RESUMO
Baleen whales (mysticetes) use vocalizations to mediate their complex social and reproductive behaviours in vast, opaque marine environments1. Adapting to an obligate aquatic lifestyle demanded fundamental physiological changes to efficiently produce sound, including laryngeal specializations2-4. Whereas toothed whales (odontocetes) evolved a nasal vocal organ5, mysticetes have been thought to use the larynx for sound production1,6-8. However, there has been no direct demonstration that the mysticete larynx can phonate, or if it does, how it produces the great diversity of mysticete sounds9. Here we combine experiments on the excised larynx of three mysticete species with detailed anatomy and computational models to show that mysticetes evolved unique laryngeal structures for sound production. These structures allow some of the largest animals that ever lived to efficiently produce frequency-modulated, low-frequency calls. Furthermore, we show that this phonation mechanism is likely to be ancestral to all mysticetes and shares its fundamental physical basis with most terrestrial mammals, including humans10, birds11, and their closest relatives, odontocetes5. However, these laryngeal structures set insurmountable physiological limits to the frequency range and depth of their vocalizations, preventing them from escaping anthropogenic vessel noise12,13 and communicating at great depths14, thereby greatly reducing their active communication range.
Assuntos
Evolução Biológica , Baleias , Animais , Humanos , Baleias/fisiologia , SomRESUMO
Oxytetracycline (OTC) in the waste water can be removed by biochar adsorption. How to separate the biochar adsorbed antibiotics from the wastewater was also a problem. The nontoxic magnetic biochar was prepared from Suaeda biochar (800SBC) by mafic bimetal modification, and used for the removal of OTC. The results of XRD and VSM indicated that the main composition of biochar was ferrite. Then through batch adsorption experiments, the adsorption kinetics, isothermal adsorption, thermodynamics, and coexisting ion and adsorbent regeneration experiments were studied. Through the fitting of the adsorption model, it was found that Mg-Fe@800SBC(1:1) and 800SBC belonged to chemisorption. 800SBC was consistent with the Langmuir model, mainly monolayer adsorption, and Mg-Fe@800SBC(1:1) was consistent with the Freundlich model, mainly multilayer adsorption. The adsorption processes of the two materials were spontaneous, endothermic and entropic decreasing processes. The maximum adsorption capacity of the Mg-Fe@800SBC(1:1) for OTC from the Sips L-F model was 82.83 mg/g. Through various characterizations of magnetic biochar, it was found that the adsorption mechanism of the modified biochar included the hydrogen bonds between the oxygen-containing functional group of biochar and the -NH2 group of OTC, π-π EDA interaction, electrostatic attraction and complexation. Coexistence anions (CO32- and PO43-) have a negative effect on the adsorption process.
Assuntos
Oxitetraciclina , Poluentes Químicos da Água , Oxitetraciclina/química , Adsorção , Poluentes Químicos da Água/análise , Águas Residuárias , Cinética , Fenômenos MagnéticosRESUMO
Underwater acoustic sensor networks have a wide range of applications in both civil and military fields, but the complex and changing underwater environment makes them vulnerable to multiple security threats. Trust mechanisms are effective ways to enhance network security and reliability. In order to improve the accuracy of trust evaluation and the detection rate of abnormal nodes, this paper proposes an adaptive trust evaluation model based on fuzzy logic. This model adopts a variable weight fuzzy comprehensive evaluation algorithm to dynamically adjust the weights of three direct trust indicators to ensure the accuracy of direct trust evaluation. Then, it uses fuzzy closeness to eliminate unreliable recommendation trust and adjusts the weight of recommendation trust through deviation to improve the accuracy of indirect trust. The simulation results show that the model can effectively improve the accuracy of trust evaluation and the detection rate of abnormal nodes. Especially when the link quality is unstable, the success rate of detecting abnormal nodes in this model is improved by more than 10% compared with the existing trust model.
RESUMO
Adsorption was an available way to eliminate Tetracycline (TC) from waste water. Suaeda biochar (800SBC) and iron modified biochar (Fe-800SBC) were prepared using pyrolysis under oxygen-limiting conditions. BET and SEM showed that the surface of Fe-800SBC was rougher, and the specific surface area (SBET) was 7 times that of 800SBC. There existed pore filling, ion exchange, metal ion complexation, hydrogen bonds and cation-π interaction mechanism. Both 800SBC and Fe-800SBC conformed to quasi-second-order kinetics model, belonged to chemisorption. Fe-800SBC conformed to Elovich model too. The adsorption process of 800SBC conformed to Freundlich and Sips L-F models, Fe-800SBC conformed to the Sips L-F and Temkin models, identifying the presence of physical and chemical adsorption during adsorption. Response surface method (RSM) was used to optimize important process parameters. The quadratic model was sufficient to predict TC removal response in the range of studied parameters.
Assuntos
Poluentes Químicos da Água , Adsorção , Poluentes Químicos da Água/análise , Antibacterianos , Tetraciclina/química , Carvão Vegetal/química , CinéticaRESUMO
Voiced sound production is the primary form of acoustic communication in terrestrial vertebrates, particularly birds and mammals, including humans. Developing a causal physics-based model that ultimately links descending vocal motor control to tissue vibration and sound requires embodied approaches that include realistic representations of voice physiology. Here, we first implement and then experimentally test a high-fidelity three-dimensional (3D) continuum model for voiced sound production in birds. Driven by individual-based physiologically quantifiable inputs, combined with noninvasive inverse methods for tissue material parameterization, our model accurately predicts observed key vibratory and acoustic performance traits. These results demonstrate that realistic models lead to accurate predictions and support the continuum model approach as a critical tool toward a causal model of voiced sound production.
Assuntos
Acústica , Simulação por Computador , Laringe/fisiologia , Vocalização Animal , Animais , Columbidae , HidrodinâmicaRESUMO
BACKGROUND: Rodent ultrasonic vocalizations (USVs) are crucial to their social communication and a widely used translational tool for linking gene mutations to behavior. To maximize the causal interpretation of experimental treatments, we need to understand how neural control affects USV production. However, both the aerodynamics of USV production and its neural control remain poorly understood. RESULTS: Here, we test three intralaryngeal whistle mechanisms-the wall and alar edge impingement, and shallow cavity tone-by combining in vitro larynx physiology and individual-based 3D airway reconstructions with fluid dynamics simulations. Our results show that in the mouse and rat larynx, USVs are produced by a glottal jet impinging on the thyroid inner wall. Furthermore, we implemented an empirically based motor control model that predicts motor gesture trajectories of USV call types. CONCLUSIONS: Our results identify wall impingement as the aerodynamic mechanism of USV production in rats and mice. Furthermore, our empirically based motor control model shows that both neural and anatomical components contribute to USV production, which suggests that changes in strain specific USVs or USV changes in disease models can result from both altered motor programs and laryngeal geometry. Our work provides a quantitative neuromechanical framework to evaluate the contributions of brain and body in shaping USVs and a first step in linking descending motor control to USV production.
Assuntos
Ultrassom , Vocalização Animal , Animais , Comunicação , Camundongos , Ratos , Vocalização Animal/fisiologiaRESUMO
OBJECTIVES: Coronary computed tomography angiography (CCTA) has rapidly developed in the coronary artery disease (CAD) field. However, manual coronary artery tree segmentation and reconstruction are time-consuming and tedious. Deep learning algorithms have been successfully developed for medical image analysis to process extensive data. Thus, we aimed to develop a deep learning tool for automatic coronary artery reconstruction and an automated CAD diagnosis model based on a large, single-centre retrospective CCTA cohort. METHODS: Automatic CAD diagnosis consists of two subtasks. One is a segmentation task, which aims to extract the region of interest (ROI) from original images with U-Net. The second task is an identification task, which we implemented using 3DNet. The coronary artery tree images and clinical parameters were input into 3DNet, and the CAD diagnosis result was output. RESULTS: We built a coronary artery segmentation model based on CCTA images with the corresponding labelling. The segmentation model had a mean Dice value of 0.771 ± 0.021. Based on this model, we built an automated diagnosis model (classification model) for CAD. The average accuracy and area under the receiver operating characteristic curve (AUC) were 0.750 ± 0.056 and 0.737, respectively. CONCLUSION: Herein, using a deep learning algorithm, we realized the rapid classification and diagnosis of CAD from CCTA images in two steps. Our deep learning model can automatically segment the coronary artery quickly and accurately and can deliver a diagnosis of ≥ 50% coronary artery stenosis. Artificial intelligence methods such as deep learning have the potential to elevate the efficiency in CCTA image analysis considerably. KEY POINTS: ⢠The deep learning model rapidly achieved a high Dice value (0.771 ± 0.0210) in the autosegmentation of coronary arteries using CCTA images. ⢠Based on the segmentation model, we built a CAD autoclassifier with the 3DNet algorithm, which achieved a good diagnostic performance (AUC) of 0.737. ⢠The deep neural network could be used in the image postprocessing of coronary computed tomography angiography to achieve a quick and accurate diagnosis of CAD.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Aprendizado Profundo , Inteligência Artificial , Angiografia por Tomografia Computadorizada/métodos , Constrição Patológica , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Humanos , Estudos RetrospectivosRESUMO
This paper proposes a deep learning-based generalized empirical flow model (EFM) that can provide a fast and accurate prediction of the glottal flow during normal phonation. The approach is based on the assumption that the vibration of the vocal folds can be represented by a universal kinematics equation (UKE), which is used to generate a glottal shape library. For each shape in the library, the ground truth values of the flow rate and pressure distribution are obtained from the high-fidelity Navier-Stokes (N-S) solution. A fully connected deep neural network (DNN) is then trained to build the empirical mapping between the shapes and the flow rate and pressure distributions. The obtained DNN-based EFM is coupled with a finite element method (FEM)-based solid dynamics solver for fluid-structure-interaction (FSI) simulation of phonation. The EFM is evaluated by comparing the N-S solutions in both static glottal shapes and FSI simulations. The results demonstrate a good prediction performance in accuracy and efficiency.
Assuntos
Aprendizado Profundo , Simulação por Computador , Glote , Modelos Biológicos , Fonação , Vibração , Prega VocalRESUMO
A combined experimental-numerical work was conducted to comprehensively validate a subject-specific continuum model of voice production in larynx using excised canine laryngeal experiments. The computational model is a coupling of the Navier-Stokes equations for glottal flow dynamics and a finite element model of vocal fold dynamics. The numerical simulations employed a cover-body vocal fold structure with the geometry reconstructed from magnetic resonance imaging scans and the material properties determined through an optimization-based inverse process of experimental indentation measurement. The results showed that the simulations predicted key features of the dynamics observed in the experiments, including the skewing of the glottal flow waveform, mucosal wave propagation, continuous increase of the divergent angle and intraglottal swirl strength during glottal closing, and flow recirculation between glottal jet and vocal fold. The simulations also predicted the increase of the divergent angle, glottal jet speed, and intraglottal flow swirl strength with the subglottal pressure, same as in the experiments. Quantitatively, the simulations over-predicted the frequency and jet speed and under-predicted the flow rate and divergent angle for the larynx under study. The limitations of the model and their implications were discussed.
Assuntos
Laringe , Fonação , Animais , Simulação por Computador , Cães , Glote , Prega VocalRESUMO
A hydrodynamic/acoustic splitting method was used to examine the effect of supraglottal acoustics on fluid-structure interactions during human voice production in a two-dimensional computational model. The accuracy of the method in simulating compressible flows in typical human airway conditions was verified by comparing it to full compressible flow simulations. The method was coupled with a three-mass model of vocal fold lateral motion to simulate fluid-structure interactions during human voice production. By separating the acoustic perturbation components of the airflow, the method allows isolation of the role of supraglottal acoustics in fluid-structure interactions. The results showed that an acoustic resonance between a higher harmonic of the sound source and the first formant of the supraglottal tract occurred during normal human phonation when the fundamental frequency was much lower than the formants. The resonance resulted in acoustic pressure perturbation at the glottis which was of the same order as the incompressible flow pressure and found to affect vocal fold vibrations and glottal flow rate waveform. Specifically, the acoustic perturbation delayed the opening of the glottis, reduced the vertical phase difference of vocal fold vibrations, decreased flow rate and maximum flow deceleration rate (MFDR) at the glottal exit; yet, they had little effect on glottal opening. The results imply that the sound generation in the glottis and acoustic resonance in the supraglottal tract are coupled processes during human voice production and computer modeling of vocal fold vibrations needs to include supraglottal acoustics for accurate predictions.
Assuntos
FonaçãoRESUMO
The influence of vocal fold cover layer thickness on the flow-induced vibration and voice production was studied by using a continuum-mechanics based computational model. The cover-body thickness ratio of a three-layer vocal fold was systematically varied. The effect on the vocal fold stiffness, eigenfrequencies and eigenmodes, fundamental frequencies, glottal flow rate, vocal fold vibratory dynamics, and synchronization of the eigenmodes were analyzed by using the structure eigen analysis and flow-structure interaction simulations. It was found that the cover-body layer thickness ratio significantly affected the strength and synchronization of the eigenmodes during flow-structure interactions, and ultimately affected the fundamental frequency and vibration pattern. With the increasing cover-body thickness ratio, the strength of the wave-type higher-eigenfrequency modes increased, and that resulted in a nonlinear bifurcation of the system in which the system evolved from a regular periodic vibration to a periodic doubling vibration and then back to a regular periodic vibration with increased fundamental frequencies. During the transition, the system vibrated chaotically. Because of the increased strength of the wave-type modes, the maximum divergent angle of the glottis was also increased with the increasing cover-body thickness ratio.
RESUMO
A three-dimensional fluid-structure interaction computational model was used to investigate the effect of the longitudinal variation of vocal fold inner layer thickness on voice production. The computational model coupled a finite element method based continuum vocal fold model and a Navier-Stokes equation based incompressible flow model. Four vocal fold models, one with constant layer thickness and the others with different degrees of layer thickness variation in the longitudinal direction, were studied. It was found that the varied thickness resulted in up to 24% stiffness reduction at the middle and up to 47% stiffness increase near the anterior and posterior ends of the vocal fold; however, the average stiffness was not affected. The fluid-structure interaction simulations on the four models showed that the thickness variation did not affect vibration amplitude, glottal flow rate, and the waveform related parameters. However, it increased glottal angles at the middle of the vocal fold, suggesting that vocal fold vibration amplitude was determined by the average stiffness of the vocal fold, while the glottal angle was determined by the local stiffness. The models with longitudinal variation of layer thickness consumed less energy during the vibrations compared with the constant layer thickness one.
Assuntos
Hidrodinâmica , Modelos Biológicos , Fonação , Prega Vocal/fisiologia , Adulto , Fenômenos Biomecânicos , Módulo de Elasticidade , Humanos , Masculino , Fatores de Tempo , VibraçãoRESUMO
Glycosylphosphatidylinositol (GPI)-anchored alkaline phosphatase (ALP) isoforms are crucial for the intoxication of crystal proteins (Cry) to several insect species. We cloned five SeALPs from the larval midgut of Spodoptera exigua, a major pest of many crops. All five SeALPs contain a signal peptide at the N-terminus, a phosphatase domain, and a GPI-anchor site at the C-terminus. Additionally, the sequences encode two or three potential N-glycosylation sites. The five SeALPs were highly expressed at the larval stage, especially in the larval gut or Malpighian tubules. Ingestion over four consecutive days of double-stranded RNAs (dsRNAs) targeting SeALP1, SeALP2, SeALP3, SeALP4, and SeALP5 significantly reduced the corresponding mRNA levels by 60.0%, 40.0%, 65.6%, 48.1%, and 69.1% respectively, compared with the levels in control larvae that fed on non-specific dsRNA (dsEGFP). When larvae that previously ingested phosphate buffered saline (PBS)-, dsEGFP-, or five dsSeALPs-overlaid diets were then exposed to a diet containing Cry1Ca, the larval mortalities after six days were 70.0%, 71.8%, 49.1%, 54.9%, 65.3%, 52.5%, and 77.4%, respectively. ANOVA analysis revealed that the larvae that previously fed on the dsSeALP1-, dsSeALP2-, and dsSeALP4-overlaid diets had significantly lower mortalities than those that previously ingested the PBS-, dsEGFP-, dsSeALP3- and dsSeALP5-overlaid diets. The results suggest that SeALP1, SeALP2 and SeALP4 are involved in the intoxication of Cry1Ca to S. exigua larvae.
Assuntos
Fosfatase Alcalina/metabolismo , Proteínas de Bactérias/metabolismo , Endotoxinas/metabolismo , Proteínas Hemolisinas/metabolismo , Controle Biológico de Vetores/métodos , Spodoptera/enzimologia , Animais , Toxinas de Bacillus thuringiensis , LarvaRESUMO
BACKGROUND: The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants. METHODS: A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces. All registered re-treated TB patients were investigated using a structured questionnaire covering information on demographics, socio-economic characteristics, and previous anti-TB treatment experiences. RESULTS: Totally, 75.3% of 544 patients visited CTD directly for initial treatment. Patients who were female (OR:1.71, 95% CI: 1.01-2.87), over 40 years of age (OR:2.80, 95% CI: 1.24-6.33), from Jiangsu (OR:3.07, 95% CI: 1.57-6.01) and Sichuan (OR:4.47, 95% CI: 2.29-8.73) and those diagnosed before 2005 (OR:6.87, 95% CI: 4.24-11.13) had a significant higher risk receiving their initial treatment at a non-CTD. Patients were more likely to have standardized diagnosis and treatment regimens in CTD (89.8%) than in non-CTDs (65.9%). Patients treated in non-CTDs versus in CTD had a lower possibility to complete their treatment course during first TB episode (χ 2 = 3.926, P = 0.048), but there was no significant difference in the cure rate between different facilities (CTD 60.8%, Non-CTDs 59.1%). Patients in non-CTDs incurred higher costs (1,360 CNY) than those treated in CTD (920CNY). CONCLUSION: CTD play a key role in the National Tuberculosis Control Program. Patients should be guided to seek health care in county designated hospital, where they are more likely to receive appropriate examinations, treatment regimens and rigorous supervision, and to bear a lighter economic burden.
Assuntos
Antituberculosos/uso terapêutico , Hospitais Especializados , Avaliação de Resultados em Cuidados de Saúde , Retratamento/estatística & dados numéricos , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estudos Transversais , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , População Rural , Inquéritos e Questionários , Resultado do Tratamento , Tuberculose/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Maternal syphilis is a health threat to both the pregnant women and the children. This study aimed to delineate the longitudinal trend of maternal syphilis and burden of associated adverse pregnant outcomes (APOs) in Shanghai from 2001 to 2015; and to evaluate the effects of preventing mother-to-child transmission (PMTCT) of syphilis in Shanghai with regard to service coverage and APOs averted. METHODS: PMTCT program of syphilis has been implemented since 2001. Municipal and national PMTCT surveillance data were used in analysis. By using WHO estimation model, the burden of associated APOs and APOs averted were estimated. The differences in access to antenatal care and PMTCT services between resident and non-resident pregnant women were analyzed. RESULTS: The prevalence of seropositivity for maternal syphilis in Shanghai ranged from 0.20% to 0.38% during 2001-2015. The treatment rate varied from 69.8% to 96.8% and remained 83.6% in 2015. Under the PMTCT program, 2163 APOs had been averted during the 15-year period, including 852(39.4%) early fetal loss/stillbirth, 356(16.4%) neonatal death, 190(8.8%) prematurity or low birth weight, and 765(35.4%) clinical evidence of congenital syphilis. Compared with the residents, the non-resident pregnant women had a higher prevalence of syphilis (1.2 vs. 2.5) and contributed to 81.7% of the syphilis associated APOs in 2015. CONCLUSION: Screening of maternal syphilis has reached a full coverage both in residents and non-residents. Large numbers of APOs has been averted attributing to the PMTCT program. More attentions should be paid to those vulnerable non-resident pregnant women and tailored interventions including health education, PMTCT promotion and point of care should be given to maximize the effects of PMTCT in Shanghai.
Assuntos
Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Resultado da Gravidez/epidemiologia , Sífilis/epidemiologia , Sífilis/transmissão , Adulto , China/epidemiologia , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Estudos Longitudinais , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Cuidado Pré-Natal , Sífilis/tratamento farmacológico , Sífilis Congênita/transmissão , Adulto JovemRESUMO
This study aimed to investigate the organic removal efficiency and microbial population dynamics in activated sludge with pressurized aeration. The activated sludge was fed with synthetic wastewater composed of simple carbon source to avoid the effect of complex components on microbial communities. The pressurized acclimation process was conducted in a bench-scale sequencing batch reactor (SBR) under 0.3 MPa gage pressure. Another SBR was running in atmospheric environment as a control reactor, with the same operation parameters except for the pressure. Bacterial diversity was investigated by Illumina sequencing technology. The results showed that the total organic carbon removal efficiency of the pressurized reactor was significantly higher, while the mixed liquor suspended solids concentrations were much lower than those of the control reactor. Moderate pressure of 0.3 MPa had little effect on Alpha-diversity of bacterial communities due to the similar running conditions, e.g., feed water, solids retention time (SRT) and the cyclic change of dissolved oxygen (DO) concentrations. Although the relative percentage of the bacterial community changed among samples, there was no major change of predominant bacterial populations between the pressurized group and the control group. Pressurized aeration would have a far-reaching impact on microbial community in activated sludge when treating wastewaters being unfavorable to the dissolution of oxygen.
Assuntos
Fenômenos Fisiológicos Bacterianos , Reatores Biológicos , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Microbiota/fisiologiaRESUMO
OBJECTIVE: To investigate the prevalence of latent tuberculosis (TB) infection (LTBI), and to identify the risk factors in close contacts of pulmonary TB patients among non-resident population in Shanghai. METHODS: The study subjects were the close contacts of pulmonary TB patients among non-resident populations in Xuhui, Minhang and Songjiang Districts in Shanghai from 2013 to 2014.Questionnaire interview was applied to collect the socio-demographics, TB-related clinical and TB exposure information from the enrolled TB patients and their close contacts. The T-SPOT.TB test was used to identify the infection of M. TB. LTBI was defined as a positive T-SPOT.TB result inthe absence of signs and symptoms related to TB. RESULTS: In total, 182 pulmonary TB patients and 360 close contacts were enrolled in the present study. The mean age of the close contacts was (34±14) years(range, 2-83 years), including 160 men and 200 women. The T-SPOT.TB test and TB related examination revealed that 17.2% (62/360) of the close contacts were latently infected with M. TB. All the LTBI subjects were household contacts (χ(2)=16.814, P<0.001). In multivariate analysis, the risk of LTBI was statistically associated with the presence of TB symptoms of the index case (OR=2.696, 95%CI: 1.060-6.857) and duration of exposure (OR=1.007, 95%CI: 1.001-1.014); whereas there were no statistically significant associations among age, gender, diagnostic delay of index case, environment of contact place and the risk of LTBI among the studied close contacts. CONCLUSIONS: The prevalence of LTBI in close contacts of pulmonary TB patients among non-resident population in Shanghai is 17.2%.Contact with patients with TB symptoms and longer duration of exposure might increase the risk of LTBI.
Assuntos
Tuberculose Latente/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China/epidemiologia , Diagnóstico Tardio , Família , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Tuberculose Pulmonar , Adulto JovemRESUMO
BACKGROUND: Polymorphisms in cytokine genes are known to influence cytokine levels, which may influence susceptibility to tuberculosis (TB) infection and disease. Differences in cytokine expression probably determine whether TB progresses, resolves, or becomes latent. In particular, the balance between the Th1 and Th2 cytokine responses influences the expression of disease in individuals with pulmonary TB (PTB). We performed a case-control study of 120 patients diagnosed with PTB, 240 with latent TB infection (LTBI), and 480 healthy controls (HC), to explore the association between polymorphisms in cytokine genes and a predisposition to Mycobacterium tuberculosis infection and TB disease. RESULTS: A single-gene analysis showed a dominant association between the AA genotype or A allele at nucleotide -874 of the interferon γ (IFN-γ) gene and LTBI. The A allele at nucleotide -1082 of the interleukin 10 (IL-10) gene was significantly more common in PTB patients than in LTBI subjects. Moreover, the polymorphisms at IFN-γ -874 and IL10 - 1082 were associated with protein levels of IFN-γ and IL-10, respectively, in the PTB group. The genotype frequencies of other polymorphisms did not differ between the PTB patients, LTBI and HC subjects. Furthermore, combinations of polymorphisms with IFN-γ -874 were associated with LTBI, whereas combinations with IL10 - 1082 were more likely associated with PTB. CONCLUSIONS: There are positive associations between the IFN-γ -874 polymorphism and TB and between the IL10 - 1082 polymorphism and LTBI. Our data provide genetic evidence of the multiple disease hypothesis that many cytokine genes are involved in TB susceptibility.
Assuntos
Interferon gama/genética , Interleucina-10/genética , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/genética , Adulto , Estudos de Casos e Controles , China , Análise Mutacional de DNA , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
BACKGROUND: We investigated whether polymorphisms in the toll-like receptor genes or gene-gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population. METHODS: Two matched case-control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the TLR genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors. RESULTS: Sixteen markers in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9, and TIRAP were detected. In TLR2, the frequencies of the CC genotype (OR = 2.262; 95% CI: 1.433-3.570) and C allele (OR = 1.566; 95% CI: 1.223-1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR = 6.087; 95% CI: 1.687-21.968). The frequencies of the GG genotype of SNP rs7873784 in TLR4 (OR = 2.136; 95% CI: 1.312-3.478) and the CC genotype of rs3764879 in TLR8 (OR = 1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in TLR9 was significantly higher in the LTBI group than in the HC group (OR = 1.664; 95% CI: 1.201-2.306). An MDR analysis of gene-gene and gene-environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy (p = 0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy (p = 0.0001). CONCLUSIONS: Our results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.
Assuntos
Povo Asiático/genética , Tuberculose Latente/diagnóstico , Tuberculose Latente/genética , Receptores Toll-Like/genética , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Interação Gene-Ambiente , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Estatísticas não Paramétricas , Adulto JovemRESUMO
To study the temperature sensitivity of the destruction of organic compounds in supercritical water oxidation process (SCWO), oxidation effects of twelve chemicals in supercritical water were investigated. The SCWO reaction rates of different compounds improved to varying degrees with the increase of temperature, so the highest slope of the temperature-effect curve (imax) was defined as the maximum ratio of removal ratio to working temperature. It is an important index to stand for the temperature sensitivity effect in SCWO. It was proven that the higher imax is, the more significant the effect of temperature on the SCWO effect is. Since the high-temperature area of SCWO equipment is subject to considerable damage from fatigue, the temperature is of great significance in SCWO equipment operation. Generally, most compounds (imax > 0.25) can be completely oxidized when the reactor temperature reaches 500°C. However, some compounds (imax > 0.25) need a higher temperature for complete oxidation, up to 560°C. To analyze the correlation coefficients between imax and various molecular descriptors, a quantum chemical method was used in this study. The structures of the twelve organic compounds were optimized by the Density Functional Theory B3LYP/6-311G method, as well as their quantum properties. It was shown that six molecular descriptors were negatively correlated to imax while other three descriptors were positively correlated to imax. Among them, dipole moment had the greatest effect on the oxidation thermodynamics of the twelve organic compounds. Once a correlation between molecular descriptors and imax is established, SCWO can be run at an appropriate temperature according to molecular structure.