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Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.
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The degradation of chlorophyll during fruit development is essential to reveal a more 'ripe' color that signals readiness to wild dispersers of seeds and the human consumer. Here, comparative biochemical analysis of developing fruit of Actinidia deliciosa cv. Xuxiang ('XX', green-fleshed) and Actinidia chinensis cv. Jinshi No.1 ('JS', yellow-fleshed) indicated that variation in chlorophyll content is the major contributor to differences in flesh color. Four differentially expressed candidate genes were identified: the down-regulated genes AcCRD1 and AcPOR1 involved in chlorophyll biosynthesis, and the up-regulated genes AcSGR1 and AcSGR2 driving chlorophyll degradation. Prochlorophyllide and chlorophyllide, the metabolites produced by AcCRD1 and AcPOR1, progressively reduced in 'JS', but not in 'XX', indicating that chlorophyll biosynthesis was less active in yellow-fleshed fruit. AcSGR1 and AcSGR2 were verified to be involved in chlorophyll degradation, using both transient expression in tobacco and stable overexpression in kiwifruit. Furthermore, a homeobox-leucine zipper (HD-Zip II), AcHZP45, showed significantly increased expression during 'JS' fruit ripening, which led to both repressed expression of AcCRD1 and AcPOR1 and activated expression of AcSGR1 and AcSGR2. Collectively, the present study indicated that different dynamics of chlorophyll biosynthesis and degradation coordinate the changes in chlorophyll content in kiwifruit flesh, which are orchestrated by the key transcription factor AcHZP45.
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Actinidia , Humanos , Actinidia/genética , Clorofila/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
ß-ionone, an apocarotenoid derived from a C40 terpenoid has an intense, woody smell and a low odor threshold that has been widely used in as an ingredient in food and cosmetics. Yarrowia lipolytica is a promising host for ß-ionone production because of its oleaginous nature, its ability to produce high levels of acetyl-CoA (an important precursor for terpenoids), and the availability of synthetic biology tools to engineer the organism. In this study, ß-carotene-producing Y. lipolytica strain XK17 was employed for ß-ionone biosynthesis. First, we explored the effect of different sources of carotenoid cleavage dioxygenase (CCD) genes on ß-ionone production. A high-yielding strain rUinO-D14 with 122 mg/L of ß-ionone was obtained by screening promoters combined with rDNA mediated multi-round iterative transformations to optimize the expression of the CCD gene of Osmanthus fragrans. Second, to further develop a high-level production strain for ß-ionone, we optimized key genes in the mevalonate pathway by multi-round iterative transformations mediated by non-homologous end joining, combined with a protein tagging strategy. Finally, the introduction of a heterologous oxidoreductase pathway enabled the engineered Y. lipolytica strain to use xylose as a sole carbon source and produce ß-ionone. In addition, the potential for use of lignocellulosic hydrolysate as the carbon source for ß-ionone production showed that the NHA-A31 strain had a high ß-ionone productivity level. This study demonstrates that engineered Y. lipolytica can be used for the efficient, green and sustainable production of ß-ionone.
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WD repeat domain 19 (Wdr19) is a major component of the intraflagellar transport (IFT) machinery, which is involved in the function of primary cilia. However, the effects of Wdr19 on primary cilia formation, cystogenesis, and polycystic kidney disease (PKD) progression remain unclear. To study these effects, we generated three lines of kidney-specific conditional knockout mice: Wdr19-knockout (Wdr19-KO, Wdr19f/- ::Cdh16-CreTg/0 ), Pkd1-knockout (Pkd1-KO, Pkd1f/- ::Cdh16-CreTg/0 ), and Wdr19/Pkd1-double knockout (Wdr19&Pkd1-dKO, Wdr19f/- ;Pkd1f/- ::Cdh16-CreTg/0 ) mice. Ultrastructural analysis using transmission electron microscopy (TEM) indicated that the primary cilia were almost absent at postnatal day 10 in Wdr19-KO mice compared with Pkd1-KO and wild-type (WT) mice. However, the primary cilia appeared structurally normal even if malfunctional in Pkd1-deficient cysts. The Pkd1-KO mice had the most severe PKD progression, including the shortest lifespan (14 days) and the largest renal cysts, among the three knockout lines. Thus, the molecular mechanism of renal cystogenesis in Wdr19-KO mice (primary cilia abrogation) was different from that in Pkd1-KO mice (primary cilia malfunction). In summary, Wdr19 deficiency leads to primary cilia abrogation and renal cyst formation. Wdr19 is primarily proposed to participate in retrograde IFT and to be crucial for the construction of primary cilia, which are critical organelles for tubulogenesis in the developing kidneys. © 2022 The Pathological Society of Great Britain and Ireland.
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Cistos , Proteínas do Citoesqueleto/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Doenças Renais Policísticas , Rim Policístico Autossômico Dominante , Animais , Caderinas , Cistos/patologia , Modelos Animais de Doenças , Rim/patologia , Camundongos , Camundongos Knockout , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Canais de Cátion TRPP/genéticaRESUMO
BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.
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Coreia , Distonia , Proteínas de Membrana , Adolescente , Criança , Feminino , Humanos , Masculino , Coreia/genética , Distonia/genética , Proteínas de Membrana/metabolismo , Mutação/genética , FenótipoRESUMO
Two unique polyoxometalate (POM)-encapsulated tubular materials with the formula K(H2O)6[M6(btp)6(H2O)22](P2W18O62)3(Hbtp)5(btp)3·52H2O [M = Mn (1) and Co (2); btp = 2,6-bis(1,2,4-triazol-1-yl)pyridine] were designed and synthesized based on the Dawson POM and V-type btp ligand, as confirmed by IR, X-ray diffraction (XRD), and element analysis. Single-crystal XRD analyses of compound 1 show that two kinds of remarkable metal-organic supramolecular nanotubes, including trigonal and hexagonal nanotubes, are constructed along the c-axis direction via π···π-packing interactions between {Mn3(btp)3} rings and the btp ligands, of which [α-P2W18O62]6- anions are confined in channels, making the entire structure extraordinarily stable. Meanwhile, the coordinated [α-P2W18O62]6- anion within the hexagonal channel makes the channel highly hydrophilic and attracts a number of guest water molecules to fill in the free space, conducive to proton transport. Therefore, the single-crystal sample of 1 exhibits a high proton conductivity of 6.39 × 10-3 S cm-1 along one-dimensional channels, 30 times higher than that of a pellet sample at 358 K and 98% relative humidity.
RESUMO
Four novel isopolymolybdate-based coordination polymers (CPs), constructed from 2,6-bis(1,2,4-triazol-1-yl)pyridine (btp), 1,3-bis(4H-1,2,4-triazol-4-yl)benzene (btb), and 3,5-bis(1-imidazolium)pyridine (bip), have been synthesized under a hydrothermal method: {[Co(btp)(H2O)2(ß-Mo8O26)0.5]·3H2O}n (1), [Ni(btp)(H4Mo6O22)0.5]n (2), [Co(btb)(H2O)(ß-Mo8O26)0.5]n (3), and {[Co(Hbip)2(H2O)2(γ-Mo8O26)]·6H2O}n (4). Complex 1 exhibits one 3D framework with an unexpected 3-nodal 2,4,6-c net topology containing the 1D {ß-Mo8O26}n chains, 6-connected CoII centers, and V-type coordinated btp ligands. The neighboring [Mo6O22]4- anions of complex 2 are bridged by the NiII centers to build one 2D {Ni2(Mo6O22)} network, which is arranged into the 3D framework through the weak π···π stacking interactions. In compound 3, one 3D framework is formed by the adjacent 1D {Co2(btp)2}n chains connected by {ß-Mo8O26}n units, which demonstrates a rare 4,6-c fsc topology. In complex 4, one 2D {Co(Hbip)2(γ-Mo8O26)} layer with a (4, 4) network is connected to one 3D hydrogen-bonding framework via N-H···O and O-H···O hydrogen bonds. Magnetic data indicate that complexes 1 and 4 exhibit antiferromagnetic behaviors, whereas complexes 2 and 3 reveal spin-canting magnetic behavior and metamagnetic behavior, respectively. In addition, the proton conductivity of complexes 3 and 4 was investigated, showing that compound 4 has good proton conductivity at 85 °C and a relative humidity of 98% RH.
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OBJECTIVE: To examine whether the association of prepregnancy body mass index (BMI) with fetal macrosomia is mediated through maternal circulating lipid concentrations during pregnancy. STUDY DESIGN: In this prospective cohort, 3011 eligible pregnant women were enrolled. Information on demographic characteristics were collected using questionnaires, and anthropometrics and laboratory tests were performed at 24 weeks of gestation and before delivery. Macrosomia was defined as birth weight ≥4000 g. Logistic regression and multivariable linear regression, adjusted for age, fetal sex, education, gestational weight gain, fasting blood glucose, gestational diabetes, gestational hypertension, gestational age at delivery, delivery mode, and parity, were used to assess the mediation path between prepregnancy BMI, maternal serum lipids, and fetal macrosomia. RESULTS: A total of 2454 participants with completed records were included in the final analyses. Among the maternal circulating lipid biomarkers, only triglyceride was significantly associated with both prepregnancy BMI and fetal macrosomia risk, adjusting for potential confounders. Mediation analyses demonstrated that the direct effect of prepregnancy BMI on fetal macrosomia was 0.0085 (95% CI, 0.0003-0.018; P < .05), the indirect effect mediated through maternal serum triglycerides was 0.0016 (95% CI, 0.0007-0.0029; P < .001), and the estimated proportion of mediated effect was 15.7% (P < .05). CONCLUSIONS: Maternal circulating triglycerides mediate the association of prepregnancy BMI with the risk of fetal macrosomia.
Assuntos
Índice de Massa Corporal , Macrossomia Fetal/sangue , Triglicerídeos/sangue , Adulto , China , Estudos de Coortes , Feminino , Macrossomia Fetal/diagnóstico , Macrossomia Fetal/epidemiologia , Humanos , Recém-Nascido , Lipoproteínas/sangue , Modelos Logísticos , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Streptomycetes from the rhizospheric soils are a rich resource of novel secondary metabolites with various biological activities. However, there is still little information related to the isolation, antimicrobial activity and biosynthetic potential for polyketide and non-ribosomal peptide discovery associated with the rhizospheric streptomycetes of Panax notoginseng. Thus, the aims of the present study are to (i) identify culturable streptomycetes from the rhizospheric soil of P. notoginseng by 16S rRNA gene, (ii) evaluate the antimicrobial activities of isolates and analyze the biosynthetic gene encoding polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) of isolates, (iii) detect the bioactive secondary metabolites from selected streptomycetes, (iv) study the influence of the selected isolate on the growth of P. notoginseng in the continuous cropping field. This study would provide a preliminary basis for the further discovery of the secondary metabolites from streptomycetes isolated from the rhizospheric soil of P. notoginseng and their further utilization for biocontrol of plants. RESULTS: A total of 42 strains representing 42 species of the genus Streptomyces were isolated from 12 rhizospheric soil samples in the cultivation field of P. notoginseng and were analyzed by 16S rRNA gene sequencing. Overall, 40 crude cell extracts out of 42 under two culture conditions showed antibacterial and antifungal activities. Also, the presence of biosynthesis genes encoding type I and II polyketide synthase (PKS I and PKS II) and nonribosomal peptide synthetases (NRPSs) in 42 strains were established. Based on characteristic chemical profiles screening by High Performance Liquid Chromatography-Diode Array Detector (HPLC-DAD), the secondary metabolite profiles of strain SYP-A7257 were evaluated by High Performance Liquid Chromatography-High Resolution Mass Spectrometry (HPLC-HRMS). Finally, four compounds actinomycin X2 (F1), fungichromin (F2), thailandin B (F7) and antifungalmycin (F8) were isolated from strain SYP-A7257 by using chromatography techniques, UV, HR-ESI-MS and NMR, and their antimicrobial activities against the test bacteria and fungus were also evaluated. In the farm experiments, Streptomyces sp. SYP-A7257 showed healthy growth promotion and survival rate improvement of P. notoginseng in the continuous cropping field. CONCLUSIONS: We demonstrated the P. notoginseng rhizospheric soil-derived Streptomyces spp. distribution and diversity with respect to their metabolic potential for polyketides and non-ribosomal peptides, as well as the presence of biosynthesis genes PKS I, PKS II and NRPSs. Our results showed that cultivatable Streptomyces isolates from the rhizospheric soils of P. notoginseng have the ability to produce bioactive secondary metabolites. The farm experiments suggested that the rhizospheric soil Streptomyces sp. SYP-A7257 may be a potential biological control agent for healthy growth promotion and survival rate improvement of P. notoginseng in the continuous cropping field.
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Panax notoginseng/microbiologia , Peptídeo Sintases/genética , Policetídeo Sintases/genética , Streptomyces/classificação , Proteínas de Bactérias/genética , Cromatografia Líquida de Alta Pressão , DNA Bacteriano/genética , DNA Ribossômico/genética , Dactinomicina/análogos & derivados , Dactinomicina/isolamento & purificação , Farmacorresistência Bacteriana , Macrolídeos/isolamento & purificação , Filogenia , Polienos/isolamento & purificação , RNA Ribossômico 16S/genética , Rizosfera , Metabolismo Secundário , Microbiologia do Solo , Streptomyces/genética , Streptomyces/isolamento & purificaçãoRESUMO
Kiwifruit (Actinidia spp.) is a climacteric fruit with high sensitivity to ethylene, influenced by multiple ethylene-responsive structural genes and transcription factors. However, the roles of other post-transcriptional regulators (e.g. miRNAs) necessary for ripening remain elusive. High-throughput sequencing sRNAome, degradome and transcriptome methods were used to identify further contributors to ripening control in the kiwifruit (A. deliciosa cv 'Hayward'). Two NAM/ATAF/CUC domain transcription factors (AdNAC6 and AdNAC7), both predicted targets for miR164, showed significant upregulation by exogenous ethylene. Gene expression analysis and luciferase reporter assays indicated that Ade-miR164 and one of its precursor miRNAs (Ade-MIR164b) were repressed by ethylene treatment and negatively correlated with AdNAC6/7 expression. Subsequent analysis indicated that both AdNAC6 and AdNAC7 proteins are transcriptional activators and physically bind the promoters of AdACS1 (1-aminocyclopropane-1-carboxylate synthase), AdACO1 (1-aminocyclopropane-1-carboxylic acid oxidase), AdMAN1 (endo-ß-mannanase) and AaTPS1 (terpene synthase). Moreover, subcellular analysis indicated that the location of the AdNAC6/7 proteins was influenced by Ade-miR164. Multiple omics-based approaches revealed a novel regulatory link for fruit ripening that involved ethylene-miR164-NAC. The regulatory pathway for miR164-NAC is present in various fruit (e.g. Rosaceae fruit, citrus, grape), with implications for fruit ripening regulation.
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Actinidia/fisiologia , Frutas/crescimento & desenvolvimento , Estudo de Associação Genômica Ampla , MicroRNAs , RNA de Plantas/metabolismo , RNA não Traduzido/metabolismo , DNA de Plantas/genética , Frutas/metabolismo , Genoma de Planta , Filogenia , Regiões Promotoras Genéticas , RNA de Plantas/genética , RNA não Traduzido/genéticaRESUMO
PURPOSE: Patients with schizophrenia (SCZ) have a higher prevalence of known risk factors for obstructive sleep apnea (OSA). This study aims to determine if SCZ patients are at increased risk of incident OSA. METHODS: A total of 5092 newly diagnosed SCZ patients and 5092 non-SCZ controls matched by gender, age, and index year were included between 2000 and 2012 and followed to 2013. Participants newly diagnosed with OSA were defined as incidents. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence intervals (CI) of the OSA incidence rate between the two groups studied. RESULTS: SCZ patients were at increased risk of OSA compared to non-SCZ controls after adjusting for gender, age, comorbidities, and duration of antipsychotic use (2.12 versus 1.01 per 1000 person-years, HR: 1.97, 95% CI: 1.36-2.85). Also, this study confirmed the existence of some known risk factors for OSA, including male gender (HR 1.65, 95% CI 1.14-2.37), obesity (HR 2.62, 95% CI 1.19-5.80), hypertension (HR 1.61, 95% CI 1.06-2.47), hyperlipidemia (HR 1.55, 95% CI 1.04-2.38), diabetes (HR 1.53, 95% CI 1.01-2.38), and antipsychotic use (duration < 1 year (HR 1.57, 95% CI 1.13-2.37), 1-3 years (HR 1.62, 95% CI 1.06-2.82), and 3-5 years (HR 1.45, 95% CI 1.06-2.44)). CONCLUSION: This study shows SCZ patients are at increased risk of OSA, and there is still an association with higher risk of OSA after controlling for known risk factors, indicating that it is necessary to develop targeted interventions in SCZ patients to reduce the negative impact of OSA on health.
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Hipertensão , Esquizofrenia , Apneia Obstrutiva do Sono , Estudos de Coortes , Humanos , Hipertensão/epidemiologia , Masculino , Fatores de Risco , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Apneia Obstrutiva do Sono/epidemiologiaRESUMO
BACKGROUND: Water is generally considered to be a safe and green solvent suitable for use in natural product extraction. In this study, an eco-friendly subcritical water method was used to extract pectin from waste jackfruit peel (JFP-S), which was compared with pectin obtained by the traditional citric acid method (JFP-C). RESULTS: The extraction process was optimized using response surface methodology (RSM), and the optimum process parameters were as follows: extraction temperature 138 °C, extraction time 9.15 min, liquid / solid (L/S) ratio 17.03 mL g-1 . Under these conditions, the pectin yield was 149.6 g kg-1 (dry basis). Pectin obtained from the two extraction methods displayed a high degree of esterification and the monosaccharide composition was consistent. The galacturonic acid content of JFP-S and JFP-C was 52.27% and 56.99%, respectively. JFP-S had more hairy regions and side chains than JFP-C. The molecular weight of JFP-S was 113.3 kDa, which was significantly lower than that of JFP-C (174.3 kDa). Fourier-transform infrared spectroscopy (FTIR) indicated that two samples had similar pectin typical absorption peaks. According to differential scanning calorimetry (DSC), both JFP-S and JFP-C had relatively good thermal stability. JFP-S demonstrated lower apparent viscosity and elasticity than JFP-C. Meanwhile, the G' and G'' moduli of JFP-S were lower, which found expression in the gel textural characterization of the samples. CONCLUSION: This work showed that the subcritical water method is an efficient, time-saving, and eco-friendly technology for the extraction of pectin from jackfruit peel compared with the traditional citric acid method. The physicochemical properties of pectin could be changed during subcritical water extraction. © 2019 Society of Chemical Industry.
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Artocarpus/química , Química Verde/métodos , Pectinas/química , Pectinas/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Resíduos/análise , Esterificação , Peso Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , ViscosidadeRESUMO
A novel 1(2), 2(18)-diseco indole diterpenoid, drechmerin H (1), was isolated from the fermentation broth of Drechmeria sp. together with a new indole diterpenoid, 2'-epi terpendole A (3), and a known analogue, terpendole A (2). Their structures were determined by HRESIMS, 1D and 2D NMR, ECD, and X-ray single crystal diffraction analyses as well as quantum chemical calculation. The abosulte configuration of terpendole A (2) was determined for the first time. Compound 1 displayed the significant agonistic effect on pregnane X receptor (PXR) with EC50 value of 134.91⯱â¯2.01â¯nM, and its interaction with PXR was investigated by molecular docking. Meantime, a plausible biosynthetic pathway for compounds 1-3 is also discussed in the present work.
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Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Hypocreales/química , Indóis/farmacologia , Receptor de Pregnano X/agonistas , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Indóis/química , Indóis/isolamento & purificação , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Eighteen secondary metabolites were isolated from the fermentation broth of the endophytic fungus Xylaria sp. SYPF 8246, including four new compounds, xylarianins A-D (1-4), three new natural products, 6-methoxycarbonyl-2'-methyl-3,5,4',6'-tetramethoxy-diphenyl ether (5), 2-chlor-6-methoxycarbonyl-2'-rnethyl-3,5,4',6'-tetramethoxy-diphenyl ether (6), and 2-chlor-4'-hydroxy-6-methoxy carbonyl-2'-methyl-3,5,6'-trimethoxy-diphenyl ether (7), and eleven known compounds (8-18). Their structural elucidations were conducted by using 1D and 2D NMR, HRESIMS, and Rh2(OCOCF3)4-induced electronic circular dichroism (ECD) spectra analyses. The integrated 1H and 13C NMR data of three new natural products 5-7 were reported for the first time. All the isolated compounds were assayed for their inhibitory activities against human carboxylesterase 2 (hCE 2). Compounds 1, 5-9, and 18 displayed significant inhibitory activities against hCE 2 with IC50 values of 10.43⯱â¯0.51, 6.69⯱â¯0.85, 12.36⯱â¯1.27, 18.25⯱â¯1.78, 29.78⯱â¯0.48, 18.86⯱â¯1.87, and 20.72⯱â¯1.51⯵M, respectively. The interactions between compounds 1 and 5 with hCE 2 were anaylzed by molecular docking.
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Benzofenonas/química , Carboxilesterase/antagonistas & inibidores , Succinatos/química , Xylariales/química , Benzofenonas/isolamento & purificação , Carboxilesterase/química , Domínio Catalítico , Humanos , Cinética , Simulação de Acoplamento Molecular , Metabolismo Secundário , Succinatos/isolamento & purificação , Xylariales/metabolismoRESUMO
The development of an effective malaria vaccine has remained elusive even until today. This is because of our incomplete understanding of the immune mechanisms that confer and/or correlate with protection. Human volunteers have been protected experimentally from a subsequent challenge by immunization with Plasmodium falciparum sporozoites under drug cover. Here, we demonstrate that sera from the protected individuals contain neutralizing antibodies against the pre-erythrocytic stage. To identify the antigen(s) recognized by these antibodies, a newly developed library of P. falciparum antigens was screened with the neutralizing sera. Antibodies from protected individuals recognized a broad antigenic repertoire of which three antigens, PfMAEBL, PfTRAP and PfSEA1 were recognized by most protected individuals. As a proof of principle, we demonstrated that anti-PfMAEBL antibodies block liver stage development in human hepatocytes. Thus, these antigens identified are promising targets for vaccine development against malaria.
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Anticorpos Antiprotozoários/biossíntese , Antígenos de Protozoários/imunologia , Imunidade Humoral , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Receptores de Superfície Celular/imunologia , Animais , Anticorpos Neutralizantes/biossíntese , Antígenos de Protozoários/genética , Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Reações Cruzadas , Expressão Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/imunologia , Hepatócitos/parasitologia , Humanos , Soros Imunes/química , Vacinas Antimaláricas/administração & dosagem , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Biblioteca de Peptídeos , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Receptores de Superfície Celular/genética , Esporozoítos/imunologia , VacinaçãoRESUMO
A Gram-stain-positive, rod-shaped, motile bacterium designated as SYP-B691T was isolated from rhizospheric soil of Panax notoginseng. Phylogenetic analysis indicated that SYP-B691T clearly represented a member of the genus Bacillus and showed 16S rRNA gene similarity lower than 97.0â% with the type strains of species of the genus Bacillus, which indicates that it should be considered as a candidate novel species within this genus. The optimum growth of the strain was found to occur at 37 °C and pH 7.0-9.0. The genomic DNA G+C content was determined to be 45.2 mol%. It contained meso-2,6-diaminopimelic acid in the cell-wall peptidoglycan. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unknown phospholipid. MK-7 was the only menaquinone identified. The major cellular fatty acids of SYP-B691T were identified as iso-C15â:â0 and anteiso-C15â:â0. On the basis of phenotypic, chemotaxonomic and phylogenetic characteristics, SYP-B691T merits recognition as a representative of a novel species of the genus Bacillus, for which the name Bacillus notoginsengisoli sp. nov. is proposed, with SYP-B691T(=DSM 29196T=JCM 30743T) as the type strain.
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Bacillus/classificação , Panax notoginseng/microbiologia , Filogenia , Rizosfera , Microbiologia do Solo , Bacillus/genética , Bacillus/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfatidilgliceróis/análise , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
A Gram-stain-positive, aerobic actinobacterial strain (designated SYP-A7299T), which displayed a rod-coccus growth lifecycle, was isolated from the rhizosphere of Ginkgo biloba L. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SYP-A7299T belongs to the genus Arthrobacter and is most closely related to Arthrobacter halodurans JSM 078085T (97.4â% 16S rRNA gene sequence similarity). The DNA-DNA relatedness value between strain SYP-A7299T and A. halodurans JSM 078085T was 37â% ±2.9. The cell-wall peptidoglycan was A4α, and glucose and galactose were whole-cell sugars. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two glycolipids and an unknown polar lipid. The major menaquinone were MK-8(H2) (72â%) and MK-9(H2) (28â%), and the predominant cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The DNA G+C content was 68.9 mol%. Based on the morphological, physiological, biochemical and chemotaxonomic characters presented in this study, strain SYP-A7299T represents a novel species of the genus Arthrobacter, for which the name Arthrobacter ginkgonis sp. nov. is proposed. The type strain is SYP-A7299T (=DSM 100491T=KCTC 39â592T).
Assuntos
Arthrobacter/classificação , Ginkgo biloba/microbiologia , Filogenia , Rizosfera , Microbiologia do Solo , Arthrobacter/genética , Arthrobacter/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácidos Graxos/química , Glicolipídeos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/químicaRESUMO
In the search for biologically active compounds from the roots of Bupleurum chinense D C., phytochemical investigation of its ethanol extract led to the isolation and identification of a new 8-O-4' neolignan glucoside, saikolignanoside A (1), along with eight known lignans (2-9). Their structures were determined on the basis of IR, UV, HRESIMS, and NMR spectroscopic analyses. The antioxidant and cytotoxic effects of isolated compounds were evaluated in vitro. The isolated compounds (IC50 > 200 µM) did not display 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Whereas compounds 1-2, 5, 7, and 9 exhibited potent 2, 2'-azinobis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging properties with IC50 values ranging from 8.34 to 15.24 µM, while compounds 3-4, 6, 8 showed moderate properties. In addition, all compounds were evaluated for cytotoxicities against A549, HepG2, U251, Bcap-37, and MCF-7 cell lines. Compounds 5 and 9 (IC50 < 51.62 µM) possessed stronger cytotoxic activities against all the tested tumor cell lines, compared with the positive control 5-Fluorouracil.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Bupleurum/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Antineoplásicos Fitogênicos/química , Antioxidantes/química , Benzotiazóis/química , Compostos de Bifenilo/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/farmacologia , Humanos , Concentração Inibidora 50 , Lignanas/química , Células MCF-7 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Picratos/farmacologia , Raízes de Plantas/químicaRESUMO
Endothelial dysfunction is a key early step in atherosclerosis. 25-Hydroxycholesterol (25-OHC) is found in atherosclerotic lesions. However, whether 25-OHC promotes atherosclerosis is unclear. Here, we hypothesized that 25-OHC, a proinflammatory lipid, can impair endothelial function, which may play an important role in atherosclerosis. Bovine aortic endothelial cells were incubated with 25-OHC. Endothelial cell proliferation, migration, and tube formation were measured. Nitric oxide (NO) production and superoxide anion generation were determined. The expression and phosphorylation of endothelial NO synthase (eNOS) and Akt as well as the association of eNOS and heat shock protein (HSP)90 were detected by immunoblot analysis and immunoprecipitation. Endothelial cell apoptosis was monitored by TUNEL staining and caspase-3 activity, and expression of Bcl-2, Bax, cleaved caspase-9, and cleaved caspase-3 were detected by immunoblot analysis. Finally, aortic rings from Sprague-Dawley rats were isolated and treated with 25-OHC, and endothelium-dependent vasodilation was evaluated. 25-OHC significantly inhibited endothelial cell proliferation, migration, and tube formation. 25-OHC markedly decreased NO production and increased superoxide anion generation. 25-OHC reduced the phosphorylation of Akt and eNOS and the association of eNOS and HSP90. 25-OHC also enhanced endothelial cell apoptosis by decreasing Bcl-2 expression and increasing cleaved caspase-9 and cleaved caspase-3 expressions as well as caspase-3 activity. 25-OHC impaired endothelium-dependent vasodilation. These data demonstrated that 25-OHC could impair endothelial function by uncoupling and inhibiting eNOS activity as well as by inducing endothelial cell apoptosis. Our findings indicate that 25-OHC may play an important role in regulating atherosclerosis.
Assuntos
Endotélio/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Hidroxicolesteróis/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Desacopladores/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Bovinos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Técnicas In Vitro , Mediadores da Inflamação/metabolismo , Óxido Nítrico/biossíntese , Ratos , Ratos Sprague-Dawley , Superóxidos/metabolismoRESUMO
A Gram-stain-positive, aerobic and yellow actinobacterial strain, designated SYP-A7303T, was isolated from the root of Ginkgo biloba L. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SYP-A7303T belongs to the genus Nocardioides. The 16S rRNA gene sequence of strain SYP-A7303T showed highest similarity to Nocardioides marinus CL-DD14T ( = JCM 15615T) (98.3â%) and Nocardioides aquiterrae GW-9T ( = JCM 11813T) (97.1â%), and less than 96.9â% to the type strains of other species of the genus Nocardioides. Strain SYP-A7303T grew optimally at 28 °C, pH 7.0 and in the absence of NaCl. It contained ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan, with mannose, ribose, rhamnose, glucose and galactose as whole-cell sugars. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and an unknown lipid. The menaquinone was MK-8(H4) and the predominant cellular fatty acids were iso-C16â:â0, C18â:â1ω9c and C17â:â1ω8c. The DNA G+C content was 72âmol%. Mean DNA-DNA relatedness values between strain SYP-A7303T and the closely related strains N. marinus JCM 15615T and N. aquiterrae JCM 11813T were 62.5 ± 2.4 and 56.5 ± 3.5â%, respectively. Based on the morphological, physiological, biochemical and chemotaxonomic characteristics presented in this study, strain SYP-A7303T represents a novel species of the genus Nocardioides, for which the name Nocardioides ginkgobilobae sp. nov. is proposed. The type strain is SYP-A7303T ( = DSM 100492T = KCTC 39594T).