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Ginsenoside Rb1, known as gypenoside III, exerts antidepressant-like effects in previous studies. It has also been indicated that ginsenoside Rb1 regulated neuroinflammation via inhibiting NF-κB signaling. According to the evidence that astrocytes can regulate microglia and neuroinflammation by secreting complement C3, the present study aimed to demonstrate the molecular mechanisms underlying ginsenoside Rb1-induced antidepressant-like effects from the astrocytic and microglial complement C3 pathway. The complement C3 mediated mechanism of ginsenoside Rb1 was investigated in mice exposed to chronic restraint stress (CRS). The results showed that ginsenoside Rb1 reversed the depressive-like behaviors in CRS. Treatment with ginsenoside Rb1 reduced both the number of astrocytes and microglia. In addition, ginsenoside Rb1 suppressed TLR4/NF-κB/C3 signaling in the astrocytes of the hippocampus. Furthermore, ginsenoside Rb1 attenuated the contents of synaptic protein including synaptophysin and PSD95 in microglia, suggesting the inhibition of microglia-mediated synaptic elimination caused by CRS. Importantly, ginsenoside Rb1 also maintained the dendritic spines in mice. In conclusion, our results demonstrate that ginsenoside Rb1 produces the antidepressant-like effects by inhibiting astrocyte TLR4/NF-κB/C3 signaling to covert microglia from a pro-inflammatory phenotype (amoeboid) towards an anti-inflammatory phenotype (ramified), which inhibit the synaptic pruning in the hippocampus.
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Modern ray-finned fishes (Actinopterygii) comprise half of extant vertebrate species and are widely thought to have originated before or near the end of the Middle Devonian epoch (around 385 million years ago). Polypterids (bichirs and ropefish) represent the earliest-diverging lineage of living actinopterygians, with almost all Palaeozoic taxa interpreted as more closely related to other extant actinopterygians than to polypterids. By contrast, the earliest material assigned to the polypterid lineage is mid-Cretaceous in age (around 100 million years old), implying a quarter-of-a-billion-year palaeontological gap. Here we show that scanilepiforms, a widely distributed radiation from the Triassic period (around 252-201 million years ago), are stem polypterids. Importantly, these fossils break the long polypterid branch and expose many supposedly primitive features of extant polypterids as reversals. This shifts numerous Palaeozoic ray-fins to the actinopterygian stem, reducing the minimum age for the crown lineage by roughly 45 million years. Recalibration of molecular clocks to exclude phylogenetically reassigned Palaeozoic taxa results in estimates that the actinopterygian crown lineage is about 20-40 million years younger than was indicated by previous molecular analyses. These new dates are broadly consistent with our revised palaeontological timescale and coincident with an interval of conspicuous morphological and taxonomic diversification among ray-fins centred on the Devonian-Carboniferous boundary. A shifting timescale, combined with ambiguity in the relationships of late Palaeozoic actinopterygians, highlights this part of the fossil record as a major frontier in understanding the evolutionary assembly of modern vertebrate diversity.
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Peixes/anatomia & histologia , Peixes/classificação , Fósseis , Filogenia , Nadadeiras de Animais/anatomia & histologia , Animais , Crânio/anatomia & histologia , Fatores de Tempo , Tomógrafos ComputadorizadosRESUMO
This corrects the article DOI: 10.1038/nature23654.
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Maize (Zea mays subsp mays) was domesticated from its wild ancestor, teosinte (Zea mays subsp parviglumis). Maize's distinct morphology and adaptation to diverse environments required coordinated changes in various metabolic pathways. However, how the metabolome was reshaped since domestication remains poorly understood. Here, we report a comprehensive assessment of divergence in the seedling metabolome between maize and teosinte. In total, 461 metabolites exhibited significant divergence due to selection. Interestingly, teosinte and tropical and temperate maize, representing major stages of maize evolution, targeted distinct sets of metabolites. Alkaloids, terpenoids, and lipids were specifically targeted in the divergence between teosinte and tropical maize, while benzoxazinoids were specifically targeted in the divergence between tropical and temperate maize. To identify genetic factors controlling metabolic divergence, we assayed the seedling metabolome of a large maize-by-teosinte cross population. We show that the recent metabolic divergence between tropical and temperate maize tended to have simpler genetic architecture than the divergence between teosinte and tropical maize. Through integrating transcriptome data, we identified candidate genes contributing to metabolic divergence, many of which were under selection at the nucleotide and transcript levels. Through overexpression or mutant analysis, we verified the roles of Flavanone 3-hydroxylase1, Purple aleurone1, and maize terpene synthase1 in the divergence of their related biosynthesis pathways. Our findings not only provide important insights into domestication-associated changes in the metabolism but also highlight the power of combining omics data for trait dissection.
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Evolução Biológica , Domesticação , Metabolômica , Zea mays/genética , Zea mays/metabolismo , Aclimatação , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Benzoxazinas , Vias Biossintéticas/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Metaboloma/genética , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Zea mays/classificaçãoRESUMO
BACKGROUND: Complex translocation of chromosomes often causes mental retardation, dysplasia, and a variety of abnormalities in patients, which can easily lead to sperm disorders in men, and carriers are often at high risk of adverse pregnancy. METHODS: The chromosome karyotypes of the patients were analyzed by collecting peripheral blood for lymphocyte culture, chromosome harvest, section and G-banding staining. RESULTS: The results of chromosome karyotype analysis in the patient were 46,XY, T (4; 11. 6; 8)(q33; p15; p12; Q22), the translocation occurred on chromosome 4, 11, 6 and 8, and the break points were q33, p15, p12 and q22, respectively. CONCLUSIONS: Translocation occurred in 4 chromosomes of the patient, which was a complex translocation and was rare in clinic. The meiosis of the germ cells can interfere with the normal pairing and distribution of chromosomes, resulting in a high probability of abnormal gamete formation. Therefore, patients are advised to avoid natural conception, or use other people's sperm to obtain normal offspring through artificial insemination, or adopt children to achieve a successful family combination.
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Infertilidade Masculina , Sêmen , Gravidez , Feminino , Criança , Humanos , Masculino , Translocação Genética , Cariotipagem , Cariótipo , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genéticaRESUMO
Several immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1)/programmed death 1 have successfully improved the prognosis of oesophageal squamous cell carcinoma (ESCC) with approval in certain countries. However, whether the expression of PD-L1 is associated with the degree of benefit is unclear yet and a unified standard of antibody and cut-off value of PD-L1 detection is also lacking. The current meta-analysis then aimed to explore the association between PD-L1 expression and clinicopathological features as well as prognosis in ESCC.A systematic search on PubMed, Embase, Cochrane Library and Web of Science databases was performed up to 30 March 2021. The correlation between PD-L1 expression and clinicopathological features, as well as prognosis in ESCC, was estimated with the random-effects model.A total of 5368 patients from 31 retrospective studies were enrolled. The overexpression of PD-L1 was significantly associated with lymph node metastasis (OR 1.342, 95% CI 0.995 to 1.809, p=0.050) and distant metastasis (OR 1.516, 95% CI 1.001 to 2.294, p=0.050). The pooled HR showed that PD-L1 overexpression was significantly correlated with poor overall survival (OS) of patients with ESCC (HR 1.306, 95% CI 1.108 to 1.539, p<0.010) but not disease-free survival (DFS) (HR 1.180, 95% CI 0.937 to 1.487, p=0.160). Heterogeneity decreased significantly in subgroup analyses. The overexpression of PD-L1 was associated with poor DFS at the cut-off point of ≥1% (HR 1.642, 95% CI 1.367 to 1.973, p<0.010; I2=0%) and worse OS at the cut-off point of ≥10% (HR 1.575, 95% CI 1.175 to 2.111, p<0.010; I2=0%).The overexpression of PD-L1 was correlated with lymph node and distant metastasis as well as poor survival of ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Antígeno B7-H1 , Biomarcadores Tumorais/metabolismo , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Oesophagectomy, the gold standard for oesophageal cancer treatment, causes significantly high morbidity and mortality. McKeown minimally invasive oesophagectomy (MIE) is preferred for treating oesophageal malignancies; however, limited studies with large sample sizes focusing on the surgical and oncological outcomes of this procedure have been reported. We aimed to compare the clinical safety and efficacy of McKeown MIE with those of open oesophagectomy (OE). PATIENTS AND METHODS: Overall, 338 oesophageal cancer patients matched by gender, age, location, size, and T and N stages (McKeown MIE: 169 vs OE: 169) were analysed. The clinicopathologic features, operational factors, postoperative complications, and prognoses were compared between the groups. RESULTS: McKeown MIE resulted in less bleeding (200 mL vs 300 mL, p<0.01), longer operation time (335.0 h vs 240.0 h, p<0.01), and higher number of harvested lymph nodes (22 vs 9, p<0.01) than OE did. Although the rate of recurrent laryngeal nerve injury in the two groups was not significantly different, incidence of anastomotic leakage (8 vs 24, p=0.003) was significantly lower in the McKeown MIE group. In addition, patients who underwent McKeown MIE had higher 5-year overall survival than those who underwent OE (69.9% vs 40.4%, p<0.001). CONCLUSION: McKeown MIE is proved to be feasible and safe to achieve better surgical and oncological outcomes for oesophageal cancer compared with OE.
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Neoplasias Esofágicas , Esofagectomia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Yes-associated protein (YAP), a major effector of the Hippo signalling pathway, is widely implicated in vascular pathophysiology processes. Here, we identify a new role of YAP in the regulation of vascular senescence. The inhibition or deficiency and overexpression of YAP were performed in human umbilical vein endothelial cells (HUVECs) and isolated vascular tissues. Cellular and vascular senescence was assessed by analysis of the senescence-associated ß-galactosidase (SA-ß-gal) and expression of senescence markers P16, P21, P53, TERT and TRF1. We found that YAP was highly expressed in old vascular tissues, inhibition and knockdown of YAP decreased senescence, while overexpression of YAP increased the senescence in both HUVECs and vascular tissues. In addition, autophagic flux blockage and mTOR pathway activation were observed during YAP-induced HUVECs and vascular senescence, which could be relieved by the inhibition and knockdown of YAP. Moreover, YAP-promoted cellular and vascular senescence could be relieved by mTOR inhibition. Collectively, our findings indicate that YAP may serve as a potential therapeutic target for ageing-associated cardiovascular disease.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Autofagia , Vasos Sanguíneos/patologia , Senescência Celular , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Animais , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ratos Sprague-Dawley , Proteínas de Sinalização YAPRESUMO
Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.
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Biomarcadores Tumorais/imunologia , Imunoterapia , Tumores Neuroendócrinos/terapia , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/metabolismo , Carcinoma de Célula de Merkel/terapia , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/imunologia , Neoplasias do Sistema Digestório/metabolismo , Neoplasias do Sistema Digestório/terapia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Linfócitos do Interstício Tumoral , Instabilidade de Microssatélites , Mutação , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/imunologia , Tumores Neuroendócrinos/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: Serum amylase is secreted by salivary glands and pancreas and is used for the diagnosis of pancreatic and parotid diseases. A number of factors can elevate the level of serum amylase including pancreatic diseases, salivary disease, gastrointestinal diseases, liver diseases, gynecologic disease, cholecystitis, peritonitis, renal failure, and drug induced. METHODS: We reported a case with abnormally elevated serum amylase, namely hyperamylasemia. Abdominal B-ultrasound, abdominal magnetic resonance imaging (MRI), parotid computed tomography (CT), gastroscopy, and colonoscopy were used to screen the causes of hyperamylasemia. Common serum tumor markers and serum biochemistry were detected to exclude some common causes. The amylase-creatinine clearance ratio (ACCR) was calculated for the patient. RESULTS: The average value of serum amylase were 881 U/L, which was significantly higher than reference value (10 - 220 U/L). According to ACCR value, the patient was diagnosed with macroamylasemia after the exclusion of some possible causes for elevating serum amylase. CONCLUSIONS: When renal function is normal, serum amylase continues to increase and urine amylase is normal or decreased, macroamylasemia should be considered after the exclusion of pancreatic and parotid diseases. Macroamylasemia can not only be associated with autoimmune diseases, malignant tumors and other diseases, but also can be found in healthy population.
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Doenças Autoimunes , Gastroenteropatias , Hiperamilassemia , Amilases , Feminino , Humanos , PâncreasRESUMO
From its tropical origin in southwestern Mexico, maize spread over a wide latitudinal cline in the Americas. This feat defies the rule that crops are inhibited from spreading easily across latitudes. How the widespread latitudinal adaptation of maize was accomplished is largely unknown. Through positional cloning and association mapping, we resolved a flowering-time quantitative trait locus to a Harbinger-like transposable element positioned 57 kb upstream of a CCT transcription factor (ZmCCT9). The Harbinger-like element acts in cis to repress ZmCCT9 expression to promote flowering under long days. Knockout of ZmCCT9 by CRISPR/Cas9 causes early flowering under long days. ZmCCT9 is diurnally regulated and negatively regulates the expression of the florigen ZCN8, thereby resulting in late flowering under long days. Population genetics analyses revealed that the Harbinger-like transposon insertion at ZmCCT9 and the CACTA-like transposon insertion at another CCT paralog, ZmCCT10, arose sequentially following domestication and were targeted by selection for maize adaptation to higher latitudes. Our findings help explain how the dynamic maize genome with abundant transposon activity enabled maize to adapt over 90° of latitude during the pre-Columbian era.
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Adaptação Fisiológica/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Zea mays/genética , Zea mays/fisiologia , Clonagem Molecular , Flores/genética , Flores/fisiologia , Deleção de Genes , Genoma de Planta , Proteínas de Plantas/genéticaRESUMO
The presence of spoofing signals poses a significant threat to global navigation satellite system (GNSS)-based positioning applications, as it could cause a malfunction of the positioning service. Therefore, the main objective of this paper is to present a spatial-temporal technique that enables GNSS receivers to reliably detect and suppress spoofing. The technique, which is based on antenna array, can be divided into two consecutive stages. In the first stage, an improved eigen space spectrum is constructed for direction of arrival (DOA) estimation. To this end, a signal preprocessing scheme is provided to solve the signal model mismatch in the DOA estimation for navigation signals. In the second stage, we design an optimization problem for power estimation with the estimated DOA as support information. After that, the spoofing detection is achieved by combining power comparison and cross-correlation monitoring. Finally, we enhance the genuine signals by beamforming while the subspace oblique projection is used to suppress spoofing. The proposed technique does not depend on external hardware and can be readily implemented on raw digital baseband signal before the despreading of GNSS receivers. Crucially, the low-power spoofing attack and multipath can be distinguished and mitigated by this technique. The estimated DOA and power are both beneficial for subsequent spoofing localization. The simulation results demonstrate the effectiveness of our method.
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This paper investigates formation tracking control for multi-agent networks with fixed time convergence. The control task is that the follower agents are required to form a prescribed formation within a fixed time and the geometric center of the formation moves in sync with the leader. First, an error system is designed by using the information of adjacent agents and a new control protocol is designed based on the error system and terminal sliding mode control (TSMC). Then, via employing the Lyapunov stability theorem and the fixed time stability theorem, the control task is proved to be possible within a fixed time and the convergence time can be calculated by parameters. Finally, numerical results illustrate the feasibility of the proposed control protocol.
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It is challenging to construct high-performing excimer-based luminescent analytic tools at low molecular concentrations. We report that enzyme-instructed self-assembly (EISA) enables the monomer-excimer transition of a coumarin dye (Cou) at low molecular concentrations, and the resulting higher ordered luminescent supramolecular assemblies (i.e., nanofibers) efficiently record the spatiotemporal details of alkaline phosphatase (ALP) activity inâ vitro and inâ vivo. Cou was conjugated to short self-assembly peptides with a hydrophilic ALP-responsive group. By ALP triggering, EISA actuated a nanoparticles-nanofibers transition at low peptide concentrations followed by monomer-excimer transition of Cou. Analysis of structure-property relationships revealed that the self-assembly motif was a prerequisite for peptides to induce the monomer-excimer transition of Cou. Luminescent supramolecular nanofibers of pYD (LSN-pYD) illuminated the intercellular bridge of cancer cells and distinguished cancer cells (tissues) from normal cells (tissues) efficiently and rapidly, promising potential use for the early diagnosis of cancer. This work extends the functions of EISA and provides a new application of supramolecular chemistry.
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Fosfatase Alcalina/metabolismo , Cumarínicos/análise , Ensaio de Imunoadsorção Enzimática , Corantes Fluorescentes/análise , Luminescência , Imagem Óptica , Fosfatase Alcalina/química , Cumarínicos/metabolismo , Corantes Fluorescentes/metabolismo , Células HeLa , Humanos , Substâncias Macromoleculares/análise , Substâncias Macromoleculares/metabolismo , Estrutura Molecular , Nanofibras/análiseRESUMO
Abnormal expression of KDM6A and SOX9 is a key factor in the pathogenesis of osteoarthritis (OA). Cellular treatments of OA with articular cartilage chondrocytes (ACCs) and bone marrow mesenchymal stem cells (BMSCs) are promising, but their underlying mechanisms remain to be explored. The pellet size, weight and sulfated glycosaminoglycan/DNA content of ACCs were measured to evaluate the effect of BMSCs on the chondrogenic differentiation of SCCs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the proliferation of ACCs cultured along or cocultured with BMSCs. Quantitative polymerase chain reaction (qPCR) was performed to evaluate the messenger RNA expression of KDM6A, SOX9, type2 collagen, and Aggrecan in ACCs and OA rats. Western blot and immunohistochemistry were performed to analyze the expression of KDM6A and SOX9 proteins. Bisulfite sequencing PCR was performed to assess the DNA methylation level of the SOX9 promoter. Flow cytometry was used to evaluate the apoptotic status of ACCs. The chondrogenic differentiation of ACCs was significantly enhanced by coculturing with BMSCs, especially under a hypoxic condition. The expression of KDM6A, SOX9, type2 collagen, and Aggrecan was remarkably elevated in ACCs cocultured with BMSCs. Also, the DNA methylation of SOX9 promoter was decreased in ACCs cocultured with BMSCs, along with notably reduced apoptosis. Moreover, ACCs cocultured with BMSCs could repair cartilage lesions and prevent the abnormal expression of KDM6A, SOX9, type2 collagen, and Aggrecan in OA rats. In this study, we cocultured ACCs with BMSCs and used them to treat OA rats. Our findings presented a mechanistic basis for explaining the therapeutic effect of BMSCs on OA treatment.
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Condrócitos/metabolismo , Condrócitos/transplante , Histona Desmetilases/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite/metabolismo , Osteoartrite/terapia , Fatores de Transcrição SOX9/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Diferenciação Celular , Hipóxia Celular/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Condrócitos/citologia , Condrogênese/genética , Condrogênese/fisiologia , Técnicas de Cocultura , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Metilação de DNA , Modelos Animais de Doenças , Histona Desmetilases/genética , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/patologia , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fatores de Transcrição SOX9/genética , Transdução de SinaisRESUMO
BACKGROUND: It remains controversial whether prophylactic No.10 lymph node clearance is necessary for gastric cancer. Thus, the present study aims to investigate the impact of prophylactic No.10 lymph node clearance on the perioperative complications and prognosis of upper and middle third gastric cancer. METHODS: A network meta-analysis to identify both direct and indirect evidence with respect to the comparison of gastrectomy alone (G-A), gastrectomy combination with splenectomy (G + S) and gastrectomy combination with spleen-preserving splenic hilar dissection (G + SPSHD) was conducted. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies published before September 2018. Perioperative complications and overall survival were analyzed. Hazard ratios (HR) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. RESULTS: Ten retrospective studies involving 2565 patients were included. In the direct comparison analyses, G-A showed comparable 5-year overall survival rate (HR: 1.1, 95%CI: 0.97-1.3) but lower total complication rate (OR: 0.37, 95%CI: 0.17-0.77) compared with G + S. Similarly, the 5-year overall survival rate between G + SPSHD and G + S was comparable (HR: 1.1, 95%CI: 0.92-1.4), while the total complication rate of G + SPSHD was lower than that of G + S (OR: 0.50, 95%CI: 0.28-0.88). In the indirect comparison analyses, both the 5-year overall survival rate (HR: 1.0, 95%CI: 0.78-1.3) and total complication rate (OR: 0.75, 95%CI: 0.29-1.9) were comparable between G-A and G + SPSHD. CONCLUSIONS: Prophylactic No.10 lymph node clearance was not recommended for treatment of upper and middle third gastric cancer.
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Gastrectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Procedimentos Cirúrgicos Profiláticos/métodos , Baço/cirurgia , Neoplasias Gástricas/cirurgia , Humanos , Linfonodos/patologia , Metástase Linfática , Metanálise em Rede , Prognóstico , Estudos Retrospectivos , Baço/patologia , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
Ship type classification with radiated noise helps monitor the noise of shipping around the hydrophone deployment site. This paper introduces a convolutional neural network with several auditory-like mechanisms for ship type classification. The proposed model mainly includes a cochlea model and an auditory center model. In cochlea model, acoustic signal decomposition at basement membrane is implemented by time convolutional layer with auditory filters and dilated convolutions. The transformation of neural patterns at hair cells is modeled by a time frequency conversion layer to extract auditory features. In the auditory center model, auditory features are first selectively emphasized in a supervised manner. Then, spectro-temporal patterns are extracted by deep architecture with multistage auditory mechanisms. The whole model is optimized with an objective function of ship type classification to form the plasticity of the auditory system. The contributions compared with an auditory inspired convolutional neural network include the improvements in dilated convolutions, deep architecture and target layer. The proposed model can extract auditory features from a raw hydrophone signal and identify types of ships under different working conditions. The model achieved a classification accuracy of 87.2% on four ship types and ocean background noise.
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Nowadays, nanocarbon is widely employed to enwrap into fertilizers. However, the influence of nanocarbon on the transportation of contaminants from soil to plants and its mechanism remain unclear. In this study, pentachloronitrobenzene (PCNB), a typical organochlorine fungicide utilized all over the world, was chosen as the target contaminant to investigate the influence of nanocarbon on its transportation in soil-pak choi system. The maximum PCNB concentration in the root and leaf reached to 112 and 86 ng/g, respectively, demonstrating that PCNB would be absorbed by pak choi. The ratio of PCNB between leaf and root indicated that nanocarbon promoted root of pak choi to absorb PCNB. The transportation of PCNB inside plant was inhibited when pak choi was planted in soil containing higher concentration of nanocarbon. Human risk assessment showed that people consuming the pak choi in this study would not experience risk. However, in vitro toxicity test indicated that PCNB could directly impair intestinal epithelial cells (Caco-2 cells) and thus pose a potential risk to human intestine.
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Brassica/metabolismo , Fertilizantes , Nitrobenzenos/farmacocinética , Nitrobenzenos/toxicidade , Poluentes do Solo/farmacocinética , Transporte Biológico , Brassica/química , Células CACO-2 , Exposição Dietética , Contaminação de Alimentos , Fungicidas Industriais/farmacocinética , Fungicidas Industriais/toxicidade , Humanos , Nanoestruturas , Folhas de Planta/química , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Medição de Risco , Solo/química , Poluentes do Solo/toxicidade , Testes de Toxicidade AgudaRESUMO
In this study, we aimed to investigate the therapeutic effect of miR-21 in the treatment of spinal cord injury (SCI) as well as its underlying molecular mechanisms. Real-time PCR and western blot were performed to measure the expression of miR-21, PTEN, and PDCD4 in SCI rats. Locomotion recovery assessment, Nissl staining, IHC assay, and TUNEL assay were utilized to observe the therapeutic effect of miR-21 in the treatment of SCI. Bioinformatics analysis and luciferase assay were conducted to establish the signaling pathway of miR-21, PTEN, and PDCD4. The regulatory relationships between miR-21 and PTEN/PDCD4 were further validated by real-time PCR, western blot, MTT assay, and flow cytometry. Compared with sham-operated rats, SCI rats showed decreased expression of miR-21 along with increased expression of PTEN/PDCD4. Exosomes were equally distributed in MSCs transfected with miR-21, PTEN siRNA, or scramble controls. The exosomes isolated from the supernatant of cultured MSCs could improve the functional recovery of SCI rats by reducing SCI-induced neuron loss. In addition, miR-21 was shown to inhibit the expression of PTEN/PDCD4 and suppress neuron cell death. Moreover, PTEN and PDCD4 were validated as virtual targets of miR-21. In addition, the miR-21/PTEN/PDCD4 signaling pathway was shown to enhance cell viability and suppress cell death in vivo. The exosomes collected from the supernatant of transfected MSCs contained miR-21, which could improve the functional recovery of SCI rats and suppress cell death both in vivo and in vitro via the miR-21/PTEN/PDCD4 signaling pathway.
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Exossomos/genética , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Neurônios/citologia , Traumatismos da Medula Espinal/terapia , Animais , Proteínas Reguladoras de Apoptose/genética , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Células-Tronco Mesenquimais/química , PTEN Fosfo-Hidrolase/genética , Ratos , Traumatismos da Medula Espinal/genética , TransfecçãoRESUMO
BACKGROUND: In this study, we aimed to evaluate the therapeutic effects of extracellular vesicles (EVs), which were collected from differentiated PC12 cells and mesenchymal cells (MSCs), on the treatment of spinal cord injury (SCI). In addition, we aimed to identify miRNAs related to the inhibitory effect of EVs against cell apoptosis. METHODS: Electron microscopy was used to observe the distributions of EVs in the samples. Real-time PCR, western blot, thiazolyl blue tetrazolium bromide (MTT) assay, and flow cytometry were performed to establish the molecular signaling pathway underlying the effect of EVs in SCI. In addition, a Basso-Beattie-Bresnahan (BBB) score system, Nissl staining, immunohistochemistry assay, and TdT-mediated dUTP nick-end labeling (TUNEL) assay were conducted to validate the molecular signaling pathway established above. RESULTS: The expression of miR-21 and miR-19b was upregulated in EVs isolated from induced PC12 cells and MSCs, along with decreased expression of phosphatase and tensin homolog (PTEN) messenger RNA (mRNA)/protein and a lower level of cell apoptosis. The transfection of miR-21/miR-19b precursors into the cells also exhibited an inhibitory effect on cell apoptosis. In addition, in-silicon analysis and luciferase assays validated the role of PTEN as a virtual target of miR-21/miR-19b. Finally, the BBB scores and Nissl staining also validated the therapeutic effects of EVs derived from differentiated P12 cells/MSCs in SCI rats. Accordingly, the negative correlations between miR-21/miR-19b and PTEN mRNA/protein were implicated in the post-SCI recovery. CONCLUSIONS: The increased levels of miR-21/miR-19b in the EVs derived from differentiated PC12 cells and MSCs suppresses the apoptosis of neuron cells by downregulating the expression of PTEN.