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1.
Proc Natl Acad Sci U S A ; 120(39): e2307899120, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37733740

RESUMEN

The human blood-brain barrier (BBB) comprises a single layer of brain microvascular endothelial cells (HBMECs) protecting the brain from bloodborne pathogens. Meningitis is among the most serious diseases, but the mechanisms by which major meningitis-causing bacterial pathogens cross the BBB to reach the brain remain poorly understood. We found that Streptococcus pneumoniae, group B Streptococcus, and neonatal meningitis Escherichia coli commonly exploit a unique vesicle fusion mechanism to hitchhike on transferrin receptor (TfR) transcytosis to cross the BBB and illustrated the details of this process in human BBB model in vitro and mouse model. Toll-like receptor signals emanating from bacteria-containing vesicles (BCVs) trigger K33-linked polyubiquitination at Lys168 and Lys181 of the innate immune regulator TRAF3 and then activate the formation of a protein complex containing the guanine nucleotide exchange factor RCC2, the small GTPase RalA and exocyst subcomplex I (SC I) on BCVs. The distinct function of SEC6 in SC I, interacting directly with RalA on BCVs and the SNARE protein SNAP23 on TfR vesicles, tethers these two vesicles and initiates the fusion. Our results reveal that innate immunity triggers a unique modification of TRAF3 and the formation of the HBMEC-specific protein complex on BCVs to authenticate the precise recognition and selection of TfR vesicles to fuse with and facilitate bacterial penetration of the BBB.


Asunto(s)
Barrera Hematoencefálica , Células Endoteliales , Humanos , Animales , Ratones , Recién Nacido , Factor 3 Asociado a Receptor de TNF , Transcitosis , Bacterias , Receptores de Transferrina
2.
J Infect Dis ; 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38330453

RESUMEN

Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles and escapes into the cytosol by disrupting fusiform vesicle membrane using outer membrane phospholipase PldA, and establishes biofilm-like intracellular bacterial communities (IBCs) for protection from host immune clearance. Cytosolic UPEC is captured by autophagy to form autophagosomes, then transport to lysosomes, triggering the spontaneous exocytosis of lysosomes. The mechanism by which UPEC evades autophagy to recognize and form IBCs remains unclear. Here, we demonstrate that by inhibiting autophagic flux, UPEC PldA reduces the lysosome exocytosis of BECs. By reducing intracellular PI3P levels, UPEC PldA increases the accumulation of NDP52 granules and decreases the targeting of NDP52 to autophagy, hence stalling pre-autophagosome structures. Thus, our results uncover a critical role for PldA to inhibit autophagic flux, favoring UPEC escapes from lysosome exocytosis, thereby contributing to acute UTI.

3.
Microb Cell Fact ; 23(1): 113, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38622698

RESUMEN

BACKGROUND: Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. RESULTS: Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield-980.8 mg/L of isatropolone A-achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. CONCLUSION: In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.


Asunto(s)
Streptomyces , Streptomyces/metabolismo , Vías Biosintéticas/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Regiones Promotoras Genéticas , Familia de Multigenes
4.
Hepatol Res ; 54(2): 142-150, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37706554

RESUMEN

AIM: This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients. METHODS: Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies-vaccination without screening, screening-based vaccination, and no vaccination-among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties. RESULTS: It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. CONCLUSIONS: The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.

5.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38396909

RESUMEN

Single-cell RNA sequencing (scRNA-seq) data reveal the complexity and diversity of cellular ecosystems and molecular interactions in various biomedical research. Hence, identifying cell types from large-scale scRNA-seq data using existing annotations is challenging and requires stable and interpretable methods. However, the current cell type identification methods have limited performance, mainly due to the intrinsic heterogeneity among cell populations and extrinsic differences between datasets. Here, we present a robust graph artificial intelligence model, a multi-view graph convolutional network model (scMGCN) that integrates multiple graph structures from raw scRNA-seq data and applies graph convolutional networks with attention mechanisms to learn cell embeddings and predict cell labels. We evaluate our model on single-dataset, cross-species, and cross-platform experiments and compare it with other state-of-the-art methods. Our results show that scMGCN outperforms the other methods regarding stability, accuracy, and robustness to batch effects. Our main contributions are as follows: Firstly, we introduce multi-view learning and multiple graph construction methods to capture comprehensive cellular information from scRNA-seq data. Secondly, we construct a scMGCN that combines graph convolutional networks with attention mechanisms to extract shared, high-order information from cells. Finally, we demonstrate the effectiveness and superiority of the scMGCN on various datasets.


Asunto(s)
Inteligencia Artificial , Investigación Biomédica , Ecosistema , Análisis de Expresión Génica de una Sola Célula , Aprendizaje , Análisis de la Célula Individual , Análisis de Secuencia de ARN , Perfilación de la Expresión Génica , Análisis por Conglomerados , Algoritmos
6.
Sensors (Basel) ; 23(3)2023 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-36772533

RESUMEN

Corn diseases are one of the significant constraints to high-quality corn production, and accurate identification of corn diseases is of great importance for precise disease control. Corn anthracnose and brown spot are typical diseases of corn, and the early symptoms of the two diseases are similar, which can be easily misidentified by the naked eye. In this paper, to address the above problems, a three-dimensional-two-dimensional (3D-2D) hybrid convolutional neural network (CNN) model combining a band selection module is proposed based on hyperspectral image data, which combines band selection, attention mechanism, spatial-spectral feature extraction, and classification into a unified optimization process. The model first inputs hyperspectral images to both the band selection module and the attention mechanism module and then sums the outputs of the two modules as inputs to a 3D-2D hybrid CNN, resulting in a Y-shaped architecture named Y-Net. The results show that the spectral bands selected by the band selection module of Y-Net achieve more reliable classification performance than traditional feature selection methods. Y-Net obtained the best classification accuracy compared to support vector machines, one-dimensional (1D) CNNs, and two-dimensional (2D) CNNs. After the network pruned the trained Y-Net, the model size was reduced to one-third of the original size, and the accuracy rate reached 98.34%. The study results can provide new ideas and references for disease identification of corn and other crops.


Asunto(s)
Redes Neurales de la Computación , Zea mays
7.
Int J Mol Sci ; 24(24)2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38139044

RESUMEN

Salmonella enterica serovar Typhimurium (S. Typhimurium), an important foodborne pathogen, causes diarrheal illness and gastrointestinal diseases. S. Typhimurium survives and replicates in phagocytic and non-phagocytic cells for acute or chronic infections. In these cells, S. Typhimurium resides within Salmonella-containing vacuoles (SCVs), in which the phosphate (Pi) concentration is low. S. Typhimurium senses low Pi and expresses virulence factors to modify host cells. However, the mechanism by which host cells reduce the Pi concentration in SCVs is not clear. In this study, we show that through the TLR4-MyD88-NF-κB signaling pathway, S. Typhimurium upregulates PIT1, which in turn transports Pi from SCVs into the cytosol and results in Pi starvation in SCVs. Immunofluorescence and western blotting analysis reveal that after the internalization of S. Typhimurium, PIT1 is located on SCV membranes. Silencing or overexpressing PIT1 inhibits or promotes Pi starvation, Salmonella pathogenicity island-2 (SPI-2) gene expression, and replication in SCVs. The S. Typhimurium ΔmsbB mutant or silenced TLR4-MyD88-NF-κB pathway suppresses the expression of the SPI-2 genes and promotes the fusion of SCVs with lysosomes. Our results illustrate that S. Typhimurium exploits the host innate immune responses as signals to promote intracellular replication, and they provide new insights for the development of broad-spectrum therapeutics to combat bacterial infections.


Asunto(s)
Fosfatos , Vacuolas , Humanos , Proteínas Bacterianas/metabolismo , Células HeLa , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Fosfatos/metabolismo , Salmonella typhimurium/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Vacuolas/metabolismo
8.
Int J Mol Sci ; 24(3)2023 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-36768620

RESUMEN

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important human pathogen causing severe diseases, such as hemorrhagic colitis and lethal hemolytic uremic syndrome. The signal-sensing capability of EHEC O157:H7 at specific host colonization sites via different two-component systems (TCSs) is closely related to its pathogenicity during infection. However, the types of systems involved and the regulatory mechanisms are not fully understood. Here, we investigated the function of the TCS BarA/UvrY regulator UvrY in the pathogenicity regulation of EHEC O157:H7. Our results showed that UvrY acts as a positive regulator of EHEC O157:H7 for cellular adherence and mouse colonization through the transcriptional activation of the locus for enterocyte effacement (LEE) pathogenic genes. Furthermore, this regulation is mediated by the LEE island master regulator, Ler. Our results highlight the significance of UvrY in EHEC O157:H7 pathogenicity and underline the unknown importance of BarA/UvrY in colonization establishment and intestinal adaptability during infection.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli O157 , Proteínas de Escherichia coli , Animales , Humanos , Ratones , Enterocitos , Infecciones por Escherichia coli/genética , Escherichia coli O157/genética , Proteínas de Escherichia coli/genética , Proteínas de la Membrana , Fosfotransferasas , Virulencia/genética
9.
Environ Monit Assess ; 195(12): 1508, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37987867

RESUMEN

In some developing countries, particularly China, a significant number of individual farmers manage small field scale of cultivated land. However, the existing research on cultivated land quality assessment mainly focuses on large-scale regions, establishing comprehensive index systems from a macro perspective, while lacking evaluations customized to individual farmers, who constitute a crucial component in agricultural production, and a demand-driven field-scale assessment of cultivated land quality. Therefore, we developed a field-scale index system that meets the needs of individual farmers in the black soil region of Northeast China. Additionally, we proposed a machine learning model for field-scale cultivated land quality assessment. The experimental results showed that our model achieved an [Formula: see text] value of 0.9660 and an [Formula: see text] of [Formula: see text] under fourfold cross-validation, which represents an improvement of 5.19% and a reduction of 1.13%, respectively, relative to the XGBoost model. Ultimately, we conducted obstacle factor diagnosis, aiming to assist individual farmers in identifying the existing issues in their cultivated land fields. This study not only provides guidance to individual farmers but also addresses the research gap in cultivated land quality assessment by offering an individual farmer demand-driven index system for field-scale studies.


Asunto(s)
Conservación de los Recursos Naturales , Suelo , Monitoreo del Ambiente , Agricultura , China
10.
BMC Microbiol ; 22(1): 299, 2022 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-36510135

RESUMEN

BACKGROUND: RpoN, also known as σ54, first reported in Escherichia coli, is a subunit of RNA polymerase that strictly controls the expression of different genes by identifying specific promoter elements. RpoN has an important regulatory function in carbon and nitrogen metabolism and participates in the regulation of flagellar synthesis, bacterial motility and virulence. However, little is known about the effect of RpoN in Plesiomonas shigelloides. RESULTS: To identify pathways controlled by RpoN, RNA sequencing (RNA-Seq) of the WT and the rpoN deletion strain was carried out for comparison. The RNA-seq results showed that RpoN regulates ~ 13.2% of the P. shigelloides transcriptome, involves amino acid transport and metabolism, glycerophospholipid metabolism, pantothenate and CoA biosynthesis, ribosome biosynthesis, flagellar assembly and bacterial secretion system. Furthermore, we verified the results of RNA-seq using quantitative real-time reverse transcription PCR, which indicated that the absence of rpoN caused downregulation of more than half of the polar and lateral flagella genes in P. shigelloides, and the ΔrpoN mutant was also non-motile and lacked flagella. In the present study, the ability of the ΔrpoN mutant to kill E. coli MG1655 was reduced by 54.6% compared with that of the WT, which was consistent with results in RNA-seq, which showed that the type II secretion system (T2SS-2) genes and the type VI secretion system (T6SS) genes were repressed. By contrast, the expression of type III secretion system genes was largely unchanged in the ΔrpoN mutant transcriptome and the ability of the ΔrpoN mutant to infect Caco-2 cells was also not significantly different compared with the WT. CONCLUSIONS: We showed that RpoN is required for the motility and contributes to the killing ability of P. shigelloides and positively regulates the T6SS and T2SS-2 genes.


Asunto(s)
Regulación Bacteriana de la Expresión Génica , Plesiomonas , Humanos , ARN Polimerasa Sigma 54/genética , Plesiomonas/genética , Plesiomonas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Células CACO-2
11.
Int J Mol Sci ; 23(10)2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35628353

RESUMEN

Escherichia coli K1 is the most popular neonatal meningitis-causing Gram-negative bacterium. As a key virulence determinant, the K1 capsule enhances the survival of E. coli K1 in human brain microvascular endothelial cells (HBMECs) upon crossing the blood-brain barrier; however, the regulatory mechanisms of capsule synthesis during E. coli K1 invasion of HBMECs remain unclear. Here, we identified YbdO as a transcriptional regulator that promotes E. coli K1 invasion of HBMECs by directly activating K1 capsule gene expression to increase K1 capsule synthesis. We found that ybdO deletion significantly reduced HBMEC invasion by E. coli K1 and meningitis occurrence in mice. Additionally, electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative polymerase chain reaction analysis indicated that YbdO directly activates kpsMT and neuDBACES expression, which encode products involved in K1 capsule transport and synthesis by directly binding to the kpsM promoter. Furthermore, ybdO transcription was directly repressed by histone-like nucleoid structuring protein (H-NS), and we observed that acidic pH similar to that of early and late endosomes relieves this transcriptional repression. These findings demonstrated the regulatory mechanism of YbdO on K1 capsule synthesis, providing further insights into the evolution of E. coli K1 pathogenesis and host-pathogen interaction.


Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Animales , Barrera Hematoencefálica/metabolismo , Células Endoteliales/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Humanos , Ratones , Virulencia/genética
12.
Angew Chem Int Ed Engl ; 60(28): 15399-15404, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-33884733

RESUMEN

Microbial sulfur-containing secondary metabolites show various biological activities, but the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate. Furthermore, X-ray crystal structure of CxnD in complex with a substrate analogue and structure-based mutagenesis revealed intimate details of the substrate binding mode. A radical mechanism initiated by abstraction of the imino hydrogen atom or an electron from indole group of the substrate was proposed for CxnD, which provided valuable insights into the molecular basis for the intra-molecular C(sp2 )-H thiolation by the P450 in chuangxinmycin biosynthesis.


Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Biocatálisis , Ciclización , Sistema Enzimático del Citocromo P-450/química , Indoles/química , Indoles/metabolismo , Estructura Molecular
13.
Food Microbiol ; 91: 103549, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32539955

RESUMEN

Zygosaccharomyces rouxii represents the main spoilage cause of concentrated apple juice, leading to waste of products or recalls. Essential oils components derived from plants have been found to present antimicrobial activities against various microbes. However, few work has been reported about their antimicrobial activities against Z. rouxii in concentrated apple juice. In this work, reparameterized Gompertz equation was used to evaluate the antimicrobial activities of different antimicrobials to inhibit the growth of a Z. rouxii cocktail (6.3 lg colony forming units/mL) composed of six strains isolated from concentrated apple juice and two strains from honey and grape must. The obtained mathematical models presented that thymol, carvacrol and trans-cinnamaldehyde were the promising options to inhibit Z. rouxii in 30 oBrix apple juice, reaching a maximal decrease on yeast growth of around 99.65 ± 0.61%. Whereas other antimicrobials showed lower antimicrobial activities with a maximal growth decrease of ranging from 67.13 ± 3.62% to 13.38 ± 1.16%. Additionally, the sensorial characteristics were not affected when the antimicrobials assayed were applied at the effective concentrations in commercial apple juice product. This work provided a theoretical feasibility that thymol, carvacrol and trans-cinnamaldehyde could be applied as natural preservatives for the control of Z. rouxii-related spoilage in fruit juice industry.


Asunto(s)
Antifúngicos/farmacología , Jugos de Frutas y Vegetales/microbiología , Malus , Saccharomycetales/efectos de los fármacos , Recuento de Colonia Microbiana , Microbiología de Alimentos , Conservantes de Alimentos/farmacología , Jugos de Frutas y Vegetales/análisis , Modelos Teóricos , Aceites Volátiles/farmacología , Saccharomycetales/crecimiento & desarrollo , Sensación
14.
Molecules ; 24(17)2019 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-31470665

RESUMEN

Fungal infection is a leading cause of mortality in immunocompromised population; thus, it is urgent to develop new and safe antifungal agents. Different from human cells, fungi have a cell wall, which is composed mainly of polysaccharide glucan and chitin. The unique cell wall structure is an ideal target for antifungal drugs. In this research, a chemical-genetic method was used to isolate antifungal agents that target chitin synthesis in yeast cells. From a compound library, we isolated two benzothiazole compounds that showed greater toxicity to yeast mutants lacking glucan synthase Fks1 compared to wild-type yeast cells and mutants lacking chitin synthase Chs3. Both of them inhibited the activity of chitin synthase in vitro and reduced chitin level in yeast cells. Besides, these compounds showed clear synergistic antifungal effect with a glucan synthase inhibitors caspofungin. Furthermore, these compounds inhibited the growth of Saccharomyces cerevisiae and opportunistic pathogen Candida albicans. Surprisingly, the genome-wide mass-spectrometry analysis showed decreased protein level of chitin synthases in cells treated with one of these drugs, and this decrease was not a result of downregulation of gene transcription. Therefore, we successfully identified two new antifungal agents that inhibit chitin synthesis using a chemical-genetic method.


Asunto(s)
Antifúngicos/farmacología , Benzotiazoles/farmacología , Candida albicans/efectos de los fármacos , Quitina Sintasa/genética , Quitina/antagonistas & inhibidores , Equinocandinas/genética , Regulación Fúngica de la Expresión Génica , Glucosiltransferasas/genética , Proteínas de la Membrana/genética , Proteínas de Saccharomyces cerevisiae/genética , Antifúngicos/química , Benzotiazoles/química , Candida albicans/enzimología , Candida albicans/genética , Candida albicans/crecimiento & desarrollo , Caspofungina/farmacología , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo , Quitina/biosíntesis , Quitina Sintasa/antagonistas & inhibidores , Quitina Sintasa/deficiencia , Combinación de Medicamentos , Descubrimiento de Drogas , Sinergismo Farmacológico , Equinocandinas/antagonistas & inhibidores , Equinocandinas/deficiencia , Perfilación de la Expresión Génica , Glucosiltransferasas/antagonistas & inhibidores , Glucosiltransferasas/deficiencia , Ensayos Analíticos de Alto Rendimiento , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/deficiencia , Pruebas de Sensibilidad Microbiana , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Proteínas de Saccharomyces cerevisiae/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología
15.
Chemistry ; 24(2): 306-311, 2018 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-29052261

RESUMEN

Synthesis of SFE-type borosilcate zeolite was successfully carried out using a commercially available low-cost organic structure directing agent (OSDA) with ultra-low OSDA and water contents within a short crystallization time. Heteroatom (Al, Ti, V, or Fe)-substituted SFE-type zeolite analogues were also directly synthesized for the first time. The obtained Al containing zeolites exhibited promising catalytic performances in the disproportionation of isopropylnaphthalene.

16.
J Vasc Surg ; 65(4): 1180-1188.e1, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27237401

RESUMEN

OBJECTIVE: Coagulation factor V (FV) is distributed in plasma and platelet pools, which are distinguished by physical and functional differences. FV has been extensively studied for its roles in coagulation. The roles of FV in other physiologic pathways remain understudied. METHODS: Hind limb ischemia was produced in transgenic mice by femoral artery ligation, with different levels of FV gene expression restricted to the plasma or platelets. RESULTS: Hind limb blood flow perfusion in mice with higher platelet FV was significantly increased. The expression of major angiogenesis-related factors was correlated with the level of FV during ischemia. Furthermore, a platelet depletion and transfusion procedure showed that the transfusion of platelets with higher levels of FV into transgenic mice with undetectable platelet FV significantly rescued the ischemia-mediated impairments in blood flow perfusion. Immunohistochemistry analysis also indicated markedly increased capillary formation in the ischemic muscle of mice with higher platelet FV. Moreover, thrombin activity was significantly higher in the mice with higher platelet FV. Platelets expressing higher levels of FV stimulated increased endothelial cell migration. Hind limb blood flow perfusion was significantly blocked by thrombin inhibitor. CONCLUSIONS: These findings suggest that platelet-derived FV contributes to the control of angiogenesis and is likely associated with thrombin generation.


Asunto(s)
Plaquetas/metabolismo , Factor V/metabolismo , Isquemia/terapia , Músculo Esquelético/irrigación sanguínea , Neovascularización Fisiológica , Transfusión de Plaquetas , Proteínas Angiogénicas/genética , Proteínas Angiogénicas/metabolismo , Animales , Antitrombinas/farmacología , Velocidad del Flujo Sanguíneo , Movimiento Celular , Células Cultivadas , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Factor V/genética , Genotipo , Miembro Posterior , Hirudinas/farmacología , Isquemia/sangre , Isquemia/genética , Isquemia/fisiopatología , Ratones Endogámicos C57BL , Ratones Transgénicos , Fenotipo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Flujo Sanguíneo Regional , Trombina/metabolismo , Factores de Tiempo
17.
Int J Syst Evol Microbiol ; 67(10): 4210-4215, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28920829

RESUMEN

A Gram-stain-positive, non-spore-forming actinobacterial strain, designated CPCC 204077T, was isolated from the surface-sterilized root of a medicinal plant Huperzia serrata (Thunb.) collected from Sichuan Province, south-west China. The peptidoglycan type of strain CPCC 204077T was detected as A4α with an l-Lys-l-Ser-d-Asp interpeptide bridge. Galactose, glucose, rhamnose and ribose were the sugar compositions in the whole-cell hydrolysates. MK-8(H4) was the only menaquinone. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, one unidentified phospholipid and one unidentified glycolipid. The major fatty acid was iso-C16 : 0. The genomic DNA G+C content was 71.0 mol%. The phylogenetic tree based on 16S rRNA gene sequences showed that strain CPCC 204077T stood for a distinct lineage within the family Dermacoccaceaealongside the genera Branchiibius, Demetria and Barrientosiimonas, with the highest 16S rRNA gene sequence similarities to Branchiibius hedensis Mer 29717T (95.0 %), Calidifontibacter indicus PC IW02T (95.0 %), Barrientosiimonas humi 39T (94.9 %) and Demetria terragena HKI 0089T (94.7 %), and less than 94.7 % sequence similarities to all other species. Signature nucleotides in the 16S rRNA sequence showed that the strain contained the Dermacoccaceaefamily-specific 16S rRNA signature nucleotides and a genus-specific diagnostic nucleotide signature pattern. Combining the genotypic and phenotypic analyses, we propose that strain CPCC 204077T represents a novel species of a new genus in the family Dermacoccaceae with the name Allobranchiibius huperziae gen. nov., sp. nov. Strain CPCC 204077T (=NBRC 110719T=DSM 29531T) is the type strain of the type species.


Asunto(s)
Actinomycetales/clasificación , Huperzia/microbiología , Filogenia , Raíces de Plantas/microbiología , Actinomycetales/genética , Actinomycetales/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , China , ADN Bacteriano/genética , Ácidos Grasos/química , Glucolípidos/química , Peptidoglicano/química , Fosfolípidos/química , Plantas Medicinales/microbiología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
18.
Int J Syst Evol Microbiol ; 67(6): 1867-1872, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28629493

RESUMEN

An endophytic, short rod-shaped, non-motile and non-spore-forming actinobacterium, designated strain CPCC 204135T, was isolated from a surface-sterilized medicinal plant, Huperzia serrata (Thunb.), collected from Sichuan Province, south-west China. Strain CPCC 204135T was observed to grow at temperatures between 20 and 37 °C (optimum, 28-32 °C), at pH 6.0-9.0 (optimum, pH 7.0-8.0) and in the presence of 0-9.0 % (w/v) NaCl (optimum, 0-3 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204135T belonged to the genus Naumannella, showing the highest level of 16S rRNA gene sequence similarity with Naumannella halotolerans DSM 24323T (97.2 %), the only species of the genus Naumannella in the family Propionibacteriaceaewith avalidly published name. The DNA-DNA hybridization value between strain CPCC 204135T and N. halotolerans DSM 24323T was 20.1±1.8 %, which is far below the accepted 70 % threshold for species delineation. The cell-wall hydrolysates contained ll-diaminopimelic acid, alanine, glycine and glutamic acid, with the peptidoglycan type of A3γ. Diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid, one unidentified aminolipid, one unidentified polar lipid and several kinds of glycolipids were detected in the polar lipids profile. MK-9(H4) was identified as the predominant menaquinone. The major cellular fatty acids (>10 %) were anteiso-C15 : 0 and iso-C16 : 0. The G+C content of the genomic DNA of strain CPCC 204135T was determined to be 71.8 mol%. On the basis of phylogenetic analysis, and phenotypic and chemotaxonomic characteristics, we concluded that strain CPCC 204135T represents a novel species of the genus Naumannella, for which the name Naumannella huperziae sp. nov. is proposed, with strain CPCC 204135T (=DSM 101717T=NBRC 111773T) as the type strain.


Asunto(s)
Huperzia/microbiología , Filogenia , Propionibacteriaceae/clasificación , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Glucolípidos/química , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , Plantas Medicinales/microbiología , Propionibacteriaceae/genética , Propionibacteriaceae/aislamiento & purificación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
19.
J Comput Chem ; 37(17): 1559-64, 2016 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-27010673

RESUMEN

Transcription factors (TFs) are the proteins involved in the transcription process, ensuring the correct expression of specific genes. Numerous diseases arise from the dysfunction of specific TFs. In fact, over 30 TFs have been identified as therapeutic targets of about 9% of the approved drugs. In this study, we created a structural database of small molecule-transcription factor (SM-TF) complexes, available online at http://zoulab.dalton.missouri.edu/SM-TF. The 3D structures of the co-bound small molecule and the corresponding binding sites on TFs are provided in the database, serving as a valuable resource to assist structure-based drug design related to TFs. Currently, the SM-TF database contains 934 entries covering 176 TFs from a variety of species. The database is further classified into several subsets by species and organisms. The entries in the SM-TF database are linked to the UniProt database and other sequence-based TF databases. Furthermore, the druggable TFs from human and the corresponding approved drugs are linked to the DrugBank. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Bases de Datos de Proteínas , Factores de Transcripción/química , Sistemas de Liberación de Medicamentos , Humanos , Bibliotecas de Moléculas Pequeñas/química , Factores de Transcripción/metabolismo
20.
Int J Syst Evol Microbiol ; 66(10): 3972-3977, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27413046

RESUMEN

A novel endophytic actinobacterium, designated strain CPCC 204076T, was isolated from surface-sterilized tissue of the medicinal plant Huperzia serrata (Thunb.) collected from Sichuan Province, south-west China. The taxonomic position of the isolate was investigated by a polyphasic approach. The strainwas aerobic, Gram-stain-positive, non-motile, non-spore-forming and rod-shaped. Growth was observed at 10-37 °C, at pH 5.0-10.0 and with 0-3.0 % (w/v) NaCl. The polar lipid fraction consisted of diphosphatidylglycerol, a phospholipid, an aminolipid, a glycolipid, an aminophospholipid and phosphatidylinositol. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid and the peptidoglycan was of type A4γ. The menaquinone system consisted of MK-9(H4) and MK-8(H4). The major cellular fatty acids (>10 %) were iso-C16 : 0 and anteiso-C17 : 0. The genomic DNA G+C content of strain CPCC 204076T was found to be 71.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that CPCC 204076T belongs to the genus Jatrophihabitans with highest sequence similarity to Jatrophihabitans endophyticus DSM 45627T (96.5 %), Jatrophihabitans soli DSM 45908T (96.5 %) and Jatrophihabitans fulvus JCM 30448T (96.1 %), and much lower similarities (<95.0 %) to other available 16S rRNA gene sequences from validly described pure cultures. However, DNA-DNA hybridyzation values between strain CPCC 204076T and the three recognized Jatrophihabitans species were 31±3.1 % (J. endophyticus DSM 45627T), 33±2.9 % (J. soli DSM 45908T) and 37±1.7 % (J. fulvus JCM 30448T), which were all far below the recommended cut-off value of 70 %. The phenotypic and genomic characteristics distinctly indicated that strain CPCC 204076T represents a novel species of the genus Jatrophihabitans, for which the name Jatrophihabitans huperziae sp. nov. is proposed. The type strain is CPCC 204076T (I13A-01604) (=DSM 46866T=NBRC 110718T).


Asunto(s)
Actinobacteria/clasificación , Huperzia/microbiología , Filogenia , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Glucolípidos/química , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , Plantas Medicinales/microbiología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/química
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