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1.
Biochem Genet ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38379037

RESUMO

We aim to clarify the specific role of Karyopherin α2 (KPNA2) in the progression of laryngeal cancer, a kind of malignant tumor with a poor curative effect. We performed the bioinformatic analysis to obtain the ferroptosis-related differentially expressed genes. KPNA2 was screened out. Then the CCK-8 assay, wound healing assay, and transwell assay were used to clarify the changes in the proliferation, migration, and invasion abilities of laryngeal cancer cells after silencing KPNA2. The concentrations of iron ions, glutathione, superoxide dismutase, and malondialdehyde were evaluated by the corresponding detection kits. The expression levels of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, forkhead box O (FoxO)1a and FoxO3a were determined by Western Blot. A total of 45 ferroptosis-related differentially expressed genes in laryngeal cancer were obtained, and KPNA2 was selected after bioinformatic analysis. In ferroptosis-induced laryngeal cancer cells, the cell viability, migration rate, invasion ability, and the expression of glutathione peroxidase 4, glutathione, and superoxide dismutase were further decreased and the expression of cyclooxygenase 2, Acyl-CoA synthetase long-chain family member 4, iron ions, and malondialdehyde were further increased after silencing KPNA2. The expression levels of FoxO1a and FoxO3a in laryngeal cancer cells were increased by silencing KPNA2. KPNA2 may be a promising therapeutic target for laryngeal cancer. Down-regulation of KPNA2 can promote ferroptosis in laryngeal cancer by stimulating the FoxO signaling pathway.

2.
J Environ Manage ; 345: 118599, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37423185

RESUMO

Low impact development (LID) is a sustainable practice to managing urban runoff. However, its effectiveness in densely populated areas with intense rainfall, such as Hong Kong, remains unclear due to limited studies with similar climate conditions and urban patterns. The highly mixed land use and complicated drainage network present challenges for preparing a Storm Water Management Model (SWMM). This study proposed a reliable framework for setting up and calibrating SWMM by integrating multiple automated tools to address these issues. With a validated SWMM, we examined LID's effects on runoff control in a densely built catchment of Hong Kong. A designed full-scale LID implementation can reduce total and peak runoffs by around 35-45% for 2, 10 and 50-year return rainfalls. However, LID alone may not be adequate to handle the runoff in densely built areas of Hong Kong. As the rainfall return period increases, total runoff reduction increases, but peak runoff reduction remains close. Percentages of reduction in total and peak runoffs decline. The marginal control diminishes for total runoff while remaining constant for peak runoff when increasing the extent of LID implementation. In addition, the study identifies the crucial design parameters of LID facilities using global sensitivity analysis. Overall, our study contributes to accelerating the reliable application of SWMM and deepening the understanding of the effectiveness of LID in ensuring water security in densely built urban communities located near the humid-tropical climate zone, such as Hong Kong.


Assuntos
Chuva , Água , Hong Kong , Calibragem , Movimentos da Água
3.
Sleep Breath ; 25(4): 2163-2169, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33604802

RESUMO

PURPOSE: This study aimed to investigate pharyngeal paraesthesia symptoms in patients with obstructive sleep apnoea (OSA). MATERIAL AND METHODS: Patients with snoring and suspected OSA as well as age-matched controls were recruited. All participants underwent nocturnal polysomnography (PSG) and pharyngeal paraesthesia assessment using the Glasgow-Edinburgh throat scale (GETS). The incidence and severity of pharyngeal paraesthesia symptoms were compared between the groups. RESULTS: A total of 280 patients who snored or were suspected of having OSA and 35 healthy, age-matched controls were recruited. The total pharyngeal paraesthesia symptom score was significantly higher in the OSA group than in the healthy group (12 [5, 23] vs. 3 [0, 9]; p < 0.001). The most frequent pharyngeal paraesthesia symptoms in the snore patients were Q7 (catarrh down the throat) and Q3 (discomfort/irritation in the throat), which are related to the irritability of the throat. The incidence of Q7 (OSA, 58% vs. controls, 14%; χ2 = 23.66; p < 0.001), Q3 (OSA, 46% vs. controls, 3%; χ2 = 23.07; p < 0.001), Q1 (feeling of something stuck in the throat; OSA, 33% vs. controls, 6%; χ2 = 11.00; p = 0.001), Q6 (swelling in the throat; OSA, 31% vs. controls, 0%; χ2 = 14.53; p < 0.001), Q9 (want to swallow all the time; OSA, 20% vs. controls, 6%; χ2 = 6.28; p = 0.012), Q5 (throat closing off; OSA, 24% vs. controls, 6%; χ2 = 6.16; p = 0.013), and Q2 (pain in the throat; OSA, 23% vs. controls, 6%; χ2 = 5.32; p = 0.021) was significantly higher in the OSA group than in the controls CONCLUSIONS: Patients with obstructive sleep apnoea have higher pharyngeal paraesthesia symptoms scores and tend to have irritated throats compared to healthy controls. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03506178.


Assuntos
Parestesia/fisiopatologia , Doenças Faríngeas/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Ronco/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Faringite/fisiopatologia , Polissonografia
4.
BMC Cancer ; 20(1): 794, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838760

RESUMO

BACKGROUND: Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. METHODS: The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. RESULTS: OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. CONCLUSIONS: Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Laríngeas/genética , MicroRNAs/metabolismo , Fatores de Transcrição Otx/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Laringectomia , Laringe/patologia , Laringe/cirurgia , Masculino , Camundongos , Pessoa de Meia-Idade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
J Cell Mol Med ; 23(12): 8280-8291, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31578816

RESUMO

Since the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) remains poor, identification of miRNA as a potential prognostic biomarker for HSCC may help improve personalized therapy. In the 2 cohorts with a total of 511 patients with HSCC (discovery: N = 372 and validation: N = 139) after post-operative radiotherapy, we used miRNA microarray and qRT-PCR to screen out the significant miRNAs which might predict survival. Associations of miRNAs and the signature score of these miRNAs with survival were performed by Kaplan-Meier survival analysis and multivariate Cox hazard model. Among 9 candidate, miRNAs, miR-200a-3p, miR-30b-5p, miR-3161, miR-3605-5p, miR-378b and miR-4451 were up-regulated, while miR-200c-3p, miR-429 and miR-4701 were down-regulated after validation. Moreover, the patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly worse overall survival (OS) and disease-specific survival (DSS) than did those with low expression (log-rank P < .05). Patients with a high-risk score had significant worse OS and DSS than those with low-risk score. Finally, after adjusting for other important prognostic confounders, patients with high expression of miR-200a-3p, miR-30b-5p and miR-4451 had significantly high risk of overall death and death owing to HSCC and patients with a high-risk score has approximately 2-fold increased risk in overall death and death owing to HSCC compared with those with a low-risk score. These findings indicated that the 3-miRNA-based signature may be a novel independent prognostic biomarker for patients given surgery and post-operative radiotherapy, supporting that these miRNAs may jointly predict survival of HSCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/radioterapia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hipofaríngeas/radioterapia , MicroRNAs/genética , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Humanos , Neoplasias Hipofaríngeas/cirurgia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
BMC Cancer ; 19(1): 840, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455288

RESUMO

BACKGROUND: Advanced stage laryngeal squamous cell carcinoma (LSCC) presents a poor prognosis; thus, there is a great need to identify novel prognostic molecular markers. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is thought to be a novel prognostic factor in several cancers, but its role in LSCC remains unknown. Cancer stem cells (CSCs) are responsible for most instances of tumor recurrence and the development of drug resistance and have been proven to be present in head and neck cancers. Our preliminary study indicated that PLOD2 was elevated in LSCC tissues; therefore, we hypothesized that PLOD2 is related to the prognosis of LSCC patients and aimed to explore the role and underlying mechanism of PLOD2 in LSCC. METHODS: We validated the prognostic role of PLOD2 in 114 LSCC patients by immunohistochemistry. Stable PLOD2-overexpressing Hep-2 and FaDu cells were established and assessed by molecular biology and biochemistry methods both in vitro and in vivo. RESULTS: We confirmed that PLOD2 overexpression was correlated with poor prognosis in LSCC patients. PLOD2 overexpression strengthened the CSC-like properties of Hep-2 and FaDu cells, activated the Wnt signaling pathway and conferred drug resistance in LSCC in vitro and in vivo. CONCLUSIONS: We found that PLOD2 could serve as a prognostic marker in patients with LSCC and confer drug resistance in LSCC by increasing CSC-like traits; in addition, a Wnt-responsive CSC pathway was identified.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Laríngeas/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Prognóstico , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Environ Sci Technol ; 53(16): 9341-9351, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31343877

RESUMO

Since the publication of the Report of the World Commission on Environment and Development in 1987, there have been numerous studies on sustainability. These studies created new knowledge and tools for understanding and managing complex coupled human and natural systems. In this Critical Review, we used a topic modeling technique to analyze 12 526 peer-reviewed research articles and identify the research questions and the approaches that were used or developed in each of the studies. These approaches were then classified by function. The analysis revealed twenty-three categories of research questions and seven functional approach classes-design for sustainability, modeling of complexity, sustainability indicators, life cycle sustainability assessment, decision making support, sustainability governance, and engagement-each of which is described here as an individual approach or tool within a larger sustainability toolbox. The article concludes with a discussion about using the sustainability toolbox as an integrated knowledge system to support transdisciplinary study and decision-making.


Assuntos
Conservação dos Recursos Naturais , Tomada de Decisões , Humanos
8.
J Environ Manage ; 246: 564-574, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202021

RESUMO

It is an urgent challenge to coordinate industrialization and air quality in China since the rapid industrialization over the past forty years caused serious air pollution. In this paper, we measured the industrialization levels of the 31 regions in China from 2003 to 2017 as a sum of per capita gross domestic product (GDP), urban population (% of total), tertiary vs. secondary industry output ratio, non-agricultural output value (% of GDP), non-agricultural employment proportion, and the proportion of added value of manufacturing in the total added value of commodity. We measured air quality as a sum of annual SO2, NO2 and PM10 concentrations. In general, the industrialization level continuously increased while air pollution was reduced in spite of some fluctuations in China. Our results show air pollution presented N-shape relations with the industrialization level in China in the periods from 2003 to 2008, 2009 to 2013, and 2014 to 2017. Air pollution increases as the industrialization occurs but later deceases as the industrialization level improves. However, air pollution rebounds as the industrialization moves further but this rebound became weaker in recent years. With the association rule mining, we identified ranges of the six indicators for industrialization associated with good and poor air quality, respectively. Using industrialization indicators associated with poor air quality as references, we pointed out differentiated strategies for regions to coordinate the industrialization and air quality protection.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , China , Desenvolvimento Industrial , Material Particulado
9.
Mol Carcinog ; 57(3): 361-369, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29073727

RESUMO

Given the crucial role of Mouse double minute 4 (MDM4) oncoprotein in p53 pathway, single nucleotide polymorphisms (SNPs) could serve as such biomarkers for prediction of SCCOP recurrence. Thus, we investigated associations between three tagging putatively functional variants of MDM4, two in the 3' untranslated region of 3' UTR [rs11801299 (NC_000001.10:g.204529084G>A) and rs10900598(NC_000001.10:g.204525568G>T)] and one in intron 1 [rs1380576(NC_000001.10:g.204488278G>C)], and recurrence risk of SCCOP in 1,008 incident patients. A log-rank test and multivariable Cox models were used to assess associations. Patients with MDM4-rs10900598 GT/TT had a worse disease-free survival (DFS) compared with corresponding GG genotype, while those with rs11801299 AG/AA genotypes had a lower recurrence risk than the cases with rs11801299 GG genotype (both log-rank, P < 0.001). Multivariable analysis showed that significantly different recurrence risk were found among patients with MDM4-rs10900598 GT/TT and rs11801299 AG/AA variant genotypes (HR, 2.0, 95% CI, 1.4-2.9 and HR, 0.4, 95% CI, 0.3-0.6, respectively) compared with their corresponding common homozygous genotypes. Furthermore, after combining the risk genotypes of the three SNPs, patients among low-risk group had a significantly lower risk of SCCOP recurrence than those in high-risk group (HR, 0.2, 95% CI, 0.1-0.3). The risk for both individual SNPs or combined risk genotypes was restricted to HPV-positive SCCOP patients. Our findings suggest that the MDM4 polymorphisms may, individually or in combination, confer an independent risk of SCCOP recurrence, particularly in HPV-positive SCCOP patients. However, larger studies are needed to validate our findings.


Assuntos
Carcinoma de Células Escamosas/genética , Recidiva Local de Neoplasia/genética , Proteínas Nucleares/genética , Neoplasias Orofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Carcinoma de Células Escamosas/virologia , Proteínas de Ciclo Celular , Feminino , Papillomavirus Humano 16/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/virologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia
10.
Carcinogenesis ; 38(4): 432-438, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334093

RESUMO

Genetic polymorphisms at miRNA-binding sites may affect miRNA-mediated gene regulation. Thus, miRNA-binding site polymorphisms in double-strand break (DSB) repair genes may affect DNA repair capacity, which in turn could affect cancer prognosis. To determine whether miRNA-binding site polymorphisms in DSB repair genes are associated with the risk of recurrence of squamous cell carcinoma of the non-oropharynx (SCCNOP), we used a log-rank test and multivariable Cox models to evaluate the associations between miRNA-binding site polymorphisms in DSB repair genes and SCCNOP recurrence. Compared with patients without common homozygous genotypes, patients with the variant genotypes of ATM rs227091, LIG3 rs4796030, and RAD51 rs7180135 had significantly better disease-free survival (DFS) (log-rank P = 0.046, 0.002, and 0.041, respectively) and lower risk of disease recurrence [HR (95% CI) = 0.7 (0.6-0.9), 0.6 (0.5-0.9), and 0.7 (0.6-0.9), respectively]. Furthermore, patients with the variant genotypes of these 3 polymorphisms had significantly lower recurrence risk than those without common homozygous genotypes did [HR = 0.3 (95% CI = 0.2-0.7)]. Among patients who received chemoradiation, those with the individual or combined variant genotypes of the three polymorphisms had a significantly lower risk of disease recurrence than those with the individual or combined common homozygous genotypes did. The individual or combined variant genotypes of the ATM rs227091, LIG3 rs4796030, and RAD51 rs7180135 polymorphisms significantly modify the risk of SCCNOP recurrence, particularly for patients treated with chemoradiation. Future prospective studies with larger sample sizes are warranted to validate these findings to enable more effective personalized treatment for SCCNOP patients.


Assuntos
Sítios de Ligação/genética , Carcinoma de Células Escamosas/genética , Reparo do DNA/genética , Predisposição Genética para Doença/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Polimorfismo de Nucleotídeo Único/genética , Quimiorradioterapia/métodos , Quebras de DNA de Cadeia Dupla , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Risco
11.
Int J Cancer ; 141(7): 1355-1364, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28646528

RESUMO

The incidence of squamous cell carcinoma of the oropharynx (SCCOP) continues to rise because of increasing rates of human papillomavirus (HPV) infection. Inherited polymorphisms in DNA repair pathways may influence the risk of SCCOP development and the prognosis of SCCOP. We sought to determine whether polymorphisms in microRNA (miRNA)-binding sites within 3'-untranslated regions (3'UTRs) of genes in DNA repair pathways modulate the risk of SCCOP recurrence. We evaluated the associations between nine such polymorphisms and SCCOP recurrence in 1,008 patients with incident SCCOP using the log-rank test and multivariable Cox models. In an analysis of all the patients, patients with variant genotypes of BRCA1 rs12516 and RAD51 rs7180135 had better disease-free survival (log-rank, p = 0.0002 and p = 0.0003, respectively) and lower risk of SCCOP recurrence (hazard ratio [HR], 0.5, 95% confidence interval [CI], 0.2-0.8, and HR, 0.5, 95% CI, 0.3-0.9, respectively) than patients with common homozygous genotypes of the two polymorphisms after multivariable adjustment. Moreover, in tumor HPV16-positive patients, patients with variant genotypes of the same two polymorphisms also had better disease-free survival (log-rank, p = 0.004 and p = 0.003, respectively) and lower recurrence risk (HR, 0.2, 95% CI, 0.1-0.6, and HR, 0.2, 95% CI, 0.0-0.7, respectively) than patients with common homozygous genotypes of the two polymorphisms. No such significant associations were found for other polymorphisms. These findings support significant roles of BRCA1 rs12516 and RAD51 rs7180135 in modifying the risk of recurrence of SCCOP, particularly HPV16-positive SCCOP. However, these results must be validated in larger studies.


Assuntos
Carcinoma de Células Escamosas/genética , Reparo do DNA/genética , Genes BRCA1 , Variação Genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Neoplasias Orofaríngeas/genética , Rad51 Recombinase/genética , Regiões 3' não Traduzidas/genética , Sítios de Ligação/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Genótipo , Papillomavirus Humano 16 , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/virologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais
12.
Environ Manage ; 57(2): 498-507, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26404432

RESUMO

Rapid urbanization in China during the first decade of the twenty first century has brought about profound environmental changes at citywide and regional scales. In this paper, we present a comprehensive set of indicators and put forward a new evaluation method for measuring environmental impacts of urbanization from 2000 to 2010. We compared these impacts among 286 cities in mainland China and found that the overall quantity of pollutant discharge decreased as cities became more economically developed during the years 2000-2010. However, larger and denser cities, and wealthier cities in the eastern part of China tended to have larger quantities of pollutant discharge, resource consumption, and changes in land use (i.e., expansion of the built environment). The discharge increase occurred despite these cities having increased their investment in pollution control and construction of municipal environmental infrastructure. The negative impact from the intensity of pollutant discharge (i.e., discharge per unit of economic output) was generally less in more developed cities, although this was not always the case. Some cities, such as resource-based cities and old industrial cities, had both larger quantities of pollutant discharge and greater pollution intensity compared to other types of cities, indicating that environmental impacts did not necessarily decrease with increasing urbanization. The results of this study provide a promising basis for decision-making to reduce the impacts for different types of cities in the decades to come.


Assuntos
Conservação dos Recursos Naturais , Meio Ambiente , Urbanização , China , Cidades , Poluição Ambiental , Indústrias
13.
J Neurosci ; 34(49): 16166-79, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25471559

RESUMO

The MET receptor tyrosine kinase (RTK), implicated in risk for autism spectrum disorder (ASD) and in functional and structural circuit integrity in humans, is a temporally and spatially regulated receptor enriched in dorsal pallial-derived structures during mouse forebrain development. Here we report that loss or gain of function of MET in vitro or in vivo leads to changes, opposite in nature, in dendritic complexity, spine morphogenesis, and the timing of glutamatergic synapse maturation onto hippocampus CA1 neurons. Consistent with the morphological and biochemical changes, deletion of Met in mutant mice results in precocious maturation of excitatory synapse, as indicated by a reduction of the proportion of silent synapses, a faster GluN2A subunit switch, and an enhanced acquisition of AMPA receptors at synaptic sites. Thus, MET-mediated signaling appears to serve as a mechanism for controlling the timing of neuronal growth and functional maturation. These studies suggest that mistimed maturation of glutamatergic synapses leads to the aberrant neural circuits that may be associated with ASD risk.


Assuntos
Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/metabolismo , Dendritos/metabolismo , Espinhas Dendríticas/fisiologia , Neurogênese/fisiologia , Proteínas Proto-Oncogênicas c-met/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/fisiologia , Animais , Região CA1 Hipocampal/enzimologia , Região CA1 Hipocampal/crescimento & desenvolvimento , Camundongos , Mutação , Neurônios/citologia , Neurônios/fisiologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-met/genética , Receptores de AMPA/metabolismo , Transdução de Sinais/fisiologia
14.
BMC Cancer ; 15: 743, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26482899

RESUMO

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) has been shown to be associated with prognosis in various solid tumors. This study aimed to evaluate the prognostic role of NLR in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 141 LSCC patients were retrospectively reviewed. Patients' demographics were analyzed along with clinical and pathologic data. The optimal cutoff value of NLR was determined using receiver operating characteristic (ROC) curve analysis. The impact of the NLR and other potential prognostic factors on disease-free survival (DFS) and overall survival (OS) was assessed using the Kaplan-Meier method and multivariate Cox regression analysis. RESULTS: The optimal cutoff value of the NLR was 2.17. In the NLR ≤ 2.17 group, the 1-, 3-, and 5-year DFS rates were 88.2, 73.9 and 69.1 %, respectively, while in the NLR > 2.17 group, the DFS rates were 83.0, 54.6 and 49.2 %, respectively. Correspondingly, the 1-, 3-, and 5-year OS rates were 98.9, 85.1 and 77.4 % in the NLR ≤ 2.17 group and 97.9, 63.8 and 53.3 % in the NLR > 2.17 group, respectively. The multivariate Cox proportional hazard model analysis showed that NLR > 2.17 was a prognostic factor for both DFS [hazard ratio (HR) = 1.869; 95 % confidence interval (CI) 1.078-3.243; P = 0.026] and OS (HR =2.177; 95 % CI 1.208-3.924; P = 0.010). CONCLUSION: Our results showed that elevated preoperative NLR was an independent predictor of poor prognosis for patients with LSCC after surgical resection.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , China/epidemiologia , Feminino , Humanos , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida/tendências
15.
Radiol Med ; 120(12): 1153-69, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25981380

RESUMO

PURPOSE: This meta-analysis compared the efficacy of laryngectomy and three larynx-preservation treatments in patients with advanced laryngeal cancer. MATERIALS AND METHODS: Medline, Cochrane, EMBASE and Google Scholar databases were searched (until May 5, 2014) for studies that evaluated total laryngectomy followed by radiation and three larynx-preserving strategies in patients with advanced laryngeal cancer. The outcomes assessed were the 2- to 5-year overall survival (OS), disease-free survival (DFS), and laryngectomy-free survival (LFS) RESULTS: The search identified ten studies which were used for the meta-analysis (N = 2013 patients). The meta-analysis found that among different treatments, RT alone was associated with the highest rate of OS (71.6 %), DFS (57.8 %), and LFS (79.0 %). OS was similar among the following treatments: laryngectomy→RT vs. CT→RT [P = 0.402]; RT+CT vs. RT alone [P = 0.440]; and RT+CT vs CT→RT [P = 0.588]. DFS rate was higher in patients receiving laryngectomy→RT than CT→RT (P = 0.001) and was similar for RT+CT compared with CT→RT (P = 0.590). CONCLUSION: These findings suggest that of the larynx-preserving treatments, RT alone was associated with highest rates of OS, DFS, and LFS in patients with locally advanced cancer of the larynx and hypopharynx. Laryngectomy provided a better rate of DFS than CT and RT, but OS were similar across the different larynx-preserving treatments and laryngectomy.


Assuntos
Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Laringectomia , Idoso , Intervalo Livre de Doença , Humanos , Neoplasias Laríngeas/mortalidade , Pessoa de Meia-Idade
16.
Nat Commun ; 15(1): 3753, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704394

RESUMO

The European ammonia industry emits 36 million tons of carbon dioxide annually, primarily from steam methane reforming (SMR) hydrogen production. These emissions can be mitigated by producing hydrogen via water electrolysis using dedicated renewables with grid backup. This study investigates the impact of decarbonization targets for hydrogen synthesis on the economic viability and technical feasibility of retrofitting existing European ammonia plants for on-site, semi-islanded electrolytic hydrogen production. Results show that electrolytic hydrogen cuts emissions, on average, by 85% (36%-100% based on grid price and carbon intensity), even without enforcing emission limits. However, an optimal lifespan average well-to-gate emission cap of 1 kg carbon dioxide equivalent (CO2e)/kg H2 leads to a 95% reduction (92%-100%) while maintaining cost-competitiveness with SMR in renewable-rich regions (mean levelized cost of hydrogen (LCOH) of 4.1 euro/kg H2). Conversely, a 100% emissions reduction target dramatically increases costs (mean LCOH: 6.3 euro/kg H2) and land area for renewables installations, likely hindering the transition to electrolytic hydrogen in regions with poor renewables and limited land. Increasing plant flexibility effectively reduces costs, particularly in off-grid plants (mean reduction: 32%). This work guides policymakers in defining cost-effective decarbonization targets and identifying region-based strategies to support an electrolytic hydrogen-fed ammonia industry.

17.
Environ Sci Technol ; 47(19): 10744-52, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23815440

RESUMO

Low-impact development (LID) is an innovative stormwater management strategy that restores the predevelopment hydrology to prevent increased stormwater runoff from land development. Integrating LID into residential subdivisions and increasing population density by building more compact living spaces (e.g., apartment homes) can result in a more sustainable city by reducing stormwater runoff, saving infrastructural cost, increasing the number of affordable homes, and supporting public transportation. We develop an agent-based model (ABM) that describes the interactions between several decision-makers (i.e., local government, a developer, and homebuyers) and fiscal drivers (e.g., property taxes, impact fees). The model simulates the development of nine square miles of greenfield land. A more sustainable development (MSD) scenario introduces an impact fee that developers must pay if they choose not to use LID to build houses or apartment homes. Model simulations show homeowners selecting apartment homes 60% or 35% of the time after 30 years of development in MSD or business as usual (BAU) scenarios, respectively. The increased adoption of apartment homes results from the lower cost of using LID and improved quality of life for apartment homes relative to single-family homes. The MSD scenario generates more tax revenue and water savings than does BAU. A time-dependent global sensitivity analysis quantifies the importance of socioeconomic variables on the adoption rate of apartment homes. The top influential factors are the annual pay rates (or capital recovery factor) for single-family houses and apartment homes. The ABM can be used by city managers and policymakers for scenario exploration in accordance with local conditions to evaluate the effectiveness of impact fees and other policies in promoting LID and compact growth.


Assuntos
Conservação dos Recursos Naturais/métodos , Habitação/economia , Modelos Teóricos , Reforma Urbana/métodos , Conservação dos Recursos Naturais/economia , Motivação , Chuva , Engenharia Sanitária , Reforma Urbana/economia
18.
Eur Arch Otorhinolaryngol ; 270(3): 1027-34, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23241822

RESUMO

The study aimed to compare the survival rate and functional outcome of supracricoid partial laryngectomy cricohyoidoepiglottopexy (SCPL-CHEP) and vertical partial laryngectomy (VPL) in the treatment of glottic carcinoma. Thirty-nine patients underwent SCPL-CHEP and 45 patients underwent VPL between 2002 and 2007. Post-operative clinical staging were performed according to the UICC staging criteria (2002). The primary endpoints were survival time and recurrence rate. The secondary endpoints were the laryngeal functions including pronunciation, swallowing, and respiration. Overall, the estimated mean survival time was 75.6 months. There was no significant difference in survival times between the two groups (P = 0.496). The SCPL-CHEP group had a significantly lower post-operative local recurrence rate than VPL group (2.6 vs. 17.8 %, P = 0.033). Significantly longer nasogastric tube removal (22 vs. 14 days, P < 0.001) and tracheostomy decannulation (38.5 vs. 15 days, P < 0.001) times in SCPL-CHEP group was observed with the VPL group, respectively. Significantly higher aspiration rates were observed at 3, 6, and 12 months in the SCPL-CHEP group compared with the VPL group (P < 0.001, P < 0.001, P < 0.05, respectively). Although the survival rate was not significantly different between the two groups, the local regional control rate and organ preservation in the supracricoid partial laryngectomy cricohyoidoepiglottopexy group was better than those observed in the vertical partial laryngectomy group.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Recidiva Local de Neoplasia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Glote , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento
19.
Water Res ; 240: 120063, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37210969

RESUMO

This study reports, for the first time, the role of shoreward transport of organic matter (OM) from subsurface chlorophyll maximum (SCM) in triggering hypoxia off the Pearl River Estuary (PRE, an outstanding example of typical estuary-shelf systems) based on field measurements. Compared to frequently observed hypoxia driven by surface eutrophication and terrestrial OM during large river discharge, we demonstrate that the upslope-transported SCM played a critical role in forming offshore hypoxia during low river discharge. Together with the plume-sourced OM trapped below the surface plume front, upslope-transported OM originating from the SCM accumulated underneath the pycnocline and consumed dissolved oxygen (DO), enhancing the bottom hypoxia. The DO consumption induced by the SCM-associated OM was estimated to contribute ∼ 26% (±23%) of the DO depletion under the pycnocline. Based on coherent and consistent physical and biogeochemical evidence and reasoning, this study reveals the contribution of SCM to bottom hypoxia off the PRE, which is unreported and likely occurs in other coastal hypoxic systems.


Assuntos
Monitoramento Ambiental , Estuários , Humanos , Clorofila , Hipóxia , Oxigênio/análise , Rios
20.
Sci Total Environ ; 859(Pt 1): 160214, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36395837

RESUMO

Long-term planning of urban drainage systems aimed at maintaining the sustainability of urban hydrology remains challenging. In this study, an innovative multi-stage planning framework involving two adaptation pathways for optimizing hybrid low impact development and grey infrastructure (LID-GREI) layouts in opposing chronological orders was explored. The Forward Planning and Backward Planning are adaptation pathways to increase LID in chronological order based on the initial development stage of an urban built-up area and reduce LID in reverse chronological order based on the final development stage, respectively. Two resilience indicators, which considered potential risk scenarios of extreme storms and pipeline failures, were used to evaluate the performance of optimized layouts when land-use changed and evolved over time. Compared these two pathways, Forward Planning made the optimized layouts more economical and resilient in most risk scenarios when land-use changed, while the layouts optimized by Backward Planning showed higher resilience only in the initial stage. Furthermore, a decentralized scheme in Forward Planning was chosen as the optimal solution when taking costs, reliability, resilience, and land-use changes into an overall consideration. Nevertheless, this kind of reverse optimization order offers a novel exploration in planning pathways for discovering the alternative optimization schemes. More comprehensive solutions can be provided to decision-makers. The findings will shed a light on the exploration of optimized layouts in terms of spatial configuration and resilience performance in response to land-use changes. This framework can be used to support long-term investment and planning in urban drainage systems for sustainable stormwater management.


Assuntos
Aclimatação , Hidrologia , Reprodutibilidade dos Testes
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