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1.
Int J Mol Sci ; 21(5)2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150945

RESUMO

Plants are associated with hundreds of thousands of microbes that are present outside on the surfaces or colonizing inside plant organs, such as leaves and roots. Plant-associated microbiota plays a vital role in regulating various biological processes and affects a wide range of traits involved in plant growth and development, as well as plant responses to adverse environmental conditions. An increasing number of studies have illustrated the important role of microbiota in crop plant growth and environmental stress resistance, which overall assists agricultural sustainability. Beneficial bacteria and fungi have been isolated and applied, which show potential applications in the improvement of agricultural technologies, as well as plant growth promotion and stress resistance, which all lead to enhanced crop yields. The symbioses of arbuscular mycorrhizal fungi, rhizobia and Frankia species with their host plants have been intensively studied to provide mechanistic insights into the mutual beneficial relationship of plant-microbe interactions. With the advances in second generation sequencing and omic technologies, a number of important mechanisms underlying plant-microbe interactions have been unraveled. However, the associations of microbes with their host plants are more complicated than expected, and many questions remain without proper answers. These include the influence of microbiota on the allelochemical effect caused by one plant upon another via the production of chemical compounds, or how the monoculture of crops influences their rhizosphere microbial community and diversity, which in turn affects the crop growth and responses to environmental stresses. In this review, first, we systematically illustrate the impacts of beneficial microbiota, particularly beneficial bacteria and fungi on crop plant growth and development and, then, discuss the correlations between the beneficial microbiota and their host plants. Finally, we provide some perspectives for future studies on plant-microbe interactions.

2.
Brain Res Bull ; 159: 9-15, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156628

RESUMO

BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative disorders, and mainly characterized by the progressive degeneration of dopaminergic (DA) neurons in the midbrain substantia nigra and non-DA neurons in many other parts of the brain. Previous studies have shown that several genes associated with the causes of PD can influence neurite outgrowth. Mutations of PRKN (encoding parkin, an E3 ubiquitin ligase) are the most frequent cause of recessively inherited PD. The lack of a PD phenotype in Prkn-knockout mice may imply a unique vulnerability of neurons to parkin mutations. METHODS: CRISPR/Cas9 technology was used to target random mutations into exon3 of PRKN in human fibroblasts cell line MRC-5. The induced DA neurons were achieved from direct conversion of fibroblasts (with or without PRKN mutations) via a cocktail of transcriptional factors (Ascl1, Nurr1, Lmx1a, miRNA124, p53 shRNA) and chemicals (CHIR99021, Purmorphamine, TGFß3, BDNF, GDNF, NGF and Y27632). RESULTS: Herein, we successfully established human neuronal cell models with parkin mutations from fibroblast-reprogrammed neurons. In these neurons, not only were the induced ratio and number of mature neurons markedly decreased, but also the complexity of the neuronal processes, measured by total neurite length and number of terminals, was greatly reduced, in TH+ and TH-neurons with PRKN mutations. CONCLUSIONS: The results suggest that parkin not only maintains the morphological complexity of human neurons, but also influences maturation and differentiation in the fibroblast reprogramming process.

3.
CNS Neurosci Ther ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32196977

RESUMO

INTRODUCTION: Essential tremor (ET) is one of the most prevalent movement disorders. The genetic etiology of ET has not been well defined although a significant proportion (≥50%) are familial cases. Linkage analysis and genome-wide association studies (GWASs) have identified several risk variants. In recent years, whole-exome sequencing of ET has revealed several specific causal variants in FUS (p.Q290X), HTRA2 (p.G399S), and TENM4 (c.4324 G>A, c.4100C>A, and c.3412G>A) genes. OBJECTIVE: To investigate the genetic contribution of these three genes to ET, the protein-coding sequences of FUS, HTRA2, and TENM4 were analyzed in a total of 238 ET patients and 272 controls from eastern China using direct Sanger sequencing. RESULTS: We identified two synonymous coding single nucleotide polymorphisms (SNPs), rs741810 and rs1052352 in FUS, and three previously reported synonymous SNPs, rs11237621, rs689369, and rs2277277 in TENM4. No nonsynonymous exonic variants were identified in these subjects. We found that the frequency of the rs1052352C allele was significantly higher (P = .001) in the ET group than in the control group. CONCLUSION: Overall, our findings suggest that rs1052352 of FUS might contribute to ET risk in Chinese population.

4.
Org Biomol Chem ; 18(9): 1806-1811, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32096526

RESUMO

A facile method for the synthesis of 4-chalcogenylated pyrazoles has been developed via electrophilic chalcogenation/cyclization of α,ß-alkynic hydrazones. The cyclization of α,ß-alkynic aldehyde hydrazones could be induced by using either sulfenyl chloride or the S-electrophiles generated in situ from the reaction of NCS and arythiol. The developed method was successfully applied to the synthesis of the sulfenyl analogue of celecoxib.

6.
Nature ; 579(7798): 265-269, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015508

RESUMO

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.


Assuntos
Betacoronavirus/classificação , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/etiologia , Síndrome Respiratória Aguda Grave/virologia , Adulto , Betacoronavirus/genética , China , Doenças Transmissíveis Emergentes/diagnóstico por imagem , Doenças Transmissíveis Emergentes/patologia , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/patologia , Genoma Viral/genética , Humanos , Pulmão/diagnóstico por imagem , Masculino , Filogenia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/patologia , RNA Viral/genética , Recombinação Genética/genética , Síndrome Respiratória Aguda Grave/diagnóstico por imagem , Síndrome Respiratória Aguda Grave/patologia , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Genoma
7.
Int J Mol Sci ; 21(4)2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32102190

RESUMO

Perillaldehyde (PAE), an essential oil in Perilla plants, serves as a safe flavor ingredient in foods, and shows an effectively antifungal activity. Reactive oxygen species (ROS) accumulation in Aspergillus flavus plays a critical role in initiating a metacaspase-dependent apoptosis. However, the reason for ROS accumulation in A. flavus is not yet clear. Using transcriptome sequencing of A. flavus treated with different concentrations of PAE, our data showed that the ROS accumulation might have been as a result of an inhibition of energy metabolism with less production of reducing power. By means of GO and KEGG enrichment analysis, we screened four key pathways, which were divided into two distinct groups: a downregulated group that was made up of the glycolysis and pentose phosphate pathway, and an upregulated group that consisted of MAPK signaling pathway and GSH metabolism pathway. The inhibition of dehydrogenase gene expression in two glycometabolism pathways might play a crucial role in antifungal mechanism of PAE. Also, in our present study, we systematically showed a gene interaction network of how genes of four subsets are effected by PAE stress on glycometabolism, oxidant damage repair, and cell cycle control. This research may contribute to explaining an intrinsic antifungal mechanism of PAE against A. flavus.

8.
Ann Transplant ; 25: e919875, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32107364

RESUMO

BACKGROUND At present, there is no ideal conventional triple regimen that can effectively treat gastrointestinal (GI) complications in patients after kidney transplantation. We aimed to investigate the efficacy and safety of a quadruple regimen including standard-dose tacrolimus, low-dose enteric-coated mycophenolate sodium (EC-MPS), low-dose mizoribine (MZR), and corticosteroids, compared with regimens containing standard-dose tacrolimus, corticosteroids, plus either low-dose EC-MPS or standard-dose MZR in patients with mycophenolic acid (MPA)-related GI complications after renal transplantation. MATERIAL AND METHODS Between August 2016 and October 2018 in Qilu Hospital of Shandong University, 115 living donor kidney transplant recipients with MPA-related GI complications were enlisted in a single-center, prospective, randomized, control study. Thirty-six recipients were assigned to the low-dose EC-MPS plus low-dose MZR group, 37 recipients were assigned to the low-dose EC-MPS group, and 39 recipients were assigned to the standard-dose MZR group. We analyzed the Gastrointestinal Symptom Rating Scale (GSRS), estimated glomerular filtration rate (eGFR), graft rejection, serum creatinine, human leukocyte antigen (HLA) antibody, and the occurrence of adverse events among the 3 groups. RESULTS Compared with baseline, gastrointestinal symptoms improved significantly in all 3 groups. The reduction in mean subscale scores from baseline to month 3 was more significant in the standard-dose MZR group compared with the other 2 groups. The low-dose EC-MPS plus low-dose MZR group had better renal function. The incidence of graft rejection and cytomegalovirus (CMV) and polyomavirus BK (BKV) infection, as well as the incidence of hyperuricemia, in the low-dose EC-MPS plus low-dose MZR group were all significantly reduced. CONCLUSIONS This quadruple regimen may be equivalent to regimens containing standard-dose tacrolimus, corticosteroids plus either low-dose EC-MPS or standard-dose MZR in improving GI symptoms after kidney transplant, and is also advantageous for kidney function, graft rejection, and the rates of adverse events.

9.
Chem Commun (Camb) ; 56(18): 2735-2738, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32021997

RESUMO

A new route for the synthesis of sulfonated 4H-3,1-benzoxazines has been accomplished by electrochemical radical cascade cyclizations of styrenyl amides with sulfonylhydrazines. This process demonstrates a wide substrate scope with diverse functional group compatibility under metal- and external oxidant-free conditions at ambient temperature.

10.
Org Lett ; 22(4): 1414-1419, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32011150

RESUMO

Herein, we describe a palladium-catalyzed alkynylation of gem-difluorinated cyclopropanes via C-C bond activation/C-F bond cleavage, followed by C-C(sp) coupling. The new approach proceeds with broad substrate scope under mild reaction conditions, whereas both 1,1-disubstituted and complex-molecule-modified gem-difluorinated cyclopropanes react smoothly with high stereoselectivity. The developed method provides efficient and convenient ways access to diversity of important fluorinated enynes and arenes by slightly modification of the reaction conditions.

11.
Reprod Sci ; 27(2): 585-591, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32046460

RESUMO

The function of oncogenic lncRNA BLACAT1 has been studied in several types of cancer, while its role in cervical squamous cell carcinoma (CSCC) is unknown. We showed that BLACAT1 was upregulated in CSCC tissue comparing to adjacent non-cancer tissue of CSCC patients. BLACAT1 expression in CSCC tissues was not affected by HPV infection. Patients with higher BLACAT1 level in CSCC tissues showed a significantly lower overall 5-year survival rate. BLACAT1 expression was inversely correlated with several tumor-suppressive miRNAs, such as miR-424 and miR-143. miR-424 and miR-143 overexpression did not significantly affect BLACAT1, while BLACAT1 overexpression caused downregulated miR-424 and miR-143. Overexpression of miR-424 and miR-143 led to inhibited migration and invasion, while BLACAT1 overexpression led to promoted migration and invasion of CSCC cells. In addition, overexpression of miR-424 and miR-143 attenuated the effects of BLACAT1 overexpression. Therefore, BLACAT1 overexpression may promote CSCC by downregulating miR-424 and miR-143.

12.
Medicine (Baltimore) ; 99(3): e18868, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011509

RESUMO

BACKGROUND: Plenty of evidence has suggested that long non-coding RNAs (lncRNAs) have played a vital part may act as prognostic biomarkers in a variety of cancers. The aim of this study was to screen survival-related lncRNAs and to construct a lncRNA-based prognostic model in patients with cutaneous melanoma (CM). METHODS: We obtained lncRNAs expression profiles and clinicopathological data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. A lncRNA-based prognostic model was established in training set. The established prognostic model was evaluated, and validated in the validation set. Then, a prognostic nomogram combining the lncRNA-based risk score and clinicopathological characteristics was developed in training set, and assessed in the validation set. The accuracy of the model was evaluated by the discrimination and calibration plots. RESULTS: A total of 212 lncRNAs were identified to be differentially expressed in CM. After univariate analysis, LASSO penalized regression analysis, and multivariate analysis, 3 lncRNAs were used to construct risk score model. The proposed risk score model could divide patients into high-risk and low-risk groups with significantly different survival in both training set and validation set. The ROC curve showed good performance in survival prediction in both sets. Furthermore, the nomogram for predicting 3-, 5-, and 10-year OS was established based on lncRNA-based risk score and clinicopathologic factors. The prognostic accuracy of the risk model was confirmed by the discrimination and calibration plots in both training set and validation set. CONCLUSIONS: We established a novel three lncRNA-based risk score model and nomogram to predict overall survival of CM. The proposed nomogram may provide information for individualized treatment in CM patients.


Assuntos
Melanoma/genética , Melanoma/mortalidade , RNA Longo não Codificante/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Biomarcadores Tumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Prognóstico
13.
Kidney Blood Press Res ; 45(2): 331-338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982885

RESUMO

INTRODUCTION: Impaired cardiac function is one of the most concomitant symptoms in patients with kidney failure after long-term dialysis. In addition, the preservation of adequate perfusion pressure to the graft plays a significant role in the intraoperative management during kidney transplantation, but the use of positive inotropic drugs in kidney transplant patients has been studied less. We investigated the protective effects of renal function by means of cardiac inotropes in kidney transplant patients. METHODS: Eighty-nine patients that received kidney transplantation between April 2014 and December 2016 at Qilu Hospital were included and randomly divided into the treatment group receiving levosimendan and a control group. All kidney recipients received ABO-compatible donors. A poor outcome was defined as one of the following: delayed graft function, graft hemorrhage, or nephrectomy. RESULTS: The treatment group had a better composite outcome and the level of neutrophil gelatinase-associated lipocalin was also lower than in the control group. CONCLUSION: Inotropic drugs may play a protective role in renal function in kidney transplantation.

15.
Toxins (Basel) ; 12(1)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963878

RESUMO

Aspergillus flavus is one of the most opportunistic pathogens invading many important oilseed crops and foodstuffs with such toxic secondary metabolites as aflatoxin (AF) and Cyclopiazonic acid. We previously used the DNA methylation inhibitor 5-azacytidine to treat with an AF-producing A. flavus A133 strain, and isolated a mutant (NT) of A. flavus, which displayed impaired abilities of AF biosynthesis and fungal development. In this study, gas chromatography-mass spectrometry (GC-MS) analysis was used to reveal the metabolic changes between these two strains. A total of 1181 volatiles were identified in these two strains, among which 490 volatiles were found in these two strains in vitro and 332 volatiles were found in vivo. The NT mutant was found to produce decreasing volatile compounds, among which most of the fatty acid-derived volatiles were significantly downregulated in the NT mutant compared to the A133 strain, which are important precursors for AF biosynthesis. Two antioxidants and most of the amino acids derived volatiles were found significantly upregulated in the NT mutant. Overall, our results reveal the difference of metabolic profiles in two different A. flavus isolates, which may provide valuable information for controlling infections of this fungal pathogen.

16.
Org Lett ; 22(3): 908-913, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31944780

RESUMO

ortho-Selective carbene C-H insertion of unprotected phenols is achieved with dimethyl diazomalonate under the catalysis of [Rh(COD)Cl]2. After the C-H insertion, subsequent cyclization and electrophilic addition of another carbene molecule affords tris-carboxylate-substituted 2-benzofuranones as the final reaction products. The enantioselective variant has been developed with the use of chiral diene ligands. Mechanistic experiments indicate that a transient oxonium ylide directing group might be responsible for the regiocontrol at the C-H activation step.

17.
J Org Chem ; 85(4): 2456-2465, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31916760

RESUMO

Herein, we report a method for in situ generation of N-aryliminium ions via reactions of N,N-dimethylanilines with diiodomethane. We used the method to prepare tetrahydroquinolines via one-pot three-component reactions between N,N-dimethylanilines, diiodomethane, and olefins. This transformation involves initial reaction of the aniline with diiodomethane to form an iodomethylammonium salt, which undergoes fragmentation accompanied by elimination of methyl iodide to give an N-aryliminium ion, which is trapped by the olefin via [4 + 2] cycloaddition to give the final product. This method for generating N-aryliminium ions requires neither a catalyst nor a strong oxidant, suggesting that it can be expected to find broad utility, especially for substrates that are sensitive to Lewis acids, transition metals, or strong oxidants.

18.
J Agric Food Chem ; 68(5): 1354-1363, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31933364

RESUMO

Carotenoids are essential phytonutrients synthesized by all photosynthetic organisms. Acyclic lycopene is the first branching point for carotenoid biosynthesis. Lycopene ß- and ε-cyclases (LCYB and LCYE, respectively) catalyze the cyclization of its open ends and direct the metabolic flux into different downstream branches. Carotenoids of the ß,ß-branch (e.g., ß-carotene) are found in all photosynthetic organisms, but those of the ß,ε-branch (e.g., lutein) are generally absent in cyanobacteria, heterokonts, and some red algae. Although both LCYBs and LCYEs have been characterized from land plants, there are only a few reports on LCYs from cyanobacteria and algae. Here, we cloned four LCY genes from Porphyra umbilicalis and Pyropia yezoensis (susabi-nori) of Bangiales, the most primitive red algal order that synthesizes lutein. Our functional characterization in both Escherichia coli and Arabidopsis thaliana demonstrated that each species has a pair of LCYB and LCYE. Similar to LCYs from higher plants, red algal LCYBs cyclize both ends of lycopene, and their LCYEs only cyclize a single end. The characterization of LCYEs from red algae resolved the first bifurcation step toward ß-carotene and lutein biosynthesis. Our phylogenetic analysis suggests that LCYEs of the green lineage and the red algae originated separately during evolution.


Assuntos
Liases Intramoleculares/metabolismo , Luteína/metabolismo , Proteínas de Plantas/metabolismo , Rodófitas/enzimologia , Alga Marinha/enzimologia , Sequência de Aminoácidos , Liases Intramoleculares/química , Liases Intramoleculares/genética , Luteína/química , Licopeno/química , Licopeno/metabolismo , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Rodófitas/classificação , Rodófitas/genética , Rodófitas/metabolismo , Alga Marinha/classificação , Alga Marinha/genética , Alga Marinha/metabolismo , Alinhamento de Sequência
19.
BMC Med Genomics ; 13(1): 1, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900157

RESUMO

BACKGROUND: Osteoarthritis is a chronic musculoskeletal disease characterized by age-related gradual thinning and a high risk in females. Recent studies have shown that DNA methylation plays important roles in osteoarthritis. However, the genome-wide pattern of methylation in enhancers in osteoarthritis remains unclear. METHODS: To explore the function of enhancers in osteoarthritis, we quantified CpG methylation in human enhancers based on a public dataset that included methylation profiles of 470,870 CpG probes in 108 samples from patients with hip and knee osteoarthritis and hip tissues from healthy individuals. Combining various bioinformatics analysis tools, we systematically analyzed aberrant DNA methylation of the enhancers throughout the genome in knee osteoarthritis and hip osteoarthritis. RESULTS: We identified 16,816 differentially methylated CpGs, and nearly half (8111) of them were from enhancers, suggesting major DNA methylation changes in both types of osteoarthritis in the enhancer regions. A detailed analysis of hip osteoarthritis identified 2426 differentially methylated CpGs in enhancers between male and female patients, and 84.5% of them were hypomethylated in female patients and enriched in phenotypes related to hip osteoarthritis in females. Next, we explored the enhancer methylation dynamics among patients with knee osteoarthritis and identified 280 differentially methylated enhancer CpGs that were enriched in the human phenotypes and disease ontologies related to osteoarthritis. Finally, a comparison of enhancer methylation between knee osteoarthritis and hip osteoarthritis revealed organ source-dependent differences in enhancer methylation. CONCLUSION: Our findings indicate that aberrant methylation of enhancers is related to osteoarthritis phenotypes, and a comprehensive atlas of enhancer methylation is useful for further analysis of the epigenetic regulation of osteoarthritis and the development of clinical drugs for treatment of osteoarthritis.

20.
Appl Microbiol Biotechnol ; 104(4): 1695-1705, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31900559

RESUMO

The interspecies communication roles of γ-butyrolactones (GBLs) have been described for a long time but are still poorly understood. Herein, we analyzed more than 1000 Streptomyces strains and noticed a big quantitative gap between the strains with GBL biosynthetic genes and the strains with GBL receptor genes, which implies the wide-spread of GBLs as interspecies signals in Streptomyces and their great potential in the activation of silent natural product gene clusters. Streptomyces albidoflavus J1074, which has one GBL receptor gene but no GBL biosynthetic gene, was chosen as a target to study the possible interspecies communication roles of GBLs. At first, the GBL biosynthetic genes from Streptomyces coelicolor M145 were expressed in S. albidoflavus J1074, which enabled the S. albidoflavus strains to synthesize Streptomyces coelicolor butanolides (SCBs) and activated the production of paulomycins. Further studies showed that this activation process requires the participation of the GBL receptor gene XNR_4681. The results suggest that the expression of exogenous GBL biosynthetic genes can modulate the metabolisms of GBL non-producing strains, and this regulation role might be meaningful for silent gene cluster activation in Streptomyces. At final, we synthesized racemic-SCB2 and tried to simplify the activation process by adding SCB2 directly to S. albidoflavus J1074, which unfortunately failed to induce paulomycin production.

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