Gong Y

References (36)

Title : Neuroprotective effects of cordycepin inhibit glutamate-induced apoptosis in hippocampal neurons - Sun_2024_Cell.Stress.Chaperones__
Author(s) : Sun H , Wei S , Gong Y , Ding K , Tang S , Sun W , Yuan C , Huang L , Liu Z , Chen C , Yao L
Ref : Cell Stress Chaperones , : , 2024
Abstract : Glutamate is a neurotransmitter that can cause excitatory neurotoxicity when its extracellular concentration is too high, leading to disrupted calcium balance and increased production of reactive oxygen species (ROS). Cordycepin, a nucleoside adenosine derivative, has been shown to protect against excitatory neurotoxicity induced by glutamate. To investigate its potential neuroprotective effects, the present study employed fluorescence detection and spectrophotometry techniques to analyze primary hippocampal-cultured neurons. The results showed that glutamate toxicity reduced hippocampal neuron viability, increased ROS production, and increased intracellular calcium levels. Additionally, glutamate-induced cytotoxicity activated acetylcholinesterase (AChE) and decreased glutathione (GSH) levels. However, cordycepin inhibited glutamate-induced cell death, improved cell viability, reduced ROS production, and lowered Ca(2+) levels. It also inhibited AChE activation and increased GSH levels. This study suggests that cordycepin can protect against glutamate-induced neuronal injury in cell models, and this effect was inhibited by adenosine A(1) receptor blockers, indicating that its neuroprotective effect is achieved through activation of the adenosine A(1) receptor.
ESTHER : Sun_2024_Cell.Stress.Chaperones__
PubMedSearch : Sun_2024_Cell.Stress.Chaperones__
PubMedID: 38219840

Title : Current advances in the structural biology and molecular engineering of PETase - Liu_2023_Front.Bioeng.Biotechnol_11_1263996
Author(s) : Liu F , Wang T , Yang W , Zhang Y , Gong Y , Fan X , Wang G , Lu Z , Wang J
Ref : Front Bioeng Biotechnol , 11 :1263996 , 2023
Abstract : Poly(ethylene terephthalate) (PET) is a highly useful synthetic polyester plastic that is widely used in daily life. However, the increase in postconsumer PET as plastic waste that is recalcitrant to biodegradation in landfills and the natural environment has raised worldwide concern. Currently, traditional PET recycling processes with thermomechanical or chemical methods also result in the deterioration of the mechanical properties of PET. Therefore, it is urgent to develop more efficient and green strategies to address this problem. Recently, a novel mesophilic PET-degrading enzyme (IsPETase) from Ideonella sakaiensis was found to streamline PET biodegradation at 30 degreesC, albeit with a lower PET-degrading activity than chitinase or chitinase-like PET-degrading enzymes. Consequently, the molecular engineering of more efficient PETases is still required for further industrial applications. This review details current knowledge on IsPETase, MHETase, and IsPETase-like hydrolases, including the structures, ligandprotein interactions, and rational protein engineering for improved PET-degrading performance. In particular, applications of the engineered catalysts are highlighted, including metabolic engineering of the cell factories, enzyme immobilization or cell surface display. The information is expected to provide novel insights for the biodegradation of complex polymers.
ESTHER : Liu_2023_Front.Bioeng.Biotechnol_11_1263996
PubMedSearch : Liu_2023_Front.Bioeng.Biotechnol_11_1263996
PubMedID: 37795175

Title : Lack of Known Target-Site Mutations in Field Populations of Ostrinia furnacalis in China from 2019 to 2021 - Gong_2023_Toxics_11_
Author(s) : Gong Y , Li T , Xiu X , Desneux N , Hou M
Ref : Toxics , 11 : , 2023
Abstract : The Asian corn borer, Ostrinia furnacalis (Guenee) (Lepidoptera; Pyralidae), is one of the most destructive insect pests of corn, for which chemical insecticides have been the primary method of control, especially during outbreaks. Little information is currently available on the status of insecticide resistance and associated mechanisms in O. furnacalis field populations. Invasions and outbreaks of Spodoptera frugiperda in China in recent years have increased chemical application in corn fields, which adds to the selection pressure on O. furnacalis. This study was conducted to estimate the risk of insecticide resistance by investigating the frequency of insecticide resistant alleles associated with target site insensitivity in field populations of O. furnacalis. Using the individual-PCR genotype sequencing analysis, none of the six target-site insecticide resistant mutations were detected in O. furnacalis field populations collected from 2019 to 2021 in China. These investigated insecticide resistance alleles are common in resistant Lepidoptra pests and are responsible for resistance to pyrethroids, organophosphorus, carbamates, diamide, and Cry1Ab. Our results support the low insecticide resistance status in field O. furnacalis populations and betokens the unlikely development of high resistance mediated by the common target-site resistance alleles. Additionally, the findings would serve as references for further efforts toward the sustainable management of O. furnacalis.
ESTHER : Gong_2023_Toxics_11_
PubMedSearch : Gong_2023_Toxics_11_
PubMedID: 37112559

Title : Determination of carboxylesterase by fluorescence probe to guide detection of carbamate pesticide - Feng_2023_Luminescence__
Author(s) : Feng J , Gong Y , Yang S , Qiu G , Tian H , Sun B
Ref : Luminescence , : , 2023
Abstract : A carboxylesterase fluorescent probe (Probe 1) was developed for determination of carboxylesterase to guide detection of carbamate pesticide. The probe uses benzothiazole as fluorescence group and phenyldimethyl carbamate as recognition group. The solution of the fluorescent probe gradually changes from light blue to dark blue as the concentration of carbamate pesticides increases. The concentration of carbamate pesticides can be quickly calculated according to the colour of the probe solution through Get Color software on a smartphone. It showed that Probe 1 can be used as a rapid detection tool to achieve rapid detection of carbamate pesticides in juice samples without professional personnel and equipment. Furthermore, the probe has been successfully used to detect carbamate pesticides in fruit juice and vegetable juice.
ESTHER : Feng_2023_Luminescence__
PubMedSearch : Feng_2023_Luminescence__
PubMedID: 37947027

Title : Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains - Liu_2023_Angew.Chem.Int.Ed.Engl_62_e202214379
Author(s) : Liu Q , Zhang D , Gao S , Cai X , Yao M , Xu Y , Gong Y , Zheng K , Mao Y , Yang L , Yang D , Molnar I , Yang X
Ref : Angew Chem Int Ed Engl , 62 :e202214379 , 2023
Abstract : Orsellinic acid (OA) derivatives are produced by filamentous fungi using nonreducing polyketide synthases (nrPKSs). The chain-releasing thioesterase (TE) domains of such nrPKSs were proposed to also catalyze dimerization to yield didepsides, such as lecanoric acid. Here, we use combinatorial domain exchanges, domain dissections and reconstitutions to reveal that the TE domain of the lecanoric acid synthase Preu6 of Preussia isomera must collaborate with the starter acyl transferase (SAT) domain from the same nrPKS. We show that artificial SAT-TE fusion proteins are highly effective catalysts and reprogram the ketide homologation chassis to form didepsides. We also demonstrate that dissected SAT and TE domains of Preu6 physically interact, and SAT and TE domains of OA-synthesizing nrPKSs may co-evolve. Our work highlights an unexpected domain-domain interaction in nrPKSs that must be considered for the combinatorial biosynthesis of unnatural didepsides, depsidones, and diphenyl ethers.
ESTHER : Liu_2023_Angew.Chem.Int.Ed.Engl_62_e202214379
PubMedSearch : Liu_2023_Angew.Chem.Int.Ed.Engl_62_e202214379
PubMedID: 36484777
Gene_locus related to this paper: preis-preu6

Title : A colorimetric fluorescent probe for the detection of carboxylesterase and carbamate pesticides - Feng_2023_Anal.Sci__
Author(s) : Feng J , Gong Y , Yang S , Tian H , Sun B
Ref : Anal Sci , : , 2023
Abstract : A colorimetric fluorescent probe (BTCNA) was developed for the determination of carboxylesterase and carbamate pesticides. The probe used naphthalene-benzothiazole as the fluorescent group and naphthyl acetate as the recognition group. The recognition mechanism of BTCNA for carboxylesterase was based on the enzymatic hydrolysis of naphthyl acetate by carboxylesterase (CES). The test paper of the BTCNA gradually changed from light blue to bright yellow with the increase of CES activity. The probe solution gradually changed from light blue to earth-yellow as the carbaryl concentration increased. There was a linear functional relationship between the R*G (red, green) value of the photo and the CES activity. And a linear functional relationship between the carbaryl concentration and the R*G value of the photo was found. Additionally, BTCNA was successfully used to detect the concentration of carbaryl in actual samples. BTCNA is a rapid detection tool for CES activity and carbamate pesticides using a smartphone.
ESTHER : Feng_2023_Anal.Sci__
PubMedSearch : Feng_2023_Anal.Sci__
PubMedID: 37548851

Title : Neuroprotective potential of sevoflurane against isoflurane induced cognitive dysfunction in rats via anti-inflammatory and antioxidant effect - Gong_2023_Acta.Cir.Bras_38_e385523
Author(s) : Gong Y , Kang P , Wang J , Chen Y , Wei Z
Ref : Acta Cir Bras , 38 :e385523 , 2023
Abstract : PURPOSE: Intravenous anesthetics have excellent analgesic activity without inducing the side effect in the respiratory system. The aim and objective of the current experimental study was to access the neuroprotective effect of sevoflurane against isoflurane induced cognitive dysfunction in rats. METHODS: Isoflurane was used for induction the neurodysfunction in the rats, and rats received the oral administration of sevoflurane (2.5, 5 and 10 mg/kg). Morris water test was carried out for the estimation of cognitive function. Neurochemical parameters, antioxidant parameters and pro-inflammatory cytokines were also estimated. RESULTS: Sevoflurane significantly (P < 0.001) altered the neurochemical parameters such as anti-choline acetyltransferase, acetylcholine esterase, acetylcholine, protein carbonyl, choline brain-derived neurotrophic factor, and amyloid beta; antioxidant parameters such as glutathione, superoxide dismutase, and malondialdehyde; pro-inflammatory cytokines include interleukin (IL-2, IL-10, IL-4, IL-6, IL-10, IL-1beta), and tumor necrosis factor-alpha. Sevoflurane significantly reduced the activity of caspase-3. CONCLUSIONS: Sevoflurane exhibited the neuroprotection against the cognitive dysfunction in rats via anti-inflammatory and antioxidant mechanism.
ESTHER : Gong_2023_Acta.Cir.Bras_38_e385523
PubMedSearch : Gong_2023_Acta.Cir.Bras_38_e385523
PubMedID: 38055394

Title : Plant immune signaling network mediated by helper NLRs - Gong_2023_Curr.Opin.Plant.Biol_73_102354
Author(s) : Gong Y , Tian L , Kontos I , Li J , Li X
Ref : Curr Opin Plant Biol , 73 :102354 , 2023
Abstract : Plant nucleotide-binding leucine-rich repeat receptors (NLRs) are intracellular immune receptors for pathogen recognition and signaling. They include sensor NLRs (sNLRs) that detect pathogens, and helper NLRs, which transduce downstream immune signals. During immune responses, both membrane-localized pattern recognition receptors (PRRs) and sNLRs rely on helper NLRs for signal transduction. The Arabidopsis helper NLRs, ADR1s and NRG1s, along with their interacting lipase-like protein dimers, are differentially required by sNLRs. Recent structural and biochemical analyses suggest that they assemble into oligomeric resistosomes with lipase-like protein dimers upon perception of small molecules produced from enzymatic activities of upstream TIR-type sNLRs. As a result, ADR1s and NRG1s form membrane calcium channels to induce immune responses and cell death. In contrast, Solanaceous NRC clade helper NLRs transduce signals from many sNLRs and some PRRs. Here, we summarize the recent advances in plant helper NLR research, with a focus on their structural and biochemical mechanisms in immune signaling.
ESTHER : Gong_2023_Curr.Opin.Plant.Biol_73_102354
PubMedSearch : Gong_2023_Curr.Opin.Plant.Biol_73_102354
PubMedID: 37003229

Title : A potential novel biomarker: comprehensive analysis of prognostic value and immune implication of CES3 in colonic adenocarcinoma - He_2023_J.Cancer.Res.Clin.Oncol__
Author(s) : He L , Zhao C , Xu J , Li W , Lu Y , Gong Y , Gu D , Wang X , Guo F
Ref : J Cancer Research Clin Oncol , : , 2023
Abstract : PURPOSE: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3) expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. PATIENTS AND METHODS: The transcription and expression data of CES3 and corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. RESULTS: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. CONCLUSION: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD.
ESTHER : He_2023_J.Cancer.Res.Clin.Oncol__
PubMedSearch : He_2023_J.Cancer.Res.Clin.Oncol__
PubMedID: 37480527
Gene_locus related to this paper: human-CES3

Title : The preferential utilization of hepatic glycogen as energy substrates in largemouth bass (Micropterus salmoides) under short-term starvation - Zhang_2023_Fish.Physiol.Biochem__
Author(s) : Zhang N , Wang X , Han Z , Gong Y , Huang X , Chen N , Li S
Ref : Fish Physiol Biochem , : , 2023
Abstract : To elucidate the underlying mechanism of the energy metabolism in largemouth bass (Micropterus salmoides), cultured fish (initial body weight: 77.57 +/- 0.75 g) in the present study were starved for 0 h, 12 h, 24 h, 48 h, 96 h and 192 h, respectively. The proximate composition analysis showed that short-term starvation induced a significant up-regulation in crude protein proportion in hepatic of cultured fish (P < 0.05). However, short-term starvation significantly decreased the hepatosomatic index and the viscerosomatic index of cultured fish (P < 0.05). The exact hepatic glycogen content in the group starved for 92 h presented remarkable decrease (P < 0.05). Meanwhile, compared with the weight change of lipid and protein (mg) in hepatic (y = 0.0007x(2) - 0.2827x + 49.402; y = 0.0013x(2) - 0.5666x + 165.31), the decreasing trend of weight in glycogen (mg) was more pronounced (y = 0.0032x(2) - 1.817x + 326.52), which suggested the preferential utilization of hepatic glycogen as energy substrates under short-term starvation. Gene expression analysis revealed that the starvation down-regulated the expression of insulin-like growth factor 1 and genes of TOR pathway, such as target of rapamycin (tor) and ribosomal protein S6 (s6) (P < 0.05). In addition, the starvation significantly enhanced expression of lipolysis-related genes, including hormone-sensitive lipase (hsl) and carnitine palmitoyl transferase I (cpt1), but down-regulated lipogenesis as indicated by the inhibited expression of fatty acids synthase (fas), acetyl-CoA carboxylase 1 (acc1) and acetyl-CoA carboxylase 2 (acc2) (P < 0.05). Starvation of 24 h up-regulated the expression of glycolysis genes, glucokinase (gk), phosphofructokinase liver type (pfkl) and pyruvate kinase (pk), and then their expression returned to the normal level. Meanwhile, the expression of gluconeogenesis genes, such as glucose-6-phosphatase catalytic subunit (g6pc), fructose-1,6-bisphosphatase-1 (fbp1) and phosphoenolpyruvate carboxy kinase (pepck), was significantly inhibited with the short-term starvation (P < 0.05). In conclusion, short-term starvation induced an overall decline in growth performance, but it could deplete the hepatic glycogen accumulation and mobilize glycogen for energy effectively.
ESTHER : Zhang_2023_Fish.Physiol.Biochem__
PubMedSearch : Zhang_2023_Fish.Physiol.Biochem__
PubMedID: 38108936

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 : Cloning and Functional Characterization of the Polyketide Synthases Based on Genome Mining of Preussia isomera XL-1326 - Liu_2022_Front.Microbiol_13_819086
Author(s) : Liu Q , Zhang D , Xu Y , Gao S , Gong Y , Cai X , Yao M , Yang X
Ref : Front Microbiol , 13 :819086 , 2022
Abstract : Fungal polyketides (PKs) are one of the largest families of structurally diverse bioactive natural products biosynthesized by multidomain megasynthases, in which thioesterase (TE) domains act as nonequivalent decision gates determining both the shape and the yield of the polyketide intermediate. The endophytic fungus Preussia isomera XL-1326 was discovered to have an excellent capacity for secreting diverse bioactive PKs, i.e., the hot enantiomers (+/-)-preuisolactone A with antibacterial activity, the single-spiro minimoidione B with alpha-glucosidase inhibition activity, and the uncommon heptaketide setosol with antifungal activity, which drive us to illustrate how the unique PKs are biosynthesized. In this study, we first reported the genome sequence information of P. isomera. Based on genome mining, we discovered nine transcriptionally active genes encoding polyketide synthases (PKSs), Preu1-Preu9, of which those of Preu3, Preu4, and Preu6 were cloned and functionally characterized due to possessing complete sets of synthetic and release domains. Through heterologous expression in Saccharomyces cerevisiae, Preu3 and Preu6 could release high yields of orsellinic acid (OA) derivatives [3-methylorsellinic acid (3-MOA) and lecanoric acid, respectively]. Correspondingly, we found that Preu3 and Preu6 were clustered into OA derivative synthase groups by phylogenetic analysis. Next, with TE domain swapping, we constructed a novel "non-native" PKS, Preu6-TE(Preu3), which shared a very low identity with OA synthase, OrsA, from Aspergillus nidulans but could produce a large amount of OA. In addition, with the use of Preu6-TE(Preu3), we synthesized methyl 3-methylorsellinate (synthetic oak moss of great economic value) from 3-MOA as the substrate, and interestingly, 3-MOA exhibited remarkable antibacterial activities, while methyl 3-methylorsellinate displayed broad-spectrum antifungal activity. Taken together, we identified two novel PKSs to biosynthesize 3-MOA and lecanoric acid, respectively, with information on such kinds of PKSs rarely reported, and constructed one novel "non-native" PKS to largely biosynthesize OA. This work is our first step to explore the biosynthesis of the PKs in P. isomera, and it also provides a new platform for high-level environment-friendly production of OA derivatives and the development of new antimicrobial agents.
ESTHER : Liu_2022_Front.Microbiol_13_819086
PubMedSearch : Liu_2022_Front.Microbiol_13_819086
PubMedID: 35602042
Gene_locus related to this paper: preis-preu6

Title : Defining the Chemical Additives Driving In Vitro Toxicities of Plastics - Chen_2022_Environ.Sci.Technol__
Author(s) : Chen W , Gong Y , McKie M , Almuhtaram H , Sun J , Barrett H , Yang D , Wu M , Andrews RC , Peng H
Ref : Environ Sci Technol , : , 2022
Abstract : Increases in the global use of plastics have caused concerns regarding potential adverse effects on human health. Plastic products contain hundreds of potentially toxic chemical additives, yet the exact chemicals which drive toxicity currently remain unknown. In this study, we employed nontargeted analysis and in vitro bioassays to identify the toxicity drivers in plastics. A total of 56 chemical additives were tentatively identified in five commonly used plastic polymer pellets (i.e., PP, LDPE, HDPE, PET, and PVC) by employing suspect screening and nontargeted analysis. Phthalates and organophosphates were found to be dominant in PVC pellets. Triphenyl phosphate and 2-ethylhexyl diphenyl phosphate accounted for a high amount (53.6%) of the inhibition effect of PVC pellet extract on human carboxylesterase 1 (hCES1) activity. Inspired by the high abundances of chemical additives in PVC pellets, six different end-user PVC-based products including three widely used PVC water pipes were further examined. Among them, extracts of PVC pipe exerted the strongest PPARgamma activity and cell viability suppression. Organotins were identified as the primary drivers to these in vitro toxicities induced by the PVC pipe extracts. This study clearly delineates specific chemical additives responsible for hCES1 inhibition, PPARgamma activity, and cell viability suppression associated with plastic.
ESTHER : Chen_2022_Environ.Sci.Technol__
PubMedSearch : Chen_2022_Environ.Sci.Technol__
PubMedID: 36173153

Title : Thirteen cyathane diterpenoids with acetylcholinesterase inhibitory effects from the fungus Cyathus africanus - Yu_2021_Phytochemistry_193_112982
Author(s) : Yu M , Kang X , Li Q , Liang Y , Zhang M , Gong Y , Chen C , Zhu H , Zhang Y
Ref : Phytochemistry , 193 :112982 , 2021
Abstract : Eight undescribed cyathane diterpenoids, representative specialised metabolites of the genus Cyathus, named cyathins Q-X, along with five known congeners, were isolated from the liquid fermentation of Cyathus africanus. Their structures and absolute configurations were elucidated by integrating NMR spectroscopic analyses, electronic circular dichroism (ECD) calculations, and X-ray diffraction. Reasonable correction to the C-12 configuration of cyathin I was corroborated by the crystal data. The structural identification in this research expanded the number of candidates to allow for more bioactivity-screening options. Among them, (12S)-11alpha,14alpha-epoxy-13alpha,14beta,15-trihydroxycyath-3-ene displayed significant acetylcholinesterase (AChE) inhibitory effect with an IC(50) value of 4.60 +/- 0.85 microM. Molecular docking studies were also performed to unravel the underlying modes of interactions with the active sites of AChE for active compounds.
ESTHER : Yu_2021_Phytochemistry_193_112982
PubMedSearch : Yu_2021_Phytochemistry_193_112982
PubMedID: 34700067

Title : Evolution of Ycf54-independent chlorophyll biosynthesis in cyanobacteria - Chen_2021_Proc.Natl.Acad.Sci.U.S.A_118_
Author(s) : Chen GE , Hitchcock A , Mares J , Gong Y , Tichy M , Pilny J , Kovarova L , Zdvihalova B , Xu J , Hunter CN , Sobotka R
Ref : Proc Natl Acad Sci U S A , 118 : , 2021
Abstract : Chlorophylls (Chls) are essential cofactors for photosynthesis. One of the least understood steps of Chl biosynthesis is formation of the fifth (E) ring, where the red substrate, magnesium protoporphyrin IX monomethyl ester, is converted to the green product, 3,8-divinyl protochlorophyllide a In oxygenic phototrophs, this reaction is catalyzed by an oxygen-dependent cyclase, consisting of a catalytic subunit (AcsF/CycI) and an auxiliary protein, Ycf54. Deletion of Ycf54 impairs cyclase activity and results in severe Chl deficiency, but its exact role is not clear. Here, we used a deltaycf54 mutant of the model cyanobacterium Synechocystis sp. PCC 6803 to generate suppressor mutations that restore normal levels of Chl. Sequencing deltaycf54 revertants identified a single D219G amino acid substitution in CycI and frameshifts in slr1916, which encodes a putative esterase. Introduction of these mutations to the original deltaycf54 mutant validated the suppressor effect, especially in combination. However, comprehensive analysis of the deltaycf54 suppressor strains revealed that the D219G-substituted CycI is only partially active and its accumulation is misregulated, suggesting that Ycf54 controls both the level and activity of CycI. We also show that Slr1916 has Chl dephytylase activity in vitro and its inactivation up-regulates the entire Chl biosynthetic pathway, resulting in improved cyclase activity. Finally, large-scale bioinformatic analysis indicates that our laboratory evolution of Ycf54-independent CycI mimics natural evolution of AcsF in low-light-adapted ecotypes of the oceanic cyanobacteria Prochlorococcus, which lack Ycf54, providing insight into the evolutionary history of the cyclase enzyme.
ESTHER : Chen_2021_Proc.Natl.Acad.Sci.U.S.A_118_
PubMedSearch : Chen_2021_Proc.Natl.Acad.Sci.U.S.A_118_
PubMedID: 33649240
Gene_locus related to this paper: synsp-slr1916

Title : Molecular and functional characterization of three novel carboxylesterases in the detoxification of permethrin in the mosquito, Culex quinquefasciatus - Gong_2021_Insect.Sci__
Author(s) : Gong Y , Li M , Li T , Liu N
Ref : Insect Sci , : , 2021
Abstract : Carboxylesterases (CarEs) belong to a super family of multifunctional enzymes associated with the degradation of endogenous and exogenous compounds. Many insect CarEs are known to play important roles in catalyzing the hydrolysis of organophosphates (OPs), carbamates, and synthetic pyrethroids (SPs). The elevation of esterase activity through gene amplification and overexpression of estalpha2 and estbeta2 genes contributes to the development of resistance to OP insecticides in the mosquito Culex quinquefasciatus. Three additional CarE genes are upregulated in permethrin-resistant Cx. quinquefasciatus according to an RNA-seq analysis, but their function remains unknown. In this study, we, for the first time, characterized the function of these three novel genes using in vitro protein expression, an insecticide metabolism study and molecular docking analysis. All three CarE genes were significantly overexpressed in resistant mosquito larvae, but not adults, compared to susceptible strain. No gene copy differences in these three genes were found in the mosquitoes tested. In vitro high-performance liquid chromatography (HPLC) revealed that CPIJ018231, CPIJ018232, and CPIJ018233 metabolized 30.4% +/- 2.9%, 34.7% +/- 6.8%, and 23.2% +/- 2.2% of the permethrin, respectively. No mutations in resistant strains might significantly affect their CarE hydrolysis ability. A docking analysis further confirmed that these three CarEs from resistant strain all potentially metabolize permethrin. Taken together, these three carboxylesterase genes could play important roles in the development of permethrin resistance in Cx. quinquefasciatus larvae through transcriptional overexpression, metabolism, and detoxification.
ESTHER : Gong_2021_Insect.Sci__
PubMedSearch : Gong_2021_Insect.Sci__
PubMedID: 34048147
Gene_locus related to this paper: culqu-b0xfi1 , culqu-b0xfi2 , culqu-b0xfi3

Title : Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets - Gong_2020_J.Biomed.Nanotechnol_16_827
Author(s) : Gong Y , Lv S , Tian C , Gao Y , Chen B , Wen L , Gao H , Aimaiti W , Ma R , Zhao J , Wang J
Ref : J Biomed Nanotechnol , 16 :827 , 2020
Abstract : Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 mol . L (-1). Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.
ESTHER : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedSearch : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedID: 33187579

Title : Characterization of a novel deep-sea microbial esterase EstC10 and its use in the generation of (R)-methyl2-chloropropionate - Gong_2018_J.Ocean.Limnol_36_473
Author(s) : Gong Y , Ma S , Wang Y , Xu Y , Sun A , Zhang Y , Hu Y
Ref : J Ocean Limnol , 36 :473 , 2018
Abstract : A novel esterase EstC10 from Bacillus sp. CX01 isolated from the deep sea of the Western Pacific Ocean and the functionalities of EstC10 was characterized. At present, the reports about the kinetic resolution of racemic methyl 2-chloropropionate were quite rare. So we developed deep-sea microbial esterase EstC10 as a novel biocatalyst in the kinetic resolution of racemic methyl 2-chloropropionate and generate (R)-methyl 2-chloropropionate with high enantiomeric excess (>99%) after the optimization of process parameters such as pH, temperature, organic co-solvents, surfactants, substrate concentration and reaction time. Notably, the optimal substrate concentration (80 mmol/L) of esterase EstC10 was higher than the kinetic resolution of another esterase, Est12-7 (50 mmol/L). The novel microbial esterase EstC10 identified from the deep sea was a promising green biocatalyst in the generation of (R)-methyl 2-chloropropionate as well of many other valuable chiral chemicals in industry.
ESTHER : Gong_2018_J.Ocean.Limnol_36_473
PubMedSearch : Gong_2018_J.Ocean.Limnol_36_473
Gene_locus related to this paper: bacld-q65eq1

Title : Neuroprotective effects of cordycepin inhibit Abeta-induced apoptosis in hippocampal neurons - Song_2018_Neurotoxicol_68_73
Author(s) : Song H , Huang LP , Li Y , Liu C , Wang S , Meng W , Wei S , Liu XP , Gong Y , Yao LH
Ref : Neurotoxicology , 68 :73 , 2018
Abstract : In Alzheimer's disease (AD), beta-amyloid (Abeta) protein toxicity increases the formation of reactive oxygen species (ROS) and intracellular calcium levels, resulting in neuronal dysfunction, neurodegenerative disorders, and cell death. Cordycepin is a derivative of the nucleoside adenosine; also, it is speculated to exert neuroprotective effects against Abeta-induced oxidative toxicity in hippocampal neurons. In the present study, the fluorescence detection method and whole-cell patch-clamp recordings were used to study the neuroprotective effects against Abeta-induced toxicity in the primary hippocampal cultured neurons. The results revealed that Abeta25-35 toxicity causes increased cellular ROS production and abnormal calcium homeostasis in hippocampal neurons. Moreover, Abeta25-35-induced cytotoxicity led to a series of downstream events, including the activation of acetylcholinesterase, increased p-Tau expression, and increased apoptosis. Cordycepin inhibits ROS production, elevated levels of Ca(2+) induced by Abeta25-35, and the activation of acetylcholinesterase; all these are involved in oxidative-induced apoptosis. In addition, it decreases the increased p-Tau expression that plays a key role in the initiation of the AD. Results showed that the anti-apoptotic effects of cordycepin are partially dependent on the activation of adenosine A1 receptor, whereas an antagonist selectively attenuated the neuroprotective effects of cordycepin. Collectively, these results suggest that cordycepin could be a potential future therapeutic agent for neuronal disorders, such as AD.
ESTHER : Song_2018_Neurotoxicol_68_73
PubMedSearch : Song_2018_Neurotoxicol_68_73
PubMedID: 30031108

Title : Colorectal cancer stages transcriptome analysis - Huo_2017_PLoS.One_12_e0188697
Author(s) : Huo T , Canepa R , Sura A , Modave F , Gong Y
Ref : PLoS ONE , 12 :e0188697 , 2017
Abstract : Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA). Gene expression differences were evaluated across CRC stages using linear regression. Genes with p<=0.001 in expression differences were evaluated further in principal component analysis and genes with p<=0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6). Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3) had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.
ESTHER : Huo_2017_PLoS.One_12_e0188697
PubMedSearch : Huo_2017_PLoS.One_12_e0188697
PubMedID: 29182684

Title : Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-alpha and IL-1beta in an Abeta25-35-induced Rat Model of Alzheimer's Disease - Li_2017_J.Alzheimers.Dis_56_1403
Author(s) : Li L , Xu S , Liu L , Feng R , Gong Y , Zhao X , Li J , Cai J , Feng N , Wang L , Wang X , Peng Y
Ref : J Alzheimers Dis , 56 :1403 , 2017
Abstract : The dyshomeostasis of transition metal ions, accumulation of amyloid-beta (Abeta) senile plaques and neuroinflammatory response found in the brain of patients with Alzheimer's disease (AD) have been suggested to be involved in AD pathogenesis. Novel compounds capable of targeting metal-Abeta species and neuroinflammation would be valuable. AD-35 is such a patented small-molecule compound derived from innovative modification of the chemical structure of donepezil. This compound could moderately inhibit acetylcholinesterase and metal-induced Abeta aggregation in vitro and showed disassembly of Abeta aggregates. The effects of AD-35 on cognitive impairments and neuroinflammatory changes caused by intracerebroventricular injection of Abeta25-35 were studied in rats. Compared to sham group, Abeta25-35 injection significantly led to learning and memory deficits, astrocyte activation, and pro-inflammatory cytokines releases (TNF-alpha and IL-1beta). Further studies indicated that the phosphorylation of extracellular signal-regulated kinase was involved in astrocyte activation and pro-inflammatory cytokines production. Oral administration of AD-35 could markedly attenuate Abeta25-35 injection-induced astrocyte activation, pro-inflammatory cytokines TNF-alpha and IL-1beta release, and memory deficits. On the contrary, donepezil only showed inhibition of IL-1beta production, but failed to block astrocyte activation and TNF-alpha production. These results showed that AD-35 would be a novel multi-mechanism drug for the prevention and/or treatment of AD.
ESTHER : Li_2017_J.Alzheimers.Dis_56_1403
PubMedSearch : Li_2017_J.Alzheimers.Dis_56_1403
PubMedID: 28157092

Title : Effects of spirotetramat treatments on fecundity and carboxylesterase expression of Aphis gossypii Glover - Gong_2016_Ecotoxicology_25_655
Author(s) : Gong Y , Shi X , Desneux N , Gao X
Ref : Ecotoxicology , 25 :655 , 2016
Abstract : Spirotetramat is a novel tetramic acid-based insecticide, belonging to keto-enol pesticide family, with a novel mode of action; it interferes with lipid biosynthesis. Its insecticide activity against various agricultural pest insects have been demonstrated (e.g. on Myzus persicae, Bemisia tabaci and Tetranychus urticae). However, information available is currently limited on the efficacy of spirotetramat on the cotton aphid, Aphis gossypii, a key cotton pest worldwide. We assessed the spirotetramat toxicity on A. gossypii and evaluated its effects on aphid fecundity when exposed to a sublethal concentration (LC10) and to increasing lethal concentrations (LC25, LC50, and LC75). A key mechanism involved in insecticide resistance in aphids relates to esterase activity. We estimated the CarE activity and a CarE gene expression in aphids in response to spirotetramat exposure, then we tested tolerance of offspring to spirotetramat when the parents were exposed to the highest concentration tested in our study (LC75). Results showed that spirotetramat showed increasing toxicity to A. gossypii with exposure duration to treated leaves; LC50 ranged from 23,675.68 to 12.27 mg/L for 1 to 5-days exposure. In addition, spirotetramat reduced aphid daily fecundity, in all concentration treatments, especially with up to 90 % reduction in case of exposure to LC75. Total CarE activity increased dramatically and CarE mRNA expression was also up regulated in aphids after exposure to LC75 spirotetramat. Finally, the tolerance to spirotetramat in offspring (when parents were exposed to the LC75) showed a 2.5-fold increase when compared to control aphids. Consequently, spiroteramat showed potential for pest management of cotton aphids owing to both lethal and sublethal activities, notably strong impact on aphid fecundity. However, we also demonstrated that increased tolerance of A. gossypii to spirotetramat may happen through increased CarE- activity and subsequent metabolic degradation of the insecticide in aphids' body.
ESTHER : Gong_2016_Ecotoxicology_25_655
PubMedSearch : Gong_2016_Ecotoxicology_25_655
PubMedID: 26898726

Title : Green access to chiral Vince lactam in a buffer-free aqueous system using a newly identified substrate-tolerant (-)-gamma-lactamase - Yin_2016_Catal.Sci.Technol_6_6305
Author(s) : Gong Y , Zhang X-Y , Zheng G-W , Xu J-H
Ref : Catal Sci Technol , 6 :6305 , 2016
Abstract : A novel non-heme chloroperoxidase (SvGL) with promiscuous (-)-gamma-lactamase activity towards Vince lactam was identified from Streptomyces viridochromogenes by genome data-mining. SvGL possesses high activity and excellent thermal stability and enantioselectivity. Furthermore, it is able to tolerate extremely high substrate concentrations (4.0 M, 436.5 g L-1). Using the newly discovered (-)-gamma-lactamase as a biocatalyst, an efficient and environmentally benign process for the production of (+)-gamma-lactam was developed. The process allowed an enantioselective resolution of 436.5 g L-1 racemic gamma-lactam with only 0.2 g L-1 lyophilized cell-free extract, affording an extremely high substrate/catalyst ratio of 2183 (g g-1), a space-time yield of 458 g L-1 d-1, and a very low E factor (environmental factor) of 5.7 (kg waste per kg product) even when the process water is included.
ESTHER : Yin_2016_Catal.Sci.Technol_6_6305
PubMedSearch : Yin_2016_Catal.Sci.Technol_6_6305
Gene_locus related to this paper: strvt-d9xdn2

Title : Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes - Li_2016_J.Med.Chem_59_6772
Author(s) : Li S , Xu H , Cui S , Wu F , Zhang Y , Su M , Gong Y , Qiu S , Jiao Q , Qin C , Shan J , Zhang M , Wang J , Yin Q , Xu M , Liu X , Wang R , Zhu L , Li J , Xu Y , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 59 :6772 , 2016
Abstract : Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.
ESTHER : Li_2016_J.Med.Chem_59_6772
PubMedSearch : Li_2016_J.Med.Chem_59_6772
PubMedID: 27396490
Gene_locus related to this paper: human-DPP4

Title : Constructing Bayesian networks by integrating gene expression and copy number data identifies NLGN4Y as a novel regulator of prostate cancer progression - Gong_2016_Oncotarget_7_68688
Author(s) : Gong Y , Wang L , Chippada-Venkata U , Dai X , Oh WK , Zhu J
Ref : Oncotarget , 7 :68688 , 2016
Abstract : To understand the heterogeneity of prostate cancer (PCa) and identify novel underlying drivers, we constructed integrative molecular Bayesian networks (IMBNs) for PCa by integrating gene expression and copy number alteration data from published datasets. After demonstrating such IMBNs with superior network accuracy, we identified multiple sub-networks within IMBNs related to biochemical recurrence (BCR) of PCa and inferred the corresponding key drivers. The key drivers regulated a set of common effectors including genes preferentially expressed in neuronal cells. NLGN4Y-a protein involved in synaptic adhesion in neurons-was ranked as the top gene closely linked to key drivers of myogenesis subnetworks. Lower expression of NLGN4Y was associated with higher grade PCa and an increased risk of BCR. We show that restoration of the protein expression of NLGN4Y in PC-3 cells leads to decreased cell proliferation, migration and inflammatory cytokine expression. Our results suggest that NLGN4Y is an important negative regulator in prostate cancer progression. More importantly, it highlights the value of IMBNs in generating biologically and clinically relevant hypotheses about prostate cancer that can be validated by independent studies.
ESTHER : Gong_2016_Oncotarget_7_68688
PubMedSearch : Gong_2016_Oncotarget_7_68688
PubMedID: 27626693
Gene_locus related to this paper: human-NLGN4Y

Title : CES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril - Zhu_2016_Eur.J.Clin.Pharmacol_72_681
Author(s) : Zhu HJ , Langaee TY , Gong Y , Wang X , Pepine CJ , Cooper-DeHoff RM , Johnson JA , Markowitz JS
Ref : European Journal of Clinical Pharmacology , 72 :681 , 2016
Abstract : PURPOSE: The majority of angiotensin-converting enzyme inhibitors (ACEIs) are synthesized as ester prodrugs that must be converted to their active forms in vivo in order to exert therapeutic effects. Hepatic carboxylesterase 1 (CES1) is the primary enzyme responsible for the bioactivation of ACEI prodrugs in humans. The genetic variant -816A>C (rs3785161) is a common variant located in the promoter region of the CES1P1 gene. Previous studies report conflicting results with regard to the association of this variant and therapeutic outcomes of CES1 substrate drugs. The purpose of this study was to determine the effect of the variant -816A>C on the activation of the ACEI prodrug trandolapril in human livers and the blood pressure (BP)-lowering effect of trandolapril in hypertensive patients.
METHODS: The -816A>C genotypes and CES1 expression and activity on trandolapril activation were determined in 100 individual human liver samples. Furthermore, the association of the -816A>C variant and the BP lowering effect of trandolapril was evaluated in hypertensive patients who participated in the International Verapamil SR Trandolapril Study (INVEST).
RESULTS: Our in vitro study demonstrated that hepatic CES1 expression and activity did not differ among different -816A>C genotypes. Moreover, we were unable to identify a clinical association between the BP lowering effects of trandolapril and -816A>C genotypes.
CONCLUSIONS: We conclude that the -816A>C variant is not associated with interindividual variability in CES1 expression and activity or therapeutic response to ACEI prodrugs.
ESTHER : Zhu_2016_Eur.J.Clin.Pharmacol_72_681
PubMedSearch : Zhu_2016_Eur.J.Clin.Pharmacol_72_681
PubMedID: 26915813
Gene_locus related to this paper: human-CES1

Title : Functional expression of human alpha7 nicotinic acetylcholine receptor in human embryonic kidney 293 cells - Gong_2016_Mol.Med.Rep_14_2257
Author(s) : Gong Y , Jiang JH , Li ST
Ref : Mol Med Rep , 14 :2257 , 2016
Abstract : The functional expression of recombinant alpha7 nicotinic acetylcholine receptors in human embryonic kidney (HEK) 293 cells has presented a challenge. Resistance to inhibitors of cholinesterase 3 (RIC3) has been confirmed to act as a molecular chaperone of nicotinic acetylcholine receptors. The primary objectives of the present study were to investigate whether the coexpression of human (h)RIC3 with human alpha7 nicotinic acetylcholine receptor in HEK 293 cells facilitates functional expression of the alpha7 nicotinic acetylcholine receptor. Subsequent to transfection, western blotting and polymerase chain reaction were used to test the expression of alpha7 nicotinic acetylcholine receptor and RIC-3. The alpha7 nicotinic acetylcholine receptor was expressed alone or coexpressed with hRIC3 in the HEK 293 cells. Drugcontaining solution was then applied to the cells via a gravitydriven perfusion system. Calcium influx in the cells was analyzed using calcium imaging. Nicotine did not induce calcium influx in the HEK 293 cells expressing human alpha7 nicotinic acetylcholine receptor only. However, in the cells coexpressing human RIC3 and alpha7 nicotinic acetylcholine receptor, nicotine induced calcium influx via the alpha7 nicotinic acetylcholine receptor in a concentrationdependent manner (concentration required to elicit 50% of the maximal effect=29.21 microM). Taken together, the results of the present study suggested that the coexpression of RIC3 in HEK 293 cells facilitated the functional expression of the alpha7 nicotinic acetylcholine receptor.
ESTHER : Gong_2016_Mol.Med.Rep_14_2257
PubMedSearch : Gong_2016_Mol.Med.Rep_14_2257
PubMedID: 27430244

Title : CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease - Hoh_2015_J.Neurosurg__1
Author(s) : Hoh BL , Gong Y , McDonough CW , Waters MF , Royster AJ , Sheehan TO , Burkley B , Langaee TY , Mocco J , Zuckerman SL , Mummareddy N , Stephens ML, 2nd , Ingram C , Shaffer CM , Denny JC , Brilliant MH , Kitchner TE , Linneman JG , Roden DM , Johnson JA
Ref : Journal of Neurosurgery , :1 , 2015
Abstract : OBJECT Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients. METHODS Genotype testing for CYP2C19*2, *3, *8, *17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months. RESULTS The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the CYP2C19 loss of function (LOF) alleles *2, *3, and *8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03-0.62, p = 0.0101). Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08-0.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele (*2, *3, *8) than in wild-type homozygotes (OR 0.27, 95% CI 0.06-1.16, p = 0.078). Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05-1.04, p = 0.056). CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of CYP2C19 (*2, *3, *8) were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.
ESTHER : Hoh_2015_J.Neurosurg__1
PubMedSearch : Hoh_2015_J.Neurosurg__1
PubMedID: 26587656
Gene_locus related to this paper: human-CES1

Title : Comparative genomics of the white-rot fungi, Phanerochaete carnosa and P. chrysosporium, to elucidate the genetic basis of the distinct wood types they colonize - Suzuki_2012_BMC.Genomics_13_444
Author(s) : Suzuki H , MacDonald J , Syed K , Salamov A , Hori C , Aerts A , Henrissat B , Wiebenga A , vanKuyk PA , Barry K , Lindquist E , LaButti K , Lapidus A , Lucas S , Coutinho P , Gong Y , Samejima M , Mahadevan R , Abou-Zaid M , de Vries RP , Igarashi K , Yadav JS , Grigoriev IV , Master ER
Ref : BMC Genomics , 13 :444 , 2012
Abstract : BACKGROUND: Softwood is the predominant form of land plant biomass in the Northern hemisphere, and is among the most recalcitrant biomass resources to bioprocess technologies. The white rot fungus, Phanerochaete carnosa, has been isolated almost exclusively from softwoods, while most other known white-rot species, including Phanerochaete chrysosporium, were mainly isolated from hardwoods. Accordingly, it is anticipated that P. carnosa encodes a distinct set of enzymes and proteins that promote softwood decomposition. To elucidate the genetic basis of softwood bioconversion by a white-rot fungus, the present study reports the P. carnosa genome sequence and its comparative analysis with the previously reported P. chrysosporium genome.
RESULTS: P. carnosa encodes a complete set of lignocellulose-active enzymes. Comparative genomic analysis revealed that P. carnosa is enriched with genes encoding manganese peroxidase, and that the most divergent glycoside hydrolase families were predicted to encode hemicellulases and glycoprotein degrading enzymes. Most remarkably, P. carnosa possesses one of the largest P450 contingents (266 P450s) among the sequenced and annotated wood-rotting basidiomycetes, nearly double that of P. chrysosporium. Along with metabolic pathway modeling, comparative growth studies on model compounds and chemical analyses of decomposed wood components showed greater tolerance of P. carnosa to various substrates including coniferous heartwood.
CONCLUSIONS: The P. carnosa genome is enriched with genes that encode P450 monooxygenases that can participate in extractives degradation, and manganese peroxidases involved in lignin degradation. The significant expansion of P450s in P. carnosa, along with differences in carbohydrate- and lignin-degrading enzymes, could be correlated to the utilization of heartwood and sapwood preparations from both coniferous and hardwood species.
ESTHER : Suzuki_2012_BMC.Genomics_13_444
PubMedSearch : Suzuki_2012_BMC.Genomics_13_444
PubMedID: 22937793
Gene_locus related to this paper: phacs-k5whx2 , phacs-k5v2s8 , phacs-k5v5r2 , phacs-k5vyk5 , phacs-k5vzf8 , phacs-k5wbu9 , phacs-k5wc10 , phacs-k5wpw0 , phacs-k5wzn6 , phacs-k5x1t8 , phacs-k5x5g6 , phacs-k5x5p4

Title : Extensive remodeling of the Pseudomonas syringae pv. avellanae type III secretome associated with two independent host shifts onto hazelnut - O'Brien_2012_BMC.Microbiol_12_141
Author(s) : O'Brien HE , Thakur S , Gong Y , Fung P , Zhang J , Yuan L , Wang PW , Yong C , Scortichini M , Guttman DS
Ref : BMC Microbiol , 12 :141 , 2012
Abstract : BACKGROUND: Hazelnut (Corylus avellana) decline disease in Greece and Italy is caused by the convergent evolution of two distantly related lineages of Pseudomonas syringae pv. avellanae (Pav). We sequenced the genomes of three Pav isolates to determine if their convergent virulence phenotype had a common genetic basis due to either genetic exchange between lineages or parallel evolution.
RESULTS: We found little evidence for horizontal transfer (recombination) of genes between Pav lineages, but two large genomic islands (GIs) have been recently acquired by one of the lineages. Evolutionary analyses of the genes encoding type III secreted effectors (T3SEs) that are translocated into host cells and are important for both suppressing and eliciting defense responses show that the two Pav lineages have dramatically different T3SE profiles, with only two shared putatively functional T3SEs. One Pav lineage has undergone unprecedented secretome remodeling, including the acquisition of eleven new T3SEs and the loss or pseudogenization of 15, including five of the six core T3SE families that are present in the other Pav lineage. Molecular dating indicates that divergence within both of the Pav lineages predates their observation in the field. This suggest that both Pav lineages have been cryptically infecting hazelnut trees or wild relatives for many years, and that the emergence of hazelnut decline in the 1970s may have been due to changes in agricultural practice.
CONCLUSIONS: These data show that divergent lineages of P. syringae can converge on identical disease etiology on the same host plant using different virulence mechanisms and that dramatic shifts in the arsenal of T3SEs can accompany disease emergence.
ESTHER : O'Brien_2012_BMC.Microbiol_12_141
PubMedSearch : O'Brien_2012_BMC.Microbiol_12_141
PubMedID: 22800299
Gene_locus related to this paper: psesy-PSPTO2005 , psesy-PSPTO3138 , pseu2-q4zn59 , pseu2-q4zwv7 , pseap-f3ivd6 , psesx-a0a085uxb9

Title : Semi-automatic in silico gap closure enabled de novo assembly of two Dehalobacter genomes from metagenomic data - Tang_2012_PLoS.One_7_e52038
Author(s) : Tang S , Gong Y , Edwards EA
Ref : PLoS ONE , 7 :e52038 , 2012
Abstract : Typically, the assembly and closure of a complete bacterial genome requires substantial additional effort spent in a wet lab for gap resolution and genome polishing. Assembly is further confounded by subspecies polymorphism when starting from metagenome sequence data. In this paper, we describe an in silico gap-resolution strategy that can substantially improve assembly. This strategy resolves assembly gaps in scaffolds using pre-assembled contigs, followed by verification with read mapping. It is capable of resolving assembly gaps caused by repetitive elements and subspecies polymorphisms. Using this strategy, we realized the de novo assembly of the first two Dehalobacter genomes from the metagenomes of two anaerobic mixed microbial cultures capable of reductive dechlorination of chlorinated ethanes and chloroform. Only four additional PCR reactions were required even though the initial assembly with Newbler v. 2.5 produced 101 contigs within 9 scaffolds belonging to two Dehalobacter strains. By applying this strategy to the re-assembly of a recently published genome of Bacteroides, we demonstrate its potential utility for other sequencing projects, both metagenomic and genomic.
ESTHER : Tang_2012_PLoS.One_7_e52038
PubMedSearch : Tang_2012_PLoS.One_7_e52038
PubMedID: 23284863
Gene_locus related to this paper: 9firm-w0ejt1

Title : Identification of pancreatic juice proteins as biomarkers of pancreatic cancer - Gao_2010_Oncol.Rep_23_1683
Author(s) : Gao J , Zhu F , Lv S , Li Z , Ling Z , Gong Y , Jie C , Ma L
Ref : Oncol Rep , 23 :1683 , 2010
Abstract : Pancreatic juice is a potential source of proteins associated with pancreatic cancer (PC) due to the proximity of ducts to tumor tissue. Therefore, screening of proteins in pancreatic juice from PC patients may identify new PC biomarkers. We analyzed pancreatic juice from patients with pancreatic diseases including PC, chronic pancreatitis (CP) and simple choledocholithiasis (CDS) by 2-DE. Protein spots from PC patients that changed >2-fold compared with both CP and CDS were selected and identified by mass spectrometry (MS). mRNA levels were measured by QRT-PCR in PC cell lines, PC tissues and adjacent pancreatic normal (PN) tissues. Relationships between mRNA levels in PC tissues and their clinical characteristics and promoter methylation were analyzed in PC cell lines and tissues. We found that four proteins were significantly changed in PC compared to CP and simple CDS. Two proteins were up-regulated, serine proteinase-2 (PRSS2) preproprotein and pancreatic lipase-related protein-1 (PLRP1), and two proteins were down-regulated, chymotrypsinogen B (CTRB) precursor and elastase 3B (ELA3B) preproprotein. In all PC cell lines, PRSS 2 mRNA levels were elevated, while PLRP 1 mRNA was detected in 4/5 cell lines. ELA3B mRNA was undetectable in all cell lines, but CTRB mRNA was detected in 2/5 cell lines. In PC tissues compared to PN, levels of PRSS2 mRNA were significantly higher, ELA3B significantly lower, and PLRP1 and CTRB not significantly different. Elevated PRSS2 mRNA levels correlated with high T stage. The ELA3B gene promoter had higher methylation in PC cell lines and tissues compared with PN tissues, and correlated with low ELA3B gene expression. In conclusion, comparative proteomic analysis of pancreatic juice from PC patients is a powerful method to find new PC biomarkers. Hyperexpression of the PRSS2 gene and hypermethylation of ELA3B gene promoter were associated with PC, raising the possibility of their application as new biomarkers in PC diagnosis and screening.
ESTHER : Gao_2010_Oncol.Rep_23_1683
PubMedSearch : Gao_2010_Oncol.Rep_23_1683
PubMedID: 20428826

Title : Evaluation of the chitosan\/glycerol-beta-phosphate disodium salt hydrogel application in peripheral nerve regeneration - Zheng_2010_Biomed.Mater_5_35003
Author(s) : Zheng L , Ao Q , Han H , Zhang X , Gong Y
Ref : Biomed Mater , 5 :35003 , 2010
Abstract : Research efforts have been devoted to evaluating the application of the chitosan (CS)/glycerol-beta-phosphate (GP) disodium salt hydrogel in peripheral nerve regeneration. The gelation time was determined to be 770 s using ultraviolet spectrophotometry. A standard 10 mm long rat sciatic nerve defect model was employed, followed by bridging the proximal and distal stumps with chitosan conduits injected with the Schwann cell-containing hydrogel. Injections of the blank hydrogel, Schwann cell suspension and culture medium were used as controls. Two months later, electrophysiological assessment and fluorogold retrograde tracing showed that compound muscle action potentials (CMAPs) and fluorogold-labeled neurons were only detected in the Schwann cell suspension group and culture medium group. The rats were then killed, and implanted conduits were removed for examination. There were no regenerated nerves found in groups injected with the blank hydrogel or Schwann cell-containing hydrogel, while the other two groups clearly displayed regenerated nerves across the gaps. In the subsequent histological assessment, immunohistochemistry, toluidine blue staining and transmission electron microscopy were performed to evaluate the regenerated nerves. The relative wet weight ratio, Masson trichrome staining and acetylcholinesterase staining were employed for the examination of gastrocnemius muscles in all four groups. The Schwann cell suspension group showed the best results for all these indexes; the culture medium group ranked second and the two hydrogel-injected groups showed the least optimal results. In conclusion, our data revealed that the implanted CS/GP hydrogel actually impeded nerve regeneration, which is inconsistent with former in vitro reports and general supposition. We believe that the application of the CS/GP hydrogel in nerve regeneration requires a further study before a satisfactory result is obtained. In addition, the present study also confirmed that Schwann cell implantation stimulated nerve regeneration.
ESTHER : Zheng_2010_Biomed.Mater_5_35003
PubMedSearch : Zheng_2010_Biomed.Mater_5_35003
PubMedID: 20404399

Title : RanBPM is an acetylcholinesterase-interacting protein that translocates into the nucleus during apoptosis - Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
Author(s) : Gong X , Ye W , Zhou H , Ren X , Li Z , Zhou W , Wu J , Gong Y , Ouyang Q , Zhao X , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :883 , 2009
Abstract : Acetylcholinesterase (AChE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further confirmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were heterogeneously expressed in the cisplatin-untreated cytoplasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the translocation observed in case of AChE.
ESTHER : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedSearch : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedID: 19902122

Title : Large-scale cDNA transfection screening for genes related to cancer development and progression - Wan_2004_Proc.Natl.Acad.Sci.U.S.A_101_15724
Author(s) : Wan D , Gong Y , Qin W , Zhang P , Li J , Wei L , Zhou X , Li H , Qiu X , Zhong F , He L , Yu J , Yao G , Jiang H , Qian L , Yu Y , Shu H , Chen X , Xu H , Guo M , Pan Z , Chen Y , Ge C , Yang S , Gu J
Ref : Proc Natl Acad Sci U S A , 101 :15724 , 2004
Abstract : A large-scale assay was performed by transfecting 29,910 individual cDNA clones derived from human placenta, fetus, and normal liver tissues into human hepatoma cells and 22,926 cDNA clones into mouse NIH 3T3 cells. Based on the results of colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806 cDNA species (8,237 clones) were found to possess the ability of either stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895 clones) were unigenes of uncharacterized structure and function. A comprehensive analysis of the genes and the potential mechanisms for their involvement in the regulation of cell growth is provided. The genes were classified into four categories: I, genes related to the basic cellular mechanism for growth and survival; II, genes related to the cellular microenvironment; III, genes related to host-cell systemic regulation; and IV, genes of miscellaneous function. The extensive growth-regulatory activity of genes with such highly diversified functions suggests that cancer may be related to multiple levels of cellular and systemic controls. The present assay provides a direct genomewide functional screening method. It offers a better understanding of the basic machinery of oncogenesis, including previously undescribed systemic regulatory mechanisms, and also provides a tool for gene discovery with potential clinical applications.
ESTHER : Wan_2004_Proc.Natl.Acad.Sci.U.S.A_101_15724
PubMedSearch : Wan_2004_Proc.Natl.Acad.Sci.U.S.A_101_15724
PubMedID: 15498874

Title : Efficient preparation of optically active ketoprofen by Mucor javanicus lipase immobilized on an inorganic support - Kato_2000_J.Biosci.Bioeng_90_332
Author(s) : Kato K , Gong Y , Saito T , Kimoto H
Ref : J Biosci Bioeng , 90 :332 , 2000
Abstract : Lipase M from Mucor javanicus, one of nine commercially available hydrolytic enzymes, showed good enantioselectivity (E=50) for racemic ketoprofen trifluoroethyl ester in phosphate buffer (pH 7.0) containing 30% acetone. Lipase M immobilized on Toyonite 200-A showed the best selectivity (E=55) and reactivity. Moreover, the lipase could be recycled at least 5 times.
ESTHER : Kato_2000_J.Biosci.Bioeng_90_332
PubMedSearch : Kato_2000_J.Biosci.Bioeng_90_332
PubMedID: 16232865