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Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in the central nervous system, yet their role in vestibular compensation remains elusive. To address this knowledge gap, we employed unilateral labyrinthectomy (UL) in rats to establish animal models of peripheral vestibular dysfunction. Utilizing ribonucleic acid sequencing (RNA-seq), we comprehensively analysed the expression profiles of genes dysregulated in the medial vestibular nucleus (MVN) of these rats at distinct time points: 4 h, 4 days, and 14 days post-UL. Through trans-target prediction analysis integrating differentially co-expressed messenger RNAs (mRNAs) and lncRNAs, we constructed lncRNA-mRNA regulatory networks. Validation of selected mRNAs and lncRNAs was performed using RT-qPCR. Our RNA-seq analysis revealed significant aberrant expression of 3054 lncRNAs and 1135 mRNAs compared to control samples. By applying weighted gene co-expression network analysis (WGCNA), we identified 11 co-expressed modules encompassing all genes. Notably, within the MEmagenta module, we observed an initial upregulation of differentially expressed genes (DEGs) at 4 h, followed by downregulation at 4- and 14-days post-UL. Our findings indicated that 3068 lncRNAs positively regulated 1259 DEGs, while 1482 lncRNAs negatively regulated 433 DEGs in the MVN. The RT-qPCR results corroborated the RNA-seq data, validating our findings. This study offers novel insights into the lncRNA-mRNA expression landscape during vestibular compensation, paving the way for further exploration of lncRNA functions in this context.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , ARN Largo no Codificante , ARN Mensajero , Núcleos Vestibulares , Vestíbulo del Laberinto , Animales , Núcleos Vestibulares/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Masculino , Vestíbulo del Laberinto/cirugía , Vestíbulo del Laberinto/metabolismo , Regulación de la Expresión Génica , Ratas Sprague-Dawley , Transcriptoma/genéticaRESUMEN
The vestibular system may have a critical role in the integration of sensory information and the maintenance of cognitive function. A dysfunction in the vestibular system has a significant impact on quality of life. Recent research has provided evidence of a connection between vestibular information and cognitive functions, such as spatial memory, navigation and attention. Although the exact mechanisms linking the vestibular system to cognition remain elusive, researchers have identified various pathways. Vestibular dysfunction may lead to the degeneration of cortical vestibular network regions and adversely affect synaptic plasticity and neurogenesis in the hippocampus, ultimately contributing to neuronal atrophy and cell death, resulting in memory and visuospatial deficits. Furthermore, the extent of cognitive impairment varies depending on the specific type of vestibular disease. In the present study, the current literature was reviewed, potential causal relationships between vestibular dysfunction and cognitive performance were discussed and directions for future research were proposed.
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Disfunción Cognitiva , Enfermedades Vestibulares , Humanos , Cognición/fisiología , Disfunción Cognitiva/etiología , Calidad de Vida , Memoria Espacial/fisiología , Enfermedades Vestibulares/psicologíaRESUMEN
Exercise can promote adult neurogenesis and improve symptoms associated with schizophrenia and other mental disorders via parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus ErbB4 is the receptor of neurotrophic factor neuregulin 1, expressed mostly in PV-positive interneurons. Whether ErbB4 in PV-positive neurons mediates the beneficial effect of exercise and adult neurogenesis on mental disorder needs to be further investigation. Here, we first conducted a four-week study on the effects of AG1478, an ErbB4 inhibitor, on memory and neurogenesis. AG1478 significantly impaired the performance in several memory tasks, including the T-maze, Morris water maze, and contextual fear conditioning, downregulated the expression of total ErbB4 (T-ErbB4) and the ratio of phosphate-ErbB4 (p-ErbB4) to T-ErbB4, and associated with neurogenesis impairment. Interestingly, AG1478 also appeared to decrease intracellular calcium levels in PV neurons, which could be reversed by exercise. These results suggest exercise may regulate adult neurogenesis and PV neuron activity through ErbB4 signaling. Overall, these findings provide further evidence of the importance of exercise for neurogenesis and suggest that targeting ErbB4 may be a promising strategy for improving memory and other cognitive functions in individuals with mental disorders.
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Actividad Motora , Neurogénesis , Parvalbúminas , Tirfostinos , Adulto , Humanos , Neuronas , QuinazolinasRESUMEN
Background: The commissural inhibitory system between the bilateral medial vestibular nucleus (MVN) plays a key role in vestibular compensation. Calcium-binding protein parvalbumin (PV) is expressed in MVN GABAergic neurons. Whether these neurons are involved in vestibular compensation is still unknown. Methods: After unilateral labyrinthectomy (UL), we measured the activity of MVN PV neurons by in vivo calcium imaging, and observed the projection of MVN PV neurons by retrograde neural tracing. After regulating PV neurons' activity by chemogenetic technique, the effects on vestibular compensation were evaluated by behavior analysis. Results: We found PV expression and the activity of PV neurons in contralateral but not ipsilateral MVN increased 6 h following UL. ErbB4 is required to maintain GABA release for PV neurons, conditional knockout ErbB4 from PV neurons promoted vestibular compensation. Further investigation showed that vestibular compensation could be promoted by chemogenetic inhibition of contralateral MVN or activation of ipsilateral MVN PV neurons. Additional neural tracing study revealed that considerable MVN PV neurons were projecting to the opposite side of MVN, and that activating the ipsilateral MVN PV neurons projecting to contralateral MVN can promote vestibular compensation. Conclusion: Contralateral MVN PV neuron activation after UL is detrimental to vestibular compensation, and rebalancing bilateral MVN PV neuron activity can promote vestibular compensation, via commissural inhibition from the ipsilateral MVN PV neurons. Our findings provide a new understanding of vestibular compensation at the neural circuitry level and a novel potential therapeutic target for vestibular disorders.
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BACKGROUND: This study aimed to investigate the effects of unilateral labyrinthectomy (UL) on monoamine neurotransmitters in the medial vestibular nucleus (MVN) of rats. METHODS: Adult Sprague-Dawley rats were utilized for the vestibular impaired animal model through UL. The success of the model establishment and the recovery process were evaluated using vestibular behavioral tests, including spontaneous nystagmus, postural asymmetry, and balance beam test. Additionally, the expression levels of c-Fos protein in the MVN were assessed by immunofluorescence. Furthermore, changes in the expression levels of monoamine neurotransmitters, including 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), and histamine in the MVN, were analyzed using high-performance liquid chromatography (HPLC) at different time points after UL (4 h, 8 h, 1 day, 2 days, 4 days, and 7 days). RESULTS: Compared to the sham control group, the UL group exhibited the most pronounced vestibular impairment symptoms at 4 h post-UL, which significantly decreased at 4 days and almost fully recovered by 7 days. Immunofluorescence results showed a notable upregulation of c-Fos expression in the MVN subsequent to the UL-4 h, serving as a reliable indicator of heightened neuronal activity. In comparison with the sham group, HPLC analysis showed that the levels of 5-HT and NE in the ipsilesional MVN of the UL group were significantly elevated within 4 days after UL, and peaked on 1 day and 2 days, respectively. DA showed an increasing trend at different time points up to 7 days post-UL, while histamine levels significantly increased only at 1 day post-UL. CONCLUSIONS: UL-induced dynamic changes in monoamine neurotransmitters during the early compensation period in the rat MVN may be associated with the regulation of the central vestibular compensation mechanism by the MVN.
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Histamina , Vestíbulo del Laberinto , Ratas , Animales , Ratas Sprague-Dawley , Histamina/metabolismo , Serotonina/metabolismo , Neurotransmisores/metabolismo , Núcleos Vestibulares/metabolismoRESUMEN
Single therapeutic interventions have not yet been successful in restoring function after spinal cord injury. Accordingly, combinatorial interventions targeting multiple factors may hold greater promise for achieving maximal functional recovery. In this study, we applied a combinatorial approach of chronic chemogenetic neuronal activation and physical exercise including treadmill running and forelimb training tasks to promote functional recovery. In a mouse model of cervical (C5) dorsal hemisection of the spinal cord, which transects almost all descending corticospinal tract axons, combining selective activation of corticospinal motoneurons (CMNs) by intersectional chemogenetics with physical exercise significantly promoted functional recovery evaluated by the grid walking test, grid hanging test, rotarod test, and single pellet-reaching tasks. Electromyography and histological analysis showed increased activation of forelimb muscles via chemogenetic stimuli, and a greater density of vGlut1+ innervation in spinal cord grey matter rostral to the injury, suggesting enhanced neuroplasticity and connectivity. Combined therapy also enhanced activation of mTOR signaling and reduced apoptosis in spinal motoneurons, Counts revealed increased numbers of detectable choline acetyltransferase-positive motoneurons in the ventral horn. Taken together, the findings from this study validate a novel combinatorial approach to enhance motor function after spinal cord injury.
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Traumatismos de la Médula Espinal , Animales , Ratones , Neuronas Motoras/fisiología , Médula Espinal/patología , Tractos Piramidales/patología , Axones/patología , Ejercicio Físico , Recuperación de la Función/fisiologíaRESUMEN
Breast cancer is a common malignancy and early detection and treatment of it is crucial. Computer-aided diagnosis (CAD) based on deep learning has significantly advanced medical diagnostics, enhancing accuracy and efficiency in recent years. Despite the convenience, this technology also has certain limitations. When the morphological characteristics of the patient's pathological section are not evident or complex, certain small lesions or cells deep within the lesion cannot be recognized, and misdiagnosis is prone to occur. As a result, MDFF-Net, a CNN-based multidimensional feature fusion network, is proposed. The model consists of a one-dimensional feature extraction network, a two-dimensional feature extraction network, and a feature fusion classification network. The basic part of the two-dimensional feature extraction network is stacked by modules integrated with multi-scale channel shuffling networks and channel attention modules. Furthermore, inspired by natural language processing, this model integrates a one-dimensional feature extraction network to extract detailed information in the image to avoid misdiagnosis caused by insufficient information extraction such as cell morphological characteristics and differentiation degree. Finally, the extracted one-dimensional and two-dimensional features are fused in the feature fusion network and employed for the final classification. The effectiveness of MDFF-Net and classical classification models were evaluated on the BreakHis and the BACH datasets. According to experimental results, MDFF-Net achieves an accuracy of 98.86% on the BreakHis and 86.25% on the BACH dataset. Furthermore, to further assess the effectiveness of the model in other classification tasks, the colon cancer and the lung cancer datasets were employed for additional experiments, achieving a classification accuracy of 100% in both cases.
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Neoplasias de la Mama , Mama , Humanos , Femenino , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Diferenciación Celular , Diagnóstico por Computador , Almacenamiento y Recuperación de la Información , Procesamiento de Imagen Asistido por ComputadorRESUMEN
In order to accurately identify the morphological features of different differentiation stages of induced Adipose Derived Stem Cells (ADSCs) and judge the differentiation types of induced ADSCs, a morphological feature recognition method of different differentiation stages of induced ADSCs based on deep learning is proposed. Using the super-resolution image acquisition method of ADSCs differentiation based on stimulated emission depletion imaging, after obtaining the super-resolution images at different stages of inducing ADSCs differentiation, the noise of the obtained image is removed and the image quality is optimized through the ADSCs differentiation image denoising model based on low rank nonlocal sparse representation; The denoised image is taken as the recognition target of the morphological feature recognition method for ADSCs differentiation image based on the improved Visual Geometry Group (VGG-19) convolutional neural network. Through the improved VGG-19 convolutional neural network and class activation mapping method, the morphological feature recognition and visual display of the recognition results at different stages of inducing ADSCs differentiation are realized. After testing, this method can accurately identify the morphological features of different differentiation stages of induced ADSCs, and is available.
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Aprendizaje Profundo , Redes Neurales de la Computación , Diferenciación Celular/fisiología , Diagnóstico por Imagen , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
The antibiotic tetracycline (TC) and its degradation products (TDPs) in degradation solution present serious environmental problems, such as human health damage and ecological risk; thus further treatment is required before being released into the aquatic environment. Furthermore, their environmental impact on microalgae remains unclear. In this study, TC was degraded by photocatalysis using birnessite and UV irradiation, followed by biological purification using the microalga Scenedesmus obliquus. In addition, the photosynthetic activity and transcription of the microalgae were examined to evaluate the toxicity of TC and TDPs. The results show that photocatalytic degradation efficiency reached 92.7% after 30 min, and 11 intermediate products were detected. The microalgae achieved a high TC removal efficiency (99.7%) after 8 days. Exposure to the degraded TC solution (D) resulted in significantly lower (p < 0.05) biomass than the pure TC (T), and S. obliquus in the T treatment showed better resilience than the D treatment. Transcriptomic assays for different treatments revealed differential gene expression mainly involving the photosynthesis, ribosome, translation and peptide metabolic progresses. The up-regulation of photosynthesis-related genes and differential expression of chloroplast genes may be important for S. obliquus to acquire high photosynthetic efficiency and growth recovery when exposed to TC and TDPs. Our study provides a reference for TC removal using a combination of catalytic degradation and microalgal purification, and it is also helpful for understanding the environmental risk of TDPs in natural aquatic environments.
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Microalgas , Scenedesmus , Humanos , Microalgas/metabolismo , Agua/metabolismo , Fotólisis , Tetraciclina/metabolismo , Biomasa , Fotosíntesis , Antibacterianos/metabolismoRESUMEN
The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying mechanism of NAc-DBS in MDD treatment remains elusive. Using the chronic unpredictable mild stress (CUMS) mouse model, we found NAc-DBS rescued depression-like behaviors, and reversed high gamma oscillation reduction and neurogenesis impairment in the dorsal dentate gyrus. Inactivation of parvalbumin (PV)-positive interneurons (PVI) in the dorsal DG led to depression-like behavior and decreased adult neurogenesis. Further investigation elucidated the VTA-DG GABAergic projection and CA1-NAc projection might jointly participate in NAc-DBS therapeutic mechanism. Disinhibition of the VTA-DG GABAergic projection had an antidepressant effect, and inhibition of the CA1-NAc projection reduced the antidepressant effect of DBS-NAc. Moreover, disinhibiting the VTA-DG GABAergic projection or activating the CA1-NAc projection could increase PVI activity in the dorsal DG. These results showed PVI in the dorsal DG as an essential target in depression and NAc-DBS antidepressant mechanisms.
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Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC.
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Péptidos Catiónicos Antimicrobianos , Ingestión de Alimentos , Ghrelina , Proopiomelanocortina , Animales , Ratones , Peso Corporal , Ghrelina/farmacología , Neuronas/metabolismo , Proopiomelanocortina/genética , Receptores de Ghrelina/genética , Receptores de Ghrelina/metabolismo , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Conducta AlimentariaRESUMEN
Diabetic retinopathy (DR) is a common microvascular complication in patients with diabetes mellitus. DR is caused by chronic hyperglycemia and is characterized by progressive loss of vision because of damage to the retinal microvasculature. In this study, we investigated the regulatory role and clinical significance of the vascular endothelial growth factor (VEGF)/protein kinase C (PKC)/endothelin (ET)/nuclear factor-κB (NF-κB)/intercellular adhesion molecule 1 (ICAM-1) signaling pathway in DR using a rat model. Intraperitoneal injections of the VEGF agonist, streptozotocin (STZ) were used to generate the DR model rats. DR rats treated with the VEGF inhibitor (DR+VEGF inhibitor) were used to study the specific effects of VEGF on DR pathology and the underlying mechanisms. DR and DR+VEGF agonist rats were injected with the PKCß2 inhibitor, GF109203X to determine the therapeutic potential of blocking the VEGF/PKC/ET/NF-κB/ICAM-1 signaling pathway. The body weights and blood glucose levels of the rats in all groups were evaluated at 16 weeks. DR-related retinal histopathology was analyzed by hematoxylin and eosin staining. ELISA assay was used to estimate the PKC activity in the retinal tissues. Western blotting and RT-qPCR assays were used to analyze the expression levels of PKC-ß2, VEGF, ETs, NF-κB, and ICAM-1 in the retinal tissues. Immunohistochemistry was used to analyze VEGF and ICAM-1 expression in the rat retinal tissues. Our results showed that VEGF, ICAM-1, PKCß2, ET, and NF-κB expression levels as well as PKC activity were significantly increased in the retinal tissues of the DR and DR+VEGF agonist rat groups compared to the control and DR+VEGF inhibitor rat groups. DR and DR+VEGF agonist rats showed significantly lower body weight and significantly higher retinal histopathology scores and blood glucose levels compared to the control and DR+VEGF inhibitor group rats. However, treatment of DR and DR+VEGF agonist rats with GF109203X partially alleviated DR pathology by inhibiting the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway. In summary, our data demonstrated that inhibition of the VEGF/ PKC/ET/NF-κB/ICAM-1 signaling pathway significantly alleviated DR-related pathology in the rat model. Therefore, VEGF/PKC/ET/NF-κB/ICAM-1 signaling axis is a promising therapeutic target for DR.
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Diabetes Mellitus Experimental , Retinopatía Diabética , Ratas , Animales , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , FN-kappa B/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína Quinasa C beta/metabolismo , Glucemia , Diabetes Mellitus Experimental/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS. METHODS: Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins. RESULTS: Compared with controls, only MS animals in the adult stage (PND56-65) but not the adolescent stage (PND31-40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1ß, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35-65). CONCLUSIONS: MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.
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Privación Materna , Sirtuina 3 , Animales , Bromodesoxiuridina/metabolismo , Cognición , Hipocampo/metabolismo , Interleucina-6/metabolismo , NAD/metabolismo , NAD/farmacología , Neuronas/metabolismo , Niacinamida/metabolismo , Niacinamida/farmacología , Ratas , Ratas Wistar , Maduración Sexual , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: There is a growing body of evidence from biological experiments suggesting that microRNAs (miRNAs) play a significant regulatory role in both diverse cellular activities and pathological processes. Exploring miRNA-disease associations not only can decipher pathogenic mechanisms but also provide treatment solutions for diseases. As it is inefficient to identify undiscovered relationships between diseases and miRNAs using biotechnology, an explosion of computational methods have been advanced. However, the prediction accuracy of existing models is hampered by the sparsity of known association network and single-category feature, which is hard to model the complicated relationships between diseases and miRNAs. RESULTS: In this study, we advance a new computational framework (GATMDA) to discover unknown miRNA-disease associations based on graph attention network with multi-source information, which effectively fuses linear and non-linear features. In our method, the linear features of diseases and miRNAs are constructed by disease-lncRNA correlation profiles and miRNA-lncRNA correlation profiles, respectively. Then, the graph attention network is employed to extract the non-linear features of diseases and miRNAs by aggregating information of each neighbor with different weights. Finally, the random forest algorithm is applied to infer the disease-miRNA correlation pairs through fusing linear and non-linear features of diseases and miRNAs. As a result, GATMDA achieves impressive performance: an average AUC of 0.9566 with five-fold cross validation, which is superior to other previous models. In addition, case studies conducted on breast cancer, colon cancer and lymphoma indicate that 50, 50 and 48 out of the top fifty prioritized candidates are verified by biological experiments. CONCLUSIONS: The extensive experimental results justify the accuracy and utility of GATMDA and we could anticipate that it may regard as a utility tool for identifying unobserved disease-miRNA relationships.
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MicroARNs , ARN Largo no Codificante , Algoritmos , Biología Computacional/métodos , Predisposición Genética a la Enfermedad , Humanos , MicroARNs/genética , ARN Largo no Codificante/genéticaRESUMEN
Cumulative research studies have verified that multiple circRNAs are closely associated with the pathogenic mechanism and cellular level. Exploring human circRNA-disease relationships is significant to decipher pathogenic mechanisms and provide treatment plans. At present, several computational models are designed to infer potential relationships between diseases and circRNAs. However, the majority of existing approaches could not effectively utilize the multisource data and achieve poor performance in sparse networks. In this study, we develop an advanced method, GATGCN, using graph attention network (GAT) and graph convolutional network (GCN) to detect potential circRNA-disease relationships. First, several sources of biomedical information are fused via the centered kernel alignment model (CKA), which calculates the corresponding weight of different kernels. Second, we adopt the graph attention network to learn latent representation of diseases and circRNAs. Third, the graph convolutional network is deployed to effectively extract features of associations by aggregating feature vectors of neighbors. Meanwhile, GATGCN achieves the prominent AUC of 0.951 under leave-one-out cross-validation and AUC of 0.932 under 5-fold cross-validation. Furthermore, case studies on lung cancer, diabetes retinopathy, and prostate cancer verify the reliability of GATGCN for detecting latent circRNA-disease pairs.
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Mobility, group awareness, and temperature are considered as the important factors that may impact the increase in confirmed cases of the COVID-19[1]. This paper aims to verify the above factors on the COVID-19 and show the possible confounding factors of each research variable in reality. Based on this, we collected data about the epidemic from January 20, 2020 to February 24, 2021, including the relevant data of 31 provinces and regions in China. Plus, we use the directed acyclic graph (DAG)[2] to show the causal relationship between the above influencing factors and the confirmed daily epidemic cases, and the confounding is estimated based on DAG. The effective adjustment set of factors are used to perform the regression of the total causal effect among the explanatory variables and the confirmed cases of the epidemic using negative binomial regression. Through the comprehensive causal analysis of the decisive factors for the COVID-19, we provide strong evidence for population mobility, group awareness and the impact of weather on the epidemic, and estimates the possible confounding factors in all aspects of society. Incorporating the above factors, we provide suggestions for future decisions on the prevention of large-scale epidemics.
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Store-operated calcium entry (SOCE) is pivotal in maintaining intracellular Ca2+ level and cell function; however, its role in obesity development remains largely unknown. Here, we show that the stromal interaction molecule 1 (Stim1), an endoplasmic reticulum (ER) Ca2+ sensor for SOCE, is critically involved in obesity development. Pharmacological blockade of SOCE in the brain, or disruption of Stim1 in hypothalamic agouti-related peptide (AgRP)-producing neurons (ASKO), significantly ameliorates dietary obesity and its associated metabolic disorders. Conversely, constitutive activation of Stim1 in AgRP neurons leads to an obesity-like phenotype. We show that the blockade of SOCE suppresses general translation in neuronal cells via the 2',5'-oligoadenylate synthetase 3 (Oas3)-RNase L signaling. While Oas3 overexpression in AgRP neurons protects mice against dietary obesity, deactivation of RNase L in these neurons significantly abolishes the effect of ASKO. These findings highlight an important role of Stim1 and SOCE in the development of obesity.
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Proteína Relacionada con Agouti/metabolismo , Señalización del Calcio , Calcio/metabolismo , Retículo Endoplásmico/metabolismo , Hipotálamo/metabolismo , Neuronas/metabolismo , Obesidad/prevención & control , Molécula de Interacción Estromal 1/deficiencia , 2',5'-Oligoadenilato Sintetasa/metabolismo , Proteína Relacionada con Agouti/genética , Animales , Línea Celular Tumoral , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Endorribonucleasas/metabolismo , Células HEK293 , Humanos , Hipotálamo/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/genética , Obesidad/metabolismo , Obesidad/fisiopatología , Molécula de Interacción Estromal 1/genética , Aumento de PesoRESUMEN
Polyphenol oxidase(PPO) is an important antioxidant enzyme in plants. It has the functions of scavenging active oxygen and synthesizing phenols, lignin, and plant protection factors, and can enhance the plant's resistance to stress and resistance to pests and diseases. Our previous research found that Salvia miltiorrhiza PPO gene can positively regulate salvianolic acid B synthesis. In order to further explore the mechanism, a pGBKT7-PPO bait vector was constructed using the cloned S. miltiorrhiza polyphenol oxidase gene(SmPPO, GenBank accession number: KF712274.1), and verified that it had no self-activation and no toxicity. The titer of S. miltiorrhiza cDNA library constructed by our laboratory was 4.75 × 107 cfu·mL~(-1), which met the requirements for library construction. Through yeast two-hybrid test, 22 proteins that could interact with SmPPO were screened. Only yeast PAL1 and TAT interacted with SmPPO through yeast co-transformation verification. Further verification was performed by bimolecular fluorescence complementary detection(BiFC). Only TAT and SmPPO interacted, so it meant that TAT and SmPPO interacted. TAT and SmPPO were truncated according to the domain, respectively. The first 126 amino acids of SmPPO and tyrosine amino transferase(TAT) were obtained to interact on the cell membrane and chloroplast. SmPPO was obtained by subcellular localization test, which was mainly loca-lized on the nucleus and cell membrane; TAT was localized on the cell membrane. Real-time quantitative PCR results showed that the SmPPO gene was mainly expressed in roots and stems; the TAT gene was expressed in roots, and the expression level in stems and flowers was low. This article lays a solid foundation for the in-depth study of the molecular mechanism of the interaction of S. miltiorrhiza SmPPO and TAT to regulate the synthesis of phenolic substances.
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Salvia miltiorrhiza/genética , Catecol Oxidasa , Regulación de la Expresión Génica de las Plantas , Biblioteca de Genes , Proteínas de Plantas/genética , Raíces de PlantasRESUMEN
The exopolysaccharides were extracted and separated from the broth of the liquid fermentation of P. umbellatus, and the antioxidant activities and other relative bioactivities were investigated, aiming to find clues for a wider use in the future. Three novel exopolysaccharides of PPS1, PPS2 and PPS3 with molecular weight of 3.7×104-6.9×104Da were obtained. Monosaccharide analysis showed that they were mainly composed of mannose, along with galactose and glucose with different molar ratio, and their structural features were also investigated by FT-IR, NMR and SEM. The antioxidant activity assay in vitro showed these exopolysaccharides exhibited a significant scavenging effect on DPPH· and other free radicals in a dose-dependent manner. Significantly, the stimulate nitric oxide production and phagocytic activity implied that the polysaccharides could enhance the immunity of RAW 264.7 macrophages. Other assays revealed that they have obvious cellular aging delaying activity and the DNA damage protecting activity. In conclusion, these three exopolysaccharides might have potential applications in the fields of pharmaceuticals, cosmetics, and food products.
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Fermentación , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología , Polyporus/química , Polyporus/metabolismo , Animales , Senescencia Celular/efectos de los fármacos , Daño del ADN , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Monosacáridos/análisis , Óxido Nítrico/biosíntesis , Fagocitosis/efectos de los fármacos , Células RAW 264.7RESUMEN
The effects of five different microalgae-fungi on nutrient removal and CO2 removal were investigated under three different CO2 contents (35%, 45% and 55%). The results showed that the highest nutrient and CO2 removal efficiency were found at 55% CO2 by cocultivation of different microalgae and fungi. The effect of different initial CO2 concentration on the removal of CO2 from microalgae was significant, and the order of CO2 removal efficiency was 55% (v/v) >45% (v/v) >35% (v/v). The best nutrient removal and biogas purification could be achieved by co-cultivation of C. vulgaris and G. lucidum with 55% initial CO2 content. The maximum mean COD, TN, TP and CO2 removal efficiency can reach 68.29%, 61.75%, 64.21% and 64.68%, respectively under this condition. All highest COD, TN, TP and CO2 removal efficiency were more than 85%. The analysis of energy consumption economic efficiency revealed that this strategy resulted in the highest economic efficiency. The results of this work can promote simultaneously biological purification of wastewater and biogas using microalgal-fungal symbiosis.