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1.
Med Sci Monit ; 25: 8403-8411, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31699960

RESUMO

BACKGROUND This study aimed to identify hub genes and pathways in a rat model of renal ischemia-reperfusion injury (IRI) using bioinformatics analysis of the Gene Expression Omnibus (GEO) microarray dataset and integration of gene expression profiles. MATERIAL AND METHODS GEO software and the GEO2R calculation method were used to analyze two mRNA profiles, including GSE 39548 and GSE 108195. The co-expression of differentially expressed genes (DEGs) were identified and searched in the DAVID and STRING databases for pathway and protein-protein interaction (PPI) analysis. Cytoscape was used to draw the PPI network. DEGs were also analyzed using the Molecular Complex Detection (MCODE) algorithm. Cytoscape and cytoHubba were used to analyze the hub genes and visualize the molecular interaction networks. Rats (n=20) included the IRI model group (n=10) and a control group (n=10). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure and compare the expression of the identified genes in rat renal tissue in the IRI model and the control group. RESULTS Ten hub genes were identified, STAT3, CD44, ITGAM, CCL2, TIMP1, MYC, THBS1, IGF1, SOCS3, and CD14. Apart from IGF1, qRT-PCR showed that expression of these genes was significantly increased in renal tissue in the rat model of IRI. The HIF-1alpha signaling pathway was involved in IRI in the rat model, which was supported by MCODE analysis. CONCLUSIONS In a rat model of renal IRI, bioinformatics analysis of the GEO dataset and integration of gene expression profiles identified involvement of HIF-1alpha signaling and the STAT3 hub gene.

2.
Oxid Med Cell Longev ; 2019: 7902874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772709

RESUMO

Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.

3.
Sensors (Basel) ; 19(12)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208094

RESUMO

In signal array processing, high-resolution direction-of-arrival (DOA) estimation algorithms work well on the assumption that the system models are perfect. However, in practicality, there are imperfect system models in which sensor gain-and-phase errors are considered. In this paper, we propose a novel framework that can effectively solve direction-of-arrival estimation tasks in the presence of sensor gain-and-phase errors. In contrast to existing approaches based on phase retrieval, our method eliminates gain errors by using the compensated covariance matrix. Meanwhile, we propose a data preprocessing method by taking only one column of the compensated covariance matrix without losing any magnitude information. Additionally, the phase retrieval problem is formed by the proposed data preprocessing method. Furthermore, the phase retrieval problem is solved by the recently proposed sparse feasible point pursuit algorithm, and DOA estimates are obtained. To prevent the model from ambiguities, we employ the known DOA to place reference sources. Numerical results show that the proposed scheme achieves better performance compared to state-of-the-art approaches.

4.
Org Lett ; 21(8): 2927-2931, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30924668

RESUMO

A novel method for site-selective C-H functionalization of ethyl acetate mediated by pyridine-boryl radicals is presented, delivering a variety of 4-phenylbut-3-yn-2-yl acetate derivatives under mild conditions. A distinguishing feature of this reaction is that the pyridine-ligated boryl radicals can abstract the inactive α-hydrogen of the alkoxyl group instead of the α-hydrogen of carbonyl groups described in a previous report using amine-ligated boryl radicals. Significantly, substrates with halogen atoms are compatible under the reaction conditions.

5.
Chemistry ; 25(12): 2989-2994, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30624002

RESUMO

A challenging deoxygenation of alkoxyl radicals from readily accessible alcohol derivatives was developed, affording facile synthesis of functionalized alkenes with good functional group tolerance under mild reaction conditions. Because alkoxyl radicals can easily undergo ß-fragmentations or hydrogen abstractions, this new strategy for deoxygenation of alkoxyl radicals is highly valuable. Moreover, mechanistic studies revealed that the electron-neutral phosphine acts as the deoxygenation reagent.

6.
Sci Data ; 5: 180284, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30531820

RESUMO

Gene-gene (GXG) and gene-environment (GXE) interactions play important roles in pharmacogenetics study. Simultaneously incorporating multiple single nucleotide polymorphisms (SNPs) and clinical factors is needed to explore the association of their interactions with drug response and toxicity phenotypes. We genotyped 504 SNPs in a total of 490 Chinese non-small cell lung cancer (NSCLC) patients, and the correlation of GXG and GXE interactions with platinum-based chemotherapeutic efficacy and safety were analyzed. In this data descriptor, we shared our data set which could help others to reuse them. All kinds of file types needed for GXG and GXE analysis were supplied. The process of genotyping and data analysis was also introduced step by step.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Epistasia Genética , Interação Gene-Ambiente , Neoplasias Pulmonares/genética , Antineoplásicos/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Platina/uso terapêutico , Polimorfismo de Nucleotídeo Único
7.
Sci Rep ; 8(1): 15761, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30361643

RESUMO

The hybrid system of electron spins and resonator photons is an attractive architecture for quantum computing owing to the long coherence times of spins and the promise of long-distance coupling between arbitrary pairs of qubits via photons. For the device to serve as a building block for a quantum processer, it is also necessary to readout the spin qubit state. Here we analyze in detail the measurement process of an electron spin singlet-triplet qubit in quantum dots using a coupled superconducting resonator. We show that the states of the spin singlet-triplet qubit lead to readily observable features in the spectrum of a microwave field through the resonator. These features provide useful information on the hybrid system. Moreover, we discuss the working points which can be implemented with high performance in the current state-of-the-art devices. These results can be used to construct the high fidelity measurement toolbox in the spin-circuit QED system.

8.
Sensors (Basel) ; 18(3)2018 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-29495343

RESUMO

A model describing the wide variety of human behaviours called personality, is becoming increasingly popular among researchers due to the widespread availability of personal big data generated from the use of prevalent digital devices, e.g., smartphones and wearables. Such an approach can be used to model an individual and even digitally clone a person, e.g., a Cyber-I (cyber individual). This work is aimed at establishing a unique and comprehensive description for an individual to mesh with various personalized services and applications. An extensive research literature on or related to psychological modelling exists, i.e., into automatic personality computing. However, the integrity and accuracy of the results from current automatic personality computing is insufficient for the elaborate modeling in Cyber-I due to an insufficient number of data sources. To reach a comprehensive psychological description of a person, it is critical to bring in heterogeneous data sources that could provide plenty of personal data, i.e., the physiological data, and the Internet data. In addition, instead of calculating personality traits from personal data directly, an approach to a personality model derived from the theories of Carl Gustav Jung is used to measure a human subject's persona. Therefore, this research is focused on designing an archetype-based modeling of persona covering an individual's facets in different situations to approach a comprehensive personality model. Using personal big data to measure a specific persona in a certain scenario, our research is designed to ensure the accuracy and integrity of the generated personality model.


Assuntos
Personalidade , Humanos , Armazenamento e Recuperação da Informação , Internet , Aprendizagem
9.
Org Lett ; 20(8): 2351-2355, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29584434

RESUMO

A boryl radical-triggered C-H functionalization of aliphatic ethers/amines or DMF with isocyanides is developed to deliver diverse phenanthridine derivatives in good to excellent yields. The substrate scope is broad, and a wide range of functional groups are tolerated under the standard conditions. The rapid removal of HBPin species by 4-cyanopyridine 1-oxide provides the driving force for this reaction. This new method should make boryl radicals widely applicable in organic synthesis.

10.
Onco Targets Ther ; 11: 529-538, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29416353

RESUMO

Compared with various malignant tumors, lung cancer has high incidence and the highest mortality worldwide. Non-small-cell lung cancer (NSCLC), the most common kind of lung cancer, is still a great threat to the world, including China. Surgery, platinum-based chemotherapy, and radiotherapy are still the primary treatments for NSCLC patients in the clinic, whereas immunotherapy and targeted therapy are gradually playing more important roles. A next-generation tyrosine kinase inhibitor (TKI), afatinib, was developed as a targeted reagent for epidermal growth factor receptor (EGFR). This targeted drug was effective in a series of trials. The US Food and Drug Administration then approved afatinib as a new first-line treatment for EGFR L858R and exon 19 deletion mutant patients in 2013. This review focused on current clinical studies of afatinib. Although this TKI was not widely available in China until recently, we aim to provide a reference for its future use in China.

11.
FASEB J ; 32(8): 4096-4106, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29485902

RESUMO

ß-Arrestins (ß-arrestin-1 and -2) are multifunctional proteins that play important roles in the regulation of inflammation and cell survival that need to be tightly controlled; however, the mechanism that underlies their gene expression is largely unclear. Here, we demonstrate that ß-arrestin-1 is a transcriptional target of NF-κB. mRNA and protein levels of ß-arrestin-1 were up-regulated by NF-κB inducers. Inhibition of NF-κB prevented the up-regulation of ß-arrestin-1 mRNA, whereas activation of NF-κB led to increased ß-arrestin-1 expression. ß-Arrestin-1 promoter activity was consistently enhanced upon NF-κB activation as a result of the presence of a highly conserved κB site. ß-Arrestin-1, in turn, suppressed the transcriptional activity of NF-κB by interfering with the interaction between p65 and p50. ß-Arrestin-1-deficient mice displayed reduced TNF-α-induced cell death and increased expression of antiapoptotic genes. Reintroduction of ß-arrestin-1, but not its mutant, which is unable to interfere with the p65-p50 interaction, into ß-arrestin-deficient mouse embryonic fibroblasts partially restored sensitivity to TNF-α-induced cell death. These findings reveal NF-κB and ß-arrestin-1 to be key components of a negative feedback circuit that is necessary to regulate cell death.-Li, J., Guo, A., Wang, Q., Li, Y., Zhao, J., Lu, J., Pei, G. NF-κB directly regulates ß-arrestin-1 expression and forms a negative feedback circuit in TNF-α-induced cell death.


Assuntos
Morte Celular/genética , NF-kappa B/genética , Fator de Necrose Tumoral alfa/genética , beta-Arrestina 1/genética , Animais , Apoptose/genética , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , Transcrição Genética/genética , Regulação para Cima/genética
12.
J Cell Physiol ; 233(8): 5747-5755, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29155449

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.


Assuntos
Anti-Inflamatórios/farmacologia , Flavanonas/farmacologia , Metaplasia/patologia , Pancreatite/patologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Amilases/metabolismo , Animais , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Queratina-19/metabolismo , Lipopolissacarídeos , Macrófagos/imunologia , Medicina Tradicional Chinesa , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Ratos , Receptor Notch1/metabolismo , Fatores de Transcrição HES-1/biossíntese , Fator de Necrose Tumoral alfa/farmacologia
13.
Front Psychol ; 9: 2537, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30618958

RESUMO

In older adults, cognitive abilities, such as those associated with vision and hearing, generally decrease with age. According to several studies, audio-visual perceptual training can improve perceived competence regarding visual and auditory stimuli, suggesting that perceptual training is effective and beneficial. However, whether audio-visual perceptual training can induce far-transfer effects in other forms of untrained cognitive processing that are not directly trained in older adults remains unclear. In this study, the classic P300 component, a neurophysiological indicator of cognitive processing of a stimulus, was selected as an evaluation index of the training effect. We trained both young and older adults on the ability to judge the temporal and spatial consistency of visual and auditory stimuli. P300 amplitudes were significantly greater in the posttraining session than in the pretraining session in older adults (P = 0.001). However, perceptual training had no significant effect (P = 0.949) on the P300 component in young adults. Our results illustrate that audio-visual perceptual training can lead to far-transfer effects in healthy older adults. These findings highlight the robust malleability of the aging brain, and further provide evidence to motivate exploration to improve cognitive abilities in older adults.

14.
Sci Rep ; 7(1): 13222, 2017 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-29038567

RESUMO

Mammalian haploid embryonic stem cells (haESCs) provide new possibilities for large-scale genetic screens because they bear only one copy of each chromosome. However, haESCs are prone to spontaneous diploidization through unknown mechanisms. Here, we report that a small molecule combination could restrain mouse haESCs from diploidization by impeding exit from naïve pluripotency and by shortening the S-G2/M phases. Combined with 2i and PD166285, our chemical cocktail could maintain haESCs in the haploid state for at least five weeks without fluorescence-activated cell sorting (FACS) enrichment of haploid cells. Taken together, we established an effective chemical approach for long-term maintenance of haESCs, and highlighted that proper cell cycle progression was critical for the maintenance of haploid state.


Assuntos
Células-Tronco Embrionárias Murinas/metabolismo , Proteínas Quinases/metabolismo , Transdução de Sinais , Animais , Ciclo Celular/genética , Divisão Celular , Linhagem Celular , Citometria de Fluxo , Fase G2 , Haploidia , Camundongos , Camundongos Endogâmicos C57BL , Ploidias , Células-Tronco Pluripotentes , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
15.
Stem Cell Reports ; 8(5): 1124-1134, 2017 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-28457886

RESUMO

The recent establishment of mammalian haploid embryonic stem cells (ESCs) provides new possibilities for genetic screening and for understanding genome evolution and function. However, the dynamics of mitosis in haploid ESCs is still unclear. Here, we report that the duration of mitosis in haploid ESCs, especially the metaphase, is significantly longer than that in diploid ESCs. Delaying mitosis by chemicals increased self-diploidization of haploid ESCs, while shortening mitosis stabilized haploid ESCs. Taken together, our study suggests that the delayed mitosis of haploid ESCs is associated with self-diploidization.


Assuntos
Células-Tronco Embrionárias/citologia , Haploidia , Metáfase , Animais , Linhagem Celular , Diploide , Camundongos , Análise de Célula Única
18.
Microbiol Res ; 192: 326-335, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27664751

RESUMO

The endophytic fungus Harpophora oryzae is a beneficial endosymbiont isolated from wild rice. H. oryzae can not only promote rice growth and biomass accumulation but also protect rice roots from invasion by its close relative Magnaporthe oryzae. Autophagy is a highly evolutionary conserved process from lower to higher eukaryotic organisms, and is involved in the maintenance of normal cell differentiation and development. In this study, we isolated a gene (HoATG5) which encodes an essential protein required for autophagy from the beneficial endophyte fungus H. oryzae. Using targeted gene replacement, a ΔHoATG5 mutant was generated and used to investigate the biological functions of autophagy in H. oryzae. We found that the autophagic process was blocked in the HoATG5 deletion mutant. The mutant showed increased vegetative growth and sporulation, and was sensitive to nutrient starvation. The ΔHoATG5 mutant lost its ability to penetrate and infect the wounded barley leaves. These results provide new knowledge to elaborate the molecular machinery of autophagy in endophytic fungi.


Assuntos
Ascomicetos/fisiologia , Proteína 5 Relacionada à Autofagia/genética , Autofagia/genética , Parede Celular/genética , Parede Celular/metabolismo , Hordeum/microbiologia , Folhas de Planta/microbiologia , Esporos Fúngicos , Sequência de Bases , Clonagem Molecular , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Mutação , Fenótipo , Doenças das Plantas/microbiologia , Ligação Proteica , Análise de Sequência de DNA , Deleção de Sequência
19.
Sci Rep ; 6: 31204, 2016 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-27502542

RESUMO

Calpains are ubiquitous and well-conserved proteins that belong to the calcium-dependent, non-lysosomal cysteine protease family. In this study, 8 putative calpains were identified using Pfam domain analysis and BlastP searches in M. oryzae. Three single gene deletion mutants (ΔMocapn7, ΔMocapn9 and ΔMocapn14) and two double gene deletion mutants (ΔMocapn4ΔMocapn7 and ΔMocapn9ΔMocapn7) were obtained using the high-throughput gene knockout system. The calpain disruption mutants showed defects in colony characteristics, conidiation, sexual reproduction and cell wall integrity. The mycelia of the ΔMocapn7, ΔMocapn4ΔMocapn7 and ΔMocapn9ΔMocapn7 mutants showed reduced pathogenicity on rice and barley.


Assuntos
Calpaína/metabolismo , Parede Celular/metabolismo , Magnaporthe/genética , Magnaporthe/patogenicidade , Proteínas Fúngicas/metabolismo , Deleção de Genes , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Hordeum/microbiologia , Modelos Genéticos , Mutação , Micélio/metabolismo , Oryza/microbiologia , Doenças das Plantas/microbiologia , Proteoma , Esporos Fúngicos/crescimento & desenvolvimento , Virulência/genética
20.
Neurosci Lett ; 629: 262-266, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27369323

RESUMO

Norepinephrine (NE), from the locus coeruleus (LC), has been supported to affect GABAergic system and parallel fiber (PF)-Purkinje cell (PC) synaptic transmission via adrenoceptor in cerebellum cortex. However, the effects of NE on the spontaneous spike activity of cerebellar PCs in living mouse have not yet been fully understood. We here examined the effects of NE on the spontaneous activity of PC in urethane-anesthetized mice by electrophysiological and pharmacological methods. Cerebellar surface application of NE (2.5-25µM) reduced the PC simple spike (SS) firing rate in a dose-dependent manner. The half-inhibitory concentration (IC50) was 5.97µM. In contrast, NE significantly increased the spontaneous firing rate of molecular layer interneuron (MLI). Application of GABAA receptor antagonist, gabazine (SR95531, 20µM) not only blocked the NE-induced inhibition of PC SS firing but also revealed NE-induced excitation of cerebellar PC. Blocking AMPA receptors activity enhanced NE-induced inhibition of PC spontaneous activity. Moreover, the effects of NE on PC spontaneous activity were abolished by simultaneously blocking GABAA and AMPA receptors activity. These results indicated that NE bidirectional modulated the spontaneous activity of PCs via enhancing both inhibitory inputs from MLIs and excitatory inputs of parallel fibers, but NE-induced enhance of inhibitory inputs overwhelmed the excitatory inputs under in vivo conditions.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/administração & dosagem , Norepinefrina/administração & dosagem , Células de Purkinje/efeitos dos fármacos , Células de Purkinje/fisiologia , Animais , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Receptores de GABA-A , Camundongos , Camundongos Endogâmicos ICR , Piridazinas/administração & dosagem , Quinoxalinas/administração & dosagem , Receptores de AMPA/antagonistas & inibidores , Receptores de GABA-A/fisiologia
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