Fu X

References (22)

Title : Deficiency of neutral cholesterol ester hydrolase 1 (NCEH1) impairs endothelial function in diet-induced diabetic mice - Sun_2024_Cardiovasc.Diabetol_23_138
Author(s) : Sun HJ , Ni ZR , Liu Y , Fu X , Liu SY , Hu JY , Sun QY , Li YC , Hou XH , Zhang JR , Zhu XX , Lu QB
Ref : Cardiovasc Diabetol , 23 :138 , 2024
Abstract : BACKGROUND: Neutral cholesterol ester hydrolase 1 (NCEH1) plays a critical role in the regulation of cholesterol ester metabolism. Deficiency of NCHE1 accelerated atherosclerotic lesion formation in mice. Nonetheless, the role of NCEH1 in endothelial dysfunction associated with diabetes has not been explored. The present study sought to investigate whether NCEH1 improved endothelial function in diabetes, and the underlying mechanisms were explored. METHODS: The expression and activity of NCEH1 were determined in obese mice with high-fat diet (HFD) feeding, high glucose (HG)-induced mouse aortae or primary endothelial cells (ECs). Endothelium-dependent relaxation (EDR) in aortae response to acetylcholine (Ach) was measured. RESULTS: Results showed that the expression and activity of NCEH1 were lower in HFD-induced mouse aortae, HG-exposed mouse aortae ex vivo, and HG-incubated primary ECs. HG exposure reduced EDR in mouse aortae, which was exaggerated by endothelial-specific deficiency of NCEH1, whereas NCEH1 overexpression restored the impaired EDR. Similar results were observed in HFD mice. Mechanically, NCEH1 ameliorated the disrupted EDR by dissociating endothelial nitric oxide synthase (eNOS) from caveolin-1 (Cav-1), leading to eNOS activation and nitric oxide (NO) release. Moreover, interaction of NCEH1 with the E3 ubiquitin-protein ligase ZNRF1 led to the degradation of Cav-1 through the ubiquitination pathway. Silencing Cav-1 and upregulating ZNRF1 were sufficient to improve EDR of diabetic aortas, while overexpression of Cav-1 and downregulation of ZNRF1 abolished the effects of NCEH1 on endothelial function in diabetes. Thus, NCEH1 preserves endothelial function through increasing NO bioavailability secondary to the disruption of the Cav-1/eNOS complex in the endothelium of diabetic mice, depending on ZNRF1-induced ubiquitination of Cav-1. CONCLUSIONS: NCEH1 may be a promising candidate for the prevention and treatment of vascular complications of diabetes.
ESTHER : Sun_2024_Cardiovasc.Diabetol_23_138
PubMedSearch : Sun_2024_Cardiovasc.Diabetol_23_138
PubMedID: 38664801

Title : Lipase-mediated detoxification of host-derived antimicrobial fatty acids by Staphylococcus aureus - Kengmo_2024_Commun.Biol_7_572
Author(s) : Kengmo Tchoupa A , Elsherbini AMA , Camus J , Fu X , Hu X , Ghaneme O , Seibert L , Lebtig M , Bocker MA , Horlbeck A , Lambidis SP , Schittek B , Kretschmer D , Lammerhofer M , Peschel A
Ref : Commun Biol , 7 :572 , 2024
Abstract : Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was rare in blood, nose, and skin strains, suggesting a particularly important role of Lip2 for host - microbe interactions. In a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid (a human-specific AFA) in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth in otherwise inhospitable niches.
ESTHER : Kengmo_2024_Commun.Biol_7_572
PubMedSearch : Kengmo_2024_Commun.Biol_7_572
PubMedID: 38750133

Title : Design, synthesis and biological evaluation of new multi-target scutellarein hybrids for treatment of Alzheimer's disease - Luo_2023_Bioorg.Chem_138_106596
Author(s) : Luo K , Chen J , Li H , Wu D , Du Y , Zhao S , Liu T , Li L , Dai Z , Li Y , Zhao Y , Tang L , Fu X
Ref : Bioorg Chem , 138 :106596 , 2023
Abstract : Scutellarein hybrids were designed, synthesized and evaluated as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds 11a-i, containing a 2-hydroxymethyl-3,5,6-trimethylpyrazine fragment at the 7-position of scutellarein, were found to have balanced and effective multi-target potencies against AD. Among them, compound 11e exhibited the most potent inhibition of electric eel and human acetylcholinesterase enzymes with IC(50) values of 6.72 +/- 0.09 and 8.91 +/- 0.08 microM, respectively. In addition, compound 11e displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (91.85% and 85.62%, respectively) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.54% and 83.49% disaggregation, respectively). Moreover, 11e significantly reduced tau protein hyperphosphorylation induced by Abeta(25-35), and also exhibited good inhibition of platelet aggregation. A neuroprotective assay demonstrated that pre-treatment of PC12 cells with 11e significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax and caspase-3) and inhibited RSL3-induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 11e would have optimal blood-brain barrier and intestinal absorption characteristics. In addition, in vivo studies revealed that compound 11e significantly attenuated learning and memory impairment in an AD mice model. Toxicity experiments with the compound did not reveal any safety concerns. Notably, 11e significantly reduced beta-amyloid precursor protein (APP) and beta-site APP cleaving enzyme-1 (BACE-1) protein expression in brain tissue of scopolamine-treated mice. Taken together, these outstanding properties qualified compound 11e as a promising multi-target candidate for AD therapy, worthy of further studies.
ESTHER : Luo_2023_Bioorg.Chem_138_106596
PubMedSearch : Luo_2023_Bioorg.Chem_138_106596
PubMedID: 37186997

Title : A promising tool for clinical diagnostics: Dual-emissive carbonized polymer dots based cross-linking enhanced emission for sensitive detection of alkaline phosphatase and butyrylcholinesterase - Li_2023_Biosens.Bioelectron_238_115576
Author(s) : Li T , Wang D , Hu J , Fu X , Ji Y , Li R
Ref : Biosensors & Bioelectronics , 238 :115576 , 2023
Abstract : Compared with single signal readout, dual-signal readout commendably corrects the impact of systematic or background error, achieving more accurate results for the diagnosis of many diseases. This work aimed to design and prepare dual-emissive fluorescent probes for the construction of ratiometric fluorescence biosensors to detect liver disease biomarkers. Sodium alginate (SA) with numerous potential sub-fluorophores and active sites and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP) with macrocyclic conjugated structures were introduced to prepare the carbonized polymer dots (CPDs) with red/blue dual emission based on the cross-linking enhanced emission (CEE) effect and the luminescence of macrocyclic conjugated structures. The ratiometric fluorescence sensing systems were constructed by integrating the specific response of CPDs to Cu(2+) and the affinity difference of Cu(2+) to substrates or products of enzymes. The sensing systems, CPDs/Cu(2+)/PPi and CPDs/Cu(2+)/BTCh, were designed to detect liver disease biomarkers, alkaline phosphatase (ALP) and butyrylcholinesterase (BChE), respectively. The limit of detection for ALP and BChE was 0.35 U/L and 0.19 U/L, respectively. The proposed sensors were successfully applied to human serum samples from different health stages with satisfactory recoveries. These results demonstrate the successful design of a novel dual-emissive fluorescent probe and provide a feasible strategy for clinical detection.
ESTHER : Li_2023_Biosens.Bioelectron_238_115576
PubMedSearch : Li_2023_Biosens.Bioelectron_238_115576
PubMedID: 37557027

Title : Systems pharmacology-based mechanism exploration of Acanthopanax senticosusin for Alzheimer's disease using UPLC-Q-TOF-MS, network analysis, and experimental validation - Zhuo_2023_Eur.J.Pharmacol__175895
Author(s) : Zhuo Y , Fu X , Jiang Q , Lai Y , Gu Y , Fang S , Chen H , Liu C , Pan H , Wu Q , Fang J
Ref : European Journal of Pharmacology , :175895 , 2023
Abstract : BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease, characterized by progressive cognitive dysfunction and memory loss. However, the disease-modifying treatments for AD are still lacking. Traditional Chinese herbs, have shown their potentials as novel treatments for complex diseases, such as AD. PURPOSE: This study was aimed at investigating the mechanism of action (MOA) of Acanthopanax senticosusin (AS) for treatment of AD. METHODS: In this study, we firstly identified the chemical constituents in Acanthopanax senticosusin (AS) utilizing ultra-high performance liquid chromatography coupled with Q-TOF-mass spectrometry (UPLC-Q-TOF-MS), and next built the drug-target network of these compounds. We next performed the systems pharmacology-based analysis to preliminary explore the MOA of AS against AD. Moreover, we applied the network proximity approach to identify the potential anti-AD components in AS. Finally, experimental validations, including animal behavior test, ELISA and TUNEL staining, were conducted to verify our systems pharmacology-based analysis. RESULTS: 60 chemical constituents in AS were identified via the UPLC-Q-TOF-MS approach. The systems pharmacology-based analysis indicated that AS might exert its therapeutic effects on AD via acetylcholinesterase and apoptosis signaling pathway. To explore the material basis of AS against AD, we further identified 15 potential anti-AD components in AS. Consistently, in vivo experiments demonstrated that AS could protect cholinergic nervous system damage and decrease neuronal apoptosis caused by scopolamine. CONCLUSION: Overall, this study applied systems pharmacology approach, via UPLC-Q-TOF-MS, network analysis, and experimental validation to decipher the potential molecular mechanism of AS against AD.
ESTHER : Zhuo_2023_Eur.J.Pharmacol__175895
PubMedSearch : Zhuo_2023_Eur.J.Pharmacol__175895
PubMedID: 37422122

Title : Strigolactone and gibberellin signalling coordinately regulates metabolic adaptations to changes in nitrogen availability in rice - Sun_2023_Mol.Plant__
Author(s) : Sun H , Guo X , Zhu X , Gu P , Zhang W , Tao W , Wang D , Wu Y , Zhao Q , Xu G , Fu X , Zhang Y
Ref : Mol Plant , : , 2023
Abstract : Modern semi-dwarf rice varieties of the 'Green Revolution' require a high nitrogen (N) fertilizer supply to obtain a high yield. A better understanding of the interplay between N metabolic and developmental processes is required for improved N use efficiency (NUE) and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability, which ensure efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signalling interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the genes expression associated with N metabolism. N limitation also induces degradation of the rice DELLA protein SLENDER RICE 1 (SLR1) in the D14- and D53-dependent manners, and that is effective for the release of GRF4 from the competitive inhibition caused by SLR1. Our findings reveal a previously unknown mechanism underlying SL and gibberellin crosstalk in response to N availability, which advances our understanding of plant growth-metabolic coordination that can be useful to improve NUE in high-yield crops.
ESTHER : Sun_2023_Mol.Plant__
PubMedSearch : Sun_2023_Mol.Plant__
PubMedID: 36683328

Title : Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer's disease - Wu_2022_Bioorg.Chem_122_105760
Author(s) : Wu D , Chen J , Luo K , Li H , Liu T , Li L , Dai Z , Li Y , Zhao Y , Fu X
Ref : Bioorg Chem , 122 :105760 , 2022
Abstract : In this study, we designed, synthesized and evaluated a series of scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). Compounds containing scutellarein as the parent nucleus (6a-l) had good inhibitory activity against acetyl cholinesterase (AChE), with compound 6 h exhibiting the most potent inhibition of electric eel AChE and human AChE enzymes with IC(50) values of 6.01 +/- 1.66 and 7.91 +/- 0.49 microM, respectively. In addition, compound 6 h displayed not only excellent inhibition of self- and Cu(2+)-induced Abeta(1-42) aggregation (89.17% and 86.19% inhibition) but also induced disassembly of self- and Cu(2+)-induced Abeta fibrils (84.25% and 78.73% disaggregation). Moreover, a neuroprotective assay demonstrated that pre-treatment of PC12 cells with 6 h significantly decreased lactate dehydrogenase levels, increased cell viability, enhanced expression of relevant apoptotic proteins (Bcl-2, Bax, and caspase-3) and inhibited RSL3 induced PC12 cell ferroptosis. Furthermore, hCMEC/D3 and hPepT1-MDCK cell line permeability assays indicated that 6 h would have optimal blood-brain barrier and intestinal absorption characteristics. The in vivo experimental data suggested that 6 h ameliorated learning and memory impairment in mice by decreasing AChE activity, increasing ACh levels and alleviating pathological damage of hippocampal tissue cells. These multifunctional properties highlight compound 6 h as a promising candidate for development as a multifunctional drug against AD.
ESTHER : Wu_2022_Bioorg.Chem_122_105760
PubMedSearch : Wu_2022_Bioorg.Chem_122_105760
PubMedID: 35349945

Title : Targeted Metabolomics Study of Human Plasma Revealed Activation of the Cytochrome P450 Epoxygenase\/Epoxide Hydrolase Axis in Patients with IgA Nephropathy - Deng_2022_J.Proteome.Res__
Author(s) : Deng BQ , Li MY , Fu X , Luo Y , Qiao Q , Liu JY
Ref : J Proteome Res , : , 2022
Abstract : IgA nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of chronic kidney disease. The pathogenic mechanism of IgAN remains largely unknown and thus a specific therapeutic target is lacking. Here, we reported that the cytochrome P450 (CYP) epoxygenase/epoxide hydrolase (EH) axis was activated in the patients and is likely a therapeutic target for IgAN. Specifically, quantitative profiling of the plasma from IgAN patients and healthy controls revealed significant changes in plasma levels of CYP/EH-mediated lipid epoxides and diols. Subsequently, CYP2C8, CYP2C18, CYP2J2, EPHX1, and EPHX2 were found to be significantly increased in whole blood cells at mRNA levels from the IgAN patients when compared with those of healthy controls. Immunohistochemical analysis showed that all five CYPs and two EHs were upregulated in the kidney tissue from IgAN patients when compared with normative renal tissue, but the expression locations of the proteins were different with most of them. Treatment of HK-2 cells with IgA1 increased cell viability, compressed cell apoptosis, and increased the protein levels of CYP2C9, EPHX1, and EPHX2. All the results agreed that CYPs/EHs axis is likely the prophylactic and therapeutic target for IgAN, providing IgAN patients with a new intervention strategy.
ESTHER : Deng_2022_J.Proteome.Res__
PubMedSearch : Deng_2022_J.Proteome.Res__
PubMedID: 36301320

Title : Development and characterization of a selective chromatographic approach to the rapid discovery of ligands binding to muscarinic-3 acetylcholine receptor - Zhao_2021_J.Chromatogr.A_1653_462443
Author(s) : Zhao X , Fu X , Yuan X , Shayiranbieke A , Xu R , Cao F , Ren J , Liang Q
Ref : Journal of Chromatography A , 1653 :462443 , 2021
Abstract : The pursuit of new ligands binding to muscarinic-3 acetylcholine receptor (M(3)R) is viewed as challenging due to the lack of screening methods with high efficiency. To address such challenges, this work developed and characterized an approach to the rapid discovery of M(3)R ligands using the immobilized receptor as the chromatographic stationary phase. We fused haloalkane dehalogenase (Halo) as a tag at the C-terminus of M(3)R. The fusion M(3)R was immobilized on 6-chlorocaproic acid-activated ammino-microspheres by the specific covalent reaction between the Halo-tag and the linker. Comprehensive characterizations of the immobilized M(3)R were performed by scanning electron microscope, X-ray photoelectron spectroscopy, and the investigation on the binding of three specific ligands to the receptor. The feasibility of the immobilized M(3)R in complex matrices was tested by screening the bioactive compounds in Zhisou oral liquid, assessing the interaction between the screened compounds and the receptor using zonal elution, and evaluating the in vivo activity of the targeted compounds. The results evidenced that the immobilized M(3)R has high specificity, good stability, and the capacity to separate M(3)R ligands from complex matrices. These allowed us to identify naringin, hesperidin, liquiritigenin, platycodin D, and glycyrrhizic acid as the potential ligands of M(3)R. The association constants of the five compounds to M(3)R were 4.44 x 10(4), 1.11 x 10(4), 7.20 x 10(4), 4.15 x 10(4), and 3.36 x 10(4) M(-1). The synergistic application of the five compounds exhibited an equivalent expectorant activity to the original formula. We reasoned that the current method is possible to provide a highly efficient strategy for the discovery of receptor ligands.
ESTHER : Zhao_2021_J.Chromatogr.A_1653_462443
PubMedSearch : Zhao_2021_J.Chromatogr.A_1653_462443
PubMedID: 34365202

Title : Immobilized angiotensin II type I receptor: A powerful method of high throughput screening for antihypertensive compound identification through binding interaction analysis - Liang_2020_J.Chromatogr.A__461003
Author(s) : Liang Q , Fu X , Zhang J , Hao J , Feng G , Wang J , Li Q , Ahmad F , Zhao X
Ref : Journal of Chromatography A , :461003 , 2020
Abstract : The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT1R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT1R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0mum microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT1R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT1R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (kd) of azilsartan, candesartan, valsartan and olmesartan to AT1R were 0.01138 +/- 0.003, 0.05142 +/- 0.003, 0.07547 +/- 0.004 and 0.01310 +/- 0.005 min(-1) by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (KA: 0.12x10(4) and 1.5x10(4)/M) and slower kinetics (kd: 0.6864 +/- 0.03 and 0.3005 +/- 0.01 min(-1)) to the receptor. These results, taking together, indicated that the immobilized AT1R has the capacity to probe antihypertensive compounds.
ESTHER : Liang_2020_J.Chromatogr.A__461003
PubMedSearch : Liang_2020_J.Chromatogr.A__461003
PubMedID: 32156458

Title : The association between polymorphisms in miRNA and the cholinesterase activity of workers in an omethoate-exposed environment - Zou_2020_Int.J.Environ.Health.Res__1
Author(s) : Zou K , Zhou X , Wang W , Shi L , Fu X
Ref : Int J Environ Health Res , :1 , 2020
Abstract : To explore the association between polymorphisms in microRNAs (miRNAs) and the cholinesterase (ChE) activity in omethoate-exposed workers, we recruited 180 omethoate-exposed workers and 115 controls to measure their ChE activity using acetylcholine and dithio-bis-(nitrobenzoic acid) and genotype susceptible SNPs in their miRNA by time-of-flight mass spectrometry. ChE activity in the exposure group was lower than that in the control group (P < 0.001). The analysis of covariance result showed that ChE activity was lower in the (- -/- T) genotype in miR-30a rs111456995 (1.97 +/- 0.47) than in the TT genotype (2.23 +/- 0.59) of the exposure group (P = 0.004). Multivariate linear regression was performed to find influencing factors on ChE activity, and variables kept in the model included omethoate exposure (b = -1.094, P < 0.001), gender (b = -0.381, P < 0.001), miR-30a rs111456995 (- -/- T)(b = -0.248, P < 0.001), and drinking (b = 0.258, P =0.019). The results suggest that individuals carrying a (- -/- T) genotype in miR-30a rs111456995 were more susceptible to damage in their cholinesterase induced by omethoate exposure.
ESTHER : Zou_2020_Int.J.Environ.Health.Res__1
PubMedSearch : Zou_2020_Int.J.Environ.Health.Res__1
PubMedID: 32962420

Title : Donepezil promotes neurogenesis via Src signaling pathway in a rat model of chronic cerebral hypoperfusion - Man_2020_Brain.Res_1736_146782
Author(s) : Man J , Cui K , Fu X , Zhang D , Lu Z , Gao Y , Yu L , Li N , Wang J
Ref : Brain Research , 1736 :146782 , 2020
Abstract : Donepezil, a selective acetylcholinesterase (AchE) inhibitor, enhances stroke-induced neurogenesis within subventricular zone (SVZ). Src/Pyk-2 is one of the downstream pathways of acetylcholine receptors (AchRs), and has been shown to participate in the activation of fibroblast growth factor receptor (FGFR)/epidermal growth factor receptor (EGFR) signaling in cancer cells. In this study, we investigated whether donepezil could promote SVZ neurogenesis in chronic cerebral hypoperfusion (CCH) injury via Src signaling pathway. In the bilateral carotid artery occlusion (2VO) rat model, we observed more nestin/5-bromo-2'-deoxyuridine (BrdU)-positive cells and doublecortin (DCX)/BrdU-positive cells in the SVZ than that in the sham group. Further, donepezil obviously improved neurologic function after 2VO, induced the greater number of SVZ proliferative NSCs and neuroblasts, and elevated levels of Src, p-FGFR1, p-EGFR, p-Akt and p-Raf in ipsilateral SVZ. Lastly, Src inhibitor KX-01 abolished the beneficial effects of donepezil in 2VO rats. These results suggest that donepezil could upregulate Src signaling pathway to enhance CCH-induced SVZ neurogenesis.
ESTHER : Man_2020_Brain.Res_1736_146782
PubMedSearch : Man_2020_Brain.Res_1736_146782
PubMedID: 32184165

Title : The genome of broomcorn millet - Zou_2019_Nat.Commun_10_436
Author(s) : Zou C , Li L , Miki D , Li D , Tang Q , Xiao L , Rajput S , Deng P , Peng L , Jia W , Huang R , Zhang M , Sun Y , Hu J , Fu X , Schnable PS , Chang Y , Li F , Zhang H , Feng B , Zhu X , Liu R , Schnable JC , Zhu JK
Ref : Nat Commun , 10 :436 , 2019
Abstract : Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
ESTHER : Zou_2019_Nat.Commun_10_436
PubMedSearch : Zou_2019_Nat.Commun_10_436
PubMedID: 30683860
Gene_locus related to this paper: panmi-a0a3l6qvl9 , 9poal-a0a2s3hbt0 , panmi-a0a3l6sxg5 , 9poal-a0a2t7cdl4 , panmi-a0a3l6ta96 , panmi-a0a3l6qv47 , panmi-a0a3l6s688 , panmi-a0a3l6tph0

Title : The Rosa genome provides new insights into the domestication of modern roses - Raymond_2018_Nat.Genet_50_772
Author(s) : Raymond O , Gouzy J , Just J , Badouin H , Verdenaud M , Lemainque A , Vergne P , Moja S , Choisne N , Pont C , Carrere S , Caissard JC , Couloux A , Cottret L , Aury JM , Szecsi J , Latrasse D , Madoui MA , Francois L , Fu X , Yang SH , Dubois A , Piola F , Larrieu A , Perez M , Labadie K , Perrier L , Govetto B , Labrousse Y , Villand P , Bardoux C , Boltz V , Lopez-Roques C , Heitzler P , Vernoux T , Vandenbussche M , Quesneville H , Boualem A , Bendahmane A , Liu C , Le Bris M , Salse J , Baudino S , Benhamed M , Wincker P , Bendahmane M
Ref : Nat Genet , 50 :772 , 2018
Abstract : Roses have high cultural and economic importance as ornamental plants and in the perfume industry. We report the rose whole-genome sequencing and assembly and resequencing of major genotypes that contributed to rose domestication. We generated a homozygous genotype from a heterozygous diploid modern rose progenitor, Rosa chinensis 'Old Blush'. Using single-molecule real-time sequencing and a meta-assembly approach, we obtained one of the most comprehensive plant genomes to date. Diversity analyses highlighted the mosaic origin of 'La France', one of the first hybrids combining the growth vigor of European species and the recurrent blooming of Chinese species. Genomic segments of Chinese ancestry identified new candidate genes for recurrent blooming. Reconstructing regulatory and secondary metabolism pathways allowed us to propose a model of interconnected regulation of scent and flower color. This genome provides a foundation for understanding the mechanisms governing rose traits and should accelerate improvement in roses, Rosaceae and ornamentals.
ESTHER : Raymond_2018_Nat.Genet_50_772
PubMedSearch : Raymond_2018_Nat.Genet_50_772
PubMedID: 29713014
Gene_locus related to this paper: rosch-a0a2p6p237 , rosch-a0a2p6r1h5 , rosch-a0a2p6saq0 , rosch-a0a2p6sap4 , rosch-a0a2p6san0 , rosch-a0a2p6san7 , rosch-a0a2p6rkg2 , rosch-a0a2p6pxu1 , rosch-a0a2p6s382 , rosch-a0a2p6s367 , rosch-a0a2p6q0b7 , rosch-a0a2p6pi87 , rosch-a0a2p6p278 , rosch-a0a2p6s545 , rosch-a0a2p6r6x5 , rosch-a0a2p6rqc2

Title : The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis - Shen_2018_Mol.Plant_11_776
Author(s) : Shen Q , Zhang L , Liao Z , Wang S , Yan T , Shi P , Liu M , Fu X , Pan Q , Wang Y , Lv Z , Lu X , Zhang F , Jiang W , Ma Y , Chen M , Hao X , Li L , Tang Y , Lv G , Zhou Y , Sun X , Brodelius PE , Rose JKC , Tang K
Ref : Mol Plant , 11 :776 , 2018
Abstract : Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
ESTHER : Shen_2018_Mol.Plant_11_776
PubMedSearch : Shen_2018_Mol.Plant_11_776
PubMedID: 29703587
Gene_locus related to this paper: artan-a0a2u1ns65 , artan-a0a2u1nuf0 , artan-a0a2u1pw87 , artan-a0a2u1ql98 , artan-a0a2u1n9p7.2 , artan-a0a2u1ky94 , artan-a0a2u1pvq0 , artan-a0a2u1q8x4 , artan-a0a2u1mtd1 , artan-a0a2u1l9j8 , artan-a0a2u1lak5 , artan-a0a2u1lfl1 , artan-a0a2u1lzs1 , artan-a0a2u1m5v6 , artan-a0a2u1n4s5 , artan-a0a2u1qgg7

Title : Oxoisoaporphine alkaloid derivative 8-1 reduces Abeta1-42 secretion and toxicity in human cell and Caenorhabditis elegans models of Alzheimer's disease - Huang_2017_Neurochem.Int_108_157
Author(s) : Huang L , Luo Y , Pu Z , Kong X , Fu X , Xing H , Wei S , Chen W , Tang H
Ref : Neurochem Int , 108 :157 , 2017
Abstract : Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and a growing health problem worldwide. Because the drugs currently used to treat AD have certain drawbacks such as single targeting, there is a need to develop novel multi-target compounds, among which oxoisoaporphine alkaloid derivatives are promising candidates. In this study, the possible anti-AD activities of 14 novel oxoisoaporphine alkaloid derivatives that we synthesized were screened and evaluated. We found that, in the 14 novel derivatives, compound 8-1 significantly reduced Abeta1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human beta-amyloid precursor protein (APPsw). Next, we found that compound 8-1 could down-regulate the expression level of beta-amyloid precursor protein (APP) in APPsw cells. Moreover, compound 8-1 significantly delayed paralysis in the Abeta1-42-transgenic Caenorhabditis elegans strain GMC101, which could be explained by the fact that compound 8-1 down-regulated acetylcholinesterase activity, protected against H2O2-induced acute oxidative stress and paraquat-induced chronic oxidative stress, and enhanced autophagy activity. Taken together, our data suggest that compound 8-1 could attenuate the onset and development of AD.
ESTHER : Huang_2017_Neurochem.Int_108_157
PubMedSearch : Huang_2017_Neurochem.Int_108_157
PubMedID: 28286208

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

Title : Dibenzo-alpha-pyrones: a new class of larvicidal metabolites against Aedes aegypti from the endophytic fungus Hyalodendriella sp. Ponipodef12 - Mao_2017_Pest.Manag.Sci_73_1478
Author(s) : Mao Z , Lai D , Liu X , Fu X , Meng J , Wang A , Wang X , Sun W , Liu ZL , Zhou L , Liu Y
Ref : Pest Manag Sci , 73 :1478 , 2017
Abstract : BACKGROUND: In our search for new agrochemicals from endophytic fungi, the crude extract of the endophytic Hyalodendriella sp. Ponipodef12 associated with the hybrid 'Neva' of Populus deltoides Marsh x P. nigra L. was found to possess larvicidal activity against Aedes aegypti.
RESULTS: Fractionation of the extract has led to the isolation of 11 dibenzo-alpha-pyrones (1-11), including three new congeners: hyalodendriols A-C (1-3). The structures of the new compounds were elucidated by comprehensive spectroscopic analyses, including the modified Mosher's method for the assignment of the absolute configuration. Compounds 2-7 showed potent larvicidal activities against the fourth-instar larvae of A. aegypti with IC50 values ranging from 7.21 to 120.81 microg mL-1 . Among them, penicilliumolide D (6) displayed the strongest activity (IC50 = 7.21 microg mL-1 ). A structure-larvicidal activity relationship was discussed. The possible mode of action of these compounds was assessed for their acetylcholinesterase inhibitory activities. In addition, hyalodendriol C (3) displayed antibacterial activity against Bacillus subtilis and Xanthomonas vesicatoria, and exhibited strong inhibition against the spore germination of Magnaporthe oryzae. CONCLUSION: Our study revealed dibenzo-alpha-pyrones to be a new class of larvicidal metabolites against A. aegypti. (c) 2016 Society of Chemical Industry.
ESTHER : Mao_2017_Pest.Manag.Sci_73_1478
PubMedSearch : Mao_2017_Pest.Manag.Sci_73_1478
PubMedID: 27862895

Title : ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice - Wang_2017_Behav.Brain.Res_316_145
Author(s) : Wang J , Fu X , Zhang D , Yu L , Li N , Lu Z , Gao Y , Wang M , Liu X , Zhou C , Han W , Yan B
Ref : Behavioural Brain Research , 316 :145 , 2017
Abstract : The mechanisms of post-stroke neurogenesis in the subventricular zone (SVZ) are unclear. However, neural stem cell-intrinsic and neurogenic niche mechanisms, as well as neurotransmitters, have been shown to play important roles in SVZ neurogenesis. Recently, a previously unknown population of choline acetyltransferase (ChAT)+ neurons residing in rodent SVZ were identified to have direct control over neural stem cell proliferation by indirectly activating fibroblast growth factor receptor (FGFR). This finding revealed possible neuronal control over SVZ neurogenesis. In this study, we assessed whether these ChAT+ neurons also participate in stroke-induced neurogenesis. We used a permanent middle cerebral artery occlusion (MCAO) model produced by transcranial electrocoagulation in mice, atropine (muscarinic cholinergic receptor [mAchR] antagonist), and donepezil (acetylcholinesterase inhibitor) to investigate the role of ChAT+ neurons in stroke-induced neurogenesis. We found that mAchRs, phosphorylated protein kinase C (p-PKC), and p-38 levels in the SVZ were upregulated in mice on day 7 after MCAO. MCAO also significantly increased the number of BrdU/doublecortin-positive cells and protein levels of phosphorylated-neural cell adhesion molecule and mammalian achaete scute homolog-1. FGFR was activated in the SVZ, and doublecortin-positive cells increased in the peri-infarction region. These post-stroke neurogenic effects were enhanced by donepezil and partially decreased by atropine. Neither atropine nor donepezil affected peri-infarct microglial activation or serum concentrations of TNF-alpha, IFN-gamma, or TGF-beta on day 7 after MCAO. We conclude that ChAT+ neurons in the SVZ may participate in stroke-induced neurogenesis, suggesting a new mechanism for neurogenesis after stroke.
ESTHER : Wang_2017_Behav.Brain.Res_316_145
PubMedSearch : Wang_2017_Behav.Brain.Res_316_145
PubMedID: 27609645

Title : Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex - Huang_2013_J.Clin.Invest_123_3815
Author(s) : Huang Y , Wu Z , Riwanto M , Gao S , Levison BS , Gu X , Fu X , Wagner MA , Besler C , Gerstenecker G , Zhang R , Li XM , Didonato AJ , Gogonea V , Tang WH , Smith JD , Plow EF , Fox PL , Shih DM , Lusis AJ , Fisher EA , Didonato JA , Landmesser U , Hazen SL
Ref : J Clinical Investigation , 123 :3815 , 2013
Abstract : Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
ESTHER : Huang_2013_J.Clin.Invest_123_3815
PubMedSearch : Huang_2013_J.Clin.Invest_123_3815
PubMedID: 23908111

Title : Active screen plasma surface modification of polycaprolactone to improve cell attachment - Fu_2012_J.Biomed.Mater.Res.B.Appl.Biomater_100_314
Author(s) : Fu X , Sammons RL , Bertoti I , Jenkins MJ , Dong H
Ref : J Biomed Mater Res B Appl Biomater , 100 :314 , 2012
Abstract : To tailor polycaprolactone (PCL) surface properties for biomedical applications, film samples of PCL were surface modified by the active screen plasma nitriding (ASPN) technique. The chemical composition and structure were characterized by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The wettability of the surface modified polymers was investigated by contact angle and surface energy methods. Biocompatibility of the prepared PCL samples was evaluated in vitro using MC3T3-E1 osteoblast-like cells. The degradability was assessed by determining the self-degradation rate (catalyzed by lipase). The results show that ASPN surface modification can effectively improve osteoblast cell adhesion and spreading on the surface of PCL. The main change in chemical composition is the exchange of some carboxyl groups on the surface for hydroxyl groups. The active-screen plasma nitriding technique has been found to be an effective and practical method to effectively improve osteoblast cell adhesion and spreading on the PCL surface. Such changes have been attributed to the increase in wettablity and generation of new hydroxyl groups by plasma treatment. After active-screen plasma treatment, the PCL film is still degradable, but the enzymatic degradation rate is slower compared with untreated PCL film.
ESTHER : Fu_2012_J.Biomed.Mater.Res.B.Appl.Biomater_100_314
PubMedSearch : Fu_2012_J.Biomed.Mater.Res.B.Appl.Biomater_100_314
PubMedID: 22179939

Title : The macro domain protein family: structure, functions, and their potential therapeutic implications - Han_2011_Mutat.Res_727_86
Author(s) : Han W , Li X , Fu X
Ref : Mutat Res , 727 :86 , 2011
Abstract : Macro domains are ancient, highly evolutionarily conserved domains that are widely distributed throughout all kingdoms of life. The 'macro fold' is roughly 25kDa in size and is composed of a mixed alpha-beta fold with similarity to the P loop-containing nucleotide triphosphate hydrolases. They function as binding modules for metabolites of NAD(+), including poly(ADP-ribose) (PAR), which is synthesized by PAR polymerases (PARPs). Although there is a high degree of sequence similarity within this family, particularly for residues that might be involved in catalysis or substrates binding, it is likely that the sequence variation that does exist among macro domains is responsible for the specificity of function of individual proteins. Recent findings have indicated that macro domain proteins are functionally promiscuous and are implicated in the regulation of diverse biological functions, such as DNA repair, chromatin remodeling and transcriptional regulation. Significant advances in the field of macro domain have occurred in the past few years, including biological insights and the discovery of novel signaling pathways. To provide a framework for understanding these recent findings, this review will provide a comprehensive overview of the known and proposed biochemical, cellular and physiological roles of the macro domain family. Recent data that indicate a critical role of macro domain regulation for the proper progression of cellular differentiation programs will be discussed. In addition, the effect of dysregulated expression of macro domain proteins will be considered in the processes of tumorigenesis and bacterial pathogenesis. Finally, a series of observations will be highlighted that should be addressed in future efforts to develop macro domains as effective therapeutic targets.
ESTHER : Han_2011_Mutat.Res_727_86
PubMedSearch : Han_2011_Mutat.Res_727_86
PubMedID: 21421074