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Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.
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Carcinoma Hepatocelular , DNA Metiltransferase 3A , Epigênese Genética , L-Lactato Desidrogenase , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral/imunologia , Humanos , Animais , Camundongos , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , DNA Metiltransferase 3A/metabolismo , Regulação Neoplásica da Expressão Gênica , Metilação de DNA , Isoenzimas/genética , Isoenzimas/metabolismo , Linhagem Celular Tumoral , Inativação Gênica , PrognósticoRESUMO
Small noncoding RNAs (sncRNAs) play important regulatory roles in bacterial physiological processes and host-pathogen interactions. Meanwhile, bacterial outer membrane vesicles (OMVs), as naturally secreted outer membrane structures, play a vital role in the interaction between bacteria and their living environment, including the host environment. However, most current studies focus on the biological functions of sncRNAs in bacteria or hosts, while neglecting the roles and regulatory mechanisms of the OMVs that encapsulate these sncRNAs. Therefore, this review aims to summarize the intracellular regulatory roles of bacterial sncRNAs in promoting pathogen survival by regulating virulence, modulating bacterial drug resistance, and regulating iron metabolism, and their extracellular regulatory function for influencing host immunity through host-pathogen interactions. Additionally, we introduce the key role played by OMVs, which serve as important cargoes in bacterial sncRNA-host interactions. We propose emerging pathways of sncRNA action to further discuss the mode of host-pathogen interactions, highlighting that the inhibition of sncRNA delivery by OMVs may prevent the occurrence of infection to some extent. Hence, this review lays the foundation for future prophylactic treatments against bacterial infections and strategies for addressing bacterial drug resistance. KEY POINTS: â¢sncRNAs have intracellular and extracellular regulatory functions in bacterial physiological processes and host-pathogen interactions. â¢OMVs are potential mediators between bacterial sncRNAs and host cells. â¢OMVs encapsulating sncRNAs have more potential biological functions.
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Vesículas Extracelulares , Pequeno RNA não Traduzido , Pequeno RNA não Traduzido/genética , Proteínas da Membrana Bacteriana Externa/genética , Bactérias/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Interações entre Hospedeiro e Microrganismos , Vesículas Extracelulares/metabolismoRESUMO
The widespread prevalence of Helicobacter pylori (H. pylori) infection remains a great challenge to human health. The existing vaccines are not ideal for preventing H. pylori infection; thus, exploring highly effective adjuvants may improve the immunoprotective efficacy of H. pylori vaccines. In a previous study, we found that the outer membrane vesicles (OMVs), a type of nanoscale particle spontaneously produced by Gram-negative bacteria, could act as adjuvants to boost the immune responses to vaccine antigens. In this study, we explored the potential application of OMVs as delivery vectors for adjuvant development. We constructed recombinant OMVs containing eukaryotic expression plasmid of cytokines, including interleukin 17A or interferon-γ, and evaluated their function as adjuvants in combination with inactivated whole-cell vaccine (WCV) or UreB as vaccine antigens. Our results showed that recombinant OMVs as adjuvants could induce stronger humoral and mucosal immune responses in mice than wild-type H. pylori OMVs and the cholera toxin (CT) adjuvant. Additionally, the recombinant OMVs significantly promoted Th1/Th2/Th17-type immune responses. Furthermore, the recombinant OMV adjuvant induced more potent clearance of H. pylori than CT and wild-type OMVs. Our findings suggest that the recombinant OMVs coupled with cytokines may become potent adjuvants for the development of novel and effective vaccines against H. pylori infection.
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Infecções por Helicobacter , Helicobacter pylori , Vacinas , Humanos , Animais , Camundongos , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Citocinas/metabolismo , Infecções por Helicobacter/prevenção & controle , Adjuvantes Imunológicos , Toxina da Cólera/genética , Plasmídeos/genética , Vacinas Bacterianas , Anticorpos AntibacterianosRESUMO
BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.
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Vírus do Sarampo , Sarampo , Humanos , Vírus do Sarampo/genética , Genótipo , Filogenia , China/epidemiologia , Sarampo/epidemiologia , Sarampo/prevenção & controleRESUMO
Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNote, for comprehensive and precise glycome analysis. GlycoNote supports interpretation of tandem-mass spectrometry glycomic data from any sample source, uses a novel target-decoy method with iterative decoy searching for highly reliable result output, and embeds an open-search component analysis mode for heterogeneity analysis of monosaccharides and modifications. We tested GlycoNote on several different large-scale glycomic datasets, including human milk oligosaccharides, N- and O-glycome from human cell lines, plant polysaccharides, and atypical glycans from Caenorhabditis elegans, demonstrating its high capacity for glycome analysis. An application of GlycoNote to the analysis of labeled and derived glycans further demonstrates its broad usability in glycomic studies. By enabling generic characterization of various glycan types and elucidation of component heterogeneity in glycomic samples, the freely available GlycoNote is a promising tool for facilitating glycomics in glycobiology research.
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Glicômica , Polissacarídeos/química , Glicômica/métodos , Humanos , Espectrometria de Massas em TandemRESUMO
Photocatalytic oxidation is a popular transformation way for organic synthesis and is widely applied in academia and industry. Herein, we report a blue light-induced alkylation-oxidation tandem reaction for the synthesis of diverse ketones by combining alkyl radical addition and oxidation of alkenyl borates. This reaction shows excellent functional group compatibility in acceptable yields, and diversity of radical precursors is applicable.
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Photocatalytic valorization and selective transformation of biomass-derived platform compounds offer great opportunities for efficient utilization of renewable resources under mild conditions. Here, the novel three-dimensional hierarchical flower-like CdS/Ti3 C2 Schottky junction (MCdS) composed of surface-controlled CdS and pretreated Ti3 C2 MXene is created for photocatalytic dehydrogenation-reductive amination of biomass-derived amino acid production under ambient temperature with unprecedented activity and selectivity. Schottky junction efficiently promotes photoexcited charge migration and separation and inhibits photogenerated electron-hole recombination, which results in a super-high activity. Meanwhile, CdS with the reduced surface energy supplies sufficient hydrogen sources for imine reduction and induces the preferential orientation of alanine, thus contributing superior selectivity. Moreover, a wide range of hydroxyl acids are successfully converted into corresponding amino acids and even one-pot conversion of glucose to alanine is easily achieved over MCdS. This work illustrates the mechanism of crystal orientation control and heterojunction construction in controlling catalytic behavior of photocatalytic nanoreactor, providing a paradigm for construction of MXene-based heterostructure.
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Divergent synthesis of fluorine-containing scaffolds starting from a suite of raw materials is an intriguing topic. Herein, we report the solvent-controlled rhodium-catalyzed tunable arylation of 1-bromo-2,2-difluoroethylene. The selection of the reaction solvents provides switchable defluorinated or debrominated arylation from readily available feedstock resources (both arylboronic acids/esters and 1-bromo-2,2-difluoroethylene are commercially available). This switch is feasible because of the difference in coordination ability between the solvent (CH2 Cl2 or CH3 CN) and the rhodium center, resulting in different olefin insertion. This protocol allows the convenient synthesis of monofluoroalkenes and gem-difluoroalkenes, both of which are important scaffolds in the fields of medicine and materials. Moreover, this newly developed solvent-regulated reaction system can be applied to the site-selective dechlorinated arylation of trichloroethylene. Overall, this study provides a useful strategy for the divergent synthesis of fluorine-containing scaffolds and provides insight into the importance of solvent selection in catalytic reactions.
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BACKGROUND: 'Vegetative' and 'generative' tomato rootstock types have been proposed based on their different effects on tomato scion growth performance; however, their impacts on fruit quality have not been characterized. No study has been conducted in which the effects of rootstock on grape tomato quality attributes were assessed using sensory and instrumental methods of evaluation. Here, we conducted two experiments to examine the influence of 'DR0141TX', 'Estamino', and 'Multifort' rootstocks (vegetative, generative, and uncharacterized, respectively) on fruit quality properties of determinate and indeterminate grape tomato scions under organic production in high tunnels, including color, size, firmness, dry matter content, soluble solids content (SSC), titratable acidity (TA), pH, and consumer sensory attributes. RESULTS: In both experiments, grafting 'Sweet Hearts' indeterminate grape tomato onto 'DR0141TX', 'Estamino', or 'Multifort' increased fruit size and led to negligible effects on sensory attributes and instrumental measurements of fruit quality attributes. For 'BHN 1022' determinate grape tomato, rootstocks did not exhibit any major impact on fruit quality attributes in Experiment 1. However, fruit quality was compromised by grafting per se and rootstocks, especially 'Multifort', in Experiment 2, as reflected by reduced SSC, TA, and SSC/TA and lower scores for overall appearance, overall acceptability, tomato flavor, overall texture, and sweetness. CONCLUSION: In general, 'vegetative' and 'generative' rootstocks showed comparable effects on sensory evaluations and instrumental measurements of grape tomato quality attributes for both indeterminate and determinate scions. More research is needed to better characterize rootstock effects on fruit quality, including the flavor-related compounds under different growing conditions. © 2022 Society of Chemical Industry.
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Solanum lycopersicum , Vitis , Solanum lycopersicum/química , Frutas/química , PaladarRESUMO
This study aimed to decipher the pharmacodynamic material basis and mechanism of herbal pair Bupleurum scorzonerifolium-Paeonia lactiflora(BS-PL) against liver cancer based on UPLC-Q-TOF-MS and network pharmacology. MTT assay and human hepatocellular carcinoma HepG2 cells were used to screen the effective part of BS-PL, the active components of which were further analyzed and identified by UPLC-Q-TOF-MS. Next, we applied Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to screen the active ingredients with OB≥30%. Then TCMSP and SwissTargetPrediction were used to collect and predict component targets, followed by the search of liver cancer-related targets with GeneCards and DisGeNET. The intersection targets were obtained using Venny 2.1.0. Protein-protein interaction(PPI) network was constructed using STRING to uncover the core targets, which were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis based on DAVID. Finally, the effects of active ingredients on the expression of main proteins enriched in the key pathways of HepG2 cells were verified by Western blot. The results indicated that compared with 30%, 50%, and 70% ethanol extracts of BS-PL, the n-butanol extraction part(CSYZ) from 95% ethanol extract of BS-PL exhibited the best anti-tumor effect. UPLC-Q-TOF-MS revealed 31 ingredients, 14 of which showed OB≥30%. A total of 220 intersection targets were obtained, from which 35 were selected as the key targets under the condition of two times the median of degree. Among the 215 items with P<0.05 obtained through GO enrichment analysis, 154 were classified into biological processes, 22 into cell components and 39 into molecular functions. KEGG enrichment analysis revealed 95 significantly affected signaling pathways, and the ones(sorted in a descending order by P value) closely related to the anti-liver cancer effect of herbal pair were PI3 K-AKT signaling pathway, TNF signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, and ErbB signaling pathway. Finally, the PI3 K/AKT signaling pathway involving the largest number of targets was extrapolated, and it was found that this pathway contained 15 core targets and 8 active components. Experimental verification showed that the effective components of BS-PL significantly inhibited the expression of p-PI3 K and p-AKT, consistent with the prediction results of network pharmacology. In conclusion, the main pharmacodynamic substances of BS-PL against liver cancer are 14 components like saikosaponin a, saikosaponin d, and paeoniflorin, which exert the anti-liver cancer effect by regulating PI3 K/AKT pathway.
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Bupleurum , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Paeonia , Medicamentos de Ervas Chinesas/farmacologia , Etanol , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Proteínas Proto-Oncogênicas c-aktRESUMO
BACKGROUND: To provide a better understanding of the progress on rubella control and elimination in China, a genetic analysis was conducted to examine the transmission pattern of the endemic rubella virus in China during 2010-2019. METHODS: A total of 4895 strains were obtained from 29 of the 31 provinces in mainland China during 2010-2019. The genotyping regions of the strains were amplified, determined, and assembled. Genotyping analysis and lineage division were performed by comparisons with the World Health Organization reference strains and reported lineage reference strains, respectively. Further phylogenetic analyses were performed to compare the genetic relationship. RESULTS: During 2010-2019, the domestic lineage 1E-L1 and multiple imported lineages of rubella viruses including 2B-L1, 1E-L2, and 2B-L2c were identified. Further analysis of the circulation trend of the different lineages indicated that 2 switches occurred among the lineages. The first shift was from lineage 1E-L1 to 2B-L1, which occurred around 2015-2016, followed by the lowest rubella incidence in 2017. The second shift was from lineage 2B-L1 to 1E-L2 and 2B-L2c, which occurred around 2018-2019, coinciding with rubella resurgence and the subsequent nationwide epidemic during 2018-2019. Insufficient genomic information worldwide made it impossible to trace the origin of the imported viruses. CONCLUSIONS: China was moving toward rubella elimination, as evidenced by the fact that previous endemic lineages were not detected. However, rubella reemerged in 2018 2019 due to the newly imported rubella viruses. Therefore, to realize the rubella elimination goal, joint efforts are required for all countries worldwide.
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Vírus da Rubéola , Rubéola (Sarampo Alemão) , China/epidemiologia , Genótipo , Humanos , Filogenia , Rubéola (Sarampo Alemão)/epidemiologia , Vírus da Rubéola/genéticaRESUMO
As a new member of 2D materials, 2D tellurium (Te) has recently attracted much attention due to its intriguing properties. Through hydrothermal processing, 2D Te with tunable thickness and size has been realized, and its growth mechanism has also been studied. However, the tailored growth of 2D Te nanoflakes with symmetrical morphologies and interfacial moiré fringes has never been reported. Here, 2D Te nanoflakes have been prepared using the hydrothermal method, and mirror-symmetrical shapes (including "V-shape," "heart-shape," and "paper airplane-shape") with obvious moiré fringes in the middle of the nanoflakes are observed. Comprehensive transmission electron microscopy (TEM) techniques are utilized for structural characterization of these nanoflakes, especially the moiré fringes in the symmetry axis region of the nanoflakes. The systematic analyses of the moiré fringes and the observation of obvious overlapping edges of the composing nanoflakes from the cross-sectional samples reveal the possible mechanism of morphological evolution for these symmetrical nanoflakes. These details may fill the research gap in the controllable growth of 2D Te nanomaterials, pave the way for the fabrication of 2D Te moiré superlattices and in-plane homojunctions, and promote their future versatile applications.
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Penispidins A-C (1-3), new aromatic sesquiterpenoids with two classes of rare carbon skeletons, were isolated from the endophytic fungus Penicillium virgatum HL-110. 1 represents the first example of a dunniane-type aromatic sesquiterpenoid, possessing a novel 4/6/6 tricyclic system, while (±)-2 and 3 have a 7,12-cyclized bisabolene skeleton, featuring a 3,4-benzo-fused 2-oxabicyclo[3.3.1]nonane central framework. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and ECD calculations. 1 inhibited hepatic lipid accumulation in HepG2 cells.
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Metabolismo dos Lipídeos/efeitos dos fármacos , Penicillium/química , Sesquiterpenos/farmacologia , China , Células Hep G2 , Humanos , Estrutura Molecular , Sesquiterpenos/isolamento & purificação , Triglicerídeos/metabolismoRESUMO
In this study, the inhibitory activity of young apple polyphenols (YAP) on α-glucosidase was investigated. Composition and inhibition analyses suggested that tannic acid (TA), (-)-epicatechin (EC) and phlorizin (PH) were the main active constituents in YAP showing α-glucosidase inhibition. PH was a competitive inhibitor, while YAP, TA and EC were the mixed-type ones. YAP, TA, PH and EC quenched the fluorescence spectrum of α-glucosidase significantly. Interestingly, the constants that indicate binding interaction between α-glucosidase and TA, PH, EC, including reciprocal of competitive inhibition constant (1/Kic), fluorescence quenching constant (KFQ) and binding energy (Eb), were shown similar orders as TA > PH > EC, contrary to IC50 values. This indicates that binding interactions between polyphenols and α-glucosidase caused the enzyme inhibition. Additionally, potential enzyme unfolding by polyphenols interactions indicated by red-shift of maximum emission wavelength is supported by the decrease in α-helix and ß-sheet contents of the enzyme. Conclusively, the α-glucosidase inhibition indicates that YAP may have potentials in alleviation of type 2 diabetes symptom.
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Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Malus/química , Polifenóis/química , Polifenóis/farmacologia , Catequina/química , Catequina/farmacologia , Clostridiales/enzimologia , Simulação por Computador , Humanos , Simulação de Acoplamento Molecular , Florizina/química , Florizina/farmacologia , Taninos/química , Taninos/farmacologia , alfa-Glucosidases/química , alfa-Glucosidases/metabolismoRESUMO
The thinned-young apple polysaccharides from three varieties were obtained by hot water extraction at 88 ÌC for 120â¯min. The compositional monosaccharides of the three polysaccharides were shown to be the same (xylose, mannose, galactose and glucose) and the molecular weights of the polysaccharides were in the range of 200-300â¯kDa. Compared with "Qinyang" and "Pinklady", the polysaccharide from "Jinshiji" had the highest emulsifying capacity. Moreover, the variations in pH and cation ion concentrations had also a significant effect on the emulsifying properties of the extracted polysaccharides. At pH 2.0-4.0, the prepared emulsion had smaller droplet sizes than at higher pH values. Although the emulsion was stable at low concentrations of Na+ and Ca2+ ions, high concentrations of Na+ and Ca2+ led to significant destabilization of the emulsion. Conclusively, our results demonstrated the potential application of thinned-young apple polysaccharide as a natural polysaccharide emulsifying agent.
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Emulsificantes/química , Malus/química , Polissacarídeos/química , Cálcio/química , Cátions/química , Emulsões/química , Concentração de Íons de Hidrogênio , Monossacarídeos/química , Sódio/química , ViscosidadeRESUMO
BACKGROUND: Human adenoviruses (HAdV) are a common cause of viral conjunctivitis, making surveillance of them from sporadic cases of conjunctivitis important. METHODS: To acquire a better understanding of the epidemic genotypes of HAdV in outpatient children with adenoviral conjunctivitis in Jiangxi Province, China (2011-2012), 179 samples from cases with a high suspicion of HAdV were analyzed by PCR. Samples confirmed to be HAdV-positive by PCR were cultured in Hep-2 cells to isolate the viruses, which were then identified through hexon gene sequencing. RESULTS: The adenoviral conjunctivitis positivity rate was 74.86% (134/179), from which 71.64% (96/134) were infections in boys, and 92.54% (124/134) were infections in children under 5 years of age. Sixty-nine HAdV strains were isolated from the positive samples and 69 sequences were obtained. Phylogenetic analysis indicated that 33 strains (47.82%) clustered with HAdV-B7, 21 (30.43%) with HAdV-B3, 6 (8.70%) with HAdV-B55, 6 (8.70%) with HAdV-E4, 1 with HAdV-B21 (1.45%), 1 with HAdV-D37 (1.45%), and 1 with HAdV-D64 (1.45%). CONCLUSIONS: This is the first identification of HAdV-B55 relating to adenoviral conjunctivitis in China. These findings provide a firm basis for future surveillance of adenoviral conjunctivitis in China or other East Asian regions.
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Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/genética , Conjuntivite Viral/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Túnica Conjuntiva/virologia , DNA Viral/genética , Feminino , Genótipo , Humanos , Lactente , Masculino , Pacientes Ambulatoriais , FilogeniaRESUMO
Diabetic retinopathy (DR), a major complication of diabetes caused by vascular damage and pathological proliferation of retinal vessels, often progresses to vision loss. Vascular endothelial growth factor (VEGF) signaling plays a pivotal role in the development of DR, but the exact underlying molecular mechanisms remain ill-defined. Cellular prion protein (PrPc) is a surface protein expressed by vascular endothelial cells, and the increased expression of PrPc is associated with physiological and pathological vascularization. Nevertheless, a role for PrPc in the development of DR has not been appreciated. Here, we addressed this question. We found that the development of streptozocin (STZ)-induced DR, but not the STZ-induced hyperglycemia/diabetes itself, was significantly attenuated in PrPc-KO mice, compared to control wildtype (WT) mice, evident by measurement of retinal vascular leakage, retinal neovascularization, a retinopathy score and visual acuity assessment. Moreover, the attenuation of DR severity seemingly resulted from attenuation of retinal neovascularization via VEGF/ras/rac signaling. Together, our study suggests a previously unappreciated role for PrPc in the development of DR.
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Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Proteínas PrPC/metabolismo , Neovascularização Retiniana/metabolismo , Animais , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Camundongos , Camundongos Knockout , Proteínas PrPC/genética , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologiaRESUMO
Herein, we described a nickel-catalyzed monofluoroalkenylation through defluorinative reductive cross-coupling of gem-difluoroalkenes with alkyl halides. Key to the success of this strategy is the combination of C-F cleavage with alkyl halides activation. This reaction enables the convenient synthesis of a large variety of functionalized monofluoroalkenes under mild reaction conditions with broad functional group compatibility and excellent Z-selectivity. The combination of Ni catalysis with (Bpin)2/K3PO4 as terminal reductant promoted the efficient C(sp2)-C(sp3) formation especially the generation of all-carbon quaternary centers with high chemoselectivity.
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BACKGROUND: Human infections with different avian influenza viruses--eg, H5N1, H9N2, and H7N9--have raised concerns about pandemic potential worldwide. We report the first human infection with a novel reassortant avian influenza A H10N8 virus. METHODS: We obtained and analysed clinical, epidemiological, and virological data from a patient from Nanchang City, China. Tracheal aspirate specimens were tested for influenza virus and other possible pathogens by RT-PCR, viral culture, and sequence analyses. A maximum likelihood phylogenetic tree was constructed. FINDINGS: A woman aged 73 years presented with fever and was admitted to hospital on Nov 30, 2013. She developed multiple organ failure and died 9 days after illness onset. A novel reassortant avian influenza A H10N8 virus was isolated from the tracheal aspirate specimen obtained from the patient 7 days after onset of illness. Sequence analyses revealed that all the genes of the virus were of avian origin, with six internal genes from avian influenza A H9N2 viruses. The aminoacid motif GlnSerGly at residues 226-228 of the haemagglutinin protein indicated avian-like receptor binding preference. A mixture of glutamic acid and lysine at residue 627 in PB2 protein--which is associated with mammalian adaptation--was detected in the original tracheal aspirate samples. The virus was sensitive to neuraminidase inhibitors. Sputum and blood cultures and deep sequencing analysis indicated no co-infection with bacteria or fungi. Epidemiological investigation established that the patient had visited a live poultry market 4 days before illness onset. INTERPRETATION: The novel reassortant H10N8 virus obtained is distinct from previously reported H10N8 viruses. The virus caused human infection and could have been associated with the death of a patient. FUNDING: Emergency Research Project on human infection with avian influenza H7N9 virus, the National Basic Research Program of China, and the National Mega-projects for Infectious Diseases.
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Vírus da Influenza A/classificação , Influenza Aviária/virologia , Influenza Humana/diagnóstico , Influenza Humana/virologia , Insuficiência de Múltiplos Órgãos/virologia , Aves Domésticas/virologia , Idoso , Animais , Antivirais/farmacologia , China , Comércio , DNA Viral/análise , Evolução Fatal , Feminino , Ácido Glutâmico/metabolismo , Humanos , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Influenza Humana/tratamento farmacológico , Lisina/metabolismo , Neuraminidase/antagonistas & inibidores , Filogenia , RNA Polimerase Dependente de RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Traqueia/virologia , Proteínas Virais/metabolismoRESUMO
The single-walled carbon nanotube film photoelectric device was invented, and it can generate net photocurrent under bias voltage when it is illuminated by the laser. The influences of bias voltage, laser power and illuminating position on the net photocurrent were investigated. The experimental results showed that when the center of the film was illuminated, the photocurrent increased with the applied bias, but tended to saturate as the laser power increased. As the voltage and the laser power reached 0. 2 V and 22. 7 mW respectively, the photocurrent reached 0. 24 µA. When the voltage was removed, the photocurrent varied with the laser illuminating position on the film and its value was distributed symmetrically about the center of the device. The photocurrent reached maximum and almost zero respectively when the laser illuminated on two ends and the center of the film. Analysis proposes that the net photocurrent can be generated due to internal photoelectric effect when the device is under voltage and the laser illuminates on the center of the film. It can be also generated due to photo-thermoelectric effect when the device is under no voltage and the laser illuminates on the film, and the relation between the net photocurrent and the illuminating position was derived according to the nature of thermoelectric power of single-walled carbon nanotubes with the established temperature model, which coincides with experimental result. Two effects are the reasons for the generation and variety of the net photocurrent and they superimpose to form the result of the net photocurrent when the device is under general conditions of voltage and laser illuminating position. The device has potential applications in the areas of photovoltaic device and optical sensor for its characteristic.