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Malignant glioma is the most fatal, invasive brain cancer with limited treatment options. Our previous studies show that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1), a major metabolite of indole-3-carbinol (I3C) derived from cruciferous vegetables, produces anti-tumour effect against various tumour cell lines. In this study we characterized LTr1 as a novel anti-glioma agent. Based on screening 134 natural compounds and comparing the candidates' efficacy and toxicity, LTr1 was selected as the lead compound. We showed that LTr1 potently inhibited the viability of human glioma cell lines (SHG-44, U87, and U251) with IC50 values of 1.97, 1.84, and 2.03 µM, respectively. Furthermore, administration of LTr1 (100,300 mg· kg-1 ·d-1, i.g. for 18 days) dose-dependently suppressed the tumour growth in a U87 xenograft nude mouse model. We demonstrated that LTr1 directly bound with TrkA to inhibit its kinase activity and the downstream PI3K/AKT pathway thus inducing significant S-phase cell cycle arrest and apoptosis in SHG-44 and U87 cells by activating the mitochondrial pathway and inducing the production of reactive oxygen species (ROS). Importantly, LTr1 could cross the blood-brain barrier to achieve the therapeutic concentration in the brain. Taken together, LTr1 is a safe and promising therapeutic agent against glioma through inhibiting TrkA/PI3K/AKT pathway.
Assuntos
Glioma , Proteínas Proto-Oncogênicas c-akt , Animais , Humanos , Camundongos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Glioma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Proteína Tirosina Quinases , Verduras/metabolismoRESUMO
A large quantity of coal fly ash is generated worldwide from thermal power plants, causing a serious environmental threat owing to disposal and storage problems. In this work, for the first time, coal fly ash is converted into advanced and novel aerogel fibers and high-purity α-Al2O3. Silica-bacterial cellulose composite aerogel fibers (CAFs) were synthesized using an in situ sol-gel process under ambient pressure drying. Due to the unique "nanoscale interpenetrating network" (IPN) structure, the CAFs showed wonderful mechanical properties with an optimum tensile strength of 5.0 MPa at an ultimate elongation of 5.8%. Furthermore, CAFs with a high porosity (91.8%) and high specific surface area (588.75 m2/g) can inherit advanced features, including excellent thermal insulation, stability over a wide temperature range, and hydrophobicity (contact angle of approximately 144°). Additionally, Al2O3 was simultaneously extracted from the coal fly ash to ensure that the coal fly ash was fully exploited. Overall, low-cost woven CAFs fabrics are suitable for wearable applications and offer a great approach to comprehensively use coal fly ash to address environmental threats.
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Long-term and constant-release osmotic-pump lorcaserin hydrochloride controlled-release tablets (OP LH CRTs) were prepared, to investigate the influencing factors of LH release and optimize the formulation. The mechanism of release of LH from OP LH CRTs in vitro was investigated. By establishing a high-efficiency method for measuring LH release in vitro, and optimizing it by single-factor and orthogonal experiments, the best formulation of OP LH CRTs was determined. Then, the optimal prescription of OP LH CRTs was: LH = 20.8 mg; mannitol = 100 mg, microcrystalline cellulose = 125 mg; magnesium stearate = 5 mg; cellulose acetate = 3%; polyethylene glycol 400 = 10%; dibutyl phthalate = 10%; Wetting agent and binder was 3% polyvinyl pyrrolidone (PVP) K30 ethanol solution; aperture diameter = 0.8 mm; the coating gained 3% weight. And finally, prepared OP LH CRTs were released at a constant rate in vitro and sustained for 16 h with good reproducibility between batches. Using an orthogonal experimental design, OP LH CRTs with remarkable zero-order release characteristics within 16 h were obtained, and formulation optimization was realized.
Assuntos
Preparações de Ação Retardada , Benzazepinas , Preparações de Ação Retardada/química , Reprodutibilidade dos Testes , Solubilidade , ComprimidosRESUMO
Sugarcane (Saccharum officinarum L.) is one of the world's highly significant commercial crops. The amounts of synthetic nitrogen (N2) fertilizer required to grow the sugarcane plant at its initial growth stages are higher, which increases the production costs and adverse environmental consequences globally. To combat this issue, sustainable environmental and economic concerns among researchers are necessary. The endophytic diazotrophs can offer significant amounts of nitrogen to crops through the biological nitrogen fixation mediated nif gene. The nifH gene is the most extensively utilized molecular marker in nature for studying N2 fixing microbiomes. The present research intended to determine the existence of novel endophytic diazotrophs through culturable and unculturable bacterial communities (EDBCs). The EDBCs of different tissues (root, stem, and leaf) of five sugarcane cultivars (Saccharum officinarum L. cv. Badila, S. barberi Jesw.cv Pansahi, S. robustum, S. spontaneum, and S. sinense Roxb.cv Uba) were isolated and molecularly characterized to evaluate N2 fixation ability. The diversity of EDBCs was observed based on nifH gene Illumina MiSeq sequencing and a culturable approach. In this study, 319766 operational taxonomic units (OTUs) were identified from 15 samples. The minimum number of OTUs was recorded in leaf tissues of S. robustum and maximum reads in root tissues of S. spontaneum. These data were assessed to ascertain the structure, diversity, abundance, and relationship between the microbial community. A total of 40 bacterial families with 58 genera were detected in different sugarcane species. Bacterial communities exhibited substantially different alpha and beta diversity. In total, 16 out of 20 genera showed potent N2-fixation in sugarcane and other crops. According to principal component analysis (PCA) and hierarchical clustering (Bray-Curtis dis) evaluation of OTUs, bacterial microbiomes associated with root tissues differed significantly from stem and leaf tissues of sugarcane. Significant differences often were observed in EDBCs among the sugarcane tissues. We tracked and validated the plethora of individual phylum strains and assessed their nitrogenase activity with a culture-dependent technique. The current work illustrated the significant and novel results of many uncharted endophytic microbial communities in different tissues of sugarcane species, which provides an experimental system to evaluate the biological nitrogen fixation (BNF) mechanism in sugarcane. The novel endophytic microbial communities with N2-fixation ability play a remarkable and promising role in sustainable agriculture production.
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Microbiota , Saccharum , Bactérias/genética , Humanos , Nitrogênio , Fixação de Nitrogênio , Saccharum/genéticaRESUMO
BACKGROUND: Nitrogen is an essential element for sugarcane growth and development and is generally applied in the form of urea often much more than at recommended rates, causing serious soil degradation, particularly soil acidification, as well as groundwater and air pollution. In spite of the importance of nitrogen for plant growth, fewer reports are available to understand the application and biological role of N2 fixing bacteria to improve N2 nutrition in the sugarcane plant. RESULTS: In this study, a total of 350 different bacterial strains were isolated from rhizospheric soil samples of the sugarcane plants. Out of these, 22 isolates were selected based on plant growth promotion traits, biocontrol, and nitrogenase activity. The presence and activity of the nifH gene and the ability of nitrogen-fixation proved that all 22 selected strains have the ability to fix nitrogen. These strains were used to perform 16S rRNA and rpoB genes for their identification. The resulted amplicons were sequenced and phylogenetic analysis was constructed. Among the screened strains for nitrogen fixation, CY5 (Bacillus megaterium) and CA1 (Bacillus mycoides) were the most prominent. These two strains were examined for functional diversity using Biolog phenotyping, which confirmed the consumption of diverse carbon and nitrogen sources and tolerance to low pH and osmotic stress. The inoculated bacterial strains colonized the sugarcane rhizosphere successfully and were mostly located in root and leaf. The expression of the nifH gene in both sugarcane varieties (GT11 and GXB9) inoculated with CY5 and CA1 was confirmed. The gene expression studies showed enhanced expression of genes of various enzymes such as catalase, phenylalanine-ammonia-lyase, superoxide dismutase, chitinase and glucanase in bacterial-inoculated sugarcane plants. CONCLUSION: The results showed that a substantial number of Bacillus isolates have N-fixation and biocontrol property against two sugarcane pathogens Sporisorium scitamineum and Ceratocystis paradoxa. The increased activity of genes controlling free radical metabolism may at least in part accounts for the increased tolerance to pathogens. Nitrogen-fixation was confirmed in sugarcane inoculated with B. megaterium and B. mycoides strains using N-balance and 15N2 isotope dilution in different plant parts of sugarcane. This is the first report of Bacillus mycoides as a nitrogen-fixing rhizobacterium in sugarcane.
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Interações entre Hospedeiro e Microrganismos , Microbiota , Fixação de Nitrogênio , Bactérias Fixadoras de Nitrogênio/metabolismo , Saccharum/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Bactérias Fixadoras de Nitrogênio/classificação , Bactérias Fixadoras de Nitrogênio/isolamento & purificação , Rizoma/crescimento & desenvolvimento , Rizoma/microbiologia , Saccharum/microbiologiaRESUMO
Neuronal injury within specific brain regions is considered a critical risk factor in the pathophysiology of depression. However, the underlying mechanisms of this process, and thus the potential for development of novel therapeutic strategies in the treatment of depression, remain largely unknown. Here, we report that Il-6 protects against neuronal anomalies related with depression, in part, by suppressing oxidative stress and consequent autophagic and apoptotic hyperactivity. Specifically, we show that IL-6 is downregulated within the CA1 hippocampus in two animal models of depression and upregulated by antidepressants. Increasing levels of IL-6 in the CA1 region result in pleiotropic protective actions including reductions in oxidative stress and modulation of autophagy, anti-immuno-inflammatory activation and anti-apoptotic effects in CA1 neurons, all of which are associated with the rescue of depression-like behaviors. In contrast, IL-6 downregulation exacerbates neuronal anomalies within the CA1 region and facilitates the genesis of depression phenotypes in rats. Interestingly, in addition to attenuating oxidative damage, the antioxidant, N-acetylcysteine (NAC), is also associated with significantly decreased neuronal deficits and the display of depressive behaviors in rats. These results suggest that IL-6 may exert neuroprotection within CA1 neurons via pleiotropic mechanisms and may serve as a potential therapeutic target for the treatment of depression.
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Depressão/metabolismo , Interleucina-6/metabolismo , Animais , Antidepressivos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/fisiologia , Depressão/imunologia , Depressão/fisiopatologia , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Interleucina-6/farmacologia , Masculino , Neurônios/efeitos dos fármacos , Neuroproteção , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Estresse Psicológico/fisiopatologiaRESUMO
Smut disease is caused by Sporisorium scitamineum, an important sugarcane fungal pathogen causing an extensive loss in yield and sugar quality. The available literature suggests that there are two types of smut resistance mechanisms: external resistance by physical or chemical barriers and intrinsic internal resistance mechanisms operating at hostâ»pathogen interaction at cellular and molecular levels. The nature of smut resistance mechanisms, however, remains largely unknown. The present study investigated the changes in proteome occurring in two sugarcane varieties with contrasting susceptibility to smut-F134 and NCo310-at whip development stage after S. scitamineum infection. Total proteins from pathogen inoculated and uninoculated (control) leaves were separated by two-dimensional gel electrophoresis (2D-PAGE). Protein identification was performed using BLASTp and tBLASTn against NCBI nonredundant protein databases and EST databases, respectively. A total of thirty proteins spots representing differentially expressed proteins (DEPs), 16 from F134 and 14 from NCo310, were identified and analyzed by MALDI-TOF/TOF MS. In F134, 4 DEPs were upregulated and nine were downregulated, while, nine were upregulated and three were downregulated in NCo310. The DEPs were associated with DNA binding, metabolic processes, defense, stress response, photorespiration, protein refolding, chloroplast, nucleus and plasma membrane. Finally, the expression of CAT, SOD, and PAL with recognized roles in S. scitamineum infection in both sugarcane verities were analyzed by real-time quantitative PCR (RT-qPCR) technique. Identification of genes critical for smut resistance in sugarcane will increase our knowledge of S. scitamineum-sugarcane interaction and help to develop molecular and conventional breeding strategies for variety improvement.
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Doenças das Plantas/microbiologia , Proteômica/métodos , Saccharum/metabolismo , Ustilaginales/patogenicidade , Eletroforese em Gel Bidimensional , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
BACKGROUND/AIMS: Ginsenoside Rg1 has been demonstrated to exhibit neuroprotective effects in various studies. This study aimed to investigate the neuronal mechanisms underlying the neuroprotective and antidepressant-like effects of ginsenoside Rg1 in a rat model of depression. METHODS: Chronic unpredictable mild stress was used to induce depression-like behaviors in rats. Transmission electron microscopy was used to observe neuronal synapses within the basolateral amygdala (BLA). The expression of microRNA (miR)-134 in the BLA was verified by real-time quantitative PCR. Finally, the synaptic plasticity-associated proteins CAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were detected by immunoblotting. RESULTS: Results showed that chronic stress effectively induced depression-like behaviors in rats, which were associated with significant ultrastructural changes within BLA neurons. Moreover, chronic stress decreased the expression of miR-134 in the BLA, which was accompanied by decreased phosphorylation of CREB and decreased expression of BDNF. Remarkably, chronic administration of ginsenoside Rg1 (40 mg/kg, i.p., 5 weeks) significantly ameliorated the neuronal structural abnormalities and biochemical changes induced by chronic stress, as well as preventing depression-like behaviors in these rats. CONCLUSION: Results suggested that ginsenoside Rg1 may exhibit neuroprotection and antidepressant-like effects by activating the CREB-BDNF system within the BLA in this rat model of depression. Amelioration of depression-like behaviors by ginsenoside Rg1 appears to involve modulation of the synapse-associated factor miR-134 within the BLA. Therefore, these findings demonstrate some of the neuronal mechanisms associated with depression and the therapeutic potential of ginsenoside Rg1 for use in the treatment of depression in clinical trials.
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Complexo Nuclear Basolateral da Amígdala/metabolismo , Comportamento Animal/efeitos dos fármacos , Ginsenosídeos/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Estresse Fisiológico , Animais , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Complexo Nuclear Basolateral da Amígdala/ultraestrutura , Transtorno Depressivo/patologia , Transtorno Depressivo/prevenção & controle , Modelos Animais de Doenças , Ginsenosídeos/uso terapêutico , Locomoção/efeitos dos fármacos , Masculino , MicroRNAs/metabolismo , Microscopia Eletrônica de Transmissão , Ratos , Ratos WistarRESUMO
BACKGROUND: Neuroinflammation has recently emerged as a critical risk factor in the pathophysiology of depression. However, the underlying molecular mechanisms and the development of novel therapeutic strategies as means to target these inflammatory pathways for use in the treatment of depression remain unresolved. In the present study, we aimed to investigate the molecular events of neuroinflammation as related to its induction of depression-like behaviors. METHODS: Chronic unpredictable mild stress (CUMS) or lipopolysaccharide (LPS) was used to induce depression-like behaviors in rats. The inflammatory factors and related proteins were verified by RT-PCR, immunoblotting, and immunofluorescence assay. In vivo intracerebral injection of adenovirus-associated virus (AAV) in rats was used to overexpress or block the function of the ß form of the calcium/calmodulin-dependent protein kinase type II (ßCaMKII). In vivo intracerebroventricular injection of SB203580 was used to block p38 mitogen-activated protein kinase (MAPK). Finally, the prostaglandin E2 (PGE2) concentration was verified by using enzyme-linked assay kit. RESULTS: The expression of cyclo-oxygenase (COX)-2, which is responsible for production of the pro-inflammatory factor PGE2 and thus glial activation, was increased in the CA1 hippocampus in a rat model of depression. Further, the ßCaMKII in CA1 was significantly upregulated in depressed rats, while antidepressant treatment downregulated this kinase. Overexpression of ßCaMKII via infusion of a constructed AAV-ßCaMKII into the CA1 region resulted in phosphorylation of the p38 MAPK and the activating transcription factor 2 (ATF2). These effects were accompanied by an enhanced activity of the COX-2/PGE2 pathway and effectively induced core symptoms of depression. Conversely, knockdown of ßCaMKII within the CA1 region reversed these inflammation-related biochemical parameters and significantly rescued depression symptoms. CONCLUSION: These results demonstrate that ßCaMKII can act as a critical regulator in depression via activating neuroinflammatory pathways within the CA1 region. Moreover, this study provides new perspectives on molecular targets and drug therapies for future investigation in the treatment of depression.
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Depressão/patologia , Dinoprostona/metabolismo , Regulação da Expressão Gênica/fisiologia , Hipocampo/metabolismo , Adenoviridae/genética , Adenoviridae/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antidepressivos/uso terapêutico , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Citocinas/genética , Citocinas/metabolismo , Depressão/tratamento farmacológico , Depressão/etiologia , Modelos Animais de Doenças , Preferências Alimentares/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Imidazóis/uso terapêutico , Lipopolissacarídeos/toxicidade , Masculino , Piridinas/uso terapêutico , Interferência de RNA/fisiologia , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/complicações , Natação/psicologiaRESUMO
Toxoplasma gondii is an intracellular protozoan parasite that infects all nucleated cells except the red blood cells. Currently, nucleic acid vaccines are being widely investigated in Toxoplasma gondii control, and several nucleic acid vaccine candidate antigens have shown good protection in various studies. The aim of this study was to construct a nucleic acid vaccine with Toxoplasma gondii SRS29C as the target gene. We explored the nucleic acid vaccine with Toxoplasma surface protein SRS29C and the combined gene of SRS29C and SAG1 and evaluated its immunoprotective effect against Toxoplasma gondii. To amplify the gene fragment and clone it to the expression vector, the recombinant plasmid pEGFP-SRS29C was constructed by PCR. Eukaryotic cells were transfected with the plasmid, and the expression of the target protein was assessed using the Western blot method. The level of serum IgG was determined via ELISA, and the splenic lymphocyte proliferation ability was detected using the CCK-8 method. The percentages of CD4+ and CD8+ T cells were measured by flow cytometry. Mice were immunised three times with single-gene nucleic acid vaccine and combination vaccine. Splenic lymphocytokine expression was determined using ELISA kits. The mice's survival time was monitored and recorded during an in vivo insect assault experiment, and the vaccine's protective power was assessed. The outcomes showed that PCR-amplification of an SRS29C gene fragment was successful. The 4,733-bp vector fragment and the 1,119-bp target segment were both recognised by double digestion. Additionally, after transfection of the recombinant plasmid pEGFP-SRS29C, Western blot examination of the extracted protein revealed the presence of a target protein strip at 66â¯kDa. The test results demonstrated that the IgG content in the serum of the pEGFP-SRS29C group and the co-immunization group was significantly higher than that of the PBS group and the empty vector group. The IgG potency induced by the co-immunization group was higher than that of the pEGFP-SRS29C group and the pEGFP-SAG1 group, the number of splenic lymphocyte proliferation number was higher than that of the PBS group and the empty vector group. The CD4+/CD8+ T ratio was higher than that of the PBS group and the empty vector group. The expression of IFN-γ and TNF-α in the splenocytes of the pEGFP-SRS29C group and the combined immunisation group was significantly higher following antigen stimulation. In the worm attack experiments, mice in the PBS and empty vector groups perished within 9 days of the worm attack, whereas mice in the pEGFP-SRS29C group survived for 18 days, mice in the pEGFP-SAG1 group survived for 21 days, and mice in the co-immunization group survived for 24 days. This demonstrates that the constructed Toxoplasma gondii nucleic acid vaccine pEGFP-SRS29C and the combined gene vaccine can induce mice to develop certain humoral and cellular immune responses, and enhance their ability to resist Toxoplasma gondii infection.
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Anticorpos Antiprotozoários , Antígenos de Protozoários , Imunoglobulina G , Proteínas de Protozoários , Vacinas Protozoárias , Toxoplasma , Vacinas de DNA , Animais , Toxoplasma/imunologia , Toxoplasma/genética , Vacinas de DNA/imunologia , Vacinas de DNA/genética , Vacinas de DNA/administração & dosagem , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Vacinas Protozoárias/imunologia , Vacinas Protozoárias/genética , Camundongos , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Feminino , Toxoplasmose Animal/prevenção & controle , Toxoplasmose Animal/imunologia , Camundongos Endogâmicos BALB C , Linfócitos T CD8-Positivos/imunologia , Baço/imunologia , Baço/parasitologia , Proliferação de Células , Plasmídeos/genética , Plasmídeos/imunologia , Citocinas/metabolismoRESUMO
Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan-Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients' prognosis in DCM.
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Cálcio , Cardiomiopatia Dilatada , Idoso , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Cardiomiopatia Dilatada/diagnóstico , Mortalidade HospitalarRESUMO
Mycoplasma wenyonii is a wall-less hemotrophic prokaryote with worldwide distribution. This paper describes the development of a LAMP method targeting 16S rRNA for specific detection of M. wenyonii in its vectors and cattle. The LAMP method is specific for M. wenyonii detection and more sensitive than PCR. A total of 330 blood samples from cattle were tested by LAMP and PCR detection, 71 (21.5 %) samples were positive by the LAMP, while only 62 (18.8 %) were positive by PCR. For detecting transmission vectors, 26 lice, 30 flies, and 26 mosquitoes were collected and 18 lice, 20 flies, and 21 mosquitoes were tested positive by LAMP and PCR. These results indicate that the LAMP assay is a simple and convenient diagnostic tool for M. wenyonii detection and can be used in epidemiological surveys.
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Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Insetos Vetores/genética , Infecções por Mycoplasma/veterinária , Mycoplasma/genética , Técnicas de Amplificação de Ácido Nucleico/veterinária , Animais , Bovinos , Primers do DNA/genética , Eletroforese em Gel de Ágar/veterinária , Infecções por Mycoplasma/diagnóstico , Infecções por Mycoplasma/epidemiologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Sensibilidade e EspecificidadeRESUMO
Drought stress can severely affect sugarcane growth and yield. The objective of this research was to identify candidate genes in sugarcane tillering seedlings in response to drought stress. We performed a comparative phenotypic, physiological and transcriptomic analysis of tiller seedlings of drought-stressed and well-watered "Guire 2" sugarcane, in a time-course experiment (5 days, 9 days and 15 days). Physiological examination reviewed that SOD, proline, soluble sugars, and soluble proteins accumulated in large amounts in tiller seedlings under different intensities of drought stress, while MDA levels remained at a stable level, indicating that the accumulation of osmoregulatory substances and the enhancement of antioxidant enzyme activities helped to limit further damage caused by drought stress. RNA-seq and weighted gene co-expression network analysis (WGCNA) were performed to identify genes and modules associated with sugarcane tillering seedlings in response to drought stress. Drought stress induced huge down-regulated in gene expression profiles, most of down-regulated genes were mainly associated with photosynthesis, sugar metabolism and fatty acid synthesis. We obtained four gene co-expression modules significantly associated with the physiological changes under drought stress (three modules positively correlated, one module negatively correlated), and found that LSG1-2, ERF1-2, SHKA, TIL, HSP18.1, HSP24.1, HSP16.1 and HSFA6A may play essential regulatory roles as hub genes in increasing SOD, Pro, soluble sugar or soluble protein contents. In addition, one module was found mostly involved in tiller stem diameter, among which members of the BHLH148 were important nodes. These results provide new insights into the mechanisms by which sugarcane tillering seedlings respond to drought stress.
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Saccharum , Transcriptoma , Plântula/genética , Saccharum/genética , Secas , Superóxido Dismutase/genética , Estresse Fisiológico/genéticaRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death globally. Oxidative stress affects various molecular mechanisms and is the main driving factor of COPD. Ally isothiocyanate (AITC) is an effective component of Semen Sinapis Albae, which has favorable effects for the treatment of COPD, but its mechanism has not been fully elucidated. PURPOSE: This study aimed to elucidate the antioxidant effect of AITC on COPD and its molecular mechanism, and preliminarily determine the role of AhR in the progression of COPD. STUDY DESIGN: The COPD rat model was established by smoking combined with intratracheal instillation of lipopolysaccharide. Different doses of AITC, positive control drug acetylcysteine, AhR inhibitor alpha-naphthoflavone, and agonist beta-naphthoflavone were administered by gavage. Human bronchial epithelial cells induced by cigarette smoke extract (CSE) were used in an in vitro model to explore the molecular mechanisms of AITC. METHODS: The effects of AITC on lung function and oxidative stress in rats were evaluated in vivo using the respiratory function test, white blood cell count, enzyme-linked immunosorbent assay, and histological staining. The changes in protein expression in the lung tissue were detected by immunohistochemistry and Western blotting. RT-PCR, western blotting, and immunofluorescence were used to explore the molecular mechanisms of AITC. Enzyme-linked immunosorbent assay, reactive oxygen species probing, and flow cytometry were used to determine the antioxidant effect of AITC. RESULTS: AITC can improve the lung function of rats with COPD, restore lung tissue structure, improve oxidative stress, reduce inflammation, and inhibit lung cell apoptosis. AITC reversed the upregulation of AhR and CYP1A1 and the down-regulation of Nrf2 and NQO1 in the lung tissues of rats with COPD. CSE stimulation can increase the expressions of AhR and CYP1A1 and decrease the expressions of Nrf2 and NQO1 in 16HBE cells, leading to severe oxidative stress and inflammatory response and, ultimately, apoptosis. AITC inhibited AhR and CYP1A1 expressions, induced Nrf2 and NQO1 expressions, promoted Nrf2 nuclear translocation, and improved CSE-induced toxicological effects. CONCLUSION: AITC may improve lung oxidative stress by inhibiting the AhR / CYP1A1 and activating the Nrf2 / NQO1 pathways, thereby delaying the pathological progression of COPD.
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Fator 2 Relacionado a NF-E2 , Doença Pulmonar Obstrutiva Crônica , Ratos , Humanos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Antioxidantes/farmacologia , Transdução de Sinais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Isotiocianatos/farmacologia , Estresse Oxidativo , NAD(P)H Desidrogenase (Quinona)/metabolismoRESUMO
In recent years, two-dimensional (2D) nonlayered Bi2O2Se-based electronics and optoelectronics have drawn enormous attention owing to their high electron mobility, facile synthetic process, stability to the atmosphere, and moderate narrow band gaps. However, 2D Bi2O2Se-based photodetectors typically present large dark current, relatively slow response speed, and persistent photoconductivity effect, limiting further improvement in fast-response imaging sensors and low-consumption broadband detection. Herein, a Bi2O2Se/2H-MoTe2 van der Waals (vdWs) heterostructure obtained from the chemical vapor deposition (CVD) approach and vertical stacking is reported. The proposed type-II staggered band alignment desirable for suppression of dark current and separation of photoinduced carriers is confirmed by density functional theory (DFT) calculations, accompanied by strong interlayer coupling and efficient built-in potential at the junction. Consequently, a stable visible (405 nm) to near-infrared (1310 nm) response capability, a self-driven prominent responsivity (R) of 1.24 A·W-1, and a high specific detectivity (D*) of 3.73 × 1011 Jones under 405 nm are achieved. In particular, R, D*, fill factor, and photoelectrical conversion efficiency (PCE) can be enhanced to 4.96 A·W-1, 3.84 × 1012 Jones, 0.52, and 7.21% at Vg = -60 V through a large band offset originated from the n+-p junction. It is suggested that the present vdWs heterostructure is a promising candidate for logical integrated circuits, image sensors, and low-power consumption detection.
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The incidence of infections caused by the H7N9 subtype of the influenza virus has expanded rapidly in China in recent decades, generating massive economic loss and posing a significant threat to public health. In the absence of specialized antiviral treatments or long-term effective preventative vaccinations, it is critical to constantly enhance vaccines and create effective antiviral drugs to prevent the recurrence of pandemics. In the present study, a transmembrane-substituted (TM) virus-like particle (VLP)-based vaccine was created by replacing the transmembrane region of hemagglutinin (HA) protein with the transmembrane region of the H3 HA protein and then used to immunize BALB/c mice. Sera and T cells were collected from the immunized mice to evaluate the passive immune effects. Our results showed that naïve mice achieved 80-100% protection against homologous and heterologous H7N9 influenza strains after receiving passive serum immunization; the protective effect of the TM VLPs was more evident than that of the wild-type HA VLPs. In contrast, mice immunized with passive T cells achieved only 20 to 80% protection against homologous or heterologous strains. Our findings significantly contribute to understanding the control of the H7N9 virus and the development of a vaccine.
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Advanced SiO2-Al2O3 aerogel materials have outstanding potential in the field of thermal insulation. Nevertheless, the creation of a mechanically robust and low-cost SiO2-Al2O3 aerogel material remains a considerable challenge. In this study, SiO2-Al2O3 aerogel based on coal gangue, which is a type of zero-cost inorganic waste, was constructed in porous agarose aerogel beads, followed by simple chemical vapor deposition of trimethylchlorosilane to fabricate SiO2-Al2O3/agarose composite aerogel beads (SCABs). The resulting SCABs exhibited a unique nanoscale interpenetrating network structure, which is lightweight and has high specific surface area (538.3 m2/g), hydrophobicity (approximately 128°), and excellent thermal stability and thermal insulation performance. Moreover, the compressive strength of the SCABs was dramatically increased by approximately a factor of ten compared to that of native SiO2-Al2O3 aerogel beads. The prepared SCABs not only pave the way for the design of a novel aerogel material for use in thermal insulation without requiring expensive raw materials, but also provide an effective way to comprehensively use coal gangue.
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Mycoplasma hyopneumoniae is a highly contagious pathogen causing porcine enzootic pneumonia, which elicits prolonged inflammatory response modulated by pattern recognition receptors (PRRs). Although significant advances have been achieved in understanding the Toll-Like receptors that recognize M. hyopneumoniae, the role of nucleotide-binding oligomerization domain 1 (NOD1) in M. hyopneumoniae infected cells remains poorly understood. This study revealed that M. hyopneumoniae activates the NOD1-RIP2 pathway and is co-localized with host NOD1 during infection. siRNA knockdown of NOD1 significantly impaired the TRIF and MYD88 pathway and blocked the activation of TNF-α. In contrast, NOD1 overexpression significantly suppressed M. hyopneumoniae proliferation. Furthermore, we for the first time investigated the interaction between M. hyopneumoniae mhp390 and NOD1 receptor, and the results suggested that mhp390 and NOD1 are possibly involved in the recognition of M. hyopneumoniae. These findings may improve our understanding of the interaction between PRRs and M. hyopneumoniae and the function of NOD1 in host defense against M. hyopneumoniae infection.
Assuntos
Infecções por Mycoplasma , Mycoplasma hyopneumoniae , Pneumonia Suína Micoplasmática , Animais , Inflamação , Mycoplasma hyopneumoniae/genética , Transdução de Sinais , SuínosRESUMO
Aerogels are three-dimensional nanoporous materials with outstanding properties, especially great thermal insulation. Nevertheless, their extremely high brittleness restricts their practical application. Recently, although the mechanical properties of silica aerogels have been improved by regulating the precursor or introducing a polymer reinforcer, these preparation processes are usually tedious and time-consuming. The purpose of this study was to simplify the preparation process of these composite aerogels. A silicic acid solution treated with cation exchange resin was mixed with agarose (AG) to gel in situ, and then composite aerogels (CAs) with an interpenetrating network (IPN) structure were obtained by aging and supercritical CO2 fluid (SCF) drying. Compared to previous works, the presented CAs preparation process is briefer and more environmentally friendly. Moreover, the CAs exhibit a high specific surface area (420.5 m2/g), low thermal conductivity (28.9 mW m-1 K-1), excellent thermal insulation properties, and thermal stability. These results show that these CAs can be better used in thermal insulation.
RESUMO
RATIONALE: Most self-insertion of urethral foreign bodies is the result of exotic impulses, psychometric problems, sexual curiosity, or sexual practice while intoxicated. Ultrasound has been proven to be an effective tool for determining the presence, location, and characteristics of the urethral foreign body. PATIENT CONCERNS: A 48-year-old man presented with a mass in the urethra for 2âyears. Physical examination suggested swelling and ulcer in the scrotum. The white blood cell count was elevated (12.60â×â109/L). Urinalysis showed an increased white cell count (484.60/µL) and urine occult blood (±). DIAGNOSIS: Ultrasound examination of the genitourinary system identified an 8.3âcm linear hyperechoic object and hyperechoic spots in the urethra. Computed tomography revealed an extremely hyperdense lesion in the penis. Intraoperative findings showed electric wire bending and winding surrounded by fibrous tissues with urethral rupture. INTERVENTIONS: The patient was treated with urethrotomy as the endoscopic treatment failed. and the electric wire was removed successfully. OUTCOMES: The patient was followed up for 45âdays without discomfort. Ultrasound examination of the genitourinary system suggested that the wound was almost healed, but with a small urethral effusion, with a maximum depth of approximately 1.9âmm. LESSONS: A foreign body was inserted into the patient's urethra for 2âyears without any medical treatment. Urethral perforation was found during surgery. In such cases, ultrasound examination can determine the location, shape, and size of the urethral foreign body and play an important role in the diagnosis of foreign bodies.