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In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.
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Vision influences behavior, but ongoing behavior also modulates vision in animals ranging from insects to primates. The function and biophysical mechanisms of most such modulations remain unresolved. Here, we combine behavioral genetics, electrophysiology, and high-speed videography to advance a function for behavioral modulations of visual processing in Drosophila. We argue that a set of motion-sensitive visual neurons regulate gaze-stabilizing head movements. We describe how, during flight turns, Drosophila perform a set of head movements that require silencing their gaze-stability reflexes along the primary rotation axis of the turn. Consistent with this behavioral requirement, we find pervasive motor-related inputs to the visual neurons, which quantitatively silence their predicted visual responses to rotations around the relevant axis while preserving sensitivity around other axes. This work proposes a function for a behavioral modulation of visual processing and illustrates how the brain can remove one sensory signal from a circuit carrying multiple related signals.
Assuntos
Drosophila melanogaster/fisiologia , Vias Visuais , Animais , Drosophila melanogaster/citologia , Voo Animal , Movimentos da Cabeça , Neurônios/citologia , Fluxo Óptico , Técnicas de Patch-Clamp , Canais de Potássio Corretores do Fluxo de Internalização/metabolismoRESUMO
Many behavioural tasks require the manipulation of mathematical vectors, but, outside of computational models1-7, it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation7-10, performs vector arithmetic. First, we describe a neural signal in the fan-shaped body that explicitly tracks the allocentric travelling angle of a fly, that is, the travelling angle in reference to external cues. Past work has identified neurons in Drosophila8,11-13 and mammals14 that track the heading angle of an animal referenced to external cues (for example, head direction cells), but this new signal illuminates how the sense of space is properly updated when travelling and heading angles differ (for example, when walking sideways). We then characterize a neuronal circuit that performs an egocentric-to-allocentric (that is, body-centred to world-centred) coordinate transformation and vector addition to compute the allocentric travelling direction. This circuit operates by mapping two-dimensional vectors onto sinusoidal patterns of activity across distinct neuronal populations, with the amplitude of the sinusoid representing the length of the vector and its phase representing the angle of the vector. The principles of this circuit may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required.
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Encéfalo/fisiologia , Sinais (Psicologia) , Drosophila melanogaster/fisiologia , Matemática , Modelos Neurológicos , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Animais , Encéfalo/citologia , Drosophila melanogaster/citologia , Feminino , Voo Animal , Objetivos , Cabeça/fisiologia , Neurônios/fisiologia , Percepção Espacial/fisiologia , CaminhadaRESUMO
When an animal moves through the world, its brain receives a stream of information about the body's translational velocity from motor commands and sensory feedback signals. These incoming signals are referenced to the body, but ultimately, they must be transformed into world-centric coordinates for navigation1,2. Here we show that this computation occurs in the fan-shaped body in the brain of Drosophila melanogaster. We identify two cell types, PFNd and PFNv3-5, that conjunctively encode translational velocity and heading as a fly walks. In these cells, velocity signals are acquired from locomotor brain regions6 and are multiplied with heading signals from the compass system. PFNd neurons prefer forward-ipsilateral movement, whereas PFNv neurons prefer backward-contralateral movement, and perturbing PFNd neurons disrupts idiothetic path integration in walking flies7. Downstream, PFNd and PFNv neurons converge onto hΔB neurons, with a connectivity pattern that pools together heading and translation direction combinations corresponding to the same movement in world-centric space. This network motif effectively performs a rotation of the brain's representation of body-centric translational velocity according to the current heading direction. Consistent with our predictions, we observe that hΔB neurons form a representation of translational velocity in world-centric coordinates. By integrating this representation over time, it should be possible for the brain to form a working memory of the path travelled through the environment8-10.
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Encéfalo/fisiologia , Drosophila melanogaster/fisiologia , Locomoção/fisiologia , Modelos Neurológicos , Percepção Espacial/fisiologia , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Animais , Encéfalo/citologia , Drosophila melanogaster/citologia , Feminino , Cabeça , Memória de Curto Prazo , Inibição Neural , Vias Neurais , Neurônios/fisiologia , Rotação , Fatores de Tempo , CaminhadaRESUMO
Omics methods are widely used in basic biology and translational medicine research. More and more omics data are collected to explain the impact of certain risk factors on clinical outcomes. To explain the mechanism of the risk factors, a core question is how to find the genes/proteins/metabolites that mediate their effects on the clinical outcome. Mediation analysis is a modeling framework to study the relationship between risk factors and pathological outcomes, via mediator variables. However, high-dimensional omics data are far more challenging than traditional data: (1) From tens of thousands of genes, can we overcome the curse of dimensionality to reliably select a set of mediators? (2) How do we ensure that the selected mediators are functionally consistent? (3) Many biological mechanisms contain nonlinear effects. How do we include nonlinear effects in the high-dimensional mediation analysis? (4) How do we consider multiple risk factors at the same time? To meet these challenges, we propose a new exploratory mediation analysis framework, medNet, which focuses on finding mediators through predictive modeling. We propose new definitions for predictive exposure, predictive mediator, and predictive network mediator, using a statistical hypothesis testing framework to identify predictive exposures and mediators. Additionally, two heuristic search algorithms are proposed to identify network mediators, essentially subnetworks in the genome-scale biological network that mediate the effects of single or multiple exposures. We applied medNet on a breast cancer data set and a metabolomics data set combined with food intake questionnaire data. It identified functionally consistent network mediators for the exposures' impact on the outcome, facilitating data interpretation.
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Neoplasias da Mama , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Genômica/métodos , Feminino , Metabolômica/métodos , Fatores de Risco , Redes Reguladoras de Genes , AlgoritmosRESUMO
Social isolation and loneliness have potent effects on public health1-4. Research in social psychology suggests that compromised sleep quality is a key factor that links persistent loneliness to adverse health conditions5,6. Although experimental manipulations have been widely applied to studying the control of sleep and wakefulness in animal models, how normal sleep is perturbed by social isolation is unknown. Here we report that chronic, but not acute, social isolation reduces sleep in Drosophila. We use quantitative behavioural analysis and transcriptome profiling to differentiate between brain states associated with acute and chronic social isolation. Although the flies had uninterrupted access to food, chronic social isolation altered the expression of metabolic genes and induced a brain state that signals starvation. Chronically isolated animals exhibit sleep loss accompanied by overconsumption of food, which resonates with anecdotal findings of loneliness-associated hyperphagia in humans. Chronic social isolation reduces sleep and promotes feeding through neural activities in the peptidergic fan-shaped body columnar neurons of the fly. Artificial activation of these neurons causes misperception of acute social isolation as chronic social isolation and thereby results in sleep loss and increased feeding. These results present a mechanistic link between chronic social isolation, metabolism, and sleep, addressing a long-standing call for animal models focused on loneliness7.
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Encéfalo/metabolismo , Drosophila melanogaster/metabolismo , Comportamento Alimentar , Modelos Animais , Sono , Isolamento Social , Inanição/metabolismo , Animais , Encéfalo/citologia , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Feminino , Fome , Hiperfagia/genética , Solidão , Masculino , Neurônios/metabolismo , Sono/genética , Privação do Sono/genética , Privação do Sono/metabolismo , Inanição/genética , Fatores de Tempo , TranscriptomaRESUMO
Microwave hyperthermia using the phased array applicator is a non-invasive treatment modality for breast cancer. Hyperthermia treatment planning (HTP) is critical to accurately treating breast cancer and avoiding damage to the patient's healthy tissue. A global optimization algorithm, differential evolution (DE) algorithm, has been applied to optimize HTP for breast cancer and its ability to improve the treatment effect was proved by electromagnetic (EM) and thermal simulation results. DE algorithm is compared to time reversal (TR) technology, particle swarm optimization (PSO) algorithm, and genetic algorithm (GA) in HTP for breast cancer in terms of convergence rate and treatment results, such as treatment indicators and temperature parameters. The current approaches in breast cancer microwave hyperthermia still have the problem of hotspots in healthy tissue. DE enhances focused microwave energy absorption into the tumor and reduces the relative energy of healthy tissue during hyperthermia treatment. By comparing the treatment results of each objective function used in DE, the DE algorithm with hotspot to target quotient (HTQ) as the objective function has outstanding performance in HTP for breast cancer, which can increase the focused microwave energy of the tumor and decrease the damage to healthy tissue.
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Neoplasias da Mama , Hipertermia Induzida , Humanos , Feminino , Hipertermia Induzida/métodos , Micro-Ondas/uso terapêutico , Neoplasias da Mama/terapia , Calefação , TemperaturaRESUMO
Focused microwave-hyperthermia therapy has recently emerged as a key technology in the treatment of breast cancer due to non-invasive treatment. An applicator of a three-ring phased array consisting of ultra-wideband (UWB) microstrip antennas was designed for breast cancer therapy and operates at 0.915 GHz and 2.45 GHz. The proposed antenna has an ultra-wideband from 0.7 GHz to 5.5 GHz with resonant frequencies of 0.915 GHz and 2.45 GHz and dimensions of 15 × 43.5 × 1.575 mm3. The number of each ring was chosen to be 12 based on the SAR distribution and the performance indicators of tumor off-center focusing results for four different numbers of single-ring arrays. The homogeneous breast model is applied to a three-ring phased array consisting of 36 elements for focused simulation, and 1 cm3 and 2 cm3 tumors are placed in three different locations in the breast. The simulation results show that the proposed phased array has good performance and the capability to raise the temperature of different volumes of breast cancer above 42.5 °C after choosing a suitable operating frequency. The proposed applicator allows for precise treatment of tumors by selecting the appropriate operating frequency based on the size of the malignant tumor.
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Neoplasias da Mama , Hipertermia Induzida , Humanos , Feminino , Neoplasias da Mama/terapia , Hipertermia Induzida/métodos , Mama , Simulação por Computador , TemperaturaRESUMO
Metal oxide ZrO2has been widely explored for resistive switching application due to excellent properties like high ON/OFF ratio, superior data retention, and low operating voltage. However, the conduction mechanism at the atomistic level is still under debate. Therefore, we have performed comprehensive insights into the role of neutral and charged oxygen vacancies in conduction filament (CF) formation and rupture, which are demonstrated using the atomistic simulation based on density functional theory (DFT). Formation energy demonstrated that the fourfold coordinated oxygen vacancy is more stable. In addition, the electronic properties of the defect included supercell confirm the improvement in electrical conductivity due to the presence of additional energy states near Fermi energy. The CF formation and rupture using threefold and fourfold oxygen vacancies are demonstrated through cohesive energy, electron localization function, and band structure. Cohesive energy analysis confirms the cohesive nature of neutral oxygen vacancies while the isolated behavior for +2 charged oxygen vacancies in the CF. In addition, nudged elastic band calculation is also performed to analyze the oxygen vacancy diffusion energy under different paths. Moreover, we have computed the diffusion coefficient and drift velocity of oxygen vacancies to understand the CF. This DFT study described detailed insight into filamentary type resistive switching observed in the experimentally fabricated device. Therefore, this fundamental study provides the platform to explore the switching mechanism of other oxide materials used for memristor device application.
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Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.
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Angelica sinensis , Medicamentos de Ervas Chinesas , Angelica sinensis/química , Medicamentos de Ervas Chinesas/farmacologia , Raízes de Plantas/química , ChinaRESUMO
1,4,5,8,9,12-Hexaazatriphenylene (HAT) is one of the smallest polyheterocyclic aromatic building blocks for forming conjugated metal-organic frameworks (cMOFs). However, the strong inter-molecular steric hindrance impedes the growth of HAT-based cMOFs. Here we employ on-surface synthesis to grow single-layer two-dimensional cMOFs of M3 (HAT)2 (M=Ni, Fe, Co). Using scanning tunnelling microscopy and density-functional theory (DFT) analysis, we resolve that the frameworks comprise a hexagonal lattice of HAT molecules and a Kagome lattice of metal atoms. The DFT analysis indicates that Ni, Co and Fe carry a magnetic moment of 1.1, 2.5, and 3.7â µB, respectively. We anticipate that the small π-conjugated core of HAT and strong bidentate chelating coordination give rise to appealing electronic and magnetic properties.
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The present study explored the mechanism of Fagopyri Dibotryis Rhizoma(FDR) and its main active components in the treatment of acute lung injury(ALI) based on the network pharmacology and the in vitro experiments. The main active components of FDR were obtained from the TCMSP database and screened by oral bioavailability and drug-likeness. The related target proteins of FDR were retrieved from the PubChem database, and the target genes related to ALI were screened out from the GeneCards database. A protein-protein interaction(PPI) network of compound target proteins and ALI target genes was constructed using STRING 11.0. Ingenuity Pathway Analysis(IPA) platform was used to analyze the common pathways of the potential compound target proteins of FDR and ALI target genes, thereby predicting the key targets and potential signaling pathways of FDR for the treatment of ALI. Finally, the potential pathways and key targets were verified by the in vitro experiments of lipopolysaccharide-induced RAW264.7 cells intervened by epicatechin(EC), the active component of FDR. The results of network pharmacology showed that 15 potential active components such as EC, procyanidin B1, and luteolin presumedly functioned in the treatment of ALI through nuclear transcription factor-κB(NF-κB) signaling pathway, transforming growth factor-ß(TGF-ß) signaling pathway, and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway through key targets, such as RELA(P65). The results of in vitro experiments showed that 25 µmol·L~(-1) EC had no toxicity to cells and could inhibit the expression of the p65-phosphorylated protein in the NF-κB signaling pathway to down-regulate the expression of downstream inflammatory cytokines, including tumor necrosis factor-α(TNF-α), IL-1ß and nitric oxide(NO), and up-regulate the expression of IL-10. These results suggested that the therapeutic efficacy of FDR on ALI was achieved by inhibiting the phosphorylation of p65 protein in the NF-κB signaling pathway and down-regulating the level of proinflammatory cytokines downstream of the signaling pathways.
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Lesão Pulmonar Aguda , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Lipopolissacarídeos , NF-kappa B/genética , NF-kappa B/metabolismo , Rizoma , Transdução de SinaisRESUMO
BACKGROUND: The prevalence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) is on the rise worldwide. Polymyxins are considered as last-resort drugs for CRAB infections, but there is still controversy regarding the efficacy and safety of polymyxins based therapies in CRAB infections. The present systematic review was designed to compare the efficacy and safety of polymyxins based therapies versus non-polymyxins based therapies in CRAB infections. METHODS: We performed a systematic literature search in PubMed, Embase, CINAHL, Cochrane Library, and clinicaltrials.gov to identify eligible studies reporting the clinical outcomes of patients with CRAB infections. The meta-analysis employed a random-effects model to estimate the odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI). The primary outcome was 1-month mortality for any cause. We also examined clinical response, microbiological response, length of stay in hospital, and adverse events. RESULTS: Eleven eligible studies were analyzed (1052 patients in total), including 2 randomized clinical trials. Serious risk of bias was found in 8 out of the 11 studies. There was no statistically significant difference between polymyxins based therapies and non-polymyxins based therapies in 1-month mortality for any cause (OR, 0.95; 95% CI, 0.59 to 1.53), microbiological response (OR, 3.83; 95% CI, 0.90 to 16.29) and length of stay in hospital (SMD, 0.24; 95% CI, - 0.08 to 0.56). The pooled OR of clinical response indicated a significant difference in favor of polymyxin based therapies (OR, 1.99; 95% CI, 1.31 to 3.03). The pooled OR of adverse events showed that non-polymyxins based therapies were associated with fewer adverse events (OR, 4.32; 95% CI, 1.39 to 13.48). CONCLUSION: The performance of polymyxins based therapies was better than non-polymyxin based therapies in clinical response rate and similar to non-polymyxin based therapies in terms of 1-month mortality and microbiological response in treating CRAB infections. Due to the limitations of our study, we cannot draw a firm conclusion on the optimal treatment of CRAB infections, but polymyxins would be a relatively effective treatment for CRAB infections. Adequate and well-designed large scale randomized controlled trials are required to clarify the relative efficacy of polymyxins based and non-polymyxins based therapies.
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Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/isolamento & purificação , Polimixinas/uso terapêutico , Infecções por Acinetobacter/diagnóstico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Tempo de Internação , Razão de Chances , Polimixinas/efeitos adversos , Polimixinas/farmacologia , Resultado do TratamentoRESUMO
Alligator weed is reported to have a strong ability to adapt to potassium deficiency (LK) stress. Leaves are the primary organs responsible for photosynthesis of plants. However, quantitative proteomic changes in alligator weed leaves in response to LK stress are largely unknown. In this study, we investigated the physiological and proteomic changes in leaves of alligator weed under LK stress. We found that chloroplast and mesophyll cell contents in palisade tissue increased, and that the total chlorophyll content, superoxide dismutase (SOD) activity and net photosynthetic rate (PN) increased after 15 day of LK treatment, but the soluble protein content decreased. Quantitative proteomic analysis suggested that a total of 119 proteins were differentially abundant proteins (DAPs). KEGG analysis suggested that most represented DAPs were associated with secondary metabolism, the stress response, photosynthesis, protein synthesis, and degradation pathway. The proteomic results were verified using parallel reaction monitoring mass spectrometry (PRM-MS) analysis and quantitative real-time PCR (qRT-PCR)assays. Additional research suggested that overexpression of cationic peroxidase 1 of alligator weed (ApCPX1) in tobacco increased LK tolerance. The seed germination rate, peroxidase (POD) activity, and K+ content increased, and the hydrogen peroxide (H2O2) content decreased in the three transgenic tobacco lines after LK stress. The number of root hairs of the transgenic line was significantly higher than that of WT, and net K efflux rates were severely decreased in the transgenic line under LK stress. These results confirmed that ApCPX1 played positive roles in low-K+ signal sensing. These results provide valuable information on the adaptive mechanisms in leaves of alligator weed under LK stress and will help identify vital functional genes to apply to the molecular breeding of LK-tolerant plants in the future.
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Peroxidases/metabolismo , Folhas de Planta/metabolismo , Plantas Daninhas/metabolismo , Deficiência de Potássio/metabolismo , Proteoma , Proteômica , Estresse Fisiológico , Animais , Cromatografia Líquida de Alta Pressão , Biologia Computacional/métodos , Ontologia Genética , Fenótipo , Proteômica/métodos , Espectrometria de Massas em TandemRESUMO
To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1ß(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1ß(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1ß(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1ß(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1ß(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.
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Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Tripterygium/química , Animais , Citocinas , Humanos , Leflunomida/uso terapêutico , Metotrexato/uso terapêutico , ComprimidosRESUMO
To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.
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Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Tripterygium/química , Antirreumáticos/uso terapêutico , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Comprimidos , Resultado do TratamentoRESUMO
Exploration of brain dynamics patterns has attracted increasing attention due to its fundamental significance in understanding the working mechanism of the brain. However, due to the lack of effective modeling methods, how the simultaneously recorded LFP can inform us about the brain dynamics remains a general challenge. In this paper, we propose a novel sparse coding based method to investigate brain dynamics of freely-behaving mice from the perspective of functional connectivity, using super-long local field potential (LFP) recordings from 13 distinct regions of the mouse brain. Compared with surrogate datasets, six and four reproducible common functional connectivities were discovered to represent the space of brain dynamics in the frequency bands of alpha and theta respectively. Modeled by a finite state machine, temporal transition framework of functional connectivities was inferred for each frequency band, and evident preference was discovered. Our results offer a novel perspective for analyzing neural recording data at such high temporal resolution and recording length, as common functional connectivities and their transition framework discovered in this work reveal the nature of the brain dynamics in freely behaving mice.
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Encéfalo/fisiologia , Potenciais Evocados/fisiologia , Vias Neurais/fisiologia , Ritmo alfa , Animais , Comportamento Animal/fisiologia , Mapeamento Encefálico , Eletroencefalografia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Ritmo TetaRESUMO
The macronutrient potassium is essential to plant growth, development and stress response. Alligator weed (Alternanthera philoxeroides) has a high tolerance to potassium deficiency (LK) stress. The stem is the primary organ responsible for transporting molecules from the underground root system to the aboveground parts of the plant. However, proteomic changes in response to LK stress are largely unknown in alligator weed stems. In this study, we investigated the physiological and proteomic changes in alligator weed stems under LK stress. First, the chlorophyll and soluble protein content and SOD and POD activity were significantly altered after 15 days of LK treatment. The quantitative proteomic analysis suggested that a total of 296 proteins were differentially abundant proteins (DAPs). The functional annotation analysis revealed that LK stress elicited complex proteomic alterations that were involved in oxidative phosphorylation, plant-pathogen interactions, glycolysis/gluconeogenesis, sugar metabolism, and transport in stems. The subcellular locations analysis suggested 104 proteins showed chloroplastic localization, 81 proteins showed cytoplasmic localization and 40 showed nuclear localization. The proteinâ»protein interaction analysis revealed that 56 proteins were involved in the interaction network, including 9 proteins involved in the ribosome network and 9 in the oxidative phosphorylation network. Additionally, the expressed changes of 5 DAPs were similar between the proteomic quantification analysis and the PRM-MS analysis, and the expression levels of eight genes that encode DAPs were further verified using an RT-qPCR analysis. These results provide valuable information on the adaptive mechanisms in alligator weed stems under LK stress and facilitate the development of efficient strategies for genetically engineering potassium-tolerant crops.
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Amaranthaceae/fisiologia , Caules de Planta/metabolismo , Plantas Daninhas/metabolismo , Potássio/farmacologia , Proteoma/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Amaranthaceae/efeitos dos fármacos , Ontologia Genética , Modelos Biológicos , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Caules de Planta/efeitos dos fármacos , Plantas Daninhas/efeitos dos fármacos , Domínios Proteicos , Mapas de Interação de Proteínas , Proteômica , Frações Subcelulares/metabolismoRESUMO
The aim of this paper was to study the influence of triptolide in the immune response pathways of acquired immune deficiency syndrome( AIDS). Target proteins of triptolide and related genes of AIDS were searched in PubChem and Gene databases on line. Molecular networks and canonical pathways comparison analyses were performed by bioinformatics software( IPA). There were 15 targets proteins of triptolide and 258 related genes of AIDS. Close biological relationships of molecules of triptolide and AIDS were established by networks analysis. There were 21 common immune response pathways of triptolide and AIDS,including neuroinflammation signaling pathway,Th1 and Th2 activation pathway and role of pattern recognition receptors in recognition of bacteria and viruses. Triptolide stimulated immune response pathways by the main molecules of IFNγ,JAK2,NOD1,PTGS2,RORC. IFNγ is the focus nodes of triptolide and AIDS,and regulates genes of AIDS directly or indirectly. Triptolide may against AIDS by regulating molecules IFNγ in immune response pathways.