Author Report for: Zeng LNo contact information in database for Zeng L
Shen P, Zhang X, Ding N, Zhou Y, Wu C, Xing C, Zeng L, Du L, Yuan J, Kang Y Ref: ACS Appl Mater Interfaces, :, 2023 : PubMed ESTHER: Shen_2023_ACS.Appl.Mater.Interfaces__ PubMedSearch: Shen 2023 ACS.Appl.Mater.Interfaces PubMedID: 37083309 Abstract Conventional chemotherapy usually fails to achieve its intended effect because of the poor water solubility, poor tumor selectivity, and low tumor accumulation of chemotherapy drugs. The systemic toxicity of chemotherapy agents is also a problem that cannot be ignored. It is expected that smart nano-drug delivery systems that are able to respond to tumor microenvironments will provide better therapeutic outcomes with decreased side effects of chemotherapeutics. Nano-drug delivery systems capable of breaking the redox balance can also increase the sensitivity of tumor cells to chemotherapeutics. In this study, using polymer-containing disulfide bonds, ester bonds, and d-alpha-tocopherol polyethylene glycol succinate (TPGS), which can amplify reactive oxygen species (ROS) in tumor cells, we have successfully prepared a smart glutathione (GSH) and esterase dual-responsive nano-drug delivery system (DTX@PAMBE-SS-TPGS NPs) with the ability to deplete GSH as well as amplify ROS and effectively release an encapsulated chemotherapy drug (DTX) in tumor cells. The potential of DTX@PAMBE-SS-TPGS NPs for enhanced antitumor effects was thoroughly evaluated using in vitro as well as in vivo experiments. Our research offers a promising strategy for maximizing the efficacy of tumor therapy. Title: Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis Lang B, Han L, Zeng L, Zhang Q, Chen S, Huang L, Jia Z, Yu Q, Zhang L Ref: BMC Pediatr, 22:295, 2022 : PubMed ESTHER: Lang_2022_BMC.Pediatr_22_295 PubMedSearch: Lang 2022 BMC.Pediatr 22 295 PubMedID: 35590273 Abstract BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future. Title: Analysis of the performance of the efficient di-(2-ethylhexyl) phthalate-degrading bacterium Rhodococcus pyridinovorans DNHP-S2 and associated catabolic pathways Wang L, Gan D, Gong L, Zhang Y, Wang J, Guan R, Zeng L, Qu J, Dong M Ref: Chemosphere, 306:135610, 2022 : PubMed ESTHER: Wang_2022_Chemosphere_306_135610 PubMedSearch: Wang 2022 Chemosphere 306 135610 PubMedID: 35810862 Abstract The widespread use of plastic has led to the global occurrence of phthalate esters (PAEs) pollution. PAEs can be effectively removed from polluted environments by microbe-mediated degradation. Di-(2-ethylhexyl) phthalate (DEHP) has the highest residual concentration in agricultural soil-contaminated areas compared to other PAEs in most of China. The Rhodococcus pyridinovorans DNHP-S2 microbial isolate identified was found to efficiently degrade DEHP. Within a 72 h period, the bacteria were able to degrade 52.47% and 99.75% of 500 mg L(-1) DEHP at 10 degreesC and 35 degreesC, respectively. Dimethyl phthalate (DMP) was first identified as an intermediate metabolite of DEHP, which is different from the previously reported DEHP catabolic pathway. Genomic sequencing of DNHP-S2 identified benzoate 1,2-dioxygenase and catechol 2,3/1,2-dioxygenase as potential mediators of DEHP degradation, consistent with the existence of two downstream metabolic pathways governing DEHP degradation. Three targets DEHP metabolism-related enzymes were found to be DEHP-inducible at the mRNA level, and DNHP-S2 was able to mediate the complete degradation of DEHP at lower temperatures, as confirmed via RT-qPCR. DNHP-S2 was also found to readily break down other PAEs including DMP, di-n-butyl phthalate (DBP), di-n-octyl phthalate (DnOP), and n-butyl benzyl phthalate (BBP). Together, these results thus highlight DNHP-S2 as a bacterial strain with great promise as a tool for the remediation of PAE pollution. In addition to providing new germplasm and genetic resources for use in the context of PAE degradation, these results also offer new insight into the potential mechanisms whereby PAEs undergo catabolic degradation, making them well-suited for use in PAE-contaminated environments. Title: Genome-wide analysis and expression patterns of lipid phospholipid phospholipase gene family in Brassica napus L Su W, Raza A, Zeng L, Gao A, Lv Y, Ding X, Cheng Y, Zou X Ref: BMC Genomics, 22:548, 2021 : PubMed ESTHER: Su_2021_BMC.Genomics_22_548 PubMedSearch: Su 2021 BMC.Genomics 22 548 PubMedID: 34273948 Abstract BACKGROUND: Lipid phosphate phosphatases (LPP) are critical for regulating the production and degradation of phosphatidic acid (PA), an essential signaling molecule under stress conditions. Thus far, the LPP family genes have not been reported in rapeseed (Brassica napus L.). RESULTS: In this study, a genome-wide analysis was carried out to identify LPP family genes in rapeseed that respond to different stress conditions. Eleven BnLPPs genes were identified in the rapeseed genome. Based on phylogenetic and synteny analysis, BnLPPs were classified into four groups (Group I-Group IV). Gene structure and conserved motif analysis showed that similar intron/exon and motifs patterns occur in the same group. By evaluating cis-elements in the promoters, we recognized six hormone- and seven stress-responsive elements. Further, six putative miRNAs were identified targeting three BnLPP genes. Gene ontology analysis disclosed that BnLPP genes were closely associated with phosphatase/hydrolase activity, membrane parts, phosphorus metabolic process, and dephosphorylation. The qRT-PCR based expression profiles of BnLPP genes varied in different tissues/organs. Likewise, several gene expression were significantly up-regulated under NaCl, PEG, cold, ABA, GA, IAA, and KT treatments. CONCLUSIONS: This is the first report to describe the comprehensive genome-wide analysis of the rapeseed LPP gene family. We identified different phytohormones and abiotic stress-associated genes that could help in enlightening the plant tolerance against phytohormones and abiotic stresses. The findings unlocked new gaps for the functional verification of the BnLPP gene family during stresses, leading to rapeseed improvement. Title: In Vitro and In Vivo Anti-AChE and Antioxidative Effects of Schisandra chinensis Extract: A Potential Candidate for Alzheimer's Disease Song X, Wang T, Guo L, Jin Y, Wang J, Yin G, Jiang K, Wang L, Huang H, Zeng L Ref: Evid Based Complement Alternat Med, 2020:2804849, 2020 : PubMed ESTHER: Song_2020_Evid.Based.Complement.Alternat.Med_2020_2804849 PubMedSearch: Song 2020 Evid.Based.Complement.Alternat.Med 2020 2804849 PubMedID: 32148536 Abstract Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2'-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD. Title: Structure and Catalytic Mechanism of a Pyrethroid Carboxylesterase PytH from Sphingobium faniae JZ-2 Xu D, Gao Y, Sun B, Ran T, Zeng L, He J, Wang W Ref: Applied Environmental Microbiology, :, 2020 : PubMed ESTHER: Xu_2020_Appl.Environ.Microbiol__ PubMedSearch: Xu 2020 Appl.Environ.Microbiol PubMedID: 32303545 Gene_locus related to this paper: sphwj-c0la90 Abstract Carboxylesterase PytH, isolated from a pyrethroid degrading bacterium Sphingobium faniae JZ-2, could rapidly hydrolyze the ester bond of a wide range of pyrethroid pesticides, including permethrin, fenpropathrin, cypermethrin, fenvalerate, deltamethrin, cyhalothrin and bifenthrin. To elucidate the catalytic mechanism of PytH, here we report the crystal structures of PytH with bifenthrin (BIF) and phenylmethylsulfonyl fluoride (PMSF) and two PytH mutants. Though PytH shares low sequence identity with reported alpha/beta-hydrolase fold proteins, the typical triad catalytic center with Ser-His-Asp triad (Ser78, His230 and Asp202) is present and vital for the hydrolase activity. However, no contact was found between Ser78 and His230 in the structures we solved, which may be due to the fact that the PytH structures we determined are in their inactive or low activity forms. The structure of PytH is composed of a core domain and a lid domain; some hydrophobic amino acid residues surrounding the substrate from both domains form a deeper and wider hydrophobic pocket than its homologous structures. This indicates that the larger hydrophobic pocket makes PytH fit for its larger substrates binding; both lid and core domains are involved in substrate binding and the lid domain induced core domain movement may make the active center correctly positioned with substrates.IMPORTANCE Pyrethroid pesticides are widely applied in agriculture and household, however, extensive use of these pesticides also causes serious environmental and health problems. The hydrolysis of pyrethroids by carboxylesterases is the major pathway of microbial degradation of pyrethroids, but the structure of carboxylesterases and its catalytic mechanism are still unknown. Carboxylesterase PytH from Sphingobium faniae JZ-2 could effectively hydrolyze a wide range of pyrethroid pesticides. The crystal structures of PytH are solved in this study. It showed that it belongs to the alpha/beta-hydrolase fold proteins with typical catalytic Ser-His-Asp triad though PytH has a low sequence identity (about 20%) with them. The special large hydrophobic binding pocket endowed PytH binding bigger pyrethroids family substrates. Our structures shed light on the substrate selectivity and the future application of PytH and deeper the understanding of alpha/beta-hydrolase members. Title: Targeting QKI-7 in vivo restores endothelial cell function in diabetes Yang C, Eleftheriadou M, Kelaini S, Morrison T, Gonzalez MV, Caines R, Edwards N, Yacoub A, Edgar K and Margariti A <8 more author(s)> Yang C, Eleftheriadou M, Kelaini S, Morrison T, Gonzalez MV, Caines R, Edwards N, Yacoub A, Edgar K, Moez A, Ivetic A, Zampetaki A, Zeng L, Wilkinson FL, Lois N, Stitt AW, Grieve DJ, Margariti A (- 8) Ref: Nat Commun, 11:3812, 2020 : PubMed ESTHER: Yang_2020_Nat.Commun_11_3812 PubMedSearch: Yang 2020 Nat.Commun 11 3812 PubMedID: 32732889 Abstract Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) in iPS cell-derived ECs when exposed to hyperglycemia, and in human iPS-ECs from diabetic patients. QKI-7 is also highly expressed in human coronary arterial ECs from diabetic donors, and on blood vessels from diabetic critical limb ischemia patients undergoing a lower-limb amputation. QKI-7 expression is tightly controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion. RNA immunoprecipitation (RIP) and mRNA-decay assays reveal that QKI-7 binds and promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-alpha-stimulated gene/protein 6 (TSG-6). When hindlimb ischemia is induced in diabetic mice and QKI-7 is knocked-down in vivo in ECs, reperfusion and blood flow recovery are markedly promoted. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications. Title: Karrikin Signaling Acts Parallel to and Additively with Strigolactone Signaling to Regulate Rice Mesocotyl Elongation in Darkness Zheng J, Hong K, Zeng L, Wang L, Kang S, Qu M, Dai J, Zou L, Zhu L and Xiong G <11 more author(s)> Zheng J, Hong K, Zeng L, Wang L, Kang S, Qu M, Dai J, Zou L, Zhu L, Tang Z, Meng X, Wang B, Hu J, Zeng D, Zhao Y, Cui P, Wang Q, Qian Q, Wang Y, Li J, Xiong G (- 11) Ref: Plant Cell, 32:2780, 2020 : PubMed ESTHER: Zheng_2020_Plant.Cell_32_2780 PubMedSearch: Zheng 2020 Plant.Cell 32 2780 PubMedID: 32665307 Abstract Seedling emergence in monocots depends mainly on mesocotyl elongation, requiring coordination between developmental signals and environmental stimuli. Strigolactones (SLs) and karrikins are butenolide compounds that regulate various developmental processes; both are able to negatively regulate rice (Oryza sativa) mesocotyl elongation in the dark. Here, we report that a karrikin signaling complex, DWARF14-LIKE (D14L)-DWARF3 (D3)-O. sativa SUPPRESSOR OF MAX2 1 (OsSMAX1) mediates the regulation of rice mesocotyl elongation in the dark. We demonstrate that D14L recognizes the karrikin signal and recruits the SCF(D3) ubiquitin ligase for the ubiquitination and degradation of OsSMAX1, mirroring the SL-induced and D14- and D3-dependent ubiquitination and degradation of D53. Overexpression of OsSMAX1 promoted mesocotyl elongation in the dark, whereas knockout of OsSMAX1 suppressed the elongated-mesocotyl phenotypes of d14l and d3 OsSMAX1 localizes to the nucleus and interacts with TOPLESS-RELATED PROTEINs, regulating downstream gene expression. Moreover, we showed that the GR24 enantiomers GR24(5DS) and GR24 (ent-5DS) specifically inhibit mesocotyl elongation and regulate downstream gene expression in a D14- and D14L-dependent manner, respectively. Our work revealed that karrikin and SL signaling play parallel and additive roles in modulating downstream gene expression and negatively regulating mesocotyl elongation in the dark. Title: Complex role of titanium dioxide nanoparticles in the trophic transfer of arsenic from Nannochloropsis maritima to Artemia salina nauplii Yang F, Zeng L, Luo Z, Wang Z, Huang F, Wang Q, Drobne D, Yan C Ref: Aquat Toxicol, 198:231, 2018 : PubMed ESTHER: Yang_2018_Aquat.Toxicol_198_231 PubMedSearch: Yang 2018 Aquat.Toxicol 198 231 PubMedID: 29558708 Abstract Increasing concern has been focused on the potential risks associated with the trophic transfer to aquatic organisms of ambient contaminants in the presence of titanium dioxide nanoparticles (nano-TiO2). This study investigated the influence of nano-TiO2 on the trophic transfer of arsenic (As) from the microalgae Nannochloropsis maritima to the brine shrimp Artemia salina nauplii. We found that nano-TiO2 could significantly facilitate As sorption on N. maritima within an exposure period of 24h, and this sorption subsequently led to higher As trophic transfer from the algae to A. salina according to trophic transfer factors (TTFAs+nano-TiO2>TTFAs). However, after 48h of depuration, the retention of As in A. salina fed As-nano-TiO2-contaminated algae was even lower than that in A. salina fed As-contaminated algae at the same exposure concentrations. This result indicates that the increased food chain transfer of As in the presence of nano-TiO2 can be explained by adsorption of As onto nano-TiO2 in contaminated food (algae), but the bioavailability of As in A. salina is reduced after the introduction of nanoparticles. Although the stress enzyme activities of superoxide dismutase (SOD) and acetylcholinesterase (AChE) in A. salina at a lower As concentration treatment in the presence of nano-TiO2 were not significantly changed, they increased with higher exposure concentrations of As with or without nano-TiO2. Our study highlighted the complex role of nanomaterials in the transfer of ambient contaminants via trophic chains and the potential of nano-TiO2 to reduce the bioavailability of As via trophic transfer to saltwater zooplankton. Title: Transcriptional responses in the hepatopancreas of Eriocheir sinensis exposed to deltamethrin Yang Z, Zhang Y, Jiang Y, Zhu F, Zeng L, Wang Y, Lei X, Yao Y, Hou Y and Hu K <3 more author(s)> Yang Z, Zhang Y, Jiang Y, Zhu F, Zeng L, Wang Y, Lei X, Yao Y, Hou Y, Xu L, Xiong C, Yang X, Hu K (- 3) Ref: PLoS ONE, 12:e0184581, 2017 : PubMed ESTHER: Yang_2017_PLoS.One_12_e0184581 PubMedSearch: Yang 2017 PLoS.One 12 e0184581 PubMedID: 28910412 Abstract Deltamethrin is an important pesticide widely used against ectoparasites. Deltamethrin contamination has resulted in a threat to the healthy breeding of the Chinese mitten crab, Eriocheir sinensis. In this study, we investigated transcriptional responses in the hepatopancreas of E. sinensis exposed to deltamethrin. We obtained 99,087,448, 89,086,478, and 100,117,958 raw sequence reads from control 1, control 2, and control 3 groups, and 92,094,972, 92,883,894, and 92,500,828 raw sequence reads from test 1, test 2, and test 3 groups, respectively. After filtering and quality checking of the raw sequence reads, our analysis yielded 79,228,354, 72,336,470, 81,859,826, 77,649,400, 77,194,276, and 75,697,016 clean reads with a mean length of 150 bp from the control and test groups. After deltamethrin treatment, a total of 160 and 167 genes were significantly upregulated and downregulated, respectively. Gene ontology terms "biological process," "cellular component," and "molecular function" were enriched with respect to cell killing, cellular process, other organism part, cell part, binding, and catalytic. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes showed that the metabolic pathways were significantly enriched. We found that the CYP450 enzyme system, carboxylesterase, glutathione-S-transferase, and material (including carbohydrate, lipid, protein, and other substances) metabolism played important roles in the metabolism of deltamethrin in the hepatopancreas of E. sinensis. This study revealed differentially expressed genes related to insecticide metabolism and detoxification in E. sinensis for the first time and will help in understanding the toxicity and molecular metabolic mechanisms of deltamethrin in E. sinensis. Title: [The value of determination of serum cholinesterase levels in judgment of severity and prognosis in patients with severe pneumonia] Mo X, Tang H, Zeng L, Lu H, Guo L, Ma Z Ref: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 28:38, 2016 : PubMed ESTHER: Mo_2016_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_28_38 PubMedSearch: Mo 2016 Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue 28 38 PubMedID: 26805533 Abstract OBJECTIVE: To investigate the value of serum cholinesterase (S-ChE) levels in judgment of severity and prognosis in patients with severe pneumonia. Title: Evolutionary and population genomics of the cavity causing bacteria Streptococcus mutans Cornejo OE, Lefebure T, Bitar PD, Lang P, Richards VP, Eilertson K, Do T, Beighton D, Zeng L and Stanhope MJ <4 more author(s)> Cornejo OE, Lefebure T, Bitar PD, Lang P, Richards VP, Eilertson K, Do T, Beighton D, Zeng L, Ahn SJ, Burne RA, Siepel A, Bustamante CD, Stanhope MJ (- 4) Ref: Molecular Biology Evolution, 30:881, 2013 : PubMed ESTHER: Cornejo_2013_Mol.Biol.Evol_30_881 PubMedSearch: Cornejo 2013 Mol.Biol.Evol 30 881 PubMedID: 23228887 Abstract Streptococcus mutans is widely recognized as one of the key etiological agents of human dental caries. Despite its role in this important disease, our present knowledge of gene content variability across the species and its relationship to adaptation is minimal. Estimates of its demographic history are not available. In this study, we generated genome sequences of 57 S. mutans isolates, as well as representative strains of the most closely related species to S. mutans (S. ratti, S. macaccae, and S. criceti), to identify the overall structure and potential adaptive features of the dispensable and core components of the genome. We also performed population genetic analyses on the core genome of the species aimed at understanding the demographic history, and impact of selection shaping its genetic variation. The maximum gene content divergence among strains was approximately 23%, with the majority of strains diverging by 5-15%. The core genome consisted of 1,490 genes and the pan-genome approximately 3,296. Maximum likelihood analysis of the synonymous site frequency spectrum (SFS) suggested that the S. mutans population started expanding exponentially approximately 10,000 years ago (95% confidence interval [CI]: 3,268-14,344 years ago), coincidental with the onset of human agriculture. Analysis of the replacement SFS indicated that a majority of these substitutions are under strong negative selection, and the remainder evolved neutrally. A set of 14 genes was identified as being under positive selection, most of which were involved in either sugar metabolism or acid tolerance. Analysis of the core genome suggested that among 73 genes present in all isolates of S. mutans but absent in other species of the mutans taxonomic group, the majority can be associated with metabolic processes that could have contributed to the successful adaptation of S. mutans to its new niche, the human mouth, and with the dietary changes that accompanied the origin of agriculture. Title: Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z and Hu W <5 more author(s)> Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z, Xu H, Yang L, Zhang X, Huang M, Zhao J, Hu W (- 5) Ref: Eur Journal of Medicinal Chemistry, 52:205, 2012 : PubMed ESTHER: Xie_2012_Eur.J.Med.Chem_52_205 PubMedSearch: Xie 2012 Eur.J.Med.Chem 52 205 PubMedID: 22475866 Inhibitor(s) related to this paper: Alogliptin Abstract We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development. Title: Identification of resistance-responsive proteins in larvae of Bactrocera dorsalis (Hendel), for pyrethroid toxicity by a proteomic approach Jin T, Zeng L, Lu Y, Xu Y, Liang G Ref: Pesticide Biochemistry and Physiology, 96:1, 2010 : PubMed ESTHER: Jin_2010_Pestic.Biochem.Physiol_96_1 PubMedSearch: Jin 2010 Pestic.Biochem.Physiol 96 1 Abstract Insect resistance to the pyrethroid toxins has been examined previously using a number of traditional biochemical and molecular techniques. In this study, a proteomic approach involving two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and tandem mass spectrometry (MS/MS) were applied to examine changes in resistant stains larvae of Bactracera dorsalis Hendel induced by pyrethroid treatment over a 3 h, 6 h and 12 h time period, and a number of proteins changes were observed to change in the level of regulation. Out of total 15 proteins, 9 proteins were observed only after pyrethroid treatment; 6 proteins showed different expression. After MALDI-TOF analyses and peptide mapping method, the data was compared with those of the known proteins available in public databases. Sequence analyses revealed that resistance response correlates with up-regulation (glycerol-3-phosphate dehydrogenase) and down-regulation (ATP-ADP antiporter) of energy-related proteins. It indicated that increased metabolism and energy-indeed as a resistance response to pyrethroid toxins. The regulation of cytoskeleton proteins were possibly a B. dorsalis tissue repair response or in cell division. Up-regulation of protein synthesis would results in substantial bioenergetic enhancement, suggesting a trade-off insect resistance to pyrethroid. Down regulation of neural protein indicated that neural system was physically injured after pyrethroid stress. Some remaining proteins were not identifiable, suggesting these may be novel proteins. Oriental fruit fly proteomes of pesticide induced provide an integrative basis for consolidating our knowledge of insect resistance. The results pave the way for future investigation of the alteration of the insect resistance to chemical pesticides. | |||||||
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