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BACKGROUND: Necroptosis is a novel type of programmed cell death distinct from apoptosis. However, the role of necroptosis in ovarian cancer (OC) remains unclear. The present study investigated the prognostic value of necroptosis-related genes (NRGs) and the immune landscape in OC. METHODS: The gene expression profiling and clinical information were downloaded from the TCGA and GTEx databases. Differentially expressed NRGs (DE-NRGs) between OC and normal tissueswere identified. The regression analyses were conducted to screen the prognostic NRGs and construct the predictive risk model. Patients were then divided into high- and low-risk groups, and the GO and KEGG analyses were performed to explore bioinformatics functions between the two groups. Subsequently, the risk level and immune status correlations were assessed through the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden (TMB) and the drug sensitivity were also analyzed based on the two-NRG signature in OC. RESULTS: Totally 42 DE-NRGs were identified in OC. The regression analyses screened out two NRGs (MAPK10 and STAT4) with prognostic values for overall survival. The ROC curve showed a better predictive ability in five-year OS using the risk score. Immune-related functions were significantly enriched in the high- and low-risk group. Macrophages M1, T cells CD4 memory activated, T cells CD8, and T cells regulatory infiltration immune cells were associated with the low-risk score. The lower tumor microenvironment score was demonstrated in the high-risk group. Patients with lower TMB in the low-risk group showed a better prognosis, and a lower TIDE score suggested a better immune checkpoint inhibitor response in the high-risk group. Besides, cisplatin and paclitaxel were found to be more sensitive in the low-risk group. CONCLUSIONS: MAPK10 and STAT4 can be important prognosis factors in OC, and the two-gene signature performs well in predicting survival outcomes. Our study provided novel ways of OC prognosis estimation and potential treatment strategy.
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Necroptose , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino , Paclitaxel , Fatores de Risco , Prognóstico , Microambiente TumoralRESUMO
In this paper, we investigate a challenging but interesting task in the research of speech emotion recognition (SER), i.e., cross-corpus SER. Unlike the conventional SER, the training (source) and testing (target) samples in cross-corpus SER come from different speech corpora, which results in a feature distribution mismatch between them. Hence, the performance of most existing SER methods may sharply decrease. To cope with this problem, we propose a simple yet effective deep transfer learning method called progressive distribution adapted neural networks (PDAN). PDAN employs convolutional neural networks (CNN) as the backbone and the speech spectrum as the inputs to achieve an end-to-end learning framework. More importantly, its basic idea for solving cross-corpus SER is very straightforward, i.e., enhancing the backbone's corpus invariant feature learning ability by incorporating a progressive distribution adapted regularization term into the original loss function to guide the network training. To evaluate the proposed PDAN, extensive cross-corpus SER experiments on speech emotion corpora including EmoDB, eNTERFACE, and CASIA are conducted. Experimental results showed that the proposed PDAN outperforms most well-performing deep and subspace transfer learning methods in dealing with the cross-corpus SER tasks.
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The most common injury of preterm infants is periventricular leukomalacia (PVL) and to date there is still no safe and effective treatment. In our previous studies, leptin has been found to have neuroprotective effects on the preterm ischemia-hypoxia brain damage model rats in animal behavior. To gain insight into the neuroprotective mechanisms of leptin on preterm brain damage model rats, we constructed a comparative peptidomic profiling of hippocampal tissue between leptin-treated after model and preterm ischemia-hypoxia brain damage model rats using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by nano liquid chromatography tandem mass spectrometry. We identified and quantified 4164 peptides, 238 of which were differential expressed in hippocampal tissue in the two groups. A total of 150 peptides were up regulated and 88 peptides were down regulated. These peptides were imported into the Ingenuity Pathway Analysis (IPA) and identified putative roles in nervous system development, function and diseases. We concluded that the preterm ischemia-hypoxia brain damage model with leptin treatment induced peptides changes in hippocampus, and these peptides, especially for the peptides associated "microtubule-associated protein 1b (MAP1b), Elastin (Eln), Piccolo presynaptic cytomatrix protein (Pclo), Zinc finger homeobox 3(Zfhx3), Alpha-kinase 3(Alpk3) and Myosin XVA(Myo15a) ", could be candidate bio-active peptides and participate in neuroprotection of leptin. These may advance our current understanding of the mechanism of leptin's neuroprotective effect on preterm brain damage and may be involved in the etiology of preterm brain damage. Meanwhile, we found that repression of ILK signaling pathway plays a significant role in neuroprotection of leptin. A better understanding of the role of ILK signaling pathway in neuroprotective mechanisms will help scientists and researchers to develop selective, safe and efficacious drug for therapy against human nervous system disorders.
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Hipocampo/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Leptina/farmacologia , Fármacos Neuroprotetores/farmacologia , Peptídeos/metabolismo , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Artéria Carótida Primitiva , Proteínas do Citoesqueleto/efeitos dos fármacos , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Elastina/efeitos dos fármacos , Elastina/metabolismo , Hipocampo/efeitos dos fármacos , Proteínas de Homeodomínio/efeitos dos fármacos , Proteínas de Homeodomínio/metabolismo , Hipóxia-Isquemia Encefálica/fisiopatologia , Leucomalácia Periventricular/metabolismo , Leucomalácia Periventricular/fisiopatologia , Ligadura , Proteínas Associadas aos Microtúbulos/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Miosinas/efeitos dos fármacos , Miosinas/metabolismo , Neuropeptídeos/efeitos dos fármacos , Neuropeptídeos/metabolismo , Peptídeos/efeitos dos fármacos , Proteínas Serina-Treonina Quinases , Ratos , Transdução de SinaisRESUMO
OBJECTIVE: To observe differential peptidomics in the hippocampal tissue in a rat model of premature white matter injury, and to investigate the mechanism of premature white matter injury. METHODS: Twenty neonatal Sprague-Dawley rats were randomly and equally divided into a control group and a model group. Rats in the model group underwent permanent ligation of the right common carotid artery 2 days after birth, followed by 2 hours of hypoxia. For rats in the control group, the right common carotid artery was isolated, but without ligation and hypoxia. Brain tissue samples were collected from the two groups, and hippocampal tissue was isolated. Liquid chromatography-tandem mass spectrometry combined with tandem mass spectrometry was used for peptidomic profiling of hippocampal tissue, and the differentially expressed peptides between the two groups were subjected to bioinformatics analysis to assess their possible roles in neural development and function. RESULTS: A total of 4164 peptides were identified and quantified, and 262 of them were differentially expressed (absolute fold change ≥2.5), including 164 upregulated peptides and 98 downregulated peptides. The numbers of differentially expressed peptides of the precursor proteins ELN, PCLO, MYO15a, MAP4, and MAP1b were the most, and may play significant roles in the pathogenesis of premature white matter injury. CDK5 signaling pathway in the hippocampus was activated in the rat model of premature white matter injury. CONCLUSIONS: The differentially expressed peptides related to precursor proteins such as MAP1b may be key bioactive peptides involved in neural development and function in premature white matter injury, and activation of the CDK5 signaling pathway may be associated with premature white matter injury.
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Nascimento Prematuro , Substância Branca , Animais , Animais Recém-Nascidos , Encéfalo , Feminino , Hipocampo , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Preterm infants face lifelong disabilities, including learning disorders, as well as visual, auditory and behavioral problems. Recent studies have demonstrated that leptin, an adipocytokine encoded by a gene associated with obesity and expressed in adipose tissue, affects neurocognitive and motor function; however, the mechanisms of brain damage in preterm infants are unclear. In the present study, the neuroprotective effects of leptin in a rat model of preterm hypoxicischemic brain damage were investigated. Rats (2daysold) were subjected to brain damage (ligation of the common carotid artery followed by exposure to 6% oxygen for 2 h) and treated with vehicle (control) or leptin. Spatial memory was analyzed in the present study using the Morris water maze test 19 days following ligation. Over the 24day postsurgical observation period, captureresistance test, forelimb suspension and open field tests were conducted to evaluate motor function and anxietyassociated behavior. Treatment with leptin did not affect survival rate or body weight. Treatment with leptin increased the number of platform crossings in rats with premature brain damage in the Morris water maze test, which was used to assess spatial memory. Multivariate analysis revealed that leptin reduced the latency to finding the platform location, independent of gender and weight. In the captureresistance, forelimb suspension and open field tests, there were no differences between animals administered leptin and the sham group. Collectively, the results of the present study suggested that leptin may alleviate spatial memory impairment resulting from premature brain damage, independent of gender or weight. These results may improve understanding of the neuroprotective effects exhibited by leptin in infants with preterm brain damage.
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Lesões Encefálicas/fisiopatologia , Cognição/efeitos dos fármacos , Leptina/farmacologia , Atividade Motora/efeitos dos fármacos , Nascimento Prematuro/fisiopatologia , Animais , Peso Corporal/efeitos dos fármacos , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Humanos , Lactente , Modelos Lineares , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Análise Multivariada , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. METHODS: A total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 µg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. RESULTS: There was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P<0.05); more than 10 days after birth, the leptin intervention group had rapid growth with higher body weight than the model and sham-operation groups (P>0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (P<0.05); from the fourth day of experiment, the leptin intervention group had a similar latency period as the sham-operation and a significantly shorter latency period than the model group (P<0.05). The results of space search experiment showed that compared with the sham-operation group, the model group had a significant reduction in the number of platform crossings and a significantly longer latency period (P<0.05); compared with the model group, the leptin intervention group had a significantly increased number of platform crossings and a significantly shortened latency period (P<0.05), while there was no significant difference between the leptin intervention and sham-operation groups. CONCLUSIONS: Leptin can alleviate spatial memory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.