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The common dolphin (Delphinus delphis) is widely distributed worldwide and well adapted to various habitats. Animal genomes store clues about their pasts, and can reveal the genes underlying their evolutionary success. Here, we report the first high-quality chromosome-level genome of D. delphis. The assembled genome size was 2.56 Gb with a contig N50 of 63.85 Mb. Phylogenetically, D. delphis was close to Tursiops truncatus and T. aduncus. The genome of D. delphis exhibited 428 expanded and 1,885 contracted gene families, and 120 genes were identified as positively selected. The expansion of the HSP70 gene family suggested that D. delphis has a powerful system for buffering stress, which might be associated with its broad adaptability, longevity, and detoxification capacity. The expanded IFN-α and IFN-ω gene families, as well as the positively selected genes encoding tripartite motif-containing protein 25, peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, and p38 MAP kinase, were all involved in pathways for antiviral, anti-inflammatory, and antineoplastic mechanisms. The genome data also revealed dramatic fluctuations in the effective population size during the Pleistocene. Overall, the high-quality genome assembly and annotation represent significant molecular resources for ecological and evolutionary studies of Delphinus and help support their sustainable treatment and conservation.
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Golfinhos Comuns , Animais , Evolução Biológica , Cromossomos/genética , Imunidade Inata/genética , FilogeniaRESUMO
The ancestors of marine mammals once roamed the land and independently committed to an aquatic lifestyle. These macroevolutionary transitions have intrigued scientists for centuries. Here, we generated high-quality genome assemblies of 17 marine mammals (11 cetaceans and six pinnipeds), including eight assemblies at the chromosome level. Incorporating previously published data, we reconstructed the marine mammal phylogeny and population histories and identified numerous idiosyncratic and convergent genomic variations that possibly contributed to the transition from land to water in marine mammal lineages. Genes associated with the formation of blubber (NFIA), vascular development (SEMA3E), and heat production by brown adipose tissue (UCP1) had unique changes that may contribute to marine mammal thermoregulation. We also observed many lineage-specific changes in the marine mammals, including genes associated with deep diving and navigation. Our study advances understanding of the timing, pattern, and molecular changes associated with the evolution of mammalian lineages adapting to aquatic life.
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Adaptação Fisiológica , Evolução Molecular , Genoma , Genômica , Mamíferos/fisiologia , Filogenia , Termogênese/genética , Animais , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Seleção Genética , Semaforinas/genética , Semaforinas/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMO
BACKGROUND: Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children. METHODS: The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models. RESULTS: The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children. CONCLUSIONS: These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.
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Nascimento Prematuro , Gravidez , Lactente , Recém-Nascido , Humanos , Criança , Feminino , Masculino , Nascimento Prematuro/genética , Placenta , Encéfalo , Biologia Computacional , Apolipoproteínas ERESUMO
BACKGROUND: Preterm birth (PTB) is the main driver of newborn deaths. The identification of pregnancies at risk of PTB remains challenging, as the incomplete understanding of molecular mechanisms associated with PTB. Although several transcriptome studies have been done on the placenta and plasma from PTB women, a comprehensive description of the RNA profiles from plasma and placenta associated with PTB remains lacking. METHODS: Candidate markers with consistent trends in the placenta and plasma were identified by implementing differential expression analysis using placental tissue and maternal plasma RNA-seq datasets, and then validated by RT-qPCR in an independent cohort. In combination with bioinformatics analysis tools, we set up two protein-protein interaction networks of the significant PTB-related modules. The support vector machine (SVM) model was used to verify the prediction potential of cell free RNAs (cfRNAs) in plasma for PTB and late PTB. RESULTS: We identified 15 genes with consistent regulatory trends in placenta and plasma of PTB while the full term birth (FTB) acts as a control. Subsequently, we verified seven cfRNAs in an independent cohort by RT-qPCR in maternal plasma. The cfRNA ARHGEF28 showed consistence in the experimental validation and performed excellently in prediction of PTB in the model. The AUC achieved 0.990 for whole PTB and 0.986 for late PTB. CONCLUSIONS: In a comparison of PTB versus FTB, the combined investigation of placental and plasma RNA profiles has shown a further understanding of the mechanism of PTB. Then, the cfRNA identified has the capacity of predicting whole PTB and late PTB.
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Placenta , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Placenta/metabolismo , RNA/genética , RNA/metabolismo , Nascimento Prematuro/genética , Nascimento Prematuro/metabolismo , Biomarcadores/metabolismoRESUMO
Ocean noise negatively influences the recording of odontocete echolocation clicks. In this study, a hybrid model based on the convolutional neural network (CNN) and long short-term memory (LSTM) network-called a hybrid CNN-LSTM model-was proposed to denoise echolocation clicks. To learn the model parameters, the echolocation clicks were partially corrupted by adding ocean noise, and the model was trained to recover the original echolocation clicks. It can be difficult to collect large numbers of echolocation clicks free of ambient sea noise for training networks. Data augmentation and transfer learning were employed to address this problem. Based on Gabor functions, simulated echolocation clicks were generated to pre-train the network models, and the parameters of the networks were then fine-tuned using odontocete echolocation clicks. Finally, the performance of the proposed model was evaluated using synthetic data. The experimental results demonstrated the effectiveness of the proposed model for denoising two typical echolocation clicks-namely, narrowband high-frequency and broadband echolocation clicks. The denoising performance of hybrid models with the different number of convolution and LSTM layers was evaluated. Consequently, hybrid models with one convolutional layer and multiple LSTM layers are recommended, which can be adopted for denoising both types of echolocation clicks.
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Ecolocação , Animais , Memória de Curto Prazo , Redes Neurais de Computação , Ruído , Memória de Longo PrazoRESUMO
This experiment was designed to explore the relationship and effect of miR-1-3p expression and BDNF level in patients with primary hypertension complicated with depression. The subjects of the study were 145 patients with hypertension with a small fluctuation range of blood pressure in recent three months. Within 48 hours after admission, patients were evaluated with the Hospital Anxiety and Depression Scale (HADS) and Hamilton Depression Rating Scale (HAMD). After fasting for 12 hours, enrolled subjects were subject to blood collection (5 ml) in the morning for detecting blood lipid levels, miR-1-3p expression and BDNF by using an automatic biochemical analyzer, real-time fluorescence quantitative PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results showed that compared with the normal control group, while miR-1-3p expression increased obviously in patients with hypertension, while the level of BDNF decreased significantly; and compared with patients with simple hypertension, the expression of miR-1-3p in hypertension patients with depression was significantly increased, while BDNF level was decreased evidently (All P < 0.05). miR-1-3p expression in patients with hypertension complicated with depression was negatively correlated with serum BDNF level (r=-0.302, P < 0.05). In relative to the normal control population, the area under the curve (AUC) of ROC produced by serum miR-1-3p and BDNF in patients with primary hypertension complicated with depression was 0.971 (95% CI = 0.945-0.998, P < 0.0001) and 0.875 (95% CI = 0.808-0.942, P < 0.0001); and in relative to primary hypertension patients without depression, the AUC of ROC produced by serum miR-1-3p and BDNF in patients with primary hypertension with depression was 0.957 (95% CI = 0.925-0.989, P < 0.0001) and 0.883 (95% CI = 0.821-0.944, P < 0.0001), respectively. HADS-D score, HAMD score, course of the disease, miR-1-3p expression and BDNF level showed statistical differences in primary hypertension patients with and without depression (All P < 0.05). It was concluded that there are high miR-1-3p expression and low serum BDNF levels in patients with primary hypertension complicated with depression. miR-1-3p has a negative correlation with BDNF, and it may play a role by negatively regulating the expression of BDNF. Detecting miR-1-3p and BDNF in patients with primary hypertension can indicate the occurrence of depression to some extent.
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Hipertensão , MicroRNAs , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/complicações , Depressão/genética , Humanos , Hipertensão/complicações , Hipertensão/genética , MicroRNAs/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
To investigate the effect of the FGFR2-CCDC6 fusion gene on cell proliferation and its mechanism of action, pCDNA3.1- FGFR2bWT, pCDNA3.1- FGFR2-CCDC6 expression plasmids were transiently transfected into Hucct-1 cells using Lipo-2000 liposomes. The effect of the fusion gene on cell proliferation was examined by MTT and the expression of FGFR2/AKT/signaling pathway proteins was detected by Western blot. Results showed that Hucct-1 cells transfected with the FGFR2-CCDC6 fusion gene showed increased FGFR2 protein expression (P<0.001) and significantly higher cell proliferation capacity (P<0.001) compared to normal controls. It was concluded that The FGFR2-CCDC6 fusion gene excessively activates the AKT, and ERK signaling pathway downstream of FGFR2 and plays a role in promoting cell proliferation.
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Proteínas Proto-Oncogênicas c-akt , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Linhagem Celular Tumoral , Proliferação de Células/genética , Lipossomos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de SinaisRESUMO
This research was carried out to investigate the expression of miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins in colorectal adenocarcinoma and corresponding distal cutaneous normal mucosal tissues and their relationship with the clinicopathological parameters of colorectal adenocarcinoma as well as the correlation between miR-34a, miR-34b and PI3K/AKT/mTOR signaling pathway. The expression of p-PI3K, p-AKT, and mTOR proteins in 67 colorectal adenocarcinomas and the corresponding distal cut-off normal mucosa were assayed by immunohistochemistry. Their relationship with clinicopathological parameters and the correlation of the three proteins were evaluated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma and the corresponding distal cutaneous normal mucosa was detected by applying real-time quantitative PCR. The correlation between colorectal adenocarcinoma tissue miR-34a, miR-34b and p-PI3K, p-AKT, and mTOR proteins, respectively, was analyzed. Results showed that the expression of p-PI3K, p-AKT and mTOR proteins in colorectal adenocarcinoma tissues was higher than that in the corresponding distal cutaneous normal mucosa (P=0.000), and there was a positive correlation between the expression of the three proteins in colorectal adenocarcinoma tissues. The expression of p-PI3K and p-AKT protein in colorectal adenocarcinoma tissues were correlated with tumor size, differentiation degree, infiltration degree, lymph node metastasis and TNM stage (P<0.05). The expression of mTOR protein was related to tumor size and differentiation degree (P<0.05). The relative expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was less than that in the corresponding distal cutaneous normal mucosa (P<0.05), and the expression of miR-34a and miR-34b was positively correlated. The expression of miR-34a and miR-34b in colorectal adenocarcinoma tissues was negatively correlated with the expression of p-PI3K, p-AKT and mTOR proteins. In conclusion, the PI3K/AKT/mTOR signaling pathway may promote colorectal adenocarcinoma and differentially participate in differentiation, infiltration and lymph node metastasis. Also, miR-34a and miR-34b may inhibit colorectal adenocarcinoma. Importantly, miR-34a and miR-34b may affect the development and progression of colorectal adenocarcinoma by regulating PI3K/AKT/mTOR signaling pathway.
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Adenocarcinoma , Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Metástase Linfática , Adenocarcinoma/patologia , Neoplasias Colorretais/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
Annexin A7 has been confirmed in our previous research to be an important factor in lymph node metastasis (LNM) of hepatocellular carcinoma (HCC). SODD and ALG-2 are the binding proteins of Annexin A7 and can work in protein complexes. The present study was carried out with the constructed cell lines in mouse model of metastasis for further elaboration of possible mechanisms and identification of associated genes in the LNM of HCC. This experiment used inbred Chinese 615 mice, as well as Hca-F and Hca-P cells. Quantification of the relative messenger RNA (mRNA) expression of SODD and ALG-2 was realized by using qRT-PCR. Quantification of the protein expressions of SODD and ALG-2 was achieved by using western blot. Experimental mice (n=160) (6-8weeks old, 18-22g, SCXK [LIAO] 2008-0002) were randomly classified into four groups equally, which were separately inoculated with Hca-F, Hca-P, FAnxa7-upregulated, and PAnxa7-upregulated cells. Serum levels of SODD and ALG-2 were measured by ELISA. Immunohistochemical analysis of SODD and ALG-2 was further conducted. Tumor LNM-related factors of SODD and ALG-2 showed the same tendency in their expression correspondingly with the up-regulated expression of Annexin A7. Our experiment further explored the roles of SODD and ALG-2 based on Annexin A7 up-regulation vectors construction and the establishment of corresponding controls in vivo. Furthermore, the mouse model of primary tumors was constructed by injecting Hca-F, FAnxa7-upregulated and Hca-P, PAnxa7-upregulated cells into the mouse footpad. Mice were sacrificed at the designated time points for detecting SODD and ALG-2 expression in tumor tissue and serum samples. Collectively, our work indicates SODD in tumors and in serum and ALG-2 in serum are valuable in evaluating LNM in mice with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Anexina A7/genética , Anexina A7/metabolismo , Biomarcadores , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Neoplasias Hepáticas/patologia , Metástase Linfática , CamundongosRESUMO
Ocean noise has a negative impact on the acoustic recordings of odontocetes' echolocation clicks. In this study, deep convolutional autoencoders (DCAEs) are presented to denoise the echolocation clicks of the finless porpoise (Neophocaena phocaenoides sunameri). A DCAE consists of an encoder network and a decoder network. The encoder network is composed of convolutional layers and fully connected layers, whereas the decoder network consists of fully connected layers and transposed convolutional layers. The training scheme of the denoising autoencoder was applied to learn the DCAE parameters. In addition, transfer learning was employed to address the difficulty in collecting a large number of echolocation clicks that are free of ambient sea noise. Gabor functions were used to generate simulated clicks to pretrain the DCAEs; subsequently, the parameters of the DCAEs were fine-tuned using the echolocation clicks of the finless porpoise. The experimental results showed that a DCAE pretrained with simulated clicks achieved better denoising results than a DCAE trained only with echolocation clicks. Moreover, deep fully convolutional autoencoders, which are special DCAEs that do not contain fully connected layers, generally achieved better performance than the DCAEs that contain fully connected layers.
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Ecolocação , Toninhas , Animais , Aprendizagem , Aprendizado de Máquina , Redes Neurais de ComputaçãoRESUMO
The Irrawaddy dolphin (Orcaella brevirostris) is an endangered, small cetacean species which is widely distributed in rivers, estuaries, and coastal waters throughout the tropical and subtropical Indo-Pacific. Despite the extensive distribution of this species, little is known of individual movements or genetic exchange among regions in Thailand. Here, we evaluate the genetic diversity and genetic structure of O. brevirostris in the eastern, northern and western Gulf of Thailand, and Andaman Sea. Although phylogenetic relationships and network analysis based on 15 haplotypes obtained from 32 individuals reveal no obvious divergence, significant genetic differentiation in mitochondrial DNA (overall FST = 0.226, P < 0.001; ΦST = 0.252, P < 0.001) is apparent among regions. Of 18 tested microsatellite loci, 10 are polymorphic and successfully characterized in 28 individuals, revealing significant genetic differentiation (overall FST = 0.077, P < 0.05) among the four sampling sites. Structure analysis reveals two inferred genetic clusters. Additionally, Mantel analysis demonstrates individual-by-individual genetic distances and geographic distances follow an isolation-by-distance model. We speculate that the significant genetic structure of O. brevirostris in Thailand is associated with a combination of geographical distribution patterns, environmental and anthropogenic factors, and local adaptations.
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Human activities are considered a critical impact factor for decision-making in coupled human-nature systems, such as conservation of coastal systems. Identifying key human activities that cause significant habitat degradation for coastal species remains challenging. We improved the spatial subsidy approach to identify and prioritize control strategies for human-caused distribution shifts of marine species. We applied this method to a threatened Indo-Pacific humpback dolphin (Sousa chinensis) in Xiamen Bay, China. Our results indicate that (1) a significant distribution shift for humpback dolphins from existing nature reserves to peripheral waters occurred from 2011 to 2014; (2) coastal tourism and industrial and urban construction had more significant negative impacts on humpback dolphins than maritime transportation and reclamation; and (3) proactive management should be implemented for maritime transportation and reclamation, while reactive management should be implemented for coastal tourism and industrial and urban construction. Human impact analysis, combined with spatially explicit modeling, contributes to determining the spatial alternatives for conservation planning. In response to possible ecological damage caused by human activities, the improved spatial subsidy results help provide knowledge and platforms for ecological compensation.
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Conservação dos Recursos Naturais , Golfinhos , Animais , China , Ecossistema , Atividades HumanasRESUMO
BACKGROUND: We previously discovered that tetracyclines increase the expression of lipid phosphate phosphatases at the surface of cells. These enzymes degrade circulating lysophosphatidate and therefore doxycycline increases the turnover of plasma lysophosphatidate and decreases its concentration. Extracellular lysophosphatidate signals through six G protein-coupled receptors and it is a potent promoter of tumor growth, metastasis and chemo-resistance. These effects depend partly on the stimulation of inflammation that lysophosphatidate produces. METHODS: In this work, we used a syngeneic orthotopic mouse model of breast cancer to determine the impact of doxycycline on circulating lysophosphatidate concentrations and tumor growth. Cytokine/chemokine concentrations in tumor tissue and plasma were measured by multiplexing laser bead technology. Leukocyte infiltration in tumors was analyzed by immunohistochemistry. The expression of IL-6 in breast cancer cell lines was determined by RT-PCR. Cell growth was measured in Matrigel™ 3D culture. The effects of doxycycline on NF-κB-dependent signaling were analyzed by Western blotting. RESULTS: Doxycycline decreased plasma lysophosphatidate concentrations, delayed tumor growth and decreased the concentrations of several cytokines/chemokines (IL-1ß, IL-6, IL-9, CCL2, CCL11, CXCL1, CXCL2, CXCL9, G-CSF, LIF, VEGF) in the tumor. These results were compatible with the effects of doxycycline in decreasing the numbers of F4/80+ macrophages and CD31+ blood vessel endothelial cells in the tumor. Doxycycline also decreased the lysophosphatidate-induced growth of breast cancer cells in three-dimensional culture. Lysophosphatidate-induced Ki-67 expression was inhibited by doxycycline. NF-κB activity in HEK293 cells transiently expressing a NF-κB-luciferase reporter vectors was also inhibited by doxycycline. Treatment of breast cancer cells with doxycycline also decreased the translocation of NF-κB to the nucleus and the mRNA levels for IL-6 in the presence or absence of lysophosphatidate. CONCLUSION: These results contribute a new dimension for understanding the anti-inflammatory effects of tetracyclines, which make them potential candidates for adjuvant therapy of cancers and other inflammatory diseases.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Doxiciclina/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Lisofosfolipídeos/sangue , NF-kappa B/metabolismo , Animais , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Fosforilação , Transporte Proteico , Carga Tumoral , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Melanoma is the most common primary malignant neoplasm in adults, causing more deaths than any other skin cancer, necessitating the development of new target-based approaches. Current evidence suggests SIRT1, the mammalian nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting NAD+ biosynthetic enzyme, together comprise a novel systemic regulatory network to play a pivotal role in cell proliferation and apoptosis. Nevertheless, how the regulation of this cofactor interfaces with signal transduction network remains poorly understood in melanoma. Here, we report NAMPT is highly expressed in melanomaassociated with poor overall survival in patients. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and melanoma cell proliferation capacity, and NAMPT knockdown induced apoptosis through the activity of the tumor suppressor p53. Next, we demonstrate NAMPT regulates the transcription factor E2F family member 2 (E2F2) in the apoptosis process. Downstream, E2F2 control the mRNA and protein levels of SIRT1. Finally, we find NAMPT mediates the apoptosis resistance of melanoma cells through NAMPT-E2F2-SIRT1 axis, more than NAD+-driven transcriptional program. Accordingly, our results demonstrated that NAMPT is a prognostic marker in melanoma, and the identificationofNAMPT-E2F2-SIRT1 pathway establishes another link between NAMPT and apoptosis events in melanoma, with therapeutic implications for this deadly cancer.
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Proliferação de Células , Citocinas/metabolismo , Fator de Transcrição E2F2/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Nicotinamida Fosforribosiltransferase/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Humanos , Transdução de SinaisRESUMO
A finite element method was used to investigate the temperature influence on sound beams of the Indo-Pacific humpback dolphin. The numerical models of a dolphin, which originated from previous computed tomography (CT) scanning and physical measurement results, were used to investigate sound beam patterns of the dolphin in temperatures from 21 °C to 39 °C, in increments of 2 °C. The -3 dB beam widths across the temperatures ranged from 9.3° to 12.6°, and main beam angle ranged from 4.7° to 7.2° for these temperatures. The subsequent simulation suggested that the dolphin's sound beam patterns, side lobes in particular, were influenced by temperature.
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Acústica , Simulação por Computador , Golfinhos/psicologia , Ecolocação , Modelos Teóricos , Temperatura , Vocalização Animal , Animais , Golfinhos/classificação , Análise de Elementos Finitos , Análise Numérica Assistida por Computador , Processamento de Sinais Assistido por Computador , Especificidade da Espécie , Tomografia Computadorizada por Raios X , Vocalização Animal/classificaçãoRESUMO
We unveiled the association of Annexin A7 with vascular endothelial growth factor-C (VEGF-C) and the effect of upregulation of Annexin A7 in Hca-F and Hca-P cells on inhibiting hepatocarcinoma (HCC) lymph node metastasis (LNM) in vitro and in vivo. A total of 200 inbred 615 mice were randomly divided into four equal groups inoculated with Hca-F, Hca-P, FAnxa7-upregulated, and PAnxa7-upregulated cells, respectively. The primary tumor, popliteal, inguinal, and iliac lymph nodes were prepared for immunohistochemical (IHC) staining, real-time quantitative polymerase chain reaction (qRT-PCR) analysis, Western blot, and hematoxylin-eosin (H&E) staining. There was over 50 % increase both in the number of FAnxa7-upregulated and PAnxa7-upregulated cells migrated through the filter compared to their controls (FAnxa7-control, Hca-F and PAnxa7-control, Hca-P). However, no significant differences were noted in invasion ability between them (all P > 0.05). Tumor lymph vessels were significantly reduced in FAnxa7-upregulated and PAnxa7-upregulated tumors when compared with Hca-F and Hca-P tumors (all P < 0.05). Blood vessel density did not differ significantly between FAnxa7-upregulated and PAnxa7-upregulated tumors and Hca-F and Hca-P tumors. Enzyme-linked immunosorbent assay (ELISA) for VEGF-C showed that upregulating Annexin A7 decreased VEGF-C secretion in FAnxa7-upregulated and PAnxa7-upregulated cells (P < 0.05). The IHC staining result showed that the level of serum Annexin A7 was found to be statistically higher in all experimental groups than that in the control group (P < 0.05). The present results indicated that alterations in serum Annexin A7 expression may be of prognostic relevance in HCC lymphatic metastasis.
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Anexina A7/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Metástase Linfática , Masculino , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Regulação para Cima , Fator C de Crescimento do Endotélio Vascular/metabolismoRESUMO
Introduction: Eelgrass is a typical marine angiosperm that exhibits strong adaptability to high-salt environments. Previous studies have shown that various growth and physiological indicators were significantly affected after the nitrate reductase (NR) pathway for nitric oxide (NO) synthesis in eelgrass was blocked. Methods: To analyze the molecular mechanism of NO on the adaptability to high-salt environment in eelgrass, we treated eelgrass with artificial seawater (control group) and artificial seawater with 1 mM/L Na2WO4 (experimental group). Based on transcriptomics and metabolomics, we explored the molecular mechanism of NO affecting the salt tolerance of eelgrass. Results: We obtained 326, 368, and 859 differentially expressed genes (DEGs) by transcriptome sequencing in eelgrass roots, stems, and leaves, respectively. Meanwhile, we obtained 63, 52, and 36 differentially accumulated metabolites (DAMs) by metabolomics in roots, stems, and leaves, respectively. Finally, through the combined analysis of transcriptome and metabolome, we found that the NO regulatory mechanism of roots and leaves of eelgrass is similar to that of terrestrial plants, while the regulatory mechanism of stems has similar and unique features. Discussion: NO in eelgrass roots regulates osmotic balance and antioxidant defense by affecting genes in transmembrane transport and jasmonic acid-related pathways to improve the adaptability of eelgrass to high-salt environments. NO in eelgrass leaves regulates the downstream antioxidant defense system by affecting the signal transduction of plant hormones. NO in the stems of eelgrass regulates ion homeostasis by affecting genes related to ion homeostasis to enhance the adaptability of eelgrass to high-salt environments. Differently, after the NO synthesis was inhibited, the glyoxylate and dicarboxylate metabolism, as well as the tricarboxylic acid (TCA) cycle, was regulated by glucose metabolism as a complementary effect to cope with the high-salt environment in the stems of eelgrass. These are studies on the regulatory mechanism of NO in eelgrass, providing a theoretical basis for the study of the salt tolerance mechanism of marine plants and the improvement of terrestrial crop traits. The key genes discovered in this study can be applied to increase salt tolerance in terrestrial crops through cloning and molecular breeding methods in the future.
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Microplastics (MPs) pollution is of global concern, which poses serious threats to various marine organisms, including many threatened apex predators. In this study, MPs were investigated from nine cetaceans of four different species, comprising one common dolphin (Delphinus delphis), two pygmy sperm whales (Kogia breviceps), one ginkgo-toothed beaked whale (Mesoplodon ginkgodens), and five Indo-Pacific humpback dolphins (Sousa chinensis) stranded along the western coast of the Taiwan Strait from the East China Sea based on Fourier transform infrared (FTIR) spectroscopy analysis. Mean abundances of 778 identified MPs items were 86.44 ± 12.22 items individual-1 and 0.43 ± 0.19 items g-1 wet weight of intestine contents, which were found predominantly to be transparent, fiber-shaped polyethylene terephthalate (PET) items usually between 0.5 and 5 mm. The abundance of MPs was found at a slightly higher level and significantly correlated with intestine contents mass (p = 0.0004*). The MPs source was mainly likely from synthetic fibers-laden sewage discharged from intense textile industries. Our report represents the first study of MPs in pelagic and deep-diving cetaceans in China, which not only adds baseline data on MPs for cetaceans in Asian waters but also highlights the further risk assessment of MPs consumption in these threatened species.
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Both regular flow and infrequent outburst floods shape the mountain landscape, but their relative contributions have been widely debated, in part due to the paucity of quantitative data on historical outburst floods. In June 2000, an outburst flood was triggered by a landslide-dam failure in a rapidly exhumed region of the Eastern Himalaya. To investigate the role of this kind outburst flood on landscape evolution, we employ topographic differencing, satellite imagery, and 2D hydraulic simulations to quantify the equivalent erosion and deposition within ~ 80 km flood route downstream of the breach. The flood lasted for ~ 10 h, with a peak discharge of 105 m3/s, leading to average erosion of 10 m, and contributed ~ 1-2 × 103 times more sediment than over long-term mean fluvial processes. The flood produced extensive lateral erosion, which triggered a threefold widening of the valley floor and abundant subsequent landslides. The ubiquitous boulder bars deposited in the channel inhibited incision, and facilitated lateral erosion after the flood. The resulting channel configuration and extensive bank erosion continue to affect fluvial dynamics until the next catastrophic flood that remobilizes the boulders. Our quantitative findings highlight the profound importance of recurrent outburst floods for gorge development and landscape evolution in Eastern Himalaya.