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Long noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.
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Nefropatías Diabéticas , Transición Epitelial-Mesenquimal , Proteínas de Homeodominio , Túbulos Renales , ARN Largo no Codificante , Transición Epitelial-Mesenquimal/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Humanos , Ratones , Túbulos Renales/metabolismo , Túbulos Renales/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Masculino , Células Epiteliales/metabolismo , Células Epiteliales/patología , Glucosa/metabolismo , Glucosa/farmacología , Fibrosis , Ratones Endogámicos C57BL , Femenino , Persona de Mediana EdadRESUMEN
Estuarine areas are not only the main gathering point for human sewage but also the place where one-way and two-way fluids interact, thus forming a complex and changeable geochemical physical field. Here, heavy metals (HMs) are adsorbed and desorbed due to physical, chemical, and biochemical processes. However, the adsorption and desorption behavior of HMs in the aquatic environment is complex, and physicochemical processes occurring in the estuarine sediment-water interface control the direction and boundaries of the system. This study analyzed the migration and distribution of HMs in rivers and lakes, and established a Bayesian network model to quantitatively understand the impact of nutrients and key environmental factors on the adsorption-desorption behavior of HMs in lake and estuaries, as well as the competitive relationship between environmental factors. The influence of environmental factors and the occurrence of HMs are both important model inputs. Our findings indicated that the migration risk of Cd in Qinghai Lake was high. Environmental factors such as Cation exchange capacity (CEC), Organic matter (OM), Soluble fluoride (SFL), and pH play the most important role in the adsorption and desorption of HMs. Our findings also indicated that the exchange and activity of HMs in sediments were much higher than in the overlying water. The organic matter content was the most complex environmental factor affecting HMS adsorption and desorption at the water-sediment interface. Additionally, the mass concentration of dissolved oxygen (DO) has a linear relationship with bioavailable HMs in river and lake sediments, but has no linear relationship with the concentration of water-soluble HMs. Interestingly, there are synergistic effects between environmental factors, which directly or indirectly affect the release of bioavailable HMs. However, it is important to determine whether the effects of different environmental factors on the exchange of bioavailable HMs are negative or positive. Our findings suggested that Bayesian network (BN) signals (positive or negative) could provide insights into the transfer direction of metals in the water-sediment interface.
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Metales Pesados , Contaminantes Químicos del Agua , Humanos , Adsorción , Agua , Teorema de Bayes , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisis , Sedimentos Geológicos/química , Metales Pesados/análisis , China , LagosRESUMEN
The specification of the meristem/organ boundary is critical for plant development. Here, we investigate two previously uncharacterized NAC transcription factors: the first, OsCUC1, which is negatively regulated by osa-miR164c, dimerizes with the second, OsCUC3, and functions partially redundantly in meristem/organ boundary specification in rice (Oryza sativa). We produced knockout lines for rice OsCUC1 (the homolog of Arabidopsis CUC1 and CUC2) and OsCUC3 (the homolog of Arabidopsis CUC3), as well as an overexpression line for osa-miR164c, to study the molecular mechanism of boundary specification in rice. A single mutation in either OsCUC1 or OsCUC3 leads to defects in the establishment of the meristem/organ boundary, resulting in reduced stamen numbers and the fusion of leaves and filaments, and the defects are greatly enhanced in the double mutant. Transgenic plants overexpressing osa-miR164c showed a phenotype similar to that of the OsCUC1 knockout line. In addition, knockout of OsCUC1 leads to multiple defects, including dwarf plant architecture, male sterility and twisted-rolling leaves. Further study indicated that OsCUC1 physically interacts with leaf-rolling related protein CURLED LEAF AND DWARF 1 (CLD1) and stabilizes it in the nucleus to control leaf morphology. This work demonstrated that the interplay of osa-miR164c, OsCUC1 and OsCUC3 controls boundary specification in rice.
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Proteínas de Arabidopsis , Arabidopsis , MicroARNs , Oryza , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Meristema/genética , Meristema/metabolismo , MicroARNs/genética , Mutación/genética , Oryza/genética , Oryza/metabolismo , Fenotipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Silent information regulator 1 (Sirt1) is a deacetylase, which plays an important role in the occurrence and development of diabetic nephropathy (DN). Our previous study shows that Yin yang 1 (YY1), a widely expressed zinc finger DNA/RNA-binding transcription factor, is a novel regulator of renal fibrosis in diabetic nephropathy. Since the activity of YY1 is regulated via acetylation and deacetylation modification, this study aimed to explore whether Sirt1-induced deacetylation of YY1 mediated high glucose (HG)-induced renal tubular epithelial-mesenchymal transition (EMT) and renal fibrosis in vivo and in vitro. We first confirmed that Sirt1 expression level was significantly decreased in the kidney of db/db mice and in HG-treated HK-2 cells. Diabetes-induced Sirt1 reduction enhanced the level of YY1 acetylation and renal tubular EMT. Then, we manipulated Sirt1 expression in vivo and in vitro by injecting resveratrol (50 mg·kg-1·d-1. ip) to db/db mice for 2 weeks or application of SRT1720 (2.5 µM) in HG-treated HK-2 cells, we found that activation of Sirt1 reversed the renal tubular EMT and YY1 acetylation induced by HG condition. On the contrary, Sirt1 was knocked down in db/m mice or EX527 (1 µM) was added in HK-2 cells, we found that inhibition of Sirt1 exacerbated renal fibrosis in diabetic mice and enhanced level of YY1 acetylation in HK-2 cells. Furthermore, knockdown of YY1 inhibited the ameliorating effect of resveratrol on renal tubular EMT and renal fibrosis in db/db mice. In conclusion, this study demonstrates that Sirt1 plays an important role in renal tubular EMT of DN through mediating deacetylation of YY1.
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Diabetes Mellitus Experimental/complicaciones , Nefropatías Diabéticas/fisiopatología , Sirtuina 1/genética , Factor de Transcripción YY1/metabolismo , Animales , Línea Celular , Diabetes Mellitus Experimental/genética , Nefropatías Diabéticas/genética , Transición Epitelial-Mesenquimal/genética , Fibrosis , Técnicas de Silenciamiento del Gen , Glucosa/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Masculino , Ratones , Resveratrol/farmacología , Factor de Transcripción YY1/genéticaRESUMEN
Inflammation reaction mediated by NLRP3 inflammasome and Nrf2-related oxidative stress are vital participants in the development of diabetic nephropathy (DN) and closely associated to kidney fibrosis. Nrf2, a known antioxidative transcription factor, has been reported to activate NLRP3 inflammasome through its downstream factors (HO-1, NQO1, etc.) recently. AB38b is a newly synthesized biphenyl diester derivative with a Nrf2 activation property. This research aims to evaluate the renal protective effects of AB-38b and to elucidate the anti-inflammation mechanisms involved. Type 2 diabetic mice induced by high fat diet with streptozocin (STZ) and high glucose-cultured mouse glomerular mesangial cells (GMCs) were used in current study. Results showed that administration of AB-38b improved the kidney function while attenuated renal fibrosis progression in diabetic mice together with reducing the extracellular matrix (ECM) accumulation of GMCs cultured in high glucose. Mechanistically, treatment with AB-38b significantly decreased the high level of NLRP3 inflammasome in diabetic condition by inhibiting the ROS/TXNIP/NLRP3 signaling pathway. And meanwhile, AB-38b treatment effectively improved Nrf2 signaling during diabetic condition. Furthermore, knocking down the gene expression of Nrf2 by siRNA in GMCs abolished the inhibition effect of AB-38b on NLRP3 inflammasome activation and ECM accumulation. Taken together, our data suggest that AB-38b was able to improve the renal function of diabetic mice, and the NLRP3 inflammasome inhibition effect of AB-38b was responsible for the renal protective effect. Further exploration indicate that Nrf2 plays pivotal role in AB-38b's attenuation of DN progression through inhibiting NLRP3 inflammasome activation.
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Compuestos de Bifenilo/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Animales , Compuestos de Bifenilo/química , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología , Matriz Extracelular/metabolismo , Fibrosis/metabolismo , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Inflamasomas/farmacología , Inflamación/metabolismo , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Estreptozocina/farmacologíaRESUMEN
Unfortunately, there are some tiny errors in the data for Fig. 1a-c and Fig. 2a-e in the published online paper. Please see the correct relative data in Tables 3 and 4 given in the next page. These errors does not interfere the results and conclusions of authors study.
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Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, ß-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mM)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg-1· d-1, ig) or a positive control drug resveratrol (40 mg· kg-1· d-1, ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5-10 µM) or resveratrol (10 µM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Proteína 1 Asociada A ECH Tipo Kelch/antagonistas & inhibidores , Cetonas/farmacología , Morfolinas/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Resveratrol/farmacología , Animales , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Matriz Extracelular/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Cetonas/química , Masculino , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Morfolinas/química , Estrés Oxidativo/efectos de los fármacos , Resveratrol/química , Transducción de Señal/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Exenatide is widely used in the treatment of type 2 diabetes mellitus (T2DM) because of its established effect on lowering glucose and promotion of weight loss. However, therapeutic response to exenatide varies considerably among patients with T2DM. The purpose of this study was to determine which variables can predict the response to exenatide and to individualize specific therapies for patients with T2DM who need treatment with exenatide. METHODS: This is a retrospective cohort study of patients with T2DM who were treated with exenatide twice daily as a part of their diabetes care for at least 12 months. Patients were categorized into two cohorts based on glycaemic response to exenatide use: responders and non-responders. RESULTS AND DISCUSSION: One hundred forty-eight patients met the inclusion criteria; among them, 92 responded with an HbA1C reduction ≥1.0% from baseline HbA1C and 56 did not respond to exenatide after 6 months of exenatide treatment. Binary logistic regression analysis revealed that baseline HbA1C and duration of diabetes were identified as predictors of HbA1C reduction ≥1% at 6 months (P < .05). Linear regression analysis further identified that patients with a higher baseline HbA1C (≥7.4%) and shorter duration of diabetes (≤15.0 years) were likely to respond to exenatide, whereas those with a lower baseline HbA1C (<7.4%) and longer duration of diabetes (>15.0 years) were not likely to respond to exenatide. WHAT IS NEW AND CONCLUSION: Our data indicate that T2DM patients with a higher baseline HbA1C and a shorter duration of diabetes are more likely to have a glycaemic response to exenatide than those with a lower baseline HbA1C and a longer duration of diabetes. The identification of predictors of therapeutic response to exenatide can provide clinically useful information for characterizing the patients who could receive the greatest benefit from exenatide.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/farmacología , Hipoglucemiantes/farmacología , Adulto , Pueblo Asiatico , Estudios de Cohortes , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Perinatal period is the critical time in dairy cattle due to negative energy balance and high milk production stress. Being a key role in biosynthesis and methylation cycle, folic acid is considered essential for lactational and metabolic performance in dairy cattle. Thus, the current study was designed to evaluate the effect of folic acid supplementation on milk production phenotypic traits in periparturient cows. Transcriptomic screening was performed for milk production and metabolism-associated differentially expressed genes. The 123 cows having similar parity, weight and expected date of calving were randomly selected and divided into three groups; A (n = 41, folic acid 240 mg/500 kg cow/day), B (n = 40, FA 120 mg/500 kg cow/day) and C (Control, n = 42). Folic acid was supplemented for 21 days (14 days pre- and seven days post-calving), and three samples of blood lymphocytes were taken on day seven post-calving from each folic acid-treated and control group. In addition, the milk samples for each folic acid-treated group have been collected at 2nd, 3rd and 4th month of lactation. The increase in average milk yield noticed in group B were significantly (p-value < .05) higher than C and A. However, the data showed no noteworthy differences for milk fat and milk protein among the three groups. The transcriptomic analysis revealed that folic acid treatment regulated many key metabolic-related genes (DGAT2, ALOX5, LAP3, GPAT3, GGH, ALDOA, TKT) and pathways (glycolysis, folate biosynthesis, glutathione metabolism, etc.) in periparturient dairy cattle. It was concluded from the above findings that 120 mg/500 kg of folic acid quantity could be considered as a standard during the periparturient period to enhance the milk production performance of dairy cows. The transcriptomic profile revealed several metabolic and milk production-associated genes which could be a useful addition to the marker selection for the enhancement of metabolism and milk production of periparturient dairy cows.
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Bovinos , Suplementos Dietéticos , Ácido Fólico/farmacología , Lactancia/efectos de los fármacos , Leche , Animales , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/administración & dosificación , Regulación de la Expresión Génica/efectos de los fármacos , Lactancia/fisiología , EmbarazoRESUMEN
OBJECTIVE: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. METHODS: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240mg/ 500 kg cow/day), group B (n = 40, 120mg/ 500 kg cow/day) and group C (n = 42, 0mg/cow/day) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (High, Low, and Control) and RNA sequencing method was carried out for transcriptomic analysis. RESULTS: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways (TNF signaling, Antigen processing and presentation, Staphylococcus aureus infection and NF-kappa B signaling pathways) and the key genes (e.g. CXCL10, TNFRSFIA, CD4, BOLA-DQB, NFKBIA, and TNFSF13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. CONCLUSION: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between High vs. Control and Low vs. Control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.
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OBJECTIVE: The impact of forage feeding strategy on growth performance, ruminal fermentation and nutrient digestibility in post-weaning calves was investigated. METHODS: Forty-five female Holstein calves (body weight [BW] = 79.79±0.38 kg) were enrolled in the 35-d study at one week after weaning and randomly assigned to one of three dietary treatments. All diets were fed as total mixed ration containing 60% (dry matter [DM] basis) of basal starter feed and 40% (DM basis) of forage, but varied in composition of forage source including i) alfalfa (40% DM, AH); ii) alfalfa hay (26.7% DM)+oat hay (13.3% DM; OH); iii) alfalfa hay (26.7% DM)+corn silage (13.3% DM; WS). RESULTS: Dry matter intake was not different among treatment groups (p>0.05). However, BW (p<0.05) and average daily gain (p<0.05) of calves fed AH and OH were greater than WS-fed calves, whereas heart girth was greater in OH-fed calves than those fed AH and WS (p<0.05). Ruminal fermentation parameters including proportion of butyric acid, acetated-to-propionate ratio, concentration of total volatile fatty acid, protozoal protein, bacterial protein, and microbial protein in rumen were the highest in OH (p<0.05) and the lowest in WS. Compared with the AH and WS, feeding oat hay to postweaning calves increased crude protein digestibility (p<0.05), and decreased duration of diarrhea (p<0.05) and fecal index (p<0.05). CONCLUSION: Our results suggested that partially replacing alfalfa hay with oat hay improved ruminal fermentation, nitrogen utilization, and reduced incidence of diarrhea in post-weaning dairy calves.
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Increased galectin-3 expression has been currently showed to be associated with poor prognosis in some hematological malignancies, such as acute myeloid leukemia, diffuse large B cell lymphoma. However, little is known about the clinical significance of galectin-3 in patients with acute promyelocytic leukemia (APL). We investigated the concentration of serum galectin-3 and characterized the relationship between galectin-3 and outcome in patients with APL. Higher galectin-3 levels were detected in patients with APL compared with the healthy controls (p < 0.001). Higher galectin-3 levels were closely associated with older ages (p < 0.001), the medical history of psoriasis (p = 0.036), coagulopathy (p = 0.042), and CD34 expression (p = 0.004). Compared with patients with lower galectin-3 levels, those with higher galectin-3 levels had significant shorter overall survival (p = 0.028) and relapse-free survival (p = 0.001). Multivariate analysis showed that serum galectin-3 was an independent unfavorable factor for relapse-free survival in patients with APL treated with all-trans retinoic acid and arsenic trioxide-based frontline therapy. Clinical impact of galectin-3 should be further investigated in patients with APL.
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Galectina 3/sangre , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/genética , Proteínas de Fusión Oncogénica/genética , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trióxido de Arsénico , Arsenicales/administración & dosificación , Biomarcadores de Tumor , Estudios de Casos y Controles , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 17 , Femenino , Humanos , Inmunofenotipificación , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Óxidos/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Translocación Genética , Resultado del Tratamiento , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: S. aureus is one of the major etiological agents causing bovine subclinical mastitis. The regulatory effects of H3K27me3 on gene expression in subclinical S. aureus mastitis cows are unknown. This study aimed to profile genome-wide transcriptional changes regulated by H3K27me3 in bovine lymphocytes applied in subclinical S. aureus mastitis cows and healthy controls. RESULTS: A total of 61 differentially expressed genes (DEGs) were detected in subclinical S. aureus mastitis cows compared to the healthy controls, of which 25 DEGs are up-regulated and the rest are down-regulated genes in subclinical S.aureus mastitis cows. The up-regulated genes are mainly involved in the Jak-STAT signaling pathway, cytokine-cytokine receptor interaction, and T cell receptor-signaling pathway, while the down-regulated genes are related to metabolism pathways. Combination analysis of histone methylation and gene expression revealed that H3K27 trimethylation levels in silent genes were higher in subclinical S. aureus mastitis cattle than in healthy cows. The key regions of H3K27me3 target genes related to subclinical S. aureus mastitis were the upstream 2 kb regions of the DEGs relative to transcription start site (TSS). CONCLUSIONS: The current study provides a novel insight into the interaction between S. aureus and lymphocytes in lactating cows by histone H3 methylation regulation. The differentially expressed genes in bovine lymphocytes regulated by H3K27me3 on upstream 2 kb regions (IL10, PTX3 and etc.) may relate to S. aureus mastitis susceptibility and could be considered as key candidate genes for anti- S. aureus mastitis study and breeding.
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Metilación de ADN , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Histonas/metabolismo , Mastitis Bovina/genética , Mastitis Bovina/metabolismo , Infecciones Estafilocócicas/veterinaria , Staphylococcus aureus , Animales , Bovinos , Inmunoprecipitación de Cromatina , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Mastitis Bovina/microbiología , Unión Proteica , Reproducibilidad de los ResultadosRESUMEN
Computer aided diagnosis methods play an important role in Attention Deficit Hyperactivity Disorder (ADHD) identification. Dynamic functional connectivity (dFC) analysis has been widely used for ADHD diagnosis based on resting-state functional magnetic resonance imaging (rs-fMRI), which can help capture abnormalities of brain activity. However, most existing dFC-based methods only focus on dependencies between two adjacent timestamps, ignoring global dynamic evolution patterns. Furthermore, the majority of these methods fail to adaptively learn dFCs. In this paper, we propose an adaptive spatial-temporal neural network (ASTNet) comprising three modules for ADHD identification based on rs-fMRI time series. Specifically, we first partition rs-fMRI time series into multiple segments using non-overlapping sliding windows. Then, adaptive functional connectivity generation (AFCG) is used to model spatial relationships among regions-of-interest (ROIs) with adaptive dFCs as input. Finally, we employ a temporal dependency mining (TDM) module which combines local and global branches to capture global temporal dependencies from the spatially-dependent pattern sequences. Experimental results on the ADHD-200 dataset demonstrate the superiority of the proposed ASTNet over competing approaches in automated ADHD classification.
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Plant architecture and panicle architecture are two critical agronomic traits that greatly affect the yield of rice (Oryza sativa). PROSTRATE GROWTH 1 (PROG1) encodes a key C2H2-type zinc-finger transcription factor and has pleiotropic effects on the regulation of both plant and panicle architecture, thereby influencing the grain yield. However, the molecular mechanisms through which PROG1 controls plant and panicle architecture remain unclear. In this study, we showed that PROG1 directly binds the LAZY 1 (LA1) promoter and acts as a repressor to inhibit LA1 expression. Conversely, LA1 acts as a repressor of PROG1 by directly binding to the PROG1 promoter. These two genes play antagonistic roles in shaping plant architecture by regulating both tiller angle and tiller number. Interestingly, our data showed that PROG1 controls panicle architecture through direct binding to the intragenic regulatory regions of OsGIGANTEA (OsGI) and subsequent activation of its expression. Collectively, we have identified two crucial targets of PROG1, LA1 and OsGI, shedding light on the molecular mechanisms underlying plant and panicle architecture control by PROG1. Our study provides valuable insights into the regulation of key domestication-related traits in rice and identifies potential targets for future high-yield rice breeding.
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Oryza , Oryza/genética , Domesticación , Fitomejoramiento , Agricultura , Grano ComestibleRESUMEN
Introduction: Dynamic functional connectivity (dFC), which can capture the abnormality of brain activity over time in resting-state functional magnetic resonance imaging (rs-fMRI) data, has a natural advantage in revealing the abnormal mechanism of brain activity in patients with Attention Deficit/Hyperactivity Disorder (ADHD). Several deep learning methods have been proposed to learn dynamic changes from rs-fMRI for FC analysis, and achieved superior performance than those using static FC. However, most existing methods only consider dependencies of two adjacent timestamps, which is limited when the change is related to the course of many timestamps. Methods: In this paper, we propose a novel Temporal Dependence neural Network (TDNet) for FC representation learning and temporal-dependence relationship tracking from rs-fMRI time series for automated ADHD identification. Specifically, we first partition rs-fMRI time series into a sequence of consecutive and non-overlapping segments. For each segment, we design an FC generation module to learn more discriminative representations to construct dynamic FCs. Then, we employ the Temporal Convolutional Network (TCN) to efficiently capture long-range temporal patterns with dilated convolutions, followed by three fully connected layers for disease prediction. Results: As the results, we found that considering the dynamic characteristics of rs-fMRI time series data is beneficial to obtain better diagnostic performance. In addition, dynamic FC networks generated in a data-driven manner are more informative than those constructed by Pearson correlation coefficients. Discussion: We validate the effectiveness of the proposed approach through extensive experiments on the public ADHD-200 database, and the results demonstrate the superiority of the proposed model over state-of-the-art methods in ADHD identification.
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The gut microbiota plays a key role in the function of the host immune system and neuroimmune diseases. Alterations in the composition of the gut microbiota can lead to pathology and altered formation of microbiota-derived components and metabolites. A series of neuroimmune diseases, such as myasthenia gravis (MG), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSDs), Guillain-Barré syndrome (GBS), and autoimmune encephalitis (AIE), are associated with changes in the gut microbiota. Microecological therapy by improving the gut microbiota is expected to be an effective measure for treating and preventing some neuroimmune diseases. This article reviews the research progress related to the roles of gut microbiota and fecal microbiota transplantation (FMT) in neuroimmune diseases.
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BACKGROUND: Myocardial ischemia-reperfusion (MI/R) can exacerbate the initial cardiac damage in the myocardial functional changes, including dysfunction of left ventricular contractility. Oestrogen has been proven to protect the cardiovascular system. However, whether the oestrogen or its metabolites play the main role in attenuating dysfunction of left ventricular contractility is unknown. METHODS AND RESULTS: This study used the LC-MS/MS to detect oestrogen and its metabolites in clinical serum samples (n = 62) with heart diseases. After correlation analysis with markers of myocardial injury including cTnI (P < 0.01), CK-MB (P < 0.05), and D-Dimer (P < 0.001), 16α-OHE1 was identified. The result from LC-MS/MS in female and ovariectomised (OVX) rat serum samples (n = 5) matched the findings in patients. In MI/R model of animal, the recovery of left ventricular developed pressure (LVDP), rate pressure product (RPP), dp/dtmax and dp/dtmin after MI/R in OVX or male group were worsened than those in female group. Also, the infarction area of OVX or male group was larger than that in females (n = 5, p < 0.01). Furthermore, LC3 II in the left ventricle of OVX and male group was lower than that in females (n = 5, p < 0.01) by immunofluorescence. In H9C2 cells, after the application of 16α-OHE1, the number of autophagosomes was further increased and other organelles improved in MI/R. Simultaneously, LC3 II, Beclin1, ATG5, and p-AMPK/AMPK were increased, and p-mTOR/mTOR was decreased (n = 3, p < 0.01) by Simple Western. CONCLUSION: 16α-OHE1 could attenuate left ventricle contractility dysfunction via autophagy regulation after MI/R, which also offered fresh perspectives on therapeutical treatment for attenuating MI/R injury.
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Regular textures are frequently found in man-made environments and some biological and physical images. There are a wide range of applications for recognizing and locating regular textures. In this work, we used deep convolutional neural networks (CNNs) as a general method for modelling and classifying regular and irregular textures. We created a new regular texture database and investigated two sets of deep CNNs-based methods for regular and irregular texture classification. First, the classic CNN models (e.g. inception, residual network, etc.) were used in a standard way. These two-class CNN classifiers were trained by fine-tuning networks using our new regular texture database. Next, we transformed the trained filter features of the last convolutional layer into a vector representation using Fisher Vector pooling (FV). Such representations can be efficiently used for a wide range of machine learning tasks such as classification or clustering, thus more transferable from one domain to another. Our experiments show that the standard CNNs attained sufficient accuracy for regular texture recognition tasks. The Fisher representations combined with support vector machine (SVM) also showed high performance for regular and irregular texture classification. We also find CNNs performs sub-optimally for long-range patterns, despite the fact that their fully-connected layers pool local features into a global image representation.