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1.
Virol J ; 21(1): 128, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840203

RESUMO

The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Proteínas do Envelope Viral , Vírus da Encefalite Japonesa (Espécie)/genética , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Vírus da Encefalite Japonesa (Espécie)/efeitos dos fármacos , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo , Proteínas do Envelope Viral/química , Animais , Linhagem Celular , Virulência , Replicação Viral , Encefalite Japonesa/virologia , Humanos , Heparina/farmacologia , Substituição de Aminoácidos , Mutação de Sentido Incorreto , Camundongos , Mutação , Fatores de Virulência/genética , Glicoproteínas de Membrana
2.
Angew Chem Int Ed Engl ; 63(7): e202318550, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38155101

RESUMO

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C-C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as L -aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment.


Assuntos
Álcoois , Aminoácidos , Aminoácidos/química , Catálise
3.
Phys Chem Chem Phys ; 25(38): 26308-26315, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37747304

RESUMO

SARS-CoV-2 main protease, Mpro, plays a crucial role in the virus replication cycle, making it an important target for antiviral research. In this study, a simplified model obtained through truncation is used to explore the reaction mechanism of aldehyde warhead compounds inhibiting Mpro at the level of density functional theory. According to the calculation results, proton transfer (P_T)-nucleophilic attack (N_A) is the rate-determining step in the entire reaction pathway. The water molecule that plays a catalytic role occupies the oxyanion hole, which is unfavorable for the aldehyde warhead to approach the Cys145 SH. Through a hypothetical study of substituting the main chain NH with methylene, it is further confirmed that the P_T-N_A is a proton transfer-dominated process accompanied by a nucleophilic attack reaction. In this process, the oxyanion hole serves only to stabilize the aldehyde oxygen anion and therefore does not have a significant impact on the activation free energy barrier of the step. Our research results provide a unique perspective for understanding the covalent inhibition reaction of the Mpro active site. This study also offers theoretical guidance for the design of new Mpro covalent inhibitors.


Assuntos
Aldeídos , Antivirais , Proteases 3C de Coronavírus , SARS-CoV-2 , Humanos , Aldeídos/química , Aldeídos/farmacologia , Antivirais/química , Antivirais/farmacologia , Simulação de Acoplamento Molecular , Prótons , SARS-CoV-2/enzimologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química
4.
Physiol Mol Biol Plants ; 29(3): 435-445, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37033769

RESUMO

Low-phosphorus stress significantly impacts the development of maize kernels. In this study, the phosphor efficient maize genotype 082 and phosphor deficient maize genotype Ye107, were used to construct an F2:3 population. QTL mapping was then employed to determine the genetic basis of differences in the maize kernel traits of the two parents in a low-phosphorus environment. This analysis revealed several major QTL that control environmental impacts on kernel length, width, thickness, and weight. These QTL were detected in all three environments and were distributed on five genome segments of chromosomes 3, 5, 6, and 9, and some new kernel-trait QTL were also detected (eg: Qkwid6, Qkthi3, Qkwei9, and Qklen3-1). These environmentally insensitive QTL can be stably expressed in low phosphorus environments, indicating that they can lay a foundation for the breeding of high phosphorus utilization efficiency germplasm. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01300-0.

5.
Curr Issues Mol Biol ; 45(1): 212-222, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36661502

RESUMO

Virus infestation can seriously harm the host plant's growth and development. Turnip yellows virus (TuYV) infestation of host plants can cause symptoms, such as yellowing and curling of leaves and root chlorosis. However, the regulatory mechanisms by which TuYV affects host growth and development are unclear. Hence, it is essential to mine small RNA (sRNA) and explore the regulation of sRNAs on plant hosts for disease control. In this study, we analyzed high-throughput data before and after TuYV infestation in Arabidopsis using combined genetics, statistics, and machine learning to identify 108 specifically expressed and critical functional sRNAs after TuYV infection. First, comparing the expression levels of sRNAs before and after infestation, 508 specific sRNAs were significantly up-regulated in Arabidopsis after infestation. In addition, the results show that AI models, including SVM, RF, XGBoost, and CNN using two-dimensional convolution, have robust classification features at the sequence level, with a prediction accuracy of about 96.8%. A comparison of specific sRNAs with genome sequences revealed that 247 matched precisely with the TuYV genome sequence but not with the Arabidopsis genome, suggesting that TuYV viruses may be their source. The 247 sRNAs predicted target genes and enrichment analysis, which identified 206 Arabidopsis genes involved in nine biological processes and three KEGG pathways associated with plant growth and viral stress tolerance, corresponding to 108 sRNAs. These findings provide a reference for studying sRNA-mediated interactions in pathogen infection and are essential for establishing a vital resource of regulation network for the virus infecting plants and deepening the understanding of TuYV virus infection patterns. However, further validation of these sRNAs is needed to gain a new understanding.

6.
Phys Chem Chem Phys ; 24(39): 24447-24456, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36190779

RESUMO

Searching for materials with a high thermoelectric figure of merit (ZT) has always been the goal of scientific researchers in the energy field. Here, we combine first-principles calculations to obtain the thermoelectric characteristics of Tl3XSe4 (X = V, Nb, or Ta). First, we compared the phonon thermal transport characteristics of Tl3XSe4 by solving the Boltzmann transport equation and calculated the thermal conductivity. After that, we obtained the thermoelectric properties of Tl3XSe4 through the relaxation time approximation theory. The results show that Tl3XSe4 has a high Seebeck coefficient, high electrical conductivity, high power factor (PF) and low thermal conductivity contributed by both phonons and electrons. At the same time, the ZT value of Tl3XSe4 shows that it is a potential thermoelectric material with excellent performance. This work demonstrates the thermoelectric transport characteristics of Tl3XSe4 to explore its potential applications in many other fields of thermoelectricity and energy.

7.
Drug Dev Res ; 83(4): 952-960, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35132666

RESUMO

Evidence has demonstrated that Daphnetin has antiangiogenesis activity, indicating it might be a new multi-targeted medication for cancer therapy. Here, we aimed to reveal Daphnetin role in hepatocellular carcinoma (HCC) progression and the underlying mechanism. Huh7 and SK-HEP-1, two human HCC cell lines were used in this study. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and tumor-bearing experiments were applied to evaluate the effects of different concentrations of Daphnetin on cell viability, apoptosis, cell cycle, and in vivo tumor formation, respectively. Real-time PCR (Polymerase Chain Reaction)and western blotting were applied to measure the mRNA and protein levels of ß-catenin. We observed that Daphnetin inhibited cell viability and tumorigenesis, promoted cell apoptosis, and induced a G1 phase arrest in a dose-dependent manner in both Huh7 and SK-HEP-1 cells, which were rescued by SKL2001, an activator of the Wnt/ß-catenin signaling. Taken together, this study reveals that Daphnetin exerts an antitumor role in HCC through the inactivation of Wnt/ß-catenin signaling.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Umbeliferonas , Via de Sinalização Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo , beta Catenina/farmacologia
8.
Molecules ; 27(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36500432

RESUMO

Aminopeptidase N (APN) was closely associated with cancer invasion, metastasis, and angiogenesis. Therefore, APN inhibitors have attracted more and more attention of scientists as antitumor agents. In the current study, we designed, synthesized, and evaluated one new series of pyrazoline-based hydroxamate derivatives as APN inhibitors. Moreover, the structure-activity relationships of those were discussed in detail. 2,6-Dichloro substituted compound 14o with R1 = CH3, showed the best capacity for inhibiting APN with an IC50 value of 0.0062 ± 0.0004 µM, which was three orders of magnitude better than that of the positive control bestatin. Compound 14o possessed both potent anti-proliferative activities against tumor cells and potent anti-angiogenic activity. At the same concentration of 50 µM, compound 14o exhibited much better capacity for inhibiting the micro-vessel growth relative to bestatin in the rat thoracic aorta ring model. Additionally, the putative interactions of 14o with the active site of APN are also discussed. The hydroxamate moiety chelated the zinc ion and formed four hydrogen bonds with His297, Glu298 and His301. Meanwhile, the terminal phenyl group and another phenyl group of 14o interacted with S2' and S1 pockets via hydrophobic effects, respectively.


Assuntos
Antineoplásicos , Antígenos CD13 , Ratos , Animais , Inibidores de Proteases/química , Ácidos Hidroxâmicos/farmacologia , Antineoplásicos/farmacologia , Relação Estrutura-Atividade
9.
Fungal Genet Biol ; 147: 103505, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33347973

RESUMO

Cordyceps guangdongensis is a well-known fungus with high nutritional and medicinal value. The metabolite profile of C. guangdongensis is similar to that of Ophiocordyceps sinensis. In plants and animals, microRNAs play important roles in regulating gene expression at the post-transcriptional level. MicroRNA-like RNAs (milRNAs) have been documented in several macro-fungi. To comprehensively investigate the milRNAs in C. guangdongensis, three small RNA libraries from the differentially developmental stages were constructed. Twenty-six conserved milRNAs were identified, and 19 novel milRNA candidates were predicted. Among them, 20 milRNAs were differentially expressed across the developmental processes, and 12 milRNAs were verified using stem-loop quantitative real-time reverse transcription polymerase chain reaction. In addition, the potential target genes of milRNA were predicted to be involved in the development of fruiting bodies and metabolite biosynthesis. This study is the first to report the milRNAs of C. guangdongensis, and provides important insights into studies of milRNA regulation pathways in ascomycete fungi.


Assuntos
Cordyceps/crescimento & desenvolvimento , Cordyceps/genética , Regulação Fúngica da Expressão Gênica , MicroRNAs/genética , RNA Fúngico/genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Redes e Vias Metabólicas/genética , MicroRNAs/isolamento & purificação
10.
Appl Microbiol Biotechnol ; 104(21): 9295-9308, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918580

RESUMO

Tolypocladium guangdongense is a high-value edible fungus with various medicinal and food safety properties. However, its evolutionary and genetic information is still limited. Mitochondrial genomes are potential models for molecular evolution and phylogenetic studies. In this study, we sequenced the complete mitogenome of T. guangdongense, demonstrating circular sequence of 46,102 bp, containing 14 standard protein-coding genes (PCGs), 2 ribosomal RNA subunit genes, and 28 tRNA genes. Phylogenetic analysis based on mitochondrial genes indicated that T. guangdongense was clustered into the Tolypocladium genus with high support value, based on the core PCG dataset. In addition, rps3 is also a suitable marker in the phylogenetic analysis in Hypocreales. Gene rearrangement analysis indicated that the gene order of PCGs was highly consistent in Hypocreales, and tRNA rearrangement events occurred in most species of Hypocreales; however, the rearrangement rates were not taxonomically correlated. Divergence time estimation based on the old fossil record and previous reports revealed that T. guangdongense originated approximately in the middle Cenozoic (42 Mya, 95% highest posterior density interval: 43-116) with the Tolypocladium genus differentiation. Our results provided more mitogenomic information of T. guangdongense and shed new insights into evolution of the Tolypocladium genus. KEY POINTS: • The general and unique features of T. guangdongense mitogenome are firstly reported. • Phylogenetic analysis further verified the taxonomic status of T. guangdongense. • Divergence time estimation provides more evolutionary information of T. guangdongense.


Assuntos
Genoma Mitocondrial , Hypocreales , Evolução Molecular , Ordem dos Genes , Genes Mitocondriais , Hypocreales/genética , Filogenia , RNA de Transferência/genética
11.
Molecules ; 24(11)2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167344

RESUMO

In this work, random forest (RF), support vector machine, k-nearest neighbor and C4.5 decision tree, were used to establish classification models for predicting whether an unknown molecule is an inhibitor of human topoisomerase I (Top1) protein. All these models have achieved satisfactory results, with total prediction accuracies from 89.70% to 97.12%. Through comparative analysis, it can be found that the RF model has the best forecasting effect. The parameters were further optimized to generate the best-performing RF model. At the same time, features selection was implemented to choose properties most relevant to the inhibition of Top1 from 189 molecular descriptors through a special RF procedure. Subsequently, a ligand-based virtual screening was performed from the Maybridge database by the optimal RF model and 596 hits were picked out. Then, 67 molecules with relative probability scores over 0.7 were selected based on the screening results. Next, the 67 molecules above were docked to Top1 using AutoDock Vina. Finally, six top-ranked molecules with binding energies less than -10.0 kcal/mol were screened out and a common backbone, which is entirely different from that of existing Top1 inhibitors reported in the literature, was found.


Assuntos
Aprendizado de Máquina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/farmacologia , Algoritmos , Simulação por Computador , Humanos , Estrutura Molecular , Curva ROC , Reprodutibilidade dos Testes
12.
BMC Cancer ; 18(1): 1110, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424721

RESUMO

BACKGROUND: Earlier diagnosis is beneficial for the prognosis of hepatocellular carcinoma (HCC). Alpha fetoprotein (AFP) is the most widely used biomarker for HCC, but its sensitivity and specificity are only 60 and 90%, respectively. Therefore, it is of great clinical significance to identify early prognostic biomarkers for HCC, especially a blood-based biomarker as it offers several advantages over tissue-based biomarkers. Trefoil factor 3 (TFF3), a novel secretory protein, was over-expressed in HCC tissues, indicating it might be a blood-based biomarker for HCC. In addition, circulating microRNAs have been investigated as biomarkers for HCC, indicating that miR-7-5p and miR-203a-3p, which are reported or predicted to target TFF3, also hold promise as blood-based biomarkers for HCC. METHODS: We enrolled 43 patients who were firstly diagnosed HCC and matched 47 control subjects without HCC. The levels of TFF3, miR-7-5p and miR-203a-3p were tested in the plasma of HCC patients. Moreover, we assayed the correlation of TFF3 with its related micro RNAs, miR-7-5p and miR-203a-3p, and evaluated their predictive powers for HCC. RESULTS: Decrease of TFF3 was associated with increase of miR-203a-3p in the plasma of HCC patients and they displayed potent predictive powers for HCC diagnosis. However, there was no significant change of plasma miR-7-5p between HCC and control group. CONCLUSION: Decrease of TFF3 correlated with increase of miR-203a-3p in the plasma of HCC patients and they could be additional biomarkers to improve sensitivity and specificity in the diagnosis of HCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , MicroRNA Circulante/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico , MicroRNAs/sangue , Fator Trefoil-3/sangue , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/genética , Imageamento por Ressonância Magnética , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Tomografia Computadorizada por Raios X , Fator Trefoil-3/genética
13.
Zhongguo Zhong Yao Za Zhi ; 42(9): 1736-1741, 2017 May.
Artigo em Zh | MEDLINE | ID: mdl-29082698

RESUMO

To study the inhibitory effect of Glehniae Radix petroleum ether part on TGF-ß1-induced epithelial mesenchymal transition in non-small cell lung cancer A549 and its possible mechanism. With type Ⅱ epithelial cells of lung cancer A549 as the research object, the experiment was performed in 5 µg•L⁻¹ TGF-ß1-induced epithelial mesenchymal transition model,and blank control group, model group and Glehniae Radix petroleum ether group were set up. MTT assay was carried out to detect the effect of petroleum ether extract of Glehniae Radix on the survival of A549 cells. A549 cells induced by TGF-ß1(5 µg•L⁻¹) was intervened by different polar parts of Glehniae Radix, Real-time quantitative polymerase chain reaction(RT-qPCR) was used to analyze mRNA expressions of the epithelial mesenchymal transition markers, such as ColⅠ,E-cadherin,Vimentin and α-SMA. Enzyme linked immunosorbent assay(ELISA) was used to detect hydroxyproline(HYP) level. The migration and invasion abilities of cells were detected through wound scratch assay. According to the experimental results, the petroleum ether extract of Glehniae Radix could inhibit the growth of A549 cells in a concentration-dependent manner. Compared with model group, Glehniae Radix petroleum ether part group could effectively inhibit mRNA expressions of ColⅠ,Vimentin and α-SMA, but improve expression of E-cadherin.Glehniae Radix petroleum ether part could reduce the content of hydroxyproline in cells and inhibit the migration of A549 cells.Therefore, the petroleum ether extract of Glehniae Radix can effectively inhibit the occurrence of epithelial mesenchymal transition induced by TGF-ß1 induced alveolar epithelial cells, and Glehniae Radix petroleum ether part may be a potential drug for idiopathic pulmonary fibrosis. The mechanism may be achieved through the regulation of ColⅠ, Vimentin, α-SMA and E-cadherin.


Assuntos
Apiaceae/química , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células A549 , Actinas/metabolismo , Alcanos , Antígenos CD , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas , Colágeno/metabolismo , Células Epiteliais/citologia , Humanos , Neoplasias Pulmonares , Raízes de Plantas/química , Fator de Crescimento Transformador beta1/farmacologia , Vimentina/metabolismo
14.
Biochem Biophys Res Commun ; 470(1): 61-67, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26740180

RESUMO

Receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated signaling is essential for osteoclast differentiation, activation, and survival. Salicortin is a phenolic glycoside that has been isolated from many plants such as Populus and Salix species, and has been shown to have anti-amnesic and anti-adipogenic effects. In this study, we investigated the effect of salicortin on RANKL-induced osteoclasts formation, bone resorption, and activation of osteoclast-related signaling pathways. Salicortin suppressed RANKL-induced osteoclastogenesis in bone marrow macrophage cultures in a dose-dependent manner, and inhibited osteoclastic bone resorption activity without any cytotoxicity. Salicortin inhibited RANKL-induced c-Jun N-terminal kinase and NF-κB activation, concomitant with retarded IκBα phosphorylation and inhibition of p65 nuclear translocation, leading to impaired transcription of nuclear factor of activated T cells c1 (NFATc1) and expression of osteoclastic-specific genes. Taken together, our findings demonstrate that salicortin inhibits NF-κB and NFATc1 activation, leading to attenuation of osteoclastogenesis and bone resorption. Thus, salicortin may be of interest in developments of treatment for osteoclast related diseases.


Assuntos
Reabsorção Óssea/metabolismo , Glucosídeos/administração & dosagem , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Animais , Reabsorção Óssea/patologia , Reabsorção Óssea/prevenção & controle , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Tíbia
15.
Mol Plant Microbe Interact ; 28(10): 1091-101, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26035129

RESUMO

Botrytis cinerea is a necrotrophic pathogen that causes gray mold disease in a broad range of plants. Dihydroxynaphthalene (DHN) melanin is a major component of the extracellular matrix of B. cinerea, but knowledge of the exact role of melanin biosynthesis in this pathogen is unclear. In this study, we characterize two genes in B. cinerea, bcpks13 and bcbrn1, encoding polyketide synthase and tetrahydroxynaphthalene (THN) reductases, respectively, and both have predicted roles in DHN melanin biosynthesis. The ∆bcpks13 and ∆bcbrn1 mutants show white and orange pigmentation, respectively, and the mutants are also deficient in conidiation in vitro but show enhanced growth rates and virulence on hosts. Moreover, the mutants display elevated acidification of the complete medium (CM), probably due to oxalic acid secretion and secretion of cell wall-degrading enzymes, and preferably utilize plant cell-wall components as carbon sources for mycelium growth in vitro. In contrast, overexpression of bcbrn1 (OE::bcbrn1 strain) results in attenuated hydrolytic enzyme secretion, acidification ability, and virulence. Taken together, these results indicate that bcpks13 and bcbrn1 participate in diverse cellular and developmental processes, such as melanization and conidiation in B. cinerea in vitro, but they negatively regulate the virulence of this pathogen.


Assuntos
Botrytis , Proteínas Fúngicas/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Doenças das Plantas/microbiologia , Policetídeo Sintases/genética , Botrytis/citologia , Botrytis/genética , Botrytis/crescimento & desenvolvimento , Botrytis/patogenicidade , Capsicum/microbiologia , Frutas/microbiologia , Proteínas Fúngicas/metabolismo , Expressão Gênica , Regulação Fúngica da Expressão Gênica , Hifas , Melaninas/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Folhas de Planta/microbiologia , Policetídeo Sintases/metabolismo , Análise de Sequência de DNA , Deleção de Sequência , Nicotiana/microbiologia , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
16.
Biol Res ; 48: 26, 2015 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-25993985

RESUMO

BACKGROUND: Transforming growth factor (TGF)-ß is involved in many physiologic processes, it often promotes metastasis, and its high expression is correlated with poor prognosis. In the present study, we analyzed the correlation between transforming growth factor beta 1 (TGF-ß1) expression and prognosis in intrahepatic cholangiocarcinoma. RESULTS: We examined the expression of TGF-ß1 in 78 intrahepatic cholangiocarcinomas by immunohistochemistry and correlated the expression with clinicopathological parameters. TGF-ß1 was expressed in 37 of 78 (47.4%) intrahepatic cholangiocarcinomas. The expression of TGF-ß1 was significantly correlated with lymph node metastasis, distant metastasis, and tumour recurrence. Patients with TGF-ß1-positive tumours had significantly shorter survival time. In a multivariant analysis, the expression of TGF-ß1 and the tumour stage were independent prognostic factors. CONCLUSIONS: Our data suggest that expression of TGF-ß1 is a novel prognostic marker for intrahepatic cholangiocarcinoma.


Assuntos
Colangiocarcinoma/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Biomarcadores Tumorais/sangue , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Colangiocarcinoma/secundário , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Tempo
17.
BMC Anesthesiol ; 15: 27, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25774090

RESUMO

BACKGROUND: To determine the median effective concentration of sufentanil as an analgesic during wake-up tests after sevoflurane anesthesia during surgery for adolescent idiopathic scoliosis (AIS). METHODS: This is a randomised controlled trial. Sixty patients aged 13-18 years scheduled for AIS surgery were randomized into six groups of 10 patients each to receive target effect-site concentrations of sufentanil of 0.19, 0.1809, 0.1723, 0.1641, 0.1563, and 0.1489 ng/ml (target concentration ratio, 1.05). Wake-up time was recorded. Median EC50 and 95% confidence interval (CI) for sufentanil target-controlled infusion (TCI) were determined using Kärber's method. The primary outcome was median EC50 for sufentanil TCI as an analgesic during the wake-up test after sevoflurane anesthesia during surgery for AIS. RESULTS: The EC50 and 95% CI of sufentanil TCI were 0.1682 ng/ml and 0.1641 ~ 0.1724 ng/ml, respectively. CONCLUSIONS: The EC50 of sufentanil TCI was 0.1682 ng/ml (95% CI: 0.1641 ~ 0.1724 ng/ml) during sevoflurane anesthesia in adolescents undergoing surgery for idiopathic scoliosis with intraoperative wake-up tests. TRIAL REGISTRATION: Clinicaltrials.gov identifier: ChiCTR-TTRCC-12002696.


Assuntos
Monitorização Intraoperatória , Sufentanil/administração & dosagem , Sufentanil/farmacologia , Vigília/efeitos dos fármacos , Adolescente , Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/farmacologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Éteres Metílicos/farmacologia , Escoliose/cirurgia , Sevoflurano , Traumatismos da Medula Espinal/induzido quimicamente , Traumatismos da Medula Espinal/prevenção & controle , Sufentanil/efeitos adversos , Fatores de Tempo
18.
Chemphyschem ; 15(14): 3015-25, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-25056204

RESUMO

First-principles calculations are used to explore the strong binding of lithium to boron- and carbon-doped BC2N monolayers (BC2NBC and BC2NCN, respectively) without the formation of lithium clusters. In comparison to BC2N and BC2NCB, lithium-decorated BC2NBC and BC2NCN systems possess stronger s-p and p-p hybridization and, hence, the binding energy is higher. Lithium becomes partially positively charged by donating electron density to the more electronegative atoms of the sheet. Attractive van der Waals interactions are responsible for binding hydrogen molecules around the lithium atoms. Each lithium atom can adsorb three hydrogen molecules on both sides of the sheet, with an average hydrogen binding energy of approximately 0.2 eV, which is in the range required for practical applications. The BC2NBC-Li and BC2NCN-Li complexes can serve as high-capacity hydrogen-storage media with gravimetric hydrogen capacities of 9.88 and 9.94 wt %, respectively.

19.
Int J Clin Oncol ; 19(5): 880-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24272391

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Arsenic resistance protein 2 (Asr2) was reported to be important for microRNA (miR) biogenesis, and its depletion could reduce the levels of several miRs, including miR-21, which is over-expressed in HCC. We hypothesized that Ars2 is also overexpressed in HCC and may be involved in the biological properties of HCC. METHODS: Ars2 immunolabeling was evaluated in 132 HCCs. Ars2 immunolabeling, Ars2 qRT-PCR and miR-21 were evaluated in 20 HCCs and in paired normal tissues. Ars2 shRNA was transfected into SMCC-7721 and HepG2 HCC cells. The cell proliferation and expression of Ars2 and miR-21 were subsequently evaluated. RESULTS: Ars2 was expressed primarily in the nucleus of HCC cells. The expression of Ars2 was statistically correlated with the loss of HCC differentiation and pathological stage. The survival rates of patients with low Ars2 expression in HCC were statistically higher than patients with overexpressed Ars2 in HCC. Ars2 and miR-21 were more highly expressed in HCC specimens than normal tissues, and they were also correlated. The knockdown of Ars2 in HCC cells inhibited miR-21 expression and cell proliferation. CONCLUSIONS: Ars2 is overexpressed in HCC and may have prognostic value; it might play an important role in HCC proliferation and miR-21 expression.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Nucleares/biossíntese , Prognóstico , Adulto , Idoso , Apoptose/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células , China , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Proteínas Nucleares/genética
20.
Commun Chem ; 7(1): 64, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538750

RESUMO

Norcoclaurine synthase from Thalictrum flavum (TfNCS) demonstrated high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, achieving kinetic resolution of aldehydes. However, the mechanism and the factors contributing to the stereoselectivity remain unclear. Herein, by using quantum chemical calculations, the mechanisms of TfNCS-catalyzed reactions of dopamine with both enantiomers of α-methyl-phenylacetaldehyde are studied. The calculations reveal a mechanism mirroring the reaction of natural substrates, for which the deprotonation of the C5-H of the cyclized intermediate is rate-limiting. The calculated overall barriers are 20.1 kcal mol-1 and 21.6 kcal mol-1 for the reactions of (R)- and (S)-α-methyl-phenylacetaldehyde, respectively. The M97 and L72 residues are proposed to be the key residues contributing to the stereospecificity. The obtained detailed information is helpful for designing new variants of TfNCS with extended substrate scope, and also advancing our understanding of TfNCS reactions for potential applications.

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