch : Fu_2019_Anal.Chim.Acta_1092_126
PubMedID: 31708025

Title : Orobol: An Isoflavone Exhibiting Regulatory Multifunctionality against Four Pathological Features of Alzheimer's Disease - Nam_2019_ACS.Chem.Neurosci_10_3386
Author(s) : Nam G , Ji Y , Lee HJ , Kang J , Yi Y , Kim M , Lin Y , Lee YH , Lim MH
Ref : ACS Chem Neurosci , 10 :3386 , 2019
Abstract : We report orobol as a multifunctional isoflavone with the ability to (i) modulate the aggregation pathways of both metal-free and metal-bound amyloid-beta, (ii) interact with metal ions, (iii) scavenge free radicals, and (iv) inhibit the activity of acetylcholinesterase. Such a framework with multifunctionality could be useful for developing chemical reagents to advance our understanding of multifaceted pathologies of neurodegenerative disorders, including Alzheimer's disease.
ESTHER : Nam_2019_ACS.Chem.Neurosci_10_3386
PubMedSearch : Nam_2019_ACS.Chem.Neurosci_10_3386
PubMedID: 31199606

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 : Oxidase-Like Fe-N-C Single-Atom Nanozymes for the Detection of Acetylcholinesterase Activity - Wu_2019_Small__e1903108
Author(s) : Wu Y , Jiao L , Luo X , Xu W , Wei X , Wang H , Yan H , Gu W , Xu BZ , Du D , Lin Y , Zhu C
Ref : Small , :e1903108 , 2019
Abstract : Single-atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe-N-C SACs can mimic oxidase by activating O2 into reactive oxygen species, O2 (-) * radicals. Taking advantages of this property, single-atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe-N-C SACs as oxidase-like nanozymes is explored. Besides, the Fe-N-C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes-based biosensor is further used for monitoring the amounts of organophosphorus compounds.
ESTHER : Wu_2019_Small__e1903108
PubMedSearch : Wu_2019_Small__e1903108
PubMedID: 31482681

Title : Donepezil decreases heart rate in elderly patients with Alzheimer's disease - Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94
Author(s) : Pu Z , Xu W , Lin Y , Shen J , Sun Y
Ref : Int J Clinical Pharmacology & Therapeutics , 57 :94 , 2019
Abstract : OBJECTIVE: Donepezil is an acetylcholinesterase inhibitor (AChI) that improves cognitive function in Alzheimer's disease (AD) patients. However, AChIs are usually associated with peripheral adverse reactions. Here, we investigated the cardiac outcomes in elderly AD patients treated with donepezil. MATERIALS AND METHODS: A total of 82 AD patients (age, 75.47 +/- 6.53 years) received 5 mg or 10 mg donepezil (n = 41/group) once daily for 12 weeks. Next, we examined the heart rate (HR), cardiac rhythm, and PR, QRS, and QTc intervals. RESULTS: Compared to the 5-mg donepezil-treated group, the HR was slower in the 10-mg donepezil-treated group at the 4(th), 8(th), and 12(th) weeks of treatment (p = 0.041, 0.026, 0.008, respectively). The PR interval was longer in the 10-mg donepezil-treated group at the 12(th) week of treatment (p = 0.022). Compared to the pretreatment values, the post-treatment HR and PR interval in the 10-mg donepezil-treated group were significantly slower and longer, respectively (p = 0.002, p = 0.005). Further, the HR was significantly correlated to the donepezil dosage (p = 0.014). Similarly, donepezil dosage and treatment interval were significantly correlated (p = 0.048). CONCLUSION: Taken together, our findings suggest that 10 mg donepezil decreased the HR of elderly AD patients without inducing severe cardiac outcomes. Therefore, AD patients receiving donepezil should undergo regular cardiovascular monitoring..
ESTHER : Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94
PubMedSearch : Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94
PubMedID: 30378536

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 : Synthesis of Cyclic Megamolecules - Modica_2018_J.Am.Chem.Soc_140_6391
Author(s) : Modica JA , Lin Y , Mrksich M
Ref : Journal of the American Chemical Society , 140 :6391 , 2018
Abstract : This paper describes the synthesis of giant cyclic molecules having diameters of 10-20 nm. The molecules are prepared through the reactions of a fusion protein building block with small molecule linkers that are terminated in irreversible inhibitors of enzyme domains present in the fusion. This building block has N-terminal cutinase and C-terminal SnapTag domains that react irreversibly with p-nitrophenyl phosphonate (pNPP) and benzylguanine (BG) groups, respectively. We use a bis-BG and a BG-pNPP linker to join these fusion proteins into linear structures that can then react with a bis-pNPP linker that joins the ends into a cyclic product. The last step can occur intramolecularly, to give the macrocycle, or intermolecularly with another equivalent of linker, to give a linear product. Because these are coupled first- and second-order processes, an analysis of product yields from reactions performed at a range of linker concentrations gives rate constants for cyclization. We determined these to be 9.7 x 10(-3) s(-1), 2.3 x 10(-3) s(-1), and 8.1 x 10(-4) s(-1) for the dimer, tetramer, and hexamer, respectively. This work demonstrates an efficient route to cyclic macromolecules having nanoscale dimensions and provides new scaffolds that can be generated using the megamolecule approach.
ESTHER : Modica_2018_J.Am.Chem.Soc_140_6391
PubMedSearch : Modica_2018_J.Am.Chem.Soc_140_6391
PubMedID: 29723476

Title : Kinetic resolution of sec-alcohols catalysed by Candida antarctica lipase B displaying Pichia pastoris whole-cell biocatalyst - Zhang_2018_Enzyme.Microb.Technol_110_8
Author(s) : Zhang K , Pan Z , Diao Z , Liang S , Han S , Zheng S , Lin Y
Ref : Enzyme Microb Technol , 110 :8 , 2018
Abstract : Kinetic resolution of sec-alcohols is a green process with biocatalyst. Candida antarctica lipase B (CALB) displayed on Pichia pastoris cell-surface (Pp-CALB) was characterized in kinetic resolution of sec-alcohols with different structures. The reaction parameters including acyl donors, molar ratio of substrates, solvents and temperatures were examined with 2-octanol as model substrate. 47.4% molar conversion of 2-octanol and 99.7% eep were obtained after a 5h reaction with Pp-CALB, and 90% of its original activity still remained after being reused for 10 cycles. Pp-CALB was then used to several sec-alcohols and it showed great enzymatic activity and enantioselectivity to all tested sec-alcohols, more than 93.1% of eep. The enantioselective characteristics of Pp-CALB catalysed sec-alcohols with different structures were compared with Novozyme 435 which was almost the same. Solvent free system as one way of green chemistry was applied to Pp-CALB and Pp-CALB showed great catalytic activity and enantioselectivity. Pp-CALB was potential biocatalyst of high enzymatic activity and enantioselectivity using in resolution of sec-alcohols.
ESTHER : Zhang_2018_Enzyme.Microb.Technol_110_8
PubMedSearch : Zhang_2018_Enzyme.Microb.Technol_110_8
PubMedID: 29310860

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 : A Nanozyme- and Ambient Light-Based Smartphone Platform for Simultaneous Detection of Dual Biomarkers from Exposure to Organophosphorus Pesticides - Zhao_2018_Anal.Chem_90_7391
Author(s) : Zhao Y , Yang M , Fu Q , Ouyang H , Wen W , Song Y , Zhu C , Lin Y , Du D
Ref : Analytical Chemistry , 90 :7391 , 2018
Abstract : A transparent, lateral-flow test strip coupled with a smartphone-based ambient light sensor was first proposed for detecting enzymatic inhibition and phosphorylation. The principle of the platform is based on the simultaneous measurement of the total amount of the enzyme and enzyme activity to biomonitor exposure to organophosphorus (OP) pesticides. In this study, butyrylcholinesterase (BChE) was adopted as the model enzyme and ethyl paraoxon was chosen as an analyte representing OP pesticides. The total amount of BChE was quantified by a sensitive colorimetric signal originating from a sandwich immunochromatographic assay utilizing PtPd nanoparticles as a colorimetric probe, which exhibited excellent catalytic activity for phenols. In the sandwich immunoassay, only one antibody against BChE was simultaneously utilized as the recognition antibody and the labeling antibody due to the tetrameric structure of native BChE. The BChE activity was estimated by another colorimetric signal using the Ellman assay. Both colorimetric signals on two separated test strips were detected by the smartphone-based ambient light sensor. The proposed sensor operated with an LED in a 3D-printed substrate, which emitted excitation light and transmitted it through a transparent, lateral-flow test strip. With the increase in the colorimetric signal in the test line of the test strip, the intensity of the transmitted light decreased. The smartphone-based sensor showed excellent linear responses for assaying the total amount of BChE and active BChE ranging from 0.05 to 6.4 nM and from 0.1 to 6.4 nM, respectively. A high portability and low detection limit were simultaneously realized in the common smartphone-based device. This low-cost, portable, easy-operation, and sensitive immunoassay strategy shows great potential for online detection of OP exposure and monitoring other disease biomarkers.
ESTHER : Zhao_2018_Anal.Chem_90_7391
PubMedSearch : Zhao_2018_Anal.Chem_90_7391
PubMedID: 29792679

Title : Hyperbaric Oxygen Prevents Cognitive Impairments in Mice Induced by D-Galactose by Improving Cholinergic and Anti-apoptotic Functions - Chen_2017_Neurochem.Res_42_1240
Author(s) : Chen C , Huang L , Nong Z , Li Y , Chen W , Huang J , Pan X , Wu G , Lin Y
Ref : Neurochem Res , 42 :1240 , 2017
Abstract : Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection. Our results showed that HBO in D-gal-treated mice significantly improved behavioral performance on the open field test and passive avoidance task. Studies on the potential mechanisms of this effect showed that HBO significantly reduced oxidative stress and blocked the nuclear factor-kappaB pathway. Moreover, HBO significantly increased the levels of choline acetyltransferase and acetylcholine and decreased the activity of acetylcholinesterase in the hippocampus. Furthermore, HBO markedly increased expression of the anti-apoptosis protein Bcl-2 and glial fibrillary acidic protein meanwhile decreased expression of the pro-apoptosis proteins Bax and caspase-3. Importantly, there was a significant reduction in expression of Abeta-related genes, such as amyloid precursor protein, beta-site amyloid cleaving enzyme-1 and cathepsin B mRNA. These decreases were accompanied by significant increases in expression of neprilysin and insulin-degrading enzyme mRNA. Moreover, compared with the Vitamin E group, HBO combined with Vitamin E exhibited significant difference in part of the above mention parameters. These findings suggest that HBO may act as a neuroprotective agent in preventing cognitive impairments.
ESTHER : Chen_2017_Neurochem.Res_42_1240
PubMedSearch : Chen_2017_Neurochem.Res_42_1240
PubMedID: 28078611

Title : Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction - Ohno_2017_J.Neurochem_142 Suppl 2_64
Author(s) : Ohno K , Rahman MA , Nazim M , Nasrin F , Lin Y , Takeda JI , Masuda A
Ref : Journal of Neurochemistry , 142 Suppl 2 :64 , 2017
Abstract : We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction are also alternatively spliced. In addition, germline mutations provoke aberrant splicing by compromising binding of RNA-binding proteins, and cause congenital myasthenic syndromes (CMS). We present physiological splicing mechanisms of genes for agrin (AGRN), acetylcholinesterase (ACHE), MuSK (MUSK), acetylcholine receptor (AChR) alpha1 subunit (CHRNA1), and collagen Q (COLQ) in human, and their aberration in diseases. Splicing isoforms of AChET , AChEH , and AChER are generated by hnRNP H/F. Skipping of MUSK exon 10 makes a Wnt-insensitive MuSK isoform, which is unique to human. Skipping of exon 10 is achieved by coordinated binding of hnRNP C, YB-1, and hnRNP L to exon 10. Exon P3A of CHRNA1 is alternatively included to generate a non-functional AChR alpha1 subunit in human. Molecular dissection of splicing mutations in patients with CMS reveals that exon P3A is alternatively skipped by hnRNP H, polypyrimidine tract-binding protein 1, and hnRNP L. Similarly, analysis of an exonic mutation in COLQ exon 16 in a CMS patient discloses that constitutive splicing of exon 16 requires binding of serine arginine-rich splicing factor 1. Intronic and exonic splicing mutations in CMS enable us to dissect molecular mechanisms underlying alternative and constitutive splicing of genes expressed at the neuromuscular junction. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
ESTHER : Ohno_2017_J.Neurochem_142 Suppl 2_64
PubMedSearch : Ohno_2017_J.Neurochem_142 Suppl 2_64
PubMedID: 28072465

Title : Simultaneous detection of dual biomarkers from humans exposed to organophosphorus pesticides by combination of immunochromatographic test strip and ellman assay - Yang_2017_Biosens.Bioelectron_104_39
Author(s) : Yang M , Zhao Y , Wang L , Paulsen M , Simpson CD , Liu F , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 104 :39 , 2017
Abstract : A novel sandwich immunoassay based immunochromatographic test strip (ICTS) has been developed for simultaneously measuring both butyrylcholinesterase (BChE) activity and the total amount of BChE (including inhibited and active enzyme) from 70 muLpost-exposure human plasma sample. The principle of this method is based on the BChE monoclonal antibody (MAb) capable of acting as both capture antibody and detection antibody. The BChE MAb which was immobilized on the test line was able to recognize both organophosphorus BChE adducts (OP-BChE) and BChE and provided equal binding affinity, permitting detection of the total enzyme amount in post-exposure human plasma samples. The formed immunocomplexes on the test line can further be excised from the test-strip for subsequent off-line measurement of BChE activity using the Ellman assay. Therefore, dual biomarkers of BChE activity and phosphorylation (OP-BChE) will be obtained simultaneously. The whole sandwich-immunoassay was performed on one ICTS, greatly reducing analytical time. The ICTS sensor showed excellent linear responses for assaying total amount of BChE and active BChE ranging from 0.22 to 3.58nM and 0.22-7.17nM, respectively. Both the signal detection limits are 0.10nM. We validated the practical application of the proposed method to measure 124 human plasma samples from orchard workers and cotton farmers with long-term exposure to organophosphorus pesticides (OPs). The results were in highly agreement with LC/MS/MS which verified our method is extremely accurate. Combining the portability and rapidity of test strip and the compatibility of BChE MAb as both capture antibody and detection antibody, the developed method provides a baseline-free, low-cost and rapid tool for in-field monitoring of OP exposures.
ESTHER : Yang_2017_Biosens.Bioelectron_104_39
PubMedSearch : Yang_2017_Biosens.Bioelectron_104_39
PubMedID: 29306031

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Expression of Cellulolytic Enzyme as a Fusion Protein That Reacts Specifically With a Polymeric Scaffold - Katyal_2017_Methods.Enzymol_590_259
Author(s) : Katyal P , Yang Y , Vinogradova O , Lin Y
Ref : Methods Enzymol , 590 :259 , 2017
Abstract : The formation of higher-order assemblies of multiple proteins or enzymes is a general mechanism to achieve more sophisticated biological function in biological systems. For example, cellulosomes are large complexes consisting of multiple cellulolytic enzymes that rely on the concerted actions of different enzymes built onto a common protein scaffold to facilitate the breakdown of the polymeric substrate, cellulose. One strategy for mimicking these highly effective nanomachines may involve the use of synthetic scaffolds that can react to and organize multiple engineered enzymes to promote synergistic action between the enzymes on the scaffold. As an example of the earlier strategy, we describe here an approach for the expression of cellulolytic enzymes with a serine esterase tag, and the rapid reaction between the tag and the end-functionalized polymers to form enzyme-polymer-enzyme multienzyme conjugates. In principle, this general and versatile supramolecular approach may be used to organize specific cellulolytic enzymes onto synthetic scaffolds to form multienzyme complexes to potentially work in synergy for enhanced biological activities. Best reaction conditions, good activities of the armored cellulolytic enzymes and the design of optimal protein linker in the fusion protein are discussed in detail. If other reactive tags are included on the enzyme in future, multiple types of synergistic enzymes may be positioned at specific sites on a designed polymer scaffold that mimics the complex structure and enhanced function of natural cellulosomes. This type of nanoarmoring of multiple enzymes on a nanoscale might also enhance enzyme stability, when compared to the unprotected enzymes.
ESTHER : Katyal_2017_Methods.Enzymol_590_259
PubMedSearch : Katyal_2017_Methods.Enzymol_590_259
PubMedID: 28411640

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 : Mycobacterium tuberculosis rv1400c encodes functional lipase\/esterase - Lin_2017_Protein.Expr.Purif_129_143
Author(s) : Lin Y , Li Q , Xie L , Xie J
Ref : Protein Expr Purif , 129 :143 , 2017
Abstract : Lipases catalyze the hydrolysis of triglycerides (TAG). Open reading frames (ORF) predicted to encode enzymes involved in fatty acids breakdown are abundant in Mycobacterium tuberculosis genome. To define the function of M. tuberculosis rv1400c (LipI), a putative Hormone Sensitive Lipase (HSL) subfamily ORF, the rv1400c was cloned, expressed and purified in Escherichia coli as fusion protein. The purified LipI preferred short carbon chain substrates with an optimal activity at 37 degrees C/pH 8.0 and stable between pH 6.0 to 9.0. Its specific activity was calculated to 35.71 U/mg with pNP-butyrate as a preferred substrate. SDS, CTAB and Zn2+ can inhibit this enzyme. The conserved residues Ser165 and His291 were shown to be important for the catalysis activity of Rv1400c by site-directed mutagenesis. The biochemical and genetical data showed M. tuberculosis LipI might be a good candidate catalyst for polyunsaturated fatty acids.
ESTHER : Lin_2017_Protein.Expr.Purif_129_143
PubMedSearch : Lin_2017_Protein.Expr.Purif_129_143
PubMedID: 27154903

Title : A sensitive magnetic nanoparticle-based immunoassay of phosphorylated acetylcholinesterase using protein cage templated lead phosphate for signal amplification with graphite furnace atomic absorption spectrometry detection - Liang_2016_Analyst_141_2278
Author(s) : Liang P , Kang C , Yang E , Ge X , Du D , Lin Y
Ref : Analyst , 141 :2278 , 2016
Abstract : We developed a new magnetic nanoparticle sandwich-like immunoassay using protein cage nanoparticles (PCN) for signal amplification together with graphite furnace atomic absorption spectrometry (GFAAS) for the quantification of an organophosphorylated acetylcholinesterase adduct (OP-AChE), the biomarker of exposure to organophosphate pesticides (OPs) and nerve agents. OP-AChE adducts were firstly captured by titanium dioxide coated magnetic nanoparticles (TiO2-MNPs) from the sample matrixes through metal chelation with phospho-moieties, and then selectively recognized by anti-AChE antibody labeled on PCN which was packed with lead phosphate in its cavity (PCN-anti-AChE). The sandwich-like immunoreaction was performed among TiO2-MNPs, OP-AChE and PCN-anti-AChE to form a TiO2-MNP/OP-AChE/PCN-anti-AChE immunocomplex. The complex could be easily isolated from the sample solution with the help of magnet, and the released lead ions from PCN were detected by GFAAS for the quantification of OP-AChE. Greatly enhanced sensitivity was achieved because PCN increased the amount of metal ions in the cavity of each apoferritin. The proposed immunoassay yielded a linear response over a broad range of OP-AChE concentrations from 0.01 nM to 2 nM, with a detection limit of 2 pM, which has enough sensitivity for monitoring of low-dose exposure to OPs. This new method showed an acceptable stability and reproducibility and was validated with OP-AChE spiked human plasma.
ESTHER : Liang_2016_Analyst_141_2278
PubMedSearch : Liang_2016_Analyst_141_2278
PubMedID: 26953358

Title : Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B - Wang_2016_Appl.Microbiol.Biotechnol_100_5883
Author(s) : Wang P , He J , Sun Y , Reynolds M , Zhang L , Han S , Liang S , Sui H , Lin Y
Ref : Applied Microbiology & Biotechnology , 100 :5883 , 2016
Abstract : To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37 and 109 %, respectively, but decreased by 26 and 43 %, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells.
ESTHER : Wang_2016_Appl.Microbiol.Biotechnol_100_5883
PubMedSearch : Wang_2016_Appl.Microbiol.Biotechnol_100_5883
PubMedID: 26969039

Title : Phomopsichin A-D\; Four New Chromone Derivatives from Mangrove Endophytic Fungus Phomopsis sp. 33 - Huang_2016_Mar.Drugs_14_
Author(s) : Huang M , Li J , Liu L , Yin S , Wang J , Lin Y
Ref : Mar Drugs , 14 : , 2016
Abstract : Four new chromone derivatives, phomopsichins A-D (1-4), along with a known compound, phomoxanthone A (5), were isolated from the fermentation products of mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated based on comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction or theoretical calculations of electronic circular dichroism (ECD). They feature a tricyclic framework, in which a dihydropyran ring is fused with the chromone ring. Compounds 1-5 showed weak inhibitory activities on acetylcholinesterase as well as alpha-glucosidase, weak radical scavenging effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak antimicrobial activities. Compounds 1-4 showed no cytotoxic activity against MDA-MB-435 breast cancer cells. Their other bioactivities are worthy of further study, considering their unique molecular structures.
ESTHER : Huang_2016_Mar.Drugs_14_
PubMedSearch : Huang_2016_Mar.Drugs_14_
PubMedID: 27879655

Title : Efficacy and Safety of ABT-126 in Subjects with Mild-to-Moderate Alzheimer's Disease on Stable Doses of Acetylcholinesterase Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Study - Florian_2016_J.Alzheimers.Dis_51_1237
Author(s) : Florian H , Meier A , Gauthier S , Lipschitz S , Lin Y , Tang Q , Othman AA , Robieson WZ , Gault LM
Ref : J Alzheimers Dis , 51 :1237 , 2016
Abstract : BACKGROUND: ABT-126 is a potent, selective alpha7 nicotinic acetylcholine receptor agonist with putative procognitive effects as a monotherapy in treating Alzheimer's disease (AD). OBJECTIVE: This randomized, double-blind, placebo-controlled multicenter study (NCT01549834) investigated the efficacy and safety of ABT-126 in subjects with mild-to-moderate AD who were taking stable doses of acetylcholinesterase inhibitors (AChEIs).
METHODS: Subjects received 25 mg ABT-126 (n = 143), 75 mg ABT-126 (n = 145), or placebo (n = 146) once daily for 24 weeks. Subjects who completed the 24-week double-blind study were eligible to enroll in a 28-week open-label extension study (NCT01690195) and received 75 mg ABT-126 daily. The primary efficacy endpoint was the change from baseline to week 24 in the 11-item total score of the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog).
RESULTS: Neither dose of ABT-126 demonstrated significant improvement compared with placebo in the primary efficacy endpoint. However, 25 mg ABT-126 demonstrated significant improvement compared with placebo in ADAS-Cog scores at week 4 (least squares mean difference, -1.21; standard error, 0.51; p < 0.010, one-sided); 75 mg ABT-126 did not demonstrate significant improvements in ADAS-Cog scores compared with placebo at any time point. A treatment effect was not observed for any secondary efficacy measures of cognition, function, or global improvement. ABT-126 was generally well tolerated; the most common adverse events were agitation, constipation, diarrhea, fall, and headache.
CONCLUSIONS: Overall, the efficacy profile of ABT-126 did not warrant further development as add-on therapy to AChEIs to treat mild-to-moderate AD.
ESTHER : Florian_2016_J.Alzheimers.Dis_51_1237
PubMedSearch : Florian_2016_J.Alzheimers.Dis_51_1237
PubMedID: 26967214

Title : Pesticide levels and environmental risk in aquatic environments in China - A review - Grung_2015_Environ.Int_81_87
Author(s) : Grung M , Lin Y , Zhang H , Steen AO , Huang J , Zhang G , Larssen T
Ref : Environ Int , 81 :87 , 2015
Abstract : China is one of the largest producers and consumers of pesticides in the world today. Along with the widespread use of pesticides and industrialization, there is a growing concern for water quality. The present review aims to provide an overview of studies on pesticides in aquatic environments in China. The levels in the water, sediment and biota were scored according to a detailed environmental classification system based on ecotoxicological effect, which is therefore a useful tool for assessing the risk these compounds pose to the aquatic ecosystem. Our review reveals that the most studied areas in China are the most populated and the most developed economically and that the most frequently studied pesticides are DDT and HCH. We show maps of where studies have been conducted and show the ecotoxicological risk the pesticides pose in each of the matrices. Our review pinpoints the need for biota samples to assess the risk. A large fraction of the results from the studies are given an environmental classification of "very bad" based on levels in biota. In general, the risk is higher for DDT than HCH. A few food web studies have also been conducted, and we encourage further study of this important information from this region. The review reveals that many of the most important agricultural provinces (e.g., Henan, Hubei and Hunan) with the largest pesticide use have been the subject of few studies on the environmental levels of pesticides. We consider this to be a major knowledge gap for understanding the status of pesticide contamination and related risk in China. Furthermore, there is also a lack of studies in remote Chinese environments, which is also an important knowledge gap. The compounds analyzed and reported in the studies represent a serious bias because a great deal of attention is given to DDT and HCH, whereas the organophosphate insecticides dominating current use are less frequently investigated. For the future, we point to the need for an organized monitoring plan designed according to the knowledge gaps in terms of geographical distribution, compounds included, and risks.
ESTHER : Grung_2015_Environ.Int_81_87
PubMedSearch : Grung_2015_Environ.Int_81_87
PubMedID: 25968893

Title : A multi-enzyme microreactor-based online electrochemical system for selective and continuous monitoring of acetylcholine - Lin_2015_Analyst_140_3781
Author(s) : Lin Y , Yu P , Mao L
Ref : Analyst , 140 :3781 , 2015
Abstract : This study demonstrates an online electrochemical system (OECS) for selective and continuous measurements of acetylcholine (ACh) through efficiently integrating in vivo microdialysis, a multi-enzyme microreactor and an electrochemical detector. A multi-enzyme microreactor was prepared first by co-immobilizing two kinds of enzymes, i.e. choline oxidase (ChOx) and catalase (Cat), onto magnetite nanoparticles and then confining the as-formed nanoparticles into a fused-silica capillary with the assistance of an external magnet. The multi-enzyme microreactor was settled between an in vivo microdialysis sampling system and an electrochemical detector to suppress the interference from choline toward ACh detection. Selective detection of ACh was accomplished using the electrochemical detector with ACh esterase (AChE) and ChOx as the recognition units for ACh and Prussian blue (PB) as the electrocatalyst for the reduction of hydrogen peroxide (H2O2). The current recorded with the OECS was linear with the concentration of ACh (I/nA = -3.90CACh/muM + 1.21, gamma = 0.998) within a concentration range of 5 muM to 100 muM. The detection limit, based on a signal-to-noise ratio of 3, was calculated to be 1 muM. Interference investigation demonstrates that the OECS did not produce an observable current response toward physiological levels of common electroactive species, such as ascorbic acid (AA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and uric acid (UA). The high selectivity and the good linearity in combination with the high stability may enable the OECS developed here as a potential system for continuous monitoring of cerebral ACh release in some physiological and pathological processes.
ESTHER : Lin_2015_Analyst_140_3781
PubMedSearch : Lin_2015_Analyst_140_3781
PubMedID: 25529471

Title : Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization - Lin_2014_Anal.Bioanal.Chem_406_5213
Author(s) : Lin Y , Chen J , Yan L , Guo L , Wu B , Li C , Feng J , Liu Q , Xie J
Ref : Anal Bioanal Chem , 406 :5213 , 2014
Abstract : A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.
ESTHER : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedSearch : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedID: 24633564

Title : Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history - Zhou_2014_Nat.Genet_46_1303
Author(s) : Zhou X , Wang B , Pan Q , Zhang J , Kumar S , Sun X , Liu Z , Pan H , Lin Y , Liu G , Zhan W , Li M , Ren B , Ma X , Ruan H , Cheng C , Wang D , Shi F , Hui Y , Tao Y , Zhang C , Zhu P , Xiang Z , Jiang W , Chang J , Wang H , Cao Z , Jiang Z , Li B , Yang G , Roos C , Garber PA , Bruford MW , Li R
Ref : Nat Genet , 46 :1303 , 2014
Abstract : Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.
ESTHER : Zhou_2014_Nat.Genet_46_1303
PubMedSearch : Zhou_2014_Nat.Genet_46_1303
PubMedID: 25362486
Gene_locus related to this paper: rhibe-a0a2k6jtl7 , rhibe-ACHE , rhibe-a0a2k6k3y7 , rhibe-a0a2k6k493 , rhibe-a0a2k6lev4 , rhibe-a0a2k6lfa5 , rhibe-a0a2k6m6k8 , rhiro-a0a2k6p1u8 , rhiro-a0a2k6q1t8 , rhiro-a0a2k6q1w3 , rhibe-a0a2k6n5t9 , rhibe-a0a2k6ju46 , rhibe-a0a2k6kt48 , rhibe-a0a2k6llm5 , rhibe-a0a2k6lnt5 , rhiro-a0a2k6qzp6 , rhiro-a0a2k6q4a6 , rhibe-a0a2k6kn93 , rhibe-a0a2k6lm22 , rhibe-a0a2k6jwp8 , rhiro-a0a2k6qun2 , rhiro-a0a2k6nj56 , rhiro-a0a2k6n885 , rhiro-a0a2k6nnj4 , rhiro-a0a2k6n7n5 , rhibe-a0a2k6jvz4 , rhiro-a0a2k6nfk9 , rhiro-a0a2k6qjv0 , rhibe-a0a2k6jn19 , rhibe-a0a2k6k333 , rhibe-a0a2k6mff5

Title : Acetylcholinesterase biosensor based on a gold nanoparticle-polypyrrole-reduced graphene oxide nanocomposite modified electrode for the amperometric detection of organophosphorus pesticides - Yang_2014_Analyst_139_3055
Author(s) : Yang Y , Asiri AM , Du D , Lin Y
Ref : Analyst , 139 :3055 , 2014
Abstract : A nanohybrid of gold nanoparticles, polypyrrole, and reduced graphene oxide sheets (named as Au-PPy-rGO) was achieved by electrochemical deposition of reduced graphene oxide with pyrrole and the introduction of gold nanoparticles. Acetylcholinesterase (AChE) was further encapsulated in a silica matrix and immobilized on the Au-PPy-rGO nanocomposite by co-deposition with (NH4)2SiF6. The presence of PPy helped to avoid the aggregation of rGO caused by van der Waals interactions between individual sheets and significantly increased the surface area of the modified electrode. The obtained Au-PPy-rGO nanocomposite not only showed excellent conductivity but also exhibited a high electrocatalytic activity and specific affinity for thiocholine, the hydrolysis product of the enzyme, and thus an improved detection sensitivity. Since AChE molecules were protected by the circumambient silica matrix, which provided a biocompatible environment and facilitated mass transport, the fabricated AChE biosensor displayed high stability and excellent activity together with a fast response to organophosphorus pesticides. Under optimum conditions, the biosensor led to the rapid and sensitive detection of paraoxon-ethyl from 1.0 nM to 5 muM with a detection limit of 0.5 nM.
ESTHER : Yang_2014_Analyst_139_3055
PubMedSearch : Yang_2014_Analyst_139_3055
PubMedID: 24770670

Title : Lab-on-a-drop: biocompatible fluorescent nanoprobes of gold nanoclusters for label-free evaluation of phosphorylation-induced inhibition of acetylcholinesterase activity towards the ultrasensitive detection of pesticide residues - Zhang_2014_Analyst_139_4620
Author(s) : Zhang N , Si Y , Sun Z , Li S , Lin Y , Wang H
Ref : Analyst , 139 :4620 , 2014
Abstract : A simple, sensitive, selective, and "lab-on-a-drop"-based fluorimetric protocol has been proposed using biocompatible fluorescent nanoprobes of gold nanoclusters (AuNCs) for the label-free evaluation of the catalytic activity and phosphorylation of acetylcholinesterase (AChE) under physiologically simulated environments. Protein-stabilized AuNCs were prepared and mixed with acetylthiocholine (ATC) serving as "a drop" of fluorimetric reaction substrate. The AChE-catalyzed hydrolysis of ATC releases thiocholine to cause the aggregation of the AuNCs towards a dramatic decrease in fluorescence intensities, which could be curbed by the phosphorylation-induced inhibition of AChE activity when exposed to organophosphorus compounds (OPs). The reaction procedures and conditions of AChE catalysis and phosphorylation were monitored by fluorimetric measurements and electron microscopy imaging. Moreover, a selective and ultrasensitive fluorimetric assay has been tailored for the detection of pesticide residues using dimethyl-dichloro-vinyl phosphate (DDVP) as an example. Investigation results indicate that the specific catalysis and irreversible OP-induced phosphorylation of AChE, in combination with sensitive fluorimetric outputs could facilitate the detection of total free OPs with high selectivity and sensitivity. A linear concentration of DDVP ranging from 0.032 nM to 20 nM could be obtained with a detection limit of 13.67 pM. Particularly, pesticide residues of DDVP in vegetable samples were quantified down to approximately 36 pM. Such a label-free "lab-on-a drop"-based fluorimetry may promise wide applications for the evaluation of the physiological catalytic activity of various enzymes (i.e., cholinesterase), and especially for monitoring the direct phosphorylation biomarkers of free OPs towards rapid and early warning, and accurate diagnosis of OP exposure.
ESTHER : Zhang_2014_Analyst_139_4620
PubMedSearch : Zhang_2014_Analyst_139_4620
PubMedID: 25050413

Title : Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride in optimal heart metabolism and function - Khan_2013_Am.J.Physiol.Endocrinol.Metab_305_E1339
Author(s) : Khan RS , Lin Y , Hu Y , Son NH , Bharadwaj KG , Palacios C , Chokshi A , Ji R , Yu S , Homma S , Schulze PC , Tian R , Goldberg IJ
Ref : American Journal of Physiology Endocrinol Metab , 305 :E1339 , 2013
Abstract : Hearts utilize fatty acids as a primary source of energy. The sources of those lipids include free fatty acids and lipoprotein triglycerides. Deletion of the primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a deficiency in energetic substrates is unknown. To test whether alternative sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy, and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or training group (swimming) at 3 mo of age, which leads to increased skeletal muscle production of lactate. hLPL0 mice had greater expression of the lactate transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0 mice had adaptive hypertrophy and improved cardiac function. We conclude that defective energy intake and not the reduced uptake of fat-soluble vitamins or cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition, our studies suggest that adaptations in cardiac metabolism contribute to the beneficial effects of exercise on the myocardium of patients with heart failure.
ESTHER : Khan_2013_Am.J.Physiol.Endocrinol.Metab_305_E1339
PubMedSearch : Khan_2013_Am.J.Physiol.Endocrinol.Metab_305_E1339
PubMedID: 24085031
Gene_locus related to this paper: mouse-lipli

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

Title : Preparation, characterization of Fe(3)O(4) at TiO(2) magnetic nanoparticles and their application for immunoassay of biomarker of exposure to organophosphorus pesticides - Zhang_2013_Biosens.Bioelectron_41_669
Author(s) : Zhang X , Wang H , Yang C , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 41 :669 , 2013
Abstract : Novel Fe(3)O(4) at TiO(2) magnetic nanoparticles were prepared and developed for a new nanoparticle-based immunosensor for electrochemical quantification of organophosphorylated butyrylcholinesterase (BChE) in plasma, a specific biomarker of exposure to organophosphorus (OP) agents. The Fe(3)O(4) at TiO(2) nanoparticles were synthesized by hydrolysis of tetrabutyltitanate on the surface of Fe(3)O(4) magnetic nanospheres, and characterized by attenuated total reflection Fourier-transform infrared spectra, transmission electron microscope and X-ray diffraction. The functional Fe(3)O(4) at TiO(2) nanoparticles were performed as capture antibody to selectively enrich phosphorylated moiety instead of phosphoserine antibody in the traditional sandwich immunoassays. The secondary recognition was performed by quantum dots (QDs)-tagged anti-BChE antibody (QDs-anti-BChE). With the help of a magnet, the resulting sandwich-like complex, Fe(3)O(4) at TiO(2)/OP-BChE/QDs-anti-BChE, was easily isolated from sample solutions and the released cadmium ions were detected on a disposable screen-printed electrode (SPE). The binding affinities were investigated by both surface plasmon resonance (SPR) and square wave voltammetry (SWV). This method not only avoids the drawback of unavailability of commercial OP-specific antibody but also amplifies detection signal by QDs-tags together with easy separation of samples by magnetic forces. The proposed immunosensor yields a linear response over a broad OP-BChE concentrations range from 0.02 to 10nM, with detection limit of 0.01nM. Moreover, the disposable nanoparticle-based immunosensor has been validated with human plasma samples. It offers a new method for rapid, sensitive, selective and inexpensive screening/evaluating exposure to OP pesticides and nerve agents.
ESTHER : Zhang_2013_Biosens.Bioelectron_41_669
PubMedSearch : Zhang_2013_Biosens.Bioelectron_41_669
PubMedID: 23122753

Title : Magnetic FeO@TiO nanoparticles-based test strip immunosensing device for rapid detection of phosphorylated butyrylcholinesterase - Ge_2013_Biosens.Bioelectron_50C_486
Author(s) : Ge X , Zhang W , Lin Y , Du D
Ref : Biosensors & Bioelectronics , 50C :486 , 2013
Abstract : An integrated magnetic nanoparticles-based test strip immunosensing device was developed for rapid and sensitive quantification of phosphorylated butyrylcholinesterase (BChE), the biomarker of exposure to organophosphorous pesticides (OP), in human plasma. In order to overcome the difficulty in scarce availability of OP-specific antibody, here magnetic Fe3O4@TiO2 nanoparticles were used and adsorbed on the test strip through a small magnet inserted in the device to capture target OP-BChE through selective binding between TiO2 and OP moiety. Further recognition was completed by horseradish peroxidase (HRP) and anti-BChE antibody (Ab) co-immobilized gold nanoparticles (GNPs). Their strong affinities among Fe3O4@TiO2, OP-BChE and HRP/Ab-GNPs were characterized by quartz crystal microbalance (QCM), surface plasmon resonance (SPR) and square wave voltammetry (SWV) measurements. After cutting off from test strip, the resulted immunocomplex (HRP/Ab-GNPs/OP-BChE/Fe3O4@TiO2) was measured by SWV using a screen printed electrode under the test zone. Greatly enhanced sensitivity was achieved by introduction of GNPs to link enzyme and antibody at high ratio, which amplifies electrocatalytic signal significantly. Moreover, the use of test strip for fast immunoreactions reduces analytical time remarkably. Under the optimized conditions, the developed device shows a broader linear response over the concentration of OP-BChE from 0.05nM to 10nM within 15min, with a detection limit of 0.01nM. Coupling with a portable electrochemical detector, the integrated device with advanced nanotechnology displays great promise for sensitive, rapid and on-site evaluation of OP poisoning.
ESTHER : Ge_2013_Biosens.Bioelectron_50C_486
PubMedSearch : Ge_2013_Biosens.Bioelectron_50C_486
PubMedID: 23911770

Title : Structure-guided modification of Rhizomucor miehei lipase for production of structured lipids - Zhang_2013_PLoS.One_8_e67892
Author(s) : Zhang JH , Jiang YY , Lin Y , Sun YF , Zheng SP , Han SY
Ref : PLoS ONE , 8 :e67892 , 2013
Abstract : To improve the performance of yeast surface-displayed Rhizomucor miehei lipase (RML) in the production of human milk fat substitute (HMFS), we mutated amino acids in the lipase substrate-binding pocket based on protein hydrophobicity, to improve esterification activity. Five mutants: Asn87Ile, Asn87Ile/Asp91Val, His108Leu/Lys109Ile, Asp256Ile/His257Leu, and His108Leu/Lys109Ile/Asp256Ile/His257Leu were obtained and their hydrolytic and esterification activities were assayed. Using Discovery Studio 3.1 to build models and calculate the binding energy between lipase and substrates, compared to wild-type, the mutant Asp256Ile/His257Leu was found to have significantly lower energy when oleic acid (3.97 KJ/mol decrease) and tripalmitin (7.55 KJ/mol decrease) were substrates. This result was in accordance with the esterification activity of Asp256Ile/His257Leu (2.37-fold of wild-type). The four mutants were also evaluated for the production of HMFS in organic solvent and in a solvent-free system. Asp256Ile/His257Leu had an oleic acid incorporation of 28.27% for catalyzing tripalmitin and oleic acid, and 53.18% for the reaction of palm oil with oleic acid. The efficiency of Asp256Ile/His257Leu was 1.82-fold and 1.65-fold that of the wild-type enzyme for the two reactions. The oleic acid incorporation of Asp256Ile/His257Leu was similar to commercial Lipozyme RM IM for palm oil acidolysis with oleic acid. Yeast surface-displayed RML mutant Asp256Ile/His257Leu is a potential, economically feasible catalyst for the production of structured lipids.
ESTHER : Zhang_2013_PLoS.One_8_e67892
PubMedSearch : Zhang_2013_PLoS.One_8_e67892
PubMedID: 23844120

Title : Electrochemical detection of dual exposure biomarkers of organophosphorus agents based on reactivation of inhibited cholinesterase - Ge_2013_Anal.Chem_85_9686
Author(s) : Ge X , Tao Y , Zhang A , Lin Y , Du D
Ref : Analytical Chemistry , 85 :9686 , 2013
Abstract : Considering inter- or intra-individual variation in the normal levels of acetylcholinesterase (AChE), real-time measurement of AChE via the reactivation from a postexposure sample was used, and thus a baseline-free and reliable approach was proposed for detecting/screening low-dose organophosphorus pesticides (OPs) poisons. The principle of this technology is on the basis of parallel measurements of AChE activity before and after reactivation from a postexposure to simultaneously provide the content of dual biomarkers of both enzyme inhibition and enzyme adducts. It is more accurate and reliable compared with only one biomarker (inhibition or adduct). Reactivation from a postexposure sample is a better individual enzyme baseline compared to pre-exposure from the population average level in currently available approaches. AChE activity was measured with an electrochemical method. Greatly enhanced sensitivity was achieved by using Fe3O4/Au nanocomposites to enrich thiocholine, the hydrolysis product of active AChE, followed by electrochemical oxidative desorption of the adsorbed thiocholine. The validation of this method for measurement of OP exposures was further explored with in vitro paraoxon inhibited human red blood cells (RBCs) samples and demonstrated its practicability.
ESTHER : Ge_2013_Anal.Chem_85_9686
PubMedSearch : Ge_2013_Anal.Chem_85_9686
PubMedID: 24020883

Title : Asperterpenols A and B, New Sesterterpenoids Isolated from a Mangrove Endophytic Fungus Aspergillus sp. 085242 - Xiao_2013_Org.Lett_15_2522
Author(s) : Xiao Z , Huang H , Shao C , Xia X , Ma L , Huang X , Lu Y , Lin Y , Long Y , She Z
Ref : Org Lett , 15 :2522 , 2013
Abstract : Asperterpenol A (1) and asperterpenol B (2), two novel sesterterpenoids with an unusual 5/8/6/6 tetracyclic ring skeleton, were isolated from a mangrove endophytic fungus Aspergillus sp. 085242. The structures were elucidated on the basis of spectroscopic methods and the absolute configurations determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 inhibit acetylcholinesterase with IC50 values of 2.3 and 3.0 muM, respectively.
ESTHER : Xiao_2013_Org.Lett_15_2522
PubMedSearch : Xiao_2013_Org.Lett_15_2522
PubMedID: 23642191

Title : High-throughput screening of B factor saturation mutated Rhizomucor miehei lipase thermostability based on synthetic reaction - Zhang_2012_Enzyme.Microb.Technol_50_325
Author(s) : Zhang JH , Lin Y , Sun YF , Ye YR , Zheng SP , Han SY
Ref : Enzyme Microb Technol , 50 :325 , 2012
Abstract : Conventional lipase screening methods are mostly based on hydrolytic activity, which may not always be the best method to assess the enzyme activity, especially for evaluating synthetic activity. Here we developed a high throughput and visual method to screen clones with high synthetic activity and used it to assess lipases thermostability. All mutants' lipase synthetic activity were identified through esterification of caprylic acid and ethanol with methyl red as the pH indicator adding in the substrates on according to the color change halo around the colony on culture plates since synthetic reaction was often accompanied with a rise in pH. After two rounds operation with the pH indicator screening method, we obtained a double mutant Asn120Lys/Lys131Phe from the Rhizomucor miehei lipase saturation mutated library based on amino acid residue B factors. The mutant's initial synthetic activity was a little higher than wild type and its thermostability in synthetic reaction was enhanced, which remained 63.1% residual activity after being heated at 70 degrees C for 5h comparing to 51.0% of wild type. The double mutant with the two residue replacements balanced well between stability and activity. Yeast surface display technology and the pH indicator method, combined with colony screening were shown to facilitate high-throughput screening for lipase synthetic activity.
ESTHER : Zhang_2012_Enzyme.Microb.Technol_50_325
PubMedSearch : Zhang_2012_Enzyme.Microb.Technol_50_325
PubMedID: 22500900

Title : Biosensor based on Prussian blue nanocubes\/reduced graphene oxide nanocomposite for detection of organophosphorus pesticides - Zhang_2012_Nanoscale_4_4674
Author(s) : Zhang L , Zhang A , Du D , Lin Y
Ref : Nanoscale , 4 :4674 , 2012
Abstract : We demonstrate a facile procedure to efficiently prepare Prussian blue nanocubes/reduced graphene oxide (PBNCs/rGO) nanocomposite by directly mixing Fe(3+) and [Fe(CN)(6)]((3)-) in the presence of GO in polyethyleneimine aqueous solution, resulting in a novel acetylcholinesterase (AChE) biosensor for detection of organophosphorus pesticides (OPs). The obtained nanocomposite was characterized by X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) microanalysis. It was clearly observed that the nanosheet has been decorated with cubic PB nanoparticles and nearly all the nanoparticles are distributed uniformly only on the surface of the reduced GO. No isolated PB nanoparticles were observed, indicating the strong interaction between PB nanocubes and the reduced GO and the formation of PBNCs/rGO nanocomposite. The obtained PBNCs/rGO based AChE biosensor make the peak potential shift negatively to 220 mV. The over-potential decreases approximately 460 mV compared to that on a bare electrode, suggesting that PBNCs/rGO has a high electrocatalytic activity towards the oxidation of thiocholine. The AChE biosensor shows rapid response and high sensitivity for detection of monocrotophos with a linear range from 1.0 to 600 ng mL(-1) and a detection limit of 0.1 ng mL(-1). These results suggest that the PBNCs/rGO hybrids nanocomposite exhibited high electrocatalytic activity towards the oxidation of thiocholine, which lead to the sensitive detection of OP pesticides.
ESTHER : Zhang_2012_Nanoscale_4_4674
PubMedSearch : Zhang_2012_Nanoscale_4_4674
PubMedID: 22732870

Title : Integrated lateral flow test strip with electrochemical sensor for quantification of phosphorylated cholinesterase: biomarker of exposure to organophosphorus agents - Du_2012_Anal.Chem_84_1380
Author(s) : Du D , Wang J , Wang L , Lu D , Lin Y
Ref : Analytical Chemistry , 84 :1380 , 2012
Abstract : An integrated lateral flow test strip with an electrochemical sensor (LFTSES) device with rapid, selective, and sensitive response for quantification of exposure to organophosphorus (OP) pesticides and nerve agents has been developed. The principle of this approach is based on parallel measurements of postexposure and baseline acetylcholinesterase (AChE) enzyme activity, where reactivation of the phosphorylated AChE is exploited to enable measurement of the total amount of AChE (including inhibited and active) which is used as a baseline for calculation of AChE inhibition. Quantitative measurement of phosphorylated adduct (OP-AChE) was realized by subtracting the active AChE from the total amount of AChE. The proposed LFTSES device integrates immunochromatographic test strip technology with electrochemical measurement using a disposable screen printed electrode which is located under the test zone. It shows a linear response between AChE enzyme activity and enzyme concentration from 0.05 to 10 nM, with a detection limit of 0.02 nM. On the basis of this reactivation approach, the LFTSES device has been successfully applied for in vitro red blood cells inhibition studies using chlorpyrifos oxon as a model OP agent. This approach not only eliminates the difficulty in screening of low-dose OP exposure because of individual variation of normal AChE values but also avoids the problem in overlapping substrate specificity with cholinesterases and avoids potential interference from other electroactive species in biological samples. It is baseline free and thus provides a rapid, sensitive, selective, and inexpensive tool for in-field and point-of-care assessment of exposures to OP pesticides and nerve agents.
ESTHER : Du_2012_Anal.Chem_84_1380
PubMedSearch : Du_2012_Anal.Chem_84_1380
PubMedID: 22243414

Title : Identification of phosphorylated butyrylcholinesterase in human plasma using immunoaffinity purification and mass spectrometry - Aryal_2012_Anal.Chim.Acta_723_68
Author(s) : Aryal UK , Lin CT , Kim JS , Heibeck TH , Wang J , Qian WJ , Lin Y
Ref : Anal Chim Acta , 723 :68 , 2012
Abstract : Paraoxon (diethyl 4-nitrophenyl phosphate) is an active metabolite of the common insecticide parathion and is acutely toxic due to the inhibition of cholinesterase (ChE) activity in the nervous systems. The inhibition of butyrylcholinesterase (BChE) activity by paraoxon is due to the formation of phosphorylated BChE adduct, and the detection of the phosphorylated BChE adduct in human plasma can serve as an exposure biomarker of organophosphate pesticides and nerve agents. In this study, we developed an immunoaffinity purification and liquid chromatography-mass spectrometry (LC-MS) strategy for identifying phosphorylated BChE in human plasma treated by paraoxon. BChE was captured by biotinylated anti-BChE polyclonal antibodies conjugated to streptavidin magnetic beads. Western blot analysis showed that the antibody was effective to recognize both native and modified BChE with high specificity. Using a purified BChE protein, we initially identified the exact phosphorylation site on the serine residue (S198) with a 108 Da modification by both MS/MS and accurately measured parent ion masses and quantified the extent of phosphorylation on S198 following paraoxon treatment to be >99.9%. Then, the phosphorylated BChE peptide in paraoxon-treated human plasma following immunoaffinity purification was successfully identified based on the accurate measured mass and retention time information initially obtained from the purified BChE protein. Thus, immunoaffinity purification combined with LC-MS represents a viable approach for the detection and quantification of phosphorylated BChE as an exposure biomarker of organophosphates and nerve agents.
ESTHER : Aryal_2012_Anal.Chim.Acta_723_68
PubMedSearch : Aryal_2012_Anal.Chim.Acta_723_68
PubMedID: 22444575

Title : Genome sequence of Corynebacterium glutamicum ATCC 14067, which provides insight into amino acid biosynthesis in coryneform bacteria - Lv_2012_J.Bacteriol_194_742
Author(s) : Lv Y , Liao J , Wu Z , Han S , Lin Y , Zheng S
Ref : Journal of Bacteriology , 194 :742 , 2012
Abstract : We report the genome sequence of Corynebacterium glutamicum ATCC 14067 (once named Brevibacterium flavum), which is useful for taxonomy research and further molecular breeding in amino acid production. Preliminary comparison with those of the reported coryneform strains revealed some notable differences that might be related to the difficulties in molecular manipulation.
ESTHER : Lv_2012_J.Bacteriol_194_742
PubMedSearch : Lv_2012_J.Bacteriol_194_742
PubMedID: 22247536
Gene_locus related to this paper: corgl-Cgl1133 , corgl-Cgl2249 , corgl-CGL2393 , corgl-q8nlr5 , corgl-q8nlz1 , corgt-g6wsn6

Title : Highly sensitive and selective immuno-capture\/electrochemical assay of acetylcholinesterase activity in red blood cells: a biomarker of exposure to organophosphorus pesticides and nerve agents - Chen_2012_Environ.Sci.Technol_46_1828
Author(s) : Chen A , Du D , Lin Y
Ref : Environ Sci Technol , 46 :1828 , 2012
Abstract : Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold (MWCNTs-Au) nanocomposites modified screen printed carbon electrode (SPCE), which is used for the immobilization of AChE specific antibody. Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentrations of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to OP concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposure to OPs.
ESTHER : Chen_2012_Environ.Sci.Technol_46_1828
PubMedSearch : Chen_2012_Environ.Sci.Technol_46_1828
PubMedID: 22208309

Title : Genome sequence of the highly efficient arsenite-oxidizing bacterium Achromobacter arsenitoxydans SY8 - Li_2012_J.Bacteriol_194_1243
Author(s) : Li X , Hu Y , Gong J , Lin Y , Johnstone L , Rensing C , Wang G
Ref : Journal of Bacteriology , 194 :1243 , 2012
Abstract : We report the draft genome sequence of Achromobacter arsenitoxydans SY8, the first reported arsenite-oxidizing bacterium belonging to the genus Achromobacter and containing a genomic arsenic island, an intact type III secretion system, and multiple metal(loid) transporters. The genome may be helpful to explore the mechanisms intertwining metal(loid) resistance and pathogenicity.
ESTHER : Li_2012_J.Bacteriol_194_1243
PubMedSearch : Li_2012_J.Bacteriol_194_1243
PubMedID: 22328747
Gene_locus related to this paper: 9burk-h0faw9 , 9burk-h0f9y5 , 9burk-h0fda6

Title : Draft genome sequence of Halomonas sp. strain HAL1, a moderately halophilic arsenite-oxidizing bacterium isolated from gold-mine soil - Lin_2012_J.Bacteriol_194_199
Author(s) : Lin Y , Fan H , Hao X , Johnstone L , Hu Y , Wei G , Alwathnani HA , Wang G , Rensing C
Ref : Journal of Bacteriology , 194 :199 , 2012
Abstract : We report the draft genome sequence of arsenite-oxidizing Halomonas sp. strain HAL1, isolated from the soil of a gold mine. Genes encoding proteins involved in arsenic resistance and transformation, phosphate utilization and uptake, and betaine biosynthesis were identified. Their identification might help in understanding how arsenic and phosphate metabolism are intertwined.
ESTHER : Lin_2012_J.Bacteriol_194_199
PubMedSearch : Lin_2012_J.Bacteriol_194_199
PubMedID: 22156396
Gene_locus related to this paper: 9gamm-g4fal7 , 9gamm-g4f104

Title : Pharmacokinetics and Pharmacodynamics of Chlorpyrifos and 3,5,6-Trichloro-2-pyridinol in Rat Saliva After Chlorpyrifos Administration - Smith_2012_Toxicol.Sci_130_245
Author(s) : Smith JN , Wang J , Lin Y , Klohe EM , Timchalk C
Ref : Toxicol Sci , 130 :245 , 2012
Abstract : Sensors have been developed for noninvasive biomonitoring of the organophosphate pesticide chlorpyrifos (CPF), and previous studies have suggested consistent partitioning of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of CPF, into saliva after exposure to TCPy. The objective of this study was to quantitatively evaluate in vivo pharmacokinetics and pharmacodynamics of CPF and TCPy in saliva after CPF administration. Rats were coadministered CPF (0.5-5mg/kg) and pilocarpine (~13mg/kg) iv. Saliva and blood were collected, and levels of CPF, TCPy, and cholinesterase (ChE) activity were quantified. Experimental results suggest that CPF is rapidly metabolized after iv administration. Formation of TCPy from administered CPF at the low dose (0.5mg/kg) was slower than from higher CPF doses, potentially due to differences in plasma protein binding to CPF. CPF was measured in saliva only at the first time point sampled (0-15min), indicating low partitioning and rapid metabolism. After formation, TCPy pharmacokinetics were very similar in blood and saliva. Saliva/blood TCPy concentration ratios were not affected by TCPy concentration in blood, saliva flow rate, or salivary pH and were consistent with previous studies. ChE activity in plasma demonstrated a dose-dependent decrease, and ChE activity in saliva was extremely variable and demonstrated no dose relationship. A physiologically based pharmacokinetic and pharmacodynamic model for CPF was modified and predicted the data reasonably well. It is envisioned that a combination of biomonitoring compounds like TCPy in saliva coupled with computational modeling will form an approach to measure pesticide exposure to susceptible human populations such as agricultural workers.
ESTHER : Smith_2012_Toxicol.Sci_130_245
PubMedSearch : Smith_2012_Toxicol.Sci_130_245
PubMedID: 22874420

Title : Genome sequence of the arsenite-oxidizing strain Agrobacterium tumefaciens 5A - Hao_2012_J.Bacteriol_194_903
Author(s) : Hao X , Lin Y , Johnstone L , Liu G , Wang G , Wei G , McDermott T , Rensing C
Ref : Journal of Bacteriology , 194 :903 , 2012
Abstract : Microbial transformations of arsenic influence its mobility and toxicity. We report the draft genome sequence of the arsenite-oxidizing strain Agrobacterium tumefaciens 5A isolated from an As-contaminated soil in the Madison River Valley, MT. A large number of metal (or metalloid) resistance genes, especially contributing to arsenite oxidation, were identified.
ESTHER : Hao_2012_J.Bacteriol_194_903
PubMedSearch : Hao_2012_J.Bacteriol_194_903
PubMedID: 22275101
Gene_locus related to this paper: agrsh-f0lb16 , rhird-h0hik8

Title : Draft genome sequence of plant growth-promoting rhizobium Mesorhizobium amorphae, isolated from zinc-lead mine tailings - Hao_2012_J.Bacteriol_194_736
Author(s) : Hao X , Lin Y , Johnstone L , Baltrus DA , Miller SJ , Wei G , Rensing C
Ref : Journal of Bacteriology , 194 :736 , 2012
Abstract : Here, we describe the draft genome sequence of Mesorhizobium amorphae strain CCNWGS0123, isolated from nodules of Robinia pseudoacacia growing on zinc-lead mine tailings. A large number of metal(loid) resistance genes, as well as genes reported to promote plant growth, were identified, presenting a great future potential for aiding phytoremediation in metal(loid)-contaminated soil.
ESTHER : Hao_2012_J.Bacteriol_194_736
PubMedSearch : Hao_2012_J.Bacteriol_194_736
PubMedID: 22247533
Gene_locus related to this paper: 9rhiz-g6y654 , 9rhiz-g6yin5 , 9rhiz-g6yg34

Title : Draft genome sequence of Pseudomonas psychrotolerans L19, isolated from copper alloy coins - Santo_2012_J.Bacteriol_194_1623
Author(s) : Santo CE , Lin Y , Hao X , Wei G , Rensing C , Grass G
Ref : Journal of Bacteriology , 194 :1623 , 2012
Abstract : We report the draft genome sequence of Pseudomonas psychrotolerans strain L19, isolated from a European 50-cent copper alloy coin. Multiple genes potentially involved in copper resistance were identified; however, it is unknown if these copper ion resistance determinants contribute to prolonged survival of this strain on dry metallic copper.
ESTHER : Santo_2012_J.Bacteriol_194_1623
PubMedSearch : Santo_2012_J.Bacteriol_194_1623
PubMedID: 22374955
Gene_locus related to this paper: 9psed-h0jhr8 , 9psed-h0jeb0

Title : Complete genome sequence of Bacillus amyloliquefaciens XH7, which exhibits production of purine nucleosides - Yang_2011_J.Bacteriol_193_5593
Author(s) : Yang H , Liao Y , Wang B , Lin Y , Pan L
Ref : Journal of Bacteriology , 193 :5593 , 2011
Abstract : Here, we report the complete annotated genome sequence of Bacillus amyloliquefaciens XH7, which is used to produce purine nucleosides in industry. The genome sequence will allow for the characterization of the molecular mechanisms underlying its beneficial properties.
ESTHER : Yang_2011_J.Bacteriol_193_5593
PubMedSearch : Yang_2011_J.Bacteriol_193_5593
PubMedID: 21914895
Gene_locus related to this paper: baca2-a7z811 , bacas-e1ur92

Title : [Construction of Aspergillus niger lipase mutants with oil-water interface independence] - Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
Author(s) : Chen D , Shu Z , Xue L , Lin R , Wu J , Jiang Y , Li X , Lin Y , Huang J
Ref : Sheng Wu Gong Cheng Xue Bao , 27 :860 , 2011
Abstract : Based on previous bioinformational analysis results, two Aspergillus niger lipase (ANL) mutants, ANL-Ser84Gly and ANL-Asp99Pro were constructed to screen ANL mutants with oil-water interface independence. ANL-Ser84Gly still displayed a pronounced interfacial activation, while ANL-Asp99Pro displayed no interfacial activation. The specific activity of ANL-Ser84Gly towards p-nitrophenyl palmitate (-myristate, -laurate and -decanoate) decreased by 29.8% (53.1, 60.1 and 77.1, respectively) than that of ANL, while the specific activity of ANL-Asp99Pro towards p-nitrophenyl palmitate increased by 2.2-fold. The mutation in the hinge region at both sides of the lid domain also destabilized various secondary structure factors of ANL-S84G and ANL-D99P, which resulted in a substantial decrease in thermostability. The achievement to construct oil-water interface-independent ANL mutants would help to further understand lipase interfacial activation mechanism.
ESTHER : Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
PubMedSearch : Chen_2011_Sheng.Wu.Gong.Cheng.Xue.Bao_27_860
PubMedID: 22034814

Title : Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study - Franceschini_2011_Circ.Cardiovasc.Genet_4_661
Author(s) : Franceschini N , Carty C , Buzkova P , Reiner AP , Garrett T , Lin Y , Vockler JS , Hindorff LA , Cole SA , Boerwinkle E , Lin DY , Bookman E , Best LG , Bella JN , Eaton C , Greenland P , Jenny N , North KE , Taverna D , Young AM , Deelman E , Kooperberg C , Psaty B , Heiss G
Ref : Circ Cardiovasc Genet , 4 :661 , 2011
Abstract : BACKGROUND: Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts. METHODS AND
RESULTS: The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hispanic individuals (113 events), 3669 American Indian individuals (595 events), and 885 Asian/Pacific Islander individuals (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex, and ancestry (as needed). Nine loci were statistically associated with incident CHD events in white participants: 9p21 (rs10757278; P=4.7 x 10(-41)), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7 x 10(-6)), MTHFD1L (rs6922269, P=5.1 x 10(-10)), APOE (rs429358; P=2.7x10(-18)), ZNF627 (rs4804611; P=5.0 x 10(-8)), CXCL12 (rs501120; P=1.4 x 10(-6)) and LPL (rs268; P=2.7 x 10(-17)). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals age 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in black participants, and associations varied in other US minorities.
CONCLUSIONS: Prospective analyses of white participants replicated several reported cross-sectional CHD-SNP associations.
ESTHER : Franceschini_2011_Circ.Cardiovasc.Genet_4_661
PubMedSearch : Franceschini_2011_Circ.Cardiovasc.Genet_4_661
PubMedID: 22042884

Title : Genome sequence of Corynebacterium glutamicum S9114, a strain for industrial production of glutamate - Lv_2011_J.Bacteriol_193_6096
Author(s) : Lv Y , Wu Z , Han S , Lin Y , Zheng S
Ref : Journal of Bacteriology , 193 :6096 , 2011
Abstract : Here we report the genome sequence of Corynebacterium glutamicum S9114, an industrial producer widely used in production of glutamate in China. Preliminary comparison with the sequences of the Corynebacterium glutamicum strains ATCC 13032 and R revealed some notable mutagenesis that might be related to the high yield of glutamate.
ESTHER : Lv_2011_J.Bacteriol_193_6096
PubMedSearch : Lv_2011_J.Bacteriol_193_6096
PubMedID: 21994927
Gene_locus related to this paper: corgl-Cgl1133 , corgl-Cgl2249 , corgl-CGL2393 , corgl-q8nlr5 , corgt-g6wsn6

Title : Azaphilones and p-terphenyls from the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2) isolated from the South China Sea - Huang_2011_J.Nat.Prod_74_997
Author(s) : Huang H , Feng X , Xiao Z , Liu L , Li H , Ma L , Lu Y , Ju J , She Z , Lin Y
Ref : Journal of Natural Products , 74 :997 , 2011
Abstract : Eight secondary metabolites, including three new azaphilones (chermesinones A-C, 1-3), three new p-terphenyls (6'-O-desmethylterphenyllin, 4; 3-hydroxy-6'-O-desmethylterphenyllin, 5; 3''-deoxy-6'-O-desmethylcandidusin B, 7), and two known p-terphenyls (6, 8), were isolated from the culture of the mangrove endophytic fungus Penicillium chermesinum (ZH4-E2). Their structures were established by spectroscopic analysis. The absolute configuration of 1 was determined by X-ray crystallography. Terphenyls 4, 5, and 6 exhibited strong inhibitory effects against alpha-glucosidase with IC50 values of 0.9, 4.9, and 2.5 muM, respectively. Terphenyls 7 and 8 showed inhibitory activity toward acetylcholinesterase with IC50 values of 7.8 and 5.2 muM.
ESTHER : Huang_2011_J.Nat.Prod_74_997
PubMedSearch : Huang_2011_J.Nat.Prod_74_997
PubMedID: 21510637

Title : Enzyme-linked immunosorbent assay for detection of organophosphorylated butyrylcholinesterase: A biomarker of exposure to organophosphate agents - Wang_2011_Anal.Chim.Acta_693_1
Author(s) : Wang L , Du D , Lu D , Lin CT , Smith JN , Timchalk C , Liu F , Wang J , Lin Y
Ref : Anal Chim Acta , 693 :1 , 2011
Abstract : A sandwich enzyme-linked immunosorbent assay (sELISA) has been developed for detection of organophosphorylated butyrylcholinesterase (OP-BChE), a potential biomarker for human exposure to organophosphate insecticides and nerve agents. A pair of antibodies specific to OP-BChE adduct were identified through systematic screening of several anti BChE antibodies (anti-BChE) and anti-phosphoserine antibodies (anti-P(ser)) from different sources. The selected anti-BChE (set as capture antibody) antibodies recognize both phosphorylated and nonphosphorylated BChE. These antibodies can therefore be used to capture both BChE and OP-BChE from the sample matrices. The anti-P(ser) (set as detecting antibody) was used to recognize the OP moiety of OP-BChE adducts. With the combination of the selected antibody pair, several key parameters (such as the concentration of anti-BChE and anti-P(ser), and the blocking agent) were optimized to enhance the sensitivity and selectivity of the sELISA. Under the optimal conditions, the sELISA has shown a wide linear range from 0.03 nM to 30 nM, with a detection limit of 0.03 nM. Furthermore, the sELISA was successfully applied to detect OP-BChE using in vitro biological samples such as rat plasma spiked with OP-BChE with excellent adduct recovery (z>99%). These results demonstrate that this novel approach holds great promise to develop an ELISA kit and offers a simple and cost-effective tool for screening/evaluating exposure to organophosphate insecticides and nerve agents.
ESTHER : Wang_2011_Anal.Chim.Acta_693_1
PubMedSearch : Wang_2011_Anal.Chim.Acta_693_1
PubMedID: 21504805

Title : Genome sequence of Escherichia coli XH140A, which produces L-threonine - Yang_2011_J.Bacteriol_193_6090
Author(s) : Yang H , Liao Y , Wang B , Lin Y , Pan L
Ref : Journal of Bacteriology , 193 :6090 , 2011
Abstract : Here we report the draft annotated genome sequence of Escherichia coli XH140A, which is used to produce l-threonine in industry. The genome sequence will allow the characterization of the molecular mechanisms underlying its beneficial properties.
ESTHER : Yang_2011_J.Bacteriol_193_6090
PubMedSearch : Yang_2011_J.Bacteriol_193_6090
PubMedID: 21994923
Gene_locus related to this paper: ecoli-ybff , ecoli-ycfp , ecoli-yqia , ecoli-YfhR

Title : Nanoparticle-based immunosensor with apoferritin templated metallic phosphate label for quantification of phosphorylated acetylcholinesterase - Du_2011_Biosens.Bioelectron_26_3857
Author(s) : Du D , Chen A , Xie Y , Zhang A , Lin Y
Ref : Biosensors & Bioelectronics , 26 :3857 , 2011
Abstract : A new sandwich-like electrochemical immunosensor has been developed for quantification of organophosphorylated acetylcholinesterase (OP-AChE), an exposure biomarker of organophosphate pesticides and nerve agents. Zirconia nanoparticles (ZrO2 NPs) were anchored on a screen printed electrode (SPE) to preferably capture OP-AChE adducts by metal chelation with phospho-moieties, which was selectively recognized by lead phosphate-apoferritin labeled anti-AChE antibody (LPA-anti-AChE). The sandwich-like immunoreactions were performed among ZrO2 NPs, OP-AChE and LPA-anti-AChE to form ZrO2/OP-AChE/LPA-anti-AChE complex and the released lead ions were detected on a disposable SPE. The binding affinity was investigated by both square wave voltammetry (SWV) and quartz crystal microbalance (QCM) measurements. The proposed immunosensor yielded a linear response current over a broad OP-AChE concentrations range from 0.05 nM to 10 nM, with detection limit of 0.02 nM, which has enough sensitivity for monitoring of low-dose exposure to OPs. This method avoids the drawback of unavailability of commercial OP-specific antibody as well as amplifies detection signal by using apoferritin encoded metallic phosphate nanoparticle tags. This nanoparticle-based immunosensor offers a new method for rapid, sensitive, selective and inexpensive quantification of phosphorylated adducts for monitoring of OP pesticides and nerve agents exposures.
ESTHER : Du_2011_Biosens.Bioelectron_26_3857
PubMedSearch : Du_2011_Biosens.Bioelectron_26_3857
PubMedID: 21481580

Title : Magnetic electrochemical sensing platform for biomonitoring of exposure to organophosphorus pesticides and nerve agents based on simultaneous measurement of total enzyme amount and enzyme activity - Du_2011_Anal.Chem_83_3770
Author(s) : Du D , Wang J , Wang L , Lu D , Smith JN , Timchalk C , Lin Y
Ref : Analytical Chemistry , 83 :3770 , 2011
Abstract : We report a new approach for electrochemical quantification of enzymatic inhibition and phosphorylation for biomonitoring of exposure to organophosphorus (OP) pesticides and nerve agents based on a magnetic bead (MB) immunosensing platform. The principle of this approach is based on the combination of MB immunocapture-based enzyme activity assay and competitive immunoassay of the total amount of enzyme for simultaneous detection of enzyme inhibition and phosphorylation in biological fluids. Butyrylcholinesterase (BChE) was chosen as a model enzyme. In competitive immunoassay, the target BChE in a sample competes with the BChE immobilized on the MBs to bind to the limited sites of anti-BChE antibody labeled with quantum dots (QD-anti-BChE), followed by stripping voltammetric analysis of the bound QD conjugate on the MBs. This assay shows a linear response over the total BChE concentration range of 0.1-20 nM. Simultaneous real time BChE activity was measured on an electrochemical carbon nanotube-based sensor coupled with a microflow injection system after immunocapture by the MB-anti-BChE conjugate. Therefore, the formed phosphorylated BChE adduct (OP-BChE) can be estimated by the difference values of the total amount of BChE (including active and OP-inhibited) and active BChE from established calibration curves. This approach not only eliminates the difficulty in screening of low-dose OP exposure (less than 20% inhibition of BChE) because of individual variation of BChE values but also avoids the drawback of the scarce availability of OP-BChE antibody. It is sensitive enough to detect 0.5 nM OP-BChE, which is less than 2% BChE inhibition. This method offers a new method for rapid, accurate, selective, and inexpensive quantification of OP-BChE and enzyme inhibition for biomonitoring of OP and nerve agent exposures.
ESTHER : Du_2011_Anal.Chem_83_3770
PubMedSearch : Du_2011_Anal.Chem_83_3770
PubMedID: 21462919

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

Title : Display of Candida antarctica lipase B on Pichia pastoris and its application to flavor ester synthesis - Su_2010_Appl.Microbiol.Biotechnol_86_1493
Author(s) : Su GD , Huang DF , Han SY , Zheng SP , Lin Y
Ref : Applied Microbiology & Biotechnology , 86 :1493 , 2010
Abstract : Two alternative cell-surface display systems were developed in Pichia pastoris using the alpha-agglutinin and Flo1p (FS) anchor systems, respectively. Both the anchor cell wall proteins were obtained originally from Saccharomyces cerevisiae. Candida antarctica lipase B (CALB) was displayed functionally on the cell surface of P. pastoris using the anchor proteins alpha-agglutinin and FS. The activity of CALB displayed on P. pastoris was tenfold higher than that of S. cerevisiae. The hydrolytic and synthetic activities of CALB fused with alpha-agglutinin and FS anchored on P. pastoris were investigated. The hydrolytic activities of both lipases displayed on yeast cells surface were more than 200 U/g dry cell after 120 h of culture (200 and 270 U/g dry cell, respectively). However, the synthetic activity of CALB fused with alpha-agglutinin on P. pastoris was threefold higher than that of the FS fusion protein when applied to the synthesis of ethyl caproate. Similarly, the CALB displayed on P. pastoris using alpha-agglutinin had a higher catalytic efficiency with respect to the synthesis of other short-chain flavor esters than that displayed using the FS anchor. Interestingly, for some short-chain esters, the synthetic activity of displaying CALB fused with alpha-agglutinin on P. pastoris was even higher than that of the commercial CALB Novozyme 435.
ESTHER : Su_2010_Appl.Microbiol.Biotechnol_86_1493
PubMedSearch : Su_2010_Appl.Microbiol.Biotechnol_86_1493
PubMedID: 20033404

Title : EQCM immunoassay for phosphorylated acetylcholinesterase as a biomarker for organophosphate exposures based on selective zirconia adsorption and enzyme-catalytic precipitation - Wang_2009_Biosens.Bioelectron_24_2377
Author(s) : Wang H , Wang J , Choi D , Tang Z , Wu H , Lin Y
Ref : Biosensors & Bioelectronics , 24 :2377 , 2009
Abstract : A zirconia (ZrO(2)) adsorption-based immunoassay by electrochemical quartz crystal microbalance (EQCM) has been initially developed, aiming at the detection of phosphorylated acetylcholinesterase (Phospho-AChE) as a potential biomarker for bio-monitoring exposures to organophosphate (OP) pesticides and chemical warfare agents. Hydroxyl-derivatized monolayer was preferably chosen to modify the crystal serving as the template for directing the electro-deposition of ZrO(2) film with uniform nanostructures. The resulting ZrO(2) film was utilized to selectively capture Phospho-AChE from the sample media. Horseradish peroxidase (HRP)-labeled anti-AChE antibodies were further employed to recognize the captured phosphorylated proteins. Enzyme-catalytic oxidation of the benzidine substrate resulted in the accumulation of insoluble product on the functionalized crystal. Ultrasensitive EQCM quantification by mass-amplified frequency responses as well as rapid qualification by visual color changes of product could be thus, achieved. Moreover, 4-chloro-1-naphthol (CN) was studied as an ideal chromogenic substrate for the enzyme-catalytic precipitation. Experimental results show that the developed EQCM technique can allow for the detection of Phospho-AChE in human plasma with a detection limit of 0.020 nM. Such an EQCM immunosensing format opens a new door towards the development of simple, sensitive, and field-applicable biosensor for biologically monitoring low-level OP exposures.
ESTHER : Wang_2009_Biosens.Bioelectron_24_2377
PubMedSearch : Wang_2009_Biosens.Bioelectron_24_2377
PubMedID: 19135350

Title : Biomonitoring of organophosphorus agent exposure by reactivation of cholinesterase enzyme based on carbon nanotube-enhanced flow-injection amperometric detection - Du_2009_Anal.Chem_81_9314
Author(s) : Du D , Wang J , Smith JN , Timchalk C , Lin Y
Ref : Analytical Chemistry , 81 :9314 , 2009
Abstract : A portable, rapid, and sensitive assessment of subclinical organophosphorus (OP) agent exposure based on reactivation of cholinesterase (ChE) from OP-inhibited ChE using rat saliva (in vitro) was developed using an electrochemical sensor coupled with a microflow-injection system. The sensor was based on a carbon nanotube (CNT)-modified screen printed carbon electrode (SPE), which was integrated into a flow cell. Because of the extent of interindividual ChE activity variability, ChE biomonitoring often requires an initial baseline determination (noninhibited) of enzyme activity which is then directly compared with activity after OP exposure. This manuscript describes an alternative strategy where reactivation of the phosphorylated enzyme was exploited to enable measurement of both inhibited and baseline ChE activity (after reactivation by an oxime, i.e., pralidoxime iodide) in the same sample. The use of CNT makes the electrochemical detection of the products from enzymatic reactions more feasible with extremely high sensitivity (5% ChE inhibition) and selectivity. Paraoxon was selected as a model OP compound for in vitro inhibition studies. Some experimental parameters, e.g., inhibition and reactivation time, have been optimized such that 92-95% of ChE reactivation can be achieved over a broad range of ChE inhibition (5-94%) with paraoxon. The extent of enzyme inhibition using this electrochemical sensor correlates well with conventional enzyme activity measurements. On the basis of the double determinations of enzyme activity, this flow-injection device has been successfully used to detect paraoxon inhibition efficiency in saliva samples (95% of ChE activity is due to butyrylcholinesterase), which demonstrated its promise as a sensitive monitor of OP exposure in biological fluids. Since it excludes inter- or intraindividual variation in the normal levels of ChE, this new CNT-based electrochemical sensor thus provides a sensitive and quantitative tool for point-of-care assessment and noninvasive biomonitoring of the exposure to OP pesticides and chemical nerve agents.
ESTHER : Du_2009_Anal.Chem_81_9314
PubMedSearch : Du_2009_Anal.Chem_81_9314
PubMedID: 19839597

Title : Enhancing thermostability of a Rhizomucor miehei lipase by engineering a disulfide bond and displaying on the yeast cell surface - Han_2009_Appl.Microbiol.Biotechnol_85_117
Author(s) : Han ZL , Han SY , Zheng SP , Lin Y
Ref : Applied Microbiology & Biotechnology , 85 :117 , 2009
Abstract : To increase the thermostability of Rhizomucor miehei lipase, the software Disulfide by Design was used to engineer a novel disulfide bond between residues 96 and 106, and the corresponding double cysteine mutants were constructed. The R. miehei lipase mutant could be expressed by Pichia pastoris in a free secreted form or could be displayed on the cell surface. The new disulfide bond spontaneously formed in the mutant R. miehei lipase. Thermostability was examined by measuring of hydrolysis activity using 4-nitrophenyl caprylate as a substrate. The engineered disulfide bond contributed to thermostability in the free form of the R. miehei lipase variant. The variant displayed on the yeast cell surface had significantly increased residual hydrolytic activity in aqueous solution after incubation at 60 degrees C for 5 h and increased synthetic activity in organic solvent at 60 degrees C. These results indicated that yeast surface display might improve the stability of R. miehei lipase, as well as amplifying the thermostability through the engineered disulfide bond.
ESTHER : Han_2009_Appl.Microbiol.Biotechnol_85_117
PubMedSearch : Han_2009_Appl.Microbiol.Biotechnol_85_117
PubMedID: 19533118
Gene_locus related to this paper: rhimi-lipas

Title : The genome of a lepidopteran model insect, the silkworm Bombyx mori - Xia_2008_Insect.Biochem.Mol.Biol_38_1036
Author(s) : Xia Q , Wang J , Zhou Z , Li R , Fan W , Cheng D , Cheng T , Qin J , Duana J , Xu H , Li Q , Li N , Wang M , Dai F , Liu C , Lin Y , Zhao P , Zhang H , Liu S , Zha X , Li C , Zhao A , Pan M , Pan G , Shen Y , Gao Z , Wang Z , Wang G , Wu Z , Hou Y , Chai C , Yu Q , He N , Zhang Z , Li S , Yang H , Lu C , Xiang Z , Mita K , Kasahara M , Nakatani Y , Yamamoto K , Abe H , Ahsan B , Daimoni T , Doi K , Fujii T , Fujiwara H , Fujiyama A , Futahashi R , Hashimotol S , Ishibashi J , Iwami M , Kadono-Okuda K , Kanamori H , Kataoka H , Katsuma S , Kawaoka S , Kawasaki H , Kohara Y , Kozaki T , Kuroshu RM , Kuwazaki S , Matsushima K , Minami H , Nagayasu Y , Nakagawa T , Narukawa J , Nohata J , Ohishi K , Ono Y , Osanai-Futahashi M , Ozaki K , Qu W , Roller L , Sasaki S , Sasaki T , Seino A , Shimomura M , Shin-I T , Shinoda T , Shiotsuki T , Suetsugu Y , Sugano S , Suwa M , Suzuki Y , Takiya S , Tamura T , Tanaka H , Tanaka Y , Touhara K , Yamada T , Yamakawa M , Yamanaka N , Yoshikawa H , Zhong YS , Shimada T , Morishita S
Ref : Insect Biochemistry & Molecular Biology , 38 :1036 , 2008
Abstract : Bombyx mori, the domesticated silkworm, is a major insect model for research, and the first lepidopteran for which draft genome sequences became available in 2004. Two independent data sets from whole-genome shotgun sequencing were merged and assembled together with newly obtained fosmid- and BAC-end sequences. The remarkably improved new assembly is presented here. The 8.5-fold sequence coverage of an estimated 432 Mb genome was assembled into scaffolds with an N50 size of approximately 3.7 Mb; the largest scaffold was 14.5 million base pairs. With help of a high-density SNP linkage map, we anchored 87% of the scaffold sequences to all 28 chromosomes. A particular feature was the high repetitive sequence content estimated to be 43.6% and that consisted mainly of transposable elements. We predicted 14,623 gene models based on a GLEAN-based algorithm, a more accurate prediction than the previous gene models for this species. Over three thousand silkworm genes have no homologs in other insect or vertebrate genomes. Some insights into gene evolution and into characteristic biological processes are presented here and in other papers in this issue. The massive silk production correlates with the existence of specific tRNA clusters, and of several sericin genes assembled in a cluster. The silkworm's adaptation to feeding on mulberry leaves, which contain toxic alkaloids, is likely linked to the presence of new-type sucrase genes, apparently acquired from bacteria. The silkworm genome also revealed the cascade of genes involved in the juvenile hormone biosynthesis pathway, and a large number of cuticular protein genes.
ESTHER : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedSearch : Xia_2008_Insect.Biochem.Mol.Biol_38_1036
PubMedID: 19121390
Gene_locus related to this paper: bommo-a0mnw6 , bommo-a1yw85 , bommo-a9ls22 , bommo-ACHE1 , bommo-ACHE2 , bommo-b0fgv8 , bommo-b1q137 , bommo-b1q139 , bommo-b1q140 , bommo-b1q141 , bommo-b2zdz0 , bommo-b3gef6 , bommo-b3gef7 , bommo-b3gs55 , bommo-b3gs56 , bommo-d2ktu3 , bommo-d2ktu5 , bommo-d9ile0 , bommo-e1cga5 , bommo-e1cga6 , bommo-g8fpz6 , bommo-h9iu43 , bommo-h9iu46 , bommo-h9iu47.1 , bommo-h9iu47.2 , bommo-h9iue5 , bommo-h9ivg2 , bommo-h9iwj7 , bommo-h9iwj8 , bommo-h9ix58 , bommo-h9ixi1.1 , bommo-h9ixi1.2 , bommo-h9iy47 , bommo-h9izw1 , bommo-h9j0s4 , bommo-h9j1y0 , bommo-h9j3r0 , bommo-h9j3w6 , bommo-h9j3w7 , bommo-h9j5t0 , bommo-h9j8g3 , bommo-h9j9k9 , bommo-h9j066 , bommo-h9j067 , bommo-h9j593 , bommo-h9j594 , bommo-h9j990 , bommo-h9jde8 , bommo-h9jde9 , bommo-h9jdf0 , bommo-h9jds4 , bommo-h9jle7 , bommo-h9jn83 , bommo-h9jn85 , bommo-h9jrg2 , bommo-h9jyh9 , bommo-JHE , bommo-m1rmh6 , bommo-q1hq05 , bommo-q4tte1 , bommo-h9j592 , bommo-h9j604 , bommo-h9jpm8 , bommo-h9iss4 , bommo-h9j2c7

Title : Nanoparticle-based electrochemical immunosensor for the detection of phosphorylated acetylcholinesterase: an exposure biomarker of organophosphate pesticides and nerve agents - Liu_2008_Chemistry_14_9951
Author(s) : Liu G , Wang J , Barry R , Petersen C , Timchalk C , Gassman PL , Lin Y
Ref : Chemistry , 14 :9951 , 2008
Abstract : A nanoparticle-based electrochemical immunosensor has been developed for the detection of phosphorylated acetylcholinesterase (AChE), which is a potential biomarker of exposure to organophosphate (OP) pesticides and chemical warfare nerve agents. Zirconia nanoparticles (ZrO(2) NPs) were used as selective sorbents to capture the phosphorylated AChE adduct, and quantum dots (ZnS@CdS, QDs) were used as tags to label monoclonal anti-AChE antibody to quantify the immunorecognition events. The sandwich-like immunoreactions were performed among the ZrO(2) NPs, which were pre-coated on a screen printed electrode (SPE) by electrodeposition, phosphorylated AChE and QD-anti-AChE. The captured QD tags were determined on the SPE by electrochemical stripping analysis of its metallic component (cadmium) after an acid-dissolution step. Paraoxon was used as the model OP insecticide to prepare the phosphorylated AChE adducts to demonstrate proof of principle for the sensor. The phosphorylated AChE adduct was characterized by Fourier transform infrared spectroscopy (FTIR) and mass spectroscopy. The binding affinity of anti-AChE to the phosphorylated AChE was validated with an enzyme-linked immunosorbent assay. The parameters (e.g., amount of ZrO(2) NP, QD-anti-AChE concentration,) that govern the electrochemical response of immunosensors were optimized. The voltammetric response of the immunosensor is highly linear over the range of 10 pM to 4 nM phosphorylated AChE, and the limit of detection is estimated to be 8.0 pM. The immunosensor also successfully detected phosphorylated AChE in human plasma. This new nanoparticle-based electrochemical immunosensor provides an opportunity to develop field-deployable, sensitive, and quantitative biosensors for monitoring exposure to a variety of OP pesticides and nerve agents.
ESTHER : Liu_2008_Chemistry_14_9951
PubMedSearch : Liu_2008_Chemistry_14_9951
PubMedID: 18942695

Title : Carbon nanotube-based electrochemical sensor for assay of salivary cholinesterase enzyme activity: an exposure biomarker of organophosphate pesticides and nerve agents - Wang_2008_Environ.Sci.Technol_42_2688
Author(s) : Wang J , Timchalk C , Lin Y
Ref : Environ Sci Technol , 42 :2688 , 2008
Abstract : Certain saliva enzymes may be useful biomarkers for detecting exposures to organophosphate pesticides and chemical nerve agents. In this regard, saliva biomonitoring offers a simple and noninvasive approach for rapidly evaluating those exposures in real time. An electrochemical sensor coupled with a microflow injection system was developed for a simple, rapid, and sensitive characterization of cholinesterase (ChE) enzyme activities in rat saliva. The electrochemical sensor is based on a carbon nanotube (CNT)-modified screen-printed carbon electrode (SPE), which is integrated into a flow cell. Because of the excellent electrocatalytic activity of the CNTs, the sensor can detect electroactive species that are produced from enzymatic reactions with extremely high sensitivity and at low potentials. The electrochemical properties of acetylcholinesterase (AChE) enzymatic products were studied using a CNT-modified SPE, and the operation parameters such as the applied potential and substrate concentration were optimized to achieve the best performance. The AChE enzyme activity was further investigated using the CNT-based electrochemical sensor with commercially available purified AChE and ChE in saliva obtained from nave rats. It is found that the calibration curve is linear over a wide range of AChE concentrations from 5 pM to 0.5 nM, and the sensor is very sensitive with the detection limit down to 2 pM. The dynamics of the ChE enzyme activity in saliva with organophosphate pesticides was further studied using this sensor. The results showthatthe senor can be used to characterize salivary enzyme activity and to detect the exposure to organophosphate compounds. This new CNT-based electrochemical sensor thus provides a sensitive and quantitative tool for noninvasive biomonitoring of the exposure to organophosphate pesticides and nerve agents.
ESTHER : Wang_2008_Environ.Sci.Technol_42_2688
PubMedSearch : Wang_2008_Environ.Sci.Technol_42_2688
PubMedID: 18505017

Title : Magnetic electrochemical immunoassays with quantum dot labels for detection of phosphorylated acetylcholinesterase in plasma - Wang_2008_Anal.Chem_80_8477
Author(s) : Wang H , Wang J , Timchalk C , Lin Y
Ref : Analytical Chemistry , 80 :8477 , 2008
Abstract : A new magnetic electrochemical immunoassay has been developed as a tool for biomonitoring exposures to organophosphate (OP) compounds, e.g., insecticides and chemical nerve agents, by directly detecting organophosphorylated acetylcholinesterase (OP-AChE). This immunoassay uniquely incorporates highly efficient magnetic separation with ultrasensitive square wave voltammetry (SWV) analysis with quantum dots (QDs) as labels. A pair of antibodies was used to achieve the specific recognition of OP-AChE that was prepared with paraoxon as an OP model agent. Antiphosphoserine polyclonal antibodies were anchored on amorphous magnetic particles preferably chosen to capture OP-AChE from the sample matrixes by binding their phosphoserine moieties that were exposed through unfolding the protein adducts. This was validated by electrochemical examinations and enzyme-linked immunosorbent assays. Furthermore, antihuman AChE monoclonal antibodies were labeled with cadmium-source QDs to selectively recognize the captured OP-AChE, as characterized by transmission electron microscopy. The subsequent electrochemical SWV analysis of the cadmium component released by acid from the coupled QDs was conducted on disposable screen-printed electrodes. Experimental results indicated that the SWV-based immunoassays could yield a linear response over a broad concentration range of 0.3-300 ng/mL OP-AChE in human plasma with a detection limit of 0.15 ng/mL. Such a novel electrochemical immunoassay holds great promise as a simple, selective, sensitive, and field-deployable tool for the effective biomonitoring and diagnosis of potential exposures to nerve agents and pesticides.
ESTHER : Wang_2008_Anal.Chem_80_8477
PubMedSearch : Wang_2008_Anal.Chem_80_8477
PubMedID: 18855408

Title : [Expression of Candida antarctica lipase B on yeast surface and synthesis of ethyl hexanoate catalyzed by CALB] - Pan_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_673
Author(s) : Pan Z , Han S , Lin Y , Zheng S
Ref : Sheng Wu Gong Cheng Xue Bao , 24 :673 , 2008
Abstract : Short-chain esters play a significant role in the food industry as flavor and aroma constituents. Candida antarctica lipase B (CALB) is one of the most effective catalysts for organic synthesis. We constructed a CALB-displaying yeast whole-cell biocatalyst and applied it to esterification from caproic acid and ethanol. CALB was fused with the alpha-agglutinin C-terminal and the signal peptide of Glucoamylase in pICAS, a yeast surface display vector, to construct plasmid pICAS-CALB. An extremely Asn-rich linker, named celAL was inserted in the Xho I of pICAS-CALB to construct plasmid pICAS-celAL-CALB. The fused gene was under the control of GAPDH promoter. After incubated at 30 degrees C for 96 h the lipase hydrolytic activity of the yeast whole cells reached a plateau, 26.26 u/(g x dry cell). In nonaqeous media, the yield of 98.0% ethyl hexanoate was obtained after 24 h esterification from caproic acid and ethanol (the molar ratio of caproic acid : ethanol = 1 : 1.25) using lyophilized CALB displaying yeast whole cells.
ESTHER : Pan_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_673
PubMedSearch : Pan_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_673
PubMedID: 18616181

Title : Biosensor based on self-assembling acetylcholinesterase on carbon nanotubes for flow injection\/amperometric detection of organophosphate pesticides and nerve agents - Liu_2006_Anal.Chem_78_835
Author(s) : Liu G , Lin Y
Ref : Analytical Chemistry , 78 :835 , 2006
Abstract : A highly sensitive flow injection amperometric biosensor for organophosphate pesticides and nerve agents based on self-assembled acetylcholinesterase (AChE) on a carbon nanotube (CNT)-modified glassy carbon (GC) electrode is described. AChE is immobilized on the negatively charged CNT surface by alternatively assembling a cationic poly(diallyldimethylammonium chloride) (PDDA) layer and an AChE layer. Transmission electron microscopy images confirm the formation of layer-by-layer nanostructures on carboxyl-functionalized CNTs. Fourier transform infrared reflectance spectrum indicates the AChE was immobilized successfully on the CNT/PDDA surface. The unique sandwich-like structure (PDDA/AChE/PDDA) on the CNT surface formed by self-assembling provides a favorable microenvironment to keep the bioactivity of AChE. The electrocatalytic activity of CNT leads to a greatly improved electrochemical detection of the enzymatically generated thiocholine product, including a low oxidation overvoltage (+150 mV), higher sensitivity, and stability. The developed PDDA/AChE/PDDA/CNT/GC biosensor integrated into a flow injection system was used to monitor organophosphate pesticides and nerve agents, such as paraoxon. The sensor performance, including inhibition time and regeneration conditions, was optimized with respect to operating conditions. Under the optimal conditions, the biosensor was used to measure as low as 0.4 pM paraoxon with a 6-min inhibition time. The biosensor had excellent operational lifetime stability with no decrease in the activity of enzymes for more than 20 repeated measurements over a 1-week period. The developed biosensor system is an ideal tool for online monitoring of organophosphate pesticides and nerve agents.
ESTHER : Liu_2006_Anal.Chem_78_835
PubMedSearch : Liu_2006_Anal.Chem_78_835
PubMedID: 16448058

Title : Regulation of M2 muscarinic acetylcholine receptor expression and signaling by prolonged exposure to allosteric modulators - May_2005_J.Pharmacol.Exp.Ther_312_382
Author(s) : May LT , Lin Y , Sexton PM , Christopoulos A
Ref : Journal of Pharmacology & Experimental Therapeutics , 312 :382 , 2005
Abstract : The effects of prolonged exposure of M(2) muscarinic acetylcholine receptors (mAChRs), stably expressed in Chinese hamster ovary cells, to the allosteric modulators gallamine, alcuronium, and heptane-1,7-bis (dimethyl-3'-phthalimidopropyl)-ammonium bromide (C(7)/3'-phth) were compared with the effects of the agonist carbachol (CCh) and antagonists atropine and N-methylscopolamine (NMS). Intact cell saturation binding assays using [(3)H]NMS found that pretreatment of the cells for 24 h with CCh caused a significant down-regulation of receptor number, whereas atropine, NMS, and all three allosteric modulators caused receptor up-regulation. Functional assays using a cytosensor microphysiometer to measure whole-cell metabolic rate found no acute effects of gallamine on receptor signaling, whereas atropine seemed to behave as an inverse agonist. Pretreatment of the cells with gallamine (20 microM) or atropine (20 nM) resulted in a significant enhancement of the maximal effect evoked by CCh. In contrast, CCh (100 microM) pretreatment resulted in a significant reduction in maximal receptor signaling capacity. Time-course experiments revealed that the effects of atropine and gallamine on receptor up-regulation are only visualized after at least 12-h ligand exposure, compared with the more rapid effects of CCh, which achieve steady-state down-regulation within 90 min. Additional experiments monitoring CCh-mediated M(2) mAChR internalization in the presence of gallamine revealed that part of the mechanism underlying the effects of the modulator on receptor expression may involve a change in receptor internalization properties. These findings suggest that, like orthosteric ligands, G protein-coupled receptor allosteric modulators also are able to mediate long-term effects on receptor regulation.
ESTHER : May_2005_J.Pharmacol.Exp.Ther_312_382
PubMedSearch : May_2005_J.Pharmacol.Exp.Ther_312_382
PubMedID: 15333678

Title : Noninvasive biomonitoring approaches to determine dosimetry and risk following acute chemical exposure: analysis of lead or organophosphate insecticide in saliva - Timchalk_2004_J.Toxicol.Environ.Health.A_67_635
Author(s) : Timchalk C , Poet TS , Kousba AA , Campbell JA , Lin Y
Ref : J Toxicol Environ Health A , 67 :635 , 2004
Abstract : There is a need to develop approaches for assessing risk associated with acute exposures to a broad range of metals and chemical agents and to rapidly determine the potential implications to human health. Noninvasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants, including heavy metals and pesticides. To advance the application of noninvasive biomonitoring a microfluidic/electrochemical device has also been developed for the analysis of lead (Pb), using square-wave anodic stripping voltametry. The system demonstrates a linear response over a broad concentration range (1-2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for noninvasive biomonitoring can provide a sensitive and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these noninvasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for evaluating acute exposure and health risk.
ESTHER : Timchalk_2004_J.Toxicol.Environ.Health.A_67_635
PubMedSearch : Timchalk_2004_J.Toxicol.Environ.Health.A_67_635
PubMedID: 15192859

Title : Five unique compounds: xyloketals from mangrove fungus Xylaria sp. from the South China Sea coast - Lin_2001_J.Org.Chem_66_6252
Author(s) : Lin Y , Wu X , Feng S , Jiang G , Luo J , Zhou S , Vrijmoed LL , Jones EB , Krohn K , Steingrover K , Zsila F
Ref : J Org Chem , 66 :6252 , 2001
Abstract : Five unique metabolites, xyloketals A (1), B (2), C (3), D (4), and E (5), and the known 6 were isolated from mangrove fungus Xylaria sp. (no. 2508), obtained from the South China Sea. The structures of these compounds were elucidated by spectroscopic and X-ray diffraction experiments. Xyloketal A is a ketal compound with a C(3) symmetry and xyloketals B-E are its analogues. It was found that xytoketal C slowly rearranged to xytoketal B in DMSO-d(6)() solution at room temperature. Xyloketal A exhibited the activity of inhibiting acetylcholine esterase.
ESTHER : Lin_2001_J.Org.Chem_66_6252
PubMedSearch : Lin_2001_J.Org.Chem_66_6252
PubMedID: 11559170

Title : Recombinant expression of alpha-bungarotoxin in Pichia pastoris facilitates identification of mutant toxins engineered to recognize neuronal nicotinic acetylcholine receptors - Levandoski_2000_J.Neurochem_74_1279
Author(s) : Levandoski MM , Caffery PM , Rogowski RS , Lin Y , Shi QL , Hawrot E
Ref : Journal of Neurochemistry , 74 :1279 , 2000
Abstract : A snake venom-derived alpha-neurotoxin, alpha-bungarotoxin (alphaBgtx), is the classic competitive antagonist of nicotinic acetylcholine receptors (nAChRs). The very high specificity and essentially irreversible binding of alphaBgtx to various nAChRs make alphaBgtx the prime candidate for studying the molecular determinants of specificity for nAChR-ligand interactions. To facilitate site-directed mutagenesis of alphaBgtx for functional analysis, we have developed a recombinant expression system for alphaBgtx using the methylotropic yeast Pichia pastoris. A synthetic gene coding for alphaBgtx was subcloned into an expression vector that directs secretion of the recombinant alphaBgtx (rBgtx) when stably integrated into the yeast genome. Expression of rBgtx was induced by growth of yeast cultures with methanol as the sole carbon source. The activity of the rBgtx in the cell-free medium was measured by competition with 1251-Bgtx for binding to Torpedo nAChR-enriched membranes. The rBgtx, purified to homogeneity by standard HPLC, has the correct predicted amino terminal sequence and molecular mass. Its circular dichroism spectrum is very similar to that of authentic venom-derived alphaBgtx, and the biological activity of the rBgtx is identical to that of authentic alphaBgtx. We have used the Pichia expression system to study a double point mutation of alphaBgtx, rBgtx-K38P/L42Q, that has a high affinity for alpha3beta2 neuronal nAChRs. This is the first demonstration of engineering an alpha-neurotoxin to recognize non-alpha7 neuronal nicotinic receptors.
ESTHER : Levandoski_2000_J.Neurochem_74_1279
PubMedSearch : Levandoski_2000_J.Neurochem_74_1279
PubMedID: 10693962

Title : Chimeric analysis of a neuronal nicotinic acetylcholine receptor reveals amino acids conferring sensitivity to alpha-bungarotoxin - Levandoski_1999_J.Biol.Chem_274_26113
Author(s) : Levandoski MM , Lin Y , Moise L , McLaughlin JT , Cooper E , Hawrot E
Ref : Journal of Biological Chemistry , 274 :26113 , 1999
Abstract : We have investigated the molecular determinants responsible for alpha-bungarotoxin (alphaBgtx) binding to nicotinic acetylcholine receptors through chimeric analysis of two homologous alpha subunits, one highly sensitive to alphaBgtx block (alpha1) and the other, alphaBgtx-insensitive (alpha3). By replacing rat alpha3 residues 184-191 with the corresponding region from the Torpedo alpha1 subunit, we introduced a cluster of five alpha1 residues (Trp-184, Trp-187, Val-188, Tyr-189, and Thr-191) into the alpha3 subunit. Functional activity and alphaBgtx sensitivity were assessed following co-expression in Xenopus oocytes of the chimeric alpha3 subunit (alpha3/alpha1[5]) with either rat beta2 or beta4 subunits. Agonist-evoked responses of alpha3/alpha1[5]-containing receptors were blocked by alphaBgtx with nanomolar affinity (IC(50) values: 41 nM for alpha3/alpha1[5]beta2 and 19 nM for alpha3/alpha1[5]beta4). Furthermore, receptors containing the single point mutation alpha3K189Y acquire significant sensitivity to alphaBgtx block (IC(50) values: 186 nM for alpha3K189Ybeta2 and 179 nM for alpha3K189Ybeta4). Another alpha3 chimeric subunit, alpha3/alpha7[6], similar to alpha3/alpha1[5] but incorporating the corresponding residues from the alphaBgtx-sensitive alpha7 subunit, also conferred potent alphaBgtx sensitivity to chimeric receptors when co-expressed with the beta4 subunit (IC(50) value = 31 nM). Our findings demonstrate that the residues between positions 184 and 191 of the alphaBgtx-sensitive subunits alpha1 and alpha7 play a critical functional role in the interaction of alphaBgtx with nicotinic acetylcholine receptors sensitive to this toxin.
ESTHER : Levandoski_1999_J.Biol.Chem_274_26113
PubMedSearch : Levandoski_1999_J.Biol.Chem_274_26113
PubMedID: 10473561