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Based on one-year observation, the concentration, sources, and potential source areas of volatile organic compounds (VOCs) were comprehensively analyzed to investigate the pollution characteristics of ambient VOCs in Haikou, China. The results showed that the annual average concentration of total VOCs (TVOCs) was 11.4 ppbV, and the composition was dominated by alkanes (8.2 ppbV, 71.4%) and alkenes (1.3 ppbV, 20.5%). The diurnal variation in the concentration of dominant VOC species showed a distinct bimodal distribution with peaks in the morning and evening. The greatest contribution to ozone formation potential (OFP) was made by alkenes (51.6%), followed by alkanes (27.2%). The concentrations of VOCs and nitrogen dioxide (NO2) in spring and summer were low, and it was difficult to generate high ozone (O3) concentrations through photochemical reactions. The significant increase in O3 concentrations in autumn and winter was mainly related to the transmission of pollutants from the northeast. Traffic sources (40.1%), industrial sources (19.4%), combustion sources (18.6%), solvent usage sources (15.5%) and plant sources (6.4%) were identified as major sources of VOCs through the positive matrix factorization (PMF) model. The southeastern coastal areas of China were identified as major potential source areas of VOCs through the potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models. Overall, the concentration of ambient VOCs in Haikou was strongly influenced by traffic sources and long-distance transport, and the control of VOCs emitted from vehicles should be strengthened to reduce the active species of ambient VOCs in Haikou, thereby reducing the generation of O3.
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Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Emissões de Veículos/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Ozônio/química , Alcanos/análise , Alcenos , ChinaRESUMO
BACKGROUND: Sporadic lymphangioleiomyomatosis (S-LAM) is a rare neoplasm with heterogeneous clinical features that is conventionally considered to be related to TSC2. This study serves to elucidate the mutation landscape and potential correlation between S-LAM genomic profiles and clinical phenotypes. METHODS: Genomic profiles of 22 S-LAM patients were obtained by sequencing genomic DNA and cell-free DNA from various specimens using an NGS (next-generation sequencing)-based tumor-driver gene panel. Detected mutations were summarized. Symptoms, serum vascular endothelial growth factor D (VEGF-D) values, pulmonary function, and six-minute walk distance (6MWD) were compared among groups with different TSC2 status and genotypes to analyze genotype-phenotype correlations. RESULTS: 67 Variants in 43 genes were detected, with a TSC2 mutation detection rate of 68.2%. The TSC2 detection rate was similar in specimens obtained either through transbronchial lung biopsy (TBLB) or surgical lung biopsy (70.0% vs. 69.2%, p > 0.05). A novel mutation in VEZF1 (c.A659G) was detected in four participants and may represent a mild disease state. TSC2 mutation was significantly related to a shorter 6MWD (p < 0.05), and a higher percentage of VEGF-D over 800 pg/mL (p < 0.05); stop-gain mutation was significantly related to a higher prevalence of pneumothorax. CONCLUSIONS: Tumor-driver mutations in genes other than TSC2 may have a role in S-LAM, and TBLB specimens are practical alternatives for genomic analysis. TSC2 mutation detectability and types are related to the disease severity and phenotypes of S-LAM.
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Proteínas de Ligação a DNA , Neoplasias Pulmonares , Linfangioleiomiomatose , Fatores de Transcrição , Proteína 2 do Complexo Esclerose Tuberosa , Ácidos Nucleicos Livres , Proteínas de Ligação a DNA/genética , Estudos de Associação Genética , Humanos , Neoplasias Pulmonares/genética , Linfangioleiomiomatose/genética , Mutação , Fatores de Transcrição/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Fator D de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Transbronchial lung biopsy (TBLB) in the diagnosis of lymphangioleiomyomatosis (LAM) is not a common approach, although TBLB is often performed in diffuse lung diseases. We aimed to examine the diagnostic value and safety of TBLB in LAM patients based on the data collected in our center. METHODS: We reviewed LAM patients registered in our LAM Clinic from December 8, 2006, to December 31, 2019. All patients with definite or probable diagnosis of LAM who had been examined using TBLB were included. All available pathology slides were reviewed by an experienced LAM pathologist. All complications were reviewed by the medical records and confirmed using telephone interviews. RESULTS: The pathology results of 86 patients (including 74 definite LAM and 12 probable LAM) were available. The positive rate of TBLB in LAM patients was 49/86 (57.0%). The positive rates of SMA, HMB-45, ER, and PR in LAM patients were 97.6%, 93%, 84.6%, and 78.4% respectively. The positive rate of TBLB was 40%, 60% and 60.8% in patients with CT Grade I, Grade II, and Grade III respectively, and the difference was not significant. Patients who had 3-4 or 5-6 biopsied specimens had a higher rate of diagnosis than those with 1-2 biopsied specimens. Four patients (5.6%) reported pneumothorax. No major hemoptysis was reported. CONCLUSIONS: TBLB is a feasible and safe procedure for obtaining a pathological diagnosis of LAM. Taking more than 2 samples during the biopsy procedure increased the rate of diagnosis.
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Broncoscopia/métodos , Pneumopatias/diagnóstico , Linfangioleiomiomatose/diagnóstico , Pneumotórax/etiologia , Adulto , Biópsia/efeitos adversos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Lymphangioleiomyomatosis (LAM) is a slow albeit progressive rare neoplastic disease featured with diffuse thin-walled cysts in lungs and angiomyolipomas in kidneys. LAM affects almost exclusively women and has one of the strongest gender predispositions of any extragenital human disease. Two forms of LAM present clinically, sporadic (S-LAM) and tuberous sclerosis complex-associated (TSC-LAM). TSC is an autosomal dominant genetic multisystems neoplastic disease. A high prevalence of LAM can be detected in adult female TSC patients. Tremendous progress has been made in our understanding and management of this rare disease. Both LAM and TSC are TSC2 or TSC1 mutated diseases that result in overactivation of the mechanistic target of rapamycin (mTOR) pathway. Sirolimus, an mTOR inhibitor, has been approved for LAM treatment in the United States and many other countries. Therapies targeting female sex hormones have shown preclinical efficacy in animal and cell culture-based experiments, but have not been properly investigated clinically. In this review, we summarize current recommendations in the diagnosis and treatment of LAM.
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Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/terapia , Animais , Humanos , Linfangioleiomiomatose/genética , Linfangioleiomiomatose/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/genética , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose TuberosaRESUMO
BACKGROUND: Exposure to air pollution is associated with chronic obstructive pulmonary disease (COPD). However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce. This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China. METHODS: We enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China. Follow-ups were performed every 3 months for each participant. Serum levels of 20 cytokines were detected every 6 months. Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing. Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures. A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up. RESULTS: A total of 84 COPD patients were enrolled at baseline. Of those, 75 COPD patients completed the first-year of follow-up. We found adverse cumulative effects of particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD. Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L). CONCLUSION: Acute exposures to PM2.5, NO2, SO2 and CO were associated with a reduction in FVC % pred in COPD patients. Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines.
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Poluição do Ar/efeitos adversos , Citocinas/sangue , Inflamação/fisiopatologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Adulto , Idoso , Pequim , Feminino , Humanos , Inflamação/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Pacientes , Testes de Função Respiratória , Soro/química , Fatores de Tempo , Adulto JovemRESUMO
Dirac cones of an acoustic system are the foundation of most topological phase transitions and topological states and have recently become a research hotspot. Although the Dirac cones, Dirac-like cones, double Dirac cones, and semi-Dirac points are all skillfully designed, it is still indispensable to realize a tunable Dirac cone in a novel acoustic structure. This paper proposes two-dimensional acoustic metamaterials with matryoshka structure to achieve tunable Dirac cones and topological spin states. Dirac points can be obtained on the dispersion curves owing to the high symmetry. The concentric circular scattering units of the matryoshka structure are arranged in honeycomb lattices. By a rotating-scatterer mechanism to break the symmetry, the Dirac cone at K (K') is split and the topological spin states appear at the band valley. The existence of a topological transition with opposite Chern numbers as the rotating angle varies is also verified, and helical edge states are obtained along the interfaces separating the topologically opposite spin states insulators. Moreover, the frequency of the Dirac cone is tuned by rotating the inner structure in a double-layer matryoshka structure.
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Recently, the study of topological phase transitions and edge states for acoustic wave systems has become a research hotspot. However, most current studies on topological edge states are based on Bragg scattering, which is not practical to apply in situations involving low-frequency sound because of the large structural dimensions. Therefore, the authors construct, in this study, a graphene-like structure based on a sub-wavelength resonant unit Helmholtz resonator and adjust the acoustic capacitance diameter of adjacent units to change the local resonance frequency, and thereby impose the degeneracy of the Dirac cone and topological spin states, which is characterized by valley Chern numbers of opposite sign. The authors also check topological valley edge states at zigzag and armchair interfaces and find that gapless topological valley edge states only appear at zigzag interfaces, whereas armchair interfaces host gap edge states. Moreover, the results show that the transmission properties of edge states in a zigzag rectangular waveguide are immune to backscattering and defects.
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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. The present study aimed to examine roles of T and MDSC subsets in lung malignancy. The study analyzed 102 cases with lung malignancy and 34 healthy individuals. Flow cytometry was performed for identification of T cell and MDSC subsets and their phenotypic characteristics in peripheral blood. The lung malignancy cases exhibited lower frequencies of granulocyte-like MDSCs (G-MDSCs) expressing PD-L2 and PD-L1 than healthy controls (P=0.013 and P<0.001, respectively). Additionally, there was a higher frequency of monocyte-like MDSCs (M-MDSCs) expressing PD-L1 in the peripheral blood of patients with lung malignancy than healthy controls (P<0.001). The frequencies of G-MDSCs and M-MDSCs were positively correlated with proportions of PD-1+ and CTLA-4+ regulatory T cells (Tregs). In vitro co-culture assay demonstrated M-MDSCs of lung malignancy enhanced naive T cell apoptosis and promoted Treg subset differentiation compared with M-MDSCs of healthy controls. The findings suggested accumulation of MDSC subsets in lung malignancy and MDSCs expressing PD-L2 and PD-L1 induced Treg expansion by binding to PD-1 on the surface of Tregs.
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In the context of clean air actions in China, vehicle emission limits have been continuously tightened, which has facilitated the reduction of volatile organic compounds (VOCs) emissions. However, the characteristics of VOC emissions from vehicles with strict emission limits are poorly understood. This study investigated the VOC emission characteristics from vehicles under the latest standards based on tunnel measurements, and identified future control strategies for vehicle emissions. The results showed that the highest percentage of VOCs from vehicle consisted of alkanes (80.9 %), followed by aromatics (15.8 %) and alkenes (3.1 %). Alkanes had the most significant ozone formation potential due to their high concentrations, in contrast to the aromatics that have been dominant in previous studies. The measured fleet-average VOC emission factor was 71.3 mg·km-1, including tailpipe emissions of 39.6 mg·km-1 and evaporative emissions of 31.7 mg·km-1. The VOC emission factors of the subgroups were obtained. The emission of evaporated VOCs accounted for 44.5 % of the total vehicle VOC emissions, which have increased substantially from previous studies. In addition, the emission characteristics of vehicles that are under the latest emission threshold values have changed significantly, and the mixing ratio of toluene/benzene (T/B) has been updated to 3:1. This study updates the VOCs emission factors of vehicles under clean air actions and highlights the future mitigation policies should focus on reducing evaporative VOC emissions.
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The ambient air quality standard (AAQS) is a vital policy instrument for protecting the environment and human health. Hainan Province is at the forefront of China's efforts to protect its ecological environment, with an official goal to achieve world-leading air quality by 2035. However, neither the national AAQS nor the World Health Organization guideline offers sufficient guidance for improving air quality in Hainan because Hainan has well met the former while the latter is excessively stringent. Consequently, the establishment of Hainan's local AAQS becomes imperative. Nonetheless, research regarding the development of local AAQS is scarce, especially in comparatively more polluted countries such as China. The relatively high background values and significant interannual fluctuations in air pollutant concentrations in Hainan present challenges in the development of local AAQS. Our research proposes a world-class local AAQS of Hainan Province by reviewing the AAQS in major countries or regions worldwide, analyzing the influence of different statistical forms, and carefully evaluating the attainability of the standard. In the proposed AAQS, the annual mean concentration limit for PM2.5, the annual 95th percentile of daily maximum 8-h mean (MDA8) concentration limit for O3, and the peak season concentration limit for O3 are set at 10, 120, and 85 µg/m3, respectively. Our study indicates that, with effective control policies, Hainan is projected to achieve compliance with the new standard by 2035. The implementation of the local AAQS is estimated to avoid 1,526 (1,253-1,789) and 259 (132-501) premature deaths attributable to long-term exposure to PM2.5 and O3 in Hainan in 2035, respectively.
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BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.
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Sirolimo , Humanos , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Criança , Feminino , Adolescente , Pré-Escolar , Adulto , Masculino , Lactente , Adulto Jovem , Pessoa de Meia-Idade , Recém-Nascido , Idoso , Esclerose Tuberosa/tratamento farmacológico , Linfangioleiomiomatose/tratamento farmacológico , Estudos ProspectivosRESUMO
Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its mechanism. Therefore, the manipulation of animal models of knee osteoarthritis is critical. This protocol provides a standard process for Tuina manipulation on KOA rats and a preliminary exploration of the mechanism of Tuina for KOA. The press and kneading manipulation method (a kind of Tuina manipulation that refers to pressing and kneading the specific area of the body surface) is applied on 5 acupoints around the knee joint of rats. The force and frequency of the manipulation were standardized by finger pressure recordings, and the position of the rat during manipulation is described in detail in the protocol. The effect of manipulation can be measured by pain behavior tests and microscopic findings in synovial and cartilage. KOA rats showed significant improvement in pain behavior. The synovial tissue inflammatory infiltration was reduced in the Tuina group, and the expression of tumor necrosis factor (TNF)-α was significantly lower. Compared to the control group, chondrocyte apoptosis was less in the Tuina group. This study provides a standardized protocol for Tuina manipulation on KOA rats and preliminary proof that the therapeutic effects of Tuina may be related to reducing synovial inflammation and delayed chondrocyte apoptosis.
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Osteoartrite do Joelho , Ratos , Animais , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/metabolismo , Inflamação/metabolismo , Cartilagem/metabolismo , Membrana Sinovial/patologia , Articulação do Joelho/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have been reported to expand and have a potent ability in the expansion of regulatory T cells in malignant and infectious disease. The current study was performed to investigate the role of MDSCs and possible immune mechanisms in dampening immune responses of community acquired pneumonia (CAP). METHODS: This was a single-center cross-sectional study. The distribution of MDSCs subsets, the PD-1/PD-L1(L2) level of MDSCs subsets and Tregs in the peripheral blood of adult CAP patients and healthy control were measured by flow cytometry analysis. RESULTS: Peripheral blood mononuclear cells (PBMCs) from 63 adult CAP patients contained an elevated frequency of both G-MDSC (4.92±0.30 vs 2.25±0.21,p<0.0001) and M-MDSC (19.40±1.30 vs 9.64±0.57,p<0.001) compared to healthy controls. Treg in the peripheral blood of CAP patients exhibited increased expression of PD-1 and CTLA-4, accompanied by no difference of their frequency. Moreover, up-regulated expression of PD-L1 on MDSC subsets in the peripheral blood of CAP patients was also revealed. Of note, the frequency of circulating MDSCs subset displayed a positive correlation with neutrophil count percentage in blood in CAP patients. CONCLUSIONS: In summary, the significant expansion of circulating MDSCs subsets and the up-regulated expression of PD-1/PD-L1 level in CAP patients may suggest the possible involvement of PD-1/PD-L1axis in MDSCs mediated immune regulation on Treg at least partially in CAP patients.
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Infecções Comunitárias Adquiridas , Células Supressoras Mieloides , Pneumonia , Humanos , Adulto , Regulação para Cima , Antígeno B7-H1 , Estudos Transversais , Leucócitos Mononucleares , Receptor de Morte Celular Programada 1RESUMO
Based on ambient air quality data, meteorological observation data, and satellite remote sensing data, the temporal and spatial variations in ozone (O3) pollution, the sensitivity of O3, and its relationship with meteorological factors in Hainan Island were analyzed in this study. The results showed that the maximum daily 8-h moving mean (O3-8h) in western and northern cities in Hainan Island was higher than that in the central, eastern, and southern cities. O3-8h was the highest in 2015, and O3-8h exceeding the standard proportion was the largest in 2019. In addition, O3-8h was positively correlated with average temperature (P<0.1), sunshine duration (P<0.01), total solar radiation (P<0.01), atmospheric pressure, and average wind speed and was negatively correlated with precipitation (P<0.05) and relative humidity. The satellite remote sensing data showed that the tropospheric NO2 column concentration (NO2-OMI) and HCHO column concentration (HCHO-OMI) displayed opposite trends in Hainan Island from 2015 to 2020. Compared with those in 2015, NO2-OMI increased by 7.74% and HCHO-OMI decreased by 10.2% in 2020. Moreover, Hainan Island belongs to the NOx control area, and the FNR value exhibited a fluctuating downward trend in the past 6 years, with a trend coefficient and climatic trend rate of -0.514 and -0.123 a-1, respectively. A strong correlation was observed between meteorological factors and the FNR value of Hainan Island.
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Neuropathic pain is a prevalent condition that affects 6.9%-10% of the population and results from nerve damage due to various etiologies, such as lumbar disc herniation, spinal canal stenosis, and intervertebral foramen stenosis. Although Tuina, a traditional Chinese manual therapy, has shown analgesic effects in clinical practice for the treatment of neuropathic pain, its underlying neurobiological mechanisms remain unclear. Animal models are essential for elucidating the basic principles of Tuina. In this study, we propose a standardized Tuina protocol for rats with compression of the dorsal root ganglion (DRG), which involves inducing DRG compression by inserting a stainless steel rod into the intervertebral foramen, performing Tuina manipulation with specific parameters of location, intensity, and frequency in a controlled environment, and assessing the behavioral and histopathological outcomes of Tuina treatment. This article also discusses the potential clinical implications and limitations of the study and suggests directions for future research on Tuina.
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Gânglios Espinais , Neuralgia , Ratos , Animais , Ratos Sprague-Dawley , Constrição Patológica/patologia , AnalgésicosRESUMO
Based on the 181 tropical cyclones data in the western North Pacific Ocean from 2015 to 2020, hourly ozone (O3) concentration data, and meteorological observation data of 18 cities and counties in Hainan Island, this study analyzed the impacts of tropical cyclones on ozone pollution in Hainan Island. We found that 40 (22.1%) tropical cyclones experienced O3 pollution in Hainan Island during the lifetime of tropical cyclones in the past six years. During the years with more tropical cyclones, more O3- polluted days occurred in Hainan Island. Highly polluted days, which were defined as more than or equal to three cities and counties exceeding the standard, were the most serious in 2019 with 39 (54.9%) polluted days. The tropical cyclones related to high pollution (HP) showed an increasing trend, with the trend coefficient and climatic trend rate of 0.725 (exceeding the 95% significance level) and 0.667 a-1, respectively. Tropical cyclone intensity was positively correlated with the maximum 8 h moving average (O3-8h) concentration in Hainan Island. Among them, HP-type tropical cyclones accounted for 35.4% of all samples in the typhoon (TY) intensity level. Cluster analysis of tropical cyclone paths showed that tropical cyclones from the South China Sea (type A) were the most common of the 67 (37%) and were the most likely to cause large-scale and high-concentration O3 pollution events in Hainan Island. The average number of HP tropical cyclones and ρ(O3-8h) of Hainan Island in type A were 7 and 121.90 µg·m-3, respectively. In addition, the tropical cyclone centers were located generally in the middle part of the South China Sea and the western Pacific Ocean near the Bashi Strait during the HP period. The change in meteorological conditions in Hainan Island under the influence of HP tropical cyclones was conducive to the increase in O3 concentration.
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In order to explore the influence of the 2016 typhoon Nangka on ozone (O3) concentration in Hainan Island, this study employed correlation analysis and backward trajectory simulated methods, using the hourly air quality monitoring data, meteorological data, EAR5 reanalysis data, and bright temperature (TBB) infrared from the Himawari-8 satellite from October 10 to 14, 2020. The results showed that, during the typhoon process from October 11 to 13, the O3-8h (maximum of 8 hours sliding average) concentration exceeded the standard. The averaged ρ(O3-8h) of Hainan Island reached its peak value (130.5 µg·m-3) in October 12, 2020, with the O3-8h concentration exceeding the standard in four cities and counties, in which Lingao County reached the highest concentration of 198.44 µg·m-3. During the typhoon process, the hourly O3 concentration was negatively correlated with precipitation, relative humidity, and wind speed and positively correlated with air pressure and air temperature. Moreover, the correlation coefficients between O3 with precipitation, air pressure, and relative humidity exceeded the 99.9% confidence level. The southeastern coastal provinces of China were the main contribution source area for this ozone pollution process on Hainan Island. Affected by the downdraft inside the western Pacific subtropical high (WPSH) and the downdraft outside the circumference of typhoon Nangka, vertical transport in the atmosphere appeared over the contribution source area. The meteorological conditions were favorable for atmospheric photochemical reactions. Air pollutants were transported to Hainan Island along the northeast airflow around the typhoon, resulting in the occurrence of an O3 pollution event. In addition, this study built a weather conceptual model of O3 pollution in Hainan Island affected by typhoon Nangka, which can be used as a reference for the joint pollution prevention and control by air pollution prediction, early warning, and environmental management departments.
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Primary ciliary dyskinesia (PCD) is a highly heterogeneous recessive inherited disorder. FAP54, the homolog of CFAP54 in Chlamydomonas reinhardtii, was previously demonstrated as the C1d projection of the central microtubule apparatus of flagella. A Cfap54 knockout mouse model was then reported to have PCD-relevant phenotypes. Through whole-exome sequencing, compound heterozygous variants c.2649_2657delinC (p. E883Dfs*47) and c.7312_7313insCGCAGGCTGAATTCTTGG (p. T2438delinsTQAEFLA) in a new suspected PCD-relevant gene, CFAP54, were identified in an individual with PCD. Two missense variants, c.4112A>C (p. E1371A) and c.6559C>T (p. P2187S), in CFAP54 were detected in another unrelated patient. In this study, a minigene assay was conducted on the frameshift mutation showing a reduction in mRNA expression. In addition, a CFAP54 in-frame variant knock-in mouse model was established, which recapitulated the typical symptoms of PCD, including hydrocephalus, infertility, and mucus accumulation in nasal sinuses. Correspondingly, two missense variants were deleterious, with a dramatic reduction in mRNA abundance from bronchial tissue and sperm. The identification of PCD-causing variants of CFAP54 in two unrelated patients with PCD for the first time provides strong supportive evidence that CFAP54 is a new PCD-causing gene. This study further helps expand the disease-associated gene spectrum and improve genetic testing for PCD diagnosis in the future.
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Síndrome de Kartagener , Camundongos , Animais , Humanos , Masculino , Síndrome de Kartagener/genética , Síndrome de Kartagener/metabolismo , Cílios/genética , Cílios/metabolismo , Sêmen , Testes Genéticos , RNA Mensageiro , MutaçãoRESUMO
To investigate the pollution characteristics and formation mechanism of ambient air ozone(O3) in a typical tropical seaside city, we conducted an observational experiment on O3 and its precursors at an urban site in Haikou, Hainan Province, from June to October 2019. The O3 pollution characteristics were analyzed comprehensively; the O3-NOx-VOCs sensitivities and key precursors were determined, and the control strategies for O3 pollution were carried out. The results were as follows:1 O3 pollution in Haikou mainly occurred in September and October, with daily maximum 8-h O3 concentrations in the range of 39-190 µg·m-3, and the daily variation in O3 was unimodal, peaking at approximately 14:00. 2 The concentrations of NO2 and VOCs were higher during O3 pollution episodes than their respective mean values in Haikou City. The increased O3 precursor concentrations were an important factor leading to O3 pollution, whereas O3 pollution was also influenced by regional transport, with pollutants mainly transported from the northeastern part of Haikou City. 3 O3-NOx-VOCs sensitivity in Haikou City was in the VOCs and NOx transitional regime, and the most sensitive precursors in various months were different. O3 formation in September was sensitive to anthropogenic VOCs the most; however, in October it was sensitive to NOx. 4 In the future, the reduction ratio of VOCs to NOx should be 1:1-4:1 to control O3 pollution effectively in Haikou.