Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 505
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Org Lett ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32402203

RESUMO

The biosynthetic gene cluster of the fungal meroterpenoid emeridone F (8) was discovered in the genome of Aspergillus sp. TJ23, and its late-stage biosynthesis was elucidated by characterizing two α-ketoglutarate (αKG)-dependent dioxygenases, SptF and SptN. SptF catalyzes oxidative rearrangement followed by epoxidation, whereas SptN serves as the C-9 hydroxylase. Our study provides insight into the biosynthetic mechanisms of other andiconin (1)-derived natural products, exemplifying the important roles of αKG-dependent enzymes in the structural complexifications.

2.
Nanoscale ; 12(18): 10026-10034, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32367083

RESUMO

Nanopore-based DNA detection and analysis have been intensively pursued theoretically and experimentally over the past decade. Owing to their nanometer thickness, 2D nanopores, such as boron nitride nanopores, show great potential for achieving DNA detection at base resolution. Although 2D nanopore devices hold great promise for next-generation DNA detection, efficiently and reliably detecting different DNA sequences is still a challenging problem. To date, most of the investigated nanopores adopt circular shapes. Because of the successful fabrication of triangular nanopores, investigating the shape effect of nanopores for DNA detection has become more and more important. In this study, boron nitride nanopores with circular, hexagonal, quadrangular and triangular shapes were modeled at various sizes. The translocation of homogeneous dsDNA through these nanopores was investigated by all-atom molecular dynamic simulations. The ionic conductivity of these nanopores was characterized and formulas for the total resistance based on the pore and access resistance were derived. The ionic current, dwell time and conductance blockade of homogeneous dsDNA were compared for nanopores with different shapes. We demonstrate that the charge distribution at the pore mouth plays an important role in the transportation of ions and DNA molecules. Our findings may shed light on the design of 2D nanopores and can facilitate the development of fast, low-cost and reliable nanopore-based DNA detection.

3.
Bioorg Chem ; 100: 103887, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32371250

RESUMO

Fusicoccane-derived diterpenoids bearing a unique bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane (5-9-5 ring system) core skeleton represent a rarely reported class of rearranged terpenoids, which traced back to fusicoccanes with a classical dicyclopenta[a,d]cyclooctane (5-8-5 ring system) core skeleton via a crucial Wagner-Meerwein rearrangement reaction. In this research, alterbrassicenes B-D (1-3), three new rearranged fusicoccane diterpenoids bearing a rare bridgehead double-bond-containing tricyclo[9.2.1.03,7]tetradecane core skeleton, together with two known congeners, brassicicenes O and K (4 and 5), were isolated from the modified cultures of fungus Alternaria brassicicola. Their structures were elucidated by comprehensive analyses of the NMR and HRESIMS data, and the absolute configurations of 1 and 4 were further confirmed via a combination of 13C NMR and ECD calculations and single-crystal X-ray diffraction analysis (Cu Kα). Interestingly, alterbrassicene B (1) represented the second case of bridgehead C-10-C-11 double-bond-containing natural products with a bicyclo[6.2.1]undecane core skeleton, and also featured an undescribed oxygen bridge between C-6 and C-14 to construct an unprecedentedly caged tetracyclic system. Alterbrassicenes B-D showed moderate cytotoxic activity against certain human tumor cell lines with IC50 values in the range of 15.87-36.85 µM.

4.
iScience ; 23(4): 101001, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32259671

RESUMO

Oxidation of formate to CO2 is catalyzed via the donation of electrons from formate dehydrogenase (FDH) to nicotinamide adenine dinucleotide (NAD+), and thus the charge transport characteristics of FDH become essential but remain unexplored. Here, we investigated the charge transport through single-enzyme junctions of FDH using the scanning tunneling microscope break junction technique (STM-BJ). We found that the coupling of NAD+ with FDH boosts the charge transport by ∼2,100%, and the single-enzyme conductance highly correlates with the enzyme activity. The combined flicker noise analysis demonstrated the switching of the coenzyme-mediated charge transport pathway and supported by the significantly reduced HOMO-LUMO gap from calculations. Site-specific mutagenesis analysis demonstrated that FDH-NAD+ stably combined own higher bioactivity and boosts charge transport, and the coupling has been optimized via the natural selection. Our work provides evidence of hydrogen bond coupling in bioactivity but also bridges the charge transport through single-enzyme junctions and enzyme activities.

5.
Environ Int ; 139: 105682, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32248024

RESUMO

BACKGROUND: The placenta performs crucial functions to ensure normal fetal development. Experimental studies have indicated associations between exposure to elevated temperatures during pregnancy and reduction in placental weight and volume. However, epidemiological studies in humans are lacking. OBJECTIVE: To estimate the associations between prenatal exposure to ambient temperature with placental weight, volume, and the placental weight to birth weight ratio (PFR). METHODS: We conducted a prospective birth cohort study using the Prenatal Environment and Offspring Health Cohort (PEOH Cohort) beginning in 2016 in Guangzhou, China. Women in early pregnancy were recruited and followed up during their hospitalization for childbirth. An inverse distance-weighted method was employed to estimate the average temperature exposure of every 4 weeks as well as the trimester-specific average temperature exposure at the individual's residential address. A generalized linear model was applied to estimate the effects of temperature exposure during pregnancy on the placental weight, volume, and PFR. RESULTS: A total of 4051 pregnant women were enrolled. Compared with the reference temperature of 20 °C, maternal exposure to 29 °C (95th centile) during late pregnancy was associated with an average of -6.03 g (95% confidence interval [CI]: -11.28 g, -0.78 g) in placental weight, -16.15 cm3 (95% CI: -26.24 cm3, -6.07 cm3) in placental volume, and 0.26 (95% CI: 0.07, 0.45) in PFR. The peak effects of high temperatures on placental weight, volume, and PFR were found from 29 to 32 weeks (ß = -3.79 g, 95% CI: -8.39 g, 0.82 g), 37 to 40 weeks (ß = -19.34 cm3, 95% CI: -30.99 cm3, -7.69 cm3), and 25 to 28 weeks (ß = 0.35, 95% CI: 0.04, 0.66), respectively. CONCLUSIONS: Maternal exposure to elevated temperatures was associated with a decrease in placental weight and volume and an increase in PFR. The associations were stronger when exposures occurred during late pregnancy.

6.
J Asian Nat Prod Res ; : 1-7, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32290693

RESUMO

One new spirocyclic lactone, terreinlactone C (1), and one new benzopyran derivative, 2,2-dimethyl-3-hydroxychroman-6-aldehyde (2), were discovered from the fungus Aspergillus terreus. The chemical structures of compounds 1 and 2 were elucidated by detailedly analyzing NMR and HRESIMS data. Compound 1 is the first natural product with a 1-oxaspiro[4.5]decan-2-one ring system and a possible biogenetic pathway is proposed. Two compounds were tested for their cytotoxic activities against five human cancer cell lines.[Formula: see text].

7.
Brain Res Bull ; 160: 33-39, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32298780

RESUMO

OBJECTIVE: To explore the unified and disease specific structural features of the brain in patients spanning six mental disorders who experience own-thought auditory verbal hallucinations (OTAVH). METHODS: A pilot study was conducted on 25 patients with schizophrenia (FUSCH-OTAVH), 20 patients with major depression disorder (FUMDD-OTAVH), 28 patients with bipolar disorder (FUBD-OTAVH), 22 patients with posttraumatic stress disorder (FUPTSD-OTAVH), 21 patients with anxiety disorder (FUAD-OTAVH), and 27 patients with borderline personality disorder (FUBPD-OTAVH). Twenty-five healthy controls (HCs) were also recruited. Auditory Hallucinations Rating Scale (AHRS) multiple psychometric scales were adopted to assess the clinical features of voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and multiple regression in all patients. Common and specific brain features of OTAVH among these mental disorders were investigated. RESULTS: Compared to HCs, GMV aberrant pattern across all the six categories patients with OTAVH decreased in the occipital cortex, left parietal lobe, prefrontal cortex (PFC), and insular cortex (IC). Aberrant patterns in white matter (WM) were detected in the corpus callosum and impairment of the fronto-occipital fasciculus. Structural differences in the brain were observed for each mental disorder versus HCs. CONCLUSIONS: The unified brain aberrant features of OTAVH across six mental disorders were characterized by decreased GMV and WM impairments in some regions and the specific brain features of each disease were also characterized. In conclusion, this study provides evidence for the structural basis of OTAVH and potential avenues for investigating disease specific brain features of OTAVH.

8.
Phytochemistry ; 175: 112374, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32315839

RESUMO

Seven undescribed alkaloids, namely fischeramides A and B, 5,6-dimethoxycircumdatin C, 6-hydroxyacetylaszonalenin, 3-methoxyglyantrypine, 9-methoxyfumitremorgin C, and spirotryprostatin M, one undescribed natural product, namely 11-deacetyl pyripyropene A, together with nine known congeners, were isolated from the solid cultures of fungus Neosartorya fischeri, which was separated from a medicinal insect Cryptotympana atrata. Their structures were elucidated by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analyses. Structurally, fischeramides A and B represented a pair of rare geometric isomers of the benzodiazepinedione derivatives with a highly conjugated feature. Fischeramide A showed potential immunosuppressive activity in LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with IC50 values of 7.08 and 6.31 µM, respectively, and also showed anti-inflammatory activity against the lipopolysaccharide-induced nitric oxide production with an IC50 value of 25 ± 1 µM. In addition, 5,6-dimethoxycircumdatin C showed remarkable antibacterial activity against ESBL-producing E. coli with an MIC value of 2.0 µg/mL.

9.
Materials (Basel) ; 13(8)2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32331238

RESUMO

This paper studies the radiation resistance for GaInP/GaInAs/Ge triple-junction space solar cells with a GaInP back-surface field (BSF) in the GaInAs middle subcell compared with those with an AlGaAs BSF. The results show that the initial electrical performance is almost the same for both of them. However, the radiation resistance of the GaInP BSF cell was improved. After irradiation by 1 MeV electron beam with a cumulative dose of 1015 e/cm2, the Jsc declined by 4.73% and 6.61% for the GaInP BSF cell and the AlGaAs BSF cell, respectively; the efficiency degradation was 13.64% and 14.61% for the GaInP BSF cell and the AlGaAs BSF cell, respectively, leading to a reduced degradation level of 6%. The mechanism for GaInP BSF to improve the radiation resistance of GaInP/GaInAs/Ge triple-junction solar cells is also discussed in this work. Similar results were obtained when irradiation cumulative doses varied from 1 × 1014 e/cm2 to 1 × 1016 e/cm2.

10.
Curr Med Sci ; 40(2): 232-238, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337684

RESUMO

Metarhizosides A-G (1-7), seven new polysubstituted phenyl glucosides, were isolated from the extracts of solid rice medium of a marine-derived fungus Metarrhizium anisopliae. Compounds 1-7 all contain a polysubstituted phenyl group and the sugar unit is identified as 4'-O-methyl-ß-D-glucopyranose. Their structures were elucidated by NMR spectroscopy and chemical method. These compounds were evaluated for anti-inflammatory activity by using LPS-stimulated murine macrophage RAW 264.7 cells and the cytotoxicities against four human cancer cell lines.

11.
Bioorg Chem ; 99: 103760, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32251946

RESUMO

Eight unexpected vibralactone homodimers, bisvibralactones A-H (1-8), and three new vibralactone monomers, hirsutumins A-C (9-11), were isolated from the culture of Stereum hirsutum. Their structures and absolute configurations were determined by detailed analyses of NMR, optical rotations, ECD, and high-resolution mass spectra as well as chemical transformation. Compounds 1-8 are unusual vibralactone dimers formed by the esterification of two vibralactone monomers. The absolute configurations of compounds 1 and 5 were determined by chemical conversions. All of the isolated compounds were evaluated for Porcine Pancreatic Lipase (PPL) inhibitory activities, and compound 10 showed significant inhibitory activity against PPL, with an IC50 value of 8.31 ± 1.04 µM.

12.
Bioorg Chem ; 99: 103816, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32305693

RESUMO

Three previously undescribed compounds, including a meroterpenoid, guignardone T (1), and two ophiobolin-type sesterterpenoids, maydispenoids A and B (2 and 3), along with four known compounds (4-7), were isolated from the phytopathogenic fungus Bipolaris maydis collected from Anoectochilus roxburghii (Wall.) Lindl leaves. The structures of all undescribed compounds were elucidated by spectroscopic analysis, electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction. Structurally, maydispenoids A was characterized by a fascinating decahydro-3-oxacycloocta[cd]pentalene fragment. It is notable that the compounds 2 and 3 exhibited potential inhibitory activity in anti-CD3/anti-CD28 monoclonal antibodies (mAbs) stimulated murine splenocytes proliferation, with IC50 values of 5.28 and 9.38 µM, respectively, and also suppress the murine splenocytes proliferation activated by lipopolysaccharide (LPS), with IC50 values of 7.25 and 16.82 µM, respectively. This is the first report of ophiobolin-type sesterterpenoids as immunosuppressor, and may provide new chemical templates for the development of new immunosuppressive drugs for autoimmune disease treatment.

13.
Fitoterapia ; 143: 104532, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32151636

RESUMO

Six new compounds, including two new isochromane lactones, versicoisochromanes A and B (1 and 2), two new benzolactones, versicobenzos A and B (3 and 4), one furancarboxylic derivate, asperfuran A (6) and one ergosterol-type steroid, asperergoster A (7), along with five known steroids (8-12), were isolated from the Anoectochilus roxburghii endophytic fungus Aspergillus versicolor. The structures of these new compounds were determined by extensive spectroscopic techniques and electronic circular dichroism (ECD) calculations. It is notable that the new compound 7 exhibited obvious IL-1ß, NO and TNF-α inhibitory activity in LPS-stimulated RAW264.7 macrophages, with IC50 values of 35.5, 33.9 and 31.3 µM, respectively. Furthermore, compounds 7 and 8 displayed potential inhibitory effects on murine splenocytes proliferation stimulated by anti-CD3/anti-CD28 monoclonal antibodies (mAbs), meanwhile suppress the lipopolysaccharide (LPS) irritated murine splenocytes proliferation.

14.
Phytochemistry ; 174: 112327, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222549

RESUMO

Eight undescribed quinolone alkaloids, pesimquinolones A-H, as well as six known compounds, were isolated from the solid culture broth of the fungus Penicillium simplicissimum. Their chemical structures were characterized by combined analyses of NMR spectroscopy and single-crystal X-ray crystallography. Pesimquinolones A-G are the first examples of naturally occurring quinolone alkaloids possessing a limonene moiety. Their anti-inflammatory activities on LPS-induced nitric oxide (NO) production in adherent cells were evaluated. Pesimquinolones A, E, G, and H showed promising suppressive effect on the production of NO with IC50 values of 1.94, 1.29, 1.20, and 1.23 µM, respectively.


Assuntos
Alcaloides , Penicillium , Anti-Inflamatórios , Estrutura Molecular , Óxido Nítrico
15.
Bioinformatics ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170933

RESUMO

While many quantitative structure-activity relationship (QSAR) models are trained and evaluated for their predictive merits, understanding what models have been learning is of critical importance. However, the interpretation and visualization of QSAR model results remain challenging, especially for 'black box' models such as deep neural network (DNN). Here we take a step forward to interpret the learned chemical features from DNN QSAR models, and present VISAR, an interactive tool for visualizing the structure-activity relationship (SAR). VISAR firstly provides functions to construct and train DNN models. Then VISAR builds the activity landscapes based on a series of compounds using the trained model, showing the correlation between the chemical feature space and the experimental activity space after model training, and allowing for knowledge mining from a global perspective. VISAR also maps the gradients of the chemical features to the corresponding compounds as contribution weights for each atom, and visualizes the positive and negative contributor substructures suggested by the models from a local perspective. Using the web application of VISAR, users could interactively explore the activity landscape and the color-coded atom contributions. We propose that VISAR could serve as a helpful tool for training and interactive analysis of the DNN QSAR model, providing insights for drug design, and an additional level of model validation. AVAILABILITY AND IMPLEMENTATION: The source code and usage instructions for VISAR are available on github https://github.com/Svvord/visar. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

16.
J Org Chem ; 85(7): 4973-4980, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32118426

RESUMO

Four unusual polyketides possessing three unambiguous chemical architectures were discovered from the fermentation of Penicillium canescens assisted by the one strain-many compounds (OSMAC) strategy and MS2-based molecular networking. Penicanone (1) is the first naturally occurring polyketide characterized by a 6/6/8 tricyclic carbon skeleton incorporating an unusual bicyclo[5.3.1]hendecane core. Penicanesones A-C (2-4) are aromatic polyketide dimers simultaneously featuring inconsistent 6/5/5/6 and 6/6/5/6 heterotetracyclic ring cores. Their plausible biosynthetic pathways and screening of biological activity were described here.

17.
Medicine (Baltimore) ; 99(11): e19426, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176069

RESUMO

BACKGROUND: Osteoporosis is an important cause of bone fractures and even a cause of threaten to the lives of elderly people. Mind-body exercises are beneficial interventions for improving flexibility, controlling body balance, and reducing pain. To assess the effect of mind-body exercise on osteoporosis in aging people, we will perform this systematic review. METHODS: Randomized controlled trials (RCTs) which carried out about mind-body exercise for osteoporosis will be included. Web of Science, PubMed, Science Direct, Medline, Cochrane Library, China National Knowledge Infrastructure, and Wanfang will be searched from inception to January 2020. The outcomes will include bone mineral density (BMD), bone mineral content (BMC), body balance, function of lower extremity, pain, fearing level, and quality of life. Trial reporting quality will be assessed by 2 reviewers independently and Review Manager 5.3 software will be used for meta-analysis. Trial registration is under PROSPERO (CRD42020165385). RESULTS: Based on the current evidence, the potential rank of the efficacy and safety of mind-body exercises for BMD, BMC, body balance, function of lower extremity, pain, fearing level and quality of life will be assessed, and a prioritization regimen will be summarized. CONCLUSIONS: Evidence from this systematic review could be useful for patients, clinical practitioners, and guideline-makers to select an optimum proposal of mild-body exercises for older adults with osteoporosis.


Assuntos
Terapias Mente-Corpo , Osteoporose/terapia , Idoso , Teorema de Bayes , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Artigo em Inglês | MEDLINE | ID: mdl-32160364

RESUMO

While halogenated nucleosides are used as common anticancer and antiviral drugs, naturally occurring halogenated nucleosides are rare. Adechlorin (ade) is a 2'-chloro nucleoside natural product first identified from Actinomadura sp. ATCC 39365. However, the installation of chlorine in the ade biosynthetic pathway remains elusive. Reported herein is a Fe2+ -α-ketoglutarate halogenase AdeV that can install a chlorine atom at the C2' position of 2'-deoxyadenosine monophosphate to afford 2'-chloro-2'-deoxyadenosine monophosphate. Furthermore, 2',3'-dideoxyadenosine-5'-monophosphate and 2'-deoxyinosine-5'-monophosphate can also be converted, albeit 20-fold and 2-fold, respectively, less efficiently relative to the conversion of 2'-deoxyadenosine monophosphate. AdeV represents the first example of a Fe2+ -α-ketoglutarate-dependent halogenase that converts nucleotides into chlorinated analogues.

19.
Org Lett ; 22(6): 2162-2166, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32129633

RESUMO

The study of Aspergillus micronesiensis led to the isolation of three unprecedented cytochalasans (1-3). Dimericchalasine A (1) is the first cytochalasan homodimer fused by a C-20/C-20' single bond. Amichalasines D (2) and E (3) represent a new type of cytochalasan heterotrimer with a decacyclic 5/6/11/5/5/6/5/12/6/5 ring system. Their structures were determined by extensive spectroscopic data and single-crystal X-ray diffraction. The plausible biosynthetic pathways of 1-3 were proposed.

20.
Phytochemistry ; 173: 112295, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32113065

RESUMO

Four undescribed bioxanthracene derivatives, dongtinganthracenes A-D, along with a previously reported analog, ES-242-3, were obtained from the solid culture broth of the fungus Penicillium sp. DT10, which was isolated from wetland soil obtained from Dongting Lake. Their structures and absolute configurations were elucidated based on extensive NMR analyses, mass spectroscopic analyses, and ECD calculations. Dongtinganthracene A represents the first 7',8'-seco-bioxanthracene produced via oxidation, and dongtinganthracenes A-D show a much higher degree of oxidation in aromatic rings compared with normal naturally occurring bioxanthracene derivatives. Dongtinganthracenes B and D and ES-242-3 exhibit cytotoxic activity, while dongtinganthracene A shows inhibitory activity against LPS-induced NO production.


Assuntos
Penicillium , Lagos , Estrutura Molecular , Solo , Áreas Alagadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA