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Sudden cardiac death (SCD) remains a major cause of global mortality. In addition to modern interventions, botanical folk medicines have long been used to treat cardiovascular disease, although the efficacy and underlying mechanisms are often unresolved. Aloperine, a bioactive quinolizidine alkaloid isolated from Sophora alopecuroides plants, exhibits antioxidant, anti-inflammatory, antitumor, and vasorelaxant properties, but possible antiarrhythmic effects of aloperine in SCD are unclear. Here, we examined whether aloperine protects against ischemia and reperfusion injury-associated lethal ventricular arrhythmia and sudden cardiac death. Rats were divided into sham, control, and aloperine groups, and reperfusion-provoked ventricular arrhythmogenesis, cardiac damage markers, and signaling pathways quantified following left main coronary artery ischemia and reperfusion. In vitro studies of effects of aloperine on hERG and Kv4.3 cardiac voltage-gated potassium (Kv) channels were performed using two-electrode voltage clamp analysis of cloned channels expressed in Xenopus laevis oocytes. Aloperine pretreatment (10 mg/kg) did not affect baseline cardiac electrical stability; yet, it reduced ventricular arrhythmogenesis and susceptibility to SCD (mortality rate: control: 64.3%; aloperine: 0%) induced by reperfusion injury. Aloperine also reduced serum levels of LDH, CK-MB, α-HBDH, and cTnI post-I/R, and stimulated phosphorylation of ventricular ERK1/2 and STAT-3, which are key components of RISK and SAFE signaling pathways. Inhibition of either ERK1/2 (with U0126) or STAT-3 (with Ag490) abolished aloperine-induced anti-arrhythmic effects and ERK1/2 and STAT-3 phosphorylation. Interestingly, while aloperine (100 µM) had no effect on cloned Kv4.3 activity, aloperine (1 µM and up) negative-shifted the voltage dependence of hERG activation by ~10 mV and increased peak hERG current by 35%. Thus, aloperine exerts striking anti-arrhythmic effects against myocardial ischemia and reperfusion injury-induced severe lethal ventricular arrhythmia and sudden cardiac death via the ERK1/2/STAT-3 signaling pathway, with potential additional contribution from increased cardiac myocyte repolarization capacity via augmented hERG activity.
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Alcaloides , Traumatismo por Reperfusão Miocárdica , Ratos , Animais , Antiarrítmicos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Morte Súbita Cardíaca/prevenção & controle , Miócitos Cardíacos/metabolismo , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/prevenção & controle , Piperidinas/farmacologia , Alcaloides/farmacologiaRESUMO
OBJECTIVE: The SGLT2 inhibitor, canagliflozin, not only reduces glycemia in patients with type 2 diabetes but also exerts cardioprotective effects in individuals without diabetes. However, its potential beneficial effects in cardiac arrest have not been characterized. The purpose of this study was to examine the protective effect of canagliflozin pretreatment on postresuscitation-induced cardiac dysfunction in vivo. METHODS: Male C57/BL6 mice were randomized to vehicle (sham and control) or canagliflozin treatment groups. All mice except for the sham-operated mice were subjected to potassium chloride-induced cardiac arrest followed by chest compressions and intravenous epinephrine for resuscitation. Canagliflozin therapy efficacies were evaluated by electrocardiogram, echocardiography, histological analysis, inflammatory response, serum markers of myocardial injury, protein phosphorylation analysis, and immunohistological assessment. RESULTS: Canagliflozin-pretreated mice exhibited a higher survival rate (P < 0.05), a shorter return of spontaneous circulation (ROSC) time (P < 0.01) and a higher neurological score (P < 0.01 or P < 0.001) than control mice after resuscitation. Canagliflozin was effective at improving cardiac arrest and resuscitation-associated cardiac dysfunction, indicated by increased left ventricular ejection fraction and fractional shortening (P < 0.001). Canagliflozin reduced serum levels of LDH, CK-MB and α-HBDH, ameliorated systemic inflammatory response, and diminished the incidence of early resuscitation-induced arrhythmia. Notably, canagliflozin promoted phosphorylation of cardiac STAT-3 postresuscitation. Furthermore, pharmacological inhibition of STAT-3 by Ag490 blunted STAT-3 phosphorylation and abolished the cardioprotective actions of canagliflozin. CONCLUSIONS: Canagliflozin offered a strong cardioprotective effect against cardiac arrest and resuscitation-induced cardiac dysfunction. This canagliflozin-induced cardioprotection is mediated by the STAT-3-dependent cell-survival signaling pathway.
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Cardiomiopatias , Reanimação Cardiopulmonar , Diabetes Mellitus Tipo 2 , Parada Cardíaca , Animais , Humanos , Masculino , Camundongos , Canagliflozina/farmacologia , Modelos Animais de Doenças , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Torsion of the spermatic cord is a urological emergency that must be treated immediately with surgery, yet detorsion of the testis can cause testicular tissue damage because of ischemia-reperfusion (I/R) injury. I/R injury is a complex pathophysiological process that may affect the functions of distant organs. Here, we examined whether testicular torsion/detorsion (TT) causes myocardial dysfunction. We next investigated the potential beneficial effect and underlying mechanisms of remote ischemic postconditioning (RIPost) on cardiac function after testicular torsion/detorsion. Male Sprague-Dawley rats were assigned to three different sets of experimental groups. Testicular I/R was induced by rotating the right testis to 1080° clockwise for 3 h followed by 3 h of detorsion. RIPost was induced at the onset of testicular detorsion by four cycles of 5-min bilateral femoral artery occlusion with 5-min reperfusion. Cardiac function was determined postdetorsion, and the cardioprotective effect of RIPost was examined. Testicular torsion/detorsion-treated rats had reduced serum testosterone levels, impaired systemic hemodynamics, elevated systemic inflammatory responses, and increased serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), α-hydroxybutyrate dehydrogenase (α-HBDH), and cardiac troponin I (cTnI). However, RIPost attenuated remote heart dysfunction induced by testicular torsion/detorsion. Furthermore, RIPost enhanced the phosphorylation of ventricular signal transducer and activator of transcription (STAT)-3, which is a key component of the survivor activating factor enhancement (SAFE) signaling pathways. Inhibition of STAT-3 with Ag490 abolished the RIPost-induced cardioprotection and STAT-3 phosphorylation. Testicular torsion followed by detorsion may cause impaired cardiac function in rats. RIPost effectively attenuates this remote cardiac dysfunction. RIPost-induced protective effects may be mediated by the STAT-3 signaling pathway.
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Pós-Condicionamento Isquêmico , Traumatismo por Reperfusão , Torção do Cordão Espermático , Humanos , Ratos , Masculino , Animais , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/metabolismo , Torção do Cordão Espermático/prevenção & controle , Ratos Sprague-Dawley , Pós-Condicionamento Isquêmico/efeitos adversos , Testículo/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismoRESUMO
Deep Learning (DL) open sources libraries such as TensorFlow, Keras, and PyTorch have been widely and successfully applied for many applications in a forward model. We have developed the DL radiative transfer model over Oceans under a clear-sky condition. However, the derived physical model from the DL forward model has difficulties in predicting physical properties such as the Jacobian, because multiple solutions can fit the forward model results during the deep learning training process. The Jacobian model in a radiative transfer can calculate radiance sensitivities on geophysical parameters, which are required by satellite radiance assimilation in support of weather forecasts and for retrieving environmental data records. In this study, we introduce a physics constraint into our deep learning training for deriving the forward model that retains right physics. With this physics constraint, the radiance sensitivities are well captured by this new DL radiative transfer.
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PURPOSE: To explore the effectiveness of flexible bronchoscopy in pediatric Mycoplasma pneumoniae pneumonia (MPP). METHODS: This retrospective cohort study included children with MPP admitted between 2016 and 2019 in Shanghai. Tracheobronchial manifestations, etiologic findings, therapeutic effect, and health-economic indicators were assessed in bronchoscopy (plus bronchoalveolar lavage (BAL)) and non-bronchoscopy group. We used propensity-score matching and multivariable logistic regression to investigate the effect of bronchoscopy and BAL on disease recovery. RESULTS: In 900 children with MPP, 24/278 (8.6%) of those who underwent bronchoscopy had sputum plugs. Coinfection rate was four-fold enhanced by BAL (19.6% vs. 4.5%, p < 0.01) in patients with severe MPP (SMPP) and nearly doubled (10.8% vs. 5.9%, p = 0.03) in those without SMPP, compared with no BAL. Total of 224 (24.9%) patients had multilobar consolidation; after BAL, a significantly shorter lesion-resolution duration was observed on imaging (OR: 0.2, 95% CI: 0.0-0.7). However, longer fever duration (OR: 2.8, 95% CI: 1.7-4.8), hospital stay (OR: 3.1, 95% CI: 1.9-5.1), and higher costs were found in the bronchoscopy group than in the non-bronchoscopy group. CONCLUSIONS: Through BAL, coinfection may explain one-fifth of causes for SMPP. Bronchoscopy with BAL may increase the detection rate of pathogen and resolve pulmonary lesions in patients with multilobar consolidation. IMPACT: Flexible bronchoscopy with bronchoalveolar lavage is of great assistance in the timely detection of coinfection, sputum plug and inflammatory polyps in children with Mycoplasma pneumoniae pneumonia (MPP), and improves the recovery of lung damage in MPP patients with multilobar consolidation. This study provides new insights into the indications of flexible bronchoscopy for the diagnosis and treatment of pediatric patients with MPP.
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Coinfecção , Pneumonia por Mycoplasma , Humanos , Criança , Mycoplasma pneumoniae , Estudos Retrospectivos , China , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/terapiaRESUMO
OBJECTIVE: To establish the predicted value of pulmonary function determined by impulse oscillometry (IOS) in children (4-17 years old) in China. METHODS: A total of 6270 healthy children aged 4-17 years in China were included. The Master Screen IOS pulmonary function device (Jaeger Co, Germany) was used to detect the respiratory impedance (Zrs), resonant frequency (Fres), respiratory system resistance (Rrs) and respiratory system reactance (Xrs) at various oscillation frequencies, and the indices above were analysed. Stepwise multivariate regression was used to establish the regression equation of related parameters of IOS in different sexes, ages, height, and weight. RESULTS: The differences in the main IOS parameters between different age stages were statistically significant regardless of sex (P < 0.05). The stepwise multivariate regression analysis showed that IOS parameters were related to height, age, and weight, and most IOS parameters were most closely related to height (the absolute value of the regression coefficient was the largest). With increasing age and height, the values of Z5, R5, R20, R5-R20, and Fres decreased, while the value of X5 increased. Through height, age, and weight, we obtained the normal predicted values equation of children's IOS parameters. Compared with the other reference equations, our reference equation is more suitable for Chinese children. CONCLUSIONS: The study revealed the reference values of IOS parameters in healthy Chinese children. In the evaluation of results for lung function measurements, this predicted value equation is more consistent with the characteristics of Chinese children than other reference equations. CLINICAL TRIAL: ChiCTR: 1800019029.
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Pulmão , Adolescente , Criança , Pré-Escolar , China , Humanos , Oscilometria/métodos , Valores de Referência , Testes de Função Respiratória/métodos , EspirometriaRESUMO
BACKGROUND: No reliable biological marker for the diagnosis of asthma in younger children is currently available. In this study, we analyzed the differences in basophil activation test (BAT) results among children with recurrent wheezing episodes who had different asthma outcomes. RESULTS: A prospective cohort study was conducted in children aged under 5 years who visited our pediatric respiratory clinic and ward for wheezing. After enrollment, the participants provided samples for a CD63-based BAT performed using an inhalant allergen mixture as a stimulant. Histories of personal allergic diseases and family allergic diseases were evaluated by using a questionnaire. All participants were followed up for 2 years, and their asthma outcomes were evaluated at the end of the follow-up period. The correlation between the BAT results and asthma outcomes was analyzed. Of the 45 originally enrolled children, 38 completed both the follow-up and a BAT. After stimulation with the inhalant mixture, the CD63 expression on basophils and the rate of positive CD63-based BAT results in children diagnosed with asthma were both significantly higher than those in children who were not diagnosed with asthma (p < 0.05 and p < 0.01, respectively). For the prediction of asthma, the positive predictive value and negative predictive value of CD63-based BAT was 71.8 and 69.2%, respectively. The positive likelihood ratio and negative likelihood ratio of CD63-based BAT were 1.70 and 0.3, respectively. CONCLUSIONS: Our pilot study indicates that CD63-based BAT has potential clinical value for predicting asthma outcome in young children with wheezing episodes.
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Asma/diagnóstico , Basófilos/imunologia , Sons Respiratórios/diagnóstico , Alérgenos/imunologia , Asma/imunologia , Basófilos/metabolismo , Pré-Escolar , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Masculino , Avaliação de Resultados da Assistência ao Paciente , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Sons Respiratórios/imunologia , Tetraspanina 30/metabolismoRESUMO
NEW FINDINGS: What is the central question of this study? Can remote limb ischaemic conditioning produce cardioprotection in rats with testicular ischaemia-reperfusion injury? What is the main finding and its importance? Testicular ischaemia-reperfusion (TI/R)-injured rats were predisposed to myocardial reperfusion-induced atrioventricular block. Remote limb ischaemia preconditioning and postconditioning protected TI/R hearts against ischaemia-provoked ventricular arrhythmia and ultimately reduced the incidence of sudden cardiac death, with a possible role of c-Jun N-terminal kinase inhibition and connexin 43 activation. ABSTRACT: Remote ischaemic conditioning can protect hearts against arrhythmia. Testicular ischaemia-reperfusion (TI/R) injury is associated with electrocardiographic abnormalities. We investigated the effect of remote limb ischaemia preconditioning (RIPre) and postconditioning (RIPost) on arrhythmogenesis in TI/R rats, and determined the potential role of c-Jun N-terminal kinase (JNK)/connexin 43 (Cx43) signalling. Rats were randomized to sham-operated, control, TI/R, RIPre and RIPost groups. TI/R rats were more predisposed to myocardial reperfusion-induced atrioventricular block (AVB). RIPre and RIPost reduced the incidence of sudden cardiac death (SCD) or AVB, and duration of ventricular tachyarrhythmias during myocardial reperfusion. RIPre and RIPost decreased myocardial I/R-induced phosphorylation level of JNK, while preserving myocardial Cx43 expression in TI/R rats. Taken together, TI/R rats were predisposed to myocardial reperfusion-induced AVB. RIPre and RIPost protected TI/R hearts against ischaemia-provoked ventricular arrhythmia and ultimately reduced the incidence of SCD by suppressing JNK activation and restoring Cx43 expression.
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Precondicionamento Isquêmico Miocárdico , Traumatismo por Reperfusão , Animais , Coração , Isquemia/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Ratos , Traumatismo por Reperfusão/metabolismoRESUMO
BACKGROUND: A number of studies have examined the association between mold exposure and childhood asthma. However, the conclusions were inconsistent, which might be partly attributable to the lack of consideration of gene function, especially the key genes affecting the pathogenesis of childhood asthma. Research on the interactions between genes and mold exposure on childhood asthma is still very limited. We therefore examined whether there is an interaction between inflammation-related genes and mold exposure on childhood asthma. METHODS: A case-control study with 645 asthmatic children and 910 non-asthmatic children aged 3-12 years old was conducted. Eight single nucleotide polymorphisms (SNPs) in inflammation-related genes were genotyped using MassARRAY assay. Mold exposure was defined as self-reported visible mold on the walls. Associations between visible mold exposure, SNPs and childhood asthma were evaluated using logistic regression models. In addition, crossover analyses were used to estimate the gene-environment interactions on childhood asthma on an additive scale. RESULTS: After excluding children without information on visible mold exposure or SNPs, 608 asthmatic and 839 non-asthmatic children were included in the analyses. Visible mold exposure was reported in 151 asthmatic (24.8%) and 119 non-asthmatic children (14.2%) (aOR 2.19, 95% CI 1.62-2.97). The rs7216389 SNP in gasdermin B gene (GSDMB) increased the risk of childhood asthma with each C to T substitution in a dose-dependent pattern (additive model, aOR 1.32, 95% CI 1.11-1.57). Children carrying the rs7216389 T allele and exposed to visible mold dramatically increased the risk of childhood asthma (aOR 3.21; 95% CI 1.77-5.99). The attributable proportion due to the interaction (AP: 0.47, 95% CI 0.03-0.90) and the relative excess risk due to the interaction (RERI: 1.49, 95% CI 0-2.99) were statistically significant. CONCLUSIONS: In the present study, there was a significant additive interaction between visible mold exposure and rs7216389 SNP on childhood asthma. Future studies need to consider the gene-environment interactions when exploring the risk factors of childhood asthma.
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Asma/genética , Asma/microbiologia , Exposição Ambiental , Fungos , Interação Gene-Ambiente , Proteínas de Neoplasias/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Inflamação/microbiologia , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
BACKGROUND: Wheezing is common in younger children and often related to viral infection. It is lack of reliable indicators for asthma prediction. OBJECTIVE: To evaluate the relationship between circulation CD4+CCR6+CRTh2+ memory Th2 cells and asthma diagnosis in wheezing children. METHODS: A prospective study was performed in children under 5 years old presented with wheezing or at last one episode of documented wheezing history. After inclusion, the level of serum allergen-specific serum IgE (sIgE) and circulating CD4+CCR6+CRTh2+cells were detected. The patients' personal and family histories of allergic disease were acquired by questionnaire. The children were followed up over 2 years. Diagnosis of asthma was assessed at the end follow-up. The risk factors in predicting asthma diagnosis were evaluated. RESULTS: A total of 43 children completed follow-up. Higher wheezing frequency were found in children with asthma diagnosis. The mean of circulating CD4+CCR6+CRTh2+cells in children diagnosed with or without asthma was 1.6 %±0.8 and 0.8 %±0.6 %, respectively, and was significantly higher in children diagnosed with asthma (p < 0.01). There was no significant difference between children with and without allergic diseases history or family allergic diseases in level of circulating CD4+CCR6+CRTh2+ cells. Logistic regression analysis indicated that circulating CD4+CCR6+CRTh2+ cells (EXP, 8.986; 95 % CI,1.886-42.816) and wheezing frequency(EXP, 0.127; 95 % CI, 0.023-0.703)were high risk factors for asthma. CONCLUSIONS: Our exploratory study shown that circulating CD4+CCR6+CRTh2+ memory Th2 cells increased in asthma diagnosed children and it was a high-risk factor for asthma. Detection of this type of cells could be helpful in predicting the risk of asthma in wheezing children.
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Asma , Sons Respiratórios , Asma/diagnóstico , Asma/etiologia , Linfócitos T CD4-Positivos , Criança , Pré-Escolar , Humanos , Projetos Piloto , Estudos Prospectivos , Receptores CCR6 , Sons Respiratórios/etiologiaRESUMO
BACKGROUND: Eczema is usually the first allergic manifestation to appear in life attributed to gene-environment interactions. IL13, IL4, MS4A2 and ILR4A are four key inflammatory genes associated with atopy. This study aimed to explore gene-environment interactions on eczema in early life among the above four genes and environmental factors in Chinese Han children. METHODS: Five hundred ninety-seven children from a birth cohort who completed two-year follow-up were enrolled and their cord blood was collected. Subjects were genotyped for six polymorphisms in the aforementioned four genes. The children were followed at 6, 12 and 24 months, with epidemiologic information and medical history of eczema collected by questionnaire and eczema assessed by dermatologists. RESULTS: Among the 597 children, 168 were diagnosed with eczema and the others were not after 2 years of follow-up. MS4A2 rs569108 GG genotype (P = 1.68E-02, odds ratio (OR) = 4.66) and antibiotic use (P = 3.75E-4, OR = 2.02) were found independently associated with development of childhood eczema. Children with both antibiotic use and MS4A2 rs569108 GG genotype were more likely to develop eczema than those with only antibiotic use or GG homozygote (OR = 6.24 VS. 2.04 or 4.68). CONCLUSIONS: MS4A2 rs569108 polymorphism and antibiotic use were solely associated with eczema, and they interacted with each other to increase the risk of developing the disease in Chinese Han toddlers. Long-term follow-up along with functional and replication studies are still needed.
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Dermatite Atópica , Eczema , Receptores de IgE/genética , Antibacterianos , Estudos de Coortes , Dermatite Atópica/genética , Eczema/genética , Humanos , Lactente , Polimorfismo Genético , Estudos ProspectivosRESUMO
INTRODUCTION AND OBJECTIVES: Previous studies reported that history of pregnancy and delivery and family environment might influence cord blood IgE (CB-IgE) levels and development of allergies; however, the association between them is not well-established. This study aimed at investigating the IgE level in the newborn's umbilical cord blood and its relationship with maternal, fetal, and environmental factors. MATERIALS AND METHODS: A total of 989 mothers and their infants were analyzed in this study. Mothers were given a questionnaire that had a series of questions to evaluate demographic information, maternal allergic status, and environmental exposures during pregnancy. Neonatal cord blood samples were taken at the same time for IgE assay. RESULTS: By univariate analysis, we found statistically significant correlations between CB-IgE levels and gender (P = 0.000) and delivery mode (P = 0.017). By multivariate analysis, gender was found to have a significant association with CB-IgE levels (P = 0.001). No significant difference was found between CB-IgE levels and antenatal complications, the season of birth, birth weight, gestational age, and household income (P > 0.050). CONCLUSIONS: In this study, newborn gender was found to be a strong predictor of elevated CB-IgE. The delivery mode was a probable predictor.
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Sangue Fetal/imunologia , Hipersensibilidade/etiologia , Imunoglobulina E/sangue , Fatores Sexuais , Adulto , Análise de Variância , Peso ao Nascer , China , Parto Obstétrico/métodos , Exposição Ambiental , Família , Feminino , Idade Gestacional , Humanos , Hipersensibilidade/imunologia , Renda , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/epidemiologia , Estações do AnoRESUMO
BACKGROUND: Prenatal exposure to perfluoroalkyl substances (PFAS) is considered to affect adversely the immune function. However, the effect of prenatal PFAS exposure on respiratory tract infections (RTIs) in children is unclear. Thus, we evaluated whether cord blood PFAS levels were associated with RTI in the first 5 years of life. METHODS: The Shanghai Prenatal Cohort is an on-going birth cohort, which included all the mothers during pregnancy. Children were followed by paediatricians once a year after birth. The levels of 10 PFAS in cord blood were tested using liquid chromatography-mass spectrometry. RTIs were diagnosed based on face-to-face interviews with the parents and review of medical records. Immunoglobulin G (IgG) and immunoglobulin E (IgE) levels, as biomarkers of humoral immunity, were assessed using enzyme-linked immunosorbent assay at age 5 years. Multivariable logistic and linear regression models were applied to study the association between prenatal PFAS exposure and RTIs. RESULTS: A total of 743 children completed the follow-up, 344 of them had detail information of cord blood PFAS, IgG, and IgE concentrations. Eight PFAS were detected in more than 90% of the cord blood samples, except for perfluoroheptanoic acid (PFHpA) and perfluorooctane sulfonamide (FOSA). During the 5-year follow-up period, the frequency of RTIs increased with age, reaching a peak at age 4. Moreover, 20.6% of the children were diagnosed with recurrent RTIs. Children with recurrent RTIs had higher prenatal perfluorobutane sulfonic acid (PFBS) concentration. Higher prenatal PFBS concentration was positively associated with total RTI frequency (ß = 6.05, 95% CI [0.84, 11.26]) in first 5 years of life and negatively associated with IgG level (ß = -0.82, 95% CI [-1.67, -0.01]) at age 5. CONCLUSIONS: Children with higher prenatal PFBS were more vulnerable to RTIs in early life, which may be attributed to immunosuppression of IgG production. These findings need to be further verified in larger prospective studies.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Infecções Respiratórias , Ácidos Alcanossulfônicos/toxicidade , Pré-Escolar , China/epidemiologia , Feminino , Fluorocarbonos/toxicidade , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos ProspectivosRESUMO
Cold air stimulus is an important environmental factor that exacerbates asthma. At the molecular level, the transient receptor potential melastatin 8 (TRPM8) plays a crucial part in cold detection. The roles of TRPM8 in airway inflammation and remodeling in a murine model of asthma with cold stimulus and the related molecular mechanism are largely unknown. In this study, C57BL/6 mice were randomly divided into four groups: phosphate-buffered saline control group (control), ovalbumin (OVA)-induced asthma group (OVA), OVA with cold air stimulus group (OVA+cold), and OVA+cold+shTRPM8 (TRPM8 short hairpin RNA) group. We showed that cold air stimulus-induced TRPM8 upregulation in the OVA+cold group. Moreover, TRPM8 knockdown significantly attenuated cold-induced inflammation and infiltration, decreased levels of immunoglobulin E, restored the Th1/Th2 balance, and reduced inflammatory cell accumulation and airway remodeling. Furthermore, we demonstrated that TRPM8 knockdown dramatically inhibited mitogen-activated protein kinase and nuclear factor-κB pathways. Collectively, these results revealed that cold air stimulus induced an airway inflammatory response and remodeling by increasing TRPM8 expression and that downregulation of TRPM8 alleviated these responses.
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Ar , Remodelação das Vias Aéreas/imunologia , Asma/imunologia , Temperatura Baixa , Pneumonia/imunologia , Canais de Cátion TRPM/imunologia , Remodelação das Vias Aéreas/genética , Animais , Asma/genética , Asma/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/imunologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/imunologia , NF-kappa B/metabolismo , Ovalbumina/imunologia , Pneumonia/genética , Pneumonia/metabolismo , Interferência de RNA , Distribuição Aleatória , Transdução de Sinais/imunologia , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismoRESUMO
In the field of sensor signal processing, windows are time-/frequency-domain weighting functions that are widely applied to reduce the well-known Gibbs oscillations. Conventional methods generally control the spectral characteristics of windows by adjusting several of the parameters of closed-form expressions. Designers must make trade-offs among the mainlobe width (MW), the peak sidelobe level (PSL), and sometimes the sidelobe fall-off rate (SLFOR) of windows by carefully adjusting these parameters. Generally, not all sidelobes need to be suppressed in specified applications. In this paper, a novel method, i.e., the inverse of the shaped output using the cyclic algorithm (ISO-CA), for designing window functions with flexible spectral characteristics is proposed. Simulations are conducted to test the effectiveness, flexibility and versatility of the method. Some experiments based on real measured data are also presented to demonstrate the practicability. The results show that the window functions generated using the cyclic algorithm (CA) yield better performance overall than the windows of conventional methods, achieving a narrower MW, a lower PSL, and a controllable SLFOR. In addition, steerable sidelobes over specified regions can be acquired both easily and flexibly while maintaining the original properties of the initial window as much as possible.
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Pulse Doppler (PD) systems are widely used for moving target detection, especially in scenarios with clutter. Range ambiguity, which arises from fixed parameters in waveforms, is an inherent drawback in conventional systems. By using a diverse pulse train such as a train of coherent diverse phase coded pulses, these ambiguous peaks can be suppressed effectively but at the cost of sidelobe dispersions. In this work, a novel efficient PD process is proposed to suppress range ambiguity and detect moving targets under strong clutter. Poly-phase coded pulses are employed along with optimal receiving filters, by which the dispersed sidelobes are mitigated to a great extent. Moreover, a novel clutter suppression procedure is included in the PD process, by which strong clutter can be greatly suppressed. Well-designed receiving and inverse filters are employed. Simulation examples are presented to verify the theories. Compared with conventional methods, much better detection results are obtained for both near and remote targets, especially in scenarios with strong clutter.
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The linear stepped frequency and linear frequency shift keying (FSK) signal has been widely used in radar systems. However, such linear modulation signals suffer from the range-Doppler coupling that degrades radar multi-target resolution. Moreover, the fixed frequency-hopping or frequency-coded sequence can be easily predicted by the interception receiver in the electronic countermeasures (ECM) environments, which limits radar anti-jamming performance. In addition, the single FSK modulation reduces the radar low probability of intercept (LPI) performance, for it cannot achieve a large time-bandwidth product. To solve such problems, we propose a novel chaos-based stepped frequency (CSF) synthesized wideband signal in this paper. The signal introduces chaotic frequency hopping between the coherent stepped frequency pulses, and adopts a chaotic frequency shift keying (CFSK) and phase shift keying (PSK) composited coded modulation in a subpulse, called CSF-CFSK/PSK. Correspondingly, the processing method for the signal has been proposed. According to our theoretical analyses and the simulations, the proposed signal and processing method achieve better multi-target resolution and LPI performance. Furthermore, flexible modulation is able to increase the robustness against identification of the interception receiver and improve the anti-jamming performance of the radar.
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The interrupted sampling repeater jamming (ISRJ) based on a digital radio frequency memory (DRFM) device is a new type of coherent jamming. This kind of jamming usually occurs as main-lobe jamming and has the advantages of low power requirements and easy parameter adjustment, posing a serious threat to the modern radar systems. In order to suppress the ISRJ, this paper proposes an adaptive transmitting scheme based on a phase-coded signal. The scheme firstly performs jamming perception to estimate the jamming parameters, then, on this basis, optimizes the waveform with genetic algorithm. With the optimized waveform, the jamming signal is orthogonal to the target echo, thus it can be easily suppressed with pulse compression. Simulation experiments are performed to verify the effectiveness of the scheme and the results suggest that the peak-to-side-lobe ratio (PSR) and integrated side-lobe level (ISL) of the pulse compression can be improved by about 16 dB and 15 dB, respectively, for the case where the jamming-to-signal ratio (JSR) is 13 dB.
RESUMO
Distributed array radar can improve radar detection capability and measurement accuracy. However, it will suffer cyclic ambiguity in its angle estimates according to the spatial Nyquist sampling theorem since the large sparse array is undersampling. Consequently, the state estimation accuracy and track validity probability degrades when the ambiguous angles are directly used for target tracking. This paper proposes a second probability data association filter (SePDAF)-based tracking method for distributed array radar. Firstly, the target motion model and radar measurement model is built. Secondly, the fusion result of each radar's estimation is employed to the extended Kalman filter (EKF) to finish the first filtering. Thirdly, taking this result as prior knowledge, and associating with the array-processed ambiguous angles, the SePDAF is applied to accomplish the second filtering, and then achieving a high accuracy and stable trajectory with relatively low computational complexity. Moreover, the azimuth filtering accuracy will be promoted dramatically and the position filtering accuracy will also improve. Finally, simulations illustrate the effectiveness of the proposed method.